(12) SARS A ER 8 A A (19) Lola RUB Zz NT 0 1 = (10) ARRAS 4) RA AL eS 2013 F516 Bl (16.08.2013) mice ipcT WO 2013/067666 Al 61) BRERA (2) BHA: CO7D 405/04 (2006.01) CO7H 19/06 (2006.01) 7S) RBAA (LS): SFE (1, Jinliang) — WONG], EE in BH 4 37 OCB 1479 BARE PCTICNDOI1/081856 at 201203 (CN) + LAM. (ZHAO, Naw) 22) BS. 2011 11.97 A 07.11.2011) lowicny; + GL RL bet dk AH 1479 a : Shanghai 201203 (CN) (LIU, Shu) (CNCN): Oka = TE AP ATMA OK 0H 1479 Shanghai (26) BABE: 8 201203 (CN), FERAAB (CHENG, Fenghua) (CN/CN}, To — ; TBE ef A BDH AE 1479 5, Shang c» BRA camehiosreiee rs bapaserg PRE . - MeAREA HD (SHANGHAL DESARO PHARMA. DI2P(). ARIE (SIONG, Yayo) [CNN CEUTICALS INVESTMENT CO.,LTD) [CN(CN}; EE TT 3 Sk SUB 1479 - Shang Aa be eee en 201203 (CN). ARR ZHOU, Chunteng) [CNN ASA 147, shanghai 01203 2208 (CN) LIRAR. CAROL, Chunteg) C1 (CX). EMILE RAT CHAN PB 9K 1479 5, Shana HAL DESANO CHEMICAL PHARMACEUTICAL 21203(CN) CO. LID) CNCNI. MELLIN AAI EEE (oy RBA: EMCAIRARIE AEA RLA RL HANG: 280k 15. Shanghai 201203 (CN). APMED “WAL PATENT. & TRADEMARK LAW OFFICE, RARAA (ANGSU PUXIN PHARMACEUTIC LLC), P Bib i Th HEF 435, Shanghai 200233 ALS DEVELOPMENT CO. LTD) (CN(CN}. ‘FHF (cr. QML JER DCE TWD, Hangs 2 . oy an a ee (8 HUE GR AHO, BORAT ArT pL IMR 4"): AB, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW? BY, BZ, CA. CH, CL, CNC CZ DE, DK, DM, DO, DZ, EC, EE, EGE [ei a) (64 Title: METHOD FOR PREPARING ZIDOVUDINE AND INTERMEDIATE THEREOF (54) BOA RMG : tel Ft BACHE RSP PR TI (c) (60) Abstenet: Disclosed is a method for preparing zidovudine (B). The method comprises the following steps: 1) 2-halothymidine (A) is wed as the raw material fo obtain compound of Komnula(D by protecting the hydroxyl group thereo inthe 5-position; 2) the compound of forme (Di subjected to the acylation of dhe bydoxyl group inthe 3-postion to obtain a compound of formula (V2; 3) the eompound of formula (VI) is dehalogensted to obtain a compound of formula (111); 4) the eompound of fomnmla (Hl) s ub jected to an elimination reaction to obtain 2 compound of formula (IV); 5) the compound of formula (LV) is subjected 10 an azidation ction fo obtain a compound of formula (V); and 6) the compound of formula (V) is deprotected to obiain zidovudine (B); the sp cif reaction formula being shown in (C)below. In the formulae: X is halogen, Pi a protecting group for hydroxyl and Ps is C Calkylsulfony, huoro-C\-Ce alkylsulonyl,arysulfonyl or -CS-R, wherein is CC alkyl 67, RE A GRA: 1) ULI ARBATE CA) YI, ABE Sf PITA. FERMILAB (VD (hth 3) 3% CVD th SemeewT BRA CN) ee: sVBat CV) HAs. 5) ab CV) Hee FUG REE BI Cv) HB: 6) KV) AeA G SAB RG CB). FURAN RBERITE CC) 2 ak Pe RJR: PONFEREDRP A Pe CERES. ACI Co FAEORNRAE. TARBALL CSR, JEP RI Cael < 2 3 S x Se s a S a ZWO 2013/067666 A1 IMIIINNIIN NEI 1 ANON GP, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR. (84) HEM RAI, SOR NA RW, see (4): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, TZ, UG, ZM, ZW), WE (AM, AZ, BY, MD, RU, TJ, TM), HHL (AL, AT, BE, BG, CH, CY, CZ, DE, DK, FE, FS, FI, FR, GB, HR, HU, IF, 1S, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL; PT, RO, RS, SE, SI, SK, SM, TR), OAPI GBF, Bl CF, CG, Cl, CM, GA, GN, GQ, GW, ML, MR, NE, SN, 1D, 16), AER AAG: — ARR EEL CREM 2 Oy,WO 20131067666 PCTICN2011/081856 BFS AKER TT RAG ARABELLA S CLR HAY iil Ht & Ke 1 Tad SLAB UGE Hil HFS KEN ITI RBA FEB FE AE AE FEE APR AR FB PDA EH AE? i SE Bjin, BiWar Sia), Wey sa fe WEA ALS WESt 0 FE Paths FB KEES BP RAI A Ae Fei Hy CF oH HON N oO ns® e yar EPH A He HY HH Ae BEE 9G TN FUSS 1244424 EAN BRE: A, 9 A on One , “yy Ho NO p ° Me Me Hy Hy NaNyOME Da J aaneon Be OO 0 —— oO N’ °. ° 13 ce) N, Ns Scheme |WO 20131067666 PCTICN2011/081856 FA SOS- BATE AEP be Re A TE fie it FA AJ BASF SED TP TBR COL CAP RERED 2005, 29 (7) , 327-331) : KR ry oN : : Scheme 2 TEE HRCA BO oe B+ HALT HE FRE PRY 57 iFee EI A 10%-15%fi37,5°- FERRI PE, Leb: SAP Ba PDAS TF He we (1 7 sh BEAM ER AE, Be 3 tH AE FFG BUHE PR» AS USSR GAEDE — 2 BA RA 7 EB AEB KE Tike BAA AR BLA LE SEE RT KE MTT,WO 20131067666 PCTICN2011/081856 {6 3°,S°- FEAR DN OP Ee, PEPE AB BRA ES — SF SB BG Bd Ee OT AEA RELA Fr, REDE AP BE AY HD FFA HE ITI WT SBD EATS GF ER 1) VA2- Pa FRAT BL RES EAT RP, #4 SSK CD eM: 2 XD KAWAI A AI CVD ai: DA VD KAVAKAGA AUDA: 4) Xt CID (APPR BI INAV ka, 5) XV) KAWAB ALR MASI CV) 1AM: 6) KR CV) BURT BF B KE; FUR IN BKB 4 Pa Si Ge — eee _— \ Ok Promo +H oe epo ON . eth] te Scheme 3 SUH: KOU PERE, ARE: PLUS, Obi abe FERRC3.6hit HEB IE, SEDI I) AS FE NE POE a PB Es PLAC SEA IE. BUR NIC «eA ESE . IF ALLL IERN-CS-R, FEHR VC afc Hes ULI PE. SOP FE FERL-CS-R, JEYR I HUE.WO 20131067666 PCTICN2011/081856 CEE KM AAS, CVD tea CID ey SHIRA EAT FP LL ET fe TA ST KD A. RVD KAA BU CID He Wr ASE 5} Bs BEAT Fab Be, Mam SEY WOW TE. CEES AE, ER A Fs 1) V2? BEART UR, SG SARE ATER, #9 BIS"- SRF E-2°- BME s 2) 5° SLR HUE" IPP AS 3° FF IED He AB 5° HE -37= FFB -2 = Pa FE s 3) 57S FR FP E-3°- FEA SIE -2 *= 2 HE BA IE BT BS? FAUE-3°— FEU SIE EE 4) S°-S ARIF E-3°— UIP HE BFF CEB HE KF I BR GS -S ASF AR-2,3 7A HEE, 5) 57-9 IF HE-2,3 >A AC INE 8 BH ZI BY SR -3 BUI: 6) S°- =A FB AE-3°- TT CE PTE REP BR 9 BF IAL 2” LRT EE BY > US49 142334 aE AY Ja 3 EAT Hil a. TERE NY 92 HE LA): BEE, ABEL) IN 52 MARLEE 2920-80°C, PLié40-70°C; ME A WE A WL a, AEE BES, AER) I SIMI POs BINA IEE DY 0-5°C SLICE Hy BTCA A, ULE RUT Bete, 23) AY SIR SN TE R/S ZA JQ MII E Yy 20-60°C, PLUE30-SO°C: KOMP URIS. EE HE 4WO 20131067666 PCTICN2011/081856 AE. BEEN, AE IRA) BTS CHE EE 1 Tk J /DMSO, BF Ha EU ERE, UAL NR A A BE Re BRA BLN AAC HHL FRR A PAARL, EAR RR EK A, CHAR ADBU, PERERA. DEAR RNA: BN FA ES YAS HA HE Hy ER CME: BPM Jy 20-80°C , JLi50-70 fcr etki, RS) RMR NER, RAR, Be ERC RN BNE RUC HY / TE Ak A UE (= % I FR AR LO 2-3: O.8-1.2: 1), KALI DMF; RIE I 60-120°C, Heit 80-110°C.. BUENA, 2 FRO) JIT RI METER PP A aR PRK BL. CR KE HOB TORTI, UC ARAB KAT ARR, ME FRE AA, OL Es QAR 10-50°C, hi 25-40°C. FETE NSE ET RC) OER, 2 RL BAY SQ INHER EE 20-80 Cs BENITA YE A LIA TA: AP BRZ) AY NERA Dy Fs JQ INA 0-5°C BONER A RICE Fils 20 R39 201k BSA WA AR ZARA, RINE 9 20-60°C s BRD PA THN BE Rs APRA) ITE AYE 2 (dG le DMSO, BY AN SR FRR, AC RH RSL He A, RN RAR A REN KAR, TORK, PPAR AA, = ZK MADBU; MYA MPA HEA ZINE IY 20-80°C; AE HRS) MY RMA RAY, ROYER DMF; (ZNEMAKE 4 60-120°C; LAA WR) FO Ea EI BRE AR EAE OR AAC PAL GP A A I BOR SAM; SQ DMPA TA RSA FAs DMLHHLIEE 2 10-50°C CE EIA HY SE HE A NCL) BE HA Hs, 20> LZ PILE 9940-70 5WO 20131067666 PCTICN2011/081856 Cs KATA Mme; AFBE2) A BRN Aah a Ay FEES: PML IE HNO-5°C BRINE AU — SEs BR) ASH RE a AY TR J DRI CRAVE, RINE IY 30-50°C ; RMR FY HBR; 224) FT GSO BRE AA Hoe BR A HT RRL ACP: ME HA APE ZANE: BE RMYERIE y 50-70°C s HFRS) (1 SQ DAA HH Dy EE al AL, BREE RUE RITE Ak SC SRL le A SP Ti 1 RE ASH 2-3: 0.8-1.2: 1, KEM MEYDMF: KONIAE80-110°C: LL RA FRO) Fp HAS 1 BRE AE a aR AC A HL FER: NA Ts SQW EN 25-40°C TEAS RY SB — Fe Md» BER A HFS AR ET Ta TL, FX(VD Siar: Py, g H “oN eo pro * “< vi ° TUX ARR, PLN RUBS POURRA, DER Dy Me A BRC cbt AE BE, HENLE Ay SAS ES RE SAE ae = ELEM s Py ACETAL AIC eH EAE . IF ATA K-CS-R, FEPRAC aed: PN AE. = SCE SP AS DE JER-CS-R, HORA HE. CE SE AEH, XL: Py SAB EE SEPT AE: Pa FATE AE act FF RAIL AE fe HE Se Ht, XA UI PLA SAE, Pay FP EAE OAT OEE. CAR BOG HFT, BEML AR HH AEN PH, tL ROMA:WO 20131067666 PCTICN2011/081856 Pa Q4 meee I TRH, XO PERS, HRC: PLU FEAR ARA IE, PR Dea BEC AcE BE, HEIL Ay SAS AE, Re SCARE ae = FELT 5 CePA SE TA, XN LSP SAB SE 2k = EPA. HE OE HY HME HX Dy SUR PLD SAS FE BG NR She As Be WA EI IG 35 BY RE 7° AG” S°=- ERA, WT ABE FSFE HEI MCS, BN Dy 28 TY AA Cee eee CEA DAB T, BRAT SEABED, A RARER ACT FR A EI PRAT RARE GE AT UAE PNT BAR TD SET fh BE FLAS, HUTA CE DEW BHP re TEE EHR, RTD. EI PE AIRY TEAL 2 Ja BRAS HS IME Ty DA BE RAS TAF AE BLAS 5 UAL AU BER SAI “AB” Ze aR A AIBIAIIN 48 46, ‘BL FR” 2 as Vn Fs eA AN,“ TW Se Jk/DMSO” AAR TALS ARH ihe AMDMSO; “ft RUC, Bot UAL A/F AK SL HORUS” RANE RCE, BoP TA A AR. FE KS MR. “TAS Cie” Rael A a AM ZI TP AE ER ASE HAE, Ee RAR AC] BAR, RES ASL FAS a8) AS Ae BD TAS FAN PR A AS Be FS i aWO 20131067666 PCTICN2011/081856 ATEN BA PEI TIE, HH i PUTER ARE. RAE Sh EO, ATMEL oP LEA fh Bete EB SE Sti FRE -2°- 26 TF (9 ad SAB HE ZH HOM A 300ml Be, 2-8 ITY (500g, 0.16mol, Se er » SFRAES A be 0.19mol) . Fik760'C, TOF ERR RE RMA. INA TRE AL IN RUE RAS HBR ons F 600m be Hh, FAR UEER QIK, FOAM THR. WE, WURRAET. AB) 100g 4.3L VRARTA HK. "H-NMR: 6 1.43(s, 3H), 3.03(d, 1H), 3.45(d, 1H), 3.58(d, 1H), 4.28(s, 1H), 4.49(d, 1H), 4.64(t, 1H), 6.26(d, 1H), 7.28(m, 3H), 7.36(m, 6H), 7.38(m, 6H), 7.57(s, 1H), 9.56(s, 1H) 5 =A FH AE -3 °F PEED” EF A il iF MA 40m BE, 57S HE HILO AF (10.0g, 0.018mol) » He AEO'C. TAME SP HI AREAL SC (2.0m1, 0.026mol) Ail4miilt ie, #57) HEART S°C 6 TLORR RRR RL DY, FEA» WRAY. TERMI GA AR. GR EL AB th eT CCRC: IE be=1 2), ABA BM. Ilt#. "H-NMR: 8 1.43(s, 3H), 3.16(s, 3H), 3.50(d, 1H), 3.63(d, 1H), 4.55(d, 1H), 4.70(t, 1H), 5.55(m, 1H), 6.26(d, 1H), 7.36-7.48(m, 15H), 7.57(s, 1H), 9.09(s, 1H). SR FA AE-3°— FEE DF El Se FE bik PA SOml RE, 15 gi FAR, 2.0m1=Z Hi, HR PIAA. BPE F FP 240°C, TLORER RELI & TAL. THUS, WIR HART. TERA AR GR BH EERE AE PRM. Ma (CRGAR IER b=A1> 3), BIA {lH fk. 'H-NMR: 6 1.43(s, 3H), 2.45(m, 1H), 2.65(m, 1H), 3.03(s, 8 TEAWO 20131067666 PCTICN2011/081856 3H), 3.48(m, 2H), 4.30m, 1H), 5.39(m, 1H), 6.400, 1H), 7.28-7.38(m, 15H), 7.56(s, 1H), 8.65(s, 1H). 5° SK FY BE-2,37 JE AR AEF 1 6 Li BR BH HP MA SO FARE Sm RAT ie FR AN AC PAE SJ PASTEL TL» TLOSR BR RSL IN TE Jai» BEA 40°C ai FR RAHA HH BK. SRM IMA 2m, HH GELOOMIA AIL, AIA BLA. FBLA AY 0 Oe th ak FARRAR. UE. UHR WRT T. 4 B18.08% 1 FIR PR, WC 395%. 'H-NMR: 6 1.90(s, 3H), 2.35(m, 1H), 2.64(m, 1H), 3.38(m, 2H), 4.28(m, 1H), 5.13(m, 1H), 5.45(d, 1H), 6.81(m, 1H), 7.30-7.48(m, 15H), HR AA -3 7 EY A ld FHI A2SOmI DMF, #2K4 (19.0g, 0.39mol) KC EWAY (60.0g, 0.13mol) , Ft it 78 100°C ALIN GEA J» o HE PERE EAE A S00mIAK , HATER ARSAT IR 2 5 HH, BIR FIRS $62.92 IAM, e3896%. 'H-NMR: 6 1.55(s, 3H), 2.48(m, 1H), 2.66(m, 1H), 4.18(m, 1H), 4.31(m, 1H), 4.58(m, 2H), 6.20(m, 1H), 7.15(s, 1H), 7.25-7.36(m, 15H), 8.83(s, 1H). FS REN BESEF I A 250ml FBR 5?- = 48 AE -3 9-4 LAF C50. Oe 0.098mol) A2mIyK ALAR, BUF s Arh, MAO 8g2h FC PAE Ik BLY 6 Bei 8 Ry We MA25OmUK, JNARAE7S'C, HEHE LANIS « LE HE BRAS ANA VERE. INAZ00mI ZH NEMA. A AROO'C BBE, IEA EK AP, 4 H265¢ RABI. Ah A i th 49 BU Ey 99.8% FES KE 248g, WC 3E 95% MS: m/z 267 (M*) «WO 20131067666 PCTICN2011/081856 Se HEB 2 SAE DLE E-2°- RW EF 0 Hl Si FE DAP A 100m Mk we, 2?- SW EF (14.0¢, 0.052mol) . ‘HEAR AESL (8.0Oml, 0.065mol) - Fifik#40°C, TLC BALERS DEL SE RBI EAE WAKE AE IRIN 5 DR SEB BL ARs HER DA HEF 200ml — SH EH. FAR BERRI, TE A Wa Bt LOWE, WUE YRMIAEP. 7 BI18 078 11 WIA. 'H-NMR: 6 1.20(s, 9H), 1.45(s, 3H), 3.41(d, 1H), 3.62(t, 1H), 4.14(s, 1H), 4.36(d, 1H), 4.53(t, 1H), 5.02(m, 1H), 6.19(d, 1H), 7.56(s, 1H), 9.47(s, 1H) 57-5 DR EAE-3°- FF BDA -2 SA EF 0 hl KONA MA SOmI— aR KE, 18 eH IKI HE, BEE EAR, VARY HIARO'C . ALIN GD AIA RAL (4.8m, 0.062mol) AMLOMIMML GE, PE MEARS Co TLOSRR ROS BON SE Js ENB HA A 30m td AL FR A AACA UE SSRIS 5 ALL Jee i ee 8 DH GE, GR YD EL BEBE AF 2G 2 SR DPE AE-3"— FFE HE Ha TF Hl Se ii P Ze LIRR HH A 100mI HAE, 1.8g S%O fe, EHR 44 (S5.1g, 0.062mol) . Het. HAR PIBAR. TLCR RS. Ke VCP aba. HE, WURIRAIE, ERP ER, 74 B14.7¢ PERT CAIM AE, I—4870%. 'H-NMR: 6 1.18(s, 9H), 2.05-2.20(d, 2H), 2.35(s, 3H), 3.15(s, 3H), 4.05-4.25(m, 2H), 4.55(m, 1H), 5.05(m, 1H), 5,46(m, 1H), 7.45(s, 1H), 9.28(s, 1H). 5° BE RE AE-2,3°— ABE AA EE OH FE BRIN BE AA S55 SD RE 3° FE EE EF 10.08, 0.025mol) » 75mlGBZ, 1 Sm tty ABE RANK AE nd 2 Lt TLE Ba i Arlt WER AE40°C, WFR IRATE HH BAAR. HRY MASOMUR, HARP ETSI SKA, A TRATBLA. AP BLA 10WO 20131067666 PCTICN2011/081856 FAAP ER ARERR, TOA EE. LTB. URW HR MAE 49 5)7.0g 25 4 (1M PE HL AH. WC 91%. 'H-NMR: 6 1.18(s, 9H), 2.05-2.20(d, 2H), 2.35(s, 3H), 3.45(m, 1H), 4.05-4.25(m, 2H), 4.48(m, 1H), 4.55(m, 1H), 6.48(s, 1H). 5° DR BD 3°- ENTE (0 Hl Be BPE PK HUM A 320ml DMF, 2G (4.5g, 0.069mol) , LSghK SUH (15g, 0.035mol) , HL (15g, 0,028mol) , S°HRE RPE IE-3? 2-H AK EWEY (5.0g, 0.016mol) , Ft ik 28 110°C KM. TORRE RMA, SRR, ERY. BEE Be StS ASOmiK, TUTE HRRIT IR 305 Hh. HME, BERL PRBS. 12 BEET A, CH 91%. "H-NMR: 8 1.20(s, 9H), 1.68(s, 3H), 2.10-2.30(m, 2H), 4.15(m, 1H), 4.28(m, 1H), 4.47(m, 1H), 4.54(m, 1H), 6.18(t, 1H), 7.19(s, 1H), 8.3%(s, 1H). FBR FEA Hl BEEK OA 6Sml FIRE 5°~ 485 MR AEE -3°- RLY 50g, 0.014mol) , 6.5ml 25% Ht AHN AY FERRER, Fk PEEL SIN. TLC PRE UR: ME a. ASR LER CDowex 50-200%8) All VApHA64e A, REELING, HERES. APU, HEE RR MBE FRR ARE AE BU ENS 1 6 TE A Se A, AL EO 99. 5% FFE KiE3.2g, WAE86%~ MS: m/z 267 (M") « Se hi (913 ak FA = FELT AE ~2”~ SAL EF 1 Hl 2% Se Yi P CE BQ DY HH DO A200 mt BE , 2-4 TY (50.02, 0.18mol), FIER GE (60.0g, 0.21mol) . FRAO0'C, TLOW RE GUS RITES. WAN. HK ROC, TATU RES (16.5ml, 0.22mol) , Fi RABE TSC. TLOF EE! FEAT >» WAAR IE BIN RFR SAE HH BA 1000mI = GET. FY fe HRA VEU. TEAK Bi RR ER. iWO 20131067666 PCTICN2011/081856 NT, FSI 10g 4 CIB VRARTA (S. 'H-NMR: 6 1.41(s, 3H), 3.15(s, 3H), 3.50(d, 1H), 3.63(d, 1H), 4.53(d, 1H), 4.68(t, 1H), 5.54(m, 1H), 6.25(d, 1H), 7.35-7.45(m, 15H), 7.51(s, 1H), 9.06(s, 1H). Se HABA 5°- = FA AE PUPAE -3°- Zi PAE -2°- SR Hd RF 4e A 100ml = Fe, 2°-SUW EY (14.0g, 0.052mol) » = "PIEPER (8.0ml, 0.065mol) , 1OmlritGE. Ft HAA40°C, TLORRR MAAR RM IEE. HMAC, HAL BEER (3.0m1, 0.042mol) » Heil RIMABEKRT 15°C. TLR ER SDL TE IG RIAA 3 Om td 1 Be 0 A A AE AS I BC DN Hi FR HR Le SSE, REN ERE AB 2 2M. TH-NMR: 6 1.03(m, 9H), 1.12(s, 3H), 1.33(m, 2H), 1.45(s, 3H), 3.39(d, 1H), 3.60(t, IH), 4.12(s, 1H), 4.34(d, 1H), 4.52(¢, 1H), 4.95(m, 1H), 6.16(d, 1H), 7.52(s, 1H), 9.31(s, 1H) 5°- = FADE PA EAE -3°- 2. Hi EAE HF OD Hl SA FE BR PMA 100m AE, 2g SMM, AGAR #4 (6.0g, 0.073mol) , Pitt, MIE PIAA. TLOR ER UR Wise a GEA ANTE, UR IRATE. PE RAR EL TEBLA PP RIM 57S ASE EAE-2,3° 1h AK EF A CED RP IMA L00mIZ Iii, FRAIREF (8.6g, 0.062mol) , INSEL Y TLR ER BUR RITE Jai, WE AR4O'C, WR RA RAR. RM IMA SOMA, HE SUA GE100mI Fy 32K ARI, AE FBLA. FT PLAN AMO AN Ee BR ABEL, FEAR IR ERP 1B, Ue BORER, SIT. 12 IR. TH-NMR: 6 1.01(m, 9H), 1.95(m, 2H), 2.01-2.15(d, 2H), 2.31(s, 3H), 3.43(m, 1H), 4.01-4.15(m, 2H), 4.45(m, 1H), 4.53(m, 1H), 6.50(s, 1H) 12WO 20131067666 PCTICN2011/081856 5° FE PA PUES -3 Bb EF Ol DUPE F REIN ABOmI DMF. L7H (65g. 0.10mol) . t 2b 7 ah DMF LOmI¥ i, BEES Fh AE 110°C BEIM.» TLS Be BRL WotR, ORB, BRAID. BEEF HY ENE A 80m TK, WATEIGAREEAT A Wt. HE, BORER AF 5.6958 £6 IAI HE. 1H-NMR: 6 1,05(m, 9H), 1.58(m, 2H), 1.62(s, 3H), 1.75(m, 1H), 1.88(m, 1H), 2.12(m, 1H), 4.05-4.15(d, 2H), 4.17(m, 1H), 5.35(m, 1H), 7.53(s, 1H), 9.67(s, 1H) FER EN BAER MA GSmIF BE, 5° FF METAR AL-3?-e RUIN TT (5.08, 0.014mol) , 6.5ml 25% FF BEANE ABE, SC PAPEL kh. TLO FER ORL 2 SEA, FARR YE MEI Dowex 50-200%8) ‘Al, WApH®62e47, AUCH, TRRDERR. API. TATE BEE RHR MAB PENS 1 C6 TB PP A ah, AF BA HE 99%WIF & KE 2.280 MS: m/z 267 (M+) » AEA BE DHE BRA IT AT SCHR A LEAST SFL fe > DT Es SCR AG TE BSS TE Hh AR, ZEB BET AS BWA ER PE ZI, ATRL AA AT AT AR Be HL HE fh BABE, FX BETTE SUA] PEGE FAS HT PT BS A A BE RH IT YelHl.WO 2013/067666 PCTICN2011/081856 1. RFE KENT TIE» TS TT EH Fb 1) EA2?- BO AUR ORE, IES fire EET RA, 79 BK CD eM: 2 XD HAMA AEE BI CVD ha: DK VD KAMA AGAR UIDKAD: 4) 0 CID (eR AIG AI IV Kaw, 5) Xk CV) LAMA BAIC RMA AIR CV) A: 6) CV) He WI BERD FS BITS Ke; FLARE BIN SR UR: BUT: XA Rs PLVPIER PIE: PLC beat EAE. FNC eI. 77 PTEIER~CS-R, JER YC abd. 2. MUA BER LTR ATI, SORTECE TD) XN GLBRYL: Pye SR TGES p SU AAG = EPPA, Ply A Se BE, MAURIE RL-CS-R, TPR HUGE. 3. WBA BORA PTB IN TT, SONIRAET. Beat st (WD HAMAR (UID CA WARE 1 ABET FG I, SEL — habia. 4. WAR UTE AIA, TORECED, eK (EA 14WO 20131067666 PCTICN2011/081856 DX VD CAMARA DRL BS PET BH Wi, SOL — a TS 0 5. WUBI BER PTB TE, SORMIECET » BTR ISAT DAE SWAMI Hy Oh AE 2 BR 1) D2 PEAR HOTT UR, 4G SAR ES Ae, APB S?- SFR UE-27- pa 5 2) 57S FR FA L-27— AE ZB 3~ 07 FTE 1 8 9° = EPH -37- FE LAE -2- Pa HEF s 3) 57-2 FR FBE-3 = FPR SIE -2 = a HEB A IE BS? SS FAE-3°— FUG BE SiS AE A) 57-98 RE-3°- FE DP CECH ZB EP BR BSS FS FUIE-2,3 7° ACE, 5) 57S FR IF HE-2,3 BL A INF EZ BL ZI BS SE -3 BAI 6) 5°- =A FG AE-3°-Bh ET CE PTE RPP BR 9 BSH 6. WALA BERS TM IIA, FONRMIECET AHR) ASRS E Hy 20-80°C 5 BEIM Fi Hal ME AT DLA as BRD) RMA TER: AEA 0-5S'C, BOE AI a ACEH ADRS) YAIR ARN TE R/S AA, BNE F420-60°C BaP Fy BPS HI AE URAD (TNE & PFE A hae /DMSO, AP AY SR EE PBL AUC BN Cal ALAC EY EE, RN HR we FARR. PR A, OR AC, = Z eae DBU; Az) fl MPSA As NAM EE 20-80°C; URS) WLR RW, BAY DMP; Be pata Fy60-120°C; LAR BORO) TTR MRE AR PE A BPR AK HL. ERR KR 15WO 20131067666 PCTICN2011/081856 BOT HY OSI: BEDS BRAIN: | BQ DNCIEL IEE Ay 10-50°C 7. MOA BERS PBN ATE, TORIEET AG BRLD AY SEINE 40-70°C ; BEIN.PAE FAY ML Es BRD) RRA ERs AEA 0-5°C, BRINE A yl bes ADRS) YAIR ARAN TE R/S AA, BNE Wy30-50°Cs BEIM IR AU HIME: BE DRA) SIT SA TNO ZR AEH A BRN. PRR PR aN PRT Ek is ETA ZW; SQM 50-70°C ; BPRS) UN BRR SD ae IG HL, BR ER RA JE IK SA HL ACE A SAF ZA TEAR LE 2-3: 0.8-1.2: 1, ROLEAYDMF; WIRE 80-110°Cs DLR VEO) TTR NYRR EE ARF Ha AR Hk HT SIR, SCE FAME: Sz WAH DBE 9 25-40°C 8. que thd Tay WOE RVD Si AR: Py mt SUX BOR: PUPP SE: Pedic REAGAN. FAHY Cate RSE. FHAEMAERK-CS-R, HR AC shed. 9. WAR AUSE OR ZA IAR AS TH, SORE IEAET XW SBR: Py Oy SRE, ORE DU PULAE Bk = FARE DUBE, 2 Jo FEILER FA A Wise. 10. WU AUBERT AH Ta A, DORRMILET XW LB: PL a SR GE Py FTES Bled FAS DEAEInternational application No, INTERNATIONAL SEARCH REPORT PCTICN2011/081856 CLASSIFICATION OF SUBJECT MATTER See the extra sheet According to International Patent Classification (IPC) oo both national classification and IPC B. FIELDS SEARCHED “Minimum documentation searched (classification system followed hy classification symbols) IPC: COID 405/-, COTH 191 Documentation searched other than minimums documentation to dhe extent that such documents are included in the Fels searched lectronie database consulted during the intemational search (name of data base and, where practicable, search terms used) EPODOC, WPI, CNPAT, CNKI, STN-CAPLUS, STN-REGISTRY: shanghai distinuo chemical pharmaceutical co Itd, shangha isainuo medical de c0 ld, zidovudine, azido, deoxy. thymidine, azidothymidine, AZT, AIDS methanesulfonyl,30516-87-1 ©. DOCUMENTS CONSIDERED TO BE RELEVANT sry" Citation of document, with indication, where appropriate, ofthe relevant passages X | CHEN, Bang-Chi etal. A new Syathess of the Anti AIDS Drug AZ from 5-Methyluridine 10 y | Tetrahedron Letters, 1995, Vol. 36, No.4, pages 7961-7968 io see pages 7961-7962 X | HUANG. Jai-Tung etal. Huorinated Sugar Analogues of Potential Anti-HIV-I Nucleosides, S10 y | Journal of Medicinal Chemistry, 1991, Vol. 34, No.5, pages 1640-1646 o see page 1641, scheme Mand page 1642 scheme I, page 1644 let column the third parigriph snd eight column the fourth paragraph 1 Further documents az listed in th continuation of BoxC, See patent family annex. later document published after the international filing date ‘or priority date and not in conflict withthe application but cited to understand the prineiple or theory underlying the + Special categories of cited documents ‘A document defining the general state ofthe art which is not considered to be of particular relevance invention -arlier application or patent but published on or after the “X" document of particular relevance: the claimed invention intemational filing date anol be consieed novel or cannot be considered to involve tn inventive step when the document is taken alone “Y" document of particular relevance: the claimed invention cannot be considered to involve an inventive step when the citation or other special reason (as specified) document is combined with one or more ater sich “0” document refering to an orl disclosure, use, exhibition or documents, such combination being obvious a person shill in the art 1L® document which may throw doubts on priority claims) or ‘which is cited to establish the publication da of another other means “P* document published prior the international filing date “&"doeurent member ofthe same patent Fai but ater than the priority date claimed Date of the actual completion ofthe intemational search Date of mailing of the international earch report, 12.un,2012(12.06.2012 12.1, 2012112072012) Tame and mailing addres of the ISA State Inellectual Property Office ofthe P. R. China No.6, Xitueheng Road, Jimengiao WANG Mingzhe Heidian District, Beijing 100088, China scsimile No, (8610362019451 ‘Authorized officer Telephone No. (86-10)82246726 Form PCT/ISA F310 (second shoo) (uly 2009)INTERNATIONAL SEARCH REPORT. International application No, PCT/CN2O11/081856 (Continuation of: A. CLASSIFICATION OF SUBJECT MATTER COTDENS/N4 (2006.01) 4 (€07H19/06 (2006.01) 1 Form PCT/ISA 210 (extra seed) uly 2009)as FP eS BRAG BR PCT/CN2011/081856 A, EMAAR SAA INE HH Ee Al 5} SSUPC) sh # ALIN HAGERTY ALAC PENSE BAG ee ACR WO IS REAP IS) IPC: COTDADS/=, COTHLY/- ) 2 cE Hee Re ARE SCHR A SP CHR Anse Ls FAH CA PEP, AMET AH] CU FELD) lEPODOC, WPI, CNPAT, CNKI, STN-CAPL TRY: HHA, HA, BUA, OAT, BRUNET, MOTE, Bit, Est] ase ARL AAT, La REMC A, PHT, ridowudine, azide, deoxy, thymidine, _azidothymidine, AZT. AIDS, methanestl fony, 305 CEE x Ms SUSCPE, QR, SORA BEI RATHER X __|CHEN, Bang-Chi cal, A New Syathesis ofthe Ant-AIDS Drug AZ fom #10 YY _|5-Metiyluriine, Tetrahedron Letters, 1995, Vol. 36, No, 44, pages 7961-7964 a ls 88 rao1-7902 3 X HUANG, ta-Tung eat, Fluorinated Sugar Analogues of Potential Anti-HIV-1 en YY }Nucteosies, Journal of Medicinal Chemisty, 1991, Vol. No, 5, pages 1640-1646 = [5058 1641 GUBE PH EE TT JRA 1642 GC SEPKERTIT, 38 1644 GEARS 3 Be ATES nae 0 secrete cH meRTOH INA. Opis usn et + SLAC PR MSA “T” {EA ARHRALA Zia ts. SEAR, YT SAP DARE HR ARENT BAT BR ARATE FRNA ZI ia IR AEE CE SE ADR ANE TIER AL “xX? ROWADRINICEE, SUBAREA HD “LY PIRERT HEIGL RRR EH CPE, NE 5 — BRAS ET ARS PA aE HE SUF SCA ats EG 1 FD I TT Y" HRA, SRC HS AIEEE FRERSIC A COT EL SE BH SET PPS RE A TAA TL “O" DRAKA. (EAL, EAR R ATF CTE BRR HY RAR AA NE PEA FRA ELE TRRERMIMERLEMDCRE “e” PALE RE sem A ee a A 12.6 FJ 2012 (12.06.2012) 12.7 J 2012 (12.07.2012) FTSA/CN (19-22 Be AU 25 Hk: PERCE Bi FA BRS A TPS me SA Seo Ha GT HPP RH 6 % 100088 EM? HEM: (86-10)62019451 PLIES: (86-10) 82246726 PCTISA/210 48(98 2 HL) 2009 4.7 H)nie RRA bn PCT/CN2011/081856 She A, 218 COTDAD5/04 (2006.01) 1 COTHI9#06 (2006.01) PCTISA/210 (LINE) 2009 4 7H)