Methanesulfonic Acid → 6-chloro-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purin-8(9H)-one

HRID 2074179노트

반응식

HRID 2074179 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C:10]1[N:18]=[C:17]2[C:13]([NH:14][C:15](=[O:30])[N:16]2[C@H:19]2[C:28]3[C:23](=[C:24]([F:29])[CH:25]=[CH:26][CH:27]=3)[O:22][CH2:21][CH2:20]2)=[C:12]([Cl:31])[N:11]=1.[CH3:32]OC(OC)OC.CS(O)(=O)=O>CO>[Cl:31][C:12]1[N:11]=[C:10]([N:9]2[C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[N:1]=[CH:32]2)[N:18]=[C:17]2[C:13]=1[NH:14][C:15](=[O:30])[N:16]2[C@H:19]1[C:28]2[C:23](=[C:24]([F:29])[CH:25]=[CH:26][CH:27]=2)[O:22][CH2:21][CH2:20]1

참가 물질

5

반응물 3

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 86622939(R)-2-(2-amino-5-fluorophenylamino)-6-chloro-9-(8-fluorochroman-4-yl)-7H-purin-8(9H)-one

생성물 1

HCID 576126986-chloro-2-(6-fluoro-1H-benzo[d]imidazol-1-yl)-9-((R)-8-fluorochroman-4-yl)-7H-purin-8(9H)-one수율 62%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a round bottom flask containing (R)-2-(2-amino-5-fluorophenylamino)-6-chloro-9-(8-fluorochroman-4-yl)-7H-purin-8(9H)-one (0.65 mmol) was added anhydrous methanol (45 mL), followed by anhydrous trimethylorthoformate (5 mL) and methane sulfonic acid (0.1 mL) and the reaction mixture was stirred under Ar at room temperature until it was complete (HPLC monitoring). Preparative HPLC purification, after evaporation of solvent and drying, provided the desired product (184 mg, 62% yield on two steps), as a white solid. 1H NMR (300 MHz, CDCl3) δ, ppm: 9.38 (br s, 1H), 9.01 (s, 1H), 7.84-7.79 (m, 1H), 7.64-7.60 (m, 1H), 7.20-7.13 (m, 1H), 7.10-7.03 (m, 1H), 6.79-6.67 (m, 2H), 5.97-5.92 (m, 1H), 4.68-4.62 (m, 1H), 4.51-4.40 (m, 1H), 2.95-2.83 (m, 1H), 2.41-2.36 (m, 1H); MS (EI) m/z 454.9 (MH)+.

후처리

  1. customPreparative HPLC purification
  2. customafter evaporation of solvent
  3. customdrying

출처 및 근거

ORD 기록
ord-68fa897864304a22b78ec3b134da0787
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919490B2

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