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 2074179ノート

反応式

HRID 2074179 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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)+.

後処理

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

出典と根拠

ORDレコード
ord-68fa897864304a22b78ec3b134da0787
出典データセット
uspto-grants-2011_04
特許番号
US07919490B2

反応ノート

読み込み中…