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 2074179Notes

Reaction equation

HRID 2074179 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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)+.

Workup

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

Sources & evidence

ORD record
ord-68fa897864304a22b78ec3b134da0787
Source dataset
uspto-grants-2011_04
Patent number
US07919490B2

Reaction notes

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