Methanesulfonic Acid → 2-(6-chloro-1H-benzo[d]imidazol-1-yl)-8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purine

HRID 2074169Notes

Reaction equation

HRID 2074169 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH3:24])[N:15]3[CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:11]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[N:10]=2)[C:5]([NH2:31])=[CH:4][CH:3]=1.[CH3:32]OC(OC)OC.CS(O)(=O)=O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:31]=[CH:32][N:8]([C:9]3[N:17]=[C:16]4[C:12]([N:13]=[C:14]([CH3:24])[N:15]4[CH:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:11]([C:25]4[CH:26]=[CH:27][N:28]=[CH:29][CH:30]=4)[N:10]=3)[C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 9005Trimethyl orthoformateHCID 670596105-chloro-N1-(8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-yl)benzene-1,2-diamine

Product 1

HCID 461746802-(6-chloro-1H-benzo[d]imidazol-1-yl)-8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purineYield 22%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a vial containing crude 5-chloro-N1-(8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-yl)benzene-1,2-diamine (0.035 mmol) was added anhydrous methanol (2.5 mL), followed by anhydrous trimethylorthoformate (0.5 mL) and methane sulfonic acid (catalytic amount) and the reaction mixture was stirred under Ar at room temperature for 4 h (HPLC monitoring). Preparative HPLC purification, after evaporation of solvent and drying, provided the desired product (3.5 mg, 22% yield on two steps), as a yellow oil. TFA salt. 1H NMR (300 MHz, CD3OD+CDCl3) δ, ppm: 9.32 (s, 1H), 8.91 (br m, 4H), 8.79 (s, 1H), 7.78 (d, J=8.6 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 4.76-4.72 (m, 1H), 4.32-4.29 (m, 2H), 3.72 (app t, J=11.7 Hz, 2H), 3.08-3.05 (m, 2H), 2.87 (s, 3H), 2.02 (br d, J=10.9 Hz, 2H); MS (EI) m/z 446.3 (MH)+.

Workup

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

Sources & evidence

ORD record
ord-42bf6d2acc6f4f3e8990da1239e6a728
Source dataset
uspto-grants-2011_04
Patent number
US07919490B2

Reaction notes

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