p-Toluenesulfonic acid → 2-(6-chloro-1H-benzo[d]imidazol-1-yl)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

HRID 600410Notes

Reaction equation

HRID 600410 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[NH:9][C:10]1[N:18]=[C:17]2[C:13]([NH:14][C:15](=[O:25])[N:16]2[CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[C:12]([C:26]2[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=2)[N:11]=1.[CH3:32]OC(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[CH:32][N:9]([C:10]3[N:18]=[C:17]4[C:13]([NH:14][C:15](=[O:25])[N:16]4[CH:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[C:12]([C:26]4[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=4)[N:11]=3)[C:3]=2[CH:4]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 670595852-(2-amino-5-chlorophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

Product 1

HCID 248310082-(6-chloro-1H-benzo[d]imidazol-1-yl)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-oneYield 18%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a vial containing crude 2-(2-amino-5-chlorophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one (0.015 mmol) was added anhydrous methanol (2.5 mL), followed by anhydrous trimethylorthoformate (0.5 mL) and p-toluene sulfonic acid (1 mg) 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 (1.2 mg, 18% yield on two steps), as a yellow solid. TFA salt. 1H NMR (300 MHz, CD3OD) δ, ppm: 9.18 (s, 1H), 8.83 (br m, 2H), 8.71 (s, 1H), 8.07 (br m, 2H), 7.76 (d, J=8.6 Hz, 1H), 7.41 (d, J=8.9 Hz, 1H), 4.76-4.72 (m, 1H), 4.26-4.23 (m, 2H), 3.66 (app t, J=11.5 Hz, 2H), 2.90-2.87 (m, 2H), 1.91 (br d, J=12.8 Hz, 2H); MS (EI) m/z 448.3 (MH)+.

Workup

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

Sources & evidence

ORD record
ord-7a556b47185844c495ed207637bcc8dc
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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