Trimethylsilyldiazomethane → HCID 86616863, compound

HRID 1373840Notes

Reaction equation

HRID 1373840 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:14]=[C:13]([C:23]([OH:25])=[O:24])[CH:12]=3)=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH3:33][Si](C=[N+]=[N-])(C)C>CO>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:14]=[C:13]([C:23]([O:25][CH3:33])=[O:24])[CH:12]=3)=[C:6]2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 167693Trimethylsilyldiazomethane2×HCID 10182484HCID 10182484, compound

Product 1

HCID 86616863HCID 86616863, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-(cyclopentylamino)-4-pyrimidinecarboxylic acid (340 mg, 0.752 mmol) in methanol (20 mL) was added (trimethylsilyl)diazomethane (376 μL, 2.0 M in hexanes, 0.752 mmol). The reaction mixture was stirred at room temperature for 16 hours. Excess (trimethylsilyl)diazomethane was added and the reaction mixture was stirred 3 days. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (49-1 to 29-1 dichloromethane-methanol) provided methyl 6-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-(cyclopentylamino)pyrimidine-4-carboxylate (45 mg, 13%). 1H NMR (CDCl3) δ 8.44 (d, 1H), 7.65 (m, 2H), 7.34 (t, 1H), 7.17 (t, 2H), 7.11 (d, 1H), 7.03 (s, 1H), 5.43 (br, 1H), 4.36 (m, 1H), 3.89 (s, 3H), 2.05 (m, 2H), 1.76–1.55 (m, 6H); MS m/z 466 (M+1).

Workup

  1. stirringthe reaction mixture was stirred 3 days
  2. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-b72959e6d0ce4d4998b560f41381ab51
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Reaction notes

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