Formaldehyde → 5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246523Notes

Reaction equation

HRID 246523 reaction equation
OCC([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](N3C4C(=CC=CC=4)C(C4CCNCC4)=N3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])(C)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[N:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:11][CH:10]=[C:9]([C:7]([NH2:6])=[O:8])[C:17]=12

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 71280834N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-(piperidin-4-yl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 866779755H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 198.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-(piperidin-4-yl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 177 μmol) in methanol (4 mL), cooled to 0° C. with an ice bath, was added 37% aqueous formaldehyde (1 mL, 13.4 mmol), followed by the addition of sodium triacetoxyborohydride (84.6 mg, 399 μmol). The reaction mixture was stirred at room temperature for 15 h then concentrated in vacuo. Purification by chromatography (silica, 4 g Analogix column, 0-6% methanol containing 10% ammonium hydroxide in dichloromethane) gave N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-(1-methylpiperidin-4-yl)-1H-indazol-1-yl)-5-(2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (57 mg, 56%). MS (M+H)+=578.

Workup

  1. concentrationthen concentrated in vacuo
  2. customPurification by chromatography (silica, 4 g Analogix column, 0-6% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-13decf215f994775ac81f8869aaf8328
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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