Formaldehyde → 5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246511Notes

Reaction equation

HRID 246511 reaction equation
C([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](C3C4C(=CC=C(OC(F)F)C=4)N(CC4OCCNC4)N=3)[N:15]=2)[N:10]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:9]=1)=[O:7])(C)(C)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:42][Si:41]([CH3:44])([CH3:43])[CH2:40][CH2:39][O:38][CH2:37][N:10]1[C:11]2=[N:12][CH:13]=[CH:14][N:15]=[C:16]2[C:8]([C:6]([NH2:5])=[O:7])=[CH:9]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 71279850N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 866779835-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 135.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(morpholin-2-ylmethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 159 μmol) in methanol (4 mL), cooled to 0° C. with ice bath, was added aqueous formaldehyde (1 mL, 13.4 mmol), followed by the addition of sodium triacetoxyborohydride (75.7 mg, 357 μmol). The reaction mixture was stirred at room temperature for 15 h then concentrated in vacuo. Purification by chromatography (silica, 4 g Analogix column, 0-10% methanol containing 10% ammonium hydroxide in dichloromethane) gave N-tert-butyl-2-(5-(difluoromethoxy)-1-(4-methylmorpholin-2-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (63 mg, 62%). MS (M+H)+=644.

Workup

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

Sources & evidence

ORD record
ord-95249ac262494d1782262f191e4d5874
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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