Formaldehyde → N-tert-butyl-2-(5-(difluoromethoxy)-1-((1-methylazetidin-3-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246508Notes

Reaction equation

HRID 246508 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][N:6]2[C:14]3[C:9](=[CH:10][C:11]([O:15][CH:16]([F:18])[F:17])=[CH:12][CH:13]=3)[C:8]([C:19]3[N:20]=[C:21]4[C:27]([C:28]([NH:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:26][N:25]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:22]4=[N:23][CH:24]=3)=[N:7]2)[CH2:2]1.C=O.[C:45](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[C:31]([NH:30][C:28]([C:27]1[C:21]2[C:22](=[N:23][CH:24]=[C:19]([C:8]3[C:9]4[C:14](=[CH:13][CH:12]=[C:11]([O:15][CH:16]([F:18])[F:17])[CH:10]=4)[N:6]([CH2:5][CH:3]4[CH2:4][N:1]([CH3:45])[CH2:2]4)[N:7]=3)[N:20]=2)[N:25]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:26]=1)=[O:29])([CH3:33])([CH3:34])[CH3:32]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 712799372-(1-(Azetidin-3-ylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279599N-tert-butyl-2-(5-(difluoromethoxy)-1-((1-methylazetidin-3-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 87.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(1-(azetidin-3-ylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (37 mg, 61.7 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 (29.4 mg, 139 μmol). The reaction mixture was stirred at room temperature for 15 h then concentrated and purified by chromatography (silica, 4 g Analogix column, 0-10% methanol containing 10% ammonium hydroxide in dichloromethane) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-((1-methylazetidin-3-yl)methyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (33 mg, 87%). MS (M+H)+=614.

Workup

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

Sources & evidence

ORD record
ord-21cce788a4544d3b895d2a0bff2e1363
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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