Tert-Butylamine → tert-butyl 3-((3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-6-fluoro-1H-indazol-1-yl)methyl)azetidine-1-carboxylate

HRID 246527Notes

Reaction equation

HRID 246527 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([F:22])[CH:20]=3)[C:15]([C:23]3[N:24]=[C:25]4[C:31]([C:32](O)=[O:33])=[CH:30][N:29]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:26]4=[N:27][CH:28]=3)=[N:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:43][C:44]([NH2:47])([CH3:46])[CH3:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>CN(C)C=O>[C:44]([NH:47][C:32]([C:31]1[C:25]2[C:26](=[N:27][CH:28]=[C:23]([C:15]3[C:16]4[C:21](=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[N:13]([CH2:12][CH:10]4[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9]4)[N:14]=3)[N:24]=2)[N:29]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:41])[CH3:42])[CH:30]=1)=[O:33])([CH3:46])([CH3:45])[CH3:43]

Participants

6

Reactant 4

HCID 6385Tert-ButylamineHCID 7912DiisopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712801702-(1-((1-(tert-Butoxycarbonyl)azetidin-3-yl)methyl)-6-fluoro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280418tert-butyl 3-((3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-6-fluoro-1H-indazol-1-yl)methyl)azetidine-1-carboxylateYield 91.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1-((1-(tert-butoxycarbonyl)azetidin-3-yl)methyl)-6-fluoro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 251 μmol), 2-methylpropan-2-amine (18.4 mg, 251 μmol), HATU (105 mg, 277 μmol) and diisopropylamine (97.5 mg, 754 μmol) in dimethylformamide (12 mL) were stirred at room temperature for 15 h. The mixture was partitioned between ethyl acetate and water then the organic phase was washed with water then dried, filtered and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave tert-butyl 3-((3-(7-(tert-butylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-6-fluoro-1H-indazol-1-yl)methyl)azetidine-1-carboxylate (150 mg, 91.5%).

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. washthe organic phase was washed with water
  3. customthen dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e8c825a0b8fc4336a8ec5634d79afc22
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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