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

HRID 246525Notes

Reaction equation

HRID 246525 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.I[CH2:31][CH:32]1[CH2:35][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH2:31][CH:32]2[CH2:35][N:34]([C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[CH2:33]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 53249943tert-Butyl 3-(iodomethyl)azetidine-1-carboxylateHCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 86677984tert-butyl 3-((6-fluoro-3-(7-formyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1H-indazol-1-yl)methyl)azetidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(6-Fluoro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (225 mg, 547 μmol), tert-butyl 3-(iodomethyl)azetidine-1-carboxylate (162 mg, 547 μmol) and cesium carbonate (534 mg, 1.64 mmol) in dimethylformamide (4 mL) were heated in a microwave at 150° C. for 30 min. The mixture was partitioned between ethyl acetate and water. Then the organic phase was washed with water 3 times, dried and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave tert-butyl 3-((6-fluoro-3-(7-formyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1H-indazol-1-yl)methyl)azetidine-1-carboxylate (202 mg, 64%).

Workup

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

Sources & evidence

ORD record
ord-c059302543d742f894e6819e730087eb
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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