Cesium carbonate → 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 246284Notes

Reaction equation

HRID 246284 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.Br[CH:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:40]([O:39][C:37]([N:34]1[CH2:35][CH2:36][CH:31]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=3)[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]2)[CH2:32][CH2:33]1)=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 15541517tert-Butyl 4-bromopiperidine-1-carboxylateHCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 866779724-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl esterYield 41.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (182 mg, 0.44 mmol), tert-butyl 4-bromopiperidine-1-carboxylate (234 mg, 0.89 mmol), cesium carbonate (432 mg, 1.33 mmol) and DMF (2 ml). The vial was flushed with argon, sealed, and heated in a microwave reactor at 100° C. for 2 h. The reaction was quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc to give 108 mg (41%) of 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester as a light brown solid.

Workup

  1. customThe vial was flushed with argon
  2. customsealed
  3. customThe reaction was quenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient

Sources & evidence

ORD record
ord-503e43106d8c4b6e8e10a647ee6d4ab5
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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