(Trifluoromethyl)trimethylsilane → HCID 11534251, compound

HRID 2100411Notes

Reaction equation

HRID 2100411 reaction equation
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH:11][C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[NH:20][CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]([N:31]4[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]4)=[O:30])[CH:23]=3)=[O:13])[CH:7]=[CH:8]2)=[N:3]1.[F:38][C:39]([Si](C)(C)C)([F:41])[F:40].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH:11][C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[NH:20][CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]([N:31]4[CH2:32][CH2:33][C:34]([OH:37])([C:39]([F:41])([F:40])[F:38])[CH2:35][CH2:36]4)=[O:30])[CH:23]=3)=[O:13])[CH:7]=[CH:8]2)=[N:3]1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 57798921HCID 57798921, compound

Product 1

HCID 11534251HCID 11534251, compoundYield 9.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-oxo-piperidine-1-carboxylic acid (4-{[2-(2-methyl-2H-indazol-6-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (140 mg, 0.28 mmol) in dry THF was treated successively with trifluoromethyltrimethylsilane (0.06 mL, 0.42 mmol) and tetra-n-butylammonium fluoride (1M solution in THF, 0.28 mL, 0.28 mmol). The reaction was stirred at rt overnight before it was partitioned between EtOAc and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on Isolute® Flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 10:1) to give 4-hydroxy-4-trifluoromethyl-piperidine-1-carboxylic acid (4-{[2-(2-methyl-2H-indazol-6-ylcarbamoyl)-phenylamino]-methyl}-pyridin-2-yl)-amide (15 mg, 9%) as a solid; 1H-NMR (300 MHz, d6-DMSO) 10.14 (1H, s), 9.21 (1H, s), 8.25 (1H, s), 8.15 (1H, d), 8.10 (1H, s), 7.95 (1H, t), 7.80 (1H, s), 7.72 (1H, d), 7.63 (1H, d), 7.23-7.32 (2H, m), 6.94 (1H, d), 6.66 (1H, t), 6.53 (1H, d), 6.02 (1H, s), 4.44 (2H, d), 4.07-4.17 (5H, m), 2.95-3.05 (2H, m), 1.55-1.63 (4H, m); m/z (ES+) 568 [M+H]+.

Workup

  1. customwas partitioned between EtOAc and water
  2. washThe organic phase was washed with brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by chromatography on Isolute® Flash silica gel (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 10:1)

Sources & evidence

ORD record
ord-8c5ed4bc4a134abf97b25be517797543
Source dataset
uspto-grants-2009_08
Patent number
US07572794B2

Reaction notes

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