Trifluoroacetic acid → (R)-(3-Aminopiperidin-1-yl)(1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]-pyridin-2-yl)-1H-benzo[d]imidazol-5-yl)methanone

HRID 2275037Notes

Reaction equation

HRID 2275037 reaction equation
C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:39]=[CH:38][C:19]3[N:20]([CH3:37])[C:21]([C:23]4[N:31]([CH2:32][C:33]([F:36])([F:35])[F:34])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:39]=[CH:38][C:19]3[N:20]([CH3:37])[C:21]([C:23]4[N:31]([CH2:32][C:33]([F:36])([F:35])[F:34])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118178621(R)-tert-Butyl(1-(1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate

Product 1

HCID 73052773(R)-(3-Aminopiperidin-1-yl)(1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]-pyridin-2-yl)-1H-benzo[d]imidazol-5-yl)methanoneYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-tert-butyl(1-(1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate (1.9336 g, 3.47 mmol) in dichloromethane (DCM) (5.5 ml) was added TFA (5.05 ml, 66.0 mmol) dropwise. The reaction mixture was stirred for 45 min. The mixture was concentrated in vacuo, dissolved in methanol and purified by SPE on a pre-conditioned sulfonic acid (SCX) 70 g cartridge. The column was washed with methanol (5 CV) and the product was eluted with a 2M Ammonia in methanol solution (4 CV). The appropriate fractions were combined and the solvent was evaporated in vacuo to give a crude product that was purified by preparative HPLC (MDAP Method E). Appropriate fractions were combined and concentrated in vacuo to yield the title compound (1.35 g)

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutiondissolved in methanol
  3. custompurified by SPE on a pre-conditioned sulfonic acid (SCX) 70 g cartridge
  4. washThe column was washed with methanol (5 CV)
  5. washthe product was eluted with a 2M Ammonia in methanol solution (4 CV)
  6. customthe solvent was evaporated in vacuo
  7. customto give a crude product that
  8. customwas purified by preparative HPLC (MDAP Method E)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b80b03b4b41c4d758a678f66de409206
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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