6-cyano-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide → 6-(aminomethyl)-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

HRID 85470Notes

Reaction equation

HRID 85470 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:6]2[CH:7]=[N:8][N:9]([CH:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:10]=2[CH:11]=1)#[N:2]>C(O)(=O)C.CO>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:17]([NH:19][CH2:20][C:21]2[C:22](=[O:29])[NH:23][C:24]([CH3:28])=[CH:25][C:26]=2[CH3:27])=[O:18])[C:6]2[CH:7]=[N:8][N:9]([CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16]3)[C:10]=2[CH:11]=1

Participants

4

Reactant 1

HCID 545972996-cyano-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Product 1

HCID 545973006-(aminomethyl)-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

6-cyano-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.10 g, 0.257 mmol) was suspended in acetic acid (8 mL). The contents were placed heated at 40° C. under an atmosphere of hydrogen (50 psi; H-cube reactor) at a flow rate of 1 mL/min with recirculation 2 h. Then contents were diluted with MeOH, concentrated in vacuo, and dried under hi vacuum for 18 h. The crude product was dissolved in DCM and purified by silica gel chromatography (eluent: 10-100% gradient of chloroform (containing 10% 2M ammonia in methanol) and dichloromethane. The product was concentrated from MTBE and dried in a vacuum oven at 45° C. for 4 h. The title compound was collected as 68 mg (66%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.75 (m, 2H), 1.82-1.93 (m, 2H), 1.94-2.04 (m, 2H), 2.06-2.17 (m, 6H), 2.21 (s, 3H), 3.85 (s, 2H), 4.35 (d, J=5.05 Hz, 2H), 5.14 (t, J=7.07 Hz, 1H), 5.89 (s, 1H), 7.54 (s, 1H), 7.76 (s, 1H), 8.27 (s, 1H), 8.32 (t, J=5.05 Hz, 1H);

Workup

  1. concentrationconcentrated in vacuo
  2. customdried under hi vacuum for 18 h
  3. dissolutionThe crude product was dissolved in DCM
  4. custompurified by silica gel chromatography (eluent
  5. concentrationThe product was concentrated from MTBE
  6. customdried in a vacuum oven at 45° C. for 4 h
  7. customThe title compound was collected as 68 mg (66%)

Sources & evidence

ORD record
ord-591850fcdf8443c4a11ff7cd2ba34bdb
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

Loading…