Acetic Acid → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(2-methyl-4-(morpholinomethyl)phenyl)-1H-indazole-4-carboxamide

HRID 1909298Notes

Reaction equation

HRID 1909298 reaction equation
[CH:1]1([N:6]2[C:14]3[CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][C:18]([CH:21]=O)=[CH:17][C:16]=4[CH3:23])[CH:11]=[C:10]([C:24]([NH:26][CH2:27][C:28]4[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=4[CH3:34])=[O:25])[C:9]=3[CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH:1]1([N:6]2[C:14]3[CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)=[CH:17][C:16]=4[CH3:23])[CH:11]=[C:10]([C:24]([NH:26][CH2:27][C:28]4[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=4[CH3:34])=[O:25])[C:9]=3[CH:8]=[N:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 867034381-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-formyl-2-methylphenyl)-1H-indazole-4-carboxamide

Product 1

HCID 665510451-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(2-methyl-4-(morpholinomethyl)phenyl)-1H-indazole-4-carboxamideYield 34%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-formyl-2-methylphenyl)-1H-indazole-4-carboxamide (0.15 g, 0.31 mmol) in methanol (5 mL), morpholine (0.081 g, 0.93 mmol) and acetic acid (0.01 g, 0.311 mmol) were added at room temperature and reaction stirred at room temperature for 18 h. Then NaBH3CN (0.023 g, 0.37 mmol) was added and reaction stirred again at room temperature for 18 h. On completion, methanol was removed under reduced pressure and water added to the residue. The aqueous phase was extracted with 10% MeOH/DCM and the combined organic layers dried over sodium sulfate and concentrated to obtain crude material which was purified by column chromatography to afford 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(2-methyl-4-(morpholinomethyl)phenyl)-1H-indazole-4-carboxamide (34% yield). LCMS: 554.30 (M+1)+; HPLC: 95.54% (@ 254 nm) (Rt;5.595); 1H NMR (DMSO-d6, 400 MHz) δ 11.49 (s, 1H), 8.52 (t, 1H), 8.38 (s, 1H), 7.78 (s, 1H), 7.54 (s, 1H), 7.02-7.28 (m, 3H), 5.86 (s, 1H), 5.22-5.26 (m, 1H), 4.34 (d, 2H, J=4.4 Hz), 3.58 (t, 4H), 3.47 (s, 2H), 2.37 (s, 4H), 2.25 (s, 3H), 2.18 (s, 3H), 2.09-2.06 (m, 2H), 2.09 (s, 3H), 1.98-2.03 (m, 2H), 1.86 (m, 2H), 1.66-1.69 (m, 2H).

Workup

  1. customreaction
  2. customreaction
  3. stirringstirred again at room temperature for 18 h
  4. customOn completion, methanol was removed under reduced pressure and water
  5. additionadded to the residue
  6. extractionThe aqueous phase was extracted with 10% MeOH/DCM
  7. dry with materialthe combined organic layers dried over sodium sulfate
  8. concentrationconcentrated
  9. customto obtain crude material which
  10. customwas purified by column chromatography

Sources & evidence

ORD record
ord-050a3d3831fe45c4a65489c29b71a1e8
Source dataset
uspto-grants-2013_12
Patent number
US08598167B1

Reaction notes

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