Acetic Acid → HCID 68350975, compound

HRID 1909336Notes

Reaction equation

HRID 1909336 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([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:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[CH3:30][N:31]1[CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]1.CO.C(O)(=O)C.[BH3-]C#N.[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]([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:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH:34]4[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]4)[CH2:13][CH2:12]3)[C:9]=2[CH:10]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 887MethanolHCID 740491-Methyl-4-piperidoneHCID 5003444Sodium cyanoborohydrideHCID 68294878HCID 68294878, compound

Product 1

HCID 68350975HCID 68350975, compoundYield 24%

Procedure

To a stirred solution of 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(piperidin-4-yl)-1H-indazole-4-carboxamide (1 equiv.) and 1-methylpiperidin-4-one (1.5 equiv.) in methanol (5 mL per 0.3 mmol), acetic acid (1 equiv.) was added and reaction stirred at room temperature for 5 h. Then NaBH3CN (1 equiv.) was added and the reaction stirred overnight. On completion, the solvent was removed under reduced pressure and the residue purified by column chromatography (24% yield). LCMS: 555.15 (M+1)+; HPLC: 92.59% (@ 254 nm) (Rt;4.143); 1H NMR (DMSO-d6, 400 MHz) δ 11.52 (s, 1H), 8.60 (t, 1H, J=5.2 Hz), 8.35 (s, 1H), 8.24 (s, 1H), 7.68 (s, 1H), 5.88 (s, 1H), 4.63-4.68 (m, 1H), 4.32 (d, 2H, J=4.8 Hz), 2.97 (d, 2H, J=11.6 Hz), 2.79 (d, 2H, J=10.8 Hz), 2.22-2.40 (m, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 2.11 (s, 3H), 1.99-2.08 (m, 2H), 1.81-1.88 (m, 4H), 1.69 (d, 2H, J=11.2 Hz), 1.43-1.48 (m, 2H).

Workup

  1. customreaction
  2. stirringthe reaction stirred overnight
  3. customOn completion, the solvent was removed under reduced pressure
  4. customthe residue purified by column chromatography (24% yield)

Sources & evidence

ORD record
ord-d75bbfc11dc5465dbca24041e4a09756
Source dataset
uspto-grants-2013_12
Patent number
US08598167B1

Reaction notes

Loading…