Acetic Acid → 3-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(morpholinomethyl)pyridin-3-yl)benzamide

HRID 1616395Notes

Reaction equation

HRID 1616395 reaction equation
[CH:1]1([N:7]([CH3:36])[C:8]2[C:9]([CH3:35])=[C:10]([CH:24]=[C:25]([C:27]3[CH:28]=[N:29][C:30]([CH:33]=O)=[CH:31][CH:32]=3)[CH:26]=2)[C:11]([NH:13][CH2:14][C:15]2[C:16](=[O:23])[NH:17][C:18]([CH3:22])=[CH:19][C:20]=2[CH3:21])=[O:12])[CH2:6][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.C([BH3-])#N.[Na+]>CO>[CH:1]1([N:7]([CH3:36])[C:8]2[C:9]([CH3:35])=[C:10]([CH:24]=[C:25]([C:27]3[CH:28]=[N:29][C:30]([CH2:33][N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[CH:31][CH:32]=3)[CH:26]=2)[C:11]([NH:13][CH2:14][C:15]2[C:16](=[O:23])[NH:17][C:18]([CH3:22])=[CH:19][C:20]=2[CH3:21])=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 866726513-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(6-formylpyridin-3-yl)-2-methylbenzamide

Product 1

HCID 708724183-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(morpholinomethyl)pyridin-3-yl)benzamideYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of compound 3-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(6-formylpyridin-3-yl)-2-methylbenzamide (1 equiv.) and morpholine (5 equiv.) in methanol (10 mL), acetic acid (2 equiv.) was added and reaction stirred at room temperature for 8 h. Then sodium cyanoborohydride (2.5 equiv.) was added at 0° C. and reaction stirred overnight at room temperature. On completion, solvent was removed under reduced pressure and crude material was purified by column chromatography to afford 3-(cyclohexyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(6-(morpholinomethyl)pyridin-3-yl)benzamide (0.089 g, 53% yield). LCMS: 558.35 (M+1)+; HPLC: 96.52% (@ 254 nm) (Rt; 4.375; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.46 (s, 1H), 8.75 (s, 1H), 8.18 (t, 1H), 8.01 (d, 1H, J=6.8 Hz), 7.49 (d, 1H, J=8 Hz), 7.33 (s, 1H), 7.18 (s, 1H), 5.85 (s, 1H), 4.28 (d, 2H, J=3.6 Hz), 3.59-3.61 (m, 6H), 2.75 (m, 1H), 2.65 (s, 3H), 2.43 (bs, 4H), 2.21 (s, 3H), 2.20 (s, 3H), 2.10 (s, 3H), 1.70 (bs, 4H), 1.53-1.56 (m, 1H), 1.42-1.44 (m, 1H), 1.09-1.23 (m, 4H).

Workup

  1. customreaction
  2. customreaction
  3. stirringstirred overnight at room temperature
  4. customOn completion, solvent was removed under reduced pressure and crude material
  5. customwas purified by column chromatography

Sources & evidence

ORD record
ord-a70943ee9b2646a88afdf51f7fc082cf
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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