Formaldehyde → HCID 70874784, compound

HRID 2208715Notes

Reaction equation

HRID 2208715 reaction equation
[CH:1]1([N:6]([CH3:33])[C:7]2[C:8]([CH3:32])=[C:9]([CH:23]=[C:24]([C:26]3[CH2:27][CH2:28][NH:29][CH2:30][CH:31]=3)[CH:25]=2)[C:10]([NH:12][CH2:13][C:14]2[C:15](=[O:22])[NH:16][C:17]([CH3:21])=[CH:18][C:19]=2[CH3:20])=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[C:36]([BH3-])#N.[Na+]>CO>[CH:1]1([N:6]([CH3:33])[C:7]2[C:8]([CH3:32])=[C:9]([CH:23]=[C:24]([C:26]3[CH2:27][CH2:28][N:29]([CH3:36])[CH2:30][CH:31]=3)[CH:25]=2)[C:10]([NH:12][CH2:13][C:14]2[C:15](=[O:22])[NH:16][C:17]([CH3:21])=[CH:18][C:19]=2[CH3:20])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 70874367HCID 70874367, compound

Product 1

HCID 70874784HCID 70874784, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

3-(Cyclopentyl(methyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-5-(1,2,3,6-tetrahydropyridin-4-yl)benzamide (0.100 g, 0.223 mmol) was dissolved in methanol (5 mL) and cooled to 0° C., formalin (0.067 g, 0.19 mL, 2.23 mmol) was added. Resulting reaction mass was stirred at same temperature for 30 minutes. Sodium cyanoborohydride (0.041 g, 0.66 mmol) was added to above reaction mass and stirred at room temperature for 4 h. After completion, solvent were removed under reduced pressure and water was added to the residue, extraction was carried out using DCM. Combined organic layers were dried, concentrated and purified by column chromatography to provide the desired compound (0.065 g, 63%): LCMS: 463.40 (M+1)+; HPLC: 98.79% (@ 254 nm) (Rt; 3.911; 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 11.43 (s, 1H), 8.04 (t, 1H, J=4.8 Hz), 7.17 (s, 1H), 6.95 (s, 1H), 6.07 (s, 1H), 5.85 (s, 1H), 4.25 (d, 2H, J=4.8 Hz), 3.45 (m, 1H), 2.98 (bs, 2H), 2.53 (m, 2H), 2.42 (bs, 2H), 2.26 (s, 3H), 2.18 (s, 3H), 2.17 (s, 3H), 2.10 (s, 3H), 1.67 (m, 2H), 1.59 (m, 2H), 1.49 (m, 2H), 1.40 (m, 2H).

Workup

  1. customResulting
  2. customreaction mass
  3. stirringstirred at room temperature for 4 h
  4. customAfter completion, solvent were removed under reduced pressure and water
  5. additionwas added to the residue, extraction
  6. customCombined organic layers were dried
  7. concentrationconcentrated
  8. custompurified by column chromatography

Sources & evidence

ORD record
ord-e0dec9bc92d8448d8232fc08ac9d1bd8
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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