Sodium hydride → HCID 70872580, compound

HRID 1616463Notes

Reaction equation

HRID 1616463 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([N:15]([CH2:22][CH3:23])[CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:12]([CH3:24])=[C:11]([C:25]([NH:27][CH2:28][C:29]3[C:30](=[O:37])[NH:31][C:32]([CH3:36])=[CH:33][C:34]=3[CH3:35])=[O:26])[CH:10]=2)=[CH:5][CH:4]=1.[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][C:39]1=[O:44].[H-].[Na+]>CN(C=O)C>[CH3:35][C:34]1[CH:33]=[C:32]([CH3:36])[NH:31][C:30](=[O:37])[C:29]=1[CH2:28][NH:27][C:25]([C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][N:38]3[CH2:43][CH2:42][O:41][CH2:40][C:39]3=[O:44])=[CH:4][CH:5]=2)[CH:14]=[C:13]([N:15]([CH2:22][CH3:23])[CH:16]2[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[C:12]=1[CH3:24])=[O:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 669533-MorpholinoneHCID 86672666HCID 86672666, compound

Product 1

HCID 70872580HCID 70872580, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice cooled stirred solution of 4′-(bromomethyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-[1,1′-biphenyl]-3-carboxamide (250 mg, 0.44 mmol) and morpholin-3-one (67 mg, 0.66 mmol) in DMF (30 mL) was added sodium hydride (27 mg, 0.66 mmol). After 10 minutes, ice was removed and stirring continued for 16 h at room temperature. On completion, water was added and extracted with DCM (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic and prep. HPLC purification afforded the title compound (75 mg, 29%). LCMS: 587.35 (M+1)+; HPLC: 98.69% (@ 254 nm) (Rt; 4.604; 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 11.50 (bs, 1H), 8.25 (m, 1H), 7.65 (m, 2H), 7.37-7.35 (m, 3H), 5.87 (s, 1H), 4.59 (m, 2H), 4.29 (d, 2H), 4.12 (s, 2H), 3.82 (m, 4H), 3.28 (m, 4H), 3.17-3.09 (m, 2H), 2.32-2.28 (m, 4H), 2.22 (s, 3H), 2.11 (s, 3H), 1.57 (m, 4H), 0.86 (t, 3H).

Workup

  1. customice was removed
  2. waitcontinued for 16 h at room temperature
  3. additionOn completion, water was added
  4. extractionextracted with DCM (3 times)
  5. dry with materialCombined organic layer was dried over sodium sulphate
  6. customRemoval of the solvent under reduced pressure
  7. customHPLC purification

Sources & evidence

ORD record
ord-6c9c9f5aa3364ec581c82722b6c6ccf4
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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