Water → HCID 123766439, compound

HRID 1509128Notes

Reaction equation

HRID 1509128 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[NH:26][C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl.Cl[CH2:40][CH2:41][N:42]([CH3:44])[CH3:43].O>CN(C=O)C>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:20][C:21]4[N:26]([CH2:40][CH2:41][N:42]([CH3:44])[CH3:43])[C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 67256382HCID 67256382, compound

Product 1

HCID 123766439HCID 123766439, compoundYield 32.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of tert-butyl(1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (19 mg, 0.04 mmol) in dry DMF (1 mL) was added sodium hydride (8 mg, 0.18 mmol) at 0° C. under nitrogen. After 1 h at 0° C., 2-chloro-N,N-dimethylethanamine.hydrochloride (18 mg, 0.12 mmol) was added and the resulting mixture was stirred for an additional 5 h at 40° C. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting residue was purified by silica gel chromatography (gradient 0 to 3% MeOH in dichloromethane) to give the title compound (7 mg, 32%). 1H NMR (500 MHz, CDCl3): 7.38 (1H, s), 7.31-7.24 (7H,m), 7.20-7.18 (2H,m), 5.01 (1H, br s), 4.88 (2H, s), 4.08 (2H,t), 2.60 (2H, t), 2.55-2.25 (4H, m), 2.33 (6H, s), 2.09-2.01 (1H, m), 1.85-1.76 (1H, m), 1.44-1.15 (9H, br).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (gradient 0 to 3% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-a839e9a71fa14597834395af72d7fbad
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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