Sodium hydride → HCID 53262117, compound

HRID 1509154Notes

Reaction equation

HRID 1509154 reaction equation
C(OC(=O)[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)(C)(C)C.[H-].[Na+].Br[CH2:39][CH:40]1[CH2:43][CH2:42][CH2:41]1.C([O-])(O)=O.[Na+]>CN(C=O)C>[NH2:7][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[N:26]([CH2:39][CH:40]5[CH2:43][CH2:42][CH2:41]5)[C:25](=[O:27])[CH2:24][O:23][C:22]=4[N:28]=3)=[CH:14][CH:13]=2)[CH2:9][CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 67256382HCID 67256382, compound

Product 1

HCID 53262117HCID 53262117, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (44 mg, 0.09 mmol) in dry DMF (1 ml) was added sodium hydride (9 mg, 0.22 mmol) and (bromomethyl)cyclobutane (130, 0.11 mmol) under nitrogen. The resulting mixture was stirred for 1 h at 80 C. A saturated solution of NaHCO3 was added and the mixture was extracted with dichloromethane (3×10 ml) using a phase separator (Isolute® SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 40% EtOAc in cyclohexane) to give the title compound (8 mg, 16%). 1H NMR (500 MHz, CDCl3): 7.23-7.17 (8H, m), 7.13-7.11 (2H, m), 4.95 (1H, s), 4.80 (2H, s), 3.96 (2H, d), 2.68-2.64 (1H, m), 2.52-2.20 (4H, m), 2.00-1.95 (3H, m), 1.86-1.50 (5H, m), 1.44-1.15 (9H, br).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×10 ml)
  2. concentrationThe combined organic phases were concentrated to dryness under reduced pressure
  3. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-0cecd67d431648009763eab0a155068d
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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