Sodium hydride → HCID 53262117, 화합물

HRID 1509154노트

반응식

HRID 1509154 반응식
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

참가 물질

6

반응물 4

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

생성물 1

HCID 53262117HCID 53262117, 화합물수율 20.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0cecd67d431648009763eab0a155068d
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221838B2

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