Dimethylformamide → HCID 86683573、化合物

HRID 1509146ノート

反応式

HRID 1509146 の反応式
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:20][C:21]4[NH:26][CH2:25][CH2:24][O:23][C:22]=4[N:27]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])(C)C.C(=O)([O-])[O-].[K+].[K+].Br[CH2:42][C:43]#N.[C:45]([O-])(O)=O.[Na+].C[N:51]([CH:53]=O)C>>[C:53]([CH2:45][N:26]1[CH2:25][CH2:24][O:23][C:22]2[N:27]=[C:18]([C:15]3[CH:14]=[CH:13][C:12]([C:8]4([NH:7][C:6](=[O:34])[O:5][CH2:1][CH2:4][CH2:42][CH3:43])[CH2:11][CH2:10][CH2:9]4)=[CH:17][CH:16]=3)[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:20][C:21]1=2)#[N:51]

参加物

6

反応物 5

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 516892Sodium BicarbonateHCID 123843496HCID 123843496、化合物

生成物 1

HCID 86683573HCID 86683573、化合物収率 19%

実験手順

To a solution of tert-butyl(1-(4-(7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (24 mg, 0.05 mmol) in dry DMF (1 ml) was added potassium carbonate (93 mg, 1.57 mmol) and bromoacetonitrile (110 μl, 1.57 mmol) under nitrogen. The resulting mixture was stirred for 4 hours 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 60% EtOAc in cyclohexane) to give the title compound (5 mg, 19%). 1H NMR (500 MHz, CDCl3): 7.22-7.11 (9H, m), 6.93 (1H, s), 4.92 (1H, s), 4.51-4.49 (2H, m), 4.15 (2H, s), 3.39-3.37 (2H, m), 2.55-2.25 (4H, m), 1.99-1.94 (1H, m), 1.75-1.63 (1H, m), 1.44-1.15 (9H, br).

後処理

  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 60% EtOAc in cyclohexane)

出典と根拠

ORDレコード
ord-b8e8b36bf0504b23b3bb72720aafa5b8
出典データセット
uspto-grants-2015_12
特許番号
US09221838B2

反応ノート

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