Dimethylformamide → Ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

HRID 1056241ノート

反応式

HRID 1056241 の反応式
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:11](=[O:18])[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:34][C:35]([C:37]1[C:46](F)=[CH:45][CH:44]=[C:43]2[C:38]=1[N:39]=[C:40]([NH:49][CH:50]1[CH2:52][CH2:51]1)[C:41]([CH3:48])=[N:42]2)=[O:36].CN(C=O)C>[NH4+].[Cl-]>[CH2:1]([O:8][CH2:9][CH:10]([NH:19][C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[C:11](=[O:18])[CH:12]([CH2:34][C:35]([C:37]1[CH:46]=[CH:45][CH:44]=[C:43]2[C:38]=1[N:39]=[C:40]([NH:49][CH:50]1[CH2:52][CH2:51]1)[C:41]([CH3:48])=[N:42]2)=[O:36])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 897821632-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanoneHCID 131736415(R)-ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxopentanoate

生成物 1

HCID 89782030Ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

試薬・触媒・溶媒 1

HCID 25517Ammonium Chloride溶媒

実験手順

To a 25-mL round-bottomed flask was added (R)-ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (612) (0.78 g, 2.15 mmol), K2CO3 (0.67 g, 4.88 mmol), 2-bromo-1-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)ethanone (613) (0.62 g, 1.95 mmol), and DMF (4 mL). The reaction mixture was stirred at RT for 30 min. The reaction mixture was diluted with sat NH4Cl (5 mL) and extracted with EtOAc (10 mL). The organic extract was washed with water (5 mL), dried over Na2SO4, and concentrated. Ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate (364a) was obtained as a yellow solid and used without further purification. m/z (ESI, +ve) 605.3 (M+H)+. To a 20-mL glass tube was added ethyl 5-(benzyloxy)-4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate (364a), crude from previous step, NH4OAc (0.45 g, 5.85 mmol), EtOH (6 mL), and AcOH (1.5 mL). The tube was sealed and heated at 60° C. for 5 h. The reaction mixture was cooled to RT and was concentrated to half of its volume. The mixture was diluted with EtOAc (10 mL) and water (5 mL). The organic extract was washed with NaOH (1 N, 5 mL), water (5 mL), brine (5 mL), dried over Na2SO4, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 10-30% EtOAc in hexanes to give ethyl 2-(2-(benzyloxy)-1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-(cyclopropylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (364b) (0.48 g, 42% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 12.56 (br. s., 1H), 7.60 (dd, J=0.98, 8.02 Hz, 1H), 7.54 (d, J=1.96 Hz, 1H), 7.31-7.39 (m, 2H), 7.06 (br. s., 1H), 4.50 (d, J=5.48 Hz, 2H), 4.22 (q, J=7.04 Hz, 2H), 3.03 (br. s., 1H), 2.49 (s, 3H) 1.38 (s, 9H), 1.30 (t, J=7.04 Hz, 3H), 0.96-1.02 (m, 2H), 0.62-0.69 (m, 2H). m/z (ESI, +ve) 586.2 (M+H)+.

後処理

  1. extractionextracted with EtOAc (10 mL)
  2. extractionThe organic extract
  3. washwas washed with water (5 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-ef43d5f990ea4610a1b1d4e81434817e
出典データセット
uspto-grants-2016_07
特許番号
US09394297B2

反応ノート

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