Potassium Carbonate → Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate

HRID 1056186ノート

反応式

HRID 1056186 の反応式
Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]([CH3:15])=[N:10]2)=[O:4].[C:21]([O:25][C:26]([NH:28][C:29]1([C:32](=[O:39])[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:31][CH2:30]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[K+].[K+]>C1COCC1.CN(C=O)C.CCOC(C)=O>[C:21]([O:25][C:26]([NH:28][C:29]1([C:32]([CH:33]([CH2:2][C:3]([C:5]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:6]=2[N:7]=[C:8]([NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]([CH3:15])=[N:10]3)=[O:4])[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[O:39])[CH2:31][CH2:30]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 89781999Ethyl 3-(1-{[(tert-butoxy)carbonyl]amino}cyclopropyl)-3-oxopropanoateHCID 897821422-Bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone

生成物 1

HCID 89781965Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

At RT, a mixture of 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (1.01 g, 3.00 mmol) and ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604) (0.978 g, 3.60 mmol) in 5 mL of THF and 5 mL of DMF was treated with K2CO3 (1.04 g, 7.51 mmol). After the reaction mixture was stirred at RT for 18 h, it was diluted with 100 mL of EtOAc and filtered. The filtrate was washed with sat. NH4Cl (2×15 mL) followed by brine (10 mL), and concentrated. The crude material was purified by silica gel chromatography (25-50% EtOAc in hexanes) to afford ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate as a yellow amorphous solid (324a). m/z (ESI, +ve) 527.3 (M+H)+. In a glass tube, a solution of ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate as a yellow amorphous solid (324a) in 5 mL of EtOH and 2.5 mL of AcOH was treated with NH4OAc (1.39 g, 18.02 mmol). The glass tube was sealed, and heated in an oil bath at 55° C. for 8 h. The reaction mixture was concentrated to half of its volume. The residue was diluted with 150 mL of EtOAc and washed sequentially with 15 mL of water, 10 mL of 0.5 N NaOH and 10 mL of brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (25-50% EtOAc in hexanes) to provide ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (1.4 g, 2.76 mmol, 92% yield) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.21 (1H, br.), 7.87 (1H, d, J=7.2 Hz), 7.61 (1H, dd, J=8.0, 1.4 Hz), 7.40 (1H, d, J=2.7 Hz), 7.35 (1H, t, J=7.8 Hz), 6.92 (1H, br.), 5.90 (1H, s), 4.25 (2H, q, J=7.1 Hz), 2.56 (3H, s), 1.58 (9H, s), 1.26-1.39 (14H, m), 1.13 (2H, m). m/z (ESI, +ve) 508.3 (M+H)+.

後処理

  1. filtrationfiltered
  2. washThe filtrate was washed with sat. NH4Cl (2×15 mL)
  3. concentrationconcentrated
  4. customThe crude material was purified by silica gel chromatography (25-50% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-7387afc0145f4482918a0c36e57a7acb
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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