Dimethylformamide → ethyl (4S)-4-((tert-butoxycarbonyl)amino)-2-(2-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)-2-oxoethyl)-3-oxopentanoate

HRID 1056200ノート

反応式

HRID 1056200 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]1([CH3:20])[CH2:19][CH2:18]1)[C:9]([CH3:15])=[N:10]2)=[O:4].CN(C=O)C.[C:26]([O:30][C:31]([NH:33][C@H:34]([CH3:43])[C:35](=[O:42])[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:32])([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[K+].[K+]>C([O-])(O)=O.[Na+].C1COCC1>[C:26]([O:30][C:31]([NH:33][C@@H:34]([CH3:43])[C:35](=[O:42])[CH:36]([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]1([CH3:20])[CH2:19][CH2:18]1)[C:9]([CH3:15])=[N:10]2)=[O:4])[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:32])([CH3:28])([CH3:29])[CH3:27]

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11288402Ethyl (4R)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-oxopentanoateHCID 897821052-Bromo-1-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)ethanone

生成物 1

HCID 131736420ethyl (4S)-4-((tert-butoxycarbonyl)amino)-2-(2-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)-2-oxoethyl)-3-oxopentanoate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

To a 1000 mL round bottomed flask was added 2-bromo-1-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)ethanone (611) (14.6 g, 43.7 mmol), DMF (35 mL), THF (35 mL), ethyl (4R)-4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (602) (13.7 g, 52.7 mmol) and K2CO3 (15.1 g, 109 mmol). The mixture was stirred at RT. After 4 h, the mixture was diluted with sat NaHCO3 and extracted with EtOAc (3×100 mL). The combined extracts were washed with water (2×100 mL) and brine (100 mL) and then dried (Na2SO4) and concentrated to afford ethyl (4S)-4-((tert-butoxycarbonyl)amino)-2-(2-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)-2-oxoethyl)-3-oxopentanoate as a brown amorphous solid which was used without further purification. m/z (ESI, +ve) 513.2 (M+H)+. The brown amorphous solid was treated with EtOH (80 mL), AcOH (8.0 mL), and finally NH4OAc (10.1 g, 131 mmol). The mixture was stirred at RT for 12 h. The solution was partially concentrated and then was diluted with sat NaHCO3 and EtOAc. The phases were separated and the organic phase was washed with water, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (half of the material was purified on a Redisep Gold 330 g column, 0-50% EtOAc/hexanes and the other half on an Interchim 300 g column, 25 micron, 10 to 35% isocratic at 35% EtOAc/Hex) afforded ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(2-methyl-3-((1-methylcyclopropyl)amino)-5-quinoxalinyl)-1H-pyrrole-3-carboxylate (6.96 g, 14.1 mmol, 32% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.72 (br s., 1H), 7.87-7.96 (m, 2H), 7.59 (dd, J=8.0, 1.2 Hz, 1H), 7.47 (s, 1H), 7.33-7.40 (m, 1H), 7.06 (d, J=7.0 Hz, 1H), 5.32-5.45 (m, 1H), 4.17-4.28 (m, 2H), 2.47 (s, 3H), 1.57 (s, 3H), 1.32-1.44 (m, 12H), 1.28 (t, J=7.0 Hz, 3H), 0.91-1.05 (m, 2H), 0.80-0.91 (m, 2H). m/z (ESI, +ve) 494.1 (M+H)+.

後処理

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined extracts were washed with water (2×100 mL) and brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-c4ed63e286264ae5ab98d8489075eee5
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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