Potassium Carbonate → Methyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

HRID 1056191ノート

反応式

HRID 1056191 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:17])[C:10](=[O:16])[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:19][C:20]([C:22]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:23]=1[N:24]=[C:25]([NH:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:26]([CH3:32])=[N:27]2)=[O:21].C([O-])([O-])=O.[K+].[K+]>C1COCC1.CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][CH:9]([CH3:17])[C:10](=[O:16])[CH:11]([CH2:19][C:20]([C:22]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:23]=1[N:24]=[C:25]([NH:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:26]([CH3:32])=[N:27]2)=[O:21])[C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:3])([CH3:4])[CH3:2]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 14560628(R)-methyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoateHCID 897821422-Bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone

生成物 1

HCID 89782367Methyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

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 solution of (R)-methyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (603) (5.38 g, 21.95 mmol) in 20 mL of THF and 20 mL of DMF was treated with 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (5.44 g, 16.18 mmol) and K2CO3 (5.59 g, 40.4 mmol) and stirred at RT for 6 h. It was diluted with 250 mL of EtOAc, filtered through a flitted funnel, rinsed with 2×15 mL of EtOAc. The filtrate was washed with sat NH4Cl (2×25 mL) followed by brine (15 mL). The organic solution was dried over Na2SO4 and concentrated. The residue was passed through a short column (35-75% EtOAc in hexanes) to get rid of the solvent front peaks and the base line peaks. Fractions with m/z (ESI, +ve) 501.2 (M+H)1 were collected and concentrated to give methyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate (326a) as a brown residue. To the brown residue in a glass tube in 25 mL of EtOH and 10 mL of HOAc was added NH4OAc (8.46 g, 110 mmol). The tube was sealed and heated in an oil bath at 50° C. for 8 h. The mixture was concentrated to half of its volume, diluted with 250 mL of EtOAc, washed sequentially with 15 mL of water, 15 mL of 1 N NaOH and 5 mL of brine. The organic solution was concentrated and the residue was purified on a silica gel column (eluted with a gradient of 35-65% EtOAc in hexanes) to give methyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (326b) (6.3 g, 71% yield) as a yellow amorphous. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.42 (1H, br.), 7.76 (1H, dd, J=7.4, 1.2 Hz), 7.63 (1H, dd, J=8.0, 1.2 Hz), 7.38 (2H, m), 7.03 (1H, d, J=7.8 Hz), 5.94 (1H, s), 5.44 (1H, m), 3.77 (3H, s), 2.56 (3H, s), 1.58 (9H, s), 1.40 (12H, m). m/z (ESI, +ve) 482.1 (M+H)+.

後処理

  1. filtrationfiltered through a flitted funnel
  2. washrinsed with 2×15 mL of EtOAc
  3. washThe filtrate was washed with sat NH4Cl (2×25 mL)
  4. dry with materialThe organic solution was dried over Na2SO4
  5. concentrationconcentrated
  6. customto get rid of the solvent front peaks
  7. customFractions with m/z (ESI, +ve) 501.2 (M+H)1 were collected
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-ed1e64791b4f4378a5c31cfc8b11a1ac
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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