Dichloromethane → (S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide

HRID 883170노트

반응식

HRID 883170 반응식
O=C1CC([O:8][C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)CCO1.[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28](Br)=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C1(C)C=CC=CC=1.C(OCC)(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:15]([NH:22][C:23]([C:25]1[S:29][C:28]([N:12]2[CH2:13][C@@H:9]([OH:8])[CH2:10][C:11]2=[O:14])=[N:27][C:26]=1[CH3:31])=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamideHCID 68495162(4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one

생성물 1

HCID 24801838(S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide수율 53%

시약·촉매·용매 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
50 °C

실험 절차

A mixture of (4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one (0.036 g, 0.19 mmol), N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.050 g, 0.16 mmol), cesium carbonate (0.079 g, 0.24 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.003 g, 0.003 mmol) and xantphos (0.004 g, 0.006 mmol) in anhydrous toluene (3 mL) was subjected to microwave irradiation at 80° C. for 20 min. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (4 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in ethanol and a catalytic amount of pyridinium p-toluenesulfonate was added to the solution. The reaction mixture was heated at 50° C. for 6 hours and concentrated in vacuo. The residue was dissolved in dichloromethane (15 mL) and washed with water (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained white solid was washed with diethyl ether (25 mL) and dried in air to afford the title compound (0.028 g, 53%): mp 203-204° C. (diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.60 (t, J=6.0 Hz, 1H), 7.33-7.17 (m, 5H), 5.46 (d, J=3.8 Hz, 1H), 4.47-4.41 (m, 1H), 4.35 (d, J=6.0 Hz, 2H), 4.12-4.04 (m, 1H), 3.93-3.85 (m, 1H), 3.00-2.90 (m, 1H), 2.48 (s, 3H), 2.42-2.33 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 173.3, 162.1, 155.9, 140.0, 128.7, 127.7, 127.2, 119.4, 63.6, 57.0, 43.1, 41.7, 17.5; MS (ES+) m/z 332.2 (M+1).

후처리

  1. customirradiation at 80° C. for 20 min
  2. washwashed with water (4 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in ethanol
  7. additiona catalytic amount of pyridinium p-toluenesulfonate was added to the solution
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in dichloromethane (15 mL)
  10. washwashed with water (5 mL)
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. washThe obtained white solid was washed with diethyl ether (25 mL)
  15. customdried in air

출처 및 근거

ORD 기록
ord-990c3c50656042f8aa410aad2d8bb536
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236835B2

반응 노트

불러오는 중…