Water → N'-(3-(Benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 80699노트

반응식

HRID 80699 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:37])[CH2:10][NH:11][C:12]([C:14]2[N:15]=[C:16]3[C:22]4([NH:25][C:26](=[O:32])[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH2:23][CH2:24][CH:19]([CH2:20][CH2:21]4)[CH2:18][N:17]3[C:33](=[O:36])[C:34]=2[OH:35])=[O:13])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.O>CN(C=O)C>[CH2:45]([O:35][C:34]1[C:33](=[O:36])[N:17]2[CH2:18][CH:19]3[CH2:24][CH2:23][C:22]([NH:25][C:26](=[O:32])[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])([C:16]2=[N:15][C:14]=1[C:12](=[O:13])[NH:11][CH2:10][C:9](=[O:37])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:21][CH2:20]3)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 67960391N'-(2-((3-(4-Fluorophenyl)-2-oxopropyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

생성물 1

HCID 67960337N'-(3-(Benzyloxy)-2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide수율 59.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of N′-(2-((3-(4-fluorophenyl)-2-oxopropyl)carbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide, Intermediate 15 (140 mg, 0.273 mmol) in DMF (5 mL) was added K2CO3 (67.8 mg, 0.491 mmol) followed by (bromomethyl)benzene (0.049 mL, 0.409 mmol) and the resulting mixture stirred at room temp for 16 h. Water was then added and the mixture was extracted with ethyl acetate (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography to afford the title compound (140 mg, 0.162 mmol, 59.5% yield) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 8.73 (1H, s), 8.31 (1H, s), 7.53-7.59 (2H, m), 7.31-7.38 (3H, m), 7.18-7.24 (2H, m), 7.02-7.07 (2H, m), 5.35 (2H, s), 4.73 (2H, s), 4.29 (2H, d, J=5.49 Hz), 4.16 (2H, d, J=3.66 Hz), 2.94 (3H, s), 2.91 (3H, s), 2.70-2.79 (2H, m), 2.53 (1H, br. s.), 1.98-2.12 (4H, m), 1.70-1.80 (2H, m). LCMS (M+H)=604.31.

후처리

  1. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-caad076cfc2a42a486e36ec43c119bc7
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846659B2

반응 노트

불러오는 중…