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 80699ノート

反応式

HRID 80699 の反応式
[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

参加物

6

反応物 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

生成物 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-dimethylethanediamide収率 59.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-caad076cfc2a42a486e36ec43c119bc7
出典データセット
uspto-grants-2014_09
特許番号
US08846659B2

反応ノート

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