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 80699Notes

Reaction equation

HRID 80699 reaction equation
[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

Participants

6

Reactant 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

Product 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-dimethylethanediamideYield 59.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-caad076cfc2a42a486e36ec43c119bc7
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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