Triethylamine → Benzyl(3-(benzyloxy)-2-((2-((4-fluorophenyl)acetyl)hydrazinyl)carbonyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

HRID 80694Notes

Reaction equation

HRID 80694 reaction equation
[CH2:1]([O:8][C:9](=[O:37])[NH:10][C:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]1[C:20](=[O:36])[C:21]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:22]([C:24]([NH:26][NH2:27])=[O:25])[N:23]=[C:12]21)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C:53](Cl)=[O:54])=[CH:48][CH:47]=1>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:37])[NH:10][C:11]12[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19]1)[CH2:14][N:13]1[C:20](=[O:36])[C:21]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[C:22]([C:24]([NH:26][NH:27][C:53](=[O:54])[CH2:52][C:49]3[CH:50]=[CH:51][C:46]([F:45])=[CH:47][CH:48]=3)=[O:25])[N:23]=[C:12]21)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 37449884-Fluorophenylacetyl chlorideHCID 71100904Benzyl(3-(benzyloxy)-2-(hydrazinylcarbonyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

Product 1

HCID 71100908Benzyl(3-(benzyloxy)-2-((2-((4-fluorophenyl)acetyl)hydrazinyl)carbonyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamateYield 13.78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl(3-(benzyloxy)-2-(hydrazinylcarbonyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate, Intermediate 9 (400 mg, 0.794 mmol) in CH2Cl2 (15 mL) at 0° C. was added triethylamine (0.221 mL, 1.589 mmol) followed by 2-(4-fluorophenyl)acetyl chloride (0.098 mL, 0.715 mmol) and the resulting mixture stirred for 1 h. The mixture was allowed to warm to room temp and stirred for 3 h. The mixture was then concentrated and purified by preparative HPLC to afford the title compound (70 mg, 0.109 mmol, 13.78% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 10.00 (1H, br. s.), 8.35 (1H, br. s.), 7.48-7.53 (2H, m), 7.27-7.38 (10H, m), 7.00-7.07 (2H, m), 6.55 (1H, br. s.), 5.39 (2H, s), 5.05 (2H, s), 4.10 (2H, d, J=3.36 Hz), 3.60 (2H, s), 2.56-2.70 (2H, m), 2.47 (1H, br. s.), 1.88-2.04 (4H, m), 1.59-1.71 (2H, m). LCMS (M+H)=640.35.

Workup

  1. stirringstirred for 3 h
  2. concentrationThe mixture was then concentrated
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-724512fb89184c798c33cb01c0d796a8
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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