Hydrochloric Acid → 10-Amino-N-(3-(4-fluorophenyl)-2-oxopropyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide

HRID 80697Notes

Reaction equation

HRID 80697 reaction equation
C(OC(=O)[NH:10][C:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]1[C:20](=[O:46])[C:21]([O:38]CC3C=CC=CC=3)=[C:22]([C:24](=[O:37])[NH:25][CH2:26][C:27](=[O:36])[CH2:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[N:23]=[C:12]21)C1C=CC=CC=1.Cl>CO.[Pd]>[NH2:10][C:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]1[C:20](=[O:46])[C:21]([OH:38])=[C:22]([C:24]([NH:25][CH2:26][C:27](=[O:36])[CH2:28][C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)=[O:37])[N:23]=[C:12]21

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 71100903benzyl(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)carbamate

Product 1

HCID 6796033610-Amino-N-(3-(4-fluorophenyl)-2-oxopropyl)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamideYield 83%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a mixture of benzyl(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)carbamate, Intermediate 13 (540 mg, 0.845 mmol) in MeOH (8 mL) was added 1N HCl (0.930 mL, 0.930 mmol) followed by 10% Pd/C (90 mg, 0.085 mmol) and the mixture stirred under a hydrogen atmosphere for 2 h. The mixture was then filtered and thoroughly washed with ethyl acetate. The filtrate was concentrated in vacuo and dried under high vacuum overnight to afford the title compound (318 mg, 0.705 mmol, 83% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.07 (1H, br. s.), 9.61 (1H, t, J=5.95 Hz), 7.24-7.30 (2H, m), 7.13-7.20 (2H, m), 4.33 (2H, d, J=6.10 Hz), 4.00 (2H, d, J=3.66 Hz), 3.92 (2H, s), 2.46 (1H, br. s.), 2.01-2.13 (4H, m), 1.79-1.88 (2H, m), 1.68-1.77 (2H, m). LCMS (M+H)=415.15.

Workup

  1. filtrationThe mixture was then filtered
  2. washthoroughly washed with ethyl acetate
  3. concentrationThe filtrate was concentrated in vacuo
  4. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-135db842ebfe43c996bcf5513b4bf09a
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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