Dimethylamine → N'-(2-(Benzylcarbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamide

HRID 1093132Notes

Reaction equation

HRID 1093132 reaction equation
[CH3:1][N:2]([C:4](=[O:36])[C:5]([NH:7][C:8]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[CH2:11][N:10]1[C:17](=[O:35])[C:18]([O:26]C(C3C=CC=CC=3)=O)=[C:19]([C:21]([O:23]CC)=O)[N:20]=[C:9]21)=[O:6])[CH3:3].N(C)C.[C:40]1([CH2:46][NH2:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(CC)CC)C>C(O)C>[CH2:46]([NH:47][C:21]([C:19]1[N:20]=[C:9]2[C:8]3([NH:7][C:5](=[O:6])[C:4]([N:2]([CH3:3])[CH3:1])=[O:36])[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]3)[CH2:11][N:10]2[C:17](=[O:35])[C:18]=1[OH:26])=[O:23])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 7504BenzylamineHCID 8471TriethylamineHCID 66588776Ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

Product 1

HCID 57905259N'-(2-(Benzylcarbamoyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)-N,N-dimethylethanediamideYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate (20 mg, 0.040 mmol) in ethanol (2 mL) was added 2M Me2NH (0.040 mL, 0.081 mmol) and the mixture heated at 50° C. for 1 h (mixture became clear after 5-10 min at 50° C. and then precepitate formed). Phenylmethanamine (0.022 mL, 0.201 mmol) followed by triethylamine (0.028 mL, 0.201 mmol) were then added and the mixture heated at 90° C. for 18 h. After work-up the crude product was purified by preparative HPLC to afford the title compound (7 mg, 0.015 mmol, 38% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ: 12.04 (1 H, s), 8.53 (1 H, brs), 8.29 (1 H, s), 7.35-7.39 (2 H, m), 7.28-7.34 (2 H, m), 7.24-7.27 (1 H, m), 4.57 (2 H, d, J=6.27 Hz), 4.14 (2 H, d, J=4.02 Hz), 3.26 (3 H, s), 2.87 (3 H, s), 2.44-2.58 (3 H, m), 2.01-2.10 (2 H, m), 1.86-1.99 (2 H, m), 1.64-1.75 (2 H, m). LCMS (M+H)=454.73. HPLC purity: >95%.

Workup

  1. customprecepitate formed)
  2. additionwere then added
  3. temperaturethe mixture heated at 90° C. for 18 h
  4. customAfter work-up the crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-8bd39d66b9e1488fb3212f5dc472d009
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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