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

HRID 80693Notes

Reaction equation

HRID 80693 reaction equation
[CH2:1]([O:8][C:9]1[C:32](=[O:33])[N:13]2[CH2:14][CH:15]3[CH2:20][CH2:19][C:18]([NH:21][C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])([C:12]2=[N:11][C:10]=1[C:34](O)=[O:35])[CH2:17][CH2:16]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:43][NH2:44].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[CH2:25]([O:24][C:22](=[O:23])[NH:21][C:18]12[CH2:17][CH2:16][CH:15]([CH2:20][CH2:19]1)[CH2:14][N:13]1[C:32](=[O:33])[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:10]([C:34]([NH:43][NH2:44])=[O:35])[N:11]=[C:12]21)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 9321HydrazineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 67960313HCID 67960313, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid, Intermediate 4 (1 g, 2.043 mmol) in CH2Cl2 (20 mL) was added oxalyl chloride (0.286 mL, 3.27 mmol). A few drops of DMF were added and the mixture stirred at room temperature for 2 h. Solvent was then removed under reduced pressure. The crude acid chloride was then diluted with dichloromethane (10 mL)) and added to a stirred solution of hydrazine (0.641 mL, 20.43 mmol) and triethylamine (2.85 mL, 20.43 mmol) in CH2Cl2 (20 mL) and the resulting solution stirred at room temperature. After 16 h the reaction mixture was poured into sat. NaHCO3 and extracted with dichloromethane (50 mL×3), dried (Na2SO4), filtered and concentrated to give a yellow oil which was used in the next step without further purification. LCMS (M+H)=504.10.

Workup

  1. customSolvent was then removed under reduced pressure
  2. additionThe crude acid chloride was then diluted with dichloromethane (10 mL)) and
  3. stirringthe resulting solution stirred at room temperature
  4. extractionextracted with dichloromethane (50 mL×3)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil which
  9. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-b6b67545f9ed4ee6a9b5e11386eda489
Source dataset
uspto-grants-2014_09
Patent number
US08846659B2

Reaction notes

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