Ammonia → HCID 131727110, compound

HRID 2116614Notes

Reaction equation

HRID 2116614 reaction equation
[O:1]=[C:2]1[N:8]2[CH2:9][C@H:4]([C:5]3[CH:16]=[N:15][NH:14][C:6]=3[C@H:7]2[C:10]([O:12][CH3:13])=[O:11])[N:3]1[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O=C(Cl)[O:27][C:28](Cl)(Cl)Cl.[NH3:33]>ClCCl>[NH2:33][C:28]([N:15]1[CH:16]=[C:5]2[C:6]([C@@H:7]([C:10]([O:12][CH3:13])=[O:11])[N:8]3[CH2:9][C@H:4]2[N:3]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:2]3=[O:1])=[N:14]1)=[O:27]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 10426DiphosgeneHCID 131727109HCID 131727109, compound

Product 1

HCID 131727110HCID 131727110, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.188 g of the product obtained in Stage K of Example 1 is dissolved in 30 ml of dichloromethane, in a round-bottomed flask placed under an argon atmosphere at 0° C. 70 μl of diphosgene are added and then after 1 h 15 min 0.49 ml of a concentrated aqueous ammonia solution is added. After one hour, methylene chloride is added to the reaction medium and the organic phase is washed with an aqueous NaH2PO4 solution and then with an aqueous NaCl solution. The organic phases are dried over magnesium sulfate, filtered and the solvent is evaporated under reduced pressure. The crude product obtained is purified by chromatography on silica, eluting with a methylene chloride/ethyl acetate/triethylamine, 8/2/0.1%, mixture, and then next eluting with a dichloromethane/ethyl acetate/triethylamine, 7/3/0.1%, mixture. After evaporation of the fractions, 32 mg of the isomer A of compound methyl trans-1-(aminocarbonyl)-4,5,6,8-tetrahydro-6-oxo-5-(phenylmethoxy)-1H-4,7-methanopyrazolo[3,4-e][1,3]diazepine-8-carboxylate are obtained with a yield of 15%, and 79 mg of the isomer B of the compound methyl trans-2-(aminocarbonyl)-2,5,6,8-tetrahydro-6-oxo-5-(phenylmethoxy)-4H-4,7-methanopyrazolo[3,4-e][1,3]diazepine-8-carboxylate with a yield of 37%. The empirical formulae of the isomers are C17H17N5O5 (M=371.36 g).

Workup

  1. customplaced under an argon atmosphere at 0° C
  2. washthe organic phase is washed with an aqueous NaH2PO4 solution
  3. dry with materialThe organic phases are dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent is evaporated under reduced pressure
  6. customThe crude product obtained
  7. customis purified by chromatography on silica
  8. washeluting with a methylene chloride/ethyl acetate/triethylamine, 8/2/0.1%, mixture
  9. washnext eluting with a dichloromethane/ethyl acetate/triethylamine, 7/3/0.1%, mixture
  10. customAfter evaporation of the fractions, 32 mg of the isomer A of compound methyl trans-1-(aminocarbonyl)-4,5,6,8-tetrahydro-6-oxo-5-(phenylmethoxy)-1H-4,7-methanopyrazolo[3,4-e][1,3]diazepine-8-carboxylate

Sources & evidence

ORD record
ord-6e6da4e8041c48caafdb968e48c7c89f
Source dataset
uspto-grants-2008_10
Patent number
US07439253B2

Reaction notes

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