Ammonium Hydroxide → HCID 19081335, compound

HRID 963488Notes

Reaction equation

HRID 963488 reaction equation
C(OC([NH:8][CH:9]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[N:11]([CH2:27][C:28]2[C:33](C(O)=O)=[CH:32][CH:31]=[CH:30][N:29]=2)[C:10]1=[O:37])=O)(C)(C)C.O.ON1C2C=CC=C[C:43]=2N=N1.[OH-].[NH4+].N1C(=O)C=NC=C2C=CC=CC=12>O1CCCC1>[NH2:8][CH:9]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[N:11]([CH2:27][C:28]2[CH:33]=[C:32]([CH3:43])[CH:31]=[CH:30][N:29]=2)[C:10]1=[O:37]

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 27960291-Hydroxybenzotriazole hydrateHCID 218646392H-1,4-Benzodiazepin-2-oneHCID 54541607HCID 54541607, compound

Product 1

HCID 19081335HCID 19081335, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1-(3-hydroxycarbonylpyridin-2-yl) methyl-1H-1,4-benzodiazepin-2-one (0.71 g) in tetrahydrofuran (20 ml) was treated with dicyclohexylcalbodiimide (0.29 g) and 1-hydroxybenzotriazole monohydrate (0.215 g) at room temperature. The mixture was stirred for 2 hours at the same condition. To the mixture was added dropwise a solution of ammonium hydroxide (28% ammonia in water, 0.359 g) in tetrahydrofuran (1 ml) at ambient temperature under stirring. The mixture was stirred overnight at ambient temperature. The resultant mixture was concentrated in vacuo, and the residue was taken up with ethyl acetate. The organic layer was washed with a brine and dried over sodium sulfate. Filtration and evaporation gave a crude product. The crude product was purified by column chromatography on silica gel with a mixture of chloroform and methanol to afford (3RS)-1-(3-aminocarbonylpyridin-2-yl)methyl-3-tert-butoxycarbonyl-amino-2,3-dihydro-5-(2-fluorophenyl)-1H,-1,4-benzodiazepin-2-one (0.32 g) as a yellow form.

Workup

  1. stirringunder stirring
  2. stirringThe mixture was stirred overnight at ambient temperature
  3. concentrationThe resultant mixture was concentrated in vacuo
  4. washThe organic layer was washed with a brine
  5. dry with materialdried over sodium sulfate
  6. filtrationFiltration and evaporation
  7. customgave a crude product
  8. customThe crude product was purified by column chromatography on silica gel with a mixture of chloroform and methanol
  9. customto afford (3RS)-1-(3-aminocarbonylpyridin-2-yl)methyl-3-tert-butoxycarbonyl-amino-2,3-dihydro-5-(2-fluorophenyl)-1H

Sources & evidence

ORD record
ord-09fea7c26bbb4756805a62e7942d4672
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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