Ammonium formate → 3-Amino-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 2223094Notes

Reaction equation

HRID 2223094 reaction equation
C([O-])=O.[NH4+].[N:5]([CH:8]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[N:16]=2)[C:12]2[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:11]=2[N:10]([CH3:28])[C:9]1=[O:29])=[N+]=[N-]>CO.[Pd]>[NH2:5][CH:8]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[N:16]=2)[C:12]2[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:11]=2[N:10]([CH3:28])[C:9]1=[O:29]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 597141213-azido-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 597139813-Amino-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-oneYield 78.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

As illustrated in the scheme above, a suspension of Pd/C (0.005 g of 10% on C) in MeOH (0.5 mL) under N2 was treated with ammonium formate (0.0252 g, 0.400 mmol). The mixture was stirred for 10 min. and then transferred via Pasteur pipette to a suspension of 3-azido-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-one (0.0204 g, 0.0572 mmol) in MeOH (1.2 mL). The resulting mixture was stirred at room temperature for 3 h and was then filtered through a small pad of Celite. The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (100% EtOAc, followed by 4:1 CH2Cl2:EtOAc) to provide the title compound (0.0148 g, 78%). 1H-NMR (CDCl3): δ 7.82 (dd, J=0.8 Hz, J=7.6 Hz, 1H), 7.71-7.66 (m, 2H), 7.51 (dd, 2.4 Hz, J=8.8 Hz, 1H), 7.28 (d, J=8.8 Hz, 1H), 6.83 (dd, J=0.8 Hz, J=8.4 Hz, 1H), 4.56 (s, 1H), 3.80 (s, 3H), 3.44 (s, 3H), 2.53 (br s, 2H). MS (ESI) (M+H)+=331.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 3 h
  2. filtrationwas then filtered through a small pad of Celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by silica gel column chromatography (100% EtOAc, followed by 4:1 CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-5a024fe8790a487ebeebb04490da23ea
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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