3-Amino-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-one → N-[7-Chloro-2,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-[2-methyl-4-(4-morpholinyl)phenyl]thiourea

HRID 2223095Notes

Reaction equation

HRID 2223095 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[N:10]=2)[C:6]2[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:5]=2[N:4]([CH3:22])[C:3]1=[O:23].[N:24]([C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][C:28]=1[CH3:39])=[C:25]=[S:26]>>[Cl:21][C:18]1[CH:19]=[CH:20][C:5]2[N:4]([CH3:22])[C:3](=[O:23])[CH:2]([NH:1][C:25]([NH:24][C:27]3[CH:32]=[CH:31][C:30]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[CH:29][C:28]=3[CH3:39])=[S:26])[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[N:10]=3)[C:6]=2[CH:17]=1

Participants

3

Reactant 2

HCID 597139813-Amino-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-oneHCID 597143844-(4-Isothiocyanato-3-methylphenyl)morpholine

Product 1

HCID 59713974N-[7-Chloro-2,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-[2-methyl-4-(4-morpholinyl)phenyl]thioureaYield 89.5%

Conditions

Temperature
70 °C

Procedure

As illustrated in the scheme above, a solution of 3-amino-7-chloro-1,3-dihydro-5-(6-methoxy-2-pyridinyl)-1-methyl-2H-1,4-benzodiazepin-2-one (0.0113 g, 0.0342 mmol) and 4-(4-isothiocyanato-3-methylphenyl)morpholine (0.0080 g, 0.034 mmol) in (CH2Cl)2 (0.9 mL) was heated at 70° C. for 20 h. The reaction was cooled and concentrated in vacuo, and the residue was purified by silica gel column chromatography (2:1 CH2Cl2:EtOAc) to provide the title compound (0.0172 g, 89%) as a slightly yellow solid. 1H-NMR (CDCl3): δ 7.79 (dd, J=0.8 Hz, J=7.2 Hz, 1H), 7.70-7.65 (m, 2H), 7.54 (dd, J=2.4 Hz, J=8.8 Hz, 1H), 7.42 (br s, 1H), 7.30 (d, J=8.8 Hz, 1H), 7.28-7.25 (m partially hidden under CHCl3, 2H), 6.85-6.80 (m, 3H), 6.14 (m, 1H), 3.88-3.85 (m, 4H), 3.78 (s, 3H), 3.40 (s, 3H), 3.22-3.18 (m, 4H), 2.36 (s, 3H). MS (M+H+=565.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated in vacuo
  3. customthe residue was purified by silica gel column chromatography (2:1 CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-05873dbb440a492ca7259fe6c4697ce2
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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