4-(4-Isothiocyanato-3-methylphenyl)morpholine → N-(7-Fluoro-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N'-[2-methyl-4-(4-morpholinyl)phenyl]thiourea

HRID 2223091Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

As illustrated in the scheme above, a solution of 3-amino-7-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (0.0056 g, 0.020 mmol) and 4-(4-isothiocyanato-3-methylphenyl)morpholine (0.0048 g, 0.020 mmol) in DMA (0.5 mL) was heated at 70° C. for 16 h. The reaction was cooled and concentrated in vacuo, and the residue was lyophilized to provide the title compound (0.0104 g, quantitative). 1H-NMR (CDCl3): δ 7.63-7.58 (m, 2H), 7.50-7.45 (m, 1H), 7.44-7.36 (m, 4H), 7.36-7.26 (m, 3H), 7.09 (dd, J=2.4 Hz, J=8.4 Hz, 1H), 6.85-6.78 (m, 2H), 6.09-6.05 (m, 1H), 3.90-3.83 (br m, 4H), 3.41 (s, 3H), 3.21-3.15 (br s, 4H), 2.36 (s, 3H). MS (ESI) (M+H)+=518.HRMS calculated for (C28H28FN5O2S+H) (M+H)+: 518.2026. Found (ESI): 518.2117.

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-94b5046125ca4c55bef660862729cf0d
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07375101B2

Reaction notes

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