Disilathiane, 1,1,1,3,3,3-hexamethyl- → 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-thiobenzamide

HRID 1265765Notes

Reaction equation

HRID 1265765 reaction equation
[Cl:1][C:2]1[C:22]([N:23]([CH3:25])[CH3:24])=[CH:21][C:5]2[N:6]=[C:7]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([NH2:17])=[S:16])[CH2:8][C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.ClC1C(N(C)C)=CC2N=[C:32](C3C=C(C=CC=3)C#N)[CH2:33][C:34](=[O:36])NC=2C=1.C[Si](C)(C)S[Si](C)(C)C.C[O-].[Na+]>CN1CCN(C)C1=O.O>[Cl:1][C:2]1[C:22]([N:23]([CH3:25])[CH3:24])=[CH:21][C:5]2[N:6]=[C:7]([C:12]3[CH:20]=[CH:19][CH:18]=[C:14]([C:15]4[S:16][CH:32]=[C:33]([CH2:34][OH:36])[N:17]=4)[CH:13]=3)[CH2:8][C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.[Cl:1][C:2]1[C:22]([N:23]([CH3:25])[CH3:24])=[CH:21][C:5]2[N:6]=[C:7]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([NH2:17])=[S:16])[CH2:8][C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 76920Disilathiane, 1,1,1,3,3,3-hexamethyl-HCID 10942334Sodium MethoxideHCID 186131143-(7-Chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-benzonitrile2×HCID 186133103-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-thiobenzamide

Product 2

HCID 186133103-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-thiobenzamideHCID 186133618-Chloro-7-dimethylamino-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-1,3-dihydro-benzo[b][1,4]diazepin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 66611,3-Dimethyl-2-imidazolidinoneSolvent2×

Procedure

The title compound was prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-thiobenzamide {prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4] diazepin-2-yl)-benzonitrile (Example 1) as follows: To a solution of hexamethyldisilthiane (0.55 mL, 2.6 mmol) in 1,3-dimethyl-2-imidazolidinone (2.6 mL) was added at 20° C. sodium methoxide (0.13 g, 2.5 mmol). The mixture was stirred for 15 min. and the blue solution formed was then added to a solution of 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-benzonitrile (Example 1) (0.34 g, 1.0 mmol) in 1,3-dimethyl-2-imidazolidinone (2 mL). The mixture was stirred for 3 h at 20° C. and then poured into water. The precipitate was isolated by filtration and triturated with acetone to give 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-thiobenzamide (0.35 g) as yellow solid, mp 234° C. dec.MS (ISP) 373.2 [(M+H)+].} (0.71 g, 1.9 mmol), 1,3-dichloro-2-propanone (0.36 g, 2.85 mmol) and sodium bicarbonate (0.24 g, 2.85 mmol) in 1,4-dioxane (15 mL) was heated to 60° C. for 48 h. The clear solution was evaporated in vacuum. The a solution of the residue in 1,4-dioxane (5 mL) was added 2N KOH (3.8 mL) and the mixture was stirred at 20° C. for 1 h. Water (100 mL) was added and the mixture was stirred for 0.5 h.

Workup

  1. customthe blue solution formed
  2. stirringThe mixture was stirred for 3 h at 20° C.
  3. customThe precipitate was isolated by filtration
  4. customtriturated with acetone

Sources & evidence

ORD record
ord-dbc95103e6fc4141bda6572a8d74ba62
Source dataset
uspto-grants-2003_04
Patent number
US06544985B2

Reaction notes

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