Sodium hydride → (5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[2-trifluoromethyl-4-(3-trifluoromethyl-pyrazol-1-yl)-phenyl]-methanone

HRID 1978184Notes

Reaction equation

HRID 1978184 reaction equation
[H-].[Na+].[F:3][C:4]([F:11])([F:10])[C:5]1[CH:9]=[CH:8][NH:7][N:6]=1.[N:12]1[C:17]2[NH:18][C:19]3[CH:39]=[CH:38][CH:37]=[CH:36][C:20]=3[N:21]([C:23]([C:25]3[CH:30]=[CH:29][C:28](F)=[CH:27][C:26]=3[C:32]([F:35])([F:34])[F:33])=[O:24])[CH2:22][C:16]=2[CH:15]=[CH:14][CH:13]=1>CCCCCC>[F:35][C:32]([F:33])([F:34])[C:26]1[CH:27]=[C:28]([N:7]2[CH:8]=[CH:9][C:5]([C:4]([F:11])([F:10])[F:3])=[N:6]2)[CH:29]=[CH:30][C:25]=1[C:23]([N:21]1[C:20]2[CH:36]=[CH:37][CH:38]=[CH:39][C:19]=2[NH:18][C:17]2[N:12]=[CH:13][CH:14]=[CH:15][C:16]=2[CH2:22]1)=[O:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18070343-(Trifluoromethyl)pyrazoleHCID 15513330(6,11-Dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethyl-phenyl)-methanone

Product 1

HCID 9827424(5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[2-trifluoromethyl-4-(3-trifluoromethyl-pyrazol-1-yl)-phenyl]-methanoneYield 58.4%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 0.17 g, 4.25 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (10 mL). 3-trifluoromethyl pyrazole (0.34 g, 2.5 mmol) was added in one portion. After the gas evolution subsided stirring was continued at room temperature. The (6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethyl-phenyl)-methanone of Example 4, Step B (0.75 g, 1.94 mmol) was added in one portion and the mixture was placed in an oil bath (preheated at 130° C.) overnight. After cooling, the mixture was partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate, and evaporated to dryness in vacuo. The residue was crystallized from ethanol to yield the title compound (0.57 g) as an off-white solid, m.p. 127-129° C.

Workup

  1. customdried under nitrogen
  2. customwas continued at room temperature
  3. customthe mixture was placed in an oil bath
  4. custom(preheated at 130° C.) overnight
  5. temperatureAfter cooling
  6. customthe mixture was partitioned between water and ethyl acetate
  7. dry with materialThe organic extracts were dried over sodium sulfate
  8. customevaporated to dryness in vacuo
  9. customThe residue was crystallized from ethanol

Sources & evidence

ORD record
ord-a35bb187a86b4036a92aa743d3bb1f8c
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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