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

HRID 1978191Notes

Reaction equation

HRID 1978191 reaction equation
[H-].[Na+].[C:3]([C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)([CH3:6])([CH3:5])[CH3:4].[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>[C:3]([C:7]1[CH:11]=[CH:10][N:9]([C:28]2[CH:29]=[CH:30][C:25]([C:23]([N:21]3[C:20]4[CH:36]=[CH:37][CH:38]=[CH:39][C:19]=4[NH:18][C:17]4[N:12]=[CH:13][CH:14]=[CH:15][C:16]=4[CH2:22]3)=[O:24])=[C:26]([C:32]([F:33])([F:35])[F:34])[CH:27]=2)[N:8]=1)([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15513330(6,11-Dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethyl-phenyl)-methanoneHCID 178441177HCID 178441177, compound

Product 1

HCID 9935347[4-(3-tert-Butyl-1H-pyrazol-1-yl)-2-(trifluoromethyl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanoneYield 36%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 0.12 g, 3.0 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (10 mL). 3-tert-butylpyrazole (0.20 g, 1.6 mmol) was added in one portion at ambient temperature, and the stirring was continued until the gas evolution subsided. 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 (0.50 g, 1.3 mmol) was added in one portion to the clear solution. The mixture was placed in an oil bath (preheated at 130° C.) for 30 minutes and then heated at reflux for 5 hours. After cooling, the mixture was partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The crude residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 25% ethyl acetate in hexane provided the title product (0.23 g) as a foam which crystallized by trituration with hexane-ether, m.p. 136-140° C.

Workup

  1. customdried under nitrogen
  2. customThe mixture was placed in an oil bath
  3. temperatureheated
  4. temperatureat reflux for 5 hours
  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
  9. dissolutionThe crude residue was dissolved in dichloromethane
  10. customabsorbed onto a silica Merck-60 flash column
  11. washElution with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-63cd77906c1549aaaca4070d499da2ae
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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