N-Methylisobutylamine → 4-(3-{2-[(Isobutyl-methyl-amino)-methyl]-pyridin-4-yl}-phenyl)-7-methyl-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one

HRID 498823Notes

Reaction equation

HRID 498823 reaction equation
O[CH2:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[C:11]([C:15]3[CH2:21][C:20](=[O:22])[NH:19][C:18]4[CH:23]=[C:24]([C:28]([F:31])([F:30])[F:29])[C:25]([CH3:27])=[CH:26][C:17]=4[N:16]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]=1.S(Cl)(Cl)=O.[CH2:36]([NH:40][CH3:41])[CH:37]([CH3:39])[CH3:38]>C(Cl)Cl>[CH2:36]([N:40]([CH2:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[C:11]([C:15]3[CH2:21][C:20](=[O:22])[NH:19][C:18]4[CH:23]=[C:24]([C:28]([F:31])([F:30])[F:29])[C:25]([CH3:27])=[CH:26][C:17]=4[N:16]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]=1)[CH3:41])[CH:37]([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 12249N-MethylisobutylamineHCID 24386Thionyl ChlorideHCID 11212447HCID 11212447, compound

Product 1

HCID 223171384-(3-{2-[(Isobutyl-methyl-amino)-methyl]-pyridin-4-yl}-phenyl)-7-methyl-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-oneYield 57.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred suspension of 4-[3-(2-hydroxymethyl-pyridin-4-yl)-phenyl]-7-methyl-8-trifluoromethyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one (Example 283) (213 mg, 0.50 mmol) and thionyl chloride (0.11 ml, 1.50 mmol) in CH2Cl2 was refluxed for 45 min, evaporated to dryness and dissolved in DMF (3 ml). To the stirred solution N-isobutyl-methyl-amine (436 mg, 5.0 mmol) was added and the reaction mixture was stirred at RT for 1 h. Aqueous work-up (CH2Cl2) and further purification by column chromatography on silica gel (CH2Cl2/MeOH 15:1) yielded the title compound as a light yellow solid (142 mg, 57%).

Workup

  1. temperaturewas refluxed for 45 min
  2. customevaporated to dryness
  3. dissolutiondissolved in DMF (3 ml)
  4. customAqueous work-up (CH2Cl2) and further purification by column chromatography on silica gel (CH2Cl2/MeOH 15:1)

Sources & evidence

ORD record
ord-7b92003a470d4836883aeba9623dbb62
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Reaction notes

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