Diisopropylethylamine → 1-(5-{4-[2-tert-Butyl-6-(trifluoromethyl)pyrimidin-4-yl]piperazin-1-yl}pentanoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one

HRID 2240625Notes

Reaction equation

HRID 2240625 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12](=[O:19])[CH2:11][CH2:10][CH2:9]1)=[O:7].[C:20]([C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:27]=[C:26]([C:36]([F:39])([F:38])[F:37])[N:25]=1)([CH3:23])([CH3:22])[CH3:21].[Na+].[Br-].C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[C:20]([C:24]1[N:29]=[C:28]([N:30]2[CH2:31][CH2:32][N:33]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([N:8]3[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=4[C:12](=[O:19])[CH2:11][CH2:10][CH2:9]3)=[O:7])[CH2:34][CH2:35]2)[CH:27]=[C:26]([C:36]([F:37])([F:38])[F:39])[N:25]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 253881Sodium BromideHCID 183996102-(tert-Butyl)-4-(piperazin-1-yl)-6-(trifluoromethyl)pyrimidineHCID 685842441-(5-Chloropentanoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one

Product 1

HCID 685831501-(5-{4-[2-tert-Butyl-6-(trifluoromethyl)pyrimidin-4-yl]piperazin-1-yl}pentanoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-oneYield 40.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-(5-Chloropentanoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one from Example 12a (1.43 mmol, 0.50 g), 2-tert-butyl-4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine (1.43 mmol, 0.41 g, preparation according to DE 19735410), NaBr (7.14 mmol, 0.74 g), DIPEA (diisopropylethylamine) (14.01 mmol, 1.81 g) and N-methylpyrrolidinone (0.6 ml) were heated to 120° C. for 5 h. Subsequently, the reaction mixture was filtered and the resulting filtrate was concentrated to dryness. Afterward, ethyl acetate was added to the resulting residue and it was washed with saturated, aqueous sodium chloride solution. The organic phase was dried and then concentrated to dryness. The residue was purified by chromatography on silica gel, eluent: methyl tert-butyl ether/methanol (0-100%); to obtain 0.31 g of the title compound.

Workup

  1. filtrationSubsequently, the reaction mixture was filtered
  2. concentrationthe resulting filtrate was concentrated to dryness
  3. additionAfterward, ethyl acetate was added to the resulting residue and it
  4. washwas washed with saturated, aqueous sodium chloride solution
  5. customThe organic phase was dried
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by chromatography on silica gel, eluent

Sources & evidence

ORD record
ord-0bf6ada100454ad289e813f797a45e3f
Source dataset
uspto-grants-2010_05
Patent number
US07723384B2

Reaction notes

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