Diisopropylethylamine → 1-(4-(4-(2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

HRID 2386171Notes

Reaction equation

HRID 2386171 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][CH2:8][C:7]1=[O:17].BrCCCCN1C2C=CC=CC=2CCCC1=O.[C:35]([C:39]1[N:44]=[C:43]([N:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH:42]=[C:41]([C:51]([F:54])([F:53])[F:52])[N:40]=1)([CH3:38])([CH3:37])[CH3:36].[Na+].[Br-].C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[C:35]([C:39]1[N:44]=[C:43]([N:45]2[CH2:46][CH2:47][N:48]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=4[CH2:10][CH2:9][CH2:8][C:7]3=[O:17])[CH2:49][CH2:50]2)[CH:42]=[C:41]([C:51]([F:52])([F:53])[F:54])[N:40]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 253881Sodium BromideHCID 183996102-(tert-Butyl)-4-(piperazin-1-yl)-6-(trifluoromethyl)pyrimidineHCID 431652441-(4-bromobutyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-oneHCID 617222001-(4-chlorobutyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

Product 1

HCID 444074361-(4-(4-(2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butyl)-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(4-chlorobutyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one and 1-(4-bromobutyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (0.40 g), 2-tert-butyl-4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine (1.59 mmol, 0.46 g, prepared as in DE 19735410), NaBr (7.94 mmol, 0.82 g), diisopropylethylamine (15.57 mmol, 2.01 g) and N-methylpyrrolidinone (0.6 ml) was heated at 120° C. for 5 hours. The suspension was then filtered, and the filtrate was evaporated to dryness. The residue was taken up in ethyl acetate and extracted with saturated brine. The organic phase was dried, the desiccant was filtered off, and the solution was evaporated to dryness. The residue was purified by chromatography on silica gel (eluent: dichloromethane/MeOH (0-100%), resulting in 0.58 g of the title compound.

Workup

  1. filtrationThe suspension was then filtered
  2. customthe filtrate was evaporated to dryness
  3. extractionextracted with saturated brine
  4. customThe organic phase was dried
  5. filtrationthe desiccant was filtered off
  6. customthe solution was evaporated to dryness
  7. customThe residue was purified by chromatography on silica gel (eluent

Sources & evidence

ORD record
ord-9de8c70aecab49148f8da99249fa5d0a
Source dataset
uspto-grants-2012_09
Patent number
US08268815B2

Reaction notes

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