7-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine → 7-chloro-6-[4-(1-methyl-1H-imidazol-2-yl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911369Notes

Reaction equation

HRID 911369 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[CH3:27][N:28]1[CH:32]=[CH:31][N:30]=[C:29]1[C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][CH:34]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:38][CH2:37][C:36]1[CH:35]=[CH:34][C:33]([C:29]2[N:28]([CH3:27])[CH:32]=[CH:31][N:30]=2)=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 57656174(4-(1-Methyl-1H-imidazol-2-yl)phenyl)methanamine

Product 1

HCID 866296137-chloro-6-[4-(1-methyl-1H-imidazol-2-yl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 93%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 5-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (455 mg, 1.1 mmol) with 4-(1-methyl-1H-imidazol-2-yl)-benzylamine (240 mg, 1.3 mmol) in toluene (8 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1) followed by SCX chromatography [pre-wash column with methanol followed by DCM, load material dissolved in DCM, then elute with DCM/2M ammonia in methanol (1:1) and concentrate in vacuo] to obtain 7-chloro-6-[4-(1-methyl-1H-imidazol-2-yl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (429 mg, 93%). MS (ES+) m/z: 463 (4+H)+.

Workup

  1. customPurify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1)
  2. washpre-wash column with methanol
  3. dissolutiondissolved in DCM
  4. washelute with DCM/2M ammonia in methanol (1:1)
  5. concentrationconcentrate in vacuo]

Sources & evidence

ORD record
ord-1db29f43bda4439f947e16e528da9690
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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