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

HRID 1191150Notes

Reaction equation

HRID 1191150 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][CH:28]([CH3:45])[CH2:29][CH2:30][NH:31][C:32]1[S:33][CH:34]=[C:35]([C:37]2[CH:44]=[CH:43][C:40]([CH2:41][NH2:42])=[CH:39][CH:38]=2)[N:36]=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:14])([F:13])[F:15])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:42][CH2:41][C:40]1[CH:39]=[CH:38][C:37]([C:35]2[N:36]=[C:32]([NH:31][CH2:30][CH2:29][CH:28]([CH3:45])[CH3:27])[S:33][CH:34]=2)=[CH:44][CH:43]=1

Participants

4

Reactant 2

HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 598288274-[2-(3-Methyl-butylamino)-thiazol-4-yl]-benzylamine

Product 1

HCID 866241857-chloro-6-{4-[2-(3-methyl-butylamino)-thiazol-4-yl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 75%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (380 mg, 0.89 mmol) with 4-[2-(3-methyl-butylamino)-thiazol-4-yl]-benzylamine (443 mg, 1.6 mmol) in toluene (12 mL). Purify the crude mixture by chromatography on silica gel (25 g) eluting with hexane/(EtOAc with 1% methanol) (20:1 to 7:3 gradient) to obtain 7-chloro-6-{4-[2-(3-methyl-butylamino)-thiazol-4-yl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (368 mg, 75%). MS (ES+) m/z: 551.4 (M+H)+.

Workup

  1. customPurify the crude mixture by chromatography on silica gel (25 g)
  2. washeluting with hexane/(EtOAc with 1% methanol) (20:1 to 7:3 gradient)

Sources & evidence

ORD record
ord-305bc95479894224847b0a489ab31f9a
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

Loading…