7-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine → 7-chloro-6-{[5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridin-2-ylmethyl]-amino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1191151Notes

Reaction equation

HRID 1191151 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.[NH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:36]=[C:37]([NH:40][CH2:41][CH:42]3[CH2:44][CH2:43]3)[S:38][CH:39]=2)=[CH:31][N:30]=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:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:36]=[C:37]([NH:40][CH2:41][CH:42]3[CH2:44][CH2:43]3)[S:38][CH:39]=2)=[CH:31][N:30]=1

Participants

4

Reactant 2

HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 598288662-Aminomethyl-5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

Product 1

HCID 866241867-chloro-6-{[5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridin-2-ylmethyl]-amino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 30.3%

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 (316 mg, 0.74 mmol) with 2-aminomethyl-5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine (290 mg, 1.11 mmol) in toluene (8 mL). Filter the crude mixture over Celite®, followed by activated charcoal and wash with dichloromethane. Concentrate the filtrate in vacuo and purify the crude mixture by chromatography on silica gel (12 g) eluting with hexane/(EtOAc with 1% methanol) (20:1 to 3:2 gradient) to obtain 7-chloro-6-{[5-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridin-2-ylmethyl]-amino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (120 mg, 30%). MS (ES+) m/z: 536.3 (M+H)+.

Workup

  1. filtrationFilter the crude mixture over Celite®
  2. washwash with dichloromethane
  3. concentrationConcentrate the filtrate in vacuo
  4. custompurify the crude mixture by chromatography on silica gel (12 g)
  5. washeluting with hexane/(EtOAc with 1% methanol) (20:1 to 3:2 gradient)

Sources & evidence

ORD record
ord-b5ebe6c6c4774fabb9c16d476a398d4b
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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