N-(but-3-yn-1-yl)pivalamide → 7-chloro-6-[4-(2,2-dimethyl-propionylamino)-but-1-ynyl]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1965979Notes

Reaction equation

HRID 1965979 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.[CH2:27]([NH:31][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:28][C:29]#[CH:30]>CN(C=O)C>[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[C:30]#[C:29][CH2:28][CH2:27][NH:31][C:32](=[O:37])[C:33]([CH3:35])([CH3:34])[CH3:36]

Participants

4

Reactant 2

HCID 56765707N-(but-3-yn-1-yl)pivalamideHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 866227837-chloro-6-[4-(2,2-dimethyl-propionylamino)-but-1-ynyl]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 101.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Use a method similar to the General Procedure 3 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (425 mg, 1 mmol) with N-but-3-ynyl-2,2-dimethyl-propionamide (306 mg, 2 mmol) in DMF (10 mL). Purify by chromatography on silica gel eluting with cyclohexane/EtOAc (85:15 to 0:100 gradient) to obtain 7-chloro-6-[4-(2,2-dimethyl-propionylamino)-but-1-ynyl]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (437 mg, 99%).

Workup

  1. customPurify by chromatography on silica gel eluting with cyclohexane/EtOAc (85:15 to 0:100 gradient)

Sources & evidence

ORD record
ord-506864644e764e249ddbc73174410cac
Source dataset
uspto-grants-2013_04
Patent number
US08420631B2

Reaction notes

Loading…