3,5-Dichlorobenzoyl chloride → US10385022, Example 21

HRID 877989Notes

Reaction equation

HRID 877989 reaction equation
OC(C(F)(F)F)=O.[CH3:8][NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:15]=1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]1[CH3:22].CCN(C(C)C)C(C)C.[Cl:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([Cl:42])[CH:41]=1)[C:36](Cl)=[O:37]>C(Cl)Cl>[Cl:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([Cl:42])[CH:41]=1)[C:36]([N:9]([CH3:8])[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:15]=1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]1[CH3:22])=[O:37]

Participants

5

Reactant 3

HCID 761913,5-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 70663603Methyl-(2-methyl-3,4,5,6-tetrahydro-2H-[1,4]bipyridinyl-3'-yl)-amine trifluoroacetic acid salt

Product 1

HCID 70663385US10385022, Example 21Yield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl-(2-methyl-3,4,5,6-tetrahydro-2H-[1,4]bipyridinyl-3′-yl)-carbamic acid tert-butyl ester (60 mg, 0.20 mmol, example 20, intermediate b) was stirred in a solution of TFA (300 μL) and CH2Cl2 (2 mL) for 1 h after which all volatiles were removed under reduced pressure to give crude methyl-(2-methyl-3,4,5,6-tetrahydro-2H-[1,4]bipyridinyl-3′-yl)-amine TFA salt. The crude TFA salt was dissolved in CH2Cl2 (2 mL) and treated with DIPEA (100 μL, 590 mmol) and 3,5-dichlorobenzoyl chloride (54 mg, 0.26 mmol, CAS RN 2905-62-6). The reaction mixture was loaded directly on a silica gel column and elution with 66% EtOAc in n-hexane gave the title product (12 mg, 16%). MS (ESI): m/z=378.0 [M+H]+.

Workup

  1. washThe reaction mixture was loaded directly on a silica gel column and elution with 66% EtOAc in n-hexane

Sources & evidence

ORD record
ord-f3a6f494d9404c19b0cdf996e02bd861
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

Loading…