1-Hydroxybenzotriazole → 2,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide

HRID 1056664Notes

Reaction equation

HRID 1056664 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([C:12]([OH:14])=O)=[C:7]([Cl:15])[CH:6]=[CH:5][C:4]=2[N:3]=1.[F:16][C:17]1([F:25])[CH2:22][CH2:21][CH:20](NC)[CH2:19][CH2:18]1.Cl.[CH3:27][N:28](C)CCCN=C=NCC.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([C:12]([NH:28][CH2:27][CH:20]3[CH2:19][CH2:18][C:17]([F:16])([F:25])[CH2:22][CH2:21]3)=[O:14])=[C:7]([Cl:15])[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222249964,4-difluoro-N-methylcyclohexan-1-amineHCID 577339932,6-Dichloroquinoline-5-carboxylic acid

Product 1

HCID 1185559652,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amideYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2,6-dichloro-quinoline-5-carboxylic acid (1500.00 mg; 6.20 mmol; 1.00 eq.), (4,4-difluoro-cyclohexyl)-methylamine (1380.48 mg; 7.44 mmol; 1.20 eq.), (3-dimethylamino-propyl)-ethyl-carbodiimide hydrochloride (1425.53 mg; 7.44 mmol; 1.20 eq.) (EDCI), benzotriazol-1-ol (1004.81 mg; 7.44 mmol; 1.20 eq.) (HOBt) and ethyl-diisopropyl-amine (2402.70 mg; 18.59 mmol; 3.00 eq.) in DMF (10.0 mL) was stirred at room temperature overnight. The mixture was poured into water, the solid was collected by filtration and washed with ethyl acetate, then dried over. The product, 2,6-dichloro-N-((4,4-difluorocyclohexyl)methyl)quinoline-5-carboxamide (1.78 g, 77% yield) was used for the next reaction without further purification. m/z: 374 [M+H]+

Workup

  1. filtrationthe solid was collected by filtration
  2. washwashed with ethyl acetate
  3. customdried over

Sources & evidence

ORD record
ord-c66b439a398343a3b71227317d3266e3
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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