Hydrochloric Acid → HCID 66703694, compound

HRID 426017Notes

Reaction equation

HRID 426017 reaction equation
[N:1]1([C@H:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]2[NH:12][C:13]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:14]=2[C:15](O)=[O:16])[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([NH2:36])[CH:34]=2)[CH:29]=[CH:28][CH:27]=1.[ClH:37].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O>[ClH:37].[ClH:37].[N:1]1([C@H:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]2[NH:12][C:13]2[CH:21]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:19]=[CH:18][C:14]=2[C:15]([NH:36][C:33]2[CH:34]=[C:35]3[C:30]([CH:29]=[CH:28][CH:27]=[N:26]3)=[CH:31][CH:32]=2)=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 113777-AminoquinolineHCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 66703575HCID 66703575, compound

Product 1

HCID 66703694HCID 66703694, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

2-{[(1R,2S)-2-Pyrrolidin-1-ylcyclohexyl]amino}-4-(trifluoromethyl)benzoic acid (150 mg), quinolin-7-amine (67 mg), hydrochloride of 1-ethyl-3-[3-(N,N-dimethylamino)propyl]carbodiimide (121 mg) and 1-hydroxybenzotriazole (57 mg) were stirred at 110° C. for 15 minutes in N-methylpyrrolidone under microwave irradiation. A potassium carbonate aqueous solution was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (basic silica gel, hexane:ethyl acetate, 7:3 to 1:1). By treating the resulting free base with 4 M hydrogen chloride/ethyl acetate, 2-{[(1R,2S)-2-pyrrolidin-1-ylcyclohexyl]amino}-N-quinolin-7-yl-4-(trifluoromethyl)benzamide dihydrochloride (66 mg) was obtained as an amorphous.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. concentrationThe organic layer was concentrated under a reduced pressure
  3. customthe residue was purified by silica gel column chromatography (basic silica gel, hexane:ethyl acetate, 7:3 to 1:1)
  4. additionBy treating the resulting free base with 4 M hydrogen chloride/ethyl acetate

Sources & evidence

ORD record
ord-e4cd92620ae741ad86531aaf8341f883
Source dataset
uspto-grants-2012_01
Patent number
US08106190B2

Reaction notes

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