1,4-Dibromobutane → 2-{[(1S,2S)-2-pyrrolidin-1-ylcyclohexyl]amino}-6-(trifluoromethyl)nicotinic acid

HRID 425981Notes

Reaction equation

C(N(C(C)C)CC)(C)C.[C@H:10]1([NH2:17])[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]1[NH2:16].Cl[C:19]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:20]=1[C:21]([OH:23])=[O:22].C(=O)([O-])[O-].[K+].[K+].Br[CH2:39][CH2:40][CH2:41][CH2:42]Br>C(#N)C>[N:16]1([C@H:11]2[CH2:12][CH2:13][CH2:14][CH2:15][C@@H:10]2[NH:17][C:19]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:20]=2[C:21]([OH:23])=[O:22])[CH2:42][CH2:41][CH2:40][CH2:39]1

Participants

Conditions

Temperature: 140 °C

Procedure

Diisopropylethylamine and (1S,2S)-1,2-cyclohexandiamine were added to 2-chloro-6-(trifluoromethyl)nicotinic acid, followed by stirring at 100° C. for 30 minutes and at 140° C. for 10 minutes using a microwave reaction device. The reaction liquid was dissolved in acetonitrile, potassium carbonate and 1,4-dibromobutane were added, followed by stirring at 50° C. for 8 hours. By dissolving the residue extracted with chloroform in methanol and THF, adding 1 M sodium hydroxide aqueous solution thereto and carrying out the reaction at 50° C., 2-{[(1S,2S)-2-pyrrolidin-1-ylcyclohexyl]amino}-6-(trifluoromethyl)nicotinic acid was obtained.

Workup

customa microwave reaction device
customThe reaction liquid
stirringby stirring at 50° C. for 8 hours
dissolutionBy dissolving the residue
extractionextracted with chloroform in methanol and THF
additionadding 1 M sodium hydroxide aqueous solution
customthe reaction at 50° C.

Sources & evidence

ORD record: ord-370d398e98a64cbc875cc54855b89c8b
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106190B2

Reaction notes

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