Dimethylformamide → 6-Methylamino-5-nitro-2-(4-trifluoromethyl-piperidinyl)-nicotinic acid

HRID 450333Notes

Reaction equation

HRID 450333 reaction equation
[F:1][C:2]([F:10])([F:9])[CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.FC(F)CO[C:15]1[N:23]=[C:22]([NH:24][CH3:25])[C:21]([N+:26]([O-:28])=[O:27])=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].CN(C=O)C.C([O-])([O-])=O.[Cs+].[Cs+]>O.CC#N>[CH3:25][NH:24][C:22]1[C:21]([N+:26]([O-:28])=[O:27])=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[C:15]([N:6]2[CH2:7][CH2:8][CH:3]([C:2]([F:10])([F:9])[F:1])[CH2:4][CH2:5]2)[N:23]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1364694-(Trifluoromethyl)piperidineHCID 866692912-(2,2-Difluoro-ethoxy)-6-methylamino-5-nitro-nicotinic acid

Product 1

HCID 679584096-Methylamino-5-nitro-2-(4-trifluoromethyl-piperidinyl)-nicotinic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-trifluoromethyl-piperidine (330 mg, 2.2 mmol), TEA (1.00 mL, 7.2 mmol), 2-(2,2-difluoro-ethoxy)-6-methylamino-5-nitro-nicotinic acid (500 mg, 1.8 mmol, prepared according to WO2010/34799), DMF (5 mL) and MeCN (5 mL) is stirred for 3 h at rt. Then Cs2CO3 (1.5 g, 4.6 mmol) is added and it is stirred overnight at rt and for 6 h at 70° C. Water is added and the mixture is concentrated i.vac. The residue is diluted with water, HCOOH is added and the resulting precipitate is filtered, washed with water and dried.

Workup

  1. stirringit is stirred overnight at rt and for 6 h at 70° C
  2. concentrationthe mixture is concentrated i.vac
  3. additionThe residue is diluted with water, HCOOH
  4. additionis added
  5. filtrationthe resulting precipitate is filtered
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-c82ba926a9e74a0ea90cf87315144d7f
Source dataset
uspto-grants-2013_07
Patent number
US08486968B2

Reaction notes

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