4-Amino-3-fluorobenzoic acid → 4-amino-3-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234381Notes

Reaction equation

HRID 2234381 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[O:8])=[CH:4][C:3]=1[F:11]

Participants

7

Reactant 4

HCID 99714-Amino-3-fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 626798464-amino-3-fluoro-N-(1-methyl-4-piperidyl)benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Procedure

4-Amino-3-Fluorobenzoic acid (Fluorochem; 1 g, 6.44 mmol), 4-Amino-1-methylpiperidine (Fluorochem; 811 mg, 7.09 mmol), HATU (2.70 g, 7.09 mmol), DIPEA (3.4 mL, 19.32 mmol) and DMF (15 mL) were combined and stirred for 18 hrs at room temperature. The solvent was evaporated and the resultant material dissolved in DCM (with a little MeOH to aid solubility) and chromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM. Fractions containing product were combined and evaporated to give an orange solid which was dissolved in MeOH and added to a 50 g SCX-2 column pre-wet with MeOH (2 column volumes). The column was flushed with MeOH (2 column volumes) and the product eluted with 2M ammonia in MeOH. Product containing fractions were evaporated to yield the title compound as a beige solid. (1.72 g, 100%)

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe resultant material dissolved in DCM (with a little MeOH to aid solubility) and
  3. customchromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM
  4. additionFractions containing product
  5. customevaporated
  6. customto give an orange solid which
  7. customThe column was flushed with MeOH (2 column volumes)
  8. washthe product eluted with 2M ammonia in MeOH
  9. additionProduct containing fractions
  10. customwere evaporated

Sources & evidence

ORD record
ord-fa97c1b401ad4a80a195e0a416e068f6
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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