Acetic Anhydride → HCID 59743801, compound

HRID 602086Notes

Reaction equation

HRID 602086 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:29]=[CH:28][C:11]([C:12]([NH:14][CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH:16]3[C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:13])=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:30](OC(=O)C)(=[O:32])[CH3:31]>C(Cl)Cl.CN(C1C=CN=CC=1)C.O>[C:30]([N:18]1[CH2:19][CH2:20][CH:15]([NH:14][C:12](=[O:13])[C:11]2[CH:28]=[CH:29][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)[CH:16]([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[CH2:17]1)(=[O:32])[CH3:31]

Participants

6

Reactant 2

HCID 7918Acetic AnhydrideHCID 59743883HCID 59743883, compound

Product 1

HCID 59743801HCID 59743801, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-(3-fluorophenyl)-N-[3-(4-fluorophenyl)piperidin-4-yl]nicotinamide (250 mg, 0.64 mmol) in DCM (5 mL) at 0° C. was added TEA (0.11 mL, 0.76 mmol ), DMAP (7.76 mg, 0.064 mmol ) and acetic anhydride (97.3 mg, 0.95 mmol ). After stirring at rt for 1 hr the reaction was diluted with water and then extracted with dcm. The organic extracts were combined, dried (Na2SO4) and solvent removed to give an oil, which after chromatography gave the desired product, N-[1-acetyl-3-(4-fluorophenyl)piperidin-4-yl]-6-(3-fluorophenyl)nicotinamide (235 mg, 85% yield). 1H NMR (400 MHz, DMSO-d6) □ ppm 8.76-8.89 (1 H, m), 8.27-8.51 (1H, m), 8.03-8.17 (2H, m), 7.87-8.02 (2H, m), 7.50-7.62 (1H, m), 7.22-7.46 (3 H, m), 7.03-7.17 (2H, m), 4.33-4.62 (1H, m), 3.89-4.12 (1H, m), 3.54-3.86 (2H, m), 3.34-3.44 (1 H, m), 2.63-2.92 (1H, m), 2.05-2.14 (3H, m), 1.94-2.04 (1H, m), 1.71-1.92 (1H, m). LC/MS (M+H)=436.0 observed, 436.18 expected.

Workup

  1. extractionextracted with dcm
  2. dry with materialdried (Na2SO4) and solvent
  3. customremoved
  4. customto give an oil, which after chromatography

Sources & evidence

ORD record
ord-3ac9536be96344a6913108d95da4bbe7
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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