Dichloromethane → N-(1-(6-(4-Cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl)-N-methyl-4-(trifluoromethyl)nicotinamide hydrochloride

HRID 1890774Notes

Reaction equation

HRID 1890774 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH:15][CH3:16])[CH2:11][CH2:10]2)[N:5]=[N:4][C:3]=1[C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1.[F:25][C:26]([F:37])([F:36])[C:27]1[C:32]([C:33]([OH:35])=O)=[CH:31][N:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.C(Cl)[Cl:57]>O>[ClH:57].[C:21]([C:20]1[CH:23]=[CH:24][C:17]([C:3]2[N:4]=[N:5][C:6]([N:9]3[CH2:14][CH2:13][CH:12]([N:15]([CH3:16])[C:33](=[O:35])[C:32]4[C:27]([C:26]([F:25])([F:37])[F:36])=[CH:28][CH:29]=[N:30][CH:31]=4)[CH2:11][CH2:10]3)=[C:7]([CH3:8])[C:2]=2[CH3:1])=[CH:18][CH:19]=1)#[N:22]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27775493-Pyridinecarboxylic acid, 4-(trifluoromethyl)-HCID 67370777HCID 67370777, compound

Product 1

HCID 46203697N-(1-(6-(4-Cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl)-N-methyl-4-(trifluoromethyl)nicotinamide hydrochlorideYield 49%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Treat a solution of 4-(4,5-dimethyl-6-(4-(methylamino)piperidin-1-yl)pyridazin-3-yl)benzonitrile (102 mg, 0.32 mmol), 4-(trifluoromethyl)nicotinic acid (81 mg, 0.42 mmol), triethylamine (0.07 mL, 0.5 mmol) in CH2Cl2 (4 mL) with EDCI (99 mg, 0.52 mmol) and stir for 3 d. Pour the reaction mixture into H2O and extract with EtOAc. Wash the organic layer with H2O, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify by flash silica gel chromatography (gradient of 0 to 10% MeOH in CH2Cl2). Dissolve the free base in MeOH (2 mL) and add 1 M HCl in Et2O (0.5 mL). Concentrate to provide the title compound (82 mg, 49%). ES/MS m/z 495.2 (M+1).

Workup

  1. extractionextract with EtOAc
  2. washWash the organic layer with H2O
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customPurify by flash silica gel chromatography (gradient of 0 to 10% MeOH in CH2Cl2)
  7. dissolutionDissolve the free base in MeOH (2 mL)
  8. additionadd 1 M HCl in Et2O (0.5 mL)
  9. concentrationConcentrate

Sources & evidence

ORD record
ord-9ed8c64485e54a3a85d5aaa44840e3a1
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

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