Triethylamine → 4-Amino-N-[2-(3,4-difluorophenyl)-1-methylethyl]-2-(trifluoromethyl)-3-pyridinecarboxamide

HRID 1170909Notes

Reaction equation

HRID 1170909 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([C:11]([F:14])([F:13])[F:12])[N:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:22][C:23]1[CH:24]=[C:25]([CH2:30][CH:31]([NH2:33])[CH3:32])[CH:26]=[CH:27][C:28]=1[F:29].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]([NH:33][CH:31]([CH3:32])[CH2:30][C:25]2[CH:26]=[CH:27][C:28]([F:29])=[C:23]([F:22])[CH:24]=2)=[O:10])=[C:6]([C:11]([F:14])([F:13])[F:12])[N:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111828881-(3,4-difluorophenyl)propan-2-amineHCID 469351864-Amino-2-(trifluoromethyl)pyridine-3-carboxylic acid

Product 1

HCID 595538824-Amino-N-[2-(3,4-difluorophenyl)-1-methylethyl]-2-(trifluoromethyl)-3-pyridinecarboxamideYield 100.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-amino-2-(trifluoromethyl)nicotinic acid (4.4 g, 18.14 mmol) was suspended in a mixture of anhydrous DMF (100 mL) and anhydrous dichloromethane (200 mL). To this was added triethylamine (6 g, 60 mmol), followed by 1-(3,4-difluorophenyl)propan-2-amine (3.75 g, 21.90 mmol). HBTU (9.63 g, 25.4 mmol) was added and the mixture was allowed to stir at room temperature overnight. The reaction mixture was concentrated in vacuo to remove dichloromethane. The resultant DMF solution was poured into water and extracted twice with ethyl acetate. The organic layer was washed successively with 1N NaOH and water, then dried over magnesium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel column chromatography using 20-40% acetone/hexanes as eluant to provide the product as a colorless solid (6.57 g, 55% yield). 1H NMR (400 MHz, CDCl3) δ 8.2 (d, 1H), 7.1 (m, 2H), 6.95 (m, 1H), 6.7 (d, 1H), 4.07 (m, 1H), 4.9 (bd, 2H), 4.4 (m, 1H), 2.7-2.9 (dd, 2H), 1.2 (d, 2H). MS m/z 360.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto remove dichloromethane
  3. additionThe resultant DMF solution was poured into water
  4. extractionextracted twice with ethyl acetate
  5. washThe organic layer was washed successively with 1N NaOH and water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. customThis oil was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bd037a2778254ddd9e2e638a25d6eed7
Source dataset
uspto-grants-2010_11
Patent number
US07829572B2

Reaction notes

Loading…