1,2-Dichloroethane → 1-(5-Fluoropyridin-2-yl)-3-(2-methyl-1,3-thiazol-5-yl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-pyrazole-4-carboxamide

HRID 1842574Notes

Reaction equation

HRID 1842574 reaction equation
[Cl-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[C:13]([C:15]([OH:17])=O)[C:12]([C:18]3[S:22][C:21]([CH3:23])=[N:20][CH:19]=3)=[N:11]2)=[N:8][CH:9]=1.[O-:24][N+:25]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:28]=[C:27]([C@H:35]([NH2:37])[CH3:36])[CH:26]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[C:13]([C:15]([NH:37][C@@H:35]([C:27]3[CH:26]=[N+:25]([O-:24])[C:30]([C:31]([F:32])([F:33])[F:34])=[CH:29][CH:28]=3)[CH3:36])=[O:17])[C:12]([C:18]3[S:22][C:21]([CH3:23])=[N:20][CH:19]=3)=[N:11]2)=[N:8][CH:9]=1

Participants

9

Reactant 7

HCID 111,2-DichloroethaneHCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 59539683(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamineHCID 666794761-(5-Fluoropyridin-2-yl)-3-(2-methyl-1,3-thiazol-5-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 666798441-(5-Fluoropyridin-2-yl)-3-(2-methyl-1,3-thiazol-5-yl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-pyrazole-4-carboxamideYield 58.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of sodium chloride salt of 1-(5-fluoropyridin-2-yl)-3-(2-methyl-1,3-thiazol-5-yl)-1H-pyrazole-4-carboxylic acid (0.14 g, 0.25 mmol) in DMF (2.5 mL) was added (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (66.2 mg, 0.27 mmol), EDC (83.0 mg, 0.43 mmol), HOAT (16.9 mg, 0.12 mmol) and triethylamine (0.21 mL, 1.49 mmol). The mixture was stirred at 50° C. After 2 h, saturated aqueous NaHCO3 were added and the mixture was extracted with dichloromethane (3×). The combined organic extracts was dried over MgSO4, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane 85% dichloromethane/methanol) gave the title compound (72 mg). HRMS 493.1070 (M+1). 1H NMR (500 MHz, DMSO): δ 9.41 (s, 1H); 8.61 (s, 1H); 8.56 (s, 1H); 8.48 (s, 1H); 8.04-8.02 (m, 2H); 7.94 (d, J=8.4 Hz, 1H); 7.56 (d, J=8.3 Hz, 1H); 5.17-5.14 (m, 1H); 2.67 (s, 3H); 1.51 (d, J=7.1 Hz, 3H).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×)
  2. dry with materialThe combined organic extracts was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (100% dichloromethane 85% dichloromethane/methanol)

Sources & evidence

ORD record
ord-0bba8f936ffd41c4a58edb98711493e7
Source dataset
uspto-grants-2015_02
Patent number
US08946231B2

Reaction notes

Loading…