1,2-Dichloroethane → HCID 86657034, compound

HRID 1909137Notes

Reaction equation

HRID 1909137 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([CH:18]([OH:23])[C:19]([F:22])([F:21])[F:20])[N:17]=1)[C:12](O)=[O:13].[O-:24][N+:25]1[C:30]([C:31]([F:34])([F:33])F)=[CH:29][CH:28]=[C:27]([C@H:35]([NH2:37])[CH3:36])[CH:26]=1.[CH2:38](Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[F:34][C:31]([C:30]1[N+:25]([O-:24])=[CH:26][C:27]([C@H:35]([NH:37][C:12](=[O:13])[C:11]2[CH:15]=[C:16]([CH:18]([OH:23])[C:19]([F:22])([F:20])[F:21])[N:17]=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:10]=2)[CH3:36])=[CH:28][CH:29]=1)([F:33])[CH3:38]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 59539683(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamineHCID 67339494HCID 67339494, compound

Product 1

HCID 86657034HCID 86657034, compoundYield 77.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(2,4-difluorophenyl)-6-(2,2,2-trifluoro-1-hydroxyethyl)isonicotinic acid (0.15 g, 0.45 mmol) in DMF (2.5 mL) were added hydrochloride salt of (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (0.16 g, 0.59 mmol), EDC (0.17 g, 0.90 mmol), HOAT (61.3 mg, 0.45 mmol) and triethylamine (0.38 mL, 2.7 mmol). The mixture was stirred at 60° C. After 1 h, the mixture was cooled to ambient temperature and saturated aqueous NaHCO3 was added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The mixture was suspended in dichloromethane and the solid was filtered. The solid cake was washed with cold dichloromethane and dried under hi-vac. The product was treated with HCl (2.0 M in ether) to give the hydrochloride salt of the title compound (0.18 g). HRMS 522.1063 (M+1). 1H NMR (400 MHz, CD3OD): δ 8.48 (s, 1H); 8.17 (s, 1H); 8.09-7.99 (m, 2H); 7.89 (d, J=8.4 Hz, 1H); 7.65 (d, J=8.4 Hz, 1H); 7.10 (t, J=9.1 Hz, 2H); 5.28-5.18 (m, 2H); 1.62 (d, J=7.2 Hz, 3H).

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. filtrationthe solid was filtered
  8. washThe solid cake was washed with cold dichloromethane
  9. customdried under hi-vac
  10. additionThe product was treated with HCl (2.0 M in ether)

Sources & evidence

ORD record
ord-6ae883dece604426a4c80de9e826cba7
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

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