Water → HCID 52913378, compound

HRID 540798Notes

Reaction equation

HRID 540798 reaction equation
[NH2:1][C:2]1([C:6]2[CH:7]=[C:8]([C:12]3[CH:16]=[C:15]([O:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=4)[N:14]([CH2:28][C:29]([N:31]([CH3:33])[CH3:32])=[O:30])[N:13]=3)[CH:9]=[CH:10][CH:11]=2)[CH2:5][O:4][CH2:3]1.C(N(CC)CC)C.[F:41][C:42]([F:49])([F:48])[CH2:43][S:44](Cl)(=[O:46])=[O:45].O>C(Cl)Cl>[F:27][C:24]([F:25])([F:26])[C:21]1[CH:20]=[CH:19][C:18]([O:17][C:15]2[N:14]([CH2:28][C:29]([N:31]([CH3:33])[CH3:32])=[O:30])[N:13]=[C:12]([C:8]3[CH:9]=[CH:10][CH:11]=[C:6]([C:2]4([NH:1][S:44]([CH2:43][C:42]([F:49])([F:48])[F:41])(=[O:46])=[O:45])[CH2:5][O:4][CH2:3]4)[CH:7]=3)[CH:16]=2)=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 742422,2,2-Trifluoroethanesulfonyl chlorideHCID 69933247HCID 69933247, compound

Product 1

HCID 52913378HCID 52913378, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 2-{3-[3-(3-aminooxetan-3-yl)phenyl]-5-(4-trifluoromethylphenoxy)-1H-pyrazol-1-yl}-N,N-dimethylacetamide (46 mg, 0.10 mmol) in 1 mL of CH2Cl2 was cooled in an ice bath. Triethylamine (0.021 mL, 0.15 mmol) was added, followed by trifluoroethylsulfonyl chloride (0.013 mL, 0.12 mmol), and the mixture was stirred for 30 min. Water was added and the mixture was extracted with CH2Cl2. The combined organic phases were washed with water and brine, then dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. The residue was purified on a C18 reverse phase column using a gradient elution of 20-70% CH3CN:H2O with 0.1% TFA over 20 min at 20 mL/min. Fractions containing pure product were combined and the solvents were removed under reduced pressure to give 2-[5-(4-trifluoromethylphenoxy)-3-(3-{3-[(2,2,2-trifluoroethylsulfonyl)amino]oxetan-3-yl}phenyl)-1H-pyrazol-1-yl]-N,N-dimethylacetamide as a foam. Calcd (M+1)+: 607.1444. Found: 607.1468. 1H NMR (400 MHz, CDCl3) δ 7.75 (m, 2H), 7.64 (d, J=7, 2H), 7.44 (t, J=7, 1H), 7.35 (m, 2H), 7.28 (s, 1H), 6.38 (s, 1H), 6.04 (s, 1H), 5.04 (d, J=7, 2H), 4.98 (d, J=7, 2H), 4.94 (s, 2H), 3.09 (s, 3H), 2.97 (overlapping s and q, 5H).

Workup

  1. extractionthe mixture was extracted with CH2Cl2
  2. washThe combined organic phases were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified on a C18 reverse phase column
  7. washa gradient elution of 20-70% CH3CN
  8. waitH2O with 0.1% TFA over 20 min at 20 mL/min
  9. additionFractions containing pure product
  10. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-5a9008afed1d4b62b35c860f67778408
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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