Trifluoroacetic acid → HCID 12096247, compound

HRID 2120099Notes

Reaction equation

HRID 2120099 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1(C(O)=O)[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=2)[NH:4]1.S(Cl)(Cl)=O.CC([CH:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[C:37]([C:38]3[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=3)[C:32]=2[S:31](=[O:46])(=[O:45])[N:30]1[C:47]([O-:49])=[O:48])(C)C.FC(F)(F)[C:52]([OH:54])=O>C(#N)C.CN(C1C=CN=CC=1)C.C(Cl)Cl.CO.[Pd]>[NH2:15][CH2:14][C:10]1[CH:9]=[C:8]([N:5]2[C:6]([C:52]([NH:44][C:41]3[CH:40]=[CH:39][C:38]([C:37]4[C:32]5[S:31](=[O:46])(=[O:45])[N:30]([C:47]([O:49][C:10]([CH3:14])([CH3:11])[CH3:9])=[O:48])[CH2:29][C:33]=5[CH:34]=[CH:35][CH:36]=4)=[CH:43][CH:42]=3)=[O:54])=[CH:7][C:3]([C:2]([F:1])([F:19])[F:20])=[N:4]2)[CH:13]=[CH:12][CH:11]=1

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24386Thionyl ChlorideHCID 68805857HCID 68805857, compoundHCID 86587421HCID 86587421, compound

Product 1

HCID 12096247HCID 12096247, compoundYield 15%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To the solution of 3-(trifluoromethyl)-l-(3-cyanophenyl)-1H-pyrazolecarboxylic acid (0.1 g, 0.3 mmol) in dry acetonitrile (10 mL) was added thionyl chloride (0.15 mL, 1.8 mmol). The reaction mixture was warmed up at 50 C for 1 h. The solvent and excess of thionyl chloride were removed under reduced pressure and dried on a vacuum pump over 18 h. To this dried resudue was added a mixture of 1,1-dimethylethyl-7-(4-aminophenyl)-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide (0.1 g, 0.3 mmol) and DMAP (0.13 g, 1.8 mmol) in dry methylene chloride (10 mL). The reaction mixture was allowed to stir at ambient temperature for 18 h, then concentrated and purified by flash chromatography (ethyl acetate/hexane, 1:1) to afford the intermediate product. This material was reduced under an atmosphere of hydrogen gas (55 psi) in methanol (5 mL) and trifluoroacetic acid (5 mL) in the presence of 10% palladium on carbon catalyst (15 mg) over a period of 18 h at ambient temperature. The reaction mixture was filtered over a pad of Celite and washed with methanol (5 mL×3). The residue was purified by HPLC utilizing gradient elution with a mixture of water: acetonitrile with 0.05% of trifluoroacetic acid on a reverse phase C1-8 (60 angstrom) column to give 1,1-dimethylethyl 7-[4-[[[1-[3-(aminomethyl)phenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]phenyl]-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide (32 mg, 15%). LRMS (ES+): 628.3 (M+H)+.

Workup

  1. temperatureThe reaction mixture was warmed up at 50 C for 1 h
  2. customThe solvent and excess of thionyl chloride were removed under reduced pressure
  3. customdried on a vacuum pump over 18 h
  4. additionTo this dried resudue was added
  5. concentrationconcentrated
  6. custompurified by flash chromatography (ethyl acetate/hexane, 1:1)
  7. customto afford the intermediate product
  8. filtrationThe reaction mixture was filtered over a pad of Celite
  9. washwashed with methanol (5 mL×3)
  10. customThe residue was purified by HPLC
  11. washelution
  12. additionwith a mixture of water

Sources & evidence

ORD record
ord-8fb2a0f4a1f848228f950ef5b9731d3a
Source dataset
uspto-grants-2004_02
Patent number
US06689770B2

Reaction notes

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