Trifluoroacetic acid → HCID 12096247, compound

HRID 2185010Notes

Reaction equation

HRID 2185010 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.[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53]>C(#N)C.CN(C1C=CN=CC=1)C.C(Cl)Cl.CO.[Pd]>[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53].[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

11

Reactant 4

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

Product 2

HCID 6422Trifluoroacetic acidYield 0.05%HCID 12096247HCID 12096247, compoundYield 15%

Reagents, catalysts & solvents 5

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

Conditions

Temperature
50 °C

Procedure

To the solution of 3-(trifluoromethyl)-1-(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 C18 (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. customThe solvent and excess of thionyl chloride were removed under reduced pressure
  2. customdried on a vacuum pump over 18 h
  3. additionTo this dried resudue was added
  4. concentrationconcentrated
  5. custompurified by flash chromatography (ethyl acetate/hexane, 1:1)
  6. customto afford the intermediate product
  7. filtrationThe reaction mixture was filtered over a pad of Celite
  8. washwashed with methanol (5 mL×3)
  9. customThe residue was purified by HPLC
  10. washelution
  11. additionwith a mixture of water

Sources & evidence

ORD record
ord-4b01adb1f5e34983a6de99caaa128064
Source dataset
uspto-grants-2002_06
Patent number
US06399644B1

Reaction notes

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