Acetone, oxime → HCID 12096249, compound

HRID 2120100Notes

Reaction equation

HRID 2120100 reaction equation
[CH3:1][C:2](=[N:4][OH:5])[CH3:3].CC(C)([O-])C.[Na+].F[C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]([C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[C:41]5[S:40](=[O:43])(=[O:42])[N:39]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:38][C:37]=5[CH:36]=[CH:35][CH:34]=4)=[CH:29][CH:28]=3)=[O:25])=[CH:22][C:21]([C:51]([F:54])([F:53])[F:52])=[N:20]2)=[CH:15][C:14]=1[C:55]#[N:56]>CN(C=O)C>[C:2](=[N:4][O:5][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]([C:24]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([C:33]4[C:41]5[S:40](=[O:43])(=[O:42])[N:39]([C:44]([O:46][C:47]([CH3:50])([CH3:48])[CH3:49])=[O:45])[CH2:38][C:37]=5[CH:36]=[CH:35][CH:34]=4)=[CH:31][CH:32]=3)=[O:25])=[CH:22][C:21]([C:51]([F:52])([F:53])[F:54])=[N:20]2)=[CH:15][C:14]=1[C:55]#[N:56])([CH3:3])[CH3:1]

Participants

5

Reactant 3

HCID 67180Acetone, oximeHCID 12096248HCID 12096248, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 12096249HCID 12096249, compoundYield 42.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of acetone oxime (74 mg, 1.0 mmol) in DMF (6 mL) was added sodium t-butoxide (1 M in THF, 1.0 mL). The mixture was stirred at room temperature for half hour followed by addition of a solution of 1,1-dimethylethyl 7-[4-[[[1-[4-fluoro-3-cyanophenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]phenyl]-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide (0.22 g, 0.34 mmol) prepared according to Example 15 in DMF (4 mL). The reaction was stirred at room temperature for 5 hours. The reaction mixture was then partitioned between ethyl acetate and HCl (5%), washed with HCl (5%), four times with water, brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography (30% ethyl acetate/hexane) gave 100 mg of 1,1-dimethylethyl 7-[4-[[[1-[4-isopropylideneaminooxy-3-cyanophenyl]-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]phenyl]-1,2-benzisothiazole-2(3H)-carboxylate 1,1-dioxide. The intermediate (100 mg, 0.14 mmol) was dissolved in ethanol (4 mL) and to the solution was added HCl (20%, 4 mL). The reaction mixture was stirred at 80° C. for three hours. The reaction mixture was cooled to room temperature. The white precipitate was filtered to give the product that 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 the title compound (37 mg, 19%). LRMS (ES+) 577.1 (M+Na)+.

Workup

  1. customprepared
  2. stirringThe reaction was stirred at room temperature for 5 hours
  3. customThe reaction mixture was then partitioned between ethyl acetate and HCl (5%)
  4. washwashed with HCl (5%), four times with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-73bb59fbb4be4efb910ed5c5e5a9098f
Source dataset
uspto-grants-2004_02
Patent number
US06689770B2

Reaction notes

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