Succinimide → HCID 59633121, compound

HRID 2369090Notes

Reaction equation

HRID 2369090 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[S:15][C:14]([C:16]3[N:20]([C:21]4[C:22]([C:27]([F:30])([F:29])[F:28])=[N:23][CH:24]=[CH:25][CH:26]=4)[N:19]=[C:18]([C:31]([OH:34])([CH3:33])[CH3:32])[CH:17]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].[Cl:35]N1C(=O)CCC1=O.C1(=O)NC(=O)CC1>CC#N.C(Cl)Cl>[Cl:35][C:17]1[C:18]([C:31]([OH:34])([CH3:32])[CH3:33])=[N:19][N:20]([C:21]2[C:22]([C:27]([F:30])([F:29])[F:28])=[N:23][CH:24]=[CH:25][CH:26]=2)[C:16]=1[C:14]1[S:15][C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 11439SuccinimideHCID 31398ChlorosuccinimideHCID 59631880HCID 59631880, compound

Product 1

HCID 59633121HCID 59633121, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2-(5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1-(2-(trifluoromethyl)-pyridin-3-yl)-1H-pyrazol-3-yl)propan-2-ol (10.6 g, 21 mmol) in MeCN (200 mL) was added N-chlorosuccinimide. The resulting solution was heated to 75° C. in a heating mantle. After stirring for 3 hours at 75° C. heating was discontinued and the solution was concentrated under reduced pressure to afford a yellow foam. This crude product was purified by flash column chromatography eluting with a gradient from 0% to 100% EtOAc/hexane. Fractions that Were pure by TLC analysis were combined and concentrated under reduced pressure to afford a white sticky foam that was contaminated with succinimide as evidenced by NMR analysis. This material was taken up in CH2Cl2 and washed with saturated aqueous Na2CO3 (2×). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford 2-(4-chloro-5-{5-[3-(methylsulfonyl)phenyl]-2-thienyl}-1-[2-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-3-yl)propan-2-ol (6.7 g, 60% yield) as an off-white foam. 1H NMR (400 MHz CDCl3): δ 8.85 (1H, m), 8.06 (1H, t), 7.86 (1H, m), 7.82-7.73 (2H, m), 7.67-7.62 (1H, m), 7.58 (1H, t), 7.28 (1H, d), 7.01 (1H, d), 3.08 (3H, s), 2.93 (1H, s), 1.73 (6H, s). MS(ES): 542 [M+H]+.

Workup

  1. temperatureheating
  2. concentrationthe solution was concentrated under reduced pressure
  3. customto afford a yellow foam
  4. customThis crude product was purified by flash column chromatography
  5. washeluting with a gradient from 0% to 100% EtOAc/hexane
  6. concentrationconcentrated under reduced pressure
  7. customto afford a white sticky foam that
  8. washwashed with saturated aqueous Na2CO3 (2×)
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0cb130f1f33b41b3a4aa383ce8411e74
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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