Ammonium Chloride → HCID 59632902, compound

HRID 2369052Notes

Reaction equation

HRID 2369052 reaction equation
[CH3:1][CH2:2][Mg+].[Br-].CO[C:7]([C:9]1[CH:13]=[C:12]([C:14]2[S:15][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:20]=3)=[CH:17][CH:18]=2)[N:11]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])[N:10]=1)=[O:8].[NH4+].[Cl-]>C1COCC1.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[Cl:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[N:11]1[C:12]([C:14]2[S:15][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:20]=3)=[CH:17][CH:18]=2)=[CH:13][C:9]([C:7]2([OH:8])[CH2:2][CH2:1]2)=[N:10]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 59631939HCID 59631939, compoundHCID 178461630HCID 178461630, compound

Product 1

HCID 59632902HCID 59632902, compoundYield 0.1%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of EtMgBr in THF (1.0M, 11 mL) was added dropwise at it to a stirred solution of 1-(2-chloro-phenyl)-5-[5-(3-methanesulfonyl-phenyl)-thiophen-2-yl]-1H-pyrazole-3-carboxylic acid methyl ester (950 mg, 2 mmol) and Ti(OiPr)4 (0.7 mL, 2.4 mmol) in anhydrous THF (50 mL) under N2. The resulting dark mixture was stirred at it for 2 h. At 0° C. aqueous NH4Cl solution was added, extracted with Et2O. The combined extracts were washed with brine, dried over Na2SO4, and evaporated in vacuo. The crude product was purified first by flash chromatography (0-60% EtOAc/hexanes) and then by reverse HPLC to give the title compounds as a white solid (85 mg, 0.1%). 1HNMR (CDCl3): δ 8.04 (d, 1H), 7.83-7.81 (m, 1H), 7.74-7.71 (m, 1H), 7.57-7.43 (m, 5H), 7.2 (d, 1H), 6.72 (d, 1H), 6.50 9s, 1H), 3.07 (s, 3H), 2.92 (brs, 1H), 1.31 (m, 2H), 1.17 (m, 2H). MS(ES): 471[M+H]+, 453 (M-OH).

Workup

  1. extractionextracted with Et2O
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe crude product was purified first by flash chromatography (0-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6acc091848a84da7ba4ed4c783d8af6f
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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