Oxalyl chloride → HCID 59632269, compound

HRID 2369106Notes

Reaction equation

HRID 2369106 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[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:27]([F:30])([F:29])[F:28])[N:19]=[C:18]([C:31](O)=[O:32])[CH:17]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].C(Cl)(=O)C(Cl)=O.[CH3:40][S:41]([NH2:44])(=[O:43])=[O:42].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl.ClCCCl.CN(C=O)C>[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[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:27]([F:30])([F:28])[F:29])[N:19]=[C:18]([C:31]([NH:44][S:41]([CH3:40])(=[O:43])=[O:42])=[O:32])[CH:17]=3)=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 59632370HCID 59632370, compound

Product 1

HCID 59632269HCID 59632269, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To round bottom flask was added 5-[5-(3-Methanesulfonyl-phenyl)-thiophen-2-yl]-1-(2-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid (302 mg, 615 mmol), oxalyl chloride (0.54 mL), anhydrous DCM (10 mL), and anhydrous DMF (100 μL). The reaction solution was stirred at room temperature for approximately 1 hr prior to concentration in vacuo. The resulting crude acid chloride intermediate was used in the next reaction without further purification. To a glass vial was added acid chloride (615 μmol theoretical), methanesulfonamide (117 mg, 1.23 mmol), 1,2-dichloroethane (9 mL), DIEA (200 μL), and DMAP (10 mg). The reaction solution was stirred at 45° C. for 3 hrs. The reaction solution was diluted with DCM (60 mL) and transferred to a separatory funnel. The solution was washed with aq NH4Cl (50 mL×2) and with aq NaCl (50 mL). The organic phase was dried over Na2SO4, filtered, concentrated on the Rotavapor and chromatographed through a 25 g SiO2 column using a mobile phase gradient of 100% Hx to 70% EtOAc to afford 182 mg (52% yield) of the title compound. 1H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.02 (s, 1H), 7.91 (m, 1H), 7.84 (d, 1H), 7.74-7.80 (m, 2H), 7.69 (d, 1H), 7.55 (t, 1H), 7.48 (m, 1H), 7.23 (s, 1H), 7.21 (d, 1H), 6.77 (d, 1H), 3.42 (s, 3H), 3.07 (s, 3H); 19F NMR (400 MHz, CDCl3) δ −60.5 ppm MS (ES) 570.2 [M+H]+.

Workup

  1. concentrationto concentration in vacuo
  2. customThe resulting crude acid chloride intermediate was used in the next reaction without further purification
  3. stirringThe reaction solution was stirred at 45° C. for 3 hrs
  4. customtransferred to a separatory funnel
  5. washThe solution was washed with aq NH4Cl (50 mL×2) and with aq NaCl (50 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated on the Rotavapor
  9. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-ba828de36a9649a4a5d355e7e0743ece
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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