Chloride → HCID 66580905, compound

HRID 1521862Notes

Reaction equation

HRID 1521862 reaction equation
[N:1]1([C:7]([C:9]2[C:10]3[CH2:29][S:28](=[O:31])(=[O:30])[C:27]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:11]=3[N:12]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20]O)=[CH:16][CH:15]=3)[N:13]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Cl-].[I-].[Na+].C([O-])([O-])=O.[K+].[K+].[CH3:50][CH:51]1[CH2:56][O:55][CH2:54][CH2:53][NH:52]1.S(Cl)(Cl)(=O)=O>C(Cl)Cl.CN(C=O)C.O>[CH3:50][CH:51]1[CH2:56][O:55][CH2:54][CH2:53][N:52]1[CH2:20][C:17]1[CH:16]=[CH:15][C:14]([N:12]2[C:11]3[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=4[S:28](=[O:31])(=[O:30])[CH2:29][C:10]=3[C:9]([C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:8])=[N:13]2)=[CH:19][CH:18]=1

Participants

11

Reactant 7

HCID 312ChlorideHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 2921033-MethylmorpholineHCID 66578644HCID 66578644, compound

Product 1

HCID 66580905HCID 66580905, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of {4-[3-(morpholin-4-ylcarbonyl)-5,5-dioxidothiochromeno[4,3-c]pyrazol-1(4H)-yl]phenyl}methanol (123 mg; 0.28 mmol; 1 eq.) and DIEA (330 μl; 1.93 mmol; 2.56 eq.) in DCM (13 mL) is added at 0° C. methanesulfonlyl chloride (75 μl; 0.97 mmol; 1.3 eq.). The solution is stirred for 30 min and allowed to warm up to rt. After this time, a suspension of sodium iodide (32 mg; 0.21 mmol; 0.28 eq.), K2CO3 (336 mg; 2.43 mmol; 3.22 eq.) and 3-methylmorpholine (166 μl; 1.51 mmol; 2 eq.) in DMF (50 mL) is added on the sulfonylchloride mixture. The resulting suspension is stirred at 80° C. for 2h after which time water is added after return to RT. The product is extracted with DCM and the combined organic layer is washed with brine, dried over MgSO4 and purified by MD-Autoprep then triturated in a mixture of DCM and pentane to afford the title compound as an orange powder. 1H NMR (DMSO-d6): δ 8.02-7.98 (m, 1H), 7.69-7.43 (m, 6H), 6.87-6.79 (m, 111), 4.91 (s, 211), 4.18-4.03 (m, 111), 4.03-3.88 (m, 2H), 3.79-3.56 (m, 8H), 3.56-3.41 (m, 1H), 3.33-3.24 (m, 2H), 3.24-3.10 (m, 1H), 2.52-2.66 (m, 1H), 2.50-2.36 (m, 111), 2.29-2.09 (m, 1H), 1.03 (d, J=6.3 Hz, 3H). HPLC (max plot) 98.1%; Rt 2.09 min. HPLC (max plot) 76.8%; Rt 2.15 min. MS (ESI+): 523.4.

Workup

  1. additionis added after return to RT
  2. extractionThe product is extracted with DCM
  3. washthe combined organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. custompurified by MD-Autoprep
  6. customthen triturated in a mixture of DCM and pentane

Sources & evidence

ORD record
ord-5aedd6d9a82449d08df74e869a632ef5
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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