Sodium Iodide → 1-{3-[2-(1H-Imidazol-1-yl)ethoxy]phenyl}-3-(morpholin-4-ylcarbonyl)-1,4-dihydrothiochromeno[4,3-c]pyrazole 5,5-dioxide

HRID 1521861Notes

Reaction equation

HRID 1521861 reaction equation
[N:1]1([C:7]([C:9]2[C:10]3[CH2:28][S:27](=[O:30])(=[O:29])[C:26]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:11]=3[N:12]([C:14]3[CH:15]=[C:16]([OH:20])[CH:17]=[CH:18][CH:19]=3)[N:13]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl.Cl[CH2:41][CH2:42][N:43]1[CH:47]=[CH:46][N:45]=[CH:44]1>CN(C=O)C.O>[N:43]1([CH2:42][CH2:41][O:20][C:16]2[CH:15]=[C:14]([N:12]3[C:11]4[C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=5[S:27](=[O:29])(=[O:30])[CH2:28][C:10]=4[C:9]([C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[O:8])=[N:13]3)[CH:19]=[CH:18][CH:17]=2)[CH:47]=[CH:46][N:45]=[CH:44]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27575031-(2-chloroethyl)-1H-imidazole hydrochlorideHCID 665789283-[3-(Morpholin-4-ylcarbonyl)-5,5-dioxidothiochromeno[4,3-c]pyrazol-1(4H)-yl]phenol

Product 1

HCID 665809621-{3-[2-(1H-Imidazol-1-yl)ethoxy]phenyl}-3-(morpholin-4-ylcarbonyl)-1,4-dihydrothiochromeno[4,3-c]pyrazole 5,5-dioxide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 3-[3-(morpholin-4-ylcarbonyl)-5,5-dioxidothiochromeno[4,3-c]pyrazol-1(4H)-yl]phenol (206.5 mg; 0.49 mmol; 1 eq.), potassium carbonate (401.6 mg; 2.91 mmol; 5.99 eq.) and sodium iodide (11.7 mg; 0.08 mmol; 0.16 eq.) in DMF (4 ml) is added N-(2-chloroethyl)-imidazole hydrochloride (158.4 mg; 0.95 mmol; 1.95 eq.). The suspension is stirred at 80° C. 2 days then in the microwave at 120° C. for 30 min. The reaction mixture is diluted with water and the product is extracted with EtOAc. The combined organic layer is washed with water then with brine, dried over MgSO4 and the solvent removed under vacuum to afford a brown residue. After purification by flask chromatography (silica; DCM/MeOH 98/2 to 0/100), it affords the title compound as a fluffy yellow powder. 1H NMR (DMSO-d6): δ 8.07-7.98 (m, 1H), 7.73-7.55 (m, 3H), 7.55-7.44 (m, 1H), 7.28-7.13 (m, 3H), 7.09-7.00 (m, 1H), 6.93-6.83 (m, 2H), 4.10 (s, 2H), 4.44-4.22 (m, 4H), 4.00-3.87 (m, 2H), 3.75-3.55 (m, 6H). HPLC (max plot) 93.5%; Rt 2.48 min. MS (ESI+): 520.4.

Workup

  1. extractionthe product is extracted with EtOAc
  2. washThe combined organic layer is washed with water
  3. dry with materialwith brine, dried over MgSO4
  4. customthe solvent removed under vacuum
  5. customto afford a brown residue
  6. customAfter purification by flask chromatography (silica; DCM/MeOH 98/2 to 0/100), it

Sources & evidence

ORD record
ord-4de4d34a6f0a4806b02ba947c6fcd329
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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