Morpholine → HCID 66578983, compound

HRID 1521856Notes

Reaction equation

HRID 1521856 reaction equation
[C:1]1([N:7]2[C:11]3[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=4[S:18](=[O:21])(=[O:20])[CH2:19][C:10]=3[C:9]([C:22](O)=[O:23])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>C(Cl)Cl.CN(C=O)C.Cl>[N:31]1([C:22]([C:9]2[C:10]3[CH2:19][S:18](=[O:20])(=[O:21])[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:11]=3[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)=[O:23])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 65578Oxalyl chlorideHCID 3309845,5-dioxo-1-phenyl-4H-thiochromeno[4,3-c]pyrazole-3-carboxylic acid

Product 1

HCID 66578983HCID 66578983, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

1-phenyl-1,4-dihydrothiochromeno[4,3-c]pyrazole-3-carboxylic acid 5,5-dioxide (150.00 mg; 0.44 mmol; 1.00 Eq) is suspended in DCM (4.00 ml) and 2 drops of DMF and then Oxalyl chloride (3 mL) is added dropwise. The reaction mixture is stirred at room temperature for 30 min. The solution is evaporated to dryness. The residue is suspended in DCM (4.00 ml) and morpholine (350.00 μL; 4.02 mmol; 9.12 Eq) is added dropwise. The reaction mixture is stirred at rt for 30 min then diluted with aq. solution of HCl 0.05 M. The two layers are separated. The aqueous layer is extracted with DCM (2×). The organic layers are washed with a saturated solution of NaHCO3 and brine, dried over MgSO4 and evaporated to give foam. The foam is recrystallised in EtOH to the title compound as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.04-8.01 (m, 1H), 7.67-7.53 (m, 7H), 6.85-6.82 (m, 1H), 4.91 (s, 2H), 3.98-3.94 (m, 2H), 3.68-3.61 (m, 6H). UPLC/MS: (ES+): 410.1, (ES−): 408.1. HPLC (max plot) 100.0%; Rt 3.36 min.

Workup

  1. customThe solution is evaporated to dryness
  2. stirringThe reaction mixture is stirred at rt for 30 min
  3. customThe two layers are separated
  4. extractionThe aqueous layer is extracted with DCM (2×)
  5. washThe organic layers are washed with a saturated solution of NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customto give foam
  9. customThe foam is recrystallised in EtOH to the title compound as a white solid

Sources & evidence

ORD record
ord-5fcebdb167314cca90335f6677848093
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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