Morpholine → HCID 52950345, compound

HRID 1521854Notes

Reaction equation

HRID 1521854 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[S:9](=[O:26])(=[O:25])[CH2:10][C:11]3[C:15]([C:16]([OH:18])=O)=[N:14][N:13]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:12]=3[C:7]=2[CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCOC(C)=O.[NH:58]1[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1>C1COCC1>[CH3:1][O:2][C:3]1[C:8]2[S:9](=[O:26])(=[O:25])[CH2:10][C:11]3[C:15]([C:16]([N:58]4[CH2:63][CH2:62][O:61][CH2:60][CH2:59]4)=[O:18])=[N:14][N:13]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:12]=3[C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 66578670HCID 66578670, compound

Product 1

HCID 52950345HCID 52950345, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-methoxy-1-phenyl-1,4-dihydrothiochromeno[4,3-c]pyrazole-3-carboxylic acid 5,5-dioxide (0.20 g, 0.54 mmol) in THF (20 mL) is added triethylamine (0.20 mL, 1.63 mmol) followed by 50% propane phosphonic acid anhydride in EtOAc (0.70 mL, 0.347 g, 1.09 mmol). The reaction mixture is cooled to 0° C. and then morpholine (0.049 g, 0.59 mmol) is added and the reaction mixture is stirred overnight at room temperature. The solvent is removed under reduced pressure and the residue is diluted with EtOAc. The organic layer is washed with 10% NaHCO3 then brine, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by column chromatography (eluent 1 to 2% MeOH in DCM) to afford the title compound as an off-white solid. 1H NMR (DMSO-d6, 400 MHz): δ 7.59-7.58 (m, 3H) 7.46-7.42 (m, 3H) 7.25 (d, J=8.60 Hz, 1H), 6.35 (d, J=7.92 Hz, 1H), 4.82 (s, 2H), 3.95 (br, 2H), 3.90 (s, 3H), 3.65 (br, 4H), 3.59 (br, 2H). MS (ESI+): 440.0. HPLC (max plot) 96.0%; Rt 4.81 min.

Workup

  1. customThe solvent is removed under reduced pressure
  2. additionthe residue is diluted with EtOAc
  3. washThe organic layer is washed with 10% NaHCO3
  4. dry with materialbrine, dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by column chromatography (eluent 1 to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-90ca023542d54f468a41147985a300cd
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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