Triethylamine → HCID 66581099, compound

HRID 1521832Notes

Reaction equation

HRID 1521832 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH2:27][S:26](=[O:29])(=[O:28])[C:25]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:8]=2[N:9]([C:11]2[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=2)[N:10]=1)=[O:5])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1>[OH:16][CH2:15][C:14]1[CH:13]=[CH:12][C:11]([N:9]2[C:8]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[S:26](=[O:29])(=[O:28])[CH2:27][C:7]=3[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[N:10]2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydride2×HCID 66581075HCID 66581075, compound

Product 1

HCID 66581099HCID 66581099, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-[3-(ethoxycarbonyl)-5,5-dioxidothiochromeno[4,3-c]pyrazol-1 (4H)-yl]benzoic acid (21.88 g; 53.05 mmol; 1 eq.) in THF (350 ml) is added triethylamine (14.71 ml; 106.11 mmol; 2 eq.) followed by isobutyl chloroformate (13.83 ml; 106.11 mmol; 2 eq.) at 0° C. under nitrogen. The reaction mixture is stirred at rt for 30 min then cooled at 0° C. Sodium borohydride (10 g; 265.27 mmol; 5 eq.) is added portionwise. After 5 h, THF (100 mL) is added and the reaction mixture is heated at 35° C. for 1 day then at rt for 2 days. Sodium borohydride is added (1 eq) and after 6 h stirring the reaction is quenched by dropwise addition of water at 0° C. over 2 h. The product is extracted with EtOAc, the organic layers washed with HCl 1 m (2×) and brine then dried over MgSO4. After evaporation of the solvent, the residue is taken up in DCM and HCl 1 m. The precipitate formed is filtered off and recrystallized in DCE to afford the title compound as a white solid. 1H NMR (DMSO-d6) δ 8.05-8.02 (m, 1H), 7.68-7.48 (m, 6H), 6.88-6.84 (m, 1H), 5.76 (s, 2H), 4.99 (s, 2H), 4.37 (q, J=7.1 Hz, 2H), 3.90 (s, 1H), 1.35 (t, J=7.1 Hz, 3H). HPLC (max plot) 68.2%; Rt 3.02 min. MS (ESI+): 398.9

Workup

  1. temperaturethen cooled at 0° C
  2. waitAfter 5 h
  3. temperaturethe reaction mixture is heated at 35° C. for 1 day
  4. waitat rt for 2 days
  5. stirringafter 6 h stirring the reaction
  6. customis quenched by dropwise addition of water at 0° C. over 2 h
  7. extractionThe product is extracted with EtOAc
  8. washthe organic layers washed with HCl 1 m (2×) and brine
  9. dry with materialthen dried over MgSO4
  10. customAfter evaporation of the solvent
  11. customThe precipitate formed
  12. filtrationis filtered off
  13. customrecrystallized in DCE

Sources & evidence

ORD record
ord-8433c45e28c546cf8dae16a319ff116c
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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