Hydrochloric Acid → HCID 66802488, compound

HRID 1057210Notes

Reaction equation

HRID 1057210 reaction equation
Cl.[C:2]1(/[C:8](/[CH2:38][CH3:39])=[C:9](\[C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[CH:31]=[C:30]([C:35]([OH:37])=[O:36])[CH:29]=[CH:28]3)/[C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15](C2CCCCO2)[N:14]=[CH:13]3)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCO.[OH-].[Li+]>O>[NH:15]1[C:16]2[C:12](=[CH:11][C:10](/[C:9](/[C:25]3[CH:26]=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH:31]=[C:30]([C:35]([OH:37])=[O:36])[CH:29]=[CH:28]4)=[C:8](/[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)\[CH2:38][CH3:39])=[CH:18][CH:17]=2)[CH:13]=[N:14]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 3939Lithium HydroxideHCID 66802165HCID 66802165, compound

Product 1

HCID 66802488HCID 66802488, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Hydrochloric acid (1 mL, 2M in ethyl ether) was added to a solution of (E)-6-(2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)-2-naphthoic acid (190 mg, 0.38 mmol) and EtOH (5 mL). The reaction was heated at 70° C. for 30 min, concentrated, and then redissolved in THF:EtOH (1:1, 5 mL). Lithium hydroxide (90 mg, 3.8 mmol) in H2O was added. The reaction was stirred at room temperature for 2 h, acidified to pH 3 with 1.0 M aqueous HCl soln, and then extracted with EtOAc (×2). The organic layers were combined, washed with water then brine, dried over Na2SO4, and concentrated. The crude material was purified on a reversed phase C-18 column eluted with 70-90% acetonitrile in water in the presence of 0.1% TFA affording the title compound as a beige solid (42 mg, 26%). 1H NMR (DMSO-d6, 300 MHz): δ 13.08 (br, 2H), 8.39 (s, 1H), 8.09 (d, 1H), 7.82-7.65 (m, 4H), 7.53 (d, 1H), 7.44 (s, 1H), 7.21-7.06 (m, 7H), 2.49 (q, 2H), 0.93 (t, 3H); LCMS: 419 (M+H)+.

Workup

  1. concentrationconcentrated
  2. dissolutionredissolved in THF:EtOH (1:1, 5 mL)
  3. extractionextracted with EtOAc (×2)
  4. washwashed with water
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude material was purified on a reversed phase C-18 column
  8. washeluted with 70-90% acetonitrile in water in the presence of 0.1% TFA affording the title compound as a beige solid (42 mg, 26%)

Sources & evidence

ORD record
ord-2bf56e02ea7c4ab9ad99ca96317f876a
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

Loading…