Hydrochloric Acid → HCID 56942246, compound

HRID 1057182Notes

Reaction equation

HRID 1057182 reaction equation
[Li+].[OH-].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1/[C:11](/[CH2:35][CH3:36])=[C:12](\[C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([O:32]CC)=[O:31])=[CH:24][CH:23]=1)/[C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[CH:16]2.Cl>O.CCO>[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1/[C:11](/[CH2:35][CH3:36])=[C:12](\[C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31])=[CH:24][CH:23]=1)/[C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[CH:16]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66794638HCID 66794638, compound2×

Product 1

HCID 56942246HCID 56942246, compoundYield 58.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

A solution of LiOH (0.23 g, 9.6 mmol) in water (3.2 mL) was added to a solution of (E)-ethyl 3-(4-((E)-2-(2,4-dichlorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate (2.37 g, 4.8 mmol; Compound 196) in EtOH (20 mL) at room temperature. The resulting mixture was stirred overnight. Upon completion, 1N aqueous HCl was added until the pH was 3. The mixture was diluted with water and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water (50 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated. The crude product was purified on a preparative reversed-phased HPLC column using 80-95% acetonitrile in water in the presence of 0.1% TFA to give the title compound (1.3 g) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 13.11 (s, 1H), 12.36 (br, 1H), 8.11 (d, 1H), 7.69 (s, 1H), 7.57-7.53 (m, 2H), 7.44-7.35 (m, 5H), 7.19 (dd, 1H), 6.97 (d, 2H), 6.39 (d, 1H), 2.39 (q, 2H), 0.90 (t, 3H); LCMS: 463 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washThe combined organic layers were washed with water (50 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified on a preparative reversed-phased HPLC column

Sources & evidence

ORD record
ord-c932f34e591040c5bfc56e413ed454a3
Source dataset
uspto-grants-2016_07
Patent number
US09399646B2

Reaction notes

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