Dimethylformamide → HCID 66793255, compound

HRID 1254472Notes

Reaction equation

HRID 1254472 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1/[C:8](/[CH2:30][CH3:31])=[C:9](\[C:19]1[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28])=[CH:21][CH:20]=1)/[C:10]1[CH:11]=[C:12]2C(=[CH:17][CH:18]=1)N[N:14]=[CH:13]2.[C:32]([O-])([O-])=O.[Cs+].[Cs+].IC.C[N:41]([CH:43]=O)[CH3:42]>O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1/[C:8](/[CH2:30][CH3:31])=[C:9](\[C:19]1[CH:20]=[CH:21][C:22](/[CH:25]=[CH:26]/[C:27]([O:29][CH3:32])=[O:28])=[CH:23][CH:24]=1)/[C:10]1[CH:11]=[C:12]2[C:43](=[CH:17][CH:18]=1)[N:41]([CH3:42])[N:14]=[CH:13]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 56940798HCID 56940798, compound2×

Product 1

HCID 66793255HCID 66793255, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of (E)-3-(4-((E)-2-(2-chlorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acid (80 mg, 0.19 mmol; Compound 14) and Cs2CO3 (0.15 g, 0.46 mmol) in DMF (3.8 mL) at room temperature, iodomethane (65 mg, 0.46 mmol) was added. The mixture was stirred at room temperature overnight, diluted with water, extracted with EtOAc, and concentrated to give the (E)-methyl 3-(4-((E)-2-(2-chlorophenyl)-1-(1-methyl-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate. This residue was redissolved in THF-MeOH (3.8 mL) and an aqueous solution of LiOH (89 mg, 3.7 mmol; dissolved in a minimum amount of water) was added at room temperature. The reaction mixture was stirred overnight, quenched with 1N HCl, extracted with EtOAc, dried over sodium sulfate, filtered and concentrated to give the crude material. This crude product was purified on a RP-C18 column using 50-100% acetonitrile in water in the presence of 0.1% TFA to afford the title compound. 1H NMR (300 MHz, DMSO-d6): δ 12.28 (s, 1H), 8.07 (s, 1H), 7.67-7.64 (m, 2H), 7.48-7.11 (m, 8H), 6.95 (d, 2H), 6.35 (d, 1H), 4.05 (s, 3H), 2.36 (q, 2H), 0.90 (t, 3H). LCMS: 443 (M+H)+.

Workup

  1. extractionextracted with EtOAc
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-cb9e59aaf0da4e5fa24b6987963d646b
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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