Hydrochloric Acid → HCID 69298139, compound

HRID 2054602Notes

Reaction equation

HRID 2054602 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:39])[CH2:6][CH2:7][C:8]([C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Cl:19])[CH:17]=2)[N:12]([CH2:20][C:21]2[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:24]=[C:23]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:22]=2)[CH:11]=1)=[O:9].Cl>O1CCCC1.CO.O>[Cl:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:24]=[C:23]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:22]=1)[CH:11]=[C:10]2[C:8](=[O:9])[CH2:7][CH2:6][C:5]([OH:39])=[O:4]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69298223HCID 69298223, compound

Product 1

HCID 69298139HCID 69298139, compoundYield 98%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2N Sodium hydroxide solution (1.45 mL, 2.9 mmol) was added dropwise to a stirred solution of methyl-4-[5-chloro-1-(2,6-diphenyl-pyridin-4-ylmethyl)-1H-indol-3-yl]-4-oxobutyrate (254 mg, 0.5 mmol) in tetrahydrofuran (10 mL) and methanol (2 mL). The clear reaction mixture was stirred at room temperature until the reaction was complete (TLC control), and then diluted with water (10 mL), and acidified to pH 3 with 2N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (2×20 mL). The combined extract was washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 5-10% methanol in methylene chloride as eluent, afforded the title compound as a white solid (240 mg, 98%): Rf: 0.45 (10% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 12.09 (1H, s, COOH), 8.80 (1H, s, ArH), 8.15 (1H, d, J=2 Hz, ArH), 8.09 (4H, m, ArH), 7.83 (2H, s, ArH), 7.69 (1H, d, J=8 Hz, ArH), 7.46 (6H, m, ArH), 7.24 (1H, dd, J=8, 2 Hz, ArH), 5.66 (2H, s, CH2N), 3.17 (2H, t, J=7 Hz, CH2CO), 2.59 (2H, t, J=7 Hz, CH2CO); ESI-LCMS e/z calculated for C30H23ClN2O3 494.976, found 495 [M+H (35Cl)]+, 497 [M+H (37Cl)]+, 517 [M+Na (35Cl)]+, 519 [M+Na (37Cl)]+.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (2×20 mL)
  2. extractionThe combined extract
  3. washwas washed with water, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the product by flash column chromatography

Sources & evidence

ORD record
ord-d71e50287fb74e8db1999ccbf2b31cff
Source dataset
uspto-grants-2008_02
Patent number
US07329680B2

Reaction notes

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