Hydrochloric Acid → 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid

HRID 2381380Notes

Reaction equation

HRID 2381380 reaction equation
C[O:2][C:3](=[O:28])[CH:4]([N:11]1[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[CH:21]=[CH:22][NH:23]3)[CH:13]=[N:12]1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Na+].Cl>CO.O>[CH:6]1([CH2:5][CH:4]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:20]=3[CH:21]=[CH:22][NH:23]4)[CH:13]=[N:12]2)[C:3]([OH:28])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 668911313-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester

Product 1

HCID 579192293-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acidYield 42%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid methyl ester (500 mg, 1.3 mmol) in methanol (3 mL) was treated with a 4N aqueous sodium hydroxide solution (63 mg, 1.57 mmol). The reaction solution was stirred at 25° C. overnight. At this time, the reaction mixture was diluted with water (10 mL) and was acidified with a 1N aqueous hydrochloric acid solution until pH=2. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Chromatography afforded 3-cyclopentyl-2-[4-(1H-indol-4-yloxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid as an off-white solid (0.2 g, 42%); LC-MS: 368 [M+1]+, tR=4.21 min. Purity on HPLC: 95.1% (254 nm), 96.6% (214 nm), tR=7.26 min. 1H NMR (300 MHz, CDCl3): δ 13.00 (s, 1H), 11.50 (s, 1H), 8.17 (d, 1H, J=2.4 Hz), 7.42 (d, 2H, J=7.8 Hz), 7.17 (t, 1H, J=7.8 Hz), 6.89 (d, 1H, J=7.8 Hz), 6.26 (s, 1H), 5.63 (d, 1H, J=2.4 Hz), 5.31 (dd, 1H, J1=10.5 Hz, J2=4.2 Hz), 2.23˜2.13 (m, 1H), 2.02˜1.94 (m, 1H), 1.59˜1.44 (m, 7H), 1.18˜1.04 (m, 2H).

Workup

  1. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  2. washThe combined organics were washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-93e51d0633f349c3a7d782103893d052
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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