Methanol → 1-isopropyl-3-methyl-6-(pyridazin-4-yl)-1H-indole-4-carboxylic acid

HRID 516788Notes

Reaction equation

HRID 516788 reaction equation
[CH:1]([N:4]1[C:12]2[CH:11]=[C:10]([C:13]3[CH:18]=[CH:17][N:16]=[N:15][CH:14]=3)[CH:9]=[C:8]([C:19]([O:21]C)=[O:20])[C:7]=2[C:6]([CH3:23])=[CH:5]1)([CH3:3])[CH3:2].CO.[OH-].[Li+].O>O1CCCC1>[CH:1]([N:4]1[C:12]2[CH:11]=[C:10]([C:13]3[CH:18]=[CH:17][N:16]=[N:15][CH:14]=3)[CH:9]=[C:8]([C:19]([OH:21])=[O:20])[C:7]=2[C:6]([CH3:23])=[CH:5]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 962Water2×HCID 3939Lithium Hydroxide2×HCID 67465466methyl 1-isopropyl-3-methyl-6-(pyridazin-4-yl)-1H-indole-4-carboxylate

Product 1

HCID 674650041-isopropyl-3-methyl-6-(pyridazin-4-yl)-1H-indole-4-carboxylic acidYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a 100 ml round bottom flask was added methyl 1-isopropyl-3-methyl-6-(pyridazin-4-yl)-1H-indole-4-carboxylate (74.0 mg, 0.239 mmol), Methanol (1595 μl), Tetrahydrofuran (THF) (3189 μl) and a magnetic stir bar. To the same was added lithium hydroxide, H2O (30.1 mg, 0.718 mmol) and the mixture was stirred at 55° C. Reaction progress was monitored by LCMS. LCMS(weekend) showed 50% conversion. To the reaction mixture was added lithium hydroxide, H2O (20.08 mg, 0.478 mmol) The reaction was continued to stir and heated to 55° C. After complete conversion the reaction solvent was removed and the remaining residue dissolved with water (1.5 ml). The aqueous solution was made acidic drop wise with 1N HCl until precipitation was complete. The solid was collected by vacuum filtration and washed with water (5 ml). The solid was dried under vacuum open to the air overnight. The product, 1-isopropyl-3-methyl-6-(pyridazin-4-yl)-1H-indole-4-carboxylic acid (68 mg, 0.228 mmol, 95% yield), was obtained as a brown solid. 1H NMR (400 MHz, DMSO-β6) δ 9.71-9.83 (m, 1H), 9.23 (dd, J=1.26, 5.56 Hz, 1H), 8.32 (s, 1H), 8.11 (dd, J=2.65, 5.43 Hz, 1H), 7.86 (s, 1H), 7.58 (s, 1H), 4.90-5.09 (m, 1H), 2.34 (s, 3H), 1.47 (d, J=6.82 Hz, 6H). MS(ES) [M+H]+ 296.2.

Workup

  1. customReaction progress
  2. stirringto stir
  3. temperatureheated to 55° C
  4. customAfter complete conversion the reaction solvent was removed
  5. dissolutionthe remaining residue dissolved with water (1.5 ml)
  6. customuntil precipitation
  7. filtrationThe solid was collected by vacuum filtration
  8. washwashed with water (5 ml)
  9. customThe solid was dried under vacuum open to the air overnight

Sources & evidence

ORD record
ord-eb0112eafdeb44268d6d728c1f9ce978
Source dataset
uspto-grants-2015_08
Patent number
US09114141B2

Reaction notes

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