Sodium Hydroxide → 4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

HRID 528791Notes

Reaction equation

HRID 528791 reaction equation
[Cl:1][C:2]1[C:3]([C:31](=[O:41])[N:32]([CH2:37][CH2:38][CH2:39][CH3:40])[CH2:33][CH2:34][CH2:35][CH3:36])=[N:4][N:5]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14]CC)=[O:13])=[CH:10][C:9]=2[C:19]([N:21]2[CH2:30][CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[C:6]=1[CH3:7].[OH-].[Na+]>CCO.C1COCC1>[Cl:1][C:2]1[C:3]([C:31](=[O:41])[N:32]([CH2:37][CH2:38][CH2:39][CH3:40])[CH2:33][CH2:34][CH2:35][CH3:36])=[N:4][N:5]([C:8]2[CH:18]=[CH:17][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=2[C:19]([N:21]2[CH2:30][CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[C:6]=1[CH3:7]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71062392Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Product 1

HCID 710621944-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acidYield 99.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (930 mg, 1.61 mmol) in EtOH (5.0 mL) and THF (5.0 mL) was added 2N NaOH (4.0 mL, 8.03 mmol). The resulting reaction mixture was stirred at 40° C. for 1 h, cooled to room temperature and quenched with 6N HCl. The solution was extracted with CHCl3 (3×), and the combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to afford the title compound (885 mg, 99%), which was used without further purification. 1H NMR (DMSO-d6, 2:1 mixture of amide rotamers) δ 8.32 (s, 0.5H), 8.14 (dd, J=8.36, 1.98 Hz, 1H), 8.07-7.98 (m, 1H), 7.83-7.72 (m, 1H), 7.28-7.06 (m, 3H), 7.03-6.93 (m, 0.5H), 4.86-4.68 (m, 0.5H), 4.65-4.47 (m, 1H), 4.42-4.24 (m, 0.5H), 3.88-3.70 (m, 0.5H), 3.66-3.34 (m, 3.5H), 3.23-3.06 (m, 1H), 3.04-2.94 (m, 1H), 2.87-2.70 (m, 2H), 2.26 (s, 2H), 2.21 (s, 1H), 1.47-1.34 (m, 0.5H), 1.33-1.06 (m, 5.5H), 1.01-0.91 (m, 2H), 0.88-0.82 (m, 3H), 0.70-0.62 (m, 3H); MS(ESI+) m/z 551.3 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to room temperature
  3. customquenched with 6N HCl
  4. extractionThe solution was extracted with CHCl3 (3×)
  5. dry with materialthe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e14f88939d4045a59186947537d6b3a5
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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