Sodium Hydroxide → HCID 70681580, compound

HRID 528981Notes

Reaction equation

HRID 528981 reaction equation
[CH2:1]([C:5]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:8]=[C:7]([C:16]([O:18]CC)=[O:17])[C:6]=1[C:21]1[CH:26]=[CH:25][C:24]([C:27](=[O:42])[NH:28][S:29]([C:32]2[CH:41]=[CH:40][C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:33]=2)(=[O:31])=[O:30])=[CH:23][C:22]=1[C:43]([N:45]1[CH2:54][CH2:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:46]1)=[O:44])[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>C1COCC1>[CH2:1]([C:5]1[N:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:8]=[C:7]([C:16]([OH:18])=[O:17])[C:6]=1[C:21]1[CH:26]=[CH:25][C:24]([C:27](=[O:42])[NH:28][S:29]([C:32]2[CH:41]=[CH:40][C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:33]=2)(=[O:30])=[O:31])=[CH:23][C:22]=1[C:43]([N:45]1[CH2:54][CH2:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:46]1)=[O:44])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 70694200HCID 70694200, compound

Product 1

HCID 70681580HCID 70681580, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 25 mL round bottom flask was charged with ethyl 5-butyl-4-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1-phenyl-1H-pyrazole-3-carboxylate (Example 223, 52 mg, 0.070 mmol). THF (2.0 mL) and then 1N aq. NaOH solution (0.140 mL, 0.140 mmol) were added. The reaction mixture was stirred at room temperature overnight. After concentration in vacuo to remove the THF, the reaction mixture was made acidic (pH 3-4) with conc. HCl. The product was extracted with EtOAc and the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give the crude product (50 mg, 100%) as a yellow oil. A portion (approx. 10 mg) was purified by preparative HPLC to give the title compound (4 mg). 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.63 (s, 1H), 8.11-8.05 (m, 3H), 8.01-7.98 (m, 1H), 7.94 (d, J=4 Hz, 1H), 7.90 (d, J=4 Hz, 1H), 7.61-7.55 (m, 2H), 7.52-7.35 (m, 6H), 7.19-7.04 (m, 3.5H), 6.86-6.82 (m, 0.5H), 4.90-4.80 (m, 0.5H), 4.51-4.36 (m, 1.5H), 3.65-3.43 (m, 2H), 2.88-2.49 (m, 4H), 1.12-0.89 (m, 4H), 0.61-0.56 (m, 3H); MS (ESI+) m/z 713.3 (M+H)+.

Workup

  1. concentrationAfter concentration in vacuo
  2. customto remove the THF
  3. extractionThe product was extracted with EtOAc
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give the crude product (50 mg, 100%) as a yellow oil
  7. customA portion (approx. 10 mg) was purified by preparative HPLC

Sources & evidence

ORD record
ord-3ccd3c52101a4ed8b76e17a7cf24412b
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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