Hydrochloric Acid → HCID 86719438, compound

HRID 2278695Notes

Reaction equation

HRID 2278695 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:37])=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[C@@H:26]([CH2:27][C:28]([O:30]C)=[O:29])[C@H:25]([CH3:32])[C:24]([C:33]([F:36])([F:35])[F:34])=[N:23]4)=[CH:18][CH:17]=3)[CH2:11][CH2:10]2)[CH:8]=1.[Li+].[OH-].Cl>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:37])=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[CH:17]=[CH:18][C:19]([N:22]4[C@@H:26]([CH2:27][C:28]([OH:30])=[O:29])[C@H:25]([CH3:32])[C:24]([C:33]([F:36])([F:35])[F:34])=[N:23]4)=[CH:20][CH:21]=3)[CH2:11][CH2:10]2)[CH:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86719439HCID 86719439, compound

Product 1

HCID 86719438HCID 86719438, compoundYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a round bottom flask was added methyl 2-((4S,5S)-1-(4-((1-(5-methoxy-2-methylphenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate (45 mg, 0.087 mmol), 2M LiOH (0.26 mL, 0.52 mmol) and THF (1 mL). The reaction solution was stirred at rt for 1.5 h, and the solution was acidified with 1N HCl to pH<4. The mixture was extracted with EtOAc (10 mL). The organic layer was washed with water (10 mL) and brine (10 mL), and then it was dried over MgSO4, filtered and concentrated. The residue was purified by Prep-HPLC to give 2-((4S,5S)-1-(4-(1-(5-methoxy-2-methylphenyl)piperidin-4-yloxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetic acid (31 mg, 0.062 mmol, 71% yield). LC-MS Anal. Calc'd for C26H30F3N3O4: 505.2. found [M+H] 506.1. 1H NMR (500 MHz, DMSO-d6) δ 7.12-7.03 (m, 3H), 6.99 (d, J=9.1 Hz, 2H), 6.59 (br. s., 1H), 6.55 (dd, J=8.3, 1.9 Hz, 1H), 4.45 (d, J=3.9 Hz, 2H), 3.72 (s, 4H), 3.39-3.33 (m, 2H), 3.05 (d, J=4.4 Hz, 2H), 2.78 (t, J=9.9 Hz, 2H), 2.66 (dd, J=16.2, 3.0 Hz, 1H), 2.18 (s, 3H), 2.05 (br. s., 2H), 1.85-1.72 (m, 2H), 1.27 (d, J=6.9 Hz, 3H). hGPR40 EC50=161 nM.

Workup

  1. extractionThe mixture was extracted with EtOAc (10 mL)
  2. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  3. dry with materialit was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by Prep-HPLC

Sources & evidence

ORD record
ord-157b78ee92d9440aa4fc997358befb6c
Source dataset
uspto-grants-2015_09
Patent number
US09133163B2

Reaction notes

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