Lithium hydroxide, monohydrate → {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid

HRID 2365715Notes

Reaction equation

HRID 2365715 reaction equation
C([O:5][C:6](=[O:37])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:36])[C@@H:15]([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[C:31]([F:34])([F:33])[F:32])[C:23]2=[O:35])[CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:9]1)(C)(C)C.O.[OH-].[Li+]>O1CCCC1.O>[CH:17]1([CH2:16][C@H:15]([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[C:31]([F:33])([F:34])[F:32])[C:23]2=[O:35])[C:14]([NH:13][C:10]2[CH:11]=[CH:12][N:8]([CH2:7][C:6]([OH:37])=[O:5])[N:9]=2)=[O:36])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 70674336{3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid tert-butyl ester

Product 1

HCID 70674337{3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acidYield 98%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A mixture of {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid tert-butyl ester (133 mg, 0.26 mmol, prepared as in Example 3) and lithium hydroxide monohydrate (22 mg, 0.52 mmol) in tetrahydrofuran:water (1:1, 10 mL) at room temperature was stirred for 2 h. The reaction mixture was then concentrated in vacuo and partitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate. The organic layer was then dried over magnesium sulfate, filtered to remove the drying agent, and the filtrate concentrated in vacuo to afford {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid (118 mg, 98%) as a white foam: HR-ES(+) m/e calcd for C22H23N4O4F3 [M+H]+ 465.1744, observed 465.1744; 1H NMR (400 MHz, DMSO-d6) δ ppm 10.93 (s, 1H), 8.01 (dd, J=7.67, 13.00 Hz, 2H), 7.69-7.80 (m, 1H), 7.59 (d, J=2.13 Hz, 1H), 6.45 (d, J=2.13 Hz, 1H), 4.95-5.12 (m, 2H), 4.81 (s, 2H), 4.72 (d, J=17.90 Hz, 1H), 1.09-2.11 (m, 11H).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. custompartitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate
  3. dry with materialThe organic layer was then dried over magnesium sulfate
  4. filtrationfiltered
  5. customto remove the drying agent
  6. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-58b7d43a505144f8baffe54d7d0f412a
Source dataset
uspto-grants-2014_04
Patent number
US08697705B2

Reaction notes

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