Potassium Hydroxide → 2-{5-[1-(Isoquinoline-5-sulfonyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid

HRID 889718Notes

Reaction equation

C([O:3][C:4](=[O:45])[CH:5]([C:10]1[CH:11]=[C:12]([C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([S:22]([C:25]3[C:26]4[CH:27]=[CH:28][N:29]=[CH:30][C:31]=4[CH:32]=[CH:33][CH:34]=3)(=[O:24])=[O:23])[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[K+]>CCO>[CH:30]1[C:31]2[CH:32]=[CH:33][CH:34]=[C:25]([S:22]([N:18]3[CH2:19][CH2:20][CH2:21][CH:16]([C:14]4[CH:15]=[C:10]([CH:5]([CH2:6][CH:7]([CH3:9])[CH3:8])[C:4]([OH:45])=[O:3])[CH:11]=[C:12]([C:35]5[CH:40]=[CH:39][C:38]([C:41]([F:42])([F:43])[F:44])=[CH:37][CH:36]=5)[CH:13]=4)[CH2:17]3)(=[O:24])=[O:23])[C:26]=2[CH:27]=[CH:28][N:29]=1

Participants

Conditions

Temperature: 78 °C

Procedure

To a solution of compound 41a, 2-{5-[1-(Isoquinoline-5-sulfonyl)-piperidin-3-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester (59.0 mg, 0.092 mmol) in EtOH (4.6 ml) was added 2M KOH (0.46 ml, 0.92 mmol). The reaction was heated to 78° C. for 2 hours, cooled to room temperature, and concentrated in vacuo. Purification via Gilson HPLC, gave the product (35.7 mg, 63% ) 1H NMR (300 MHz, MeOD) δ ppm 0.79-0.86 (m, 6 H) 1.33-1.46 (m, J=13.21, 6.78, 6.65, 6.65, 6.65 Hz, 1 H) 1.49-1.64 (m, 3 H) 1.76-1.92 (m, 3 H) 2.64-2.72 (m, 1 H) 2.74-2.81 (m, 2 H) 3.62 (t, J=7.91 Hz, 1 H) 3.86 (d, J=10.55 Hz, 2 H) 7.13 (s, 1 H) 7.31 (s, 1 H) 7.40 (s, 1 H) 7.61-7.69 (m, 4 H) 8.00 (t, J=7.72 Hz, 1 H) 8.57-8.66 (m, 3 H) 8.99 (d, J=5.65 Hz, 1 H) 9.73 (s, 1 H) Calcd for C33H33F3N204S (M+H) 610.69, Found 611.2.

Workup

temperaturecooled to room temperature
concentrationconcentrated in vacuo
customPurification via Gilson HPLC

Sources & evidence

ORD record: ord-18bba4b33f8648ce8b99efb004806cbf
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252935B2

Reaction notes

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