Hydrochloric Acid → 4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acid

HRID 1505707Notes

Reaction equation

HRID 1505707 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH:9]([N:12]2[CH:16]=[C:15]([C:17]3[CH:18]=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]5[CH:30]=[N:31][N:32]([CH3:34])[CH:33]=5)[CH:24]=4)=[N:21][CH:22]=3)[CH:14]=[N:13]2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].Cl>CC(O)C>[CH3:34][N:32]1[CH:33]=[C:29]([C:25]2[CH:24]=[C:23]([C:20]3[N:21]=[CH:22][C:17]([C:15]4[CH:14]=[N:13][N:12]([CH:9]5[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]5)[CH:16]=4)=[CH:18][N:19]=3)[CH:28]=[CH:27][CH:26]=2)[CH:30]=[N:31]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 899244074-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acid ethyl ester

Product 1

HCID 729439964-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acidYield 63.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acid ethyl ester (50 mg; 0.11 mmol; 1.0 eq.) and NaOH (5.00 mL of a 1N solution; 5.0 mmol; 46 eq.) in iPrOH (20 mL) was stirred at RT for 16 h. It was then poured into a 1 N solution of HCl and extracted with EtOAc (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated to give a cis-trans mixture of the title compound as a yellow solid (30 mg, 59%). 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 2H), 8.57-8.47 (m, 2H), 8.27 (s, 1H), 8.24-8.17 (m, 1H), 8.13 (s, 1H), 7.92 (s, 1H), 7.78-7.66 (m, 1H), 7.51 (t, J=7.8 Hz, 1H), 4.31-4.15 (m, 1H), 3.89 (s, 3H), 2.66-1.45 (m, 9H). HPLC (Condition A): Rt 3.23 min (purity 93.0%). HPLC (Chiralpak IA, EtOH:TFA:THF 90:0.1:10): Rt 7.23; 10.97 min (purity 30.2: 66.6%); MS (ESI+): 429.2.

Workup

  1. extractionextracted with EtOAc (twice)
  2. washCombined organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give

Sources & evidence

ORD record
ord-6834fc521dac49d699e89f40bd13805a
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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