Methanesulfonic Acid → HCID 10095153, compound

HRID 1823228Notes

Reaction equation

HRID 1823228 reaction equation
[CH2:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)[N:14]=[C:13]([CH2:23][CH:24]([C:28]3[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=3)[C:25]([OH:27])=[O:26])[CH:12]=2)=[CH:7][CH:6]=1)[CH:2]=[CH2:3].CS(O)(=O)=O>C(O)C.[Pd]>[N:4]1[C:5]2[C:10](=[CH:9][C:8]([C:11]3[N:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[N:14]=[C:13]([CH2:23][CH:24]([C:28]4[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=4)[C:25]([OH:27])=[O:26])[CH:12]=3)=[CH:7][CH:6]=2)[CH:3]=[CH:2][CH:1]=1.[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)[N:14]=[C:13]([CH2:23][CH:24]([C:28]3[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=3)[C:25]([OH:27])=[O:26])[CH:12]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 2

HCID 6395Methanesulfonic AcidHCID 22171008HCID 22171008, compound

Product 2

HCID 10095153HCID 10095153, compoundYield 35%HCID 22171069HCID 22171069, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-[5-(4-allylamino-phenyl)-1-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester (Example 94, Step A; 70 mg, 0.15 mmol) in ethanol (1 mL) was added 10% Pd/C (26 mg) and methanesulfonic acid (0.01 mL, 0.15 mmol, 1 equiv). The mixture was stirred at 65° C. for 2 h. The catalyst was removed by filtering the reaction mixture through a CELITE® pad, and the pad was rinsed with EtOH (1.5 mL). The combined filtrates were concentrated under reduced pressure. The crude residue was dissolved in 1:1 THF/H2O (1.5 mL), and LiOH was added (10 mg, 0.45 mmol, 3 equiv). After 3 h at 45° C., the mixture was purified by preparative reversed-phase HPLC (acetonitrile/water) to afford the title compound (26 mg, 35%) along with 3-[5-(4-amino-phenyl)-1-p-tolyl-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid (20 mg, 35%). HPLC: Rt=3.18 (Method A). MS (ESI): mass calculated for C29H25N3O2, 447.19; m/z found, 448.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.43 (d, J=8.5 Hz, 1H), 8.25 (d, J=8.8 Hz, 1H), 7.85 (d, J=1.7 Hz, 1H), 7.68 (dd, J=8.3, 4.8 Hz, 1H), 7.59 (dd, J=8.8, 1.7 Hz, 1H), 7.26-7.23 (m, 2H), 7.12 (s, 4H), 6.42 (s, 1H), 4.17 (dd, J=9.8, 5.3 Hz, 1H), 3.58 (dd, J=14.9, 9.8 Hz, 1H), 3.17 (dd, J=14.9, 5.3 Hz, 1H), 2.36 (s, 3H).

Workup

  1. customThe catalyst was removed
  2. filtrationby filtering the reaction mixture through a CELITE® pad
  3. washthe pad was rinsed with EtOH (1.5 mL)
  4. concentrationThe combined filtrates were concentrated under reduced pressure
  5. dissolutionThe crude residue was dissolved in 1:1 THF/H2O (1.5 mL), and LiOH
  6. additionwas added (10 mg, 0.45 mmol, 3 equiv)
  7. waitAfter 3 h at 45° C.
  8. customthe mixture was purified by preparative reversed-phase HPLC (acetonitrile/water)

Sources & evidence

ORD record
ord-f61319c74ad44e169d2fd9bfc0c2ae9a
Source dataset
uspto-grants-2006_05
Patent number
US07037931B2

Reaction notes

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