Methanesulfonic Acid → HCID 10095153, compound

HRID 2376230Notes

Reaction equation

HRID 2376230 reaction equation
C([O:3][C:4](=[O:36])[CH:5]([C:29]1[CH:30]=[C:31]([CH3:35])[CH:32]=[CH:33][CH:34]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][CH2:19][CH:20]=[CH2:21])=[CH:14][CH:13]=2)[N:9]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)[N:8]=1)C.CS(O)(=O)=O>C(O)C.[Pd]>[N:18]1[C:15]2[C:16](=[CH:17][C:12]([C:10]3[N:9]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)[N:8]=[C:7]([CH2:6][CH:5]([C:29]4[CH:30]=[C:31]([CH3:35])[CH:32]=[CH:33][CH:34]=4)[C:4]([OH:3])=[O:36])[CH:11]=3)=[CH:13][CH:14]=2)[CH:21]=[CH:20][CH:19]=1.[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[N:9]([C:22]3[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=3)[N:8]=[C:7]([CH2:6][CH:5]([C:29]3[CH:30]=[C:31]([CH3:35])[CH:32]=[CH:33][CH:34]=3)[C:4]([OH:36])=[O:3])[CH:11]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 2

HCID 6395Methanesulfonic AcidHCID 23568905HCID 23568905, 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-f2fb4d0faba5495e9bd96b02258a833b
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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