HCID 57882765, compound → HCID 57518490, compound

HRID 1817760Notes

Reaction equation

HRID 1817760 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12](OS(C(F)(F)F)(=O)=O)[N:11]([C@H:22]([C:24]3[CH:41]=[CH:40][C:27]([C:28]([NH:30][CH2:31][CH2:32][C:33]([O:35]C(C)(C)C)=[O:34])=[O:29])=[CH:26][CH:25]=3)[CH3:23])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:42][C:43]([F:59])([F:58])[O:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[C:50](B(O)O)[CH:49]=[CH:48]2>C(COC)OC>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:50]3[CH:49]=[CH:48][C:47]4[C:52](=[CH:53][CH:54]=[C:45]([O:44][C:43]([F:42])([F:59])[F:58])[CH:46]=4)[CH:51]=3)[N:11]([C@H:22]([C:24]3[CH:25]=[CH:26][C:27]([C:28]([NH:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:29])=[CH:40][CH:41]=3)[CH3:23])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

4

Reactant 2

HCID 57882765HCID 57882765, compoundHCID 60170684HCID 60170684, compound

Product 1

HCID 57518490HCID 57518490, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl N-{4-[(1S)-1-(3-(3,5-dichlorophenyl)-5-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate (10 mg, 0.016 mmol), 6-trifluoromethoxy-2-naphthylboronic acid (5.1 mg, 0.02 mmol), and TEA (14 ul, 0.1 mmol) were dissolved in dimethoxyethane (0.5 ml) and deoxygenated by vacuum-N2 fill cycles. The catalyst Pd(PPh3)4 (2 mg, 10% mol) was added and the mixture was deoxygenated again before heated in microwave reactor to 100° C. for 10 min. The mixture was quenched with 1.5 ml of CH3CN:H2O (3:1, with 5% TFA) and product separated through reverse phase preparative HPLC. The collected product was treated with 1 ml of TFA-DCM (1:2) for 30 min, and the residue lyophilized to give N-[4-((1S)-1-{3-(3,5-dichlorophenyl)-5-[6-(trifluoromethoxy)-2-naphthyl]-1H-pyrazol-1-yl}ethyl)benzoyl]-β-alanine as fine powder. NMR (500 MHz, DMSO-d6) δ: 1.91 (d, J=7.0 Hz, 3H); 2.46 (t, J=7.0 Hz, 2H); 3.41 (q, J=7.0 Hz, 2H); 5.78 (q, J=7.0 Hz, 1H); 7.21 (d, J=8.4 Hz, 2H); 7.22 (s, 1H); 7.57 (t, J=1.9 Hz, 1H; 7.58˜7.60 (m, 2H); 7.72 (d, J=8.4 Hz, 2H); 7.94 (d, J=1.9 Hz, 2H); 8.04 (br s, 1H); 8.06 (br s, 1H); 8.09 (d, J=9.1 Hz, 1H); 8.13 (d, J=8.6 Hz, 1H); 8.44 (t, J=5.5 Hz, 1H). MS C32H24Cl2F3N3O4 Cald: 641.11; Obsd (M+1): 642.22.

Workup

  1. customdeoxygenated by vacuum-N2 fill cycles
  2. additionThe catalyst Pd(PPh3)4 (2 mg, 10% mol) was added
  3. customthe mixture was deoxygenated again
  4. customThe mixture was quenched with 1.5 ml of CH3CN:H2O (3:1, with 5% TFA) and product
  5. customseparated through reverse phase preparative HPLC
  6. additionThe collected product was treated with 1 ml of TFA-DCM (1:2) for 30 min

Sources & evidence

ORD record
ord-4573f3a2cdcb4b9b94074c895d63e32b
Source dataset
uspto-grants-2009_10
Patent number
US07598285B2

Reaction notes

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