4-Toluenesulfonyl chloride → HCID 59438232、化合物

反応式

[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH3:12][N:13]1[C:17]([CH3:18])=[C:16]([CH2:19][N:20]2[CH2:25][CH2:24][N:23]([C:26]3[C:31]([N:32]4[CH2:37][CH2:36][CH:35]([CH2:38][OH:39])[CH2:34][CH2:33]4)=[N:30][CH:29]=[CH:28][N:27]=3)[CH2:22][CH2:21]2)[CH:15]=[N:14]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:12][N:13]1[C:17]([CH3:18])=[C:16]([CH2:19][N:20]2[CH2:21][CH2:22][N:23]([C:26]3[C:31]([N:32]4[CH2:37][CH2:36][CH:35]([CH2:38][O:39][S:7]([C:4]5[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=5)(=[O:9])=[O:8])[CH2:34][CH2:33]4)=[N:30][CH:29]=[CH:28][N:27]=3)[CH2:24][CH2:25]2)[CH:15]=[N:14]1

参加物

実験手順

Add p-toluenesulfonyl chloride (272 mg, 1.43 mmol, 1.1 eq) to a solution of {1-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-piperidin-4-yl}-methanol (0.5 g, 1.30 mmol, 1 eq, free base and triethylamine (1.43 mL, 10.24 mmol, 1.1 eq) in DCM (3 mL) at 0° C. Stir the mixture under nitrogen for 20.5 hr. Add a further portion of p-toluenesulfonyl chloride (0.13 g, 0.682 mmol, 0.5 eq) to the reaction mixture and continue stirring for a further 4.5 hr. Quench the reaction with saturated aqueous sodium bicarbonate solution (20 mL), and then pass through a hydrophobic frit to separate. Wash the aqueous layer twice with DCM (20 mL), combine the organic extracts and concentrate. Purify by flash chromatography on 40 g silica gel column, eluting with 0-10% methanol in DCM to give toluene-4-sulfonic acid 1-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-piperidin-4-ylmethyl ester (0.36 g, 51%). MS (m/z): 540.2 (M+1).