4-Toluenesulfonyl chloride → HCID 59438232, compound

HRID 604315Notes

Reaction equation

HRID 604315 reaction equation
[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

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 8471TriethylamineHCID 59438224HCID 59438224, compound

Product 1

HCID 59438232HCID 59438232, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  1. stirringcontinue stirring for a further 4.5 hr
  2. customQuench
  3. customthe reaction with saturated aqueous sodium bicarbonate solution (20 mL)
  4. customto separate
  5. washWash the aqueous layer twice with DCM (20 mL)
  6. concentrationconcentrate
  7. customPurify by flash chromatography on 40 g silica gel column
  8. washeluting with 0-10% methanol in DCM

Sources & evidence

ORD record
ord-4ae2bad3b97142008a0b3484c2992353
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

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