4-Toluenesulfonyl chloride → HCID 11502228, compound

HRID 1864616Notes

Reaction equation

HRID 1864616 reaction equation
C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[F:12][C:13]([F:28])([F:27])[O:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]([OH:26])=[O:25])=[N:20][NH:21]2)=[CH:17][CH:16]=1.[N:29]12[CH2:36][CH2:35][CH:32]([CH2:33][CH2:34]1)[C@H:31](O)[CH2:30]2>N1C=CC=CC=1>[F:28][C:13]([F:12])([F:27])[O:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]([O:26][C@H:31]3[CH:32]4[CH2:35][CH2:36][N:29]([CH2:34][CH2:33]4)[CH2:30]3)=[O:25])=[N:20][NH:21]2)=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 7364113-Quinuclidinol, (+)-HCID 299215486-(Trifluoromethoxy)-1H-indazole-3-carboxylic acid

Product 1

HCID 11502228HCID 11502228, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

p-Toluenesulfonyl chloride (0.16 mmol) was added to a 0° C. solution of 6-(trifluoromethoxy)-1H-indazole-3-carboxylic acid (0.81 mmol) in pyridine. (5.00 mL). (3S)-Quinuclidin-3-ol (0.81 mmol) was added and the reaction mixture was allowed to warm to rt. The reaction mixture was maintained for 16 h and was filtered and concentrated. The residue was redissolved in methanol and loaded on a 5 g SCX column. The column was washed with methanol and the product was eluted with methanol/dimethylethylamine (9/1) and concentrated. The residue was purified by preparative HPLC to produce the desired product in 16% yield. Note: this procedure works equally well when p-toluenesulfonyl chloride is replaced with oxalyl chloride. 1H NMR (CDCl3) δ 8.52 (s, 1 H), 7.96 (d, J=8.9, 1H), 7.49 (s, 1 H), 7.09 (d, J=8.9, 1H), 5.31 (m, 1 H), 3.72-3.29 (m, 6 H), 2.56 (m, 1 H), 2.32 (m, 1 H), 2.06-1.88 (m, 3 H); LC/MS (EI) tR 4.9 min, m/z 356 (M++1).

Workup

  1. temperatureThe reaction mixture was maintained for 16 h
  2. filtrationwas filtered
  3. concentrationconcentrated
  4. dissolutionThe residue was redissolved in methanol
  5. washThe column was washed with methanol
  6. washthe product was eluted with methanol/dimethylethylamine (9/1)
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-40cee8f4ad954af589f9a96c630c8d8d
Source dataset
uspto-grants-2009_12
Patent number
US07625924B2

Reaction notes

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