Thionyl Chloride → HCID 57565266, compound

HRID 2110149Notes

Reaction equation

HRID 2110149 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[C:10]([NH2:12])=[O:11].S(Cl)(Cl)=O.[CH3:17][C@H:18]1[CH2:23][N:22]([C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=2)[CH2:21][C@@H:20]([CH3:35])[N:19]1[S:36](C1C=CC=C2C=1CC(C(O)=O)C2)(=[O:38])=[O:37]>C1COCC1>[CH3:35][C@H:20]1[CH2:21][N:22]([C:24]2[CH:25]=[CH:26][C:27]([O:30][C:31]([F:34])([F:32])[F:33])=[CH:28][CH:29]=2)[CH2:23][C@@H:18]([CH3:17])[N:19]1[S:36]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[CH2:3][CH:2]([C:10]([NH2:12])=[O:11])[CH2:1]2)(=[O:37])=[O:38]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 17747011rel-4-[[(2R,6S)-2,6-Dimethyl-4-[4-(trifluoromethoxy)phenyl]-1-piperazinyl]sulfonyl]-2,3-dihydro-1H-indene-2-carboxylic acidHCID 232396192,3-dihydro-1H-indene-2-carboxamide

Product 1

HCID 57565266HCID 57565266, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-|cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl|-indan-2-carboxylic acid amide. Thionyl chloride (42 μL, 0.577 mmol) was added to 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxyphenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid (250 mg, 0.502 mmol) in THF (4 mL) at 50 C for 1 h and then concentrated. The crude mixture was then dissolved in THF (4 mL) and ammonium hydroxide (300 μL) was added. The cloudy brown solution was stirred for an additional 3 h at room temperature. The solution was then concentrated and purified by silica gel column chromatography (0-20% MeOH in dichloromethane) to afford 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid amide (190 mg, 76%). 1H NMR (400 MHz, CD3OD) δ ppm. 7.71 (d, 1H), 7.47 (d, 1H), 7.34 (t, 1H), 7.10 (d, 2H), 6.94-6.91 (m, 2H), 4.20-4.14 (m, 1H), 4.05-3.90 (m, 1H), 3.54 (d, 2H), 3.41-3.21 (m, 5H), 2.77 (dd, 1H), 2.68 (dd, 1H), 1.51 (d, 3H), 1.49 (d, 3H). LCMS: 498.7 (M+1)+.

Workup

  1. concentrationconcentrated
  2. dissolutionThe crude mixture was then dissolved in THF (4 mL)
  3. additionammonium hydroxide (300 μL) was added
  4. concentrationThe solution was then concentrated
  5. custompurified by silica gel column chromatography (0-20% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-7c2cd20f6bbf4ba082297f77feb57f6f
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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