Triethylamine → 4-[cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carbonitrile

HRID 2110150Notes

Reaction equation

HRID 2110150 reaction equation
C1C2C(=CC=CC=2)CC1C#N.C(N(CC)CC)C.P(Cl)(Cl)(Cl)=O.[CH3:24][C@H:25]1[CH2:30][N:29]([C:31]2[CH:36]=[CH:35][C:34]([O:37][C:38]([F:41])([F:40])[F:39])=[CH:33][CH:32]=2)[CH2:28][C@@H:27]([CH3:42])[N:26]1[S:43]([C:46]1[CH:54]=[CH:53][CH:52]=[C:51]2[C:47]=1[CH2:48][CH:49]([C:55]([NH2:57])=O)[CH2:50]2)(=[O:45])=[O:44]>ClC(Cl)C>[CH3:24][C@H:25]1[CH2:30][N:29]([C:31]2[CH:36]=[CH:35][C:34]([O:37][C:38]([F:40])([F:39])[F:41])=[CH:33][CH:32]=2)[CH2:28][C@@H:27]([CH3:42])[N:26]1[S:43]([C:46]1[CH:54]=[CH:53][CH:52]=[C:51]2[C:47]=1[CH2:48][CH:49]([C:55]#[N:57])[CH2:50]2)(=[O:45])=[O:44]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 232396182,3-Dihydro-1H-indene-2-carbonitrileHCID 57565266HCID 57565266, compound

Product 1

HCID 575651884-[cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carbonitrileYield 9.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

4-|cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl|-indan-2-carbonitrile. Triethylamine (200 μL, 1.4349 mmol) and phosphorus oxychloride (74 μL, 0.7939 mmol) were added to a solution of 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid amide (254 mg, 0.5105 mmol) in dichloroethane (3 mL). The reaction was stirred for 4 h at room temperature then directly purified by silica gel column chromatography (0-50% EtOAc in hexanes) to afford 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carbonitrile (23 mg, 9%). 1H NMR (400 MHz, CD3OD) δ ppm 7.77 (d, 1H), 7.54 (d, 1H), 7.42 (t, 1H), 7.10 (d, 2H), 6.93 (d, 2H), 4.20-4.00 (m, 2H), 3.65-3.60 (m, 1H), 3.60-3.40 (m, 2H), 3.40-3.20 (m, 4H), 2.80-2.60 (m, 2H), 1.50 (d, 6H). LCMS: 480.0 (M+1)+.

Workup

  1. customthen directly purified by silica gel column chromatography (0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c70027a07fb34e9babe614d7b359f273
Source dataset
uspto-grants-2009_04
Patent number
US07517884B2

Reaction notes

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