Triethylamine → n-(1-(4-Cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole-8-carboxamide

HRID 340401Notes

Reaction equation

HRID 340401 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:38]=[CH:37][C:6]([CH2:7][N:8]2[CH2:36][CH2:35][C:11]3[NH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH:21][CH:22]5[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]5)=[O:20])=[CH:17][C:18]=4[C:10]=3[CH2:9]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:48]([C:50]1[CH:55]=[CH:54][C:53]([S:56](Cl)(=[O:58])=[O:57])=[CH:52][CH:51]=1)#[N:49].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:48]([C:50]1[CH:51]=[CH:52][C:53]([S:56]([N:25]2[CH2:26][CH2:27][CH:22]([NH:21][C:19]([C:16]3[CH:15]=[CH:14][C:13]4[NH:12][C:11]5[CH2:35][CH2:36][N:8]([CH2:7][C:6]6[CH:5]=[CH:4][C:3]([C:2]([F:40])([F:1])[F:39])=[CH:38][CH:37]=6)[CH2:9][C:10]=5[C:18]=4[CH:17]=3)=[O:20])[CH2:23][CH2:24]2)(=[O:58])=[O:57])=[CH:54][CH:55]=1)#[N:49]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 394974-Cyanobenzenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 44177408tert-butyl 4-(2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamido)piperidine-1-carboxylate

Product 1

HCID 44177716n-(1-(4-Cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole-8-carboxamideYield 97%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of tert-butyl 4-(2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamido)piperidine-1-carboxylate (9, 50 mg, 90 μmol) in DCM (1.0 mL), TFA (1.0 mL) was added. After allowing the reaction mixture to stir at room temperature for 2 h, the volatiles were evaporated, DCM and toluene (10 mL) were added and the volatiles evaporated (2×). The resulting residue was dissolved in DMF (2.0 mL) and triethylamine (0.5 mL, 0.36 g, 3.6 mmol) and 4-cyanobenzenesulfonyl chloride (22 mg, 110 μmol) were added. The resulting reaction mixture was allowed to stir at room temperature overnight, poured into saturated sodium bicarbonate solution (20 mL) to give a tan solid which was triturated with ethyl ether to provide N-(1-(4-cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 21, 54 mg, 97%). 1H NMR (DMSO-d6, 300 MHZ) 11.04 (br s, 1H), 8.12 (d, J=8.5 Hz, 2H), 8.04 (d, J=7.7 Hz, 1H), 7.92 (d, J=8.3 Hz, 2H), 7.79 (s, 1H), 7.71 (d, J=8.0 Hz, 2H), 7.62 (d, J=7.7 Hz, 2H), 7.51 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.5 Hz, 1H), 3.86 (s, 2H), 3.82-3.72 (m, 1H), 3.70-3.59 (m, 4H), 2.90-2.78 (m, 4H), 2.56-2.44 (m, 2H), 1.90-1.80 (m, 2H), 1.64-1.48 (m, 2H) ppm; MS (ES) 622 (M+H).

Workup

  1. customthe volatiles were evaporated
  2. additionDCM and toluene (10 mL) were added
  3. customthe volatiles evaporated (2×)
  4. dissolutionThe resulting residue was dissolved in DMF (2.0 mL)
  5. customThe resulting reaction mixture
  6. stirringto stir at room temperature overnight
  7. customto give a tan solid which
  8. customwas triturated with ethyl ether

Sources & evidence

ORD record
ord-0ba774156cf640c1926d2781a923af15
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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