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

HRID 1042536Notes

Reaction equation

HRID 1042536 reaction equation
Cl.Cl.[F:3][C:4]([F:35])([F:34])[C:5]1[CH:33]=[CH:32][C:8]([CH2:9][N:10]2[CH2:31][CH2:30][C:13]3[NH:14][C:15]4[CH:16]=[CH:17][C:18]([C:21]([NH:23][CH:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)=[O:22])=[CH:19][C:20]=4[C:12]=3[CH2:11]2)=[CH:7][CH:6]=1.Br.Br[CH2:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[N:42]1[CH:43]=[CH:44][C:39]([CH2:38][N:27]2[CH2:28][CH2:29][CH:24]([NH:23][C:21]([C:18]3[CH:17]=[CH:16][C:15]4[NH:14][C:13]5[CH2:30][CH2:31][N:10]([CH2:9][C:8]6[CH:32]=[CH:33][C:5]([C:4]([F:3])([F:34])[F:35])=[CH:6][CH:7]=6)[CH2:11][C:12]=5[C:20]=4[CH:19]=3)=[O:22])[CH2:25][CH2:26]2)=[CH:40][CH:41]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 127522194-(Bromomethyl)pyridine hbrHCID 665896624-(2-(4-(Trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole-8-carboxamido)piperidine dihydrochloride salt

Product 1

HCID 44176731n-(1-(Pyridin-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole-8-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of the dihydrochloride salt of step 1, above (65 mg, 0.12 mmol) was dissolved in DMF (2.0 mL) and 4-(bromomethyl)pyridine hydrobromide (2×35 mg, 2×0.14 mmol) and triethylamine (2×80 μL, 2×58 mg, 2×570 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 an off-white solid which was triturated with ethyl ether to provide N-(1-(pyridin-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 50, 60%). 1H NMR (DMSO-d6, 300 MHZ) 11.02 (s, 1H), 8.49 (d, J=4.7 Hz, 2H), 7.99 (d, J=8.0 Hz, 1H), 7.84 (s, 1H), 7.71 (d, J=8.0 Hz, 2H), 7.62 (d, J=8.3 Hz, 2H), 7.55 (d, J=8.3 Hz, 1H), 7.31 (d, J=4.7 Hz, 2H), 7.25 (d, J=8.3 Hz, 1H), 3.86 (s, 2H), 3.82-3.70 (m, 1H), 3.63 (s, 2H), 3.50 (s, 2H), 2.90-2.74 (m, 6H), 2.06 (t, J=11.1 Hz, 2H), 1.77 (d, J=10.2 Hz, 2H), 1.60 (q, J=10.9 Hz, 2H) ppm; MS (ES) 548 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. customto give an off-white solid which
  3. customwas triturated with ethyl ether

Sources & evidence

ORD record
ord-0b48812c5b244785906bc3e808d776f0
Source dataset
uspto-grants-2013_10
Patent number
US08557822B2

Reaction notes

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