tert-Butyl 9-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate → 1-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-one

HRID 882030Notes

Reaction equation

HRID 882030 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([N:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:18]=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=4)=[CH:13][C:12]3=[O:27])=[CH:9][CH:10]=[C:5]2[C:4]2[CH2:28][N:29](C(OC(C)(C)C)=O)[CH2:30][CH2:31][C:3]1=2>C(Cl)Cl.CO.Cl.CCOCC>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([N:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:18]=[N:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=4)=[CH:13][C:12]3=[O:27])=[CH:9][CH:10]=[C:5]2[C:4]2[CH2:28][NH:29][CH2:30][CH2:31][C:3]1=2

Participants

6

Reactant 1

HCID 67970879tert-Butyl 9-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

Product 1

HCID 575245831-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-2(1H)-oneYield 75%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 9-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridin-3-yl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.81 g, 1.6 mmol) in CH2Cl2 (8.0 mL) was added 1.25 M HCl in MeOH (30 mL), and the resulting suspension was stirred at ambient temperature for 18 h. The suspension was diluted with CH2Cl2 (18 mL), 1.25 M HCl in MeOH (6.0 mL) was added, and the resulting suspension was stirred at ambient temperature for 72 h. The suspension was diluted with Et2O (50 mL), and the resulting solids were collected by filtration, dissolved in CH2Cl2 (30 mL), and washed with saturated NaHCO3 solution (50 mL). The resulting layers were separated, and the organic layer was concentrated under reduced pressure to dryness. Flash chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 1 column volume, increased to 0:100 over 12 column volumes and held for 30 column volumes) provided the title compound (0.50 g, 75%) as a yellow powder: 1H NMR (500 MHz, DMSO-d6) δ 9.20 (d, J=2.0 Hz, 1H), 8.50 (dd, J=8.0, 2.0 Hz, 1H), 8.10-8.02 (m, 2H), 7.94 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.5 Hz, 1H), 7.02 (d, J=2.0 Hz, 1H), 6.83 (dd, J=7.5, 20 Hz, 1H), 3.89 (s, 2H), 3.68 (s, 3H), 3.09 (t, J=5.5 Hz, 2H), 2.76 (t, J=5.5 Hz, 2H).

Workup

  1. additionwas added
  2. stirringthe resulting suspension was stirred at ambient temperature for 72 h
  3. filtrationthe resulting solids were collected by filtration
  4. dissolutiondissolved in CH2Cl2 (30 mL)
  5. washwashed with saturated NaHCO3 solution (50 mL)
  6. customThe resulting layers were separated
  7. concentrationthe organic layer was concentrated under reduced pressure to dryness
  8. temperatureFlash chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 1 column volume, increased to 0:100 over 12 column volumes and held for 30 column volumes)

Sources & evidence

ORD record
ord-9497e61f856f4f80a250c6f8a78b4eb1
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

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