Hydrochloric Acid → 1-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-one

HRID 882026Notes

Reaction equation

HRID 882026 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[N: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.Cl>CO.C(Cl)Cl>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([N:11]3[CH:16]=[CH:15][C:14]([C:17]4[N:18]=[N:19][C:20]([C:23]([F:24])([F:26])[F:25])=[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

5

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86667078tert-Butyl 9-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridazin-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 575245821-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-oneYield 68.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 9-methyl-2-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (70 mg, 0.13 mmol) was treated with 1.25 M HCl in MeOH (3.4 mL), and the resulting suspension was stirred at ambient temperature for 18 h. The resulting suspension was diluted with CH2Cl2 (1.8 mL) and stirred at ambient temperature for 4 h. To the suspension 1.25 M HCl in MeOH (2.0 mL) was added, and the resulting suspension was stirred at ambient temperature for 18 h. 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 extraction was dried over Na2SO4 and concentrated under reduced pressure to dryness. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 1 column volumes, increased to 0:100 over 20 column volumes and held for 83 column volumes) provided the title compound (38 mg, 67%) as a yellow powder: 1H NMR (500 MHz, DMSO-d6) δ 8.71 (d, J=8.5 Hz, 1H), 8.46 (d, J=9.0 Hz, 1H), 8.13 (d, J=7.0 Hz, 1H), 7.96 (d, J=8.5 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.22 (dd, J=7.5, 2.0 Hz, 1H), 3.91 (s, 2H), 3.69 (s, 3H), 3.11 (t, J=5.5 Hz, 2H), 2.78 (t, J=5.5 Hz, 2H); ESI MS m/z 427 [M+H]+.

Workup

  1. stirringstirred at ambient temperature for 4 h
  2. stirringthe resulting suspension was stirred at ambient temperature for 18 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. extractionthe organic extraction
  8. dry with materialwas dried over Na2SO4
  9. concentrationconcentrated under reduced pressure to dryness
  10. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 1 column volumes, increased to 0:100 over 20 column volumes and held for 83 column volumes)

Sources & evidence

ORD record
ord-d986db2e5e93444a93d1de2b1ff84286
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

Loading…