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)pyridin-3-yl)methoxy)pyridin-2(1H)-one

HRID 882034Notes

Reaction equation

HRID 882034 reaction equation
[CH3:1][N:2]1[C:6]2=[N:7][C:8]([N:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)=[CH:13][C:12]3=[O:29])=[CH:9][CH:10]=[C:5]2[C:4]2[CH2:30][N:31](C(OC(C)(C)C)=O)[CH2:32][CH2:33][C:3]1=2.Cl>CO.CCOCC>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([N:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:23][CH:24]=4)=[CH:13][C:12]3=[O:29])=[CH:9][CH:10]=[C:5]2[C:4]2[CH2:30][NH:31][CH2:32][CH2:33][C:3]1=2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86667079tert-Butyl 9-methyl-2-(2-oxo-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)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 575245841-(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)methoxy)pyridin-2(1H)-oneYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

tert-Butyl 9-methyl-2-(2-oxo-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.43 g, 0.77 mmol) was treated with 1.25 M HCl in MeOH (15 mL), and the resulting solution was stirred at ambient temperature for 18 h. The solution was diluted with Et2O (50 mL). The resulting solids were collected by filtration, dissolved in 10:3 CH2Cl2/MeOH (50 mL), and washed with saturated NaHCO3 solution (50 mL). The aqueous layer was extracted with CH2Cl2 (8×25 mL), and the organic extracts were combined. The remaining solids in the aqueous solution were separated by filtration and washed with MeOH (100 mL). The resulting filtrate was extracted with CH2Cl2 (3×50 mL). All the organic extracts were combined and concentrated to dryness under reduced pressure. The resulting residue was diluted in CH2Cl2, washed with brine (2×20 mL), dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure to provide the title compound (0.27 g, 76%) as an off-white powder: 1H NMR (500 MHz, DMSO-d6) δ 8.89 (d, J=1.5 Hz, 1H), 8.19 (dd, J=8.0, 1.5 Hz, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 6.19 (dd, J=7.5, 2.5 Hz, 1H), 6.03 (s, J=3.0 Hz, 1H), 5.36 (s, 2H), 3.87 (s, 2H), 3.65 (s, 3H), 3.08 (t, J=5.5 Hz, 2H), 2.74 (t, J=5.5 Hz, 2H).

Workup

  1. filtrationThe resulting solids were collected by filtration
  2. dissolutiondissolved in 10:3 CH2Cl2/MeOH (50 mL)
  3. washwashed with saturated NaHCO3 solution (50 mL)
  4. extractionThe aqueous layer was extracted with CH2Cl2 (8×25 mL)
  5. customThe remaining solids in the aqueous solution were separated by filtration
  6. washwashed with MeOH (100 mL)
  7. extractionThe resulting filtrate was extracted with CH2Cl2 (3×50 mL)
  8. concentrationconcentrated to dryness under reduced pressure
  9. additionThe resulting residue was diluted in CH2Cl2
  10. washwashed with brine (2×20 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-1411b52c0010424f8b49d1e5726ba224
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

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