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

HRID 882016Notes

Reaction equation

HRID 882016 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[N:20]=[C:19]3[N:21]([CH3:35])[C:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][C:23]=4[C:18]3=[CH:17][CH:16]=2)[C:11](=[O:36])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CO>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[N:20]=[C:19]3[N:21]([CH3:35])[C:22]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[C:18]3=[CH:17][CH:16]=2)[C:11](=[O:36])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67988826tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine-6-carboxylate

Product 1

HCID 575245054-(Benzyloxy)-1-(9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)pyridin-2(1H)-oneYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.51 g, 1.1 mmol) was treated with 1.25 M HCl in MeOH (25 mL), and the resulting solution was stirred at ambient temperature for 18 h. The solution was concentrated to dryness under reduced pressure. The resulting residue was diluted with CH2Cl2 (30 mL) and washed with saturated NaHCO3 solution (50 mL). The resulting layers were separated, and the aqueous phase was extracted with CH2Cl2 (3×30 mL). The combined organic extractions were dried over Na2SO4 and concentrated under reduced pressure to dryness. Flash chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 0:100 over 4 column volumes and held for 10 column volumes) provided the title compound (0.24 g, 59%) as an off-white film: 1H NMR (300 MHz, DMSO-d6) δ 7.87 (d, J=8.1 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.49-7.37 (m, 5H), 7.23 (d, J=8.1 Hz, 1H), 6.15 (dd, J=7.5, 2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.16 (s, 2H), 3.87 (s, 2H), 3.65 (s, 3H), 3.07 (t, J=5.1 Hz, 2H), 2.79-2.61 (m, 2H).

Workup

  1. concentrationThe solution was concentrated to dryness under reduced pressure
  2. additionThe resulting residue was diluted with CH2Cl2 (30 mL)
  3. washwashed with saturated NaHCO3 solution (50 mL)
  4. customThe resulting layers were separated
  5. extractionthe aqueous phase was extracted with CH2Cl2 (3×30 mL)
  6. extractionThe combined organic extractions
  7. dry with materialwere dried over Na2SO4
  8. concentrationconcentrated under reduced pressure to dryness
  9. temperatureFlash chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 0:100 over 4 column volumes and held for 10 column volumes)

Sources & evidence

ORD record
ord-943c9e1ce6714f949cbad4d4f9ba8fcc
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

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