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

HRID 882043Notes

Reaction equation

HRID 882043 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:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=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.C(Cl)Cl>CO>[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]=[CH: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][NH:29][CH2:30][CH2:31][C:3]1=2

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 6344DichloromethaneHCID 86667081tert-Butyl 9-methyl-2-(2-oxo-4-(4-(trifluoromethyl)phenyl)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 573839591-(9-Methyl-5,7,8,9-tetrahydro-6H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridin-2-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 46.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

tert-Butyl 9-methyl-2-(2-oxo-4-(4-(trifluoromethyl)phenyl)pyridin-1(2H)-yl)-5,7,8,9-tetrahydro-6H-pyrido[3′,4′:4,5]pyrrolo[2,3-b]pyridine-6-carboxylate (0.14 g, 0.26 mmol) was treated with 1.25 M HCl in MeOH (6.0 mL), and the resulting suspension was stirred at ambient temperature for 18 h. To the suspension was added CH2Cl2 (1.0 mL) and 1.25 M HCl in MeOH (2.0 mL), and the resulting solution was stirred at ambient temperature for 18 h. The solution was concentrated, diluted with CH2Cl2 (30 mL), washed with saturated NaHCO3 solution (2×10 mL), dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 50:50 over 20 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes and held for 30 column volumes) followed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×50.0 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) gave the title compound (51 mg, 46%) as a yellow powder: 1H NMR (500 MHz, DMSO-d6) δ 8.06-8.00 (m, 3H), 7.93 (d, J=8.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 1H), 6.89 (d, J=1.5 Hz, 1H), 6.76 (dd, J=7.5, 2.0 Hz, 1H), 3.89 (s, 2H), 3.67 (s, 3H), 3.08 (t, J=5.5 Hz, 2H), 2.75 (t, J=5.5 Hz, 2H).

Workup

  1. stirringthe resulting solution was stirred at ambient temperature for 18 h
  2. concentrationThe solution was concentrated
  3. additiondiluted with CH2Cl2 (30 mL)
  4. washwashed with saturated NaHCO3 solution (2×10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 4 column volumes, increased to 50:50 over 20 column volumes and held for 4 column volumes; increased to 0:100 over 10 column volumes and held for 30 column volumes)

Sources & evidence

ORD record
ord-baabb0a6fe0248cba230c48b43fb6ce8
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

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