P,P-Diphenylphosphinic azide → 6-[5-(1-Amino-cyclopropyl)-pyridin-3-yl]-1-methyl-1H-quinolin-2-one

HRID 1774888Notes

Reaction equation

HRID 1774888 reaction equation
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([C:18]4(C(O)=O)[CH2:20][CH2:19]4)[CH:15]=[N:16][CH:17]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4][C:3]1=[O:24].C1(P([N:39]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.C1COCC1>[NH2:39][C:18]1([C:14]2[CH:13]=[C:12]([C:8]3[CH:7]=[C:6]4[C:11](=[CH:10][CH:9]=3)[N:2]([CH3:1])[C:3](=[O:24])[CH:4]=[CH:5]4)[CH:17]=[N:16][CH:15]=2)[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 199401P,P-Diphenylphosphinic azideHCID 23665647Potassium tert-butoxideHCID 86679167HCID 86679167, compound

Product 1

HCID 866792386-[5-(1-Amino-cyclopropyl)-pyridin-3-yl]-1-methyl-1H-quinolin-2-oneYield 38.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To solution of 1-(5-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)pyridin-3-yl)cyclopropanecarboxylic acid (example 59 [C], 0.3 g, 0.931 mmol) in toluene (15 mL) were added TEA (0.141 g, 1.4 mmol) and diphenylphosphoryl azide (0.384 g, 1.4 mmol) and then the reaction mixture was heated to reflux for 4 h. The mixture was concentrated in vacuo, the residue was dissolved in THF (30 mL) and the solution cooled to 0° C. Then, a solution of KOtBu (0.627 g, 5.58 mmol) in THF (13 mL) was added and the mixture was stirred for 1 h at 0° C. and then over night at room temperature. The mixture was concentrated in vacuo, the residue was preadsorbed on silica gel and purified by silica gel flash chromatography eluting with a 0 to 10% MeOH-DCM gradient to give a yellow amorphous solid (0.104 g). This material was then further purified by reverse phase HPLC on a Gemini-NX column, eluting with a MeOH—H2O (0.05% TEA) gradient to give the title compound (0.02 g, 7%) as a colorless amorphous solid. MS: 292.3 (M+H+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 4 h
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in THF (30 mL)
  5. waitover night at room temperature
  6. concentrationThe mixture was concentrated in vacuo
  7. custompurified by silica gel flash chromatography
  8. washeluting with a 0 to 10% MeOH-DCM gradient

Sources & evidence

ORD record
ord-3e4e895825734bf4a15f12d2df3ffde2
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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