Tetrahydrofuran → 6-[5-(1-Amino-cyclopropyl)-pyridin-3-yl]-1-methyl-3,4-dihydro-1H-quinolin-2-one

HRID 1774814Notes

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.C1COCC1>C1(C)C=CC=CC=1>[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])[CH2:4][CH2:5]4)[CH:17]=[N:16][CH:15]=2)[CH2:20][CH2:19]1

Participants

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 (0.551 g, 1.52 mmol) in toluene (20 mL) were added TEA (0.185 g, 1.83 mmol) and diphenylphosphoryl azide (0.419 g, 1.52 mmol) and then the reaction mixture was heated to reflux for 4 h. After cooling to 0° C., a 1 M solution of sodium trimethylsilanoate in THF (3.04 mL, 3.04 mmol) was added and the mixture was stirred for 45 min at room temperature. After quenching with 0.1 M aq. HCl (40 mL), the aqueous solution was washed with ether (2 times), then basified with 1 M aq. NaOH and then extracted with DCM (2×100 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound (0.333 g, 71%) as a yellow foam. MS: 294.4 (M+H+).

Workup

temperaturethe reaction mixture was heated
temperatureto reflux for 4 h
customAfter quenching with 0.1 M aq. HCl (40 mL)
washthe aqueous solution was washed with ether (2 times)
extractionextracted with DCM (2×100 mL)
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated to dryness

Sources & evidence

ORD record: ord-ef25db3aead842bd8b39c2deb7fd9506
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260408B2

Reaction notes

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