Hydrazine → (1S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethanamine

HRID 75366Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:19]([N:21]3C(=O)C4C(=CC=CC=4)C3=O)[CH3:20])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.NN>CCO>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C@@H:19]([NH2:21])[CH3:20])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-((S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethyl)-isoindoline-1,3-dione (60.0 mg, 145 μmol) in EtOH (2 mL) was added NH2NH2 (1.0 mL, 1.45 mmol, 10 eq) and the resulting solution was heated to 80° C. for 2 h. A precipitate was filtered away and the filtrate was removed under reduce pressure to afford (1S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)ethanamine To the crude residue of (1S)-1-(7-fluoro-2-(3-fluorophenyl)quinolin-3-yl)-ethanamine in DMF (2 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (22 mg, 145 μmol) and DIEA (0.06 mL, 319 μmol). The resulting mixture was heated to 100° C. overnight. Solvent was removed under reduce pressure and purified via preparatory HPLC using 15-60% MeCN/H2O w/0.01% TFA to afford a white solid of 4-amino-6-((S)-1-(7-fluoro-2-(3-fluorophenyl)-quinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile (9.3 mg, 16%). 1H NMR (500 MHz, CD3OD) δ ppm 1.63 (d, J=6.85 Hz, 3H) 5.70 (q, J=7.01 Hz, 1H) 7.25-7.34 (m, 1H) 7.44-7.54 (m, 2H) 7.55-7.63 (m, 2H) 7.74 (dd, J=9.78, 2.45 Hz, 1H) 8.05 (s, 1H) 8.18 (dd, J=9.05, 5.87 Hz, 1H) 8.72 (s, 1H). Mass Spectrum (ESI) m/e=403 (M+1).

Workup

filtrationA precipitate was filtered away
customthe filtrate was removed

Sources & evidence

ORD record: ord-7eaf239f563b4b01849183db1492ec85
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835432B2

Reaction notes

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