Triethylamine → (S)-2-chloro-5-fluoro-6-((1-hydroxy-3,3-dimethylbutan-2-yl)amino)nicotinonitrile

HRID 1055084Notes

Reaction equation

[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([F:10])=[C:4](F)[N:3]=1.[NH2:12][C@@H:13]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:14][OH:15].C(N(CC)CC)C>CC#N.C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([NH:12][C@@H:13]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:14][OH:15])[C:5]([F:10])=[CH:6][C:7]=1[C:8]#[N:9]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-chloro-5,6-difluoropyridine-3-carbonitrile (6.52 g, 34.13 mmol), (2S)-2-amino-3,3-dimethyl-butan-1-ol (4.00 g, 34.13 mmol) and triethylamine (9.51 mL, 68.26 mmol) in CH3CN (50 mL) and THF (50 mL) was heated at 80° C. for 4 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The crude product was purified via silica gel chromatography (0-60% EtOAc/Hexanes gradient) to afford 6.7 g of the desired product as an off white solid: 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J=9.7 Hz, 1H), 5.32 (m, 1H), 4.19-4.08 (m, 1H), 3.95-3.83 (m, 1H), 3.74-3.51 (m, 1H), 0.92 (s, 9H); LC/MS (60-90% ACN/water 5 min with 0.9% FA) m/z 272.02 (M+H), retention time 1.02 minutes.

Workup

temperatureThe mixture was cooled to room temperature
customthe solvent was evaporated under reduced pressure
customThe crude product was purified via silica gel chromatography (0-60% EtOAc/Hexanes gradient)

Sources & evidence

ORD record: ord-735424791d2c4e01b51ad58b31d5d2bd
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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