Diisopropylethylamine → 2-{4-Chloro-6-[(3,3-difluorocyclobutyl)amino]-2-(methylsulfanyl)pyrimidin-5-yl}ethanol

HRID 1775469Notes

Reaction equation

Cl[C:2]1[C:7]([CH2:8][CH2:9][OH:10])=[C:6]([Cl:11])[N:5]=[C:4]([S:12][CH3:13])[N:3]=1.[F:14][C:15]1([F:20])[CH2:18][CH:17]([NH2:19])[CH2:16]1.CCN(C(C)C)C(C)C>C(#N)C>[Cl:11][C:6]1[C:7]([CH2:8][CH2:9][OH:10])=[C:2]([NH:19][CH:17]2[CH2:18][C:15]([F:20])([F:14])[CH2:16]2)[N:3]=[C:4]([S:12][CH3:13])[N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a vial containing 2-[4,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]ethanol (600 mg, 2.51 mmol) and 3,3-difluorocyclobutylamine (540 mg, 3.76 mmol) in acetonitrile (12.5 mL) was added DIPEA (2.21 mL, 12.5 mmol) at room temperature, and the mixture was stirred at 100° C. in an oil bath for 6.5 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified via silica gel chromatography using a gradient of EtOAc/heptane (20-40%) to afford the title compound (722.5 mg, 93%) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.60 (d, J=5.5 Hz, 1 H), 4.82 (br s, 1 H), 4.38-4.26 (m, 1 H), 3.56-3.47 (m, 2 H), 3.03-2.87 (m, 2 H), 2.83-2.65 (m, 4 H), 2.42 (s, 3 H). m/z (APCI+) for C11H14ClF2N3OS 310.1 (M+H)+.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customthe residue was purified via silica gel chromatography

Sources & evidence

ORD record: ord-0e733bc1fcdb468d92852fceff97f058
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260439B2

Reaction notes

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