Diisopropylethylamine → (s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine

HRID 573990Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([F:14])=[C:4](Cl)[N:3]=1.Cl.[F:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([NH2:26])[CH3:25])=[N:22][CH:23]=1.CCN(C(C)C)C(C)C>C(O)CCC>[Cl:1][C:2]1[N:3]=[C:4]([NH:26][C@H:24]([C:21]2[CH:20]=[CH:19][C:18]([F:17])=[CH:23][N:22]=2)[CH3:25])[C:5]([F:14])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine (Preparation 11a, 1.18 g, 4.68 mmol), (S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (prepared as described in WO2006/123113, 1.00 g, 4.69 mmol) and N,N′-diisopropylethylamine (3.27 mL, 18.77 mmol) in n-butanol (20 mL) was heated at 130° C. for two days. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine) to give the title compound (0.700 g, 42%) as one major regioisomer. The chemical structures of both regioisomers were confirmed by NMR experiments (gHSQCAD and gHMBCAD).

Workup

customThe solvent was evaporated under reduced pressure
customthe residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine)

Sources & evidence

ORD record: ord-ff3876748bcf4d1296ed001ef327b465
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034311B2

Reaction notes

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