2-Pyridineethanamine, beta,beta-difluoro-6-methyl- → HCID 57722707, compound

HRID 1987070Notes

Reaction equation

[F:1][C:2]([F:12])([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[N:6]=1)[CH2:3][NH2:4].[CH2:13]([O:15][C:16](=[O:28])[CH2:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[C:20](F)[C:19]=1[F:27])[CH3:14]>CS(C)=O>[CH2:13]([O:15][C:16](=[O:28])[CH2:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[C:20]([NH:4][CH2:3][C:2]([F:1])([F:12])[C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[N:6]=2)[C:19]=1[F:27])[CH3:14]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 2,2-Difluoro-2-(6-methyl-pyridin-2-yl)-ethylamine (223.6 mg, 1.3 mmol), as prepared in the preceding step, and (6-cyano-2,3-difluoro-phenyl)-acetic acid ethyl ester (225 mg, 1.0 mmol), as prepared in Example 2f, was dissolved in DMSO (1.0 mL) and heated at 150° C. under microwave irradiation for 1 hour. The reaction mixture was partitioned between ethyl acetate and water. The combined EtOAc extracts were dried over Na2SO4 and evaporated. The crude product was purified by flash column chromatography on silica gel (EtOAc/hexanes 2/1, v/v) to afford the product as a white solid (208 mg, 42.5% yield based on the initial amine). 1H NMR (CDCl3) δ 7.71 (t, J=8.02 Hz, 1H), 7.47 (d, J=8.15 Hz, 1H), 7.30 (dd, J=8.61 and 1.28 Hz, 1H), 7.25 (m, 1H), 6.79 (t, J=8.28 Hz, 1H), 4.18 (q, J=7.16 Hz, 2H), 4.12 (t, J=13.21 Hz, 2H), 3.81 (d, J=2.0 Hz, 2H), 2.60 (s, 3H), 1.27 (t, J=7.13 Hz, 3H); LC/MS (m/z) [M+1] 378.3 (calculated for C19H19F3N3O2, 378.1).

Workup

customas prepared in Example 2f
customThe reaction mixture was partitioned between ethyl acetate and water
dry with materialThe combined EtOAc extracts were dried over Na2SO4
customevaporated
customThe crude product was purified by flash column chromatography on silica gel (EtOAc/hexanes 2/1, v/v)

Sources & evidence

ORD record: ord-f0fc7fcd022242c48f9e7c379278ed4b
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550474B2

Reaction notes

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