Methylamine → (Z)-4-(1-(4-hydroxyphenyl)-1-(4-(2-(methylamino)ethoxy) phenyl)but-1-en-2-yl)-1-methylpyridin-2(1H)-one

HRID 626190Notes

Reaction equation

Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)=[C:12]([C:15]2[CH:20]=[CH:19][N:18]([CH3:21])[C:17](=[O:22])[CH:16]=2)[CH2:13][CH3:14])=[CH:7][CH:6]=1.[CH3:30][NH2:31]>CO>[OH:29][C:26]1[CH:27]=[CH:28][C:23](/[C:11](/[C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][NH:31][CH3:30])=[CH:6][CH:7]=2)=[C:12](/[C:15]2[CH:20]=[CH:19][N:18]([CH3:21])[C:17](=[O:22])[CH:16]=2)\[CH2:13][CH3:14])=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a stirred solution of 4-(1-(4-(2-chloroethoxy)phenyl)-1-(4-hydroxyphenyl)-but-1-en-2-yl)-1-methylpyridin-2(1H)-one (30 mg, 1.0 eq) in 10 mL MeOH was added 5 mL 30% CH3NH2 (aq), and the mixture was then heated at 85° C. for 36 h. Then the solvent was removed in vacuo, water was added to the residue and extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give the desired product (3 mg, Z-isomer), E-isomer (2 mg), and Z/E mixture (230 mg, 49% yield) as well. 1H NMR (400 MHz, CDCl3) δ 6.96-6.98 (m, 3H), 6.84 (d, J=8.8 Hz, 2H), 6.77 (d, J=8.4 Hz, 2H), 6.57 (d, J=8.8 Hz, 2H), 6.47 (d, J=2.0 Hz, 1H), 5.78 (dd, J=6.8 Hz, 2.0 Hz, 1H), 3.98 (t, J=5.2 Hz, 2H), 3.47 (s, 3H), 2.96 (t, J=5.2 Hz, 2H), 2.52 (s, 3H), 2.36-2.38 (m, 2H), 0.92 (t, J=7.2 Hz, 3H); m/z=405[M+1]+.

Workup

customThen the solvent was removed in vacuo, water
additionwas added to the residue
extractionextracted with EtOAc
customThe extract was dried
concentrationconcentrated
custompurified by column chromatography

Sources & evidence

ORD record: ord-da29ee7b102849e1a7b6245b8051ca4f
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309211B2

Reaction notes

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