Sodium Bicarbonate → 2-[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]ethanol

HRID 1614931Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[C:5]([Cl:18])=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][OH:28])[CH:23]=[CH:24][CH:25]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>O1CCOCC1>[Cl:18][C:5]1[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)=[N:7][C:2]([NH:19][C:20]2[CH:21]=[C:22]([CH2:26][CH2:27][OH:28])[CH:23]=[CH:24][CH:25]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 105 °C

Procedure

Into a reaction flask were added 2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine (0.33 g, 1.2 mmol) (prepared according to Example 1, step A), 1,4-dioxane (20 mL), 2-(3-aminophenyl)ethanol (0.22 g, 1.6 mmol), and p-toluenesulfonic acid monohydrate (0.080 g, 0.42 mmol). The mixture was heated at 105° C. for 3 hours and then an aqueous solution of NaHCO3 (saturated) was added. The organic solvent was removed under vacuum followed by the addition of water and EtOAc. The aqueous layer was extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4, and concentrated under vacuum. The crude was purified by silica gel column chromatography to provide the desired product as a white solid (0.33 g, 74% yield). LCMS for C20H22ClN4O2 (M+H)+: m/z=385.1.

Workup

customThe organic solvent was removed under vacuum
additionfollowed by the addition of water and EtOAc
extractionThe aqueous layer was extracted with EtOAc twice
dry with materialdried over Na2SO4
concentrationconcentrated under vacuum
customThe crude was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-cb797c65fe314ce8a3e67676700e9d2e
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765727B2

Reaction notes

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