3-Aminobenzyl alcohol → [3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanol

HRID 1614928Notes

Reaction equation

HRID 1614928 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]([CH:25]=[CH:26][CH:27]=1)[CH2:23][OH:24].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>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]([CH2:23][OH:24])[CH:25]=[CH:26][CH:27]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 802933-Aminobenzyl alcoholHCID 521998p-Toluenesulfonic acid monohydrateHCID 584678982,5-Dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine

Product 1

HCID 58467863[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanolYield 98%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

Into the reaction flask was added 2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine (0.82 g, 2.9 mmol), 1,4-dioxane (20 mL), 3-aminobenzyl alcohol (0.53 g, 4.3 mmol), and p-toluenesulfonic acid monohydrate (0.22 g, 1.2 mmol). The mixture was heated at 105° C. for 3 hours and then was heated at 70° C. overnight. The reaction was quenched with NaHCO3 (saturated). 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 to give the desired product as a brown powder (1.05 g, 98%). LCMS for C19H20N4O2 (M+H)+: m/z=371.1, 373.0. 1H NMR (400 MHz, DMSO-d6): δ 9.54 (s, 1H), 8.28 (s, 1H), 8.03 (s, 1H), 7.54 (s, 1H), 7.40 (d, J=8.3 Hz, 1H), 7.20 (t, J=8.3 Hz, 1H), 7.14 (t, J=7.9 Hz, 1H), 6.89 (m, 1H), 6.77 (ddd, J=8.3, 2.2, 1.4 Hz, 1H), 4.59 (d, J=6.2 Hz, 2H), 4.38 (s, 2H), 3.64 (s, 3H).

Workup

  1. temperaturewas heated at 70° C. overnight
  2. customThe reaction was quenched with NaHCO3 (saturated)
  3. customThe organic solvent was removed under vacuum
  4. additionfollowed by the addition of water and EtOAc
  5. extractionThe aqueous layer was extracted with EtOAc twice
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5ac6494ce3b6408c9d69392f3e91a13a
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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