Sodium Bicarbonate → 3-[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]propan-1-ol

HRID 1614938Notes

Reaction equation

HRID 1614938 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][CH2:28][OH:29])[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][CH2:28][OH:29])[CH:23]=[CH:24][CH:25]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 101033343-(3-Aminophenyl)propan-1-olHCID 584678982,5-Dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine

Product 1

HCID 584679043-[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]propan-1-olYield 64.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

Into a reaction flask were added 2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine (0.20 g, 0.70 mmol, prepared according to Example 1, step A), 1,4-dioxane (20 mL), 3-(3-aminophenyl)propan-1-ol (0.16 g, 1.0 mmol, prepared according to Example 12, step A & B), and p-toluenesulfonic acid monohydrate (0.049 g, 0.26 mmol). The mixture was heated at 105° C. for 2 days and NaHCO3 (saturated aqueous solution) was added. The organic solvent was removed under vacuum followed by an addition of water and EtOAc. The aqueous layer was extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under vacuum. The crude product was purified by silica gel column chromatography to give the desired product (0.18 g, 64%) as a white solid. LCMS for C21H24lN4O2 (M+H)+: m/z=399.1.

Workup

  1. customThe organic solvent was removed under vacuum
  2. additionfollowed by an addition of water and EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc twice
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e7512edac18047be85485c05141b3f93
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

Loading…