Epichlorohydrin → 5-Methyl-6-morpholino-2-(3-(oxiran-2-ylmethoxy)phenyl)-N-((R)-tetra-hydrofuran-3-yl)pyrimidin-4-amine

HRID 527466Notes

Reaction equation

HRID 527466 reaction equation
[CH3:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[N:4][C:5]([C:14]2[CH:15]=[C:16]([OH:20])[CH:17]=[CH:18][CH:19]=2)=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:13][CH2:12][O:11][CH2:10]1.Cl[CH2:28][CH:29]1[CH2:31][O:30]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:1][C:2]1[C:7]([NH:8][C@@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)=[N:6][C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:28][CH:29]3[CH2:31][O:30]3)[CH:15]=2)=[N:4][C:3]=1[N:21]1[CH2:22][CH2:23][O:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 7835EpichlorohydrinHCID 11430Potassium CarbonateHCID 90426357(R)-3-(5-methyl-4-morpholino-6-(tetrahydrofuran-3-ylamino)pyrimidin-2-yl)phenol

Product 1

HCID 904256505-Methyl-6-morpholino-2-(3-(oxiran-2-ylmethoxy)phenyl)-N-((R)-tetra-hydrofuran-3-yl)pyrimidin-4-amineYield 34.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (R)-3-(5-methyl-4-morpholino-6-(tetrahydrofuran-3-ylamino)pyrimidin-2-yl)phenol (50 mg, 0.14 mmol); 2-(chloromethyl)oxirane (16 mg, 0.17 mmol) and K2CO3 (39 mg, 0.28 mmol) in MeCN (10 mL) was heated at 80° C. in a sealed vial for 14 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by chromatographic column on silica gel (EtOAc/petroleum ether, gradient elution, from 1/5 to 4:1) to give the 5-methyl-6-morpholino-2-(3-(oxiran-2-ylmethoxy)phenyl)-N—((R)-tetrahydrofuran-3-yl)pyrimidin-4-amine (20 mg, 34% yield) as a light yellow solid. ESI-LCMS (m/z): 413.2 [M+1]+.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by chromatographic column on silica gel (EtOAc/petroleum ether, gradient elution, from 1/5 to 4:1)

Sources & evidence

ORD record
ord-ecb476062606408d98ad2aa0dd24fc96
Source dataset
uspto-grants-2016_05
Patent number
US09346802B2

Reaction notes

Loading…