1,4-Dioxane → (1R)-2-{[2-Cyclopropyl-6-(3,4-dichlorophenyl)pyrimidin-4-yl]amino}-1-phenylethanol

HRID 1908249Notes

Reaction equation

HRID 1908249 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[N:5]=[C:4]([CH:16]2[CH2:18][CH2:17]2)[N:3]=1.[NH2:19][CH2:20][C@@H:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[OH:22].C([O-])(O)=O.[Na+].O1CCOCC1>O>[CH:16]1([C:4]2[N:3]=[C:2]([NH:19][CH2:20][C@@H:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[OH:22])[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=3)[N:5]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 6951165(R)-(-)-2-Amino-1-phenylethanolHCID 809526634-Chloro-2-cyclopropyl-6-(3,4-dichloro-phenyl)-Pyrimidine

Product 1

HCID 44205060(1R)-2-{[2-Cyclopropyl-6-(3,4-dichlorophenyl)pyrimidin-4-yl]amino}-1-phenylethanolYield 82%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-chloro-2-cyclopropyl-6-(3,4-dichloro-phenyl)-pyrimidine (108 mg, 0.364 mmol), (R)-(−)-2-amino-1-phenylethanol (67.2 mg, 0.490 mmol), and NaHCO3 (190.1 mg, 2.26 mmol) and 1,4-dioxane was refluxed for 48 h. The mixture was poured into water and extracted with CH2Cl2. The organic layer was dried (Na2SO4) and concentrated. The crude residue was purified (FCC) to give the title compound as a white solid (119.4 mg, 82%). MS (ESI): mass calcd. for C21H19Cl2N3O, 399.09; m/z found, 400.1 [M+H]+. 1H NMR (CD3OD): 8.13-8.05 (m, 1H), 7.85-7.79 (m, 1H), 7.64-7.58 (m, 1H), 7.45-7.31 (m, 4H), 7.30-7.23 (m, 1H), 6.68-6.59 (m, 1H), 4.93-4.85 (m, 1H), 3.81-3.65 (m, 1H), 3.56-3.48 (m, 1H), 2.16-2.01 (m, 1H), 1.16-1.09 (m, 2H), 1.02-0.94 (m, 2H).

Workup

  1. temperaturewas refluxed for 48 h
  2. extractionextracted with CH2Cl2
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-65d87a4bc51344aea22e753149c83c2f
Source dataset
uspto-grants-2013_12
Patent number
US08598202B2

Reaction notes

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