4,6-Dichloropyrimidine → 6-chloro-N-(2-(2-methoxyphenyl)propyl)pyrimidin-4-amine

HRID 929537Notes

Reaction equation

HRID 929537 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH:17]([CH3:20])[CH2:18][NH2:19].CCN(C(C)C)C(C)C>C(O)(C)C>[Cl:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:19][CH2:18][CH:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH3:9])[CH3:20])[CH:7]=1

Participants

5

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 4080602-(2-Methoxyphenyl)propan-1-amine

Product 1

HCID 866996526-chloro-N-(2-(2-methoxyphenyl)propyl)pyrimidin-4-amineYield 77%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

As shown in step 4-v of Scheme 4, a mixture of 4,6-dichloropyrimidine (817 mg, 5.49 mmol), 2-(2-methoxyphenyl)-1-propanamine (0.997 g, 6.03 mmol), and DIEA (2.13 g, 2.87 mL, 16.5 mmol) in isopropanol (5.0 mL) was stirred for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue purified by medium pressure chromatography on silica gel (25% EtOAc in hexanes) to give 6-chloro-N-(2-(2-methoxyphenyl)propyl)pyrimidin-4-amine as a colorless solid (Compound 2012, 1.18 g, 77% yield): 1H NMR (CDCl3) δ 8.31 (s, 1H), 7.23 (dd, J=12.0, 4.5 Hz, 2H), 7.03-6.87 (m, 2H), 6.41 (s, 1H), 5.42 (s, 1H), 3.89 (s, 3H), 3.67-3.18 (m, 3H), 1.35 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue purified by medium pressure chromatography on silica gel (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fdf14f5b47f14d42a8d27dac4b0cc750
Source dataset
uspto-grants-2016_03
Patent number
US09296701B2

Reaction notes

Loading…