反応 #303356

反応方程式

2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionitrile

2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionitrile

Intermediate ( 67 )

2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionitrile

azidotributyltin

→

[2-(2,4-dichloro-phenyl)-ethyl]-(2-methyl-6-{3-[1-methyl-1-(2H-tetrazol-5-yl)-ethyl]-phenyl}-pyrimidin-4-yl)-amine

溶媒

α, α, α-trifluorotoluene

反応条件

後処理

1. 1
   その他Reaction mixture
2. 2
   濃縮is concentrated
3. 3
   その他purified via silica gel chromatography
4. 4
   洗浄eluting with 20 to 100% EtOAc in heptane

実験手順

To a solution of 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionitrile [50 mg, 0.11 mmol, Intermediate (67)] in α, α, α-trifluorotoluene (2 mL) is added azidotributyltin (0.251 mL, 0.88 mmol) and heated in microwave oven at 180° C. for 1.5 hours. Reaction mixture is concentrated and purified via silica gel chromatography eluting with 20 to 100% EtOAc in heptane to give [2-(2,4-dichloro-phenyl)-ethyl]-(2-methyl-6-{3-[1-methyl-1-(2H-tetrazol-5-yl)-ethyl]-phenyl}-pyrimidin-4-yl)-amine as a solid, which is treated with 1M hydrogen chloride in ether affording [2-(2,4-dichloro-phenyl)-ethyl]-(2-methyl-6-{3-[1-methyl-1-(2H-tetrazol-5-yl)-ethyl]-phenyl}-pyrimidin-4-yl)-amine hydrochloride [47 mg, 80%, Example 47] as a solid. LC/MS: RT=2.47 minutes, MS: 484 (M+H). 1H NMR [300 MHz, (CD3)2SO]: □8.64 (1H, br s), 7.3-7.8 (7H, m), 6.56 (1H, s), 3.98 (3H, s), 3.64 (2H, m), 3 (2H, m), 1.8 (6H, s). IC50=0.4 nM

出典