2,4-Dichloropyrimidine → 2-(2-Chloropyrimidin-4-yl)-6-methoxy-1-[4-(phenylmethoxy)benzyl]-1,2,3,4-tetrahydroisoquinoline

HRID 1358002Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=1)[NH:8][CH2:7][CH2:6]2.[Cl:28][C:29]1[N:34]=[C:33](Cl)[CH:32]=[CH:31][N:30]=1.C(=O)(O)[O-].[Na+]>C(O)C>[Cl:28][C:29]1[N:34]=[C:33]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:9]2[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=2)[CH:32]=[CH:31][N:30]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-methoxy-1-[4-(phenylmethoxy)benzyl]-1,2,3,4-tetrahydroisoquinoline (0.72 g, 2.0 mmol), 2,4-dichloropyrimidine (0.298 g, 2.0 mmol), and sodium bicarbonate (0.2 g, 2.4 mmol) in ethanol (10 mL) was heated at 80° C. for 3 hours. It was quenched with water and extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography (SiO2, 30-6-% ethyl acetate/hexane) to provide the title compound (0.749 g, 79% yield): 1H NMR (CDCl3) 7.95 (d, 1H), 7.32-7.41 (m, 4H), 6.94 (d, 2H), 6.83 (d, 2H), 6.69 (m, 3H), 6.37 (m, 1H), 5.9 (d, 1H), 5.03 (s, 2H), 4.97 (m, 1H), 3.80 (s, 3H), 3.25-3.62 (m, 2H), 3.13 (m, 1H), 2.86 (m, 3H); ES-MS (m/z) 472 [M+H]+.

Workup

customIt was quenched with water
extractionextracted with CH2Cl2
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by chromatography (SiO2, 30-6-% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-b046aba38e0d4dc987adcad92e237796
Source dataset: uspto-grants-2003_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06593322B1

Reaction notes

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