Isopropanol → 2-(pyridin-3-ylcarbonyl)-N-3-thienyl-1,2,3,4-tetrahydroisoquinolin-6-amine
Reaction equation
ClC1N=[CH:4][C:5]2[CH2:11][N:10]([C:12]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)=[O:13])[CH2:9][CH2:8][C:6]=2N=1.[S:20]1[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21]1.CCOC(C)=O.[CH:32](O)([CH3:34])[CH3:33]>>[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:12]([N:10]2[CH2:9][CH2:8][C:6]3[C:5](=[CH:4][CH:33]=[C:32]([NH:25][C:22]4[CH:23]=[CH:24][S:20][CH:21]=4)[CH:34]=3)[CH2:11]2)=[O:13])[CH:15]=1Participants
Conditions
- Temperature
- 60 °C
Procedure
A solution of (2-chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)(pyridin-3-yl)methanone, Intermediate 5 (0.025 g, 0.091 mmol) in isopropanol (0.1 mL) was treated with thiophen-3-amine (0.0099 g, 0.100 mmol). The resulting mixture was heated to 60° C. and allowed to stir overnight. After being allowed to cool to room temperature EtOAc (10 mL) was added to the reaction mixture, and the resulting solution was then washed twice with brine (10 mL). The combined aqueous layers were washed once with EtOAc (10 mL). The organic layers were combined, then dried over anhydrous Na2SO4(s), filtered and concentrated in vacuo. The resulting crude residue was then purified over silica using a MeOH/CHCl3 gradient. The desired product was obtained in 39.1% yield (0.012 g, 0.035 mmol).
Workup
- additionwas added to the reaction mixture
- washthe resulting solution was then washed twice with brine (10 mL)
- washThe combined aqueous layers were washed once with EtOAc (10 mL)
- dry with materialdried over anhydrous Na2SO4(s)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe resulting crude residue was then purified over silica using a MeOH/CHCl3 gradient
Sources & evidence
- ORD record
- ord-3ad152f8abcf4bc2967373e4ba6f2086
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296747B1
Reaction notes
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