Diisopropylethylamine → 5-chloro-N4-((S)-1-(8-chloro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)pyrimidine-2,4-diamine
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:8]([C@@H:18]([NH2:20])[CH3:19])=[CH:7]2.CCN(C(C)C)C(C)C.Cl[C:31]1[C:36]([Cl:37])=[CH:35][N:34]=[C:33]([NH2:38])[N:32]=1>C(O)CCC>[Cl:37][C:36]1[C:31]([NH:20][C@H:18]([C:8]2[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:10][C:11]3[C:6]([CH:7]=2)=[CH:5][CH:4]=[CH:3][C:2]=3[Cl:1])[CH3:19])=[N:32][C:33]([NH2:38])=[N:34][CH:35]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of (1S)-1-(8-chloro-2-(pyridin-2-yl)quinolin-3-yl)ethanamine (0.090 g, 0.32 mmol) in n-butanol (3 mL) was treated with DIEA (0.11 mL, 0.64 mmol, 2.0 eq), followed with 4,5-dichloropyrimidin-2-amine (0.062 g, 0.38 mmol, 1.2 eq) at 100° C. for 8 h. The reaction mixture was concentrated and purified by column chromatography on a Redi-Sep™ column using 0 to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 as eluent to provide 5-chloro-N4-((S)-1-(8-chloro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)pyrimidine-2,4-diamine [PI3Kδ IC50=105 nM] as a white solid. 1H-NMR (DMSO-d6) δ ppm 8.65-8.76 (m, 1H), 8.53 (s, 1H), 8.11-8.20 (m, 1H), 8.07 (d, J=1.96 Hz, 1H), 7.91-8.00 (m, 2H), 7.86 (s, 1H), 7.62 (t, J=8.02 Hz, 1H), 7.51-7.58 (m, 1H), 6.03-6.25 (m, 1H), 1.38-1.63 (d, J=7.04, 3H), Mass Spectrum (ESI) m/e=412 (M+1).
Workup
- concentrationThe reaction mixture was concentrated
- custompurified by column chromatography on a Redi-Sep™ column
Sources & evidence
- ORD record
- ord-55a1e36a7578457bac4bee6d5d543a1f
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329910B2
Reaction notes
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