2-Chloroquinoline → 2-(3-((3-(Tetrahydro-2H-pyran-4-YL)pyridin-2-YL)oxy)azetidin-1-YL)quinoline

HRID 454951Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[C:11]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[CH:10][CH:9]=[CH:8][N:7]=2)[CH2:2]1.Cl[C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:15]1[CH2:16][CH2:17][CH:12]([C:11]2[C:6]([O:5][CH:3]3[CH2:2][N:1]([C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[CH2:4]3)=[N:7][CH:8]=[CH:9][CH:10]=2)[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-(azetidin-3-yloxy)-3-(tetrahydro-2H-pyran-4-yl)pyridine (see PREPARATION P27.1; 100 mg, 0.45 mmol), 2-chloroquinoline (73 mg, 0.45 mmol), Pd2(dba)3 (56 mg, 0.062 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (40 mg, 0.06 mmol), KI (40 mg, 0.13 mmol) and sodium tert-butoxide (t-BuONa) (110 mg, 1.2 mmol) was dissolved in toluene (5 mL). The reaction mixture was heated in a microwave at 130° C. for 4 hours. The solvent was evaporated and the crude product was purified by silica gel column chromatography to give the product (6.7 mg, 0.018 mmol, yield 10%). [M+1] 363. IC50 (uM) 0.331.

Workup

customThe solvent was evaporated
customthe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-b1e1df3644c141b9b0e6ec09de9b1bf9
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497265B2

Reaction notes

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