2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(5-(methylthio)pyridin-3-yl)quinolin-4-amine

HRID 1431597Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[CH:15]=[N:16][CH:17]=[C:18]([S:20][CH3:21])[CH:19]=2)[C:3]=1[CH3:22].[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[C:34]([NH2:35])=[CH:33][C:32]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:31][N:30]=2)[CH2:25][CH2:24]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[O:23]1[CH2:28][CH2:27][N:26]([C:29]2[C:34]([NH:35][C:2]3[C:11]4[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=4[F:12])[N:5]=[C:4]([C:14]4[CH:15]=[N:16][CH:17]=[C:18]([S:20][CH3:21])[CH:19]=4)[C:3]=3[CH3:22])=[CH:33][C:32]([N:36]3[CH2:37][CH2:38][O:39][CH2:40][CH2:41]3)=[CH:31][N:30]=2)[CH2:25][CH2:24]1

Participants

Conditions

Temperature: 105 °C

Procedure

A screw-cap vial was charged with 4-chloro-5,7-difluoro-3-methyl-2-(5-(methylthio)pyridin-3-yl)quinoline (50 mg, 0.15 mmol), 2,5-dimorpholinopyridin-3-amine (39.2 mg, 0.15 mmol), tris(dibenzylideneacetone)dipalladium (0) (13.6 mg, 0.015 mmol), XPhos (14.2 mg, 0.030 mmol), sodium tert-butoxide (42.8 mg, 0.445 mmol), and toluene (1.5 mL). The mixture was stirred at 105° C. for 2 h, then cond. The resulting residue was partitioned between DCM and water, and the organic layer was dried over magnesium sulfate and cond. The crude material was purified by recrystallization in MeOH, affording N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(5-(methylthio)pyridin-3-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=565.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.61 (1H, d, J=2.3 Hz), 8.59 (1H, s), 7.86 (2H, m), 7.68 (2H, m), 7.09 (1H, m), 6.39 (1H, br. s.), 3.92 (4H, br. s.), 3.83 (4H, br. s.), 3.05-3.50 (4H, br. s.), 3.05 (4H, br. s.), 2.60 (3H, s), 2.18 (3H, br. s.).

Workup

customThe resulting residue was partitioned between DCM and water
dry with materialthe organic layer was dried over magnesium sulfate and cond
customThe crude material was purified by recrystallization in MeOH

Sources & evidence

ORD record: ord-4e8b27f95ae14d2a976079e2477fe346
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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