4-Methoxybenzylamine → 3,5-Difluoro-N4-(4-methoxybenzyl)pyridine-2,4-diamine

HRID 710565Notes

Reaction equation

[F:1][C:2]1[C:3]([NH2:10])=[N:4][CH:5]=[C:6]([F:9])[C:7]=1I.[CH3:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH2:18])=[CH:15][CH:14]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].C(=O)(O)[O-].[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>[F:1][C:2]1[C:3]([NH2:10])=[N:4][CH:5]=[C:6]([F:9])[C:7]=1[NH:18][CH2:17][C:16]1[CH:19]=[CH:20][C:13]([O:12][CH3:11])=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A stirred mixture of 3,5-Difluoro-4-iodopyridin-2-amine (3.0 g, 11.7 mmol), 4-methoxybenzylamine (1.92 g, 14 mmol), Pd2dba3 (1.07 g, 1.2 mmol), BINAP (1.46 g, 2.3 mmol), sodium t-butoxide (1.46 g, 2.3 mmol), and toluene (600 ml) was heated in a sealed vessel with stirring at 130° C. for 16 h. Aqueous sodium bicarbonate solution was added and the mixture was extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant) to provide the title compound.

Workup

temperaturewas heated in a sealed vessel
extractionthe mixture was extracted with ethyl acetate
dry with materialThe combined organic extracts were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed on silica gel (30% ethyl acetate in hexanes eluant)

Sources & evidence

ORD record: ord-80acb594515e4a3e8b8041eb50c67780
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181238B2

Reaction notes

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