2-Aminopyridine → HCID 67285900, compound

HRID 1618670Notes

Reaction equation

Cl[C:2]1[C:11]([CH3:12])=[C:10]([Cl:13])[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=1.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=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+]>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]>[Cl:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=[C:2]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 97 °C

Procedure

A mixture of 2,4-dichloro-5,7-difluoro-3-methylquinoline (400 mg, 1.61 mmol), 2-aminopyridine (152 mg, 1.61 mmol), Pd2dba3 (148 mg, 0.161 mmol), XPhos (154 mg, 0.323 mmol), sodium tert-butoxide (465 mg, 4.84 mmol) in toluene (10.8 mL) was heated at 97° C. for 18 h. Upon completion, the reaction was concentrated, diluted with EtOAc, and washed with saturated aqueous NaHCO3, water, and brine. The organic layer was then dried over MgSO4 and evaporated in vacuo. The resulting crude residue was purified by flash chromatography (silica gel, 0-15% EtOAc in hexanes as eluent) to give 4-chloro-5,7-difluoro-3-methyl-N-(pyridin-2-yl)quinolin-2-amine as a pale yellow solid. Mass Spectrum (ESI) m/e=306.0 (M+1).

Workup

concentrationUpon completion, the reaction was concentrated
additiondiluted with EtOAc
washwashed with saturated aqueous NaHCO3, water, and brine
dry with materialThe organic layer was then dried over MgSO4
customevaporated in vacuo
customThe resulting crude residue was purified by flash chromatography (silica gel, 0-15% EtOAc in hexanes as eluent)

Sources & evidence

ORD record: ord-5c431f82d6a24bcaa2fc6e6f3b7446f2
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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