Dichloromethane → 5-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

HRID 1623382Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[N:4][C:3]=1[Cl:16].C([O-])([O-])=O.[Na+].[Na+].[Cl:23][C:24]1[C:25](B(O)O)=[CH:26][C:27]([F:30])=[N:28][CH:29]=1.C(Cl)Cl>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:16][C:3]1[N:4]=[CH:5][C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[N:7][C:2]=1[C:25]1[C:24]([Cl:23])=[CH:29][N:28]=[C:27]([F:30])[CH:26]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (20 mg, 0.065 mmol), Na2CO3 (17.98 mg, 0.170 mmol) and 5-chloro-2-fluoropyridin-4-ylboronic acid (17.16 mg, 0.098 mmol) in DME (1 ml) was added PdCl2(dppf).CH2Cl2 adduct (4.26 mg, 5.22 μmol). The reaction mixture was capped in a flask and heated to 100° C. for 4 hr an oil bath. The reaction mixture was diluted with EtOAc and washed with H2O sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (50% EtOAc/Hexane) to yield 5-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (10 mg, 0.028 mmol, 42.9% yield). LCMS (m/z): 357.0 (MH+), retention time=0.95 min.

Workup

customThe reaction mixture was capped in a flask
washwashed with H2O
filtrationfiltered
concentrationconcentrated
customThe crude was purified by column chromatography on silica gel (50% EtOAc/Hexane)

Sources & evidence

ORD record: ord-f1a56a35d34740f1b04ef190e45c6907
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778951B2

Reaction notes

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