Dichloromethane → HCID 90314097, compound

HRID 1523744Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[C:14]([F:21])[CH:13]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>O1CCOCC1>[NH2:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][C:5]([C:15]2[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=2[F:21])=[CH:6][N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-amino-6-bromopyrazine-2-carbonitrile (2.00 g, 9.55 mmol) in 1,4-dioxane (48 mL), were added (4-chloro-2-fluorophenyl)boronic acid (1.66 g, 9.55 mmol) and aqueous Na2CO3 (2 M, 24 mL, 48 mmol) and the reaction mixture sparged with N2 gas for 10 min. Pd(dppf)Cl2.CH2Cl2 (0.349 g, 0.477 mmol) was then added and the reaction mixture sparged for an additional 10 min with N2 gas. The reaction vessel was sealed and heated for 3 hours at 80° Celsius. The mixture was cooled to rt, filtered through celite, and the filter cake washed with EtOAc (300 mL). The filtrate was washed with a 1:1 mixture of brine/H2O (2×100 mL). The organic phase was concentrated to dryness and subjected to FCC to give the title compound (1.99 g, 84%). MS (ESI): mass calcd. for C11H6ClFN4, 248.03; m/z found 249.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.67 (d, J=2.0, 1H), 7.83 (m, 1H), 7.25-7.08 (m, 2H), 5.36 (s, 2H).

Workup

customthe reaction mixture sparged with N2 gas for 10 min
customthe reaction mixture sparged for an additional 10 min with N2 gas
customThe reaction vessel was sealed
temperatureThe mixture was cooled to rt
filtrationfiltered through celite
washthe filter cake washed with EtOAc (300 mL)
washThe filtrate was washed with a 1:1 mixture of brine/H2O (2×100 mL)
concentrationThe organic phase was concentrated to dryness

Sources & evidence

ORD record: ord-c5b741cb60d0459e9715b22f87627ad5
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079866B2

Reaction notes

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