Binap, (A+-)- → 5-((5-Chloro-4-morpholinopyridin-2-yl)amino)pyrazine-2-carbonitrile

HRID 384640Notes

Reaction equation

[Cl:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.Br[N:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]#[N:23])[CH2:17]1.CC(C)([O-])C.[Na+].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>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[Cl:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:4][C:5]([NH:8][C:21]2[N:16]=[CH:17][C:18]([C:22]#[N:23])=[N:19][CH:20]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 140 °C

Procedure

5-Chloro-4-morpholinopyridin-2-amine (68 mg, 0.31 mmol), 4-bromo-cyanopyrazine (30 mg, 0.20 mmol), sodium tert-butoxide (45 mg, 0.47 mmol), Pd(OAc)2 (3 mg, 0.01 mmol) and BINAP (0.030 g, 0.05 mmol) were mixed under argon atmosphere before addition of mixture of DMF in toluene (2:1, 0.7 mL). The reaction mixture was heated to 140° C. by microwave irradiation for 20 minutes. The reaction mixture was purified by ion exchange chromatography on SCX-II acidic resin (500 mg) eluting with methanol, then 2M ammonia-methanol. The basic fractions were combined and solvent was evaporated. Flash chromatography on silica, eluting with ethyl acetate-hexane (1:1) gave 5-(5-chloro-4-morpholinopyridin-2-ylamino)pyrazine-2-carbonitrile as a yellow solid (20 mg, 20%).

Workup

customThe reaction mixture was purified by ion exchange chromatography on SCX-II acidic resin (500 mg)
washeluting with methanol
customsolvent was evaporated
washFlash chromatography on silica, eluting with ethyl acetate-hexane (1:1)

Sources & evidence

ORD record: ord-f13aed21e966462dad020ae697b5cf5b
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367658B2

Reaction notes

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