Binap, (A+-)- → 5-(4-(1-Methylpiperidin-4-ylamino)-5-phenylpyridin-2-ylamino)pyrazine-2-carbonitrile

HRID 556845Notes

Reaction equation

HRID 556845 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:13][N:12]=[C:11]([NH2:21])[CH:10]=2)[CH2:4][CH2:3]1.Br[C:23]1[CH:28]=[N:27][C:26]([C:29]#[N:30])=[CH:25][N:24]=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+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([NH:8][C:9]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:13][N:12]=[C:11]([NH:21][C:23]3[N:24]=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=3)[CH:10]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 378187222-Bromo-5-cyanopyrazineHCID 59613481N4-(1-Methylpiperidin-4-yl)-5-phenylpyridine-2,4-diamine

Product 1

HCID 596134445-(4-(1-Methylpiperidin-4-ylamino)-5-phenylpyridin-2-ylamino)pyrazine-2-carbonitrileYield 17.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N4-(1-methylpiperidin-4-yl)-5-phenylpyridine-2,4-diamine (0.050 g, 0.17 mmol), 2-bromo-5-cyanopyrazine (0.022 g, 0.12 mmol), BINAP (0.003 g, 0.01 mmol), sodium tert-butoxide (0.016 g, 0.16 mmol), tris(dibenzylideneacetone)dipalladium chloroform complex (0.005 g, 0.01 mmol) in toluene (0.7 mL) was stirred at r.t. under nitrogen for 10 min before being heated under microwave irradiation for 30 min at 90° C. The crude reaction mixture was purified by ion exchange on SCX-II acidic resin (0.5 g) eluting with methanol/dichloromethane (1/1), then 2M ammonia-methanol. The basic fractions were combined and the solvent was removed in vacuo. The crude mixture was purified by preparative thin layer chromatography eluting with methanol/dichloromethane (1/9) to give the desired compound as a yellow solid (0.008 g, 17%).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by ion exchange on SCX-II acidic resin (0.5 g)
  3. washeluting with methanol/dichloromethane (1/1)
  4. customthe solvent was removed in vacuo
  5. customThe crude mixture was purified by preparative thin layer chromatography
  6. washeluting with methanol/dichloromethane (1/9)

Sources & evidence

ORD record
ord-c9e40f5975504d1c9860a7ee0abc46c2
Source dataset
uspto-grants-2011_11
Patent number
US08058045B2

Reaction notes

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