Binap, (A+-)- → Tert-butyl 4-((5-chloro-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 384693Notes

Reaction equation

HRID 384693 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[C:5]([Cl:23])=[CH:4][N:3]=1.Br[C:25]1[N:26]=[CH:27][C:28]([C:31]#[N:32])=[N:29][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O1CCOCC1>[Cl:23][C:5]1[C:6]([NH:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:14][CH2:15]2)=[CH:7][C:2]([NH:1][C:25]2[CH:30]=[N:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 378187222-Bromo-5-cyanopyrazineHCID 59613409Tert-butyl 4-((2-amino-5-chloropyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 59613464Tert-butyl 4-((5-chloro-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylateYield 60.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Dry dioxane (0.45 mL) was added to a microwave reaction vial containing tert-butyl 4-((2-amino-5-chloropyridin-4-ylamino)methyl)piperidine-1-carboxylate (23 mg, 0.067 mmol), 5-bromopyrazine-2-carbonitrile (8.3 mg, 0.045 mmol), tris(dibenzylideneacetone)-dipalladium chloroform complex (1.9 mg, 4 mol %), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (2.2 mg, 8 mol %) and sodium tert-butoxide (6.1 mg, 1.4 eq.) under nitrogen. The vial was sealed and nitrogen gas was bubbled through the suspension with stirring for 5 min. The mixture was heated at 90° C. for 30 min under microwave irradiation. The mixture was diluted with methanol and adsorbed onto Isolute SCX-II acidic resin (2 g). The resin was washed with methanol, then 2M ammonia in methanol. The basic fractions were concentrated and the residue was further purified by preparative thin layer chromatography, eluting with 5% MeOH in dichloromethane, to give tert-butyl 4-((5-chloro-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (12 mg, 60%) as an off-white solid.

Workup

  1. customThe vial was sealed
  2. customnitrogen gas was bubbled through the suspension
  3. additionThe mixture was diluted with methanol
  4. washThe resin was washed with methanol
  5. concentrationThe basic fractions were concentrated
  6. customthe residue was further purified by preparative thin layer chromatography
  7. washeluting with 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-0f2224a772e04a22a0f136c5842bafff
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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