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

HRID 556854ノート

反応式

HRID 556854 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3343377f879746fd9345267211d3d8a1
出典データセット
uspto-grants-2011_11
特許番号
US08058045B2

反応ノート

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