Sodium Carbonate → (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 518243

反応式

HRID 518243 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3Cl)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1.[CH3:31][O:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[N:37][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:35]2[CH:36]=[N:37][CH:38]=[C:33]([O:32][CH3:31])[CH:34]=2)[CH3:10])[C:5]([C:29]#[N:30])=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27630875-Methoxypyridine-3-boronic AcidHCID 67950671(S)-2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

生成物 1

HCID 71270277(S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To a mixture of (S)-2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 8 (50 mg, 0.12 mmol) and (5-methoxypyridin-3-yl)boronic acid (37 mg, 0.24 mmol) in anhydrous 1,4-dioxane (4 mL), PdCl2(dppf) (9.8 mg, 0.012 mmol) and aqueous Na2CO3 solution (1 M, 0.6 mL, 0.6 mmol) were added and the resulting mixture was stirred at 120° C. for 3 h. The reaction mixture was allowed to cool to RT, quenched with water, and then extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 0-10% MeOH-DCM to afford the product, (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 9. ESI-MS m/z: 490.2 [M+H]+. Compound 2-amino-4-((S)-1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carboxamide 10 was also formed in the above reaction and it was isolated by column chromatography. ESI-MS m/z: 508.2 [M+H]+.

後処理

  1. additionwere added
  2. temperatureto cool to RT
  3. customquenched with water
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by flash column chromatography on silica gel eluting with 0-10% MeOH-DCM

出典と根拠

ORDレコード
ord-ecc326984da447868f32a60860a3c92f
出典データセット
uspto-grants-2015_08
特許番号
US09115141B2

関連ノート

読み込み中…