Potassium Phosphate, Tribasic → 4-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 1022037ノート

反応式

HRID 1022037 の反応式
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)=[N:3]1.Cl[C:27]1[C:32]([CH:33]=[O:34])=[C:31]([N:35]2[CH2:47][CH2:46][C:45]3[N:44]4[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]4)=[CH:38][C:37]=3[C:36]2=[O:48])[N:30]=[CH:29][CH:28]=1.C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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].O.C(#N)C>[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=[C:13]([C:27]3[C:32]([CH:33]=[O:34])=[C:31]([N:35]4[CH2:47][CH2:46][C:45]5[N:44]6[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]6)=[CH:38][C:37]=5[C:36]4=[O:48])[N:30]=[CH:29][CH:28]=3)[CH:14]=2)=[N:3]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580441963-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866842464-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

生成物 1

HCID 866844574-(5-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde収率 53.3%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
90 °C

実験手順

A-100 mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 242a (282 mg, 0.82 mmol, 1.5 eq.), 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 139a (180 mg, 0.55 mmol, 1.0 eq.), Pd(dppf)Cl2 (45 mg, 0.055 mmol, 0.1 eq.), sodium acetate (90 mg, 1.25 mmol, 2.0 eq.), K3PO4 (232 mg, 1.25 mmol, 2.0 eq.), acetonitrile (20 mL), and water (1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. for 1 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 242b (150 mg, 48%) as a yellow solid. MS-ESI: [M+H]+ 512.3.

後処理

  1. customA-100 mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-d48aa1783c424060aaccf139d5ec8ada
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

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