Sodium Carbonate → Tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate

HRID 577521ノート

反応式

HRID 577521 の反応式
[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:31])[C:20]([O:27][CH:28]([CH3:30])[CH3:29])=[CH:21][C:22]=3Br)[C:17]2=[O:32])=[C:13]([CH3:33])[CH:12]=[C:11]([CH3:34])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[CH:45][C:46]([N:49]3[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]3)=[N:47][CH:48]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].C(Cl)Cl.O1CCOCC1>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:31])[C:20]([O:27][CH:28]([CH3:30])[CH3:29])=[CH:21][C:22]=3[C:43]3[CH:44]=[CH:45][C:46]([N:49]4[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]4)=[N:47][CH:48]=3)[C:17]2=[O:32])=[C:13]([CH3:33])[CH:12]=[C:11]([CH3:34])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 16217947Tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 867237472-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one

生成物 1

HCID 86723748Tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate収率 58%

試薬・触媒・溶媒 2

HCID 178478472(1,1'-Bis(diphenylphosphino)ferrocene)dichloropalladium-dichloromethane (1:1)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A mixture of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (77e, 60 mg, 0.110 mmol), tert-butyl 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine-1-carboxylate (64 mg, 0.164 mmol), Na2CO3 (200 μL, 0.400 mmol, 2 M solution), PdCl2(dPPf)-DCM (9 mg, 0.011 mmol), and 1,4-dioxane (2 mL) was stirred at 120° C. in microwave for 30 minutes. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (20 mL) and water (20 mL). The organic phase was separated, washed with brine (1×20 mL), dried over sodium sulfate, concentrated under vacuum, and purified by column chromatography (0-100% EtOAc/heptanes) to give tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate (77f, 46 mg, 58% yield) as a solid.

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. customThe organic phase was separated
  4. washwashed with brine (1×20 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. custompurified by column chromatography (0-100% EtOAc/heptanes)

出典と根拠

ORDレコード
ord-c138c88880e04d2a9a729dcaa1f5fa79
出典データセット
uspto-grants-2015_05
特許番号
US09040515B2

反応ノート

読み込み中…