Dichloromethane → Tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate

HRID 1913263ノート

反応式

HRID 1913263 の反応式
[C:1]1([C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[CH3:33][Si:34]([CH3:73])([CH3:72])[CH2:35][CH2:36][O:37][CH2:38][N:39]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:40]1[N:45]2[N:46]=[CH:47][C:48](I)=[C:44]2[N:43]=[C:42]([CH2:50][CH:51]2[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]2)[CH:41]=1>O1CCOCC1.O.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]>[CH3:71][Si:68]([CH3:69])([CH3:70])[CH2:67][CH2:66][O:65][CH2:64][N:39]([CH2:38][O:37][CH2:36][CH2:35][Si:34]([CH3:33])([CH3:72])[CH3:73])[C:40]1[N:45]2[N:46]=[CH:47][C:48]([C:10]3[CH:9]=[N:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:12][CH:11]=3)=[C:44]2[N:43]=[C:42]([CH2:50][CH:51]2[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]2)[CH:41]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 457865262-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66733306Tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate

生成物 1

HCID 67494549Tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

2-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.32 mmol, 370 mg), K3PO4 (3.04 mmol, 644 mg), and PdCl2(dppf).CH2Cl2 (0.10 mmol, 83 mg) was added to a solution of tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate (Int-12e, 1.02 mmol, 726 mg) in dioxane (6 mL) and H2O (1 mL). The resulting solution was stirred at 100° C. under argon for 18 hours. The mixture was diluted with H2O and then extracted with ethyl acetate (x2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 4-((7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)methyl)piperidine-1-carboxylate (Int-12f): LCMS tR=3.47 Min (5 min run, UV254nm). Mass calculated for, M+744.2, observed m/z 745.2 (M+H).

後処理

  1. extractionextracted with ethyl acetate (x2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with Na2SO4
  4. customEvaporation and purification by column chromatography

出典と根拠

ORDレコード
ord-5a415a045d864814aeff3b3e168043f7
出典データセット
uspto-grants-2013_12
特許番号
US08609675B2

反応ノート

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