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Water → methyl 5-(1-((2-(trimethylsilyl)-ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate

HRID 1852997
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HRID 1852997 반응식
Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[N:3]=1.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[N:25][N:26]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:27]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(O)(C)C>[CH3:33][Si:32]([CH3:35])([CH3:34])[CH2:31][CH2:30][O:29][CH2:28][N:26]1[CH:27]=[C:23]([C:2]2[N:7]3[CH:8]=[CH:9][N:10]=[C:6]3[CH:5]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[N:3]=2)[CH:24]=[N:25]1
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참가 물질

8

반응물 5

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 574776664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazoleHCID 86685312Methyl 5-chloroimidazo[1,2-c]pyrimidine-7-carboxylate

생성물 1

HCID 67456583
methyl 5-(1-((2-(trimethylsilyl)-ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate
수율 27.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 3776Isopropanol용매

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온도
80 °C

실험 절차

Methyl 5-chloroimidazo[1,2-c]pyrimidine-7-carboxylate (1.00 g, 4.73 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E; 1.53 g, 4.73 mmol), K3PO4 (2.01 g, 9.45 mmol), Pd2dba3 (0.433 g, 0.473 mmol), and XPHOS (0.563 g, 1.18 mmol) were combined dry. To this was added isopropanol (20 mL) and water (0.34 mL, 19 mmol). After de-gassing for 10 minutes, the flask was sealed and heated to 80° C. for 15 hours. The reaction mixture was diluted in EtOAc and undissolved solid was removed by filtration. The filtrate was concentrated down and purified by silica chromatography using 50-100% EtOAc/Hexanes gradient to afford methyl 5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine-7-carboxylate (0.477 g, 1.28 mmol, 27.0% yield) as an orange brown solid. MS (apci) m/z=374.1 (M+H).

후처리

  1. customAfter de-gassing for 10 minutes
  2. customthe flask was sealed
  3. additionThe reaction mixture was diluted in EtOAc
  4. customundissolved solid was removed by filtration
  5. concentrationThe filtrate was concentrated down
  6. custompurified by silica chromatography

출처 및 근거

ORD 기록
ord-0fb3849e255542a0815ee3ca1e6c8e7c
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08962596B2

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