Toluene → tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamate

HRID 1466220노트

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HRID 1466220 반응식
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][CH2:13]2)=[N:4][N:3]=1.[CH3:27][N:28]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[N:29]1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[CH3:26][N:18]([CH:15]1[CH2:16][CH2:17][N:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([C:32]3[N:28]([CH3:27])[N:29]=[CH:30][CH:31]=3)=[N:3][N:4]=2)[CH2:13][CH2:14]1)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]

참가 물질

8

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59627406tert-Butyl 1-(4-bromophthalazin-1-yl)piperidin-4-yl(methyl)carbamate

생성물 1

HCID 59627389tert-butyl methyl(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)carbamate수율 69%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매

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온도
90 °C

실험 절차

Charge a reaction tube with tert-butyl 1-(4-bromophthalazin-1-yl)piperidin-4-yl(methyl)carbamate (500 mg, 1.2 mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (370 mg, 1.8 mmol), sodium carbonate (252 mg, 2.4 mmol), toluene (3.75 mL), ethanol (1.25 mL), and water (1.25 mL). Degas the reaction mixture with nitrogen for 10 min. Add tetrakis(triphenylphosphine)palladium (137.1 mg, 118.7 μmol). Bubble nitrogen through the reaction mixture for another 10 min. Cap the reaction vial and heat at 90° C. overnight. Cool the reaction and filter through a silica gel pad eluting with 5% MeOH:CH2Cl2. Concentrate the fractions under reduced pressure. Purify the resulting residue using silica gel chromatography (2% 2 N NH3 in MeOH:CH2Cl2) to obtain the final product (345.6 mg, 69%). ES/MS m/z 423.2 (M+1).

후처리

  1. customDegas the reaction mixture with nitrogen for 10 min
  2. customCap
  3. customthe reaction vial
  4. temperatureCool
  5. customthe reaction
  6. filtrationfilter through a silica gel pad
  7. washeluting with 5% MeOH
  8. concentrationConcentrate the fractions under reduced pressure
  9. customPurify the resulting residue

출처 및 근거

ORD 기록
ord-c122fa4714394f2ca80295c90279e657
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000023B2

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