(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → (+/-)-tert-Butyl 4-((1-(5-cyano-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913851노트

반응식

HRID 913851 반응식
Br[C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][N:6]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:7]=2)[CH:3]=1.[C:43]([Zn])#[N:44]>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:43]([C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][N:6]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:41])[CH3:42])[N:7]=2)[CH:3]=1)#[N:44]

참가 물질

5

반응물 2

HCID 57546111(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylateHCID 178514178HCID 178514178, 화합물

생성물 1

HCID 57546137(+/-)-tert-Butyl 4-((1-(5-cyano-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

(±)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (75 mg, 0. 113 mmol), tetrakis(triphenylphosphine) palladium(0) (13.1 mg, 0.011 mmol) and cyanozinc (20.7 mg, 0.226 mmol) were combined in dry N,N-dimethylformamide (2 mL) in a microwave tube and sealed. After flushing the mixture with nitrogen, the mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated, dissolved in ethyl acetate and washed with water and brine, concentrated and purified by flash chromatography on silica gel (20% EtOAc/Hex) to afford 21 mg (30.5%) as an oil. LC/MS (HPLC method 2): tR=3.265 min, 609.18(MH)+.

후처리

  1. customsealed
  2. customAfter flushing the mixture with nitrogen
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated
  5. dissolutiondissolved in ethyl acetate
  6. washwashed with water and brine
  7. concentrationconcentrated
  8. custompurified by flash chromatography on silica gel (20% EtOAc/Hex)
  9. customto afford 21 mg (30.5%) as an oil

출처 및 근거

ORD 기록
ord-a3cfb193c33c466b9007c7b803ef1741
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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