Dimethylaminotri-n-butyltin → (+/-)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913855

Reaktionsgleichung

Reaktionsgleichung von HRID 913855
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.[CH3:43][N:44]([Sn](CCCC)(CCCC)CCCC)[CH3:45]>C1(C)C=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.Cl[Pd]Cl>[CH3:43][N:44]([CH3:45])[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

Komponenten

5

Edukt 2

HCID 11034994Dimethylaminotri-n-butyltinHCID 57546111(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Produkt 1

HCID 57546051(+/-)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 10876480Bis(tri-o-tolylphosphine)palladium(II) DichlorideKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

(±)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (150 mg, 0.226 mmol), trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (17.79 mg, 0.023 mmol), and dimethylaminotri-n-butyltin (0.28 mL, 0.905 mmol) were combined in toluene (1.5 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, washed with water and brine, concentrated and purified by flash chromatography on silica gel (15-30% EtOAc/Hex) to afford 115 mg (80.8%) as yellow oil. 1H-NMR (CDCl3, 500 MHz) δ 7.81 (s, 1H), 7.30 (m, 2H), 6.97 (m, 2H), 6.84 (s, 1H), 5.54 (s, 1H), 5.59 (m, 2H), 4.94 (q, J=5 Hz, 1H), 3.6-3.75 (m, 2H), 3.54 (m, 2H), 3.43 (d, J=10 Hz, 1H), 3.31 (d, J=10 Hz, 2H), 3.00-3.10 (m, 2H), 2.81 (s, 6H), 2.03-2.12 (m, 2H), 1.85-1.95 (m, 2H), 1.43 (d, J=10 Hz, 3H), 1.41 (s, 9H), 0.85-0.90 (m, 2H), −0.09 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 171.1, 161.3 (d, J=975 Hz), 155.0, 147.0, 143.4, 139.2, 134.1, 128.9, 123.5, 120.9, 115.4, 115.1, 114.9, 97.2, 81.5, 79.3, 74.4, 67.0, 60.4, 41.9, 41.2, 32.3, 28.5, 27.9, 26.9, 23.1, 21.1, 17.8, 17.6, 14.3, 13.7, −1.36; Mass spec.: 627.60(MH)+.

Aufarbeitung

  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 (15-30% EtOAc/Hex)
  9. customto afford 115 mg (80.8%) as yellow oil

Quellen und Nachweise

ORD-Eintrag
ord-f89aedaecfb1420999aec5d4c27f3a8f
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026257B2

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