Sodium Bicarbonate → t-Butyl {2-[(4-{3-cyano-5-[(4-isopropylpiperazin-1-yl)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

HRID 599521Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 599521
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:34]1[N:41]=[CH:40][C:39]([CH2:42][N:43]2[CH2:48][CH2:47][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:45][CH2:44]2)=[CH:38][C:35]=1[C:36]#[N:37].C(=O)([O-])O.[Na+]>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].COCCOC>[C:36]([C:35]1[C:34]([C:20]2[CH:19]=[CH:18][C:17]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:32])=[CH:22][CH:21]=2)=[N:41][CH:40]=[C:39]([CH2:42][N:43]2[CH2:44][CH2:45][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:47][CH2:48]2)[CH:38]=1)#[N:37]

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 59830883N-(2-t-Butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 598487902-Chloro-5-[(4-isopropylpiperazin-1-yl)methyl]nicotinonitrile

Produkt 1

HCID 86624986t-Butyl {2-[(4-{3-cyano-5-[(4-isopropylpiperazin-1-yl)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

1,1′-Bis(diphenylphosphino)ferrocenedichloropalladium (II) chloride (58 mg, 0.072 mmol) was added to a mixture of N-(2-t-butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (626 mg, 1.43 mmol prepared as described in International Patent Publication Number WO03/087057, Method 13, page 60), 2-chloro-5-[(4-isopropylpiperazin-1-yl)methyl]nicotinonitrile (398 mg, 1.43 mmol; see Method 20), saturated aqueous sodium hydrogen carbonate solution (5 ml) and 1,2-dimethoxyethane (10 ml). The mixture was heated at 80° C. for 1 hour then allowed to cool to room temperature and partitioned between dichloromethane (75 ml) and water (50 ml). The aqueous layer was extracted with further dichloromethane (2×75 ml). The combined organics were dried over magnesium sulfate, filtered and then evaporated to dryness. The residue was purified by flash chromatography on silica, eluting with methanol (5-10%) in dichloromethane to afford the title compound as a yellow gum which crystallised on trituration with diethyl ether, (652 mg, 82%).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. custompartitioned between dichloromethane (75 ml) and water (50 ml)
  3. extractionThe aqueous layer was extracted with further dichloromethane (2×75 ml)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography on silica
  8. washeluting with methanol (5-10%) in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-4cd109ca320c45ceb3a072ef146053f8
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897778B2

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