Sodium Bicarbonate → Tert-butyl 2-({5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-1,1'-biphenyl-4-yl}carbonyl)hydrazinecarboxylate

HRID 31420Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 31420
[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:7]=2)[CH2:3][CH2:2]1.CC(C)(C)C([NH:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][C:34](Br)=[CH:33][CH:32]=1)=O.[C:41](=[O:44])([O-])[OH:42].[Na+]>CC(O)C.C(OCC)(=O)C.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>[CH:1]1([NH:4][C:5]([C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:34]3[CH:33]=[CH:32][C:31]([C:30]([NH:29][NH:28][C:41]([O:42][C:6]([CH3:11])([CH3:7])[CH3:5])=[O:44])=[O:38])=[CH:36][CH:35]=3)[CH:7]=2)=[O:23])[CH2:2][CH2:3]1

Komponenten

7

Edukt 3

HCID 516892Sodium BicarbonateHCID 47826934-bromo-N'-(2,2-dimethylpropanoyl)benzohydrazide2×HCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×

Produkt 1

HCID 69316615Tert-butyl 2-({5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-1,1'-biphenyl-4-yl}carbonyl)hydrazinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 3776IsopropanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

N-Cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 32) (3.27 g), 4-bromo-benzoic acid N′-(2,2-dimethyl-propionyl)-hydrazide (Intermediate 31) (3.39 g), tetrakis(triphenylphosphine)palladium (238 mg) and aqueous sodium hydrogen carbonate (1M, 21.6 ml) were mixed in propan-2-ol (20 ml) and heated at 90° C. under nitrogen for 18 hours. The cooled reaction mixture was reduced to dryness under vacuum, the residue partially dissolved in ethyl acetate and filtered. The filtrate was absorbed onto silica and purified by chromatography on silica biotage columns (2×100 g), eluting with ethyl acetate/cyclohexane (2:3). The product fractions were reduced to dryness under vacuum to give tert-butyl 2-({5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2′-methyl-1,1′-biphenyl-4-yl}carbonyl)hydrazinecarboxylate.

Aufarbeitung

  1. customThe cooled reaction mixture
  2. filtrationfiltered
  3. customThe filtrate was absorbed onto silica
  4. custompurified by chromatography on silica biotage columns (2×100 g)
  5. washeluting with ethyl acetate/cyclohexane (2:3)

Quellen und Nachweise

ORD-Eintrag
ord-815eec6cb8dd45079998f14e3ae2fc01
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07425555B2

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