Formic Acid → US9321721, Example 1

HRID 631772Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 631772
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]([NH2:26])=[O:25])=[CH:18][CH:17]=1)=[O:14].I[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(NCC)C.C(O)=O>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][C:3]=1[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19](/[C:22](/[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:23]\[C:24]([NH2:26])=[O:25])=[CH:18][CH:17]=1)=[O:14]

Komponenten

7

Edukt 4

HCID 284Formic AcidHCID 8021DiethylamineHCID 11575IodobenzeneHCID 903870243-{4-[({[2-Fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide

Produkt 1

HCID 78426979US9321721, Example 1Ausbeute 23,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysator2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A mixture of 3-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide (31.0 mg, 0.085 mmol), iodobenzene (0.010 mL, 0.089 mmol), diethylamine (0.029 mL, 0.281 mmol), formic acid (0.0083 mL, 0.221 mmol), and bis(dibenzylideneacetone)palladium(0) (3.4 mg, 0.006 mmol) in 1.1 mL EtOAc (degassed) was heated at 75° C. After 2 hours, an additional 2 mg bis(dibenzylideneacetone)palladium(0) was added and the reaction continued for 18 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous Na2CO3, brine, dried with anhydrous Na2SO4 and rotary evaporated. The crude product was chromatographed eluting with EtOAc/CHCl3 and the resulting solid again chromatographed with MeOH/CHCl3 to give the title compound as an off-white solid (8.8 mg, 23%). 1H NMR (Acetone-d6) δ: 8.79 (dd, J=7.5, 2.2 Hz, 1H), 8.43 (d, J=2.9 Hz, 1H), 8.41 (s, 1H), 7.39-7.44 (m, 2H), 7.27-7.39 (m, 7H), 7.11-7.16 (m, 3H), 6.76 (br. s., 1H), 6.49 (s, 1H)

Aufarbeitung

  1. waitthe reaction continued for 18 hours
  2. customThe reaction was partitioned between EtOAc and H2O/brine mixture
  3. washThe EtOAc layer was washed with dilute aqueous HCl
  4. dry with materialaqueous Na2CO3, brine, dried with anhydrous Na2SO4 and rotary evaporated
  5. customThe crude product was chromatographed
  6. washeluting with EtOAc/CHCl3
  7. customthe resulting solid again chromatographed with MeOH/CHCl3

Quellen und Nachweise

ORD-Eintrag
ord-19da11164be84ab9abdcb509922c61ce
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321721B2

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