Potassium Carbonate → 4-(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-3-formylpyridin-4-yl)-1-methyl-1H-pyrrole-2-carboxamide

HRID 1025598Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1025598
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[C:3]1[C:16]([NH2:18])=[O:17].[C:19]([C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:33])[CH:32]=1)[C:29](=[O:34])[N:28]([C:35]1[N:42]=[CH:41][CH:40]=[C:39](I)[C:36]=1[CH:37]=[O:38])[N:27]=[CH:26]2)([CH3:22])([CH3:21])[CH3:20].O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C.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]>[C:19]([C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:33])[CH:32]=1)[C:29](=[O:34])[N:28]([C:35]1[C:36]([CH:37]=[O:38])=[C:39]([C:5]3[CH:4]=[C:3]([C:16]([NH2:18])=[O:17])[N:2]([CH3:1])[CH:6]=3)[CH:40]=[CH:41][N:42]=1)[N:27]=[CH:26]2)([CH3:22])([CH3:20])[CH3:21]

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 710080811-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxamideHCID 866737152-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-iodonicotinaldehyde

Produkt 1

HCID 866737144-(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-3-formylpyridin-4-yl)-1-methyl-1H-pyrrole-2-carboxamideAusbeute 28,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

In a 100 mL round-bottomed flask, 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxamide (61.0 mg, 244 μmol, Eq: 1.10), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-iodonicotinaldehyde (100 mg, 222 μmol, Eq: 1.00) and [1,1′-bis(Diphenylphosphino)ferrocene]dichloro palladium (II) (16.2 mg, 22.2 μmol, Eq: 0.1) were combined with dioxane (667 μl) to give a red solution. Potassium carbonate (61.3 mg, 443 μmol, Eq: 2) in water (66.7 μl) was added and the resultant suspension was heated to 70° C. and stirred for 32 h. The reaction was diluted with ethyl acetate (10 mL), washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 15% EtOAc in hexanes to give 4-[2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-3-formyl-pyridin-4-yl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (28 mgs, 28.2%) as an off white solid. 1H NMR (DMSO-d6) δ: 10.06 (s, 1H), 8.72 (d, J=5.3 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 7.91 (d, J=1.8 Hz, 1H), 7.79 (dd, J=13.3, 1.8 Hz, 1H), 7.73 (d, J=5.3 Hz, 1H), 7.69-7.76 (m, 1H), 7.50 (d, J=1.8 Hz, 1H), 7.17 (d, J=2.0 Hz, 1H), 7.12 (br. s., 1H), 3.93 (s, 3H), 1.39 (s, 9H); MS m/e 448.5 (M+H+).

Aufarbeitung

  1. customto give a red solution
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 12 g, 10% to 15% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-f30bf4c31e8849a095f18ca807e65bf4
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08729078B2

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