Tetrahydrofuran → 1-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide

HRID 1025589Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1025589
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:45][OH:46])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]#[N:29])[C:25]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)=[O:38])=[CH:33][CH:32]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C1C[O:50]CC1>O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:45][OH:46])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]([NH2:29])=[O:50])[C:25]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([N:39]5[CH2:40][CH2:41][O:42][CH2:43][CH2:44]5)=[O:38])=[CH:33][CH:32]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Komponenten

4

Edukt 2

HCID 8028TetrahydrofuranHCID 710081901-(3-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile

Produkt 1

HCID 710081541-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amideAusbeute 76,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

1-(3-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (46 mg, 0.074 mmol) was dissolved in 4 mL of THF and 0.5 mL of water. Then dihydrogen tris(dimethylphosphinito)hydroplatinate (3 mg, 0.0069 mmol) was added and the mixture was stirred under fluxing. After 1 hr, TLC indicated complete consumption of the starting material. LC/MS indicated clean desired product formed. The mixture was evaporated and the residue was dissolved in dichloromethane and dried over sodium sulfate, filtered through micron filter and evaporated. The residue was purified through flash column chromatography using methanol in methylene chloride (1.5% to 5% methanol in 10 minutes, 12 g silica gel) to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carboxylic acid amide as a white solid (36 mg, 76.1% yield). LC/MS clacd for C34H34FN7O5 (m/e) 639.26, obsd 640.1 (M+H, ES+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (s, 9H), 3.50 (br., 4H), 3.59 (br., 4H), 4.38 (br. s., 2H), 4.78 (t, J=5.2 Hz, 1H), 7.36 (d, J=8.6 Hz, 3H), 7.52-7.69 (m, 5H), 7.76 (d, J=13.1 Hz, 2H), 7.88 (s, 1H), 8.54 (m, 2H), 9.44 (s, 1H).

Aufarbeitung

  1. customconsumption of the starting material
  2. customformed
  3. customThe mixture was evaporated
  4. dissolutionthe residue was dissolved in dichloromethane
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered through micron
  7. filtrationfilter
  8. customevaporated
  9. customThe residue was purified through flash column chromatography
  10. custommethanol in methylene chloride (1.5% to 5% methanol in 10 minutes, 12 g silica gel)

Quellen und Nachweise

ORD-Eintrag
ord-0e96d68a1bae474f9a5a32aa69ef53a8
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08729078B2

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