Hydrochloric Acid → HCID 46893522, Verbindung

HRID 625817Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 625817
[CH3:1][S:2]([CH2:5]P(=O)(OCC)OCC)(=[O:4])=[O:3].CC(C)([O-])C.[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([C:29]2[N:38]=[C:37]([NH:39][C:40]3[CH:44]=[C:43]([CH3:45])[NH:42][N:41]=3)[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]=2)=O)=[CH:23][CH:22]=1.Cl>C1COCC1.CCOC(C)=O.[Pd]>[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([C:29]2[N:38]=[C:37]([NH:39][C:40]3[CH:44]=[C:43]([CH3:45])[NH:42][N:41]=3)[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]=2)[CH2:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:23][CH:22]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 533797Diethyl (methanesulfonylmethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 46892243(4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

Produkt 1

HCID 46893522HCID 46893522, VerbindungAusbeute 4,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To diethyl methylsulfonylmethylphosphonate (746 mg, 3.24 mmol) in THF (20 mL) at 0° C. was added potassium t-butoxide (1.0 M in THF, 3.25 mL, 3.25 mmol) and the mixture was stirred for 5 min. Then (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 3 (375 mg, 1.08 mmol) was added and the mixture was stirred at rt for 4 h. The mixture was treated with 1 N HCl and the resulting mixture was extracted with EtOAc. The organic layer was washed with brine and then concentrated to a residue (700 mg), which was subjected to silica gel chromatography eluting with 1-10% MeOH/DCM to give impure material. To a portion of this material (166 mg) in EtOAc (5 mL) was added 10% Pd—C (166 mg) and the mixture was stirred under a hydrogen atmosphere at rt overnight. The mixture was filtered and to the filtrate was added palladium on carbon (10%). The mixture was stirred under a hydrogen atmosphere for several hours, and then filtered. The filtrate was concentrated to a solid, which was triturated with ether to afford 2-(1-(4-fluorophenyl)-2-(methylsulfonyl)ethyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (22 mg). 1H NMR (300 MHz, DMSO-d6) δ 2.28 (s, 3H) 2.87 (s, 3H) 3.85 (m, 1H) 4.34 (m, 1H) 4.68 (bs, 1H) 6.45 (s, 1H) 7.15 (t, 2H) 7.49 (m, 3H) 7.76 (m, 2H) 8.56 (d, 1H) 10.36 (s, 1H) 12.17 (s, 1H); LC-MS (ESI) m/z 426 (M+H)+.

Aufarbeitung

  1. stirringthe mixture was stirred at rt for 4 h
  2. extractionthe resulting mixture was extracted with EtOAc
  3. washThe organic layer was washed with brine
  4. concentrationconcentrated to a residue (700 mg), which
  5. washeluting with 1-10% MeOH/DCM
  6. customto give impure material
  7. stirringthe mixture was stirred under a hydrogen atmosphere at rt overnight
  8. filtrationThe mixture was filtered and to the filtrate
  9. additionwas added palladium on carbon (10%)
  10. stirringThe mixture was stirred under a hydrogen atmosphere for several hours
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated to a solid, which
  13. customwas triturated with ether

Quellen und Nachweise

ORD-Eintrag
ord-982cc279b47f4a71b67617a337007c44
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09308207B2

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