Potassium Phosphate, Tribasic → tert-butyl 5-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 77385

Reaktionsgleichung

Reaktionsgleichung von HRID 77385
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]([CH3:12])[C:5]2=[O:13].[CH2:14]1[CH:18]2[CH2:19][NH:20][CH2:21][CH:17]2[CH2:16][N:15]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>[CH3:12][N:6]1[C:5](=[O:13])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([N:20]3[CH2:19][CH:18]4[CH2:14][N:15]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:16][CH:17]4[CH2:21]3)[CH:3]=2)[N:8]=[CH:7]1

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 42169776-Bromo-3-methyl-3,4-dihydroquinazolin-4-one2×

Produkt 1

HCID 69928551tert-butyl 5-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateAusbeute 38 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 6-bromo-3-methylquinazolin-4(3H)-one (Intermediate 19A) (0.46 g, 1.92 mmol), tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H) carboxylate (0.49 g, 2.31 mmol), potassium phosphate, tribasic (1.33 g, 5.77 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1-biphenyl (26.9 mg, 0.06 mmol) and tris(dibenzyllideneacetone)dipalladium (0) (17.6 mg, 0.02 mmol) in dioxane (10 mL) was heated at 90° C. for 20 h. The mixture was diluted with water and the product extracted into dichloromethane. The organic layer was evaporated to dryness, re-dissolved in methanol and purified using a 5 g SCX column. The mixture was then further purified on silica (25 g SNAP column on SP4). Eluting with dichloromethane to 60/40 dichloromethane/(2M NH3 in methanol) to afford tert-butyl 5-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (270 mg, 0.73 mmol).

Aufarbeitung

  1. extractionthe product extracted into dichloromethane
  2. customThe organic layer was evaporated to dryness
  3. dissolutionre-dissolved in methanol
  4. custompurified
  5. customThe mixture was then further purified on silica (25 g SNAP column on SP4)
  6. washEluting with dichloromethane to 60/40 dichloromethane/(2M NH3 in methanol)

Quellen und Nachweise

ORD-Eintrag
ord-35b30c9d26634b1b8db5436a1b4e5161
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841289B2

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