Potassium Phosphate, Tribasic → methyl 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxylate

HRID 634212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 634212
[CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:14]=[C:13]3B2OC(C)(C)C(C)(C)O2)=[N:8][N:9]=1)([CH3:3])[CH3:2].Cl[C:39]1[N:44]=[C:43]([C:45]([O:47][CH3:48])=[O:46])[CH:42]=[C:41]([CH:49]2[CH2:51][CH2:50]2)[N:40]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:49]1([C:41]2[N:40]=[C:39]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:7]5[O:6][C:5]([NH:4][CH:1]([CH3:2])[CH3:3])=[N:9][N:8]=5)[CH:11]=4)[N:15]([S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:20])=[O:21])[CH:14]=3)[N:44]=[C:43]([C:45]([O:47][CH3:48])=[O:46])[CH:42]=2)[CH2:50][CH2:51]1

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 39243138Methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylateHCID 68328163HCID 68328163, Verbindung

Produkt 1

HCID 68328026methyl 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxylateAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

To a 5 mL glass microwave tube containing N-isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (120 mg, 0.230 mmol) was added methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylate (58.6 mg, 0.276 mmol), potassium phosphate (146 mg, 0.689 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (6.6 mg, 0.014 mmol), and Pd2(dba)3 (6.3 mg, 6.89 μmol). The tube was purged with argon, the solids were treated with dioxane (5 mL) and water (0.5 mL), the tube was sealed, and the contents were heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° C. for 25 min. The mixture was treated with H2O and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (eluting with 20-100% EtOAc in Hex) affording methyl 6-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxylate (16.4 mg, 13%) as a light yellow amorphous solid. MS (ESI, pos. ion) m/z: 397.1 (M+1).

Aufarbeitung

  1. customThe tube was purged with argon
  2. additionthe solids were treated with dioxane (5 mL) and water (0.5 mL)
  3. customthe tube was sealed
  4. additionThe mixture was treated with H2O
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography (eluting with 20-100% EtOAc in Hex)

Quellen und Nachweise

ORD-Eintrag
ord-d3fb48ac717f4cd29a81478ac36dfe69
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321756B2

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