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Potassium Phosphate, Tribasic → 5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

HRID 634226
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 634226
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]4[O:22][C:21]([NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[N:20][N:19]=4)[CH:16]=3)[N:11]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:10]=2)O1.Br[C:41]1[N:46]=[C:45]([CH:47]2[CH2:49][CH2:48]2)[CH:44]=[CH:43][N:42]=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:47]1([C:45]2[CH:44]=[CH:43][N:42]=[C:41]([C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:18]5[O:22][C:21]([NH:23][CH2:24][C:25]([F:27])([F:26])[F:28])=[N:20][N:19]=5)[CH:16]=4)[N:11]([S:29]([C:32]4[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[CH:10]=3)[N:46]=2)[CH2:49][CH2:48]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 49758247HCID 49758247, VerbindungHCID 683280655-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

Produkt 1

HCID 68328531
5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a 5 mL glass microwave tube containing 5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine (180 mg, 0.320 mmol) was added 2-bromo-4-cyclopropylpyrimidine (73.3 mg, 0.368 mmol) (CombiPhos Catalysts Inc.), potassium phosphate (204 mg, 0.960 mmol) (Sigma-Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (9.16 mg, 0.019 mmol) (Strem), and Pd2(dba)3 (8.79 mg, 9.60 μmol) (Strem). The tube was purged with argon, the solids were treated with dioxane (2.0 mL) and water (0.200 mL), the tube was sealed, and the contents were heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 20 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 (20-100% EtOAc in Hex) affording 5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine as an amorphous beige solid. MS (ESI, pos. ion) m/z: 554.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (s, 1H), 8.63-8.71 (m, 2H), 8.53 (s, 1H), 8.16 (d, J=8.8 Hz, 1H), 8.04 (m, J=8.4 Hz, 2H), 7.92 (d, J=7.2 Hz, 1H), 7.43 (m, J=8.2 Hz, 2H), 7.37 (d, J=5.1 Hz, 1H), 4.06-4.21 (m, 2H), 2.33 (s, 3H), 2.16-2.27 (m, 1H), 1.24 (br. s., 2H), 1.18 (d, J=6.7 Hz, 2H).

Aufarbeitung

  1. customThe tube was purged with argon
  2. additionthe solids were treated with dioxane (2.0 mL) and water (0.200 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 (20-100% EtOAc in Hex)

Quellen und Nachweise

ORD-Eintrag
ord-40a540e109564bb4ac20bc7d8c0e7903
Quelldatensatz
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09321756B2

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