HCID 67019715, Verbindung → HCID 86725118, Verbindung

HRID 634291Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 634291
[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].Br[C:39]1[S:40][C:41]([C:44]([NH:46][CH:47]2[CH2:49][CH2:48]2)=[O:45])=[CH:42][N:43]=1.ClC1SC(C(NC2CC2)=O)=CN=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:47]1([NH:46][C:44]([C:41]2[S: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]([CH3:3])[CH3:2])=[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:43][CH:42]=2)=[O:45])[CH2:48][CH2:49]1

Komponenten

6

Edukt 3

HCID 67019715HCID 67019715, VerbindungHCID 68328139HCID 68328139, VerbindungHCID 68328163HCID 68328163, Verbindung

Produkt 1

HCID 86725118HCID 86725118, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of 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 (150 mg, 0.287 mmol), 78 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide, Pd2(dba)3 (Strem Chemicals, 8 mg, 8.6 μmol), Xphos (Stem Chemicals, cat #15-1152, 9 mg, 17 μmol), potassium phosphate (183 mg, 0.861 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° C. for 25 min. LCMS indicated the presence of desired product (M+1=563.0), as well as a significant amount of the starting 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. To the reaction mixture was added Pd(PPh3)4 (Strem Chemicals, cat #46-2150, 10 mg) and 50 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide. It was heated again at 130° C. for 15 min in an Initiator microwave reactor. The reaction mixture was treated with water (5 mL) and extracted with EtOAc (2×25 mL). The organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes to give N-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)thiazole-5-carb oxamide (60 mg, in 75% purity) as a brown amorphous solid. MS (ESI, pos. ion) m/z: 563.0 (M+1).

Aufarbeitung

  1. additionTo the reaction mixture was added
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-d74592c715e7439db335af29415079e7
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321756B2

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