1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (R)-1-(4-(8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1H-pyrazol-1-yl)propan-2-ol

HRID 57774Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 57774
I[C:2]1[N:18]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][N:23]([CH2:25][C@H:26]([OH:28])[CH3:27])[CH:24]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.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]>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:19][C:20]4[CH:21]=[N:22][N:23]([CH2:25][C@H:26]([OH:28])[CH3:27])[CH:24]=4)[N:18]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:11][CH:12]=1

Komponenten

7

Edukt 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 55291324(R)-1-(4-amino-1H-pyrazol-1-yl)propan-2-olHCID 591990962-Iodo-8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine

Produkt 1

HCID 59199014(R)-1-(4-(8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1H-pyrazol-1-yl)propan-2-olAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

A suspension of 2-iodo-8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (53.6 mg, 0.153 mmol, 1 equiv), (R)-1-(4-amino-1H-pyrazol-1-yl)propan-2-ol (27 mg, 0.19 mmol, 1.2 equiv), sodium tert-butoxide (43.1 mg, 0.448 mmol, 2.94 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (15.2 mg, 0.0263 mmol, 0.172 equiv) and tris(dibenzylideneacetone)dipalladium (0) (10.5 mg, 0.0115 mmol, 0.0751 equiv) in dioxane (2 mL) was heated at 170° C. in the microwave for 15 min. The reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL). The organic was separated, and the aqueous layer was extracted with ethyl acetate (2×5 mL). The collected organic was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (5% methanol in dichloromethane) afforded product as a white solid (42.4 mg, 73% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.32 (s, 1H, NH), 8.64 (dd, J=6.6, 0.9 Hz, 1H), 8.13 (dd, J=8.8 Hz, 2H), 7.81 (s, 1H), 7.74 (dd, J=7.5, 0.9 Hz, 1H), 7.47 (s, 1H), 7.08 (d, J=8.9 Hz, 2H), 7.03 (t, 0.1=7.0 Hz, 1H), 4.92 (d, J=4.7 Hz, 1H, OH), 3.96 (m, 3H), 3.83 (s, 3H), 1.04 (d, J=5.8 Hz, 3H).

Aufarbeitung

  1. customThe reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL)
  2. customThe organic was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×5 mL)
  4. dry with materialThe collected organic was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (5% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-7fc5c3c17754468fbfa5f7021278b1b1
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434732B2

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