1,4-Dioxane → 4-(2-hydroxypropan-2-yl)-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1409171Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409171
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O1CCOCC1>CO>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]

Komponenten

5

Edukt 3

HCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Produkt 1

HCID 670644284-(2-hydroxypropan-2-yl)-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)benzamideAusbeute 25,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 49 mg, 0.142 mmol), phenylboronic acid (23 mg, 0.189 mmol), and [1,1′-bis[1,1′-Bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (9.3 mg, 13 mmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.76 mL of 1,4-dioxane and 0.38 mL of saturated aqueous NaHCO3) was prepared in a 10 mL microwave reaction vessel and the sealed reaction vessel warmed to 110° C. for 10 minutes in a CEM microwave reactor. The reaction mixture was cooled to rt, diluted with methanol, filtered, and purified via preparative HPLC (65-75% MeCN/H2O+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (13.9 mg, 25%). Decomposition observed at 199.8° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6H), 2.40 (s, 3H), 5.20 (br. s., 1H), 6.40 (s, 1H), 7.58-7.66 (m, 5H), 7.97 (s, 1H), 8.02 (d, J=8.59 Hz, 2H), 8.06 (dd, J=6.57, 3.03 Hz, 2H), 11.20 (s, 1H); ESI-MS: m/z 387.2 (M+H)+.

Aufarbeitung

  1. customthe sealed reaction vessel
  2. temperatureThe reaction mixture was cooled to rt
  3. filtrationfiltered
  4. custompurified via preparative HPLC (65-75% MeCN/H2O+0.01% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-00e98d5e4aea4fb49e023c047eaea62c
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921358B2

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