1,4-Dioxane → N-(7-(4-chloro-3-methoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1256421

Reaktionsgleichung

Reaktionsgleichung von HRID 1256421
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.[Cl:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][C:27]=1[O:35][CH3:36].O1CCOCC1>CO.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)=[CH:28][C:27]=1[O:35][CH3:36]

Komponenten

7

Edukt 3

HCID 312751,4-DioxaneHCID 23005377(4-Chloro-3-methoxyphenyl)boronic acidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Produkt 1

HCID 67064366N-(7-(4-chloro-3-methoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamideAusbeute 40,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24290Palladium ChlorideKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 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, 80 mg, 0.232 mmol), 4-chloro-3-methoxyphenylboronic acid (56.2 mg, 0.302 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (16 mg, 22 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.774 mL of 1,4-dioxane and 0.387 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 (65-70% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (42.3 mg, 40%). 1H NMR (DMSO-d6) δ: 11.15 (s, 1H), 7.95 (d, J=8.6 Hz, 2H), 7.91 (s, 1H), 7.78 (d, J=1.8 Hz, 1H), 7.59-7.65 (m, 1H), 7.50-7.59 (m, 3H), 6.34 (s, 1H), 3.88 (s, 3H), 2.34 (s, 3H), 1.39 (s, 6H); ESI-MS: m/z 451.1 (M+H)+.

Aufarbeitung

  1. customwas prepared in a 10 mL microwave reaction vessel
  2. customthe sealed reaction vessel
  3. temperatureThe reaction mixture was cooled to rt
  4. filtrationfiltered
  5. custompurified via preparative HPLC (65-70% MeCN/H2O gradient+0.01% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-17b3eb737334431bb52a513f2b0f98dd
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461163B2

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