1,4-Dioxane → HCID 44251165, Verbindung

HRID 1409231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409231
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.[CH3:25][N:26]1[CH2:31][CH2:30][O:29][C:28]2[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:27]1=2.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>[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:33]3[CH:34]=[CH:35][C:27]4[N:26]([CH3:25])[CH2:31][CH2:30][O:29][C:28]=4[CH:32]=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

7

Edukt 3

HCID 312751,4-DioxaneHCID 50878574(4-Methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)boronic acidHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Produkt 1

HCID 44251165HCID 44251165, VerbindungAusbeute 59 %

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, 60 mg, 0.174 mmol), 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ylboronic acid (62 mg, 0.226 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (10 mg, 13.6 mmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (0.58 mL of 1,4-dioxane and 0.29 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 (50-50% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (46.9 mg, 59%). 1H NMR (DMSO-d6) δ: 10.99 (s, 1H), 7.95 (d, J=8.6 Hz, 2H), 7.89 (s, 1H), 7.57-7.62 (m, 2H), 7.54 (d, J=8.3 Hz, 2H), 6.81 (d, J=8.8 Hz, 1H), 6.25 (s, 1H), 4.20-4.24 (m, 2H), 3.32-3.35 (m, 2H), 2.91 (s, 3H), 2.35 (s, 3H), 1.39 (s, 6H); ESI-MS: m/z 458.2 (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 (50-50% MeCN/H2O gradient+0.01% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-bf2b5c3172234d29b8fb9a0512e50661
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921358B2

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