Sodium Carbonate → 4-tert-butyl-N-(7-(3-(hydroxymethyl)phenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1409136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1409136
[C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]3[N:19]=[C:20]([CH3:22])[CH:21]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:25][CH2:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>N#N.[Cl-].[Na+].O.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>[C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:31]3[CH:30]=[CH:29][CH:28]=[C:27]([CH2:26][OH:25])[CH:32]=3)[N:15]3[N:19]=[C:20]([CH3:22])[CH:21]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 866522574-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide2×

Produkt 1

HCID 442325004-tert-butyl-N-(7-(3-(hydroxymethyl)phenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 947NitrogenLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A suspension of 4-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide (1K, 40 mg, 1.0 equivalent), 3-(hydroxymethyl)phenylboronic acid (1.9 equivalents), Pd(PPh3)4 (0.10 equivalent), and Na2CO3 (4.0 equivalents) in N2-saturated 5:1 DMF/H2O (0.05 M with respect to 1K) was stirred at 100° C. overnight. After cooling, the mixture was diluted with brine and extracted with EtOAc. Combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by chromatography (SiO2, gradient of 40 to 50% EtOAc/hexanes). The product was then recrystallized from CH2Cl2-hexanes to give the titled compound (62%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.37 (s, 9H) 2.50 (s, 3H) 4.83 (d, J=6.1 Hz, 2H) 6.29 (s, 1H) 7.44-7.71 (m, 5H) 7.88 (d, J=8.3 Hz, 2H) 8.03 (s, 1H) 8.15 (s, 1H) 8.59 (s, 1H).

Aufarbeitung

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc
  3. dry with materialCombined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (SiO2, gradient of 40 to 50% EtOAc/hexanes)
  7. customThe product was then recrystallized from CH2Cl2-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-dac96a52a1ff449d969e19d94cdd1688
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921358B2

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