Sodium Carbonate → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4,5'-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

HRID 869955Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 869955
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[C:4]([CH3:25])[C:3]=1[CH3:26].[CH3:27][O:28][C:29]1[C:34](B(O)O)=[CH:33][C:32]([CH3:38])=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:34]5[C:29]([O:28][CH3:27])=[N:30][CH:31]=[C:32]([CH3:38])[CH:33]=5)[C:3]([CH3:26])=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27631282-Methoxy-5-methylpyridine-3-boronic acidHCID 89228784HCID 89228784, Verbindung

Produkt 1

HCID 687393981-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(2'-methoxy-3,4,5'-trimethyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamideAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (114 mg, 0.3 mmol) and 2-methoxy-5-methylpyridin-3-ylboronic acid (75 mg, 0.45 mmol) in DME (3 mL) and Na2CO3 (2M, 0.3 mL, 0.6 mmol) was added Pd(PPh3)4 (17 mg, 0.015 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The reaction was re-partitioned between EtOAc and H2O and the aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (0-20% EtOAc-Hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,4,5′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (80 mg, 57%). 1H NMR (400 MHz, CDCl3) 8.02 (s, 1H), 7.99 (d, J=1.6 Hz, 1H), 7.59 (s, 1H), 7.31 (d, J=2.1 Hz, 1H), 7.20-7.16 (m, 2H), 7.04 (d, J=8.1 Hz, 1H), 3.85 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 1.95 (s, 3H), 1.73 (dd, J=3.8, 6.9 Hz, 2H), 1.14 (dd, J=3.9, 7.0 Hz, 2H). Retention time: 2.02 min; ESI-MS m/z calc. 467.5. found 468.2 (M+H)+.

Aufarbeitung

  1. customThe reaction was re-partitioned between EtOAc and H2O
  2. extractionthe aqueous layer was extracted with EtOAc twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (0-20% EtOAc-Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-32e7fa32d75b4b059d7dadec71fa22a6
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969386B2

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