Cesium carbonate → 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

HRID 1472550

Reaktionsgleichung

Reaktionsgleichung von HRID 1472550
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH3:21][N:22]1[CH:26]=[C:25]([NH2:27])[C:24]([CH3:28])=[N:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C1COCC1>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:27][C:25]2[C:24]([CH3:28])=[N:23][N:22]([CH3:21])[CH:26]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 44310561,3-dimethyl-1H-pyrazol-4-amineHCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Produkt 1

HCID 446095112-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-4-yl)-amino]-4-pyridinyl}amino)-N-(methyloxy)benzamideAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 22018518Dioxane tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (250 mg, 0.8 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (187 mg, 1.68 mmol), cesium carbonate (783 mg, 2.4 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (9 mg, 0.04 mmol) and BINAP (50 mg, 0.08 mmol) were added. The mixture was stirred in a microwave at 140° C. for 40 min. It was evaporated and the residue dissolved in MeOH was filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. Ether was added to the residue and a tan precipitate crashed out. It was filtered off and dried under vacuum at 40° C. for 2 days to afford the desired product (55 mg, 18%) as a tan solid. LC-MS (ES) m/z=387.1, [M+H]+=389.1. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.51 (br. s., 1 H) 8.03 (s, 1 H) 7.96 (s, 1 H) 7.82 (s, 1 H) 7.51-7.61 (m, 3 H) 7.07-7.15 (m, 1 H) 6.68 (s, 1 H) 3.70 (d, J=4.29 Hz, 6 H) 2.07 (s, 3 H).

Aufarbeitung

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue dissolved in MeOH
  4. filtrationwas filtered thru celite
  5. custompurified further
  6. customevaporated
  7. additionEther was added to the residue
  8. filtrationIt was filtered off
  9. customdried under vacuum at 40° C. for 2 days

Quellen und Nachweise

ORD-Eintrag
ord-c92f6648e25a4b29b2a26961092e595e
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012479B2

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