Cesium carbonate → HCID 71547300, Verbindung

HRID 1498807Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1498807
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([CH:18]3[CH2:20][CH:19]3B3OC(C)(C)C(C)(C)O3)[N:15]=[C:14]([CH3:30])[N:13]=2)[N:10]=[C:9]([CH3:31])[N:8]=1.Br[C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][N:39]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([CH:18]3[CH2:20][CH:19]3[C:38]3[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][N:39]=3)[N:15]=[C:14]([CH3:30])[N:13]=2)[N:10]=[C:9]([CH3:31])[N:8]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 5642162-Bromo-5-methylpyridineHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 867320684-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine

Produkt 1

HCID 71547300HCID 71547300, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A slurry of crude 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopropyl)pyrimidine (3-2, 88 mg, 0.179 mmol, 1.0 eq), 2-bromo-5-methylpyridine (92 mg, 0.537 mmol, 3.0 eq.), cesium carbonate (233 mg, 0.716 mmol, 4.0 eq.), palladium(II) acetate (4.02 mg, 0.018 mmol, 0.10 eq.), and butyldi-1-adamantylphosphine (19.26 mg, 0.054 mmol, 0.30 eq.) in toluene (1 ml) and water (300 μL) was heated at 100° C. for 16 hours. The solvent was removed by roto-evaporation and the resulting oil was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present) to afford 4-(5-(3,4-dimethoxybenzyl)-3-methyl-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(5-methylpyridin-2-yl)cyclopropyl)pyrimidine (3-3) as slightly yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.30 (d, 1H, J=2.0 Hz), 7.53 (s, 1H), 7.36 (dd, 1H, J=7.8, 2.2 Hz), 6.89 (d, 1H, J=2.0 Hz), 6.85 (dd, 1H, J=8.1, 2.2 Hz), 6.76 (d, 1H, J=8.1 Hz), 4.71 (s, 2H), 3.83 (s, 3H), 3.82 (s, 3H), 2.67 (bs, 4H), 2.62 (m, 1H), 2.42 (s, 3H), 2.29 (s, 3H), 1.84 (m, 2H). HRMS m/z (M+H) 495.1925 found, 495.1905 required.

Aufarbeitung

  1. customThe solvent was removed by roto-evaporation
  2. customthe resulting oil was purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% NH4OH present)

Quellen und Nachweise

ORD-Eintrag
ord-1f929328252c40f9b10ed53e8bb3e76f
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09200001B2

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