Dichloromethane → 5-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine

HRID 2409532Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2409532
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[C:32]([NH2:35])=[N:33][CH:34]=2)O1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18]([C:29]4[CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[C:32]([NH2:35])=[N:33][CH:34]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

Produkt 1

HCID 469409475-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamineAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (0.125 g, 0.312 mmol, 1 eq), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (0.119 g, 0.414 mmol, 1.33 eq), Pd(dppf)Cl2.DCM (0.008 g, 0.009 mmol, 0.03 eq) and cesium carbonate (0.305 g, 0.935 mmol, 3 eq) in DME (4 mL) and water (0.1 mL) was heated in the microwave oven (45 min, 130° C.), cooled to RT, diluted with water, extracted with EtOAc and washed with brine. The organic layers were dried (MgSO4), filtered and concentrated, and the residue was purified by silica gel chromatography (0-100% EtOAc in hexane). Product fractions were concentrated and triturated with Et2O, the solid was filtered off and dried to give the desired product (solid, 0.070 g, 52%). HPLC-MS: (50-100% B in 8 min, 0.8 mL/min): tR=1.11 min, [M+H]+ m/z 436.0. 1H NMR (300 MHz, CDCl3) δ/ppm 8.62 (d, J=1.6, 1H), 8.22 (d, J=1.6, 0H), 7.44 (d, J=2.2, 1H), 7.39 (dd, J=8.2, 2.2, 1H), 6.96 (d, J=8.5, 1H), 5.11 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 2.53 (s, 1H).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialThe organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (0-100% EtOAc in hexane)
  7. concentrationProduct fractions were concentrated
  8. customtriturated with Et2O
  9. filtrationthe solid was filtered off
  10. customdried

Quellen und Nachweise

ORD-Eintrag
ord-50585fb1ecff44d8bd6a6964917819d6
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815918B2

Notizen zur Reaktion

Wird geladen…