Sodium Carbonate → Ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate

HRID 595460

Reaktionsgleichung

Reaktionsgleichung von HRID 595460
Cl[C:2]1[CH:12]=[C:11]([NH:13][CH:14]2[CH2:17]C[CH2:15]2)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:27]=[CH:26][C:22]2[N:23]=[CH:24][S:25][C:21]=2[CH:20]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[S:25]1[C:21]2[CH:20]=[C:19]([NH:18][C:2]3[CH:12]=[C:11]([NH:13][CH:14]([CH3:15])[CH3:17])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=3)[CH:27]=[CH:26][C:22]=2[N:23]=[CH:24]1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 682886-AminobenzothiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89689654Ethyl 6-chloro-4-(cyclobutylamino)nicotinate

Produkt 1

HCID 89689730Ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

To a solution of ethyl 6-chloro-4-(isopropylamino)nicotinate (2) (5 g, 20.66 mmol) in dioxane (30 mL):H2O (5 mL), 6-amino benzothiazole (20.66 mmol, 1 equiv.), xanthphos (8.2 mmol, 0.4 equiv.) and Na2CO3 (82.6 mmol, 4 equiv.) were added and degassed for 10 min. To the reaction mixture Pd2(dba)3 (8.2 mmol, 0.4 equiv.) was added and degassed again for 10 min. It was then heated at 115° C., overnight. The reaction was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel and EtOAC:pet. Ether as eluent to afford ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate (3). LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 0.78 min; LCMS (ES-API), m/z 357.8 (M+H).

Aufarbeitung

  1. customdegassed for 10 min
  2. customdegassed again for 10 min
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through small pad of celite
  5. customThe filtrate obtained
  6. concentrationwas concentrated
  7. customto provide crude material
  8. customThe crude material was purified by column chromatography through silica gel and EtOAC

Quellen und Nachweise

ORD-Eintrag
ord-d62d0717055144049fdb26eb39c9507f
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242976B2

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