Potassium Phosphate, Tribasic → Ethyl 7-(2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-yl)-2-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylate

HRID 712316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 712316
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:10]2[S:14][C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:12][C:11]=2[CH:21]=1)(=O)=O.[CH3:30][C:31]1([C:51]([O:53][CH2:54][CH3:55])=[O:52])[O:36][C:35]2[CH:37]=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:39]=[N:40][C:34]=2[NH:33][C:32]1=[O:50].ClC1N2N=C(N)N=C2C=C(Cl)C=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CCOC(C)=O>[CH2:19]([NH:18][C:16](=[O:17])[NH:15][C:13]1[S:14][C:10]2[C:9]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[CH:8][C:7]([C:38]3[CH:39]=[N:40][C:34]4[NH:33][C:32](=[O:50])[C:31]([CH3:30])([C:51]([O:53][CH2:54][CH3:55])=[O:52])[O:36][C:35]=4[CH:37]=3)=[CH:21][C:11]=2[N:12]=1)[CH3:20]

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 594375625,7-Dichloro-[1,2,4]triazolo[1,5-A]pyridin-2-amineHCID 66977204ethyl 2-methyl-3-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylateHCID 72724619HCID 72724619, Verbindung

Produkt 1

HCID 86664029Ethyl 7-(2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-yl)-2-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylateAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To the solution of 2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-yl trifluoromethanesulfonate (0.5 g, 1.12 mmol) and ethyl 2-methyl-3-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylate (0.4 g, 1.12 mmol) in 1,4-dioxane:MeOH (5:3 mL) was added potassium phosphate (0.36 g, 1.68 mmol) at rt and the mixture degassed for 15-20 min by purging N2 followed by the addition of dichloro(1,1-bis(diphenylphosphino)(ferrocene)palladium (II) (0.091 g, 0.11 mmol). The reaction was degassed for another 15-20 min then heated to 80° C. for 5 h. After completion of reaction (by TLC), the reaction was cooled to rt, diluted with EtOAc (500 mL), passed through celite, the filtrate concentrated under reduced pressure and the crude residue purified over 100-200 M silica-gel using eluent 2.3% MeOH: DCM to obtain the desired product as an off-white solid (0.25 g, 42%). 1H NMR (DMSO-d6): δ 1.06-1.13 (m, 6H), 1.77 (s, 3H), 3.21 (q, J=7.20, 2H), 4.14 (m, 2H), 6.87 (br s, 1H), 7.45 (m, 1H), 7.97-8.03 (m, 2H), 8.09 (s, 1H), 8.29 (s, 1H), 8.55 (s, 2H), 8.80 (d, J=4.0 Hz, 1H), 10.62 (br s, 1H) and 11.73 (br s, 1H). MS: 533.24 [M+H]+.

Aufarbeitung

  1. customthe mixture degassed for 15-20 min
  2. customby purging N2
  3. customThe reaction was degassed for another 15-20 min
  4. customAfter completion of reaction (by TLC)
  5. temperaturethe reaction was cooled to rt
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customthe crude residue purified over 100-200 M silica-gel

Quellen und Nachweise

ORD-Eintrag
ord-cad16fdd0f1e4f62875d48f437be9442
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181234B2

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