Potassium Phosphate, Tribasic → (S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamide

HRID 1754258Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1754258
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Br[C:14]1[CH:35]=[CH:34][C:17]2[N:18]=[C:19]([CH2:21][C:22]3[O:26][C:25]([NH:27][C@H:28]4[CH2:32][CH2:31][NH:30][C:29]4=[O:33])=[N:24][N:23]=3)[S:20][C:16]=2[CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.CO.[Pd]>[O:33]=[C:29]1[C@@H:28]([NH:27][C:25]2[O:26][C:22]([CH2:21][C:19]3[S:20][C:16]4[CH:15]=[C:14]([C:7]5[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=5)[CH:35]=[CH:34][C:17]=4[N:18]=3)=[N:23][N:24]=2)[CH2:32][CH2:31][NH:30]1

Komponenten

9

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27378114-Aminocarbonylphenylboronic acidHCID 90047760(S)-3-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)amino)pyrrolidin-2-one

Produkt 1

HCID 90047667(S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamideAusbeute 31,9 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

To a microwave vial containing SiliaCat DPP-Pd (150 mg, 0.041 mmol) and (4-carbamoylphenyl)boronic acid (65 mg, 0.40 mmol) were added Compound 51b (104 mg, 0.260 mmol) dissolved in dioxane (2.5 mL) followed by K3PO4 (138 mg, 0.79 mmol) dissolved in water (0.3 mL) and the reaction mixture was heated in a microwave reactor at 125° C. for 1.5 h. The reaction mixture was allowed to cool to rt then diluted with a mixture of DCM and MeOH, filtered and concentrated under reduced pressure. The residue was purified on silica gel eluting with 0 to 15% MeOH/DCM to give Compound 51c (36 mg, 31% yield) as a pale brown solid. LCMS=1.33 min using analytical method (B), 435.1 (M+H). 1H NMR (400 MHz CDCl3 containing CD3OD) δ 8.05 (d, J=1.5 Hz, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.69 (dd, J=8.5, 1.8 Hz, 1H), 7.65 (d, J=8.5 Hz, 2H), 4.54 (s, 1H), 4.23 (dd, J=10.5, 8.3 Hz, 1H), 3.36-3.31 (m, 1H), 2.68-2.59 (m, 1H), 2.03 (dq, J=12.5, 9.8 Hz, 1H).

Aufarbeitung

  1. temperatureto cool to rt
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on silica gel eluting with 0 to 15% MeOH/DCM

Quellen und Nachweise

ORD-Eintrag
ord-bd3ba0e94b354749bebceb24e282a52f
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169240B2

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