Methane → 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-2,3-dihydro-1H-1,3-benzodiazol-2-one

HRID 1398510Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1398510
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14](Br)[CH:15]=[CH:16][C:11]=3[NH:10][C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.C.[S:20]1[CH:24]=[CH:23][N:22]=[C:21]1[C:25]([OH:29])([C:27]#[CH:28])[CH3:26].N1CCCCC1>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([C:28]#[C:27][C:25]([OH:29])([C:21]4[S:20][CH:24]=[CH:23][N:22]=4)[CH3:26])[CH:15]=[CH:16][C:11]=3[NH:10][C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1

Komponenten

8

Edukt 4

HCID 297MethaneHCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 681820071-(2-aminopyrimidin-4-yl)-6-bromo-2,3-dihydro-1H-1,3-benzodiazol-2-one

Produkt 1

HCID 601640701-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-2,3-dihydro-1H-1,3-benzodiazol-2-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 1-(2-aminopyrimidin-4-yl)-6-bromo-2,3-dihydro-1H-1,3-benzodiazol-2-one (230 mg, 0.751 mmol) in EtOAc was added charcoal (5 mol %). The mixture was stirred at RT for 20 min then filtered and concentrated in vacuo. To the residue in a sealed tube was added 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (230 mg, 1.50 mmol), piperidine (2 mL), tetrakis(triphenylphosphine)palladium (43.4 mg, 0.038 mmol) and copper(I) iodide (14.3 mg, 0.075 mmol). The reaction mixture was then heated at 75° C. for 18 hr then partitioned between EtOAc (15 mL) and water (2 mL). The organic layer was concentrated in vacuo and the residue purified by reverse phase preparative HPLC to afford the title compound: 1H NMR (500 MHz, DMSO) δ 1.90 (3 H, s), 6.92 (2H, s), 6.95 (1H, s), 7.04 (1H, d, J=8.04 Hz), 7.21 (1H, dd, J=8.04, 1.42 Hz), 7.40 (1H, d, J=5.52 Hz), 7.68 (1H, d, J=3.31 Hz), 7.77 (1H, d, J=3.15 Hz), 8.26-8.36 (2H, m), 11.57 (1H, br. s.); LC-MS: m/z=+379.0 (M+H)+.

Aufarbeitung

  1. filtrationthen filtered
  2. concentrationconcentrated in vacuo
  3. temperatureThe reaction mixture was then heated at 75° C. for 18 hr
  4. customthen partitioned between EtOAc (15 mL) and water (2 mL)
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe residue purified by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-f865451a239f4ca9828bbcc581a94402
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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