2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol → 4-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol

HRID 1398660

Reaktionsgleichung

Reaktionsgleichung von HRID 1398660
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[N:7]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[N:17]=3)[C:6]=2[CH:23]=1.[CH3:24][C:25]1[O:29][N:28]=[C:27]([C:30]([OH:34])([C:32]#[CH:33])[CH3:31])[CH:26]=1>CS(C)=O.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:22][C:18]1[N:17]=[C:16]([N:7]2[C:6]3[CH:23]=[C:2]([C:33]#[C:32][C:30]([C:27]4[CH:26]=[C:25]([CH3:24])[O:29][N:28]=4)([OH:34])[CH3:31])[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[CH:21]=[CH:20][N:19]=1

Komponenten

6

Edukt 2

HCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 681815834-[6-bromo-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine

Produkt 1

HCID 681816014-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-olAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

A mixture of 4-[6-bromo-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (120 mg, 0.31 mmol), 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol (120 mg, 0.79 mmol) and bis(triphenylphosphine)palladium(II) dichloride (200 mg, 0.28 mmol) in dimethylsulfoxide (2 mL) and triethylamine (1 mL) kept in a 10-mL vial under nitrogen was irradiated with microwave radiation for 2 h at 70° C. The reaction mixture was concentrated in vacuo. The crude product (120 mg) was purified by preparative HPLC to give 55 mg (39%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol as a light yellow solid: 1H NMR (400 MHz, DMSO) delta 8.45 (d, J=5.2 Hz, 1H), 8.17 (s, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.17 (s, 2H), 6.86 (d, J=5.2 Hz, 1H), 6.46 (s, 1H), 6.38 (s, 1H), 5.37-5.30 (m, 2H), 2.41 (s, 3H), 1.82 (s, 3H); LC-MS: m/z=+459 (M+H)+.

Aufarbeitung

  1. customwas irradiated with microwave radiation for 2 h at 70° C
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThe crude product (120 mg) was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-552cefe9361d461bab29340ce37d3126
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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