Potassium Carbonate → HCID 178502398, Verbindung

HRID 1776039Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776039
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:42])[NH:10][C@H:11]([C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[NH:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)[N:26]=1)=[O:16])[CH:12]([CH3:14])[CH3:13].[C:43]([O:47][C:48]([N:50]1[CH2:55][C@@H:54]([CH3:56])[N:53]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:78])[NH:64][C:65]3[CH:70]=[C:69]([O:71][C:72]([F:75])([F:74])[F:73])[C:68](Br)=[CH:67][C:66]=3[F:77])=[CH:59][N:58]=2)[CH2:52][C@@H:51]1[CH3:79])=[O:49])([CH3:46])([CH3:45])[CH3:44]>C1(C)C=CC=CC=1.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>[C:43]([O:47][C:48]([N:50]1[CH2:55][C@@H:54]([CH3:56])[N:53]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:78])[NH:64][C:65]3[C:66]([F:77])=[CH:67][C:68]([C:30]4[CH:31]=[CH:32][C:27]([C:25]5[N:26]=[C:22]([C@@H:18]6[CH2:19][CH2:20][CH2:21][N:17]6[C:15](=[O:16])[C@@H:11]([NH:10][C:9]([O:8][CH3:7])=[O:42])[CH:12]([CH3:14])[CH3:13])[NH:23][CH:24]=5)=[CH:28][CH:29]=4)=[C:69]([O:71][C:72]([F:75])([F:74])[F:73])[CH:70]=3)=[CH:59][N:58]=2)[CH2:52][C@@H:51]1[CH3:79])=[O:49])([CH3:46])([CH3:45])[CH3:44]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 67494984(2S,5R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502353HCID 178502353, Verbindung

Produkt 1

HCID 178502398HCID 178502398, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Potassium carbonate (470 mg, 3.4 mmol) was added to a solution of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (340 mg, 0.68 mmol) and (2S,5R)-4-[5-(4-bromo-2-fluoro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (400 mg, 0.68 mmol; Preparation 49) dissolved in toluene (2.5 mL) and water (0.73 mL). The reaction mixture was sparged under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (94 mg, 0.081 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. for 4 h. The reaction mixture was diluted in ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce (2S,5R)-4-[5-(5-fluoro-4′-{2-[(S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-2-trifluoromethoxy-biphenyl-4-ylcarbamoyl)-pyridin-2-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester as a red solid.

Aufarbeitung

  1. customThe reaction mixture was sparged under nitrogen
  2. customthe reaction mixture was sparged with nitrogen
  3. additionThe reaction mixture was diluted in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-6311228afa694efcaa81cb3904608967
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260414B2

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