Water → HCID 178502453, Verbindung

HRID 1504348Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1504348
[CH3:1][O:2][C:3](=[O:38])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([C:16]#[N:17])[CH2:13][C@H:12]1[C:18]1[NH:19][CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[N:22]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58](=[O:73])[NH:59][C:60]3[CH:65]=[C:64]([O:66][C:67]([F:70])([F:69])[F:68])[C:63](Br)=[CH:62][C:61]=3[Cl:72])=[CH:54][N:53]=2)[C@H:48]([CH3:74])[CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1>[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([C:58](=[O:73])[NH:59][C:60]3[C:61]([Cl:72])=[CH:62][C:63]([C:26]4[CH:27]=[CH:28][C:23]([C:21]5[N:22]=[C:18]([C@@H:12]6[CH2:13][C@H:14]([C:16]#[N:17])[CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:38])[CH:6]([CH3:7])[CH3:8])[NH:19][CH:20]=5)=[CH:24][CH:25]=4)=[C:64]([O:66][C:67]([F:70])([F:69])[F:68])[CH:65]=3)=[CH:54][N:53]=2)[C@H:48]([CH3:74])[CH2:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 67494940(R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502452[(S)-1-((2S,4S)-4-cyano-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

Produkt 1

HCID 178502453HCID 178502453, VerbindungAusbeute 7,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of [(S)-1-((2S,4S)-4-cyano-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.10 g, 0.19 mmol), (R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (113.9 mg, 0.19 mmol) and potassium carbonate (119.3 mg, 0.86 mmol) in toluene (0.46 mL) and water (0.24 mL, 13.56 mmol) was degassed with nitrogen for 20 min and then Pd(dppf)Cl2CH2Cl2 (6.27 mg, 0.0076 mmol) was added and the reaction was degassed with nitrogen for 15 min. The reaction mixture was heated at 100° C. for 12 h, concentrated under vacuum, and purified by reverse phase HPLC. The pure fractions were combined and concentrated under vacuum to afford the di-TFA salt of the title compound (13 mg, 6% yield). (m/z): [M+H]+ calcd for C44H49ClF3N9O7 908.34. found 908.7.

Aufarbeitung

  1. customthe reaction was degassed with nitrogen for 15 min
  2. concentrationconcentrated under vacuum
  3. custompurified by reverse phase HPLC
  4. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-a667ce8ab6f64e58bf1d1c531e5e11e0
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212168B2

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