Dichloromethane → (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile

HRID 1778445Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1778445
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31](=[O:35])[CH2:32][C:33]#[N:34])[CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12.[OH:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([CH3:47])([CH3:46])[CH:44]=O)[CH2:39][CH2:38]1.N1CCCC1.C(Cl)Cl>C([O-])(O)=O.[Na+]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31]([C:32](=[CH:47][C:43]([N:40]4[CH2:41][CH2:42][CH:37]([OH:36])[CH2:38][CH2:39]4)([CH3:44])[CH3:46])[C:33]#[N:34])=[O:35])[CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

Komponenten

6

Edukt 4

HCID 6344DichloromethaneHCID 31268PyrrolidineHCID 867144983-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrileHCID 900010502-(4-Hydroxy-1-piperidyl)-2-methyl-propanal

Produkt 1

HCID 123595811(R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrileAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A mixture of (R)-3-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-oxopropanenitrile (150 mg, 0.31 mmol), 2-(4-hydroxy-1-piperidyl)-2-methyl-propanal (167 mg, 0.98 mmol), pyrrolidine (0.03 mL, 0.31 mmol) and DCM (10 mL) was stirred at room temp for 2 days and then diluted with aq. NaHCO3 (40 mL) and extracted with DCM. The organic was dried (MgSO4), filtered and concentrated to an oil. The crude material was purified at Isolera (25 g column: 30% iPrOH/DCM) to obtain the product which was isolated by lyophilization to provide 61 mg (32% yield) of (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(4-hydroxypiperidin-1-yl)-4-methylpent-2-enenitrile as a powder. MS (pos. ion) m/z: 625 (M+1).

Aufarbeitung

  1. extractionextracted with DCM
  2. dry with materialThe organic was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to an oil
  5. customThe crude material was purified at Isolera (25 g column: 30% iPrOH/DCM)
  6. customto obtain the product which
  7. customwas isolated by lyophilization

Quellen und Nachweise

ORD-Eintrag
ord-28444bfcf0d140b3b31cdd9c8075d771
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266895B2

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