Diisopropylethylamine → (1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone

HRID 1931755

Reaktionsgleichung

Reaktionsgleichung von HRID 1931755
FC(F)(F)C(O)=O.[CH3:8][S:9]([C:12]1[CH:33]=[CH:32][C:15]([O:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[N:24]=[CH:25][C:18]=23)=[CH:14][CH:13]=1)(=[O:11])=[O:10].[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.C(N(C(C)C)CC)(C)C.[CH3:63][N:64]1[C:68]([CH3:69])=[CH:67][C:66]([C:70](Cl)=[O:71])=[N:65]1>ClCCl>[CH3:63][N:64]1[C:68]([CH3:69])=[CH:67][C:66]([C:70]([N:29]2[CH2:28][CH2:27][CH:26]([N:23]3[C:19]4=[N:20][CH:21]=[N:22][C:17]([O:16][C:15]5[CH:14]=[CH:13][C:12]([S:9]([CH3:8])(=[O:11])=[O:10])=[CH:33][CH:32]=5)=[C:18]4[CH:25]=[N:24]3)[CH2:31][CH2:30]2)=[O:71])=[N:65]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 27763641,5-Dimethyl-1H-Pyrazole-3-Carbonyl ChlorideHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Produkt 1

HCID 57964929(1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanoneAusbeute 43,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A mixture of 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 63 mg, 0.13 mmol), TSTU (O—(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate; 78 mg, 0.26 mmol), and diisopropylethylamine (0.14 mL, 0.8 mmol) in dichloromethane (4 mL) was shaken at room temperature for 3 h. 1,5-Dimethyl-1H-pyrazole-3-carbonyl chloride (available from Maybridge, Tintagel, Cornwall, UK; 23 mg, 0.16 mmol) was added and the mixture was shaken at room temperature overnight. The solution was diluted with dichloromethane (˜6 mL) and washed with water (2×5 mL), 1 M aqueous hydrochloric acid (5 mL), water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL). The organic layer was evaporated and the crude product was purified by HPLC to give (1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone (28 mg, 43%) as a white solid. Mass spectrum (ES) MH+=496.

Aufarbeitung

  1. stirringthe mixture was shaken at room temperature overnight
  2. washwashed with water (2×5 mL), 1 M aqueous hydrochloric acid (5 mL), water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL)
  3. customThe organic layer was evaporated
  4. customthe crude product was purified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-8f1b826f24484766a25fdc4e3483ccca
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188098B2

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