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 1931755Notes

Reaction equation

HRID 1931755 reaction equation
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

Participants

6

Reactant 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×

Product 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}-methanoneYield 43.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-8f1b826f24484766a25fdc4e3483ccca
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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