Tetrahydrofuran → HCID 57965059, compound

HRID 1931717Notes

Reaction equation

HRID 1931717 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=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].C(N(C(C)C)CC)(C)C.[O:43]1[CH2:47]CCC1>>[F:1][C:2]([F:7])([F:6])[CH:3]([O:5][C:47]([N:29]1[CH2:28][CH2:27][CH:26]([N:23]2[C:19]3=[N:20][CH:21]=[N:22][C:17]([O:16][C:15]4[CH:14]=[CH:13][C:12]([S:9]([CH3:8])(=[O:11])=[O:10])=[CH:33][CH:32]=4)=[C:18]3[CH:25]=[N:24]2)[CH2:31][CH2:30]1)=[O:43])[C:2]([F:7])([F:6])[F:1]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2×

Product 1

HCID 57965059HCID 57965059, compoundYield 28%

Procedure

Triphosgene (1.6 g, 5.5 mmol) was added in portions to a solution of 1,1,1,3,3,3-hexafluoro-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 790 mg, 5 mmol) in a mixture of pyridine (0.48 mL, 6 mmol) and carbon tetrachloride (25 mL) under nitrogen. The solution was stirred at 60° C. for 5.5 h and then cooled using an ice bath. 1 M aqueous hydrochloric acid (4 mL) was added and then the mixture was diluted with water and the layers were separated. The organic layer was dried (sodium sulfate), and filtered to give approximately 20 mL of solution, of which 6 mL were used directly in the next reaction without further purification. The solution (7 mL) as added to a mixture of 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 240 mg, 0.5 mmol) in tetrahydrofuran (1 mL). Diisopropylethylamine (0.5 mL, 2.8 mL) was added slowly and the mixture was stirred for 10 min and then evaporated to dryness and chromatographed using a 30 mm×3″ column of silica gel, eluting with 75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester (70 mg, 28%) as an off-white powder.

Workup

  1. customof which 6 mL were used directly in the next reaction without further purification
  2. customevaporated to dryness
  3. customchromatographed
  4. washeluting with 75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-218e7b8f7456420ebe02009fd51cdab9
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…