3,3,4,4-tetrafluoropyrrolidine;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 4-(5-tert-butyl-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)morpholine (example 58, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and used without further purification in the consecutive step. used without further purification in the consecutive step

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and isolated as light-yellow gum (12.6 mg, 60%). MS (m/e): 443.4 (MH+).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described in Example 47 b), 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 1 b)) was reacted with 3,3,4,4-tetrafluoropyrrolidine hydrochloride (1810-13-5) in the presence of TBTU and DIEA to obtain the title compound as colorless oil; MS (EI): m/e=410.5 [MH+].

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An ethanol solution of 16.9 g of the residue 3,3,4,4-tetrafluoro-1-benzyl-pyrrolidine hydrochloride and 1.8 g of 10% Pd/C was stirred at room temperature for 3 hours in a manner of contacting hydrogen gas under ordinary pressure. After filtration, the solvent was distilled off to provide 11 g (yield: 98%) of desired 3,3,4,4-tetrafluoro-pyrrolidine hydrochloride. After filtration the solvent was distilled off

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An ethanol solution of 16.9 g of the residue 3,3,4,4-tetrafluoro-1-benzyl-pyrrolidine hydrochloride and 1.8 g of 10% Pd/C was stirred at room temperature for 3 hours in a manner of contacting hydrogen gas under ordinary pressure. After filtration, the solvent was distilled off to provide 11 g (yield: 98%) of desired 3,3,4,4-tetrafluoro-pyrrolidine hydrochloride. After filtration the solvent was distilled off

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 4-(5-tert-butyl-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)morpholine (example 58, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and used without further purification in the consecutive step. used without further purification in the consecutive step

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 4-(5-tert-butyl-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)morpholine (example 58, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and used without further purification in the consecutive step. used without further purification in the consecutive step

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and isolated as light-yellow gum (12.6 mg, 60%). MS (m/e): 443.4 (MH+).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 3,3,4,4-tetrafluoropyrrolidine hydrochloride and isolated as light-yellow gum (12.6 mg, 60%). MS (m/e): 443.4 (MH+).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-benzyl-3,3,4,4-tetrafluoro-pyrrolidine hydrochloride (23.8 g, 88 mmol) in ethanol (300 mL) containing 10% palladium on carbon was treated with hydrogen in a Parr shaker at 45 psi for 3 hours. The mixture was filtered through Celite®, the filtrate was concentrated to dryness. The residue was triturated with ether and the solid was collected and dried (13.4 g, 85%, (mp 193-196° C.). The mixture was filtered through Celite® the filtrate was concentrated to dryness The residue was triturated with ether the solid was collected dried (13.4 g, 85%, (mp 193-196° C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-benzyl-3,3,4,4-tetrafluoro-pyrrolidine hydrochloride (23.8 g, 88 mmol) in ethanol (300 mL) containing 10% palladium on carbon was treated with hydrogen in a Parr shaker at 45 psi for 3 hours. The mixture was filtered through Celite®, the filtrate was concentrated to dryness. The residue was triturated with ether and the solid was collected and dried (13.4 g, 85%, (mp 193-196° C.). The mixture was filtered through Celite® the filtrate was concentrated to dryness The residue was triturated with ether the solid was collected dried (13.4 g, 85%, (mp 193-196° C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-benzyl-3,3,4,4-tetrafluoro-pyrrolidine hydrochloride (23.8 grams, 88 mmol) in ethanol (300 mL) containing 10% palladium on carbon was treated with hydrogen in a Parr shaker at 45 psi for 3 hours. The mixture was filtered through Celite®, the filtrate was concentrated to dryness. The residue was triturated with ether and the solid was collected and dried (13.4 grams, 85%, (melting point: 193-196° C.). 1H NMR (400 MHz, D2O) 3.93 (m, 4H), 7.26-7.41 (m, 5H). 19F NMR (376 MHz, D2O) δ−122.25 (m) The mixture was filtered through Celite® the filtrate was concentrated to dryness The residue was triturated with ether the solid was collected dried (13.4 grams, 85%, (melting point: 193-196° C.)