1,1-Dimethylethyl 4-(4-amino-2-fluorophenyl)-1-piperazinecarboxylate

3-4-2:Example 3-4-2 Preparation of [3-fluoro-4-(BOC-piperazino)]aniline To 150ml of ethyl acetate were sequentially added 9.3g (28.6 mmol) of [3-fluoro-4-(BOC-piperazino)]nitrobenzene synthesized in Preparation Example 3-4-1 and 930mg (10Wpercent) of Pd/C, followed by reaction in a hydrogen reactor under hydrogen pressure of 4bar for 6 hours. After the reaction was complete, Pd/C was filtered through celite. The filtrate was distilled under reduced pressure and dried under vacuum at about 40°C to afford 8.22g (yield: 97percent) of the desired compound. Mass (M+): 296.1 Preparation 10 :; 4- (4-Amino-2-fluoro-phenyl)-piperazine-l-carboxylic acid tert-butyl ester:; To a solution of 4-(2-fluoro-4-nitro-phenyl)-piperazine-1-carboxylic acid tert- butyl ester (9.00 grams, 27.7 mmol), obtained in preparation 7, in methanol and THF (4: 1, 140 mL) was added ammonium formate (6.98 grams, 111 mmol) followed by the addition of 10percent Pd-C (1.47 grams, 13.8 mmol) and stirred at 25-35 °C for 5 hours. The reaction mixture was filtered through a pad of celite and washed thoroughly with methanol. Removal of volatiles left a pasty mass, which was diluted with water and extracted with ethyl acetate (150 mL x 3). The combined organic layer was washed with water followed by brine and dried over sodium sulfate. Evaporation of solvent produced the title amine (7.75 grams, 95percent). 'H NMR (CDC13) : 8 6.78 (t, J= 9.1 Hz, 1H), 6.47-6. 38 (m, 2H), 3.57 (t, J= 4.8 Hz, 4H), 2.90 (t, J= 4.8 Hz, 4H), 1. 48 (s, 9H), IR (KBr, cm-1) : 3451, 3347, 1681. CI-MS (m/z) : 296 (M++1), 282, 240, 196.153, 106, 96.To a solution of 3-fluoro-4-(N-t-butoxycarbonylpiperazin-1-yl) nitrobenzene (23 g, 72 mmol) (obtained according to the procedure described in preparation 2) in EtOAc (450 ml) 10percent Pd/C (1.79 g) was added in portions while stirring. The reduction was carried out in the presence of H2 atmosphere maintained by inserting hydrogen balloon. After the reaction was over (12-14 hrs. ), the contents were filtered through a celite bed. The solvent was removed from the filtrate under vacuum to provide the title compound (19.7 g, yield 93percent), which was used for the next step without further purification.Step B. At room temperature, 3.5 g (10 mmol) of intermediate Ib was dissolved in 35 mL of 90percent EtOH and heated to 70 ° C. 0.44 g (1.5 mmol) of FeCl · 6H2O and 0.038 g (3 mmol) of activated charcoal were added and stirred for 10 min. A solution of 6.73 g (100 mmol) of 80percent hydrazine hydrate was added dropwise and heated to 90 ° C for 2 h. Reaction is completed, the hot filter, the solvent evaporated to dry the crude product, and then add 50mL of crude water, the platform stirring 0.5h, filter, filter cake with a small amount of water rinse, dry pale yellow solid 2.5g, yield 78.6 percent

Molecular Weight:295.35
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:295.16960512
Monoisotopic Mass:295.16960512
Topological Polar Surface Area:58.8
Heavy Atom Count:21
Complexity:364
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes