1、 Page 1 of 26 1 3 6 6 .6 .7 .7 .7 8 8 8 9 9 .9 10 .10 10 11 12 .12 .12 12 13 14 .14 .14 .15 .15 .16 Page 2 of 26 2 .16 .17 .17 .18 18 .19 20 .20 .20 .20 21 21 22 .22 22 23 23 23 .24 .24 .24 Page 3 of 26 3 , . i) ;ii) . . , , , . . , ( logP) , . , , . . . , , , . , . , . , , . , , , , . , , . . . , R
2、u 3 (CO) 9 (TPPTS) 3 , (CTAB) , , , . Page 4 of 26 4 1946 1 2-6 LiH, CaH 2 , LiAlH 4 , LiBH 4 , KBH 4 Mg(AlH 4 ) 2 , NaAlH 4 , AlH 3 , Al(BH 4 ) 3 , Ca(BH 4 ) 2 , NaBH(OCH 3 ) 3 LiAlH 4 NaBH 4 Sabatier 1897 7 1911 1912 8, 9 Page 5 of 26 5 NH 2 -NH 2 .H 2 O 1929 Pd/CaCO 3 10 11 12 A, B, C, D, Page 6
3、of 26 6 Pd/C Raney Ni Cl, Br and I; F SnCl 2 Abderahman Synthesis 1988, 2, 154-155 N N N N NH 2 NO 2 Na 2 N 2 O 4 , 0.2N NaOH EtOH, 40 o C, 24 h N N N N NH NH 2 Br - -p-H 2 NC 6 H 5 CH 2 OH 65% N N N N NH 2 (LAH) (LAH) (LAH) NaBH 4 -Lewis OH N O O NO 2 H 2 OH N O O NH 2 Pd/C To a solution of the sta
4、rting material (10 g) in 200 ml of ethanol was added 1.03 g of 10 percent Pd/C and the mixture was stirred for two hours at room temperature in a hydrogen atmosphere under atmospheric pressure. Insoluble matters were removed using Celite, and the filtrate was concentrated in vacuo to give 9.54 g of
5、the product. Page 7 of 26 7 O 2 NF F F OH H 2 H 2 NF F F OH Pd/C To a solution of the starting material (3 g, 16 mmol) in ethanol (100 mL) was added 10 percent Pd/C (1 g) and the resulting mixture shaken under a hydrogen atmosphere (4 bar) for 3 days. The catalyst was removed by filtration and the s
6、olvent evaporated. To the resulting oil was added a saturated solution of ethanolic hydrochloric acid (5 mL) and the solvent was evaporated. Addition of ether gave a white solid which was collected and washed with ether to provide 3-amino-1,1,1-trifluoro-2-pentanol hydrochloride (1.3 g) as a white s
7、olid; TLC: Rf =0.1, methanol:dichloromethane (10:90). NO 2 N S NH 2 N S To a suspension of the above product (6.1 g, 29.6 mmol) in ethanol (170 mL) was added Raney nickel (0.5 g) and the resultant mixture was hydrogenated at ambient pressure until the hydrogen uptake had ceased. Filtration through c
8、elite and evaporation of the solvent from the filtrate left the desired product, quantitatively. N O 2 N N H 2 N To the starting material (1.00 g, 5.88 mmol) and NaOH (0.235 g (5.88 mmol) in 5 mL of ethanol, 0.40 g of Raney nickel were added to stir the mixture under hydrogen atmosphere at 20.deg. C
9、. for 12 hours. The catalyst was filtered off, and then the filtrate was poured into 33percent HCl/isopropanol (5.0 mL) below 20.deg. C. The reaction mixture was evaporated to dryness to give crude crystal. The crude crystal was suspended in toluene (5.0 mL) and to the suspension was introduced NH 3
10、gas to stir at 20.deg. C. for 12 hours. The precipitate was filtered off and the filtrate was evaporated to afford 716 mg of the desired compound (Yield: Page 8 of 26 8 86.9%). Fe/AcOH N SN O 2 N SN 2 H To the starting material (3.1 g) was added acetic acid (24.4 mL) and then, reduced iron powder (9
11、.15 g), and the mixture was stirred for 16 hours at room temperature. The mixture was filtered with Celite, and washed with ethyl acetate. The solvent was removed under reduced pressure, and water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The organic layer
12、was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 1.4 g of the desired product. N O 2 N N H 2 N Fe/HCl To 80 percent ethanol (5.0 mL), the starting mate
13、rial (300 mg, 1.76 mmol) and concentrated hydrochloric acid (0.45 ml, 5.28 mmol) were added to stir for 10 minutes at 20C. Then, iron powder (500 mg, 8.95 mmol) was added to the mixture to further stirring for 1 hour at 20C. Insoluble matters were filtered off and the filtrate was concentrated, addi
14、ng 0.5N NaOH (10 mL) to the residue, filtering the solution to further remove insoluble matters, extracting the filtrate with chloroform, drying the extract over anhydrous sodium sulfate, concentrating the extract, and distilling the resulting crude product to afford 224 mg of the desired compound (
15、91% yield). Page 9 of 26 9 N N O O 2 N NO 2 SnCl 2 .H 2 O N N O H 2 N NH 2 A stirred solution of stannous chloride dihydrate (38 g, 0.183 mol) in concentrated hydrochloric acid (100 ml, 1.2 mol) was treated portionwise with the starting material (10 g). Ethanol (10 mL) was added to clarify the solut
16、ion and the mixture is stirred at 60 C for 3 hours. The solution was evaporated to near dryness and three 100 mL. portions of ethanol are added sequentially and evaporated from the residue. The residual syrup was stirred with 800 mL. of ether and the resulting solid is collected by filtration, washe
17、d with ether and dried at reduced pressure. This solid (a tin complex) is dissolved in 150 mL of water and the tin is precipitated as the sulfide by bubbling hydrogen sulfide gas into the solution. The mixture is filtered and the filter cake washed with water. The filtrate and washings are combined
18、and evaporated at reduced pressure. The residue is repeatedly evaporated with 100 mL portions of ethanol. The final residual gum is triturated with 30 mL of ethanol to give as a crystalline solid product dihydrochloride, which is collected by filtration, washed with ethanol and dried at reduced pres
19、sure; m.p. 155 C. S NO 2 S NH 2 A mixture of 106.6 g (0.41 mol) of the above material, 350 g (1.5 mol) of SnCl 2 .H 2 O, 1 L of MeOH, and 350 ml of AcOH was stirred and refluxed for 3 hr. The reaction mixture was then partly concentrated (500 ml collected), cooled, and treated portionwise with a col
20、d solution 700 g of K 2 CO 3in 1 L of H 2 O. Ether (600 mL) and CHCl 3(200 mL) were added and the mixture was shaken. The layers were separated and the aqueous phase was extracted twice with the same Et 2 O-CHCl 3mixture. The organic phase were combined and dried over Page 10 of 26 10 MgSO 4and the
21、solvents were removed under reduced pressure to give 90 g of residue. Ref: J. Med. Chem., 1968, Vol.11, No.2, 361-364. O O NO 2 LiAlH 4 O O NH 2 To a slurry of LiAlH 4(15.0 g, 0.395 mole) and anhydrous ether (500 mL) in a 5 liter, 3-necked flask fitted with a condenser, mechanical stirrer and dropping funn
