3-Amino-1,2,3,4-tetrahydrocarbazol

General procedure: Aqueous sulfuric acid solution (10 percent w/v, 30 mL) was taken in a round bottom flask, added (1, 4-dioxa-spiro[4.5]dec-8-yl)dimethylamine (12a, 1.5 g, 8.1 mmol) followed by phenylhydrazine (1.52 g, 14.08 mmol) at room temperature. The reaction mass was heated to reflux temperature (95-100 °C) and maintained reflux for 2-3 h. The progress of the reaction was monitored by TLC. After completion of reaction, the reaction mass was cooled to 10-15 °C. Then the mass was basified with aqueous sodium hydroxide solution (20 percent w/v) and the aqueous layer was extracted with ethyl acetate. Organic layer was washed with brine solution, dried over anhydrous sodium sulfate and organic volatiles were removed by distillation under vacuum. The crude compound was purified by flash chromatography (ethyl acetate: triethylamine 9:0.2) to obtain 0.8 g of title compound (13a), the yield being 50 percent. #10;#10;The acidic aqueous phase is made alkaline with 45% strength sodium hydroxide solution and extracted 3 times with 1 l of methylene chloride each time. The combined methylene chloride phases are dried with sodium phosphate and evaporated. 300 ml of ether and 50 ml of isopropanol are added to the residue, and the mixture is stirred. The precipitated product is filtered off with suction, washed with ether and dried in vacuo. 28.6 g (48.3% of theory) of product are obtained. Melting point: 174-176 C.Example 59 3-Amino-1, 2, 3, 4-tetrahydrocarbazole (enantiomer A) STR75 24.1 g (0.059 mol) of diastereomer 57 are dissolved in 460 ml of glacial acetic acid. 460 ml of concentrated hydrochloric acid and 24 ml of thioglycolic acid are added and heated under reflux, under nitrogen, for 3 days. The reaction mixture is then diluted with 200 ml of water and, while cooling, is adjusted to pH 5 with 45% strength sodium hydroxide solution. It is then extracted twice with 1.5 l of ethyl acetate each time, and the aqueous phase is then made alkaline with 45% strength sodium hydroxide solution and extracted 3 times with 1.5 l of ethyl acetate each time. The ethyl acetate extracts are combined, dried with sodium sulphate and evaporated. The residue is stirred in 150 ml of ether. The precipitated product is filtered off with suction and dried in vacuo. 7.8 g (71.3% of theory) of enantiomer A are obtained. Melting point: 160-166 C. Rotation [alpha]20 =78.38 (DMSO+10% water)Example 60 3-Amino-1, 2, 3, 4-tetrahydrocarbazole (enantiomer B) STR76 Enantiomer B is prepared by hydrolysis of 58 in analogy to the procedure for 59 from 57. Melting point: 162-167 C. Rotation [alpha]20 =-78.11 (DMSO+10% H2 O)The residue is further evaporated under high vacuum to remove dimethylformamide. 3 g (70% of theory) of crystalline enantiomer A are obtained from ether. Melting point: 160-166 C. Rotation: [alpha]20 =78.38 (DMSO+10% water)To a solution of 4-chloro-2-methylsulfanyl-pyrazolo[l, 5-a][l, 3, 5]triazine (500 mg, 1.69 mmol, 1 eq, HC1) in MeCN (30 mL) was added DIEA (1.31 g, 10.12 mmol, 1.76 mL, 6 eq) and (3R)- 2, 3, 4, 9-tetrahydro-lH-carbazol-3-amine (314.20 mg, 1.69 mmol, 1 eq). The mixture was stirred at 50 C for 2 h. The mixture was concentrated. The crude material was purified on silica gel column chromatography (from pure PE to PE/EtOAc = 2/1, TLC: PE/EtOAc = 3/1, Rf = 0.4) to yield (3R)- N-(2-methylsulfanylpyrazolo[1, 5-a] [1, 3, 5]triazin-4-yl)-2, 3, 4, 9-tetrahydro- lH-carbazol-3 -amine (300 mg, 770.46 muiotaetaomicron, 45.7% yield, 90% purity) as a yellow solid. NMR (400 MHz, CDCb) delta ppm 7.90-7.77 (m, 2H), 7.44 (d, J = 7.8 Hz, 1H), 7.30 (d, J = 8.1Hz, 1H), 7.18-7.12 (m, 1H), 7.11-7.06 (m, 1H), 6.61 (d, J = 8.3 Hz, 1H), 6.21 (s, 1H), 3.28 (dd, J = 5.0, 15.5 Hz, 1H), 3.00- 2.78 (m, 4H), 2.55 (s, 3H), 2.31-2.15 (m, 2H); ES-LCMS m/z 351.2 [M+H]+.[00561] Step 3 : (3S)-N-[5-(5-Fluoro-3-pyridyl)-3-isopropylpyrazolo[1, 5-a]pyrimidin-7- yl]-To a solution of 7-chloro-5-(5-fluoro-3-pyridyl)pyrazolo[1, 5-a]pyrimidine (50 mg, 166.91 muetaiotaomicron, 1.0 eq) in i-PrOH (3 mL) was added DIEA (64.71 mg, 500.72 muiotaetaomicron, 87.21 JL, 3.0 eq) and (3R)-

Molecular Weight:186.25
XLogP3:1.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:1
Exact Mass:186.115698455
Monoisotopic Mass:186.115698455
Topological Polar Surface Area:41.8
Heavy Atom Count:14
Complexity:216
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes