4-CHLORO-1H-PYRAZOLO[3,4-D]PYRIMIDIN-6-AMINE

To a suspension of 2-amino-4, 6-dichloropyrimidine-5-carbaldehyde (1.92 g, 10 mmol) and triethylamine (1.59 mL, 11.5 mmol) in a mixture of THF (40 mL) and HThe compound of formula () (2.4g, 12.5mmol) and 37.5mL THF was added 12.5mL H 2 O mixed solution Were heated to 50 ° C, was added hydrazine hydrate (1.5g, 25.2mmol), 50 ° C After stirring for 5min, stirred at room temperature for 20min, was added 100mL of ice water stirring 15min, after unscrew the THF was filtered and dried under vacuum to give a yellow solid 2.06 g, yield 97.6percent.A mixture of 2-amino-4, 6-dichloropyrimidine-5-carbaldehyde (A-1) (9.6 g, 50 mmol), THF (150 mL), and water (50 mL) at 50 °C was treated with a solution of hydrazine hydrate (5.1 mL, 100 mmol) in water (50 mL) at room temperature while stirring under nitrogen. Ten mins after addition, the reaction mixture was poured into ice-cold water (250 mL). The THF was evaporated and the remaining aqueous suspension was filtered to give 4-chloro-lH-pyrazolo[3, 4-d]pyrimidin-6-amine (A-2) (7.86 g, 93percent yield). A small portion was recrystallized from DMF/ water. 1H NMR (500 MHz, DMSO) δ ppm 7.15 (s, 2H), 7.95 (s, 1H), 13.25 (s, 1H). MS (M+l): 170, 172 (1 CI).Step 1: 4-chloro-1H-pyrazolo[3, 4-d]pyrimidin-6-ylamine To a mixture of 2-amino-4, 6-dichloro-pyrimidine-5-carbaldehyde (1.0 g, 5.2 mmol) and EtScheme 1; 3-(5-amino-7-(2-(4-(6-fluoro-3-methylbenzo[d]isoxazol-5-yl)piperazin-l- yl)ethyl)-7H-pyrazolo[4, 3-e] [1 , 2, 4]triazolo[l , 5-c]pyrimidin-2-yl)prop-2-yn- 1 -ol (9); Step 1 : 4-chloro-lH-pyrazolo[3, 4-d]pyrimidin-6-amine (2); To a solution of 2-amino-4, 6-dichloropyrimidine-5-carbaldehyde (25.0 g, 130 mmol) in DMF (100 mL) was added N, N-diisopropylethylamine (28.4 mL, 163 mmol). Then hydrazine hydrate (6.32 mL, 130 mmol) was added slowly. The reaction mixture was stirred at room temperature for 24 h and concentrated under vacuum. Water (100 mL) was added, the aqueous solution was filtered, and the filtrate was washed with water. The solid was dried under vacuum to give 4-chloro-lH- pyrazolo[3, 4-d]pyrimidin-6-amine (2) as a yellow solid (18.9 g, 85percent yield). NMR (500 MHz, OMSO-de) δ ppm 7.10 (br s), 7.95 (s, 1 H); MS (M+l): 170.1 (324 mg, 1.7 mmol) was dissolved in a mixed solution of 7 mL of tetrahydrofuran and water (3:1), warmed to 50 °C, and hydrazine hydrate (170 mg, 3.3 mmol) was dissolved in 1.7 mL of water, slowly dripping Adding to the reaction solution, stirring for 40 min, the reaction solution was poured into 8 mL of ice water and stirred for 15 min, allowed to stand for 20 min, then filtered, and the filter cake was washed with acetone to obtain 0.23 g of pale yellow solid, yield 78.4percentTo a suspension of 6-amino-4- CHLORO-LB-PYRAZOLO [3, 4-DPYRIMIDINE (30) (2.3 g, 14 mmol) in MeOH (200 mL) and aqueous ammonium hydroxide (4 ML) was ADDED 10% PD-C (500 MG). The reaction mixture was stirred under atmospheric pressure for 16 h and the catalyst was filtered through a pad of Celite. The filtrate was concentrated and chromatographed with silica gel (CH2Cl2 : MeOH = 90: 10) to yield 1.1 g of the target compound (60%).

Molecular Weight:169.57
XLogP3:0.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:169.0155228
Monoisotopic Mass:169.0155228
Topological Polar Surface Area:80.5
Heavy Atom Count:11
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes