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Chemical Structure| 151266-23-8

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Product Details of 4-AMino-3-Iodo-1H-Pyrazolo[3,4-D]PyriMidine

CAS No. :151266-23-8
Formula : C5H4IN5
M.W : 261.02
SMILES Code : NC1=C2C(NN=C2I)=NC=N1
MDL No. :MFCD03787931
InChI Key :HQAIUXZORKJOJY-UHFFFAOYSA-N
Pubchem ID :1519489

Safety of 4-AMino-3-Iodo-1H-Pyrazolo[3,4-D]PyriMidine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Application In Synthesis of 4-AMino-3-Iodo-1H-Pyrazolo[3,4-D]PyriMidine

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 151266-23-8 ]

[ 151266-23-8 ] Synthesis Path-Downstream   1~12

  • 1
  • [ 107025-44-5 ]
  • [ 151266-23-8 ]
  • [ 862728-32-3 ]
  • [ 862728-31-2 ]
YieldReaction ConditionsOperation in experiment
To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (0.626 g, 2.40 mmol) in anhydrous tetrahydrofuran (25 mL) was added triphenylphosphine (1.51 g, 5.76 mmol) and diisopropylazodicarboxylate (1.16 g, 5.76 mmol). The mixture was stirred for about five minutes at ambient temperature under a nitrogen atmosphere and <strong>[107025-44-5]4-(2-methoxyethoxy)-cyclohexanol</strong> (JP 61229865, mixture of cis- and trans-isomers, 1.04 g, 5.98 mmol) was added. The reaction mixture was stirred at ambient temperature for about three hours. The tetrahydrofuran was removed under reduced pressure and the crude mixture was stirred in a mixture of acetone (15 mL) and aqueous hydrochloric acid (2 N, 15 mL) for two hours at ambient temperature. The acetone was removed under reduced pressure and the aqueous mixture was neutralized by the addition of saturated aqueous sodium bicarbonate solution such that the pH was approximately 8. The aqueous mixture was extracted with ethyl acetate (3×25 mL) and the combined organic fractions were dried over anhydrous magnesium sulfate. The crude mixture was purified by flash column chromatography on silica gel using ethyl acetate as the mobile phase to provide pure white solids of both trans-3-iodo-1-[4-(2-methoxyethoxy)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (200 mg, 0.480 mmol); 1H NMR (DMSO-d6 400 MHz) delta8.18 (s, 1H), 4.59 (m, 1H), 3.56 (dd, 2H), 3.46 (dd 2H), 3.36 (tt 1H), 3.25 (s, 3H), 2.08 (d, 2H), 1.92 (m, 4H), 1.33-1.37 (qd, 2H); m/z: (M+H)+ 418, and cis-3-iodo-1-[4-(2-methoxyethoxy)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (120 mg, 0.288 mmol); 1H NMR (DMSO-d6, 400 MHz) delta8.18 (s, 1H), 4.63 (tt, 1H), 3.58 (t, 1H), 3.52 (td, 2H), 3.50 (td, 2H), 3.29 (s, 3H), 2.15 (q, 2H), 1.95 (d, 2H), 1.61 (m, 4H); m/z: (M+H)+ 418
  • 2
  • [ 89694-46-2 ]
  • [ 151266-23-8 ]
  • 3-(2-chloro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
16% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; N,N-dimethyl-formamide; at 80℃; for 12.5h;Inert atmosphere; Intermediate 873-(2-chloro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.0770 g, 4.12 mmoles) in DMF (10 ml), ethanol (5 ml) and water (5 ml), 2-chloro-5-methoxyphenyl boroinc acid (1.00 g, 5.364 mmoles) and sodium carbonate (2.186 g, 20.63 mmoles) were added and the system is degassed for 30 min. Tetrakis triphenylphosphine Palladium (0.905 g, 0.783 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as green solid (0.090 g, 16percent yield). 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta 13.61 (s, 1H), 8.19 (s, 1H), 7.51 (d, J=8.9 Hz, 1H), 7.09 (d, J=8.9 Hz 1H), 7.06 (d, J=2.6 Hz 1H), 3.78 (s, 3H).
  • 3
  • [ 940890-90-4 ]
  • [ 151266-23-8 ]
  • [ 1276110-38-3 ]
YieldReaction ConditionsOperation in experiment
79% With caesium carbonate; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere; The 3-iodo--1H- pyrazolo [3,4-d] pyrimidin-4-ylamine (4.3g, 16.57mM, 1.0equiv) was dissolved in N, N- dimethylformamide (60mL),And cesium carbonate were sequentially added (6.753g, 35mM, 2.1equiv), (S) -3- (methanesulfonyloxy) piperidine-l-carboxylate (5.549g,19.88mM, 1.2equiv), and heated at 80 in nitrogen, after completion of the reaction by TLC, concentrated under reduced pressure most of the N, N- dimethylFormamide, was added water (60mL), and extracted with ethyl acetate (3 × 30), and the combined organic layers were washed with water, normal saline. The organic layer wasDried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (petroleum ether: ethyl acetate = 2: 1) to give a white solid after treatment Compound 4 (5.8g,79percent).
30% With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;Inert atmosphere; Step 28a: (R)-tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (Intermediate 28a) To a stirred solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (500 mg, 1.9 mmol) in DMF (10 mL) was added cesium carbonate (1.56 g, 4.7 mmol) followed by (S)-tert-butyl 3-(methylsulfonyloxy)piperidine-1-carboxylate (535 mg, 1.9 mmol) at room temperature under N2 atmosphere. The reaction mixture was heated to 80° C. and stirred further for 16 h at that temperature. After the completion of reaction (monitored by TLC), solvent was removed under reduced pressure, water was added and extracted with ethyl acetate (2.x.25 mL). The organic layer was separated, dried over Na2SO4 and solvent was removed under reduced pressure. The crude compound was purified by silica gel column chromatography [Methanol/DCM: 2/98] to afford Intermediate 28a (240 mg, 30percent) as brown solid. TLC: 5percent MeOH/DCM:ethylactate (1:1) (Rf: 0.3). 1H-NMR (CDCl3, 200 MHz): delta 8.38 (s, 1H), 6.02 (bs, 2H), 4.82-4.64 (1H), 4.31-4.02 (m, 2H), 3.44-3.20 (m, 1H), 2.95-2.65 (m, 1H), 2.25-2.08 (m, 2H), 1.95-1.58 (m, 2H), 1.42 (s, 9H). MS: m/z=445 (M++1). Chiral HPLC purity (SAV-MA8002-56): 98.19percent at 9.73 RT (0.1percent TFA in hexane: ethanol/70:30, flow rate: 1 mL/min, Chiralpak, ADH, 250.x.4.6 mm, 5 um [SHCL061002].
10% With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;Inert atmosphere; To a suspension of fe/ -butyl (3S)-3-methylsulfonyloxypiperidine-1 -carboxylate (13.88 g, 49.7 mmol) and 3-iodo-1 H-pyrazolo[3,4-d]pyrimidin-4-amine (1 1 .47 g, 43.9 mmol) in DMF (240 mL) was added cesium carbonate (36.22 g, 1 1 1 .2 mmol) under a nitrogen atmosphere. The reaction was then heated to 80 °C for 16 h, cooled and concentrated to dryness. The residue was taken up in ethyl acetate (200 ml_), the mixture was sonicated before being filtered giving a dark orange filtrate. The filtrate was washed with water (2 chi 150 ml_), brine (2 chi 150 ml_), dried over sodium sulfate, filtered and concentrated under reduced pressure to give a dark orange film. Further purification by flash column chromatography (DCM/EtOAc 1 :1) afforded the crude product as a light yellow powder. Trituration with methanol gave fe/ -butyl (3R)-3-(4-amino-3-iodo^yrazolo[3,4-c ]pyrimidin-1 -yl)piperidine-1 -carboxylate (2.12 g, 4.77 mmol, 10percent yield) as an off white solid. UPLC-MS (ES+, Short acidic): 1 .60 min, m/z 445.2 [M+H]+ H-NMR (400 MHz, DMSO-c/6): delta (ppm) 8.22 (s, 1 H, ArH), 4.66-4.53 (m, 1 H, CH), 4.15-3.65 (m, 2H), 3.55-3.36 (m, 0.5H), 3.21 -3.08 (m, 0.5H), 3.05-2.92 (m, 1 H), 2.20-2.08 (m, 1 H), 2.07-1 .99 (m, 1 H), 1 .96-1 .80 (m, 1 H), 1 .60-1 .47 (m, 1 H), 1 .45-1 .24 (m, 9H)
26.9 g With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 10h; A suspension solution of 14.6 g of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine synthesized by the method described in WO 2007/126841, 25 g of (S)-tert-butyl 3-(methylsulfonyloxy)piperidine-1-carboxylate obtained in Step 1, and 69 g of potassium carbonate in 150 ml of DMA was heated to 100°C, and was stirred for 10 hours. The suspension solution was cooled to room temperature, and then 300 ml of water was added thereto. A solid thus obtained was collected by filtration and washed with water, and the solid was dried. Thus, 26.9 g of the title compound was obtained as a yellow solid. Physical property value: m/z [M+H]+ 446.2
13.8 g A mixture of 3-iodo-1H-pyrazolo[3,4-djpyrimidin-4-amine (Formula III, when X is iodo, 18 g), cesium carbonate (51.8 g), and dimethylaminopyridine (0.88 g) was addedto N-methylpyrrolidinone (400 mL) under nitrogen at room temperature. The temperature of the reaction mixture was raised to 70°C. A solution of tert-butyl (3S)-3- [(methylsulfonyl)oxyjpiperidine-1-carboxylate (Formula IV, when Pr? is Boc and Pr2 is methylsulfonyl, 29 g) in N-methylpyrrolidone (150 mL) was added drop-wise to thesolution over a period of one hour at 70°C. The reaction mixture was stirred overnight at70°C. Water (1.7 L) was added to the reaction mixture, then the mixture was stirred at5°C for 3 hours, and then stirred overnight at room temperature. The yellowish solidproduct was filtered, then washed with water (100 mL). The resulting solid was dried at45°C under vacuum for 9 hours to obtain the title compound.Yield: 13.8g
13.8 g With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 70℃;Inert atmosphere; Example 4: Preparation oftert-butyl (3R)-3-(4-amino-3-iodo-lH-pyrazolor3.4- dlpyrimidin-l-vDpiperidine-l-carboxylate (Formula V. when X is iodine and Pr1 is Boc) A mixture of 3-iodo-lH-pyrazolo[3,4-d]pyrimidin-4-amine (Formula III, when X is iodine, Example 1, 18 g), cesium carbonate (51.8 g), and dimethylaminopyridine (0.88 g) was added to N-methylpyrrolidone (400 mL) under nitrogen at room temperature. The temperature of the reaction mixture was raised to 70°C. A solution of tert-butyl (3S)-3- [(methylsulfonyl)oxy]piperidine-l-carboxylate (Formula IV, when Pr1 is Boc and Pr2 is mesyl, Example 3, 29 g) in N-methylpyrrolidone (150 mL) was added drop-wise over a period of 1 hour at 70°C. The reaction mixture was stirred overnight at 70°C. Water (1.7 L) was added to the reaction mixture, then the mixture was stirred at 5°C for 3 hours, and then stirred overnight at room temperature. The yellowish solid product was filtered, then washed with water (100 mL). The resulting solid was dried at 45 °C under vacuum for 9 hours to obtain the title compound. Yield: 13.8 g
With di-isopropyl azodicarboxylate; triethylphosphine; In tetrahydrofuran; at 5 - 200℃; for 12.5h; A solution of diisopropyl azodicarboxylate in tetrahydrofuran (30 mL) was added drop wise tostined solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidine-4-amine (Formula III, 5.9 g), (S)-tertbutyl-3-hydroxypiperidine-1-carboxylate (Formula IV, L=H; 10 g), triethylphosphine (11.8 g), and tetrahydrofuran (300 mL) at 5-10 °C over 30 mm. The resulting mixture was stined at room temperature for 12 h and then concentrated under vacuum. The residue was purified on silica gel column then eluted with dichloromethane and methanol (10:1) to give (R)-tert-butyl-3-(4-amino- 3 -iodo- 1 H-pyrazolo[3 ,4-d]pyrimidine- 1 -yl)piperidine- 1 -carboxylate
26.9 g With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 10h; (Step 2) Synthesis of (R)-tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (0188) A suspension solution of 14.6 g of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine synthesized by the method described in WO 2007/126841, 25 g of (S)-tert-butyl 3-(methylsulfonyloxy)piperidine-1-carboxylate obtained in Step 1, and 69 g of potassium carbonate in 150 mL of DMA was heated to 100° C., and was stirred for 10 hours. The suspension solution was cooled to room temperature, and then 300 mL of water was added thereto. A solid thus obtained was collected by filtration and washed with water, and the solid was dried. Thus, 26.9 g of the title compound was obtained as a yellow solid.
26.9 g With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 10h; (Step 2) Synthesis of (R)-tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl) piperidine-1-carboxylate 3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (14.6 g) synthesized by the method described in the pamphlet of International Publication No. WO 2007/126841, (S)-tert-butyl 3-(methylsulfonyloxy) piperidine-1-carboxylate (25 g) obtained in (Step 1), and potassium carbonate (69 g) were suspended in DMA (150 mL), and the suspension was heated to 100° C. and stirred for 10 hours. After the mixture was cooled to room temperature, water (300 mL) was added thereto, and the precipitated solid was collected by filtration, washed with water, and then dried to obtain 26.9 g of the title compound as a yellow solid. Physical property value: m/z [M+H]+ 446.2
26.9 g With potassium carbonate; In N,N-dimethyl acetamide; at 100℃; for 10h; A suspension solution of 14.6 g of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine synthesized by the method described in WO 2007/126841, 25 g of (S)-tert-butyl 3-(methylsulfonyloxy)piperidine-1-carboxylate obtained in Step 1, and 69 g of potassium carbonate in 150 mL of DMA was heated to 100° C., and was stirred for 10 hours. The suspension solution was cooled to room temperature, and then 300 mL of water was added thereto. A solid thus obtained was collected by filtration and washed with water, and the solid was dried. Thus, 26.9 g of the title compound was obtained as a yellow solid. Physical property value: m/z [M+H]+ 446.2

  • 4
  • [ 456-24-6 ]
  • [ 151266-23-8 ]
  • [ 1422828-16-7 ]
YieldReaction ConditionsOperation in experiment
68% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere; Example 28 Synthesis of (E)-N-(6-(4-amino-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyridin-3-yl)-4-(dimethylamino)-N-methylbut-2-enamide (66) To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1) (3 g, 11.5 mmol) and <strong>[456-24-6]2-fluoro-5-nitropyridine</strong> (1.96 g, 13.8 mmol) in DMF (50 mL) was added K2CO3 (4.77 g, 43.5 mmol). After the mixture was stirred at 80 C. under N2 overnight, it was slowly poured into stirred water (200 mL). The resulting precipitate was collected by filtration, washed with methanol (50 mL*3) and dried in vacuo to afford 3-iodo-1-(5-nitropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (61) (3 g, 68%) as a brown solid. LC-MS (ESI): m/z (M+1) 384.
  • 5
  • [ 305329-97-9 ]
  • [ 151266-23-8 ]
  • tert-butyl 3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine-1-yl)methyl)pyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With potassium carbonate; In N,N-dimethyl acetamide; water; at 85℃; for 3h; [00316] A suspension of 3-iodo-lH-pyrazolo[3,4-d]pyrimidin-4-amine (4.5 g, 17.24 mmol, 1.0 equiv), tert-butyl 3 -(bromomethyl)pyrrolidine-l -carboxylate (4.78 g, 18.10 mmol, 1.05 equiv) and K2CO3 (7.15 g, 51.72 mmol, 3.0 equiv) in DMA (40 mL) was heated to 85 C. The reaction was stirred at 85 C for 3 h, at which point the solution was cooled to room temperature. Then, H2O (80 mL) was added to the reaction, and a solid precipitated out. The mixture was filtered, and the solid cake was washed with H2O (2 x 40 mL), and then dried under reduced pressure to give tert-butyl 3-((4-amino-3-iodo-lH-pyrazolo[3,4-d]pyrimidin-l- yl) methyl)pyrrolidine-l -carboxylate (6 g, 78% yield) as a yellow solid. LCMS (ESI) m/z: [M + H] calcd for C15H21IN6O2: 445.08; found: 445.1.
78% With potassium carbonate; In N,N-dimethyl acetamide; at 85℃; for 3h; A suspension of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4.5 g, 17.24 mmol, 1.0 equiv), <strong>[305329-97-9]tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate</strong> (4.78 g, 18.10 mmol, 1.05 equiv) and K2CO3 (7.15 g, 51.72 mmol, 3.0 equiv) in DMA (40 mL) was heated to 85 C. The reaction was stirred at 85 C for 3 h, at which point the solution was cooled to room temperature. Then, H2O (80 mL) was added to the reaction, and a solid precipitated out. The mixture was filtered, and the solid cake was washed with H2O (2 x 40 mL), and then dried under reduced pressure to give tert-butyl 3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1- yl) methyl)pyrrolidine-1-carboxylate (6 g, 78% yield) as a yellow solid. LCMS (ESI) m/z: [M + H] calcd for C15H21IN6O2: 445.08; found 445.1.
With potassium carbonate; In N,N-dimethyl acetamide; at 85℃; for 3h; A suspension of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4.5 g, 17.24 mmol, 1.0 equiv), <strong>[305329-97-9]tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate</strong> (4.78 g, 18.10 mmol, 1.05 equiv) and K2CO3 (7.15 g, 51.72 mmol, 3.0 equiv) in DMA (40 mL) was heated to 85 C. The reaction was stirred at 85 C for 3 h, at which point the solution was cooled to room temperature. Then, H2O (80 mL) was added to the reaction, and a solid precipitated out. The mixture was filtered, and the solid cake was washed with H2O (2 x 40 mL), and then dried under reduced pressure to give tert-butyl 3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1- yl) methyl)pyrrolidine-1-carboxylate (6 g, 78% yield) as a yellow solid. LCMS (ESI) m/z: [M + H] calcd for C15H21IN6O2: 445.08; found 445.1.
  • 6
  • [ 109431-87-0 ]
  • [ 151266-23-8 ]
  • [ 1422827-96-0 ]
YieldReaction ConditionsOperation in experiment
84% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; A solution of 4-amino-3-iodo-lH-pyrazolo [3,4-D] pyrimidine (10 g, 38 mmol)(R) -1-Boc-3-hydroxypyrrole (16 g, 85 mmol)Triphenylphosphine (20 g, 76 mmol) was added to a three-necked flask,THF (120 ml) was added,Cooling to 0 ,A mixture of diisopropyl azodicarboxylate (DIAD) (15.2 g, 76 mmol) and THF (30 ml)About 1h drops finished,Slowly warmed to room temperature overnight.The reaction solution was spin-dried,Extracted with water, extracted with ethyl acetate, dried and concentrated to give the product (13.8 g, yield 84%) by column chromatography.
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 12h; General procedure: Toa stirred solution of 3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine 10 (10 mmol) and triphenylphosphine (20 mmol) in THF (25 mL) wasadded 11a-11e (20 mmol) and DIAD (20mmol) at 0,it was stirred at room temperature for 12h. Then the mixture was concentratedto a residue and purified via column chromatography (0% ethyl acetate indichloromethane to 80%) to provide the desired compound 12a-12e (Yield: 39%-55%).
  • 7
  • [ 151266-23-8 ]
  • [ 477293-60-0 ]
  • (2S,4R)-tert-butyl 4-(3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpyrrolidine-1-carboxylate [ No CAS ]
  • 8
  • [ 603-35-0 ]
  • [ 151266-23-8 ]
  • [ 477293-60-0 ]
  • (2S,4R)-tert-butyl 4-(3-iodo-4-((triphenylphosphoranylidene)amino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.387 g With di-isopropyl azodicarboxylate; In tetrahydrofuran; at 20℃;Cooling with ice; (Step 1) Synthesis of (2S,4R)-tert-butyl 4-(3-iodo-4-((triphenylphosphoranylidene)amino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpyrrolidine-1-carboxylate tert-Butyl (2S,4S)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylate (0.30 g), triphenylphosphine, and 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine were dissolved in THF (7 mL). To the solution, diisopropyl azodicarboxylate (0.443 mL) was added under ice cooling. The solution was stirred at room temperature for 2 hours, and then, THF (10 mL) was further added thereto. After overnight stirring, triphenylphosphine (0.117 g) and diisopropyl azodicarboxylate (0.089 mL) were further added thereto, and the mixture was further stirred for 1 hour. After concentration of the solution, the residue was suspended in ethyl acetate, and the resulting insoluble matter was removed. Then, the filtrate was concentrated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate) to obtain the title compound (0.387 g) as a colorless amorphous.
0.387 g With di-isopropyl azodicarboxylate; In tetrahydrofuran; at 20℃; for 3.0h;Cooling with ice; tert-Butyl (2S,4S)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylate (0.30 g), triphenylphosphine, and 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine were dissolved in THF (7 mL). To the solution, diisopropyl azodicarboxylate (0.443 mL) was added under ice cooling. The solution was stirred at room temperature for 2 hours, and then, THF (10 mL) was further added thereto. After overnight stirring, triphenylphosphine (0.117 g) and diisopropyl azodicarboxylate (0.089 mL) were further added thereto, and the mixture was further stirred for 1 hour. After concentration of the solution, the residue was suspended in ethyl acetate, and the resulting insoluble matter was removed. Then, the filtrate was concentrated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate) to obtain the title compound (0.387 g) as a colorless amorphous.
  • 9
  • [ 269410-26-6 ]
  • [ 151266-23-8 ]
  • [ 330786-24-8 ]
YieldReaction ConditionsOperation in experiment
37% With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 120℃; for 12h;Inert atmosphere; 3-Iodo-1H-[3,4-d]pyrazolopyrimidin-4-amine (435 mg, 1.7 mmol)Dissolved in N, N- mixed solvent of dimethylformamide in H2O,Add 2-(4-phenoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxolaneborane(1.5g, 5.0mmol),Potassium Phosphate (531 mg, 2.5 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloride dichloromethane complex(69 mg, 0.08 mmol), heated to 120C under nitrogen protection for 12 hours.After the reaction was completed, water was added and a large amount of solids precipitated.Extract three times with ethyl acetate, combine the organic phases, wash three times with water, dry with anhydrous sodium sulfate, spin dry the solvent, and purify by column to obtain the target compound (187 mg). The yield is 37%.
  • 10
  • [ 1402238-32-7 ]
  • [ 151266-23-8 ]
  • 3-(4-(2-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
13.5% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydroxide; In N,N-dimethyl-formamide; at 120℃; for 16h;Inert atmosphere; To a solution containing 3-iodo- f i/-pyxazoloP.4-< ]pyriMdi-4-amiae (3,0 g, I 1.5 romoi) and (4-(2-iliK>rophenoxy)phenyl)boronic acid in KN dimethylfonxutftode (20 mL) was added NaOH (900 mg, 22.9 trtmof). The reaction mixture was purged with nitrogen atmosphere and , {bisdfphciiyipiKLSphi o)ferrocciiepail diimi(Ii) dichloride (Pd(dppf)C 840 rag, 1 . 1 mmol) was slowly added at room temperature followed by beating at 1 0 C for 16 hours. The reaction mixture was cooled, filtered through eeiite and then poured info ice water and was extracted with ethyl acetate. The combined organic layer extracts were dried over anhydrous Na_SO* and ccmcenirated in vacuo to give a crude oil which was purified by column chromatography on silica gel (100-200 mesh), eiuting with 50% ethyl acetate: hexanes mixture to afford the title compound (500 rag, 13.5%) as a light brown solid. NMR ( DMS0-< 400 MHz): 5 13.55 (s, IH), 8.21 is, 1H), 7.? im, 2H), 7.66 (d, 8.6 Hz, 2H), 7.44 (m, H), 7.29 (m, 3H), 7, 12 (m, V 8.4 Hz, 2H).
  • 11
  • [ 109431-87-0 ]
  • [ 151266-23-8 ]
  • tert-butyl (S)-3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 3.5h;Inert atmosphere; Intermediate 2 (2.09g, 8mmol) was dissolved in 150mL of tetrahydrofuran,Add compound 3 (1.8g, 9.6mmol), triphenylphosphine (4.2g, 16mmol), protected by N2, stir at 0, then add diisopropyl azodicarboxylate (3.1mL, 16mmol) dropwise, add dropwise After half an hour, it was transferred to room temperature and reacted for 3 hours, followed by TLC monitoring. After the completion of the reaction, the reaction solution was concentrated, washed with water 3 times, the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the intermediate 4 (light yellow solid, 70%) was obtained by column chromatography.
70% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 3.5h;Inert atmosphere; Intermediate 2 (2.09g, 8mmol) was dissolved in 150mL of tetrahydrofuran, and compound 3 (1.8g, 9.6mmol) was added,Triphenylphosphine (4.2g, 16mmol), protected by N2, stirred at 0C, and then diisopropyl azodicarboxylate (3.1mL, 16mmol) was added dropwise,After the addition was completed, it was transferred to room temperature after half an hour and reacted for 3 hours, followed by TLC monitoring.After the completion of the reaction, the reaction solution was concentrated, washed with water 3 times, the organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography gave Intermediate 4 (light yellow solid, 70%)
32% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; for 12h;Inert atmosphere; Procedure: 3-Iodo-4-amino-1H-pyrazolo[3,4-d]pyrimidine (5.1 g, 19.5 mmol), (R)-1-Boc-3-hydroxytetrahydropyrrole (7.3 g, 39mmol), triphenylphosphine PPh3 (7.7g, 29.3mmol) was placed in a 250mL round-bottomed flask, magnets were placed, 100mL of THF was added, and stirred under nitrogen atmosphere at room temperature; diisopropyl azodicarboxylate was taken. DIAD (5.9 g, 29.3 mmol) was dissolved in about 25 mL of THF and slowly added dropwise to the reaction system. After the addition was complete, the reaction was continued for about 12 hours. According to TLC results, the reaction was stopped, and the filtrate was concentrated under reduced pressure using silica gel column chromatography. Purified with petroleum ether-ethyl acetate as eluent to obtain a white solid 2b with a yield of 32%
32% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 12h;Inert atmosphere; 3-iodo-4-amino-1H-pyrazolo [3,4-d] pyrimidine (5.1g, 19.5mmol), (R) -1-Boc-3-hydroxytetrahydropyrrole (7.3g, 39mmol), triphenylphosphine PPh3 (7.7g, 29.3mmol) was placed in a 250mL round-bottomed flask, placed in a magnet, 100mL of THF was added, and stirred at room temperature under the protection of nitrogen; diisopropyl azodicarboxylate was taken DIAD (5.9 g, 29.3 mmol) was dissolved in about 25 mL of THF, and slowly added dropwise to the reaction system. After the dropwise addition was completed, the reaction was continued for about 12 hours. According to the results of TLC, the reaction was stopped, concentrated under reduced pressure, and silica gel column chromatography was used. Purification with petroleum ether-ethyl acetate as eluent gave 2b as a white solid, yield 32%

  • 12
  • [ 151266-23-8 ]
  • [ 477293-60-0 ]
  • C15H21IN6O2 [ No CAS ]
 

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