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CAS No. : | 477600-74-1 | MDL No. : | MFCD09878608 |
Formula : | C13H19N5 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | XRIARWQZLGCQDM-KOLCDFICSA-N |
M.W : | 245.32 | Pubchem ID : | 23401507 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.82% | With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at -10 - 10℃; | Example 12 : l-((3R,4R)-4-Methyl-3-(methyl(7Hr-pyrrolo [2,3-rf] pyrimidin-4- yl)amino)piperidine-l-carbonyl)cyclopropanecarbonitrile (89)To a stirred solution of N-methyl-N-((3R,4R)-4-methylpiperidin-3-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-amine (87) (0.129 g, 0.52 mmol) in Dimethylformamide (1 mL) was added 1- cyanocyclopropanecarboxylic acid (88) (0.089 g, 1.051 mmol), diisopropylethylamine (0.27 g, 2.10 mmol) and cooled to -10 °C. To this mixture (2-(7-Aza-lH-benzotriazole-l-yl)-l, 1,3,3- tetramethyluronium hexafluorophosphate) (HATU, 0.399 g, 1.051 mmol) was added and stirred at 10 0C for 1.5 h. The reaction mixture was quenched with water (10 mL), extracted with a (9:1) mixture of ethyl acetate and methanol (3 x 50 mL). The organic layers were combined washed with water (2 x 15 mL), brine (10 mL), dried and concentrated in vacuum. The residue obtained was purified by flash column chromatography (silica gel 12 g, eluting with CMA 80 in chloroform 0 to 100percent) to afford l-((3i?,4i?)-4-Methyl-3-(methyl(7H-pyrrolo[2,3-(i]pyrimidin-4-yl)amino)piperidine- l-carbonyl)cyclopropanecarbonitrile (89) (100 mg, 56.82percent) as a light beige solid. 1HNMR (300 MHz, DMSO) delta 11.66 (s, IH), 8.10 (s, IH), 7.18 - 7.09 (m, IH), 6.58 (s, IH), 4.94 (s, IH), 4.37 - 3.63 (m, 4H), 3.33 (s, 3H), 2.47 - 2.35 (m, IH), 1.93 - 1.79 (m, IH), 1.84 - 1.45 (m, 5H), 1.04 (d, J = 7.1, 3H); MS (ES+): 339.1 (M + 1); HPLC [Zorbax SBC3, 3.0 x 150 mm, 5 mum, with a ZGC SBC3, 2.1 x 12.5 mm guard cartridge, "A" Buffer=(98percent of 0.1 M Ammonium Acetate in 2percent acetonitrile) "B" Buffer=100percent Acetonitrile, UV Absorbance; Rt = 16.65 (97.71percent)]; Analysis: Calcd for Ci8H22N6O .bul. 0.25 H2O: C, 63.04; H, 6.61; N, 24.50; Found: C, 63.40; H, 6.54; N, 24.28. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate; In dichloromethane; at 20℃; for 3h;Inert atmosphere; Cooling with ice; Enzymatic reaction; | Diisopropylethylamine (1.32 g, 10.02 mmol, 5.0 eq.) was added slowly under an ice bath under nitrogenN-[(3R,4R)-4-Methyl-3-piperidin]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.5 g, 2.04 mmol, 1.0 eq .), 5-Methylisoxazole-4-carboxylic acid (0.284 g, 2.24 mmol,1.1eq.) and 2-(7-Aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.94 g, 3.06 mmol, 1.5 Eq.) in dichloromethane (15 ml) and the reaction was stirred at room temperature for 3 hours. Then the reaction solution was extracted with dichloromethane.The organic layer was backwashed once with sodium bicarbonate solution and brine, dried over sodium sulfate and spin-dried.The crude product was purified by HPLC (Instrument: SHIMADZULC-8A, separation column: synergi-10 mum, 250×50 mm ID mobile phase, A: H2O (1?TFA, v/v) and B: acetonitrile, gradient: B 30-80%. Flow rate: 80 ml/min) ,The target components of the machine were first adjusted to pH=8 with sodium bicarbonate solution, and then extracted with ethyl acetate. The organic layer was backwashed with saline, and the organic layer was dried to obtain the target compound (800 mg, yield). Rate = 80%). |