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Chemical Structure| 1421373-36-5 Chemical Structure| 1421373-36-5

Structure of 1421373-36-5

Chemical Structure| 1421373-36-5

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Product Details of [ 1421373-36-5 ]

CAS No. :1421373-36-5
Formula : C28H34ClN7O2
M.W : 536.07
SMILES Code : O=C(NC1=CC(NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C)C)C)CCCl
MDL No. :MFCD28386961

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Application In Synthesis of [ 1421373-36-5 ]

* 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.

  • Upstream synthesis route of [ 1421373-36-5 ]
  • Downstream synthetic route of [ 1421373-36-5 ]

[ 1421373-36-5 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 1421373-36-5 ]
  • [ 1421373-65-0 ]
YieldReaction ConditionsOperation in experiment
94% With triethylamine In acetonitrile at 80℃; for 6 h; To a stirred solution of 3-chloro-N-[2-[2-dimethylaminoethyl(methyl)amino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]propanamide (Intermediate 174, 31.5 g, 58.76 mmol) in acetonitrile (310 mL) was added triethylamine (17.84 g, 176.28 mmol) at r.t. The resulting mixture was heated to 80°C for 6h then cooled to r.t.. Water (130 mL) was then added and the mixture stirred for 12h. The mixture was then filtered, washed with a mixture of water and acetonitrile (160 mL, 1:1) and dried at 50°C for overnight to give the title compound (19.2 g, 94percent) as a solid form identified herein as polymorphic form D. 1H NMR: 2.69 (3H, s), 2.83 (6H, d), 3.35 (4H, s), 3.84 (3H, s), 3.91 (3H, s), 5.75 (1H, d), 6.28 (1H, d), 6.67 (1H, dd), 7.05-7.23 (2H, m), 7.29 (1H, t), 7.43 (1H, d), 7.56 (1H, d), 8.21 (2H, s), 8.81 (1H, s), 9.47 (1H, s), 9.52 (1H, s), m/z: ES+ MH+ 500.26.
94% With sodium hydroxide In tetrahydrofuran; water at 65℃; for 10 h; (2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-[4-(1-methylindol-3-yl)pyrimidine at 0 ° C Yl) benzene-1,2,4-triamine (Intermediate 100, 10 g, 21.32 mmol) in THF (95 mL) and water (9.5 mL) was added 3-chloropropionyl chloride (3.28 G, 25.59 mmol). The mixture was stirred at room temperature for 15 minutes and then NaOH (3.48 g, 85.28 mmol) was added. The resulting mixture was heated to 65 ° C and maintained for 10 hours. The mixture was then cooled to room temperature and CH30H (40 mL) and water (70 mL) were added. The resulting mixture was stirred overnight. The resulting solid was collected by filtration, washed with water (25 mL) and dried at 50 ° C for 12 hours to give compound A (7.0 g, 94percent) as a solid.
94%
Stage #1: With triethylamine In acetonitrile at 80℃; for 6 h;
Stage #2: at 20℃; for 12 h;
To a solution of 3-chloro-N- (2- [2-dimethylaminoethyl (methyl) amino] -4-methoxy-5 - [4- (1-methylindole- Yl) pyrimidin-2-yl] amino} phenyl) propanamide(31.5 g, 58.76 mmol)In acetonitrile (310 mL)In the stirred solutionTriethylamine (17.84 g, 176.28 mmol).The resulting mixture was heated to 80 & lt; 0 & gt; C for 6 hours,Then cooled to room temperature.Then add water (130 mL),The mixture was stirred for 12 hours.The mixture was then filtered,Washed with a mixture of water and acetonitrile (160 mL, 1: 1), dried at 50 ° C overnight,The title compound was obtained as a title compound (19.2 g, 94percent).
94% With triethylamine In acetonitrile at 20 - 80℃; for 6 h; At room temperature,To 3-chloro-N-(2-[2-dimethylaminoethyl(methyl)amino]-4-methoxy-5-[4-(1-methylindol-3-yl)pyrimidine 2-yl]amino}phenyl)propanamide (31.5 g, 58.76 mmol) in acetonitrile (310 mL)Triethylamine (17.84 g, 176.28 mmol) was added to the stirred solution.The resulting mixture was heated to 80 ° C for 6 hours and then cooled to room temperature.Water (130 mL) was then added and the mixture was stirred for 12 h.The mixture was then filtered and washed with a mixture of water and acetonitrile (160 mL, 1:1).Drying at 50 ° C overnight gave the title compound (19.2 g, 94percent).
91.2% With triethylamine In acetonitrile at 80℃; Large scale N-[(4-dimethylamino-ethylamino-2-methoxy-5-chloropropionylaminophenyl)]-4-(1-methyl-1H-indol-3-yl)-2-pyrimidinamine3 kg (5.6 mol) was added to 30 L of acetonitrile, and 1.7 kg (16.7 mol) of triethylamine was added thereto with stirring, and the mixture was heated at 80 ° C overnight.The reaction was completely monitored by TLC, then 15 L of water was added, the temperature was lowered, the mixture was stirred overnight, and the mixture was filtered, and the filter cake was rinsed with a mixture of acetonitrile and water (7.5 L / 7.5 L).Drying gave 2.55 kg of an off-white powder with a yield of 91.2percent (HPLC purity: 99.6percent).
70.99 g With diethylamine; triethylamine In acetonitrile at 70℃; for 10.5 h; Acetonitrile (700 ml) was added to the compound B obtained in the first step. Triethylamine (79.43 g, 0.785 mol) was added to the system, and the temperature was raised to 70 ° C. The mixture was stirred for 10.5 h and added dropwise with water Finished, cooling and stirring.The filter cake was washed with a mixture of acetonitrile and water and dried in vacuo to give Compound C (70.99 g, 0.142 mol). HPLC purity: 99.76percent. Two-step total yield of 90.5percent.

References: [1] Patent: WO2013/14448, 2013, A1, . Location in patent: Page/Page column 65; 66.
[2] Patent: CN106674202, 2017, A, . Location in patent: Paragraph 0072.
[3] Patent: CN107043369, 2017, A, . Location in patent: Paragraph 0527; 0528; 0529; 0530; 0531; 0532.
[4] Patent: CN108929311, 2018, A, . Location in patent: Paragraph 0244-0247.
[5] Patent: CN108623567, 2018, A, . Location in patent: Paragraph 0068; 0069; 0070.
[6] Patent: CN107522690, 2017, A, . Location in patent: Paragraph 0030; 0031; 0035; 0036; 0040; 0041; 0045; 0046.
[7] Patent: CN108218839, 2018, A, . Location in patent: Paragraph 0031.
 

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