Remdesivir-004

Remdesivir-004 - Names and Identifiers

Name	4-amino-7-iodopyrrolo[2,1-f][1,2,4]triazine
Synonyms	Remdesivir-004 Starting material) Remdesivir Impurity 20 7-iodopyrrole[2,1-f][1,2,4]triazin-4-amine 4-amino-7-iodopyrrolo[2,1-f][1,2,4]triazine Pyrrolo[2,1-f][1,2,4]triazin-4-amine, 7-iodo-
CAS	1770840-43-1
EINECS	204-514-8

Remdesivir-004 - Physico-chemical Properties

Molecular Formula	C6H5IN4
Molar Mass	260.035
Density	2.43±0.1 g/cm3(Predicted)
pKa	3.04±0.30(Predicted)
Storage Condition	2-8℃
Use	Use 7-iodopyrrolo [2,1-F][1,2,4] triazin-4-amine is an amine organic substance and can be used as an intermediate of bulk medicine.

Remdesivir-004 - Upstream Downstream Industry

Downstream Products

Remdesivir N-2

Remdesivir-004 - Uses and synthesis methods

application

7-iodopyrrolo [2,1-F][1,2,4] triazin-4-amine is a pharmaceutical intermediate, which can be made of tert-butyl xenoformate and 2, 5-Dimethoxytetrahydrofuran is prepared in five steps as a starting material. There are reports that it can be used to prepare EGFR inhibitors.

Preparation

Step 1. Tert-butyl 1H-pyrrole-1-yl carbamate

tert-butyl formate (100g,0.76mol), 2,5-dimethoxytetrahydrofuran (108g,0.83mol) and dioxane (700mL) were added into a 2L three-mouth bottle. Under stirring, dilute hydrochloric acid (2M,10mL) is slowly added to the upper solution, and then heated to 100 ℃ for 48h. After the reaction is completed, the solvent is removed by distillation under reduced pressure, and the residue is dissolved in EtOAc(500mL). The ester phase is washed with saturated Na2CO3 solution and saturated NaCl aqueous solution, dried with anhydrous Na2SO4, and concentrated to obtain yellow solid after filtration. The obtained solid is dispersed in EtOH(100mL), filtered, the filter residue is washed with a small amount of EtOH, and the target substance is dried to 80g. The yield is 58%. LCMS(ESI):m/z = 183(M H).

Step 2. tert-butyl 2-cyano-1H-pyrrole-1-yl carbamate

in a 1L three-mouth bottle, add tert-butyl 1H-pyrrole-1-yl carbamate (80g,0.44mol) and anhydrous acetonitrile (500mL), and cool in an ice water bath. Chlorosulfonyl isocyanate (65g,0.46mol) was slowly dropped into the upper solution to maintain the temperature and react for 1h. Then slowly drop DMF(40mL) and maintain the temperature for 1h. After the reaction is completed, slowly add ice water to quench the reaction, and then adjust to neutral with saturated Na2CO3 solution. The aqueous phase was extracted with EtOAc. The obtained organic phase is washed with saturated NaCl solution, anhydrous Na2SO4 is dried, and 85g of product is concentrated after filtration, which is directly used for the next reaction with 95% yield. LCMS(ESI):m/z = 208(M H).

Step 3.1-Amino-1H-pyrrole-2-formonitrile

in a 1L round bottom flask, under the cooling of ice bath, tert-butyl 2-cyanide-1H-pyrrole -1-yl carbamate (85g,0.41mol) and hydrogen chloride dioxane solution (4M,500mL) were added, naturally raised to room temperature for 4h, and white solid was precipitated. After the reaction is completed, the solvent is removed by vacuum distillation, the residue is dispersed into EtOAc(100mL), filtered, the filter residue is washed with EtOAc, and the solid is dried to 50g, which is the target hydrochloride. LCMS(ESI):m/z = 108(M H).

Step 4. Pyrrole [1,2-f][1,2,4] triazin-4-amine

1-amino -1H-pyrrole -2-nitrile hydrochloride (50g), formamidine acetate (109g,1.05mol), K3PO4(222g,1.05mol) and EtOH(800mL) were added into a 2L round bottom flask, and the reflux reaction was heated for 16h. After the reaction is complete, filter and the filter residue is washed with EtOH. The filtrate is concentrated, the residue is dissolved in EtOAc, the organic phase is washed in saturated NaCl solution, anhydrous Na2SO4 is dried, and the red solid is concentrated after filtration. The obtained solid is dispersed in CH2Cl2, filtered, and the filter residue is washed with CH2Cl2 to obtain 35g of light yellow solid. LCMS(ESI):m/z = 135(M H).

Step 5.7-iodopyrrole [1,2-f][1,2,4] triazin-4-amine

Pyrrole [1,2-f][1,2,4] triazin-4-amine (35g,0.26mol) is dissolved in anhydrous DMF(150mL) and cooled in an ice water bath. NIS(29g,0.13mol) was added to the upper solution to maintain the temperature for 1h. Then NIS(29g,0.13mol) was added to maintain the temperature for 1h. After the reaction is complete, it is diluted with H2O. The aqueous phase was extracted with EtOAc. The organic phase obtained was washed with 5% Na2SO3 solution, saturated NH4Cl solution, saturated NaCl solution, anhydrous Na2SO4 dried, and concentrated to obtain 69g of dark yellow solid after filtration. The upper solid is dissolved in EtOAc, activated carbon is added, heated and refluxed for decolorization for 5 hours, filtered, and the filter residue is washed with EtOAc. The filtrate was concentrated, and the resulting residue was crystallized with EtOAc to obtain 50g of light yellow solid with 74% yield. LCMS(ESI):m/z = 261(M H).

Last Update：2024-04-10 22:29:15