Supercharge Your Innovation With Domain-Expert AI Agents!

Method for producing compound

A compound, a technology for wound healing, used in the production of pharmaceuticals

Pending Publication Date: 2020-04-10
PH PHARMA CO LTD
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, many intermediate chromatographic purifications are performed according to the methods described in WO 2009 / 080199, which are often very cost-intensive

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for producing compound
  • Method for producing compound
  • Method for producing compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0203] 4-Formyl-3-fluorobenzonitrile (XV)

[0204] 400 g (1.97 mol) of 4-bromo-2-fluorobenzaldehyde (XIV) as a solution in 2.01 DMF were mixed with 183 g (0.433 mol) of potassium hexacyanoferrate (K 4 [Fe(CN) 6 ]) and 165.5 g (1.97 mol) of sodium bicarbonate were combined, and 2.2 g (9.85 mmol) of palladium acetate were added. The resulting product was stirred at 120°C for 2.5 hours. Allow to cool to 20°C, then add 2.01 water to the batch. Extraction was performed with 4.01 MtBE, and the aqueous phase was washed again with 1.51 MtBE. The organic phases were combined and mixed with 21 water. Most of the MtBE was distilled off at 30 °C in slight vacuum. The product crystallized out. It was cooled to 3°C and stirred at this temperature for 1 hour. The product was filtered off and washed again with water (twice 0.81 each). Drying was carried out in vacuo at 40°C. Yield: 241 g (80% of theory) of beige solid.

[0205] MS(EIpos): m / z=150[M+H]+

[0206] 1H-NMR (400MHz, DMSO...

Embodiment 2

[0208] 4-Formyl-3-methylsulfonylbenzonitrile (VI)

[0209] 200 g (1.34 mol) of 4-formyl-2-fluorobenzonitrile (XV) were provided as a solution in 0.81 DMSO, and 192 g (1.88 mol) of the sodium salt of methanesulfinic acid were added. It was stirred at 50°C for 4 hours. The resulting product was cooled to 20°C. The reaction mixture was added to 8.01 water. The product crystallized out. It was stirred at room temperature for 1 hour. The product was filtered off and washed with water (2 times 0.11 each). Drying was carried out in vacuo at 40°C. Yield: 256 g (91% of theory) of beige solid.

[0210] MS(ESIpos): m / z(%)=191.1(15)[M-18] + , 161.0 (100).

[0211] 1H-NMR (400MHz, DMSO-d6): δ=3.57(s, 3H), 8.10(d, 1H), 8.38(d, 1H), 8.45(s, 1H), 10.62(s, 1H).

Embodiment 3

[0213] (racemic)-4-[4-cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-trifluoromethyl]phenyl]- Allyl 1,2,3,4-tetrahydropyrimidine-5-carboxylate (IX)

[0214] To triethyl phosphate (124.3 g, 683 mmol) was added phosphorus pentoxide (64.6 g, 455 mmol) in 3 portions at 20 °C, and the resulting product was stirred at 40 °C for 3 h. It was then diluted with THF (115ml), stirred at 20°C for 30min, and 4-formyl-3-(methylsulfonyl)benzonitrile (VI) (119g, 569mmol) and 1-[3-(tri Fluoromethyl)phenyl]urea (VII) (116 g, 569 mmol). Thereafter, allyl (VIII) acetoacetate (121 g, 852 mmol) was partitioned for 20 min, at which time the temperature was increased to around 60°C. The mixture was stirred at 80 °C for 4 h. For work-up, water (115 ml) was added at 40°C and it was stirred at 25°C for 30 min. The product was filtered off and washed with water (280ml). The residue was stirred with MtBE (280ml) for 20min, filtered off again and washed with MtBE (220ml). Drying was carried out i...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a novel and improved method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), and to the production and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I).

Description

[0001] The present invention is filed on March 15, 2016 and is entitled "For the production of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2 -Oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile method" PCT / EP2016 / 055498 invention patent application The original application entered the Chinese national phase and the national application number obtained was 201680028214.7. technical field [0002] The present invention relates to the production of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(tri Fluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile and an improved process for its crystal form (A) for the production of medicaments. Background technique [0003] Compound (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)benzene Base]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile is known from WO 2009 / 080199 A1 and corresponds to formula (I) [0004] [0005] The compound of...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D239/22A61K31/513A61P11/00A61P9/00A61P17/02A61P9/12C07C315/00C07C317/44
CPCC07D239/22A61P11/00A61P9/00A61P17/02A61P9/12C07C315/00C07B2200/13C07B2200/07C07C317/44A61P43/00A61K31/513
Inventor H.施尔默P.鲁本鲍尔B.凯尔B.奥勒尼克
Owner PH PHARMA CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com