CAS: 31169-27-4; 7-Bromo-4-Chlorothieno[3,2-D]Pyrimidine

相似化合物

41102-25-4 16269-66-2 225385-03-5

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CAS号31169-25-2 7-溴噻吩并[3,2-d]嘧啶... | CAS号16234-10-9 4-羟基噻吩并[3,2-d]嘧啶 | CAS号16269-66-2 4-氯噻吩并[3,2-d]嘧啶 | CAS号22288-78-4 3-氨基-2-噻吩甲酸甲酯 | CAS号272-68-4 噻吩并[3,2-D]嘧啶 | CAS号1318133-32-2 7-溴噻吩并[3,2-D]嘧啶-4-胺 | CAS号16269-66-2 4-氯噻吩并[3,2-d]嘧啶 | CAS号21586-25-4 7-溴噻吩并[3,2-d]嘧啶

7-溴噻吩并[3,2-D]嘧啶-4(1H)-酮置于氢溴酸,溶剂黄146,三乙胺,三氯氧磷体系中,用 甲苯 作为反应溶剂,化学反应 0.5H,以96%的收率获得产物7-溴-4-氯噻酚并[3,2-D]嘧啶
参考文献:泛 Raf 抑制剂 Belvarafenib 的高效第二代制造工艺
标题:泛 Raf 抑制剂 Belvarafenib 的高效第二代制造工艺
摘要:本文报道了泛 Raf 抑制剂贝伐非尼 (Gdc-5573) 的简化制造工艺的开发.贝尔伐非尼的过程具有许多有效的关键反应,包括强大且可扩展的 Pd 催化羰基化反应反应生成噻吩并嘧啶2和高度化学选择性的 Pt/v/c 催化硝基还原以获取倒数第二个中间体3.最终的酰胺偶联是通过温和且安全的方案完成的,采用n,N,N ',N'-四甲基氯甲脒六氟磷酸盐作为偶联剂,重结晶后得到数公斤生产规模的贝伐非尼.
DOI:10.1021/acs.Oprd.1C00277

专利信息

专利号:US-11999749-B2
优先权日:2021-06-30
标题 :Synthesis of a bis-mesylate salt of 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto
发明人：GOSSELIN FRANCIS; KOENIG STEFAN G; MERCADO-MARIN EDUARDO V; STUMPF ANDREAS; ZELL DANIEL; ZHANG HAIMING; BACHMANN STEPHAN; CARRERA DIANE E; DALZIEL MICHAEL E; GE YONGHUI; ZHANG JIE; BIGLER RAPHAEL; FINET LAURE ELIZABETH SIMONE; MONDIERE REGIS JEAN GEORGES; NAKAGAWA YUKI
权利人:GENENTECH INC; HOFFMANN LA ROCHE
摘要:A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

专利号:US-2025051351-A1
优先权日:2021-06-30
标题 :Synthesis of a bis-mesylate salt of 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto

专利号:US-2023028651-A1
优先权日:2021-06-30
标题 :Synthesis of a bis-mesylate salt of 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto

专利号:TW-202311265-A
优先权日:2021-06-30
标 题 :Synthesis of a bis-mesylate salt of 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto

专利号:WO-2023278981-A1
优先权日:2021-06-30
标 题:Synthesis of a bis-mesylate salt of 4-amino-n-(1 -((3-chloro-2- fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2- d]pyrimidine-7-carboxamide and intermediates thereto

专利号:EP-4363424-A1
优先权日:2021-06-30
标题:Synthesis of a bis-mesylate salt of 4-amino-n-(1 -((3-chloro-2- fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2- d]pyrimidine-7-carboxamide and intermediates thereto