Cesium carbonate → 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-ethyl-4-piperidyl)-2,5-difluoro-benzamide

온도

110 °C

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 100 mg, 0.33 mmol), 4-amino-N-(1-ethyl-4-piperidyl)-2,5-difluoro-benzamide (Intermediate 235; 102 mg, 0.36 mmol) and caesium carbonate (213 mg, 0.65 mmol) added to dioxane (5 mL) and the suspension bubbled with nitrogen for 10 minutes. tris-dibenzylideneacetonedipalladium (II) (18 mg, 0.02 mmol) and XANTPHOS (17 mg, 0.03 mmol) were added and the mixture heated at 110° C. overnight. The mixture was filtered, and the filtrate loaded onto to an SCX-3 cartridge (10 g) pre-wet with methanol, then washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined and evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound as a light orange gum (99 mg, 55%).

1. customthe suspension bubbled with nitrogen for 10 minutes
2. filtrationThe mixture was filtered
3. washwashed with methanol
4. washeluted with ammonia in methanol
5. additionProduct containing fractions
6. customevaporated
7. customthe resultant material purified by base modified reverse phase preparative HPLC

ORD 기록

ord-9621e82fe5a74498887eafb6a58f40d2

출처 데이터셋

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07709471B2