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1,4-Dioxane → N-(3-(2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

HRID 527433
ノート
印刷プレビュー

反応式

HRID 527433 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:21][CH3:22].[CH3:23][C:24]1[C:33]2[CH:32]=[N:31][C:30](S(C)=O)=[N:29][C:28]=2[N:27]([C:37]2[CH:38]=[C:39]([NH:43][C:44](=[O:47])[CH:45]=[CH2:46])[CH:40]=[CH:41][CH:42]=2)[C:26](=[O:48])[CH:25]=1.CCN(C(C)C)C(C)C.O1CCOCC1>C(O)(C)(C)C>[CH3:22][O:21][C:3]1[CH:4]=[C:5]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)[CH:6]=[CH:7][C:2]=1[NH:1][C:30]1[N:31]=[CH:32][C:33]2[C:24]([CH3:23])=[CH:25][C:26](=[O:48])[N:27]([C:37]3[CH:38]=[C:39]([NH:43][C:44](=[O:47])[CH:45]=[CH2:46])[CH:40]=[CH:41][CH:42]=3)[C:28]=2[N:29]=1
参加物反応条件実験手順出典と根拠反応ノート

参加物

6

反応物 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 67128946Tert-butyl 4-(4-amino-3-methoxyphenyl)piperazine-1-carboxylateHCID 86732024N-(3-(5-methyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

生成物 1

HCID 78319000N-(3-(2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

試薬・触媒・溶媒 1

HCID 6386tert-Butanol溶媒

反応条件

温度
90 °C

実験手順

To a suspension of tert-butyl 4-(4-amino-3-methoxyphenyl)piperazine-1-carboxylate (18a, 539 mg, 1.753 mmol) and N-(3-(5-methyl-2-(methylsulfinyl)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (5b, 432 mg, 1.173 mmol) in tert-butanol (15 mL) at RT was added DIEA (0.61 mL, 3.52 mmol) followed by dioxane (6 mL). The reaction mixture was heated in a heating block at 90° C. for 20 h. LC-MS analysis indicated roughly 13% conversion to the desired product along with unreacted starting materials. The reaction mixture was concentrated on the rotovap and the crude residue was suspended in Et2O and filtered. The greenish brown amorphous solid was washed with Et2O (3×20 mL) and this removed most of the aniline starting material (18a). The crude material contained roughly 19% of the desired product (18b) along with recovered 5b. m/z (ESI, +ve ion) 611.9 (M+H)+. The crude residue was used in the subsequent step without further purification.

出典と根拠

ORDレコード
ord-ab85f2eb4ad04e82930820ced58374d8
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346801B2

反応ノート

読み込み中…

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