N-(5-amino-2-cyclopropylphenyl)acetamide → N-[5-[[3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-cyclopropylphenyl]acetamide

HRID 736ノート

反応式

HRID 736 の反応式
CC(=O)Nc1cc(N)ccc1C1CC1.N#Cc1cnn2c(NC3COC3)cc(Cl)nc12>CC(=O)N(C)C.CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C([O-])[O-].[Cs+].[Cs+].[Pd].[Pd]>CC(=O)Nc1cc(Nc2cc(NC3COC3)n3ncc(C#N)c3n2)ccc1C1CC1

参加物

7

反応物 2

HCID 89098640N-(5-amino-2-cyclopropylphenyl)acetamideHCID 178418222HCID 178418222、化合物

生成物 1

HCID 72164289N-[5-[[3-cyano-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-cyclopropylphenyl]acetamide収率 6.96%

試薬・触媒・溶媒 4

HCID 10796Cesium carbonate試薬HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane触媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
150 °C

実験手順

A 10 mL microwave reactor vial was charged with 5-chloro-7-(oxetan-3-ylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.32 mmol), N-(5-amino-2-cyclopropylphenyl)acetamide (67.1 mg, 0.35 mmol), Cs2CO3 (313 mg, 0.96 mmol), Pd2(dba)3 (14.67 mg, 0.02 mmol) and 2-Di-t- butylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (13.61 mg, 0.03 mmol). The suspended in DMA (.5 mL), added via syringe. The resulting brown suspension was stirred under nitrogen, then microwave vial capped and heated at 150 °C under microwave irradiation for 20 min. LCMS indicated formation of product. The cooled reaction mixture was put through vacuum filtration and concentrated in rotovap. The crude material was purified by ISCO using MeOH and EtOAc (1:10). The solid was suspended in water, stirred for 12 h at rt, repurified with EtOAc, collected and dried to afford a light brown powder (9 mg, 6%) at 93% purity. LCMS, HPLC, and HNMR consistent with desired product- see attached.

出典と根拠

ORDレコード
ord-a242bdcea6fd4820b97f40b83c063cc9
出典データセット
750 AstraZeneca ELN dataset
元リンク
出典を表示

反応ノート

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