8-Chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine → N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine

HRID 300

反応式

HRID 300 の反応式
COc1nc(N)ccc1-c1cnn(C)c1.Cc1cc(Cl)nc2c1CN(C)CC(CC(F)(F)F)O2>CC(C)(C)[O-].Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COc1nc(Nc2cc(C)c3c(n2)OC(CC(F)(F)F)CN(C)C3)ccc1-c1cnn(C)c1

参加物

7

反応物 2

HCID 575128608-Chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepineHCID 575128666-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-ylamine

生成物 1

HCID 57512826N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine収率 9.77%

試薬・触媒・溶媒 4

HCID 23676156Sodium t-butoxide試薬HCID 634876Binap, (A+-)-触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (104 mg, 0.51 mmol), 8-chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (150 mg, 0.51 mmol), Sodium tert-butoxide (73.4 mg, 0.76 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (22.19 mg, 0.04 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (32.6 mg, 0.04 mmol) were added to a radley tube followed by toluene (6 mL). The reaction mixture was flushed with argon and the mixture was heated to 100°C and stirred overnight. The solids were filtered off and washed with DCM. The crude product was purified on prepHPLC yielding N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (23.00 mg, 9.77 %)

出典と根拠

ORDレコード
ord-916b542fdcc44d6284100092f1e92c3f
出典データセット
750 AstraZeneca ELN dataset
元リンク
出典を表示

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