Hydrochloric Acid → N2-(4,4-dimethyl-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-8-yl)-5-fluoro-N4-(octahydro-5,5-dimethylindolizin-7-yl)pyrimidine-2,4-diamine

HRID 633356ノート

反応式

HRID 633356 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:17][CH:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.[CH3:21][C:22]1([CH3:37])[O:27][C:26]2[C:28](F)=[CH:29][C:30]([NH2:32])=[CH:31][C:25]=2[N:24]2[N:34]=[N:35][N:36]=[C:23]12.Cl>CC(O)C.O1CCOCC1>[CH3:21][C:22]1([CH3:37])[O:27][C:26]2[CH:28]=[CH:29][C:30]([NH:32][C:2]3[N:7]=[C:6]([NH:8][CH:9]4[CH2:17][CH:16]5[N:12]([CH2:13][CH2:14][CH2:15]5)[C:11]([CH3:19])([CH3:18])[CH2:10]4)[C:5]([F:20])=[CH:4][N:3]=3)=[CH:31][C:25]=2[N:24]2[N:34]=[N:35][N:36]=[C:23]12

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 86704443N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amineHCID 867044684,4-dimethyl-6-fluoro-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-8-amine

生成物 1

HCID 86704467N2-(4,4-dimethyl-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-8-yl)-5-fluoro-N4-(octahydro-5,5-dimethylindolizin-7-yl)pyrimidine-2,4-diamine収率 83.4%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of (R/S,S/R)—N-(2-chloro-5-fluoropyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (D1) (0.1 g, 0.3 mmol, single diastereomer) in 3 ml of iPrOH, 4,4-dimethyl-6-fluoro-4H-benzo[b]tetrazolo[1,5-d][1,4]oxazin-8-amine (0.093 g, 0.4 mmol) and 4N HCl in dioxane (0.1 ml) were added. The reaction mixture was heated to 100° C. in a sealed vial for 12 hours. LCMS analysis of the crude reaction mixture indicated the completion of the reaction. The crude product was purified by column chromatography to give 0.12 g (Yield=72%) of the product as a mixture of two enantiomers.

後処理

  1. customLCMS analysis of the crude reaction mixture
  2. customthe completion of the reaction
  3. customThe crude product was purified by column chromatography

出典と根拠

ORDレコード
ord-e869dd3813f147fda95b26e62f82ffc5
出典データセット
uspto-grants-2016_04
特許番号
US09321763B2

反応ノート

読み込み中…