Benzenesulfonic Acid → 4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxy-2-methylpropoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrile

HRID 1754441ノート

反応式

HRID 1754441 の反応式
[NH2:1][C:2]1[C:3]([F:21])=[CH:4][C:5]([O:15][CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)[CH:7]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[CH2:38][C@H:37]3[N:33]([CH2:34][CH2:35][CH2:36]3)[C:32]([CH3:40])([CH3:39])[CH2:31]2)[C:26]([C:41]#[N:42])=[CH:25][N:24]=1.C1(S(O)(=O)=O)C=CC=CC=1>CC(O)C>[CH3:39][C:32]1([CH3:40])[CH2:31][C@H:30]([NH:29][C:27]2[C:26]([C:41]#[N:42])=[CH:25][N:24]=[C:23]([NH:1][C:2]3[CH:7]=[C:6]([N:8]4[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]4)[C:5]([O:15][CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])=[CH:4][C:3]=3[F:21])[N:28]=2)[CH2:38][C@H:37]2[N:33]1[CH2:34][CH2:35][CH2:36]2

参加物

5

反応物 3

HCID 7371Benzenesulfonic AcidHCID 86704483(7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amineHCID 867044841-(5-amino-2-(2-hydroxy-2-methylpropoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

生成物 1

HCID 718115594-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxy-2-methylpropoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrile収率 80%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
80 °C

実験手順

A mixture of 1-(5-amino-2-(2-hydroxy-2-methylpropoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (305 mg), (7R,8aS)—N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (262 mg), and benzenesulfonic acid (160 mg) in IPA (2 mL) were heated to 80° C. overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%) to give desired product (386 mg, 80%).

後処理

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe crude mixture was concentrated to dryness
  3. customThe crude product was absorbed onto silica gel
  4. custompurified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%)

出典と根拠

ORDレコード
ord-80b979e4ecf443af89db251fc0077a86
出典データセット
uspto-grants-2015_10
特許番号
US09169249B2

反応ノート

読み込み中…