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Triethylamine → 2-Amino-4-[2-(3-{[tert-butyl (dimethyl)silyl]oxy}prop-1-yn-1-yl)-1,3-thiazol-4-yl]-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)pyridine-3,5-dicarbonitrile

HRID 1969477
ノート
印刷プレビュー

反応式

HRID 1969477 の反応式
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[N:11]=[C:12](Br)[S:13][CH:14]=2)[C:5]([C:16]#[N:17])=[C:4]([S:18][CH2:19][C:20]2[N:21]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[S:23][CH:24]=2)[N:3]=1.[C:32]([Si:36]([CH3:42])([CH3:41])[O:37][CH2:38][C:39]#[CH:40])([CH3:35])([CH3:34])[CH3:33].C(N(CC)CC)C>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[N:11]=[C:12]([C:40]#[C:39][CH2:38][O:37][Si:36]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:41])[CH3:42])[S:13][CH:14]=2)[C:5]([C:16]#[N:17])=[C:4]([S:18][CH2:19][C:20]2[N:21]=[C:22]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[S:23][CH:24]=2)[N:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 8471TriethylamineHCID 3445622Propargyloxy-t-butyldimethylsilaneHCID 668979732-Amino-4-(2-bromo-1,3-thiazol-4-yl)-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)pyridine-3,5-dicarbonitrile

生成物 1

HCID 673501122-Amino-4-[2-(3-{[tert-butyl (dimethyl)silyl]oxy}prop-1-yn-1-yl)-1,3-thiazol-4-yl]-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)pyridine-3,5-dicarbonitrile収率 16%

試薬・触媒・溶媒

3
HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

Under argon, 500 mg (0.916 mmol) of 2-amino-4-(2-bromo-1,3-thiazol-4-yl)-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)pyridine-3,5-dicarbonitrile and 0.186 ml (0.916 mmol) of tert-butyl(dimethyl)(prop-2-yn-1-yloxy)silane were initially charged in 10 ml of acetonitrile, and 105 mg (0.092 mmol) of tetrakis(triphenylphosphine)palladium(0), 35 mg (0.183 mmol) of copper(I) iodide and 0.255 ml (1.832 mmol) of triethylamine were added in succession. The mixture was then heated under reflux at 100° C. for 4 h. The reaction mixture was filtered and the filtrate was purified by preparative HPLC. This gave 239 mg of the target compound in a purity of 38% (yield: 16%). The batch obtained in this manner contained the desilylated compound in a proportion of 62%. The mixture was used without further purification for the subsequent hydrogenation.

後処理

  1. temperatureThe mixture was then heated
  2. filtrationThe reaction mixture was filtered
  3. customthe filtrate was purified by preparative HPLC
  4. customThe batch obtained in this manner
  5. customThe mixture was used without further purification for the subsequent hydrogenation

出典と根拠

ORDレコード
ord-7e7c5b3f65814629b77c0b140ebff4ad
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08426602B2

反応ノート

読み込み中…

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