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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
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HRID 1969477 반응식
[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
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참가 물질

7

반응물 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

생성물 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-dicarbonitrile수율 16%

시약·촉매·용매

3
HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7e7c5b3f65814629b77c0b140ebff4ad
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08426602B2

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