4-Methylmorpholine → Methyl 4-(4-{4-[(methylsulfonyl)amino]phenyl}(1,3-thiazol-2-yl))-5-methylthiothiophene-2-carboxylate

HRID 2298620ノート

反応式

HRID 2298620 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:13]3[CH:14]=[C:15]([C:19]([O:21][CH3:22])=[S:20])[S:16][C:17]=3[CH3:18])[S:11][CH:12]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C1C=CC=CN=1)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>ClCCl>[CH3:39][S:40]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:13]3[CH:14]=[C:15]([C:19]([O:21][CH3:22])=[S:20])[S:16][C:17]=3[CH3:18])[S:11][CH:12]=2)=[CH:4][CH:3]=1)(=[O:42])=[O:41]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 86583820Methyl 4-(4-(4-aminophenyl)(1,3-thiazol-2-yl))-5-methylthiothiophene-2-carboxylate

生成物 1

HCID 86583818Methyl 4-(4-{4-[(methylsulfonyl)amino]phenyl}(1,3-thiazol-2-yl))-5-methylthiothiophene-2-carboxylate収率 66.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Methyl 4-(4-(4-aminophenyl)(1,3-thiazol-2-yl))-5-methylthiothiophene-2-carboxylate (200 mg, 0.55 mmol) was dissolved in dry dichloromethane (20 mL). To this, N-methyl morpholine (150 μL, 1.38 mmol) and dimethylaminopyridine (6.1 mg, 0.055 mmol) were added, the mixture was cooled on an ice bath, and methanesulfonyl chloride (43 μL, 0.55 mmol) was added dropwise. The mixture was then stirred for 8 days at room temperature. The mixture was partitioned between saturated sodium bicarbonate (50 mL) and dichloromethane (20 mL). The aqueous layer was extracted with dichloromethane (3×20 mL), and the combined organic layers were washed with saturated sodium bicarbonate (20 mL), brine (2×20 mL), and dried over anhydrous sodium sulfate. The solvent was remove in vacuo. Column chromatrography on silica gel (100 g) eluting with dichloromethane:methanol 99/1 (v:v), gave methyl 4-(4-{4-[(methylsulfonyl)amino]phenyl}(1,3-thiazol-2-yl))-5-methylthiothiophene-2-carboxylate (155 mg, 64%) as a solid. 1H-NMR (DMSO-d6; 300 MHz) δ9.92 (s, 1H), 8.22 (s, 1H), 8.11 (s, 1H), 8.40 and 6.90 (AB quartet, 2H, J=8.7 Hz), 3.87 (s, 3H), 3.05 (s, 3H), 2.76 (s, 3H). Mass spectrum (MALDI-TOF, CHCA matrix m/z): Calcd. for C17H16N2O4S4441.0 (M+H), found 441.2.

後処理

  1. temperaturethe mixture was cooled on an ice bath
  2. customThe mixture was partitioned between saturated sodium bicarbonate (50 mL) and dichloromethane (20 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (3×20 mL)
  4. washthe combined organic layers were washed with saturated sodium bicarbonate (20 mL), brine (2×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was remove in vacuo
  7. washColumn chromatrography on silica gel (100 g) eluting with dichloromethane

出典と根拠

ORDレコード
ord-c11afe14e695494ca923dddca9f4c89f
出典データセット
uspto-grants-2002_12
特許番号
US06492403B1

反応ノート

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