4-Methylbenzyl chloride → 5-[3-(3-Chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amide

HRID 1977840ノート

反応式

HRID 1977840 の反応式
C1(O[C:8](=[O:19])[NH:9][C:10]2[S:14][N:13]=[C:12]([SH:15])[C:11]=2[C:16](=[O:18])[NH2:17])C=CC=CC=1.[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C.[Cl:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[F:47])[CH2:42][NH2:43]>CN(C=O)C.Cl.O1CCCC1>[Cl:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[F:47])[CH2:42][NH:43][C:8](=[O:19])[NH:9][C:10]1[S:14][N:13]=[C:12]([S:15][CH2:20][C:21]2[CH:28]=[CH:27][C:24]([CH3:25])=[CH:23][CH:22]=2)[C:11]=1[C:16]([NH2:17])=[O:18]

参加物

8

反応物 4

HCID 77224-Methylbenzyl chlorideHCID 81531DiisopropylethylamineHCID 1445393-Chloro-4-fluorobenzylamineHCID 178513777HCID 178513777、化合物

生成物 1

HCID 538038185-[3-(3-Chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amide収率 22.4%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of (4-carbamoyl-3-mercapto-isothiazol-5-yl)-carbamic acid phenyl ester (0.075 g, 0.25 mmol) in 0.5 mL of DMF was added 4-methylbenzylchloride (0.036 g, 0.25 mmol), followed by N,N-diisopropylethylamine (0.033 g, 0.25 mmol). After stirring for 18 hours at ambient temperature, tetrahydrofuran (1 mL) was added, followed by 3-chloro-4-fluorobenzylamine (0.081 g, 0.51 mmol). After stirring for 24 hours at 45° C., the mixture was diluted with 1M HCl, extracted 3× with ethyl acetate, and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by radial chromatography on silica gel eluting with ethyl acetate-hexane, affording 26 mg of 5-[3-(3-chloro-4-fluoro-benzyl)-ureido]-3-(4-methyl-benzylsulfanyl)-isothiazole-4-carboxylic acid amide as a colorless solid. HPLC ret. time: 4.9 minutes. 1H NMR (400 MHz, acetone-d6) δ7.95 (bs, 1H), 7.54 (dd, 1H, J=2, 7.2 Hz), 7.39 (m, 1H), 7.31-7.25 (m, 3H), 7.11 (d, 2H, J=8.0 Hz), 7.01 (bs, 2H), 4.48 (m, 4H), 2.28 (s, 3H) ppm; MS (APCI, m/z): 465 [M+H]+.

後処理

  1. stirringAfter stirring for 24 hours at 45° C.
  2. extractionextracted 3× with ethyl acetate
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by radial chromatography on silica gel eluting with ethyl acetate-hexane

出典と根拠

ORDレコード
ord-2d701e8861f14bee8f983b0b4a9959e8
出典データセット
uspto-grants-2001_05
特許番号
US06235764B1

反応ノート

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