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

HRID 1712127노트

반응식

HRID 1712127 반응식
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.O1CCCC1.[Cl:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][C:42]=1[F:43])[CH2:38][NH2:39]>CN(C=O)C.Cl>[Cl:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][C:42]=1[F:43])[CH2:38][NH:39][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]

참가 물질

7

반응물 4

HCID 77224-Methylbenzyl chlorideHCID 8028TetrahydrofuranHCID 1445393-Chloro-4-fluorobenzylamineHCID 178513777HCID 178513777, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6228Dimethylformamide용매

실험 절차

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-disopropylethylamine (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 (0.051 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) δ 7.95 (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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-decc0b00707f44d8a825d9ce9f6295a6
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07790902B2

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