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HRID327804

反应详情

EQUATION

反应方程式

HRID 327804 的结构方程式

REACTANTS

反应物

3
结构：CCN=C=NCCCN(C)C.Cl
HCID2723939

1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

C8H18ClN3

结构：C[C@@H](CN)CC(F)(F)F.Cl
HCID12004108

未命名化合物

结构：COc1cc(C(=O)NS(=O)(=O)c2ccccc2C)ccc1Cc1cn(C)c2ccc(C(=O)O)cc12
HCID15104475

未命名化合物

PRODUCTS

生成物

1
结构：COc1cc(C(=O)NS(=O)(=O)c2ccccc2C)ccc1Cc1cn(C)c2ccc(C(=O)NC[C@H](C)CC(F)(F)F)cc12
HCID204056

3-[(4-{Hydroxy[(2-methylbenzene-1-sulfonyl)imino]methyl}-2-methoxyphenyl)methyl]-1-methyl-N-(4,4,4-trifluoro-2-methylbutyl)-1H-indole-5-carboximidic acid

C31H32F3N3O5S

收率 90.5%

AUXILIARIES

试剂、催化剂与溶剂

3
结构：CN(C)c1ccncc1
催化剂HCID14284

N,N-Dimethylpyridin-4-amine

C7H10N2

结构：C1CCOC1
溶剂HCID8028

Tetrahydrofuran

C4H8O

结构：CCOC(C)=O
溶剂HCID8857

Ethyl acetate

C4H8O2

PROCEDURE

实验过程

To a mixture of 4-(5-carboxy-1-methylindol-3-ylmethyl)-3-methoxy-N-(2-methylphenylsulfonyl)benzamide (103.5 g), 4-dimethylaminopyridine (112.4 g), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (51.8 g) in tetrahydrofuran (distilled from sodium benzophenone ketyl) (2.0 l), which had been stirred for 2 hours, was added (R)-2-methyl-4,4,4-trifluorobutylamine hydrochloride (42.6 g); and the reaction mixture was stirred overnight (about 18 hours, incomplete reaction) then heated to reflux for two hours (complete reaction). The cooled reaction mixture was diluted with ethyl acetate (2 1) washed with 1N hydrochloric acid (twice) and brine, dried (MgSO4) and evaporated. The residue (138.6 g) was combined with impure product from similar procedures (28.0 g) and purified by flash chromatography, eluting with methylene chloride:ethyl acetate (sequentially, 1:0, 9:1 and 3:1) to afford a solid which was triturated twice with ether to give the crude title compound (135.2 g) which was recrystallized from ethanol (1.2 l) and acetone (0.3 l) (concentrated by boiling to about 0.9 l and refrigerated) and dried under vacuum to provide the title compound (117.1 g, 65% recovery) as a white crystalline solid; mp 141.5°-143.5° C.; NMR (300 MHz, DMSO-d6): 1.01 (d, 3H, CH3), 2.0-2.2 (m, 2H, CF3CH2), 2.3-2.5 (m, 1H, CHCH3), 2.61 (s, 3H, ArCH3), 3.23 (br t, 2H, CH2N), 3.76 (s, 3H, NCH3), 3.92 (s, 3H, OCH3), 4.07 (s, ArCH2Ar'), 7.13 (s, 1H), 7.17 (d, 2H), 7.38-7.69 (m, 6H), 7.72 (d, 1H), 8.05 (d, 1H), 8.11 (s, 1H), 8.46 (br t, 1H, NHCO); analysis for C31H32F3N3O5S: calculated: C, 60.48; H, 5.24; N, 6.83%, found: C, 60.47; H, 5.27; N, 6.67%

WORKUP

后处理

  1. stirringand the reaction mixture was stirred overnight
  2. custom(about 18 hours, incomplete reaction)
  3. temperaturethen heated
  4. temperatureto reflux for two hours
  5. custom(complete reaction)
  6. customThe cooled reaction mixture
  7. washwashed with 1N hydrochloric acid (twice) and brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. custompurified by flash chromatography
  11. washeluting with methylene chloride
  12. customethyl acetate (sequentially, 1:0, 9:1 and 3:1) to afford a solid which
  13. customwas triturated twice with ether
  14. customto give the crude title compound (135.2 g) which
  15. customwas recrystallized from ethanol (1.2 l) and acetone (0.3 l) (concentrated by boiling to about 0.9 l and refrigerated)
  16. customdried under vacuum