HRID1707268

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID2723939

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

C8H18ClN3

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

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 104.5%

AUXILIARIES

试剂、催化剂与溶剂

催化剂HCID14284

N,N-Dimethylpyridin-4-amine

C7H10N2

溶剂HCID8028

Tetrahydrofuran

C4H8O

溶剂HCID8857

Ethyl acetate

C4H8O2

PROCEDURE

实验过程

To a mixture of 4-(5-carboxy-l-methylindol-3-yl-methyl) -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 L) washed with 1N hydrochloric acid (twice) and brine, dried (MgS04) 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 crude (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)-indol -3-ylmethyl]-N-(2-methylphenylsulphonyl)benzamide (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 form B (117.1 g, 65% recovery) as a white crystalline solid; mp 141.5°-143.5 ° C.; NHR (300 MHz, DMSO-d6): 1.01 (d, 3H, CH3), 2.0-2.2 (m, 2H, CF3C2), 2.3-2.5 (m, 1H, CHCH3), 2.61 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

stirringand the reaction mixture was stirred overnight
custom(about 18 hours, incomplete reaction)
temperaturethen heated
temperatureto reflux for two hours
custom(complete reaction)
customThe cooled reaction mixture
washwashed with 1N hydrochloric acid (twice) and brine
customdried (MgS04)
customevaporated
custompurified by flash chromatography
washeluting with methylene chloride
customethyl acetate (sequentially, 1:0, 9:1 and 3:1) to afford a solid which
customwas triturated twice with ether

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-f9d9accbca3d4a5c97499427e82d0027
来源数据集: uspto-grants-1994_10
DOI: 10.6084/m9.figshare.5104873.v1
专利: US05352694
来源说明: uspto-grants-1994_10

反应 SMILES

[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[CH:8]=[C:7]2[CH2:14][C:15]1[CH:33]=[CH:32][C:18]([C:19]([NH:21][S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])(=[O:24])=[O:23])=[O:20])=[CH:17][C:16]=1[O:34][CH3:35])(O)=[O:2].Cl.CN(C)CCCN=C=NCC.Cl.[CH3:49][C@H:50]([CH2:53][C:54]([F:57])([F:56])[F:55])[CH2:51][NH2:52]>CN(C)C1C=CN=CC=1.O1CCCC1.C(OCC)(=O)C>[CH3:35][O:34][C:16]1[CH:17]=[C:18]([CH:32]=[CH:33][C:15]=1[CH2:14][C:7]1[C:6]2[C:10](=[CH:11][CH:12]=[C:4]([C:1](=[O:2])[NH:52][CH2:51][C@H:50]([CH3:49])[CH2:53][C:54]([F:57])([F:56])[F:55])[CH:5]=2)[N:9]([CH3:13])[CH:8]=1)[C:19]([NH:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH3:31])(=[O:24])=[O:23])=[O:20]