4-((5-(((Cyclopentyloxy)carbonyl)amino)-1-methyl-1H-indol-3-yl)methyl)-3-methoxybenzoic acid → N-[4-[5-(Cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxybenzoyl]-2-(pent-1-yn-1-yl)-benzenesulfonamide

HRID 6385Notes

Reaction equation

HRID 6385 reaction equation
[C:1]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[S:12]([NH2:15])(=[O:14])=[O:13])#[C:2][CH2:3][CH2:4][CH3:5].[CH:16]1([O:21][C:22]([NH:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([CH3:34])[CH:29]=[C:28]3[CH2:35][C:36]2[CH:44]=[CH:43][C:39]([C:40](O)=[O:41])=[CH:38][C:37]=2[O:45][CH3:46])=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:16]1([O:21][C:22]([NH:24][C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([CH3:34])[CH:29]=[C:28]3[CH2:35][C:36]2[CH:44]=[CH:43][C:39]([C:40]([NH:15][S:12]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[C:1]#[C:2][CH2:3][CH2:4][CH3:5])(=[O:13])=[O:14])=[O:41])=[CH:38][C:37]=2[O:45][CH3:46])=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 112931194-((5-(((Cyclopentyloxy)carbonyl)amino)-1-methyl-1H-indol-3-yl)methyl)-3-methoxybenzoic acidHCID 197936112-(Pent-1-yn-1-yl)-benzenesulfonamide

Product 1

HCID 19793584N-[4-[5-(Cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxybenzoyl]-2-(pent-1-yn-1-yl)-benzenesulfonamideYield 74%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

1.07 g of 2-(pent-1-yn-1-yl)-benzenesulfonamide and 0.94 g of 3-[N-dimethylaminopropyl]-N-ethylcarbodiimide hydrochloride as well as 0.6 g of 4-dimethylaminopyridine are added to a solution of 2.0 g of 4-[5-(cyclopentyloxycarbonylamino)-1-methyl-indol-3-yl-methyl]-3-methoxy-benzoic acid in 50 ml of methylene chloride. The reaction mixture is stirred for 20 hours under argon and then diluted with 50 ml of methylene chloride. The methylene chloride phase is washed in a separating funnel twice with 1N hydrochloric acid and once with water. The methylene chloride phase is dried over magnesium sulfate and concentrated by evaporation at 20 torr and 40°. The residue is chromatographed on 80 g of silica gel (Merck Si60, 40-63 μm), ethyl acetate being used as eluant. The fractions containing the product are concentrated by evaporation at 20 torr and 40° to yield 2.2 g of the title compound in the form of a white amorphous solid. 1H-NMR (400 MHz, DMSO-d6): 8.76 (s, b, 1H); 8.00 (d, 1H); 7.56 (m, 2H); 7.44 (m, 4H); 7.21 (d, 1H); 7.16 (d, d, 1H); 7.08 (d, 1H); 6.91 (s, 1H); 5.07 (m, 1H); 3.94 (s, 2H); 3.88 (s, 3H); 3.66 (s, 3H); 2.33 (t, 2H); 1.90-1.53 (m, 8H); 1.47 (m, 2H); 0.89 (t, 3H).

Workup

  1. washThe methylene chloride phase is washed in a separating funnel twice with 1N hydrochloric acid and once with water
  2. dry with materialThe methylene chloride phase is dried over magnesium sulfate
  3. concentrationconcentrated by evaporation at 20 torr and 40°
  4. customThe residue is chromatographed on 80 g of silica gel (Merck Si60, 40-63 μm), ethyl acetate being
  5. additionThe fractions containing the product
  6. concentrationare concentrated by evaporation at 20 torr and 40°

Sources & evidence

ORD record
ord-6fd576943ae3459bb74deb1e7f415740
Source dataset
uspto-grants-1993_09
Patent number
US05248693

Reaction notes

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