p-Toluenesulfonic acid → 1-(Chloromethyl)-N-(2-hydroxyethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide

HRID 2238379Notes

Reaction equation

HRID 2238379 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16]([NH:19][CH2:20][CH2:21][OH:22])(=[O:18])=[O:17])=[CH:15][C:9]=3[C:8]([N+:23]([O-:25])=[O:24])=[CH:7][C:6]=2[NH:5][CH2:4]1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:34](=[C:35]([O:39][CH3:40])[C:36]=1[O:37][CH3:38])[NH:33][C:32]([C:41](O)=[O:42])=[CH:31]2.CCN=C=NCCCN(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>CO.Cl.O.CC(N(C)C)=O>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16]([NH:19][CH2:20][CH2:21][OH:22])(=[O:17])=[O:18])=[CH:15][C:9]=3[C:8]([N+:23]([O-:25])=[O:24])=[CH:7][C:6]=2[N:5]([C:41]([C:32]2[NH:33][C:34]3[C:30]([CH:31]=2)=[CH:29][C:28]([O:27][CH3:26])=[C:36]([O:37][CH3:38])[C:35]=3[O:39][CH3:40])=[O:42])[CH2:4]1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 8210525,6,7-Trimethoxy-1H-indole-2-carboxylic acidHCID 686939191-(chloromethyl)-N-(2-hydroxyethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide

Product 1

HCID 115201021-(Chloromethyl)-N-(2-hydroxyethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonamideYield 75.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 31374DimethylacetamideSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

Amine 121 (75 mg, 0.19 mmol) was dissolved in MeOH/HCl(g) at room temperature and the solution was evaporated to dryness under reduced pressure. 5,6,7-Trimethoxyindole-2-carboxylic acid (59 mg, 0.23 mmol), EDCI (149 mg, 0.78 mmol), anhydrous TsOH (30 mg, 0.17 mmol) and dry DMA (3 mL) were then added, and the mixture was stirred at room temperature for 1 h. The mixture was poured into water and the precipitate was collected and washed with water, dried, and dissolved in the minimum volume of DMW at room temperature. The solution was diluted with EtOAc, filtered, and then diluted with hexane and refrigerated to give 33 (89 mg, 74%): mp 257-258° C.; 1H NMR [(CD3)2SO] δ 11.61 (s, 1H), 9.24 (s, 1H), 8.86 (d, J=1.6 Hz, 1H), 8.43 (d, J=8.9 Hz, 1H), 8.02 (dd, J=8.9, 1.7 Hz, 1H), 7.91 (t, J=5.7 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 6.99 (s, 1H), 4.93 (t, J=10.1 Hz, 1H), 4.70-4.58 (m, 3H), 4.18-4.07 (m, 2H), 3.94 (s, 3H), 3.83 (s, 3H), 3.81 (s, 3H, 3.39 (q, J=6.0 Hz, 2H), 2.88 (q, J=6.1 Hz, 2H). Anal. (C27H27ClN4O9S) C, H, N.

Workup

  1. customthe solution was evaporated to dryness under reduced pressure
  2. customthe precipitate was collected
  3. washwashed with water
  4. customdried
  5. dissolutiondissolved in the minimum volume of DMW at room temperature
  6. additionThe solution was diluted with EtOAc
  7. filtrationfiltered
  8. additiondiluted with hexane

Sources & evidence

ORD record
ord-e55594df8b15440095410522239aaa46
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

Loading…