p-Toluenesulfonic acid → di(tert-butyl) 2-[({1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indol-7-yl}sulfonyl)amino]ethyl phosphate

HRID 2238449Notes

Reaction equation

HRID 2238449 reaction equation
[P:1]([O:13][CH2:14][CH2:15][NH:16][S:17]([C:20]1[CH:37]=[CH:36][C:23]2[C:24]3[CH:25]([CH2:34][Cl:35])[CH2:26][NH:27][C:28]=3[CH:29]=[C:30]([N+:31]([O-:33])=[O:32])[C:22]=2[CH:21]=1)(=[O:19])=[O:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:38][O:39][C:40]1[CH:41]=[C:42]2[C:46](=[C:47]([O:51][CH3:52])[C:48]=1[O:49][CH3:50])[NH:45][C:44]([C:53](O)=[O:54])=[CH:43]2.CCN=C=NCCCN(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O>[P:1]([O:13][CH2:14][CH2:15][NH:16][S:17]([C:20]1[CH:37]=[CH:36][C:23]2[C:24]3[CH:25]([CH2:34][Cl:35])[CH2:26][N:27]([C:53]([C:44]4[NH:45][C:46]5[C:42]([CH:43]=4)=[CH:41][C:40]([O:39][CH3:38])=[C:48]([O:49][CH3:50])[C:47]=5[O:51][CH3:52])=[O:54])[C:28]=3[CH:29]=[C:30]([N+:31]([O-:33])=[O:32])[C:22]=2[CH:21]=1)(=[O:19])=[O:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 8210525,6,7-Trimethoxy-1H-indole-2-carboxylic acidHCID 54762391di(tert-butyl) 2-({[1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphate

Product 1

HCID 68691667di(tert-butyl) 2-[({1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indol-7-yl}sulfonyl)amino]ethyl phosphateYield 67.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 227 (77 mg, 0.13 mmol), 5,6,7-trimethoxyindole-2-carboxylic acid (44 mg, 0.17 mmol), EDCI (102 mg, 0.52 mmol), and TsOH (5 mg, 0.03 mmol) in DMA (1.5 mL) was stirred at room temperature for 2 h. Ice-cold aqueous NaHCO3 was added and the mixture was extracted with EtOAc (×2). The combined extracts were washed with brine (×2), dried, and the solution was evaporated onto silica Chromatography, eluting with EtOAc/petroleum ether (3:2 then 4:1 then EtOAc alone) gave di(tert-butyl) 2-[({1-(chloromethyl)-5-nitro-3-(5,6,7-trimethoxyindol-2-carbonyl)-1,2-dihydro-3H-benzo[e]indol-7-yl}sulfonyl)amino]ethyl phosphate (228) (71 mg, 66%) as a yellow solid. A sample was triturated with CH2Cl2: mp 231-236° C. (dec.); 1H NMR [(CD3)2SO] δ 11.60 (d, J=1.6 Hz, 1H), 9.24 (s, 1H, 8.87 (d, J=1.7 Hz, 1H), 8.44 (d, J=8.9 Hz, 1H), 8.15 (br s, 1H), 8.01 (dd, J=8.9, 1.8 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 6.98 (s, 1H), 4.96-4.90 (m, 1H), 4.68-4.59 (m, 2H), 4.18-4.07 (m, 2H), 3.95 (s, 3H), 3.87-3.82 (ni 2H), 3.84 (s, 3H), 3.81 (s, 3H), 3.10-3.04 (m, 2H), 1.36 (s, 18H). Anal, (C35H44ClN4O12PS) C, H, N.

Workup

  1. additionIce-cold aqueous NaHCO3 was added
  2. extractionthe mixture was extracted with EtOAc (×2)
  3. washThe combined extracts were washed with brine (×2)
  4. customdried
  5. customthe solution was evaporated onto silica Chromatography
  6. washeluting with EtOAc/petroleum ether (3:2

Sources & evidence

ORD record
ord-2fe3832751f74c1c9883a7258c9a6f7a
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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