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

HRID 2238450Notes

Reaction equation

HRID 2238450 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].Cl.[CH3:39][N:40]([CH3:56])[CH2:41][CH2:42][O:43][C:44]1[CH:45]=[C:46]2[C:50](=[CH:51][CH:52]=1)[NH:49][C:48]([C:53](O)=[O:54])=[CH:47]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:48]4[NH:49][C:50]5[C:46]([CH:47]=4)=[CH:45][C:44]([O:43][CH2:42][CH2:41][N:40]([CH3:56])[CH3:39])=[CH:52][CH:51]=5)=[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 54762391di(tert-butyl) 2-({[1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphateHCID 686908585-[2-(Dimethylamino)ethoxy]indole-2-carboxylic acid hydrochloride

Product 1

HCID 68688878di(tert-butyl) 2-({[1-(chloromethyl)-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphateYield 88%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 227 (351 mg, 0.61 mmol), 5-[2-(dimethylamino)ethoxy]indole-2-carboxylic acid hydrochloride (225 mg, 0.79 mmol), EDCI (466 mg, 2.4 mmol) and TsOH (21 mg, 0.12 mmol) in DMA (3 mL) was stirred at room temperature for 3.5 h and then cooled to 0° C. Ice-cold aqueous NaHCO3 was added, and the resulting precipitate was filtered off, washed with aqueous NaHCO3 and water, and dried. Trituration with acetone gave di(tert-butyl) 2-({[1-(chloromethyl)-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphate (229) (433 mg, 88%) as a yellow solid: mp 220-225° C. (dec.); 1H NMR [(CD3)2SO] δ 11.73 (s, 1H), 9.30 (s, 1H), 8.87 (d, J=1.7 Hz, 1H), 8.45 (d, J=8.9 Hz, 1H), 8.16 (br s, 1H), 8.02 (dd, J=8.9, 1.7 Hz, 1H), 7.42 (d, J=8.9 Hz, 1H), 7.22 (d, J=1.6 Hz, 1H), 7.18 (d, J=2.4 Hz, 1H), 6.96 (dd, J=−8.9, 2.4 Hz, 1H), 5.00-4.94 (m, 1H), 4.73 (dd, J=11.0, 2.4 Hz, 1H), 4.68-4.62 (m, 1H), 4.19-4.11 (m, 2H), 4.07 (t, J=5.9 Hz, 2H), 3.87-3.80 (m, 2H), 3.08-3.03 (m, 2H), 2.66 (t, J=5.9 Hz, 2H), 2.24 (s, 6H), 1.36 (s, 18H. Anal. (C36H47ClN5O10PS.½H2O) C, H, N.

Workup

  1. temperaturecooled to 0° C
  2. additionIce-cold aqueous NaHCO3 was added
  3. filtrationthe resulting precipitate was filtered off
  4. washwashed with aqueous NaHCO3 and water
  5. customdried

Sources & evidence

ORD record
ord-b67993ad2067494a97bc84f349f1578b
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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