Ammonia → tert-butyl 1-(chloromethyl)-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-carbamate

HRID 2238445Notes

Reaction equation

HRID 2238445 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:15][C:9]=3[C:8]([N+:24]([O-:26])=[O:25])=[CH:7][C:6]=2[NH:5][CH2:4]1.Cl.[CH3:28][N:29]([CH3:45])[CH2:30][CH2:31][O:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][C:37]([C:42](O)=[O:43])=[CH:36]2.CCN=C=NCCCN(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.N>CC(N(C)C)=O>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])=[CH:15][C:9]=3[C:8]([N+:24]([O-:26])=[O:25])=[CH:7][C:6]=2[N:5]([C:42]([C:37]2[NH:38][C:39]3[C:35]([CH:36]=2)=[CH:34][C:33]([O:32][CH2:31][CH2:30][N:29]([CH3:45])[CH3:28])=[CH:41][CH:40]=3)=[O:43])[CH2:4]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 686908585-[2-(Dimethylamino)ethoxy]indole-2-carboxylic acid hydrochlorideHCID 68696256tert-butyl 1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-carbamate

Product 1

HCID 68693579tert-butyl 1-(chloromethyl)-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-carbamateYield 75%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 222 (75 mg, 0.20 mmol), 5-[2-(dimethylamino)ethoxy]indole-2-carboxylic acid hydrochloride (73 mg, 0.26 mmol), EDCI (152 mg, 0.79 mmol) and TsOH (5 mg, 0.03 mmol) in DMA (1.5 mL) was stirred at room temperature for 1 h, then poured into dilute aqueous NH3. The precipitate was collected, washed with water, and dissolved in CH2Cl2 (250 mL). The solution was dried, filtered, concentrated under reduced pressure to a small volume, and then diluted with i-Pr2O to give tert-butyl 1-(chloromethyl)-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-carbamate (223) (91 mg, 75%) as a yellow solid: mp (THF/CH2Cl2/hexane)>250° C.; 1H NMR [(CD3)2SO] δ 11.67 (d, J=1.6 Hz, 1H), 9.85 (s, 1H), 9.12 (s, 1H), 8.69 (d, J=1.9 Hz, 1H), 8.14 (d, J=9.2 Hz, 1H), 7.79 (dd, J=9.2, 2.0 Hz, 1H), 7.41 (d, J=−8.9 Hz, 1H), 7.18 (d, J=2.3 Hz, 1H), 7.15 (d, J=1.7 Hz, 1H), 6.93 (dd, J=8.9, 2.4 Hz, 1H), 4.90 (t, J=10.2 Hz, 1H), 4.67 (dd, J=10.9, 2.4 Hz, 1H), 4.58-4.51 (m, 1H), 4.16-4.03 (m, 4H), 2.66 (t, J=5.8 Hz, 2H), 2.24 (s, 6H), 1.53 (s, 9H). Anal. (C31H34ClN5O6) C, H, N.

Workup

  1. customThe precipitate was collected
  2. washwashed with water
  3. dissolutiondissolved in CH2Cl2 (250 mL)
  4. customThe solution was dried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure to a small volume
  7. additiondiluted with i-Pr2O

Sources & evidence

ORD record
ord-accf1ce9b5a948559eb073d0eb728aee
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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