Ethanolamine → 1-(chloromethyl)-N-(2-hydroxyethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide

HRID 2238378Notes

Reaction equation

HRID 2238378 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16](Cl)(=[O:18])=[O:17])=[CH:15][C:9]=3[C:8]([N+:20]([O-:22])=[O:21])=[CH:7][C:6]=2[N:5](C(=O)C(F)(F)F)[CH2:4]1.C(Cl)Cl.[CH2:32]([CH2:34][NH2:35])[OH:33].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CO.O>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16]([NH:35][CH2:34][CH2:32][OH:33])(=[O:18])=[O:17])=[CH:15][C:9]=3[C:8]([N+:20]([O-:22])=[O:21])=[CH:7][C:6]=2[NH:5][CH2:4]1

Participants

8

Reactant 4

HCID 700EthanolamineHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 866202591-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonyl chloride

Product 1

HCID 686939191-(chloromethyl)-N-(2-hydroxyethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-sulfonamideYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(Scheme C). A solution of 116 (456 mg, 1.00 mmol) in TV (5 mL) and CH2Cl2 (5 mL) was treated at 0° C. with a solution of ethanolamine (134 mg, 2.19 mmol) in THF (0.5 mL). The mixture was stirred at 0° C. for 5 min, then warmed to room temperature for 10 min and treated with a solution of Cs2CO3 (980 mg, 3 mmol) in MeOH (20 mL). After stirring at room temperature for a further 10 min, the mixture was diluted with water and extracted with EtOAc (×2). The combined organic layers were washed with water (×2), dried, filtered through a short column of silica gel, and then concentrated to a small volume and diluted with i-Pr2O/hexane to give 1-(chloromethyl)-N-(2-hydroxyethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indole-7-sulfonamide (121) (346 mg, 90%): mp 173-174° C.; 1H NMR [(CD3)2SO] δ 8.57 (d, J=1.6 Hz, 1H), 8.03 (d, J=8.9 Hz, 1H), 7.80 (dd, J=8.9, 1.7 Hz, 1H), 7.77 (s, 1H), 7.69 (br s, 1H), 6.73 (s, 1H), 4.64 (t, J=5.6 Hz, 1H), 4.29-4.19 (m, 1H), 3.95-3.84 (m, 2H), 3.80 (dd, J=11.0, 8.4 Hz, 1H), 3.74 (dd, J=10.4, 3.3 Hz, 1H), 3.35 (after D2O exchange, t, J=6.3 Hz, 2H), 2.81 (t, J=6.3 Hz, 2H). Anal. (C15H16C11N3O5S) C, H, N.

Workup

  1. temperaturewarmed to room temperature for 10 min
  2. stirringAfter stirring at room temperature for a further 10 min
  3. extractionextracted with EtOAc (×2)
  4. washThe combined organic layers were washed with water (×2)
  5. customdried
  6. filtrationfiltered through a short column of silica gel
  7. concentrationconcentrated to a small volume
  8. additiondiluted with i-Pr2O/hexane

Sources & evidence

ORD record
ord-0c73c8e28f594e21a470962afe1e89fe
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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