Triethylamine → N-[3-(9H-Carbazol-9-yl)-2-hydroxypropyl]-N-[(furan-2-yl)methyl]methanesulfonamide

HRID 1776253Notes

Reaction equation

HRID 1776253 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH:6]1[C:18]2[N:17]([CH2:19][CH:20]([OH:29])[CH2:21][NH:22][CH2:23][C:24]3[O:25][CH:26]=[CH:27][CH:28]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]=2[CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C>C(Cl)Cl>[CH:15]1[C:16]2[N:17]([CH2:19][CH:20]([OH:29])[CH2:21][N:22]([CH2:23][C:24]3[O:25][CH:26]=[CH:27][CH:28]=3)[S:2]([CH3:1])(=[O:4])=[O:3])[C:18]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:11]=2[CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 6526521-Carbazol-9-yl-3-[(furan-2-ylmethyl)-amino]-propan-2-ol

Product 1

HCID 2888648N-[3-(9H-Carbazol-9-yl)-2-hydroxypropyl]-N-[(furan-2-yl)methyl]methanesulfonamideYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.650 mL, 8.4 mmol) was added dropwise to a cold stirring solution of 1-(9H-carbazol-9-yl)-3-((furan-2-ylmethyl)amino)propan-2-ol (2.7 g, 8.4 mmol) and triethylamine (1.3 mL, 9.2 mmol) in anhydrous methylene chloride (55 mL), which was kept at 0-5° C. with an external ice bath. The solution was stirred at 0° C. for 2 hours and then diluted with methylene chloride and successively washed with 0.25N aqueous hydrochloric acid twice, water, and saturated aqueous sodium chloride. The organics were dried (anhydrous sodium sulfate), filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (0-10% ethyl acetate in methylene chloride) to give the desired product as a white solid (1.5 g, 45%). 1H NMR (d6-DMSO, 300 MHz) δ 8.09-8.06 (d, 2H, J=8.1 Hz), 7.42-7.37 (m, 5H), 7.18-7.14 (m, 2H), 6.37-6.35 (dd, 1H, J=1.8, 3 Hz), 6.31-6.30 (d, 1H, J=3 Hz), 4.52-4.39 (dd, 2H, J=15.9, 24.6 Hz), 4.39-4.30 (dd, 1H, J=3.3, 14.4 Hz), 4.22-4.10 (m, 1H), 4.20-4.05 (br m, 1H), 3.40-3.33 (m, 1H) 3.26-3.17 (m, 1H), 2.90 (s, 3H). ESI (m/z): 398.9 (M+H). HPLC analysis: (C18, 10-90% acetonitrile in water+0.1% trifluoroacetic acid over 10 min: retention time, % area at 254 nm): 8.6 min, 97.9%.

Workup

  1. customwas kept at 0-5° C. with an external ice bath
  2. washsuccessively washed with 0.25N aqueous hydrochloric acid twice
  3. dry with materialThe organics were dried (anhydrous sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by silica gel column chromatography (0-10% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-a2e67d32fa2c4a73a0fdd99746872470
Source dataset
uspto-grants-2016_02
Patent number
US09265772B2

Reaction notes

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