Pyridine → HCID 57636360, compound

HRID 2110359Notes

Reaction equation

HRID 2110359 reaction equation
[N:1]1([C@@H:10]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)[C@H:11]([OH:14])[CH2:12]O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[N:31]1C=CC=C[CH:32]=1>C(OCC)(=O)C.CN>[N:1]1([C@@H:10]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)[C@H:11]([OH:14])[CH2:12][NH:31][CH3:32])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 73974-Toluenesulfonyl chlorideHCID 68906941HCID 68906941, compound

Product 1

HCID 57636360HCID 57636360, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6329MethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,3R)-3-(1H-indol-1-yl)-3-thien-2-ylpropane-1,2-diol (102 mg, 0.37 mmol) was dissolved in pyridine (1.5 mL), para-toluenesulfonyl chloride (88 mg, 0.46 mmol) was added and the mixture was stirred for 16 hours. The mixture was diluted with ethyl acetate and washed with water, a saturated aqueous solution of copper sulfate, and saturated brine. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Isco chromatography (Redisep, silica, gradient 0%-100% ethyl acetate in hexane) to afford 140 mg that was immediately dissolved in methylamine (8M solution in ethanol, 15 mL) and stirred for 3 hours. The mixture was concentrated in vacuo and purified via flash column chromatography (silica, gradient 2%-10% methanol saturated with ammonia in chloroform) to give 65 mg (71%) of (1R,2R)-1-(1H-indol-1-yl)-3-(methylamino)-1-(2-thienyl)propan-2-ol as a colorless oil. The freebase was dissolved in diethyl ether (5 mL) and treated with a 1 N ethereal solution of hydrochloric acid (0.23 mL, 0.23 mmol, 1 equivalent). The white precipitate was collected and dried under vacuum to give (1R,2R)-1-(1H-indol-1-yl)-3-(methylamino)-1-(2-thienyl)propan-2-ol hydrochloride. HRMS: calcd for C16H18N2OS+H+, 287.12126; found (ESI, [M+H]+), 287.1209

Workup

  1. washwashed with water
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified via Isco chromatography (Redisep, silica, gradient 0%-100% ethyl acetate in hexane)
  7. customto afford 140 mg that
  8. stirringstirred for 3 hours
  9. concentrationThe mixture was concentrated in vacuo
  10. custompurified via flash column chromatography (silica, gradient 2%-10% methanol saturated with ammonia in chloroform)

Sources & evidence

ORD record
ord-8eb5f8588b744709a5fc1f161a725c14
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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