Pyridine → HCID 57636389, compound

HRID 2110356Notes

Reaction equation

HRID 2110356 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 68902973HCID 68902973, compound

Product 1

HCID 57636389HCID 57636389, compound

Reagents, catalysts & solvents 2

HCID 6329MethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,3S)-3-(1H-indol-1-yl)-3-thien-2-ylpropane-1,2-diol (250 mg, 0.91 mmol) was dissolved in pyridine (3 mL), para-toluenesulfonyl chloride (216 mg, 1.13 mmol) was added and the mixture was stirred for 2 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 360 mg that was immediately dissolved in methylamine (8M solution in ethanol, 15 mL) and stirred for 16 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 180 mg of (1S,2R)-1-(1H-indol-1-yl)-3-(methylamino)-1-(2-thienyl)propan-2-ol as a colorless oil. The freebase was dissolved in ether (5 mL) and treated with a 1N ethereal solution of hydrochloric acid (0.63 mL, 0.63 mmol, 1 equivalent). The white precipitate was collected and dried under vacuum to give 193 mg (60%) of (1S,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]+), 287.1204

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 360 mg that
  8. stirringstirred for 16 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-6b87c6fc71904966877c2c59fa282118
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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