Triethylamine → HCID 24954947, compound

HRID 1661453Notes

Reaction equation

HRID 1661453 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][C:25]([S:28][CH3:29])=[CH:24][CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:37]1([S:40](Cl)(=[O:42])=[O:41])[CH2:39][CH2:38]1>CC#N>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:23]=[CH:24][C:25]([S:28][CH3:29])=[CH:26][CH:27]=4)[C@@H:19]([NH:21][S:40]([CH:37]4[CH2:39][CH2:38]4)(=[O:42])=[O:41])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 2760919Cyclopropanesulfonyl chloride2×HCID 59339703HCID 59339703, compound

Product 1

HCID 24954947HCID 24954947, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine (29a, 100 mg, 0.24 mmol) was dissolved in MeCN (3 mL), triethylamine (0.104 mL, 0.75 mmol) was added followed by addition of cyclopropane sulfonylchloride (0.025 mL, 0.25 mmol). The reaction was followed by LC/MS. After 1 hour approximately 50% conversion was detected, more reagents cyclopropane sulfonylchloride (0.025 mL, 0.25 mmol) and triethylamine (0.07 mL, 0.50 mmol) were added in an attempt to increase conversion without any success. The reaction was quenched by addition of saturated NH4Cl (aq) and concentrated. The residual material was purified by HPLC, collected fractions was freeze dried to give the title compound as a colourless solid. Chiral HPLC was made using an Chiralpak IB™, 150×0.46 mm column, 15% EtOH in iso-Hexane, 0.5 mL/min, UV=254 nm, one major peak at 32.39 min (99.7%) and one minor peak at 30.69 min (0.3%).

Workup

  1. waitAfter 1 hour approximately 50% conversion was detected
  2. temperatureto increase conversion without any success
  3. customThe reaction was quenched by addition of saturated NH4Cl (aq)
  4. concentrationconcentrated
  5. customThe residual material was purified by HPLC
  6. customcollected fractions
  7. customdried

Sources & evidence

ORD record
ord-d77baed8239445c3b4991463fb9a6c4f
Source dataset
uspto-grants-2011_10
Patent number
US08030340B2

Reaction notes

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