1-Chloro-N,N-2-trimethylpropenylamine → HCID 89832300, compound

HRID 338121Notes

Reaction equation

HRID 338121 reaction equation
[CH2:1]([N:4]1[CH2:8][CH:7]([CH2:9]O)[C:6]([NH:17][C:18]([NH:20][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[S:19])([C:11]2[S:12][C:13]([F:16])=[CH:14][CH:15]=2)[CH2:5]1)[CH:2]=[CH2:3].ClC(N(C)C)=C(C)C>ClCCl>[CH2:1]([N:4]1[CH2:8][CH:7]2[C:6]([C:11]3[S:12][C:13]([F:16])=[CH:14][CH:15]=3)([N:17]=[C:18]([NH:20][C:21](=[O:28])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[S:19][CH2:9]2)[CH2:5]1)[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 86697922HCID 86697922, compound

Product 1

HCID 89832300HCID 89832300, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

To a stirred solution of racemic N-[[1-allyl-3-(5-fluoro-2-thienyl)-4-(hydroxymethyl)pyrrolidin-3-yl]carbamothioyl]benzamide (320 mg, 0.763 mmol) in dichloromethane (7.6 mL) at 0° C. under nitrogen is added 1-chloro-N,N,2-trimethylpropenylamine (0.2 mL, 1.53 mmol). The solution is stirred while slowly warming to 10° C. over 2 hours. The ice bath is removed and the reaction is warmed to room temperature over another 2 hours. The solution is diluted with dichloromethane (approximately 40 mL) and washed with dilute sodium bicarbonate (40 mL prepared from water (20 mL) and saturated sodium bicarbonate (20 mL)). The aqueous phase is re-extracted with dichloromethane (40 mL). The combined organic extracts are dried over sodium sulfate, filtered, and concentrated. The residue is purified by silica gel chromatography eluting with hexanes/ethyl acetate, two-step gradient from 60:40 to 50:50, to give the title compound (186 mg, 61%). ES/MS (m/e): 402 (M+H).

Workup

  1. customThe ice bath is removed
  2. temperaturethe reaction is warmed to room temperature over another 2 hours
  3. additionThe solution is diluted with dichloromethane (approximately 40 mL)
  4. washwashed with dilute sodium bicarbonate (40 mL prepared from water (20 mL) and saturated sodium bicarbonate (20 mL))
  5. extractionThe aqueous phase is re-extracted with dichloromethane (40 mL)
  6. dry with materialThe combined organic extracts are dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with hexanes/ethyl acetate, two-step gradient from 60:40 to 50:50

Sources & evidence

ORD record
ord-a1a503dae4be4163b0857d3343cbe7e9
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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