Dichloromethane → (E)-4-Methyl-1-[(3S)-3-(4-quinolylamino)pyrrolidin-1-yl]pent-2-en-1-one

HRID 333940Notes

Reaction equation

HRID 333940 reaction equation
[NH:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)[CH2:2]1.C(N(CC)CC)C.ClCCl.[CH3:27][CH:28]([CH3:34])/[CH:29]=[CH:30]/[C:31](Cl)=[O:32].ClCCl.C1(C)C(S(Cl)(=O)=O)=CC=CC=1>>[CH3:27][CH:28]([CH3:34])/[CH:29]=[CH:30]/[C:31]([N:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)[CH2:2]1)=[O:32]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8623o-Toluenesulfonyl chlorideHCID 10986269(E)-4-methylpent-2-enoyl ChlorideHCID 21882572Triethylamine methylene chlorideHCID 66835796N-[(3S)-Pyrrolidin-3-yl]quinolin-4-amine

Product 1

HCID 56948960(E)-4-Methyl-1-[(3S)-3-(4-quinolylamino)pyrrolidin-1-yl]pent-2-en-1-oneYield 39%

Procedure

To N-[(3S)-Pyrrolidin-3-yl]quinolin-4-amine (32 mg, 0.15 mmol) dissolved in 1.5 ml anhydrous dichloromethane triethylamine (0.9 mmol, 91 mg) was added with stirring followed by (E)-4-methylpent-2-enoyl chloride dissolved in anhydrous dichloromethane (29.8 mg, 0.23 mmol). The mixture was stirred at room temperature for 5 minutes after which polymer-supported toluenesulfonyl chloride (600 mg, 1-2 mmol/g) was added and the mixture was shaken for 15 minutes, filtered and the filtrate evaporated to dryness under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield 18 mg of a solid (0.58 mmol, 39%).

Workup

  1. additionwas added
  2. additionwas added
  3. stirringthe mixture was shaken for 15 minutes
  4. filtrationfiltered
  5. customthe filtrate evaporated to dryness under reduced pressure
  6. customThe raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

Sources & evidence

ORD record
ord-920f4f85a70e48439c2c4dcfabcd2c2c
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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