Diisopropylethylamine → 1-(3-benzylimidazolidin-1-yl)-3-(5-chloro-1H-indol-3-yl)propan-1-one

HRID 1918766Notes

Reaction equation

HRID 1918766 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C:13]([O:15]C(C)(C)C)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[C:24]2[CH2:30][CH2:31]C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>FC(F)(F)C(O)=O.ClCCl.CN(C=O)C>[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C:13](=[O:15])[CH2:31][CH2:30][C:24]2[C:23]3[C:27](=[CH:28][CH:29]=[C:21]([Cl:20])[CH:22]=3)[NH:26][CH:25]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 1857801H-Indole-3-propanoic acid, 5-chloro-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11436961Tert-butyl 3-benzylimidazolidine-1-carboxylate

Product 1

HCID 668316861-(3-benzylimidazolidin-1-yl)-3-(5-chloro-1H-indol-3-yl)propan-1-oneYield 7.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

The tert-butyl 3-benzylimidazolidine-1-carboxylate (0.122 g; 0.465 mmol) was dissolved in a mixture of trifluoroacetic acid (4 mL) and dichloromethane (6 mL), stirred at room temperature for 2 hours and concentrated under reduced pressure. The residue was dissolved in dichloromethane and added to a mixture of 3-(5-chloro-1H-indol-3-yl)propanoic acid (0.080 g; 0.358 mmol), HATU (0.150 g; 0.393 mmol), N,N diisopropylethylamine (0.152 mL; 0.894 mmol) in dichloromethane (5 mL) and DMF (1 mL) and stirred at room temperature overnight. The reaction mixture was concentrated underreduced pressure and dissolved in ethyl acetate, washed with sodium hydrogen sulphate, sodium carbonate, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (0 to 10% MeOH in dichloromethane) and by preparative HPLC method 4 to yield 0.0097 g (7%) of 1-(3-benzylimidazolidin-1-yl)-3-(5-chloro-1H-indol-3-yl)propan-1-one as a solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane
  3. stirringstirred at room temperature overnight
  4. concentrationThe reaction mixture was concentrated underreduced pressure
  5. dissolutiondissolved in ethyl acetate
  6. washwashed with sodium hydrogen sulphate, sodium carbonate
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe crude mixture was purified by flash chromatography on silica (0 to 10% MeOH in dichloromethane) and by preparative HPLC method 4

Sources & evidence

ORD record
ord-24f37f36f6184227a198aa90142bec9b
Source dataset
uspto-grants-2013_12
Patent number
US08618138B2

Reaction notes

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