Diisopropylethylamine → HCID 22709446, compound

HRID 352982Notes

Reaction equation

HRID 352982 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](S(C1C=CC=CC=1)(=O)=O)[C:6]([S:20]([N:23]1[CH2:28][CH2:27][NH:26][CH:25]([CH2:29][CH2:30][CH2:31][C:32]3[S:33][CH:34]=[CH:35][CH:36]=3)[CH2:24]1)(=[O:22])=[O:21])=[CH:5]2.[CH3:37][CH:38]1[NH:43][CH2:42][C:41]2[S:44][C:45]([C:47]([O-])=[O:48])=[N:46][C:40]=2[CH2:39]1.[Li+].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([S:20]([N:23]1[CH2:28][CH2:27][N:26]([C:47]([C:45]3[S:44][C:41]4[CH2:42][NH:43][CH:38]([CH3:37])[CH2:39][C:40]=4[N:46]=3)=[O:48])[CH:25]([CH2:29][CH2:30][CH2:31][C:32]3[S:33][CH:34]=[CH:35][CH:36]=3)[CH2:24]1)(=[O:21])=[O:22])=[CH:5]2

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22709756HCID 22709756, compoundHCID 23674323Lithium 6-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

Product 1

HCID 22709446HCID 22709446, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (15 ml) were dissolved 1-[(5-chloro-1-phenylsulfonylindol-2-yl)sulfonyl]-3-[3-(thien-2-yl)propyl]piperazine (257 mg), lithium 6-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (129 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (131 mg) and 1-hydroxybenzotriazole hydrate (76.4 mg). Under ice cooling, diisoproylethylamine (180 μl) was added dropwise to the resulting solution, followed by stirring at room temperature for 15.5 hours. The reaction mixture was extracted with methylene chloride and water. The organic layer was washed with saturated aqueous NaCl solution, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was subjected to column chromatography (2% methanol—methylene chloride) using as a carrier silica gel. After conversion into the corresponding hydrochloride by the addition of 1N aqueous hydrochloric acid in ethanol, methylene chloride-methanol-ether was added to solidify the hydrochloride. The resulting solid was purified again by subjecting it to thin-layer chromatography (10% methanol—methylene chloride), followed by the addition of 1N aqueous hydrochloric acid in ethanol to form the corresponding hydrochloride. Methylene chloride-methanol-ether was added to solidify the hydrochloride. The resulting solid was collected by filtration, washed with ether and then dried, whereby the title compound (62.6 mg) was obtained as colorless powder.

Workup

  1. extractionThe reaction mixture was extracted with methylene chloride and water
  2. washThe organic layer was washed with saturated aqueous NaCl solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. additionAfter conversion into the corresponding hydrochloride by the addition of 1N aqueous hydrochloric acid in ethanol, methylene chloride-methanol-ether
  7. additionwas added
  8. customThe resulting solid was purified again
  9. additionfollowed by the addition of 1N aqueous hydrochloric acid in ethanol

Sources & evidence

ORD record
ord-f8eac9e9f51049408cff41e5a2d732fb
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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