Diisopropylethylamine → HCID 44463544, compound

HRID 1881693Notes

Reaction equation

HRID 1881693 reaction equation
O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:23]=1[S:29]([N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[CH2:38][CH2:39][CH2:40][C:41](O)=[O:42])(=[O:31])=[O:30].Cl.CN(C)CCCN=C=NCC.Cl.Cl.[N:58]1([CH2:63][CH2:64][O:65][C:66]2([C:72]3[CH:73]=[N:74][CH:75]=[CH:76][CH:77]=3)[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]2)[CH2:62][CH2:61][CH2:60][CH2:59]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:23]=1[S:29]([N:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[CH2:38][CH2:39][CH2:40][C:41]([N:69]1[CH2:70][CH2:71][C:66]([C:72]2[CH:73]=[N:74][CH:75]=[CH:76][CH:77]=2)([O:65][CH2:64][CH2:63][N:58]2[CH2:59][CH2:60][CH2:61][CH2:62]2)[CH2:67][CH2:68]1)=[O:42])(=[O:30])=[O:31]

Participants

9

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57904137HCID 57904137, compoundHCID 67367355HCID 67367355, compound

Product 1

HCID 44463544HCID 44463544, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-Hydroxybenzotriazole hydrate (HOBT) (0.022 g, 0.168 mmol, 0.3 eq.) and N-ethyl-diisopropylamine (0.285 ml, 1.68 mmol, 3 eq.) were added to a solution of 4-(1-(2-chloro-6-methylphenylsulfonyl)piperidin-2-yl)butanoic acid (0.252 g, 0.7 mmol, 1.25 eq.) in methylene chloride (7 ml). The mixture was cooled to 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (0.161 g, 0.84 mmol, 1.5 eq.) was added and the mixture was stirred for 15 min. 3-(4-(2-(Pyrrolidin-1-yl)ethoxy)piperidin-4-yl)pyridine dihydrochloride (0.195 g, 0.56 mmol, 1 eq.) was then added. The reaction mixture was stirred at room temperature for 72 h. For working up, sat. sodium bicarbonate solution was added to the mixture and the mixture was diluted with ethyl acetate. The phases were separated, and the aqueous phase was extracted 2× with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography [Alox Neutral (25 g), ethyl acetate 100%→ethyl acetate/methanol 95:5]. The desired product was obtained as a yellow-white solid in a yield of 61% (0.212 g).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 72 h
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted 2× with ethyl acetate
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography [Alox Neutral (25 g), ethyl acetate 100%→ethyl acetate/methanol 95:5]

Sources & evidence

ORD record
ord-f185035b73284eb580e20b5d34d42323
Source dataset
uspto-grants-2012_11
Patent number
US08318769B2

Reaction notes

Loading…