Triethylamine → HCID 178450013, compound

HRID 1855660Notes

Reaction equation

HRID 1855660 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[NH2:14][C@H:15]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)[C:16]([N:18]1[CH2:23][CH2:22][C:21]([C:30](=[O:34])[CH2:31][CH2:32][CH3:33])([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:20][CH2:19]1)=[O:17].[NH4+].[OH-].Cl.Cl.[NH:48]1[CH:52]=[C:51]([CH2:53][CH2:54][NH2:55])[N:50]=[N:49]1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[C:30]([C:21]1([CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:22][CH2:23][N:18]([C:16](=[O:17])[C@H:15]([NH:14][C:2]([NH:55][CH2:54][CH2:53][C:51]2[N:50]=[N:49][NH:48][CH:52]=2)=[O:3])[CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[CH2:19][CH2:20]1)(=[O:34])[CH2:31][CH2:32][CH3:33]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 669876811-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-oneHCID 178478693HCID 178478693, compound

Product 1

HCID 178450013HCID 178450013, compoundYield 32.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

30 mg (0.15 mmol) of 4-nitrophenyl chloroformate are added, at 0° C., to 57 mg (0.14 mmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-one (cf. preparation 2-3) dissolved in 2 ml of DCM. The reaction mixture is stirred for 4 hours at room temperature. The reaction is stopped by adding aqueous NH4OH solution and the organic compounds are extracted with DCM. The organic phase is then washed with water and dried over MgSO4, filtered and concentrated. The oil obtained is dissolved in DMF at 80° C., and 52 mg (0.28 mmol) of 2-(1H-[1,2,3]triazol-4-yl)ethylamine dihydrochloride and 0.1 ml (0.72 mmol) of triethylamine are then added. The reaction mixture is stirred at 80° C. for 10 minutes. After cooling to room temperature, dichloromethane is added and the organic phase is washed with 1N sodium hydroxide. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 93/7 DCM/MeOH). 25 mg of 1-[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-[2-(1H-[1,2,3]triazol-4-yl)ethyl]urea are obtained in the form of a white solid in a yield of 32%.

Workup

  1. extractionthe organic compounds are extracted with DCM
  2. washThe organic phase is then washed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe oil obtained
  7. stirringThe reaction mixture is stirred at 80° C. for 10 minutes
  8. temperatureAfter cooling to room temperature
  9. washthe organic phase is washed with 1N sodium hydroxide
  10. dry with materialThe organic phase is dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product obtained
  14. customis chromatographed on silica gel (eluent: 93/7 DCM/MeOH)

Sources & evidence

ORD record
ord-05203183a6e44d29a84b7a19b795d2fb
Source dataset
uspto-grants-2015_02
Patent number
US08962846B2

Reaction notes

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