Diisopropylethylamine → HCID 178468423, compound

HRID 1855673Notes

Reaction equation

HRID 1855673 reaction equation
C(N(C(C)C)CC)(C)C.Cl[C:11]([O:13][C:14]1[CH:19]=[CH:18][C:17]([N+]([O-])=O)=[CH:16][CH:15]=1)=O.[NH2:23][C@H:24]([CH2:44]C1C=CC(OC)=CC=1)[C:25]([N:27]1[CH2:32][CH2:31][C:30]([C:39](=[O:43])CCC)([CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:29][CH2:28]1)=[O:26].F[C:54](F)(F)[C:55]([OH:57])=O.FC(F)(F)[C:62]([OH:64])=O.[NH:67]1[CH:71]=[C:70]([CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][NH2:77])[N:69]=[CH:68]1>C(Cl)Cl.CN(C=O)C.O>[CH:33]1([C:30]2([C:39]([O:57][CH2:55][CH3:54])=[O:43])[CH2:31][CH2:32][N:27]([C:25](=[O:26])[C@H:24]([NH:23][C:62]([NH:77][CH2:76][CH2:75][CH2:74][CH2:73][CH2:72][C:70]3[N:69]=[CH:68][NH:67][CH:71]=3)=[O:64])[CH2:44][C:17]3[CH:18]=[CH:19][C:14]([O:13][CH3:11])=[CH:15][CH:16]=3)[CH2:28][CH2:29]2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 669876811-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-oneHCID 178510967HCID 178510967, compound

Product 1

HCID 178468423HCID 178468423, compoundYield 13.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

16 μL of diisopropylethylamine and 10 mg (51 μmol) of 4-nitrophenyl chloroformate are added to 25 mg (47 μmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-one (cf. preparation 4.4) dissolved in 5 ml of DCM. The reaction mixture is stirred for 2 hours at room temperature. The reaction is stopped by adding water and the organic compounds are extracted with DCM. The organic phase is then dried over MgSO4, filtered and concentrated. The oil obtained is dissolved in 5 ml of DMF at 80° C., and 14 mg of 5-(1H-imidazol-4-yl)pentylamine bis(trifluoroacetate) are added. The reaction mixture is stirred at 80° C. for 5 minutes and for 18 hours at room temperature. The organic phase is washed with 1N sodium hydroxide, extracted with dichloromethane and then dried over MgSO4, filtered and concentrated. The crude product obtained is purified by preparative HPLC. 3 mg of ethyl 4-cyclohexyl-1-[(R)-2-{3-[5-(1H-imidazol-4-yl)pentyl]ureido}-3-(4-methoxy-phenyl)propionyl]piperidine-4-carboxylate are obtained in a yield of 10%.

Workup

  1. extractionthe organic compounds are extracted with DCM
  2. dry with materialThe organic phase is then dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe oil obtained
  6. stirringThe reaction mixture is stirred at 80° C. for 5 minutes and for 18 hours at room temperature
  7. washThe organic phase is washed with 1N sodium hydroxide
  8. extractionextracted with dichloromethane
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product obtained
  13. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-8d5ec75034094f21a684d0e42cbc57cf
Source dataset
uspto-grants-2015_02
Patent number
US08962846B2

Reaction notes

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