Piperidine → HCID 88140646, compound

HRID 850867Notes

Reaction equation

HRID 850867 reaction equation
C1C2C(COC([NH:18][C@H:19]([C:24]([NH:26][C@H:27]([CH:31]([O:34][CH3:35])[O:32][CH3:33])[CH2:28][C:29]#[CH:30])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=O)C3C(=CC=CC=3)C=2C=CC=1.N1CCCC[CH2:37]1.C1C2[CH:53]([CH2:55][O:56][C:57]([NH:59][C@H:60]([C:66]([OH:68])=O)[CH:61]([CH3:65])[CH:62](C)C)=[O:58])[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)C=2C=CC=1.O[C:70]1[C:78]2N=NN[C:74]=2[CH:73]=[CH:72][CH:71]=1.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH:70]1[C:78]2[CH:53]([CH2:55][O:56][C:57]([NH:59][C@H:60]([C:66]([NH:18][C@H:19]([C:24]([NH:26][C@H:27]([CH:31]([O:32][CH3:33])[O:34][CH3:35])[CH2:28][C:29]#[CH:30])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[O:68])[C:61]([CH3:62])([CH3:65])[CH3:37])=[O:58])[C:52]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:74]=2[CH:73]=[CH:72][CH:71]=1

Participants

7

Reactant 5

HCID 8082PiperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54326944HCID 54326944, compoundHCID 86755094HCID 86755094, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 88140646HCID 88140646, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

525 mg (1.1 mmol) of N2-[(9-fluorenyl)methoxycarbonyl]-N1-[1(S)-(dimethoxymethyl)-3-butynyl]-L-leucinamide were dissolved in 20 ml of dichloromethane and 5 ml of piperidine and the mixture was stirred at room temperature for 30 minutes. The mixture was evaporated to dryness and the residue was chromatographed on silica gel using firstly ethyl acetate/petrol (1:1) and then methanol/dichloromethane (1:9) for the elution. Evaporation of the dichloromethane solution gave a gum which was added to a solution of 363 mg (1.03 mmol) of N-[(9-fluorenyl)methoxycarbonyl]-3-methyl-L-leucine, 149 mg (1.1 mmol) of hydroxybenzotriazole and 288 mg (1.5 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 15 ml of dichloromethane. The mixture was stirred for 18 hours, then washed with 2M hydrochloric acid and saturated sodium bicarbonate solution, dried over magnesium sulphate and evaporated to dryness. The residue was chromatographed on silica gel using ethyl acetate/petrol (1:2) for the elution to give 501 mg of N2-[N-[(9-fluorenyl)methoxycarbonyl]-3-methyl-L-valyl]-N1-[1(S)-(dimethoxymethyl)-3-butynyl]-L-leucinamide as a white foam. MS: m/e 592.3 [M+H]+, 560.3 [M+H-MeOH]+.

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe residue was chromatographed on silica gel using firstly ethyl acetate/petrol (1:1)
  3. washmethanol/dichloromethane (1:9) for the elution
  4. customEvaporation of the dichloromethane solution
  5. customgave a gum which
  6. washwashed with 2M hydrochloric acid and saturated sodium bicarbonate solution
  7. dry with materialdried over magnesium sulphate
  8. customevaporated to dryness
  9. customThe residue was chromatographed on silica gel
  10. washfor the elution

Sources & evidence

ORD record
ord-c858f4aef1bb4e3bb7d4d2907de80e0d
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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