Trifluoroacetic acid → 4-((1r)-1-{n-Methyl-n-[(1r)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]carbamoyl}-2-(2-naphthyl)ethyl)carbamoylpiperidine-1-carboxylic acid tert-butylester

HRID 1701045Notes

Reaction equation

HRID 1701045 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([C:37]([OH:39])=O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].[NH2:40][C@H:41]([CH2:64][C:65]1[CH:74]=[CH:73][C:72]2[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=2)[CH:66]=1)[C:42]([N:44]([CH3:63])[C@@H:45]([C:57]1[O:61][N:60]=[C:59]([CH3:62])[N:58]=1)[CH2:46][C:47]1[CH:56]=[CH:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:48]=1)=[O:43].FC(F)(F)C(O)=O.C(N(CC)CC)C>CN(C)C=O>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][CH:34]([C:37](=[O:39])[NH:40][C@@H:41]([C:42](=[O:43])[N:44]([CH3:63])[C@@H:45]([C:57]2[O:61][N:60]=[C:59]([CH3:62])[N:58]=2)[CH2:46][C:47]2[CH:56]=[CH:55][C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH:48]=2)[CH2:64][C:65]2[CH:74]=[CH:73][C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH:66]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:25])([CH3:26])[CH3:27]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53797289(2R)-2-amino-N-methyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(2-naphthyl)ethyl]-3-(2-naphthyl)propionamide

Product 1

HCID 544578824-((1r)-1-{n-Methyl-n-[(1r)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]carbamoyl}-2-(2-naphthyl)ethyl)carbamoylpiperidine-1-carboxylic acid tert-butylester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.42 g, 2.2 mmol) and 1-hydroxybenzotriazole monohydrate (0.34 g, 2.2 mmol) were added to a solution of N-tert-butoxycarbonyl-4-piperidine carboxylic acid (0.50 g, 2.2 mmol) in N,N-dimethylformamide (5 ml). After 30 min at 20° C. a mixture of (2R)-2-amino-N-methyl-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]-3-(2-naphthyl)propionamide, trifluoroacetic acid (0.9 g, 1.54 mmol) and triethylamine (0.16 g, 1.54 mmol) in N,N-dimethylformamide (10 ml) were added. After 18 h at 20° C. the reaction mixture was poured on water (85 ml) and extracted several times with ethyl acetate (total 90 ml). The organic phases were collected and washed with aqueous citric acid (10%, 15 ml), a saturated solution of sodium hydrogencarbonate (15 ml) and water (3×15 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and the residue was chromatographed on silica (110 g) using ethyl acetate and heptane (1:1) as eluent to give 0.50 g of 4-((1R)-1-{N-methyl-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]carbamoyl}-2-(2naphthyl)ethyl)carbamoylpiperidine-1-carboxylic acid tert-butylester.

Workup

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured on water (85 ml)
  3. extractionextracted several times with ethyl acetate (total 90 ml)
  4. customThe organic phases were collected
  5. washwashed with aqueous citric acid (10%, 15 ml)
  6. dry with materialAfter drying (magnesium sulfate) the solution
  7. concentrationwas concentrated in vacuo
  8. customthe residue was chromatographed on silica (110 g)

Sources & evidence

ORD record
ord-d4efa8b1c8934b07b7d71473bb5c04dd
Source dataset
uspto-grants-2002_02
Patent number
US06350767B1

Reaction notes

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