Trifluoroacetic acid → (1,1-dimethyl-3-[(1R)-1-{N-methyl-N-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl}carbamoyl}-2-(2-naphthyl)ethylcarbamoyl]allyl}carbamic acid tertbutyl ester

HRID 1701035Notes

Reaction equation

HRID 1701035 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:24]([O:28][C:29]([NH:31][C:32]([CH3:39])([CH3:38])[CH:33]=[CH:34][C:35]([OH:37])=O)=[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](=[O:30])[NH:31][C:32]([CH3:39])([CH3:38])[CH:33]=[CH:34][C:35](=[O:37])[NH:40][C@@H:41]([C:42](=[O:43])[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)[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)([CH3:25])([CH3:26])[CH3:27]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 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)propionamideHCID 543222534-Tertbutoxycarbonylamino-4-methylpent-2-enoic acid

Product 1

HCID 54196845(1,1-dimethyl-3-[(1R)-1-{N-methyl-N-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl}carbamoyl}-2-(2-naphthyl)ethylcarbamoyl]allyl}carbamic acid tertbutyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.26 g, 1.38 mmol) and 1-hydroxybenzotriazole monohydrate (0.21 g, 1.38 mmol) were added to a solution of N-tertbutoxycarbonyl-4-amino-4-methylpent-2-enoic acid (0.32 g, 1.38 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 (0.57 g, 0.99 mmol) and triethylamine (0.10 g, 0.99 mmol) in N,N-dimethylformamide (6 ml) were added. After 18 h at 20° C. the reaction mixture was poured on water (75 ml) and extracted several times with ethyl acetate (total 30 ml). The organic phases were collected and washed with aqueous citric acid (10%, 15 ml), a saturated solution of sodium hydrogencarbonate (3×15 ml) and water (3×15 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo to give 0.68 g of crude (1,1-dimethyl-3-[(1R)-1-{N-methyl-N-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl}carbamoyl}-2-(2-naphthyl)ethylcarbamoyl]allyl}carbamic acid tertbutyl ester which was used for the next step without further purification.

Workup

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured on water (75 ml)
  3. extractionextracted several times with ethyl acetate (total 30 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

Sources & evidence

ORD record
ord-d7800ae36ea54f129c5116449dc3e7c0
Source dataset
uspto-grants-2002_02
Patent number
US06350767B1

Reaction notes

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