Dimethylformamide → (3-{(1r)-1-[(1r)-1-(3-Methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}-benzyl)carbamic acid tertbutyl ester

HRID 1701020Notes

Reaction equation

HRID 1701020 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2N=N1.[C:24]([O:28][C:29]([NH:31][C:32]1C=C(C=CC=1)C(O)=O)=[O:30])([CH3:27])([CH3:26])[CH3:25].Cl.[NH2:42][C@H:43]([CH2:61][C:62]1[CH:71]=[CH:70][C:69]2[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=2)[CH:63]=1)[C:44]([NH:46][C@@H:47]([C:55]1[O:59][N:58]=[C:57]([CH3:60])[N:56]=1)[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:45].C(N(CC)CC)C.CN(C)[CH:81]=[O:82]>>[C:24]([O:28][C:29](=[O:30])[NH:31][CH2:32][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:81](=[O:82])[NH:42][C@@H:43]([C:44](=[O:45])[NH:46][C@@H:47]([C:55]2[O:59][N:58]=[C:57]([CH3:60])[N:56]=2)[CH2:48][C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH2:61][C:62]2[CH:71]=[CH:70][C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[CH:63]=2)[CH:19]=1)([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 6

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 8541623-(((Tert-butoxy)carbonyl)amino)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69834587(2R)-2-amino-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethyl]-3-(2-naphthyl)propionamide hydrochloride

Product 1

HCID 53665347(3-{(1r)-1-[(1r)-1-(3-Methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}-benzyl)carbamic acid tertbutyl ester

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.92 g, 4.82 mmol) and 1-hydroxybenzotriazole monohydrate (0.74 g, 4.83 mmol) were added to a solution of N-tertbutoxycarbonyl-3-aminobenzoic acid (1.21 g, 4.82 mmol) in N,N-dimethylformamide (15 ml). After 1 h at 20° C. a mixture of (2R)-2-amino-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethyl]-3-(2-naphthyl)propionamide hydrochloride (1.50 g, 3.43 mmol) and triethylamine (0.35 g, 3.46 mmol) in N,N-dimethylformamide (15 ml) were added. After 18 h at 20° C. the reaction mixture was poured on ice water (180 ml) and extracted several times with dichloromethane (total 180 ml). The organic phases were collected and washed with aqueous citric acid (10%, 25 ml), a saturated solution of sodium hydrogencarbonate (3×25 ml) and water (3×25 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and 1.80 g of (3-{(1R)-1-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl]-2-(2-naphthyl)ethylcarbamoyl}-benzyl)carbamic acid tertbutyl ester was isolated from ethyl acetate.

Workup

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured on ice water (180 ml)
  3. extractionextracted several times with dichloromethane (total 180 ml)
  4. customThe organic phases were collected
  5. washwashed with aqueous citric acid (10%, 25 ml)
  6. dry with materialAfter drying (magnesium sulfate) the solution
  7. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-67f2c86482474a65b7700c36faf65fa1
Source dataset
uspto-grants-2002_02
Patent number
US06350767B1

Reaction notes

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