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

HRID 849828Notes

Reaction equation

HRID 849828 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].Cl.[NH2:41][C@H:42]([CH2:60][C:61]1[CH:70]=[CH:69][C:68]2[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:62]=1)[C:43]([NH:45][C@@H:46]([C:54]1[O:58][N:57]=[C:56]([CH3:59])[N:55]=1)[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:44].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:41][C@@H:42]([C:43](=[O:44])[NH:45][C@@H:46]([C:54]1[O:58][N:57]=[C:56]([CH3:59])[N:55]=1)[CH2:47][C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1)[CH2:60][C:61]1[CH:70]=[CH:69][C:68]2[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:62]=1)([CH3:25])([CH3:26])[CH3:27]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 543222534-Tertbutoxycarbonylamino-4-methylpent-2-enoic acidHCID 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 54016310{1,1-dimethyl-3-[(1R)-1-((1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl]allyl}carbamic acid tertbutyl esterYield 94.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.42 g, 2.18 mmol) and 1-hydroxybenzotriazole monohydrate (0.33 g, 2.18 mmol) were added to a solution of 4-tertbutoxycarbonylamino-4-methylpent-2-enoic acid (0.50 g, 2.18 mmol) in N,N-dimethylformamide (7 ml). After 30 min 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 (0.68 g, 1.56 mmol) and triethylamine (0.16 g, 1.56 mmol) in N,N-dimethylformamide (8 ml) were added. After 18 h at 20° C. the reaction mixture was poured on ice water (90 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 (3×15 ml) and water (3×15 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and purified by flash chromatography on silica gel (95 g) using ethyl acetate and heptane (1:1) as eluent to give 0.90 g of {1,1-dimethyl-3-[(1R)-1-((1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl]allyl}carbamic acid tertbutyl ester.

Workup

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured on ice water (90 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. custompurified by flash chromatography on silica gel (95 g)

Sources & evidence

ORD record
ord-21b36f57f0934aff9b4aba3f830ae25f
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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