HOAt → HCID 69740563, compound

HRID 1268624Notes

Reaction equation

HRID 1268624 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]([CH3:27])([CH3:26])[CH2:20]/[CH:21]=[CH:22]/[C:23](O)=[O:24])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN(C)C(=O)[C@H](NC)CC1C=CC=CC=1.[CH3:65][N:66]([CH3:95])[C:67]([C@H:69]([N:77]([CH3:94])[C:78](=[O:93])[CH:79]([NH:91][CH3:92])[CH2:80][C:81]1[CH:90]=[CH:89][C:88]2[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=2)[CH:82]=1)[CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)=[O:68]>ClCCl>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]([CH3:26])([CH3:27])[CH2:20]/[CH:21]=[CH:22]/[C:23](=[O:24])[N:91]([C@@H:79]([C:78](=[O:93])[N:77]([C@@H:69]([C:67](=[O:68])[N:66]([CH3:65])[CH3:95])[CH2:70][C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=3)[CH3:94])[CH2:80][C:81]3[CH:90]=[CH:89][C:88]4[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=4)[CH:82]=3)[CH3:92])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22326974HCID 22326974, compoundHCID 54419464HCID 54419464, compoundHCID 86587343HCID 86587343, compound

Product 1

HCID 69740563HCID 69740563, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2E)-5-(((9H-flouren-9-yl)methoxy)- carbonylamino)-5-methylhex-2-enoic acid (280 mg, 0.77 mmol) in dichloromethane (5 ml) were added 1-hydroxy-7-azabenzotriazole (126 mg, 0.92 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (207 mg, 1.08 mmol) and the mixture was stirred for 30 min. Then 2R)-N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methyl-2-methylamino-3-(2-naphthyl)propionamide (386 mg, 0.92 mmol) in dichloromethane (5 ml) and diisoprbpylethylamine (0.17 ml, 1.00 mmol) were added and the mixture was stirred overnight at room temperature. The mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1 to give 401 mg of ((3E)-4-(N-((1R)-1-(N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid 9H-flouren-9-ylmethyl ester. The obtained product was dissolved in 20% piperidine in dimethylformamide (10 ml) and stirred for 30 min. The mixture was chromatographed on silica (20 g) with dichloromethane/methanol/ammonia 89:10:1 to give 228 mg of (2E)-5-amino-5-methylhex-2-enoic acid N-((1R)-1-(N-((1R)-1-(dimethylcarbamoyl)-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylamide as an oil. The product was redissolved in water (30 ml) and acetic acid (2 ml) was added and the mixture was lyophilized to give 645 mg of the acetate salt of the title compound as an amorphous powder.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washThe mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1

Sources & evidence

ORD record
ord-2d80dfcd34ed49b4bdef90580bf064db
Source dataset
uspto-grants-2003_04
Patent number
US06555570B2

Reaction notes

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