Diisopropylethylamine → HCID 59057267, compound

HRID 366275Notes

Reaction equation

HRID 366275 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:40][NH:41][C@H:42]([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:43]([N:45]([CH3:60])[C@@H:46]([CH2:53][N:54]([CH3:59])[S:55]([CH3:58])(=[O:57])=[O:56])[CH2:47][C:48]1[S:49][CH:50]=[CH:51][CH:52]=1)=[O:44].C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13](=[O:15])[N:41]([CH3:40])[C@@H:42]([C:43](=[O:44])[N:45]([CH3:60])[C@@H:46]([CH2:53][N:54]([CH3:59])[S:55]([CH3:58])(=[O:57])=[O:56])[CH2:47][C:48]1[S:49][CH:50]=[CH:51][CH:52]=1)[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)([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 53718173HCID 53718173, compound

Product 1

HCID 59057267HCID 59057267, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2E)-5-(tert-Butoxycarbonylamino)-5-methylhex-2-enoic acid (158 mg, 0.65 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (3 ml). 1-Hydroxy-7-azabenzotriazole was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (88 mg, 0.65 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of (2R)-2-Methylamino-N-methyl-N-((1R)-1-((N-methyl-N-(methylsulfonyl)amino)methyl)-2-(2-thienyl)ethyl)-3-(2-naphthyl)propionamide in dichloromethane (3 ml) and ethyldiisopropylamine (0.12 ml, 0.65 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with 10% aqueous sodium hydrogen sulfate solution (50 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml). The organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified on silica (120 g), using ethyl acetatelheptane 2:1 (250 ml) and successively ethyl acetate/heptane 3:1 as eluent, to give 282 mg of ((3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-((N-methyl-N-(methylsulfonyl)amino)methyl)-2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with 10% aqueous sodium hydrogen sulfate solution (50 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
  5. washThe organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified on silica (120 g)

Sources & evidence

ORD record
ord-c87087e9deff41dd847215a94e726ba4
Source dataset
uspto-grants-2000_10
Patent number
US06127391

Reaction notes

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