Diisopropylethylamine → HCID 59965082, compound

HRID 366141Notes

Reaction equation

HRID 366141 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.[C:40]1([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH:45]=[CH:44][C:43]([CH2:46][C@@H:47]([NH:59][CH3:60])[C:48]([N:50]([CH3:58])[CH2:51][CH2:52][C:53]2[S:54][CH:55]=[CH:56][CH:57]=2)=[O:49])=[CH:42][CH:41]=1.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:59]([C@@H:47]([C:48](=[O:49])[N:50]([CH3:58])[CH2:51][CH2:52][C:53]1[S:54][CH:55]=[CH:56][CH:57]=1)[CH2:46][C:43]1[CH:42]=[CH:41][C:40]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[CH:45][CH:44]=1)[CH3:60])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10833541HCID 10833541, compoundHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acid

Product 1

HCID 59965082HCID 59965082, compoundYield 74.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (202 mg, 0.83 mmol) and 1-hydroxy-7-azabenzotriazole (113 mg, 0.83 mmol) in N,N-dimethyformamide (3 ml) and dichloromethane (3 ml) was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (159 mg, 0.83 mmol) was added. The reaction mixture was stirred for 10 min at 0° C. A solution of (2R)-3-(biphenyl-4-yl)-N-methyl-2-(methylamino)-N-(2-(2-thienyl)ethyl)propionamide (314 mg, 0.83 mmol) in dichloromethane (3 ml) and ethyldiisopropylamine (0.14 ml, 0.83 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 (100 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (100 ml). The aqueous solution was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with a saturated 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 (80 g), using ethyl acetate/heptane (1:1 (500 ml), then 2:1) as eluent, to give 374 mg of (3E)-4-(N-((1R)-2-(biphenyl-4-yl)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enylcarbamic 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 a 10% aqueous solution of sodium hydrogen sulfate (100 ml)
  4. extractionThe aqueous solution was extracted with ethyl acetate (2×50 ml)
  5. washThe combined organic layers were washed with a saturated 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 (80 g)

Sources & evidence

ORD record
ord-e46c643bb21d412c9d93d01bb8718ab5
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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