Diisopropylethylamine → HCID 10841685, compound

HRID 495773Notes

Reaction equation

HRID 495773 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.[CH3:28][N:29]([C@@H:46]([C:54](=[O:57])[NH:55][CH3:56])[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:30](=[O:45])[CH:31]([NH:43][CH3:44])[CH2:32][C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C)C=O>[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:43]([CH3:44])[C@@H:31]([C:30](=[O:45])[N:29]([CH3:28])[C@@H:46]([C:54](=[O:57])[NH:55][CH3:56])[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH2:32][C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 53651406HCID 53651406, compound

Product 1

HCID 10841685HCID 10841685, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acid (200 mg, 0.82 mmol), 1-hydroxy-7-azabenzotriazole (112 mg, 0.82 mmol) and 1-ethyl-3-(3-s dimethylaminopropyl)-carbodiimide hydrochloride (173 mg, 0.90 mmol) were dissolved in a mixture of methylene chloride (10 mL) and N,N-dimethylformamide (1 mL) and strirred for 15 min. N-Methyl-2-methylamino-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-3-(2-naphthyl)propionamide (332 mg, 0.82 mol) dissolved in methylene chloride (5 mL) and diisopropylethylamine (0.14 mL) were added and the mixture was stirred overnight under nitrogen atmosphere. The mixture was diluted with methylene chloride (50 mL), washed with water (50 mL), sodium hydrogen carbonate (30 mL, saturated), and sodium hydrogensulfate (30 mL, 5%). The phases were separated and the organic phase was dried with magnesium sulfate and evaporated in vacuo. The residue was chromatographed (silica, 2×40 cm) to afford 450 mg of ((3E)-1,1dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)-carbamic acid tert-butyl ester.

Workup

  1. washwashed with water (50 mL), sodium hydrogen carbonate (30 mL, saturated), and sodium hydrogensulfate (30 mL, 5%)
  2. customThe phases were separated
  3. dry with materialthe organic phase was dried with magnesium sulfate
  4. customevaporated in vacuo
  5. customThe residue was chromatographed (silica, 2×40 cm)

Sources & evidence

ORD record
ord-eb9d1205749546bb8ab0a539419bf087
Source dataset
uspto-grants-2005_09
Patent number
US06939880B2

Reaction notes

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