Diethyl cyanophosphonate → HCID 22849831, compound

HRID 1197930Notes

Reaction equation

HRID 1197930 reaction equation
[NH2:1][C@@H:2]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C@@H:3]([OH:11])[CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10].C(OC([N:26]1[CH:53]=[N:52][C:28]([CH2:29][C@@H:30]([C:49]([OH:51])=O)[NH:31][C:32](=[O:48])[C@@H:33]([CH2:41][C:42](=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:27]1)=O)(C)(C)C.C(N(CC)[CH:58]([CH3:60])[CH3:59])(C)C.[C:63](P(=O)(OCC)OCC)#N.[C:73](=[O:76])(O)[O-:74].[Na+]>C(Cl)Cl>[CH:13]1([CH2:12][C@H:2]([NH:1][C:49](=[O:51])[C@@H:30]([NH:31][C:32](=[O:48])[C@@H:33]([CH2:41][C:42](=[O:47])[C:43]([CH3:45])([CH3:44])[CH3:46])[CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:29][C:28]2[N:52]([C:73]([O:74][C:58]([CH3:60])([CH3:63])[CH3:59])=[O:76])[CH:53]=[N:26][CH:27]=2)[C@@H:3]([OH:11])[CH2:4][N:5]2[CH2:9][CH2:8][CH2:7][C:6]2=[O:10])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 22845091HCID 22845091, compoundHCID 70048063HCID 70048063, compound

Product 1

HCID 22849831HCID 22849831, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

220 mg (0.865 mmol) of 1-[(2S,3S)-3-amino-4-cyclohexyl-2-hydroxybutyl]-2-pyrrolidinone and 300 mg (0.618 mmol) of 1-(t-butoxycarbonyl)-N-[(R)-α-(3,3-dimethyl-2-oxobutyl)hydrocinnamoyl]-L-histidine were dissolved in 5 ml of methylene chloride, cooled to -20° and treated with 0.16 ml of N,N-diisopropylethylamine and 0.12 ml of diethyl cyanophosphonate. Thereupon, the reaction mixture was stirred at room temperature for 19 hours and subsequently poured into a mixture of ice and dilute sodium bicarbonate solution and extracted with methylene chloride. The methylene chloride extracts were dried over magnesium sulfate and evaporated, and the residue was chromatographed on 5 g of silica gel with a mixture of methylene chloride and isopropanol as the eluting agent, whereby there were obtained 430 g (96%) of (S)-N-[(1S,2S)-1-(cyclohexylmethyl)-2-hydroxy-3-(2-oxo-1-pyrrolidinyl)propyl]-α-[(R)-α-(3,3-dimethyl-2-oxobutyl)hydrocinnamamido]-3-t-butoxycarbonylimidazole-4propionamide as a yellow foam which was used directly in the next step.

Workup

  1. temperaturecooled to -20°
  2. extractionextracted with methylene chloride
  3. dry with materialThe methylene chloride extracts were dried over magnesium sulfate
  4. customevaporated
  5. customthe residue was chromatographed on 5 g of silica gel with a mixture of methylene chloride and isopropanol as the eluting agent

Sources & evidence

ORD record
ord-dd73091ace7e449fbcebbbe691e86992
Source dataset
uspto-grants-1994_01
Patent number
US05278148

Reaction notes

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