Imidazole → ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

HRID 500412Notes

Reaction equation

HRID 500412 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:31][N:32]([CH:38]1[CH2:40][CH2:39]1)[CH2:33][CH2:34][CH2:35][CH:36]=[CH2:37])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([NH:20][C@:21]1([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][C@H:22]1[CH:24]=[CH2:25])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:46](Cl)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:31][N:32]([CH:38]1[CH2:40][CH2:39]1)[CH2:33][CH2:34][CH2:35][CH:36]=[CH2:37])[C:10]([N:12]1[CH2:16][C@H:15]([O:17][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH2:14][C@H:13]1[C:18]([NH:20][C@:21]1([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][C@H:22]1[CH:24]=[CH2:25])=[O:19])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 59386563ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

Product 1

HCID 67331048ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate (1.55 g, 2.75 mmoL) in 10 mL of DMF was added imidazole (0.47 g, 6.88 mmoL) and tert-butyldimethylsilyl chloride (826 mg, 5.50 mmoL). The mixture was stirred at rt for 18 h, concentrated in vacuo, and partitioned between ethyl acetate and water. The organic phase was dried over magnesium sulfate, and concentrated in vacuo to obtain an off-white solid. Flash chromatography (eluting with methylene chloride and then ethyl acetate) gave ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate as a white solid (1.75 g, 94%): LC-MS (Phenomenex 10 μm C18HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nM. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.51 min), MS m/z 677 (M++1).

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customto obtain an off-white solid
  6. washFlash chromatography (eluting with methylene chloride

Sources & evidence

ORD record
ord-3f1c4d306ad54facb44565da8aaa95f1
Source dataset
uspto-grants-2010_08
Patent number
US07772183B2

Reaction notes

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