Triphenylphosphine → cis(+/-)-4-Chloro-N-(1-{5-[1-(2-cyanoethyl)-1H-tetrazol-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxylic acid amide

HRID 1425446Notes

Reaction equation

HRID 1425446 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:24]([NH:26][CH2:27][CH2:28][C:29]#[N:30])=O)=[C:21]([CH3:23])[N:22]=3)[CH2:14][C@H:13]2[O:31][CH3:32])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C[Si]([N:70]=[N+:71]=[N-:72])(C)C>C(OCC)(=O)C.C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:24]4[N:26]([CH2:27][CH2:28][C:29]#[N:30])[N:72]=[N:71][N:70]=4)=[C:21]([CH3:23])[N:22]=3)[CH2:14][C@H:13]2[O:31][CH3:32])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 78378AzidotrimethylsilaneHCID 86648855cis(+/-)-2-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-N-(2-cyanoethyl)-4-methyl-1,3-thiazole-5-carboxylic acid amide

Product 1

HCID 86648857cis(+/-)-4-Chloro-N-(1-{5-[1-(2-cyanoethyl)-1H-tetrazol-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxylic acid amideYield 41%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

THF (2 mL) was added to cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-N-(2-cyanoethyl)-4-methyl-1,3-thiazole-5-carboxylic acid amide obtained in Example (261a) (36 mg, 0.08 mmol). While the mixture was stirred, triphenylphosphine (124 mg, 0.47 mmol), diisopropyl azodicarboxylate (0.24 mL, 0.45 mmol, 1.9 M solution in toluene) and trimethylsilyl azide (7.3 g, 55.4 mmol) were added, followed by stirring at 30° C. for four days. The reaction solution was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0/10, 2/8) and preparative thin layer chromatography (developing solvent: ethyl acetate/hexane=10/1) to obtain 16 mg of the title compound as a white solid (41%).

Workup

  1. stirringby stirring at 30° C. for four days
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0/10, 2/8) and preparative thin layer chromatography (developing solvent: ethyl acetate/hexane=10/1)

Sources & evidence

ORD record
ord-3dc82ab0a8fd4253b1b813927cf97f78
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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