Triethylsilane → (1R,2S)-1-{[(1R,2R,4R)-2-(N'-tert-Butoxycarbonyl-N-hept-6-enyl-hydrazinocarbonyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 2242433Notes

Reaction equation

HRID 2242433 reaction equation
C(O[C:6]([C@@H:8]1[CH2:12][C@H:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:26]3[CH:31]=C[CH:29]=[CH:28][CH:27]=3)[CH:15]=2)[CH2:10][C@H:9]1[C:32](=[O:44])[NH:33][C@:34]1([C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:7])(C)(C)C.[CH2:45]([SiH](CC)CC)C.[C:52]([O:56][C:57]([NH:59]/[N:60]=[CH:61]/[CH2:62][CH2:63][CH2:64][CH2:65][CH:66]=[CH2:67])=[O:58])([CH3:55])([CH3:54])[CH3:53].CCN(C(C)C)C(C)C>C(Cl)Cl.FC(F)(F)C(O)=O>[CH2:42]([O:41][C:39]([C@@:34]1([NH:33][C:32]([C@@H:9]2[CH2:10][C@@H:11]([O:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:45][CH:31]=4)[CH:15]=3)[CH2:12][C@H:8]2[C:6]([N:60]([CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH:66]=[CH2:67])[NH:59][C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:58])=[O:7])=[O:44])[CH2:36][C@H:35]1[CH:37]=[CH2:38])=[O:40])[CH3:43]

Participants

7

Reactant 4

HCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 59204175(1R,2R,4R)-2-((1R,2S)-1-Ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid tert-butyl esterHCID 87444397tert-butyl N-[(E)-hept-6-enylideneamino]carbamate

Product 1

HCID 11216424(1R,2S)-1-{[(1R,2R,4R)-2-(N'-tert-Butoxycarbonyl-N-hept-6-enyl-hydrazinocarbonyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 82.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Scaffold molecule 35 (135 mg, 0.225 mmol) and triethylsilane (71 μL, 0.447 mmol) was dissolved in DCM (2 mL) after which trifluoroacetic acid (TFA) (2 mL) was added. The mixture was stirred for 2 h and thereafter co-evaporated with toluene in order to remove the TFA. The residue was dissolved in DMF (3 mL) and 47 (60 mg, 0.263 mmol) and DIEA (118 μL, 0.677 mmol) were added. The temperature was lowered to 0° C. and the coupling reagent O-(7-azabenzotriazol-1-yl)-NNN′,N′-tetramethyluronium hexafluorophosphate (HATU) (94 mg, 0.247 mmol) was added. The cold solution was allowed to stir for half an hour and then for additional 16 h in room temperature. The solvent was removed by heating the reaction flask in a water bath under diminished pressure. The residue was thereafter dissolved in ethyl acetate and the organic phase washed three times with brine, dried, filtered and evaporated. Purification by HPLC (MeOH/H2O 90:10 with 0.2% triethylamine) gave 48 (140 mg, 82%) as an oil.

Workup

  1. additionwas added
  2. customco-evaporated with toluene in order to remove the TFA
  3. dissolutionThe residue was dissolved in DMF (3 mL)
  4. customwas lowered to 0° C.
  5. stirringto stir for half an hour
  6. waitfor additional 16 h in room temperature
  7. customThe solvent was removed
  8. temperatureby heating the reaction flask in a water bath under diminished pressure
  9. dissolutionThe residue was thereafter dissolved in ethyl acetate
  10. washthe organic phase washed three times with brine
  11. customdried
  12. filtrationfiltered
  13. customevaporated
  14. customPurification by HPLC (MeOH/H2O 90:10 with 0.2% triethylamine)

Sources & evidence

ORD record
ord-ae639591d68e42fc8975dd0a67f797c9
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

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