Hydrochloric Acid → (1R)-1-[[[(1R,2R,4R)-2-[[[(1S)-1-[[[(1S)-1-Cyclohexyl-2-(methylamino)-2-oxoethyl]amino]carbonyl]-2,2-dimethylpropyl]amino]carbonyl]-4-hydroxycyclopentyl]carbonyl]amino]-2-ethenyl-cyclopropanecarboxylic acid ethyl ester

HRID 2242451Notes

Reaction equation

HRID 2242451 reaction equation
[CH:1]1([C@H:7]([NH:12][C:13]([C@@H:15]([NH:20][C:21]([C@@H:23]2[CH2:28][C@@H:27]3[CH2:29][C@H:24]2[C:25](=[O:30])[O:26]3)=[O:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:8]([NH:10][CH3:11])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl.[CH2:34]([O:36][C:37]([C:39]1([NH2:44])[CH2:41][CH:40]1[CH:42]=[CH2:43])=[O:38])[CH3:35].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1.O>[CH2:34]([O:36][C:37]([C@@:39]1([NH:44][C:25]([C@@H:24]2[CH2:29][C@H:27]([OH:26])[CH2:28][C@H:23]2[C:21]([NH:20][C@H:15]([C:13]([NH:12][C@@H:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[C:8]([NH:10][CH3:11])=[O:9])=[O:14])[C:16]([CH3:19])([CH3:17])[CH3:18])=[O:22])=[O:30])[CH2:41][CH:40]1[CH:42]=[CH2:43])=[O:38])[CH3:35]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22082824Ethyl 1-amino-2-vinylcyclopropanecarboxylateHCID 68490886(1R,4R,5R)-N-[(1S)-1-[[[(1S)-1-Cyclohexyl-2-(methylamino)-2-oxoethyl]amino]carbonyl]-2,2-dimethylpropyl]-3-oxo-2-oxabicyclo[2.2.1]heptane-5-carboxamide

Product 1

HCID 68491567(1R)-1-[[[(1R,2R,4R)-2-[[[(1S)-1-[[[(1S)-1-Cyclohexyl-2-(methylamino)-2-oxoethyl]amino]carbonyl]-2,2-dimethylpropyl]amino]carbonyl]-4-hydroxycyclopentyl]carbonyl]amino]-2-ethenyl-cyclopropanecarboxylic acid ethyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Compound 72 (60 mg, 0.14 mmol) was dissolved in dioxane (3.5 mL) and H2O (2.5 mL) and the solution was cooled to 0° C. LiOH (1 M, 280 □L, 0.28 mmol) was added dropwise during 5 min, after which the reaction mixture was stirred at 0° C. for 40 min. The pH was adjusted to 7 using 1 M HCl, and the solvents were evaporated. The residue was suspended in DMF (5 mL) and 1-amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester (32 mg, 0.17 mmol), and DIEA (146 □L, 0.84 mmol) were added. After cooling to 0° C. HATU (64 mg, 0.17 mmol) was added and the mixture was stirred at 0° C. for 1 h and at rt for 1 h. The solvent was evaporated and the product was purified using flash column chromatography (EtOAc/MeOH 9:1) to give compound 73 (67 mg, 82%) as a white solid.

Workup

  1. customthe solvents were evaporated
  2. temperatureAfter cooling to 0° C
  3. stirringthe mixture was stirred at 0° C. for 1 h and at rt for 1 h
  4. customThe solvent was evaporated
  5. customthe product was purified

Sources & evidence

ORD record
ord-c67b747a102248fd9ad9ef89c11f0b0c
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

Loading…