Hydrochloric Acid → N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamide

HRID 1429193Notes

Reaction equation

HRID 1429193 reaction equation
[Li+].[OH-].[CH2:3]([N:9]([CH3:20])[C:10]([CH:12]1[CH2:17][CH:16]2[CH2:18][CH:13]1[C:14](=[O:19])[O:15]2)=[O:11])[CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].Cl.Cl.[NH2:23][C@:24]1([C:29]([NH:31][S:32]([CH:35]2[CH2:37][CH2:36]2)(=[O:34])=[O:33])=[O:30])[CH2:26][C@H:25]1[CH:27]=[CH2:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:35]1([S:32]([NH:31][C:29]([C:24]2([NH:23][C:14]([CH:13]3[CH2:18][CH:16]([OH:15])[CH2:17][CH:12]3[C:10]([N:9]([CH2:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8])[CH3:20])=[O:11])=[O:19])[CH2:26][CH:25]2[CH:27]=[CH2:28])=[O:30])(=[O:34])=[O:33])[CH2:37][CH2:36]1

Participants

8

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 23595124(1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochlorideHCID 591654883-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carboxylic acid hex-5-enyl-methylamide

Product 1

HCID 68589808N-(1-Cyclopropanesulfonylaminocarbonyl-2-vinyl-cyclopropyl)-2-(hex-5-enyl-methyl-amino-carbonyl)-4-hydroxy-cyclopentane-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

LiOH solution (0.15M, 53 mL, 8 mmol) was added to the lactone amide 24a (996 mg, 3.96 mmol) in an ice bath and stirred for 1 h. The mixture was acidified to pH 2-3 with 1N HCl and evaporated, co-evaporated with toluene several times, and dried under vacuum overnight. (1R,2S)-cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropane-carbonyl)amide hydrochloride (4.21 mmol) and HATU (1.78 g, 4.68 mmol) were added. The mixture was cooled in an ice bath under argon, DMF (25 mL) and then DIEA (2.0 mL, 11.5 mmol) were added. After stirring for 30 min, the mixture was stirred at rt for 3 h. After evaporation of solvent, the residue was dissolved in EtOAc (120 mL), washed successively with 0.5 N HCl (20 mL) and saturated NaCl (2×20 mL), and dried over Na2SO4. Flash column chromatography (200 g YMC silica gel, 2-4% MeOH in CH2Cl2 gave white solids (1.25 g, 66%).

Workup

  1. customevaporated, co-evaporated with toluene several times
  2. customdried under vacuum overnight
  3. temperatureThe mixture was cooled in an ice bath under argon
  4. stirringAfter stirring for 30 min
  5. stirringthe mixture was stirred at rt for 3 h
  6. customAfter evaporation of solvent
  7. dissolutionthe residue was dissolved in EtOAc (120 mL)
  8. washwashed successively with 0.5 N HCl (20 mL) and saturated NaCl (2×20 mL)
  9. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-1165a538880744a7af15c80b41c13e9e
Source dataset
uspto-grants-2015_01
Patent number
US08937080B2

Reaction notes

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