HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

1,2-Dichloroethane → N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide

HRID 1058237
Notes
Print preview

Reaction equation

HRID 1058237 reaction equation
C(Cl)CCl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:21]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH:22]([F:24])[F:23])=[C:10]([CH:20]=1)[CH2:11][NH:12][C:13](=[O:19])[C@@H:14]1[CH2:18][CH2:17][CH2:16][NH:15]1.[C:34](O)(=[O:43])[C@@H:35]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[OH:36].C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:21]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[CH:22]([F:24])[F:23])=[C:10]([CH:20]=1)[CH2:11][NH:12][C:13](=[O:19])[C@@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[C:34](=[O:43])[C@@H:35]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[OH:36]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 819914(2R)-2-cyclohexyl-2-hydroxyacetic acidHCID 69939410N-(5-Chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-L-prolinamide

Product 1

HCID 69937977N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide
Yield 36.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (0.0469 g, 0.24 mmol was added to a stirred mixture of N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-L-prolinamide (0.0691 g, 0.16 mmol), (R)-hexahydromandelic acid (0.0258 g, 0.16 mmol) and HOAT (0.0111 g, 0.08 mmol) in DMF (2.0 mL). After 2 h the mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and evaporated in vacuo and the residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-70% ethyl acetate/hexanes gradient) to give N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide (0.0332 g) as a white solid; LC-MS m/z=564.4.

Workup

  1. customAfter 2 h the mixture was partitioned between EtOAc and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo
  5. customthe residue was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 10-70% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-d9e1fa7738b34fea994409aae23b1568
Source dataset
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06515011B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes