1,2-Dichloroethane → HCID 89455885, compound

HRID 1776508Notes

Reaction equation

HRID 1776508 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:25]=[CH:24][C:16]([CH2:17][N:18]([CH3:23])[CH2:19][C:20]([OH:22])=[O:21])=[CH:15][CH:14]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:28]=[N+:29]([O-:52])[CH:30]=[C:31]([Cl:51])[C:32]=1[CH2:33][C@@H:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:45])[F:44])=[C:38]([O:46][CH2:47][CH:48]2[CH2:50][CH2:49]2)[CH:37]=1)O.C(Cl)CCl.CC#N>CN(C1C=CN=CC=1)C.C(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH3:23])[CH2:19][C:20]([O:22][C@H:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]3[CH2:49][CH2:50]3)[CH:37]=2)[CH2:33][C:32]2[C:31]([Cl:51])=[CH:30][N+:29]([O-:52])=[CH:28][C:27]=2[Cl:26])=[O:21])=[CH:24][CH:25]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 6342AcetonitrileHCID 71092687HCID 71092687, compoundHCID 89459914HCID 89459914, compound

Product 1

HCID 89455885HCID 89455885, compoundYield 39.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-((4-(N-(tert-butoxycarbonyl)methylsulfonamido)benzyl)-(methyl)amino)acetic acid (0.398 g, 1.069 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.345 g, 0.822 mmol), EDC (0.473 g, 2.466 mmol), and DMAP (0.151 g, 1.233 mmol) in DCM was stirred at RT for 30 minutes. CH3CN (10 ml) and DMF (5 ml) were added to dissolve insoluble residue, and the mixture was stirred at RT for 2 days. The mixture was diluted with DCM and washed twice with HCl 1N and with NaHCO3. The organic layer was dried over Na2SO4, and the solvent was removed. The crude was purified by filtration on SCX cartridge (DCM/MeOH 1/1; MeOH/conc.aq.NH4OH 90/10). The basic fraction was portioned between EtOAc and water, and the organic phase was washed with brine and dried over Na2SO4. The solvent was removed, and the crude (S)-4-(2-(2-((4-(N-(tert-butoxycarbonyl)-methylsulfonamido)benzyl)(methyl)amino)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide was obtained as a colorless amorphous solid (0.250 g, 0.323 mmol, 39.3% yield, MS/ESI+ 774.5 [MH]+) and used in the next step without any further purification.

Workup

  1. dissolutionto dissolve insoluble residue
  2. stirringthe mixture was stirred at RT for 2 days
  3. washwashed twice with HCl 1N and with NaHCO3
  4. dry with materialThe organic layer was dried over Na2SO4
  5. customthe solvent was removed
  6. filtrationThe crude was purified by filtration on SCX cartridge (DCM/MeOH 1/1; MeOH/conc.aq.NH4OH 90/10)
  7. washthe organic phase was washed with brine
  8. dry with materialdried over Na2SO4
  9. customThe solvent was removed

Sources & evidence

ORD record
ord-eaa5e50edcd04edea24450a17b3ba02e
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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