Dichloromethane → HCID 90370352, compound

HRID 2176000Notes

Reaction equation

HRID 2176000 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24](O)=[O:25])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.ClC(N(C)C)=C(C)C.[NH2:41][C:42]1[S:43][C:44]2[CH2:71][CH2:70][CH2:69][CH2:68][C:45]=2[C:46]=1[C:47]([NH:49][C:50]1[CH:55]=[CH:54][C:53]([CH2:56][CH2:57][C:58]2[CH:67]=[CH:66][C:61]([C:62]([O:64][CH3:65])=[O:63])=[CH:60][CH:59]=2)=[CH:52][CH:51]=1)=[O:48]>N1C=CC=CC=1>[Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24]([NH:41][C:42]1[S:43][C:44]2[CH2:71][CH2:70][CH2:69][CH2:68][C:45]=2[C:46]=1[C:47]([NH:49][C:50]1[CH:51]=[CH:52][C:53]([CH2:56][CH2:57][C:58]2[CH:59]=[CH:60][C:61]([C:62]([O:64][CH3:65])=[O:63])=[CH:66][CH:67]=2)=[CH:54][CH:55]=1)=[O:48])=[O:25])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 68207883Methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoateHCID 90370043HCID 90370043, compound

Product 1

HCID 90370352HCID 90370352, compoundYield 97.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a mixture of 480 mg of 3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)benzoic acid and 10 ml of methylene chloride was added 160 mg of 1-chloro-N,N,2-trimethylpropenylamine under ice cooling, followed by stirring for 1 hour at room temperature. 10 ml of a methylene chloride solution containing 450 mg of methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate and 0.20 mL of pyridine was added to the reaction mixture under ice cooling, followed by stirring for 1 hour under ice cooling and then for 4 days at room temperature. The reaction mixture was concentrated under reduced pressure, ethyl acetate and water were added thereto, and the organic layer was separated. The organic layer was washed with a 5% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1), thereby obtaining 830 mg of methyl 4-[2-(4-{[(2-{[3-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate.

Workup

  1. additionwas added to the reaction mixture under ice cooling
  2. stirringby stirring for 1 hour under ice cooling
  3. waitfor 4 days at room temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate and water
  5. additionwere added
  6. customthe organic layer was separated
  7. washThe organic layer was washed with a 5% aqueous citric acid solution
  8. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine in this order and dried over anhydrous sodium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-d57270688f23474e88ce41de9831a0c9
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

Loading…