1,2-Dibromoethane → HCID 71468328, compound

HRID 1401068Notes

Reaction equation

HRID 1401068 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][CH:34]=1)[C:5]([NH:7][N:8]([C:12](=[O:31])/[CH:13]=[CH:14]/[C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:16]=1)[CH:9]([CH3:11])[CH3:10])=[O:6].[C:35]([O-:38])([O-])=O.[K+].[K+].BrCCBr.BrCCOC1C=C(C=CC=1)C(NN(C(=O)/C=C/[C:62]1C2[C:65](=[CH:66]C=CC=2)[N:64]([C:71](OC(C)(C)C)=O)[CH:63]=1)C(C)C)=O>C(#N)C>[CH:9]([N:8]([C:12](=[O:31])/[CH:13]=[CH:14]/[C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH:16]=1)[NH:7][C:5](=[O:6])[C:4]1[CH:32]=[CH:33][CH:34]=[C:2]([O:1][CH2:62][CH2:63][N:64]2[CH2:71][CH2:35][O:38][CH2:66][CH2:65]2)[CH:3]=1)([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 78391,2-DibromoethaneHCID 11430Potassium Carbonate2×HCID 71468216HCID 71468216, compoundHCID 86711425HCID 86711425, compound

Product 1

HCID 71468328HCID 71468328, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

To solution containing (E)-tert-butyl 3-(3-(2-(3-hydroxybenzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate (67.3 mg, 0.15 mmol) and K2CO3 (40.13 mg, 0.29 mmol) dissolved in anhydrous acetonitrile (10.0 ml), 1,2-dibromoethane (0.0313 ml, 0.36 mmol) was added drop-by-drop. The reaction mixture was refluxed at 80° C. for 48 hr. After concentration under reduced pressure, the solution was separated through silica gel chromatography (n-hexane:EtOAc:methanol=10:3:1) so that ivory solid form of (E)-tert-butyl 3-(3-(2-(3-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate was obtained (15 mg, 18.1%). The resultant (E)-tert-butyl 3-(3-(2-(3-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate (15.0 mg, 0.026 mmol) and K2CO3 (7.27 mg, 0.053 mmol) were dissolved in anhydrous acetonitrile (10.0 ml) and the solution was drop-wise added with morpoline (0.01 ml, 0.053 mmol). The reaction mixture was refluxed at 85° C. for 12 hr. After concentration under reduced pressure, the solution was separated through silica gel chromatography (MC:methanol=24:1) so that ivory solid form of (E)-tert-butyl 3-(3-(1-isopropyl-2-(3-(2-morpholinoethoxy)benzoyl)hydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate was obtained (10.6 mg, 69.9%).

Workup

  1. concentrationAfter concentration under reduced pressure
  2. customthe solution was separated through silica gel chromatography (n-hexane:EtOAc:methanol=10:3:1) so that ivory solid form of (E)-tert-butyl 3-(3-(2-(3-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate
  3. customwas obtained (15 mg, 18.1%)
  4. additionadded with morpoline (0.01 ml, 0.053 mmol)
  5. temperatureThe reaction mixture was refluxed at 85° C. for 12 hr
  6. concentrationAfter concentration under reduced pressure
  7. customthe solution was separated through silica gel chromatography (MC:methanol=24:1) so that ivory solid form of (E)-tert-butyl 3-(3-(1-isopropyl-2-(3-(2-morpholinoethoxy)benzoyl)hydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate
  8. customwas obtained (10.6 mg, 69.9%)

Sources & evidence

ORD record
ord-0b3805e386fe4c3c9f75c95d1c6eebf4
Source dataset
uspto-grants-2014_12
Patent number
US08906952B2

Reaction notes

Loading…