1,2-Dibromoethane → HCID 71468329, compound

HRID 1401069Notes

Reaction equation

HRID 1401069 reaction equation
OC1C=CC(C(NN(C(=O)/C=C/C2C3C(=CC=CC=3)N(C(OC(C)(C)C)=O)C=2)C(C)C)=O)=CC=1.C([O-])([O-])=O.[K+].[K+].BrCCBr.Br[CH2:46][CH2:47][O:48][C:49]1[CH:81]=[CH:80][C:52]([C:53]([NH:55][N:56]([C:60](=[O:79])/[CH:61]=[CH:62]/[C:63]2[C:71]3[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=3)[N:65]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[CH:64]=2)[CH:57]([CH3:59])[CH3:58])=[O:54])=[CH:51][CH:50]=1.[NH:82]1[CH2:87][CH2:86][O:85][CH2:84][CH2:83]1>C(#N)C>[CH:57]([N:56]([C:60](=[O:79])/[CH:61]=[CH:62]/[C:63]1[C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[N:65]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[CH:64]=1)[NH:55][C:53](=[O:54])[C:52]1[CH:80]=[CH:81][C:49]([O:48][CH2:47][CH2:46][N:82]2[CH2:87][CH2:86][O:85][CH2:84][CH2:83]2)=[CH:50][CH:51]=1)([CH3:59])[CH3:58]

Participants

7

Reactant 5

HCID 78391,2-DibromoethaneHCID 8083MorpholineHCID 11430Potassium Carbonate2×HCID 71468217HCID 71468217, compoundHCID 86711426HCID 86711426, compound

Product 1

HCID 71468329HCID 71468329, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
85 °C

Procedure

(E)-tert-butyl 3-(3-(2-(4-hydroxybenzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate (50.0 mg, 0.11 mmol) and K2CO3 (59.63 mg, 0.43 mmol) dissolved in anhydrous acetonitrile (10.0 ml), 1,2-dibromoethane (0.0465 ml, 0.54 mmol) was added drop-by-drop. The reaction mixture was refluxed at 85° C. for 48 hr. After concentration under reduced pressure, the solution was separated through silica gel chromatography (n-hexane:EtOAc:methanol=14:3:1) so that ivory solid form of (E)-tert-butyl 3-(3-(2-(4-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate was obtained.(34 mg, 55.3%). The resultant (E)-tert-butyl 3-(3-(2-(4-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate (34.0 mg, 0.06 mmol) and K2CO3 (16.5 mg, 0.12 mmol) were dissolved in anhydrous acetonitrile (10.0 ml), and the solution was drop-wise added with morpholine (0.01031 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=30:1) so that ivory solid form of (E)-tert-butyl3-(3-(1-isopropyl-2-(4-(2-morpholinoethoxy)benzoyl)hydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate was obtained (8.2 mg, 23.9%).

Workup

  1. concentrationAfter concentration under reduced pressure
  2. customthe solution was separated through silica gel chromatography (n-hexane:EtOAc:methanol=14:3:1) so that ivory solid form of (E)-tert-butyl 3-(3-(2-(4-(2-bromoethoxy)benzoyl)-1-isopropylhydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate
  3. customwas obtained
  4. temperatureThe reaction mixture was refluxed at 85° C. for 12 hr
  5. concentrationAfter concentration under reduced pressure
  6. customthe solution was separated through silica gel chromatography (MC:methanol=30:1) so that ivory solid form of (E)-tert-butyl3-(3-(1-isopropyl-2-(4-(2-morpholinoethoxy)benzoyl)hydrazinyl)-3-oxoprop-1-enyl)-1H-indole-1-carboxylate
  7. customwas obtained (8.2 mg, 23.9%)

Sources & evidence

ORD record
ord-1736f13ced7f43d38e27e4a89b3c269d
Source dataset
uspto-grants-2014_12
Patent number
US08906952B2

Reaction notes

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