Potassium Iodide → HCID 90830949, compound

HRID 1695306Notes

Reaction equation

HRID 1695306 reaction equation
[CH3:1]/[CH:2]=[C:3]1/[CH2:4][CH:5]2[N:16]([CH2:17]/1)[C:14](=[O:15])[C:13]1[C:8](=[CH:9][C:10]([OH:20])=[C:11]([O:18][CH3:19])[CH:12]=1)[N:7]=[CH:6]2.[C:21](=[O:24])([O-])[O-].[K+].[K+].C(OC([NH:33][CH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:43]=[C:42]([CH2:44]Br)[CH:41]=[C:40]([CH2:46]Br)[CH:39]=1)=O)C=C.[I-].[K+]>CN(C)C=O>[NH2:33][CH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:39]=[C:40]([CH2:46][O:20][C:10]2[C:11]([O:24][CH3:21])=[CH:12][C:13]3[C:14](=[O:15])[N:16]4[CH2:17][C:3](=[CH:2][CH3:1])[CH2:4][C@H:5]4[CH:6]=[N:7][C:8]=3[CH:9]=2)[CH:41]=[C:42]([CH2:44][O:20][C:10]2[C:11]([O:18][CH3:19])=[CH:12][C:13]3[C:14](=[O:15])[N:16]4[CH2:17][C:3](=[CH:2][CH3:1])[CH2:4][C@H:5]4[CH:6]=[N:7][C:8]=3[CH:9]=2)[CH:43]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5856240PRETOMAYMYCINHCID 57570963HCID 57570963, compound

Product 1

HCID 90830949HCID 90830949, compoundYield 0.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

To a stirred solution of pre-tomaymycin (21 mg) in dimethylformamide (0.7 mL), were added potassium carbonate (32 mg), 1-(3-allyloxycarbonylamino-propyloxy)-3,5-bis-(bromomethyl)-benzene (16.2 mg) and potassium iodide (12.8 mg). The reaction was stirred for 20 h at 30° C. Solids were filtered off, washed twice with dimethylformamide (0.2 mL) then discarded. Water (0.5 mL) was added to the combined dimethylformamide solution and the resulting precipitate was filtered off, washed with water and dried by centrifugal evaporation over a Jouan Model RC10.10 apparatus. To the crude compound (27 mg) dissolved in dimethylformamide (0.8 mL), tetrakis(triphenylphosphine) palladium (2 mg), triphenylphosphine (0.9 mg) and pyrrolidine (5.6 μL) were added. After stirring for 15 h at 30° C., tetrakis(triphenylphosphine) palladium (2 mg), triphenylphosphine (1 mg) and pyrrolidine (2.8 μL) were added and the reaction mixture was stirred at room temperature for another 15 h. Water (0.4 mL) was added to the dimethylformamide solution and formic acid was added until complete dissolution of the precipitate. The resulting solution was injected for HPLC purification according to method B1. The appropriate fractions were combined and concentrated by centrifugal evaporation over a Jouan Model RC10.10. apparatus to afford 8,8′-[5-(3-aminopropyloxy)-1,3-benzenediylbis-(methylenoxy)]-bis[(S)-2-eth-(E)-ylidene-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one] (0.2 mg).

Workup

  1. filtrationSolids were filtered off
  2. washwashed twice with dimethylformamide (0.2 mL)
  3. additionWater (0.5 mL) was added to the combined dimethylformamide solution
  4. filtrationthe resulting precipitate was filtered off
  5. washwashed with water
  6. customdried by centrifugal evaporation over a Jouan Model RC10.10 apparatus
  7. dissolutionTo the crude compound (27 mg) dissolved in dimethylformamide (0.8 mL)
  8. additiontetrakis(triphenylphosphine) palladium (2 mg), triphenylphosphine (0.9 mg) and pyrrolidine (5.6 μL) were added
  9. stirringAfter stirring for 15 h at 30° C.
  10. additiontetrakis(triphenylphosphine) palladium (2 mg), triphenylphosphine (1 mg) and pyrrolidine (2.8 μL) were added
  11. stirringthe reaction mixture was stirred at room temperature for another 15 h
  12. additionWater (0.4 mL) was added to the dimethylformamide solution and formic acid
  13. additionwas added until complete dissolution of the precipitate
  14. customThe resulting solution was injected for HPLC purification
  15. concentrationconcentrated by centrifugal evaporation over a Jouan Model RC10.10

Sources & evidence

ORD record
ord-334b95280c24495c864f9d9a1e0c310d
Source dataset
uspto-grants-2012_04
Patent number
US08163736B2

Reaction notes

Loading…