Hexane → 4-[2-(4-Chloro-phenyl)-6-oxo-4-thioxo-6H-1-oxa-3b,5-diaza-cyclopenta[a]pentalen-5-yl]-N-(3-dimethylamino-propyl)-3,3-dimethyl-butyramide

HRID 1713026Notes

Reaction equation

HRID 1713026 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:11]=[C:12]4[C:18](=[O:19])[N:17]([CH2:20][C:21]([CH3:27])([CH3:26])[CH2:22][C:23](O)=[O:24])[C:16](=[S:28])[N:13]4[C:14]=3[CH:15]=2)=[CH:4][CH:3]=1.O[N:30]1[C:35](=O)C2C=CC=CC=2NN1.[CH3:41]CCCCC.[CH3:47][NH:48]N(CCC)NC.C(O[CH2:59][CH3:60])(=O)C>ClCCl.CN(C)C1C=CN=CC=1.CCN(CC)CC.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:11]=[C:12]4[C:18](=[O:19])[N:17]([CH2:20][C:21]([CH3:26])([CH3:27])[CH2:22][C:23]([NH:48][CH2:47][CH2:59][CH2:60][N:30]([CH3:35])[CH3:41])=[O:24])[C:16](=[S:28])[N:13]4[C:14]=3[CH:15]=2)=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 8058HexaneHCID 8857Ethyl Acetate2×HCID 98989233-Hydroxy-dihydrobenzotriazinoneHCID 115678964-[2-(4-chloro-phenyl)-6-oxo-4-thioxo-6H-1-oxa-3b,5-diaza-cyclopenta[a]pentalen-5-yl]-3,3-dimethyl-butyric acidHCID 56982963N,N-dimethylaminopropylamine

Product 1

HCID 116130364-[2-(4-Chloro-phenyl)-6-oxo-4-thioxo-6H-1-oxa-3b,5-diaza-cyclopenta[a]pentalen-5-yl]-N-(3-dimethylamino-propyl)-3,3-dimethyl-butyramideYield 69%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
25 °C

Procedure

Compound 11 (105 mg, 0.25 mmol) was dissolved in dichloromethane (5 ml) and 3-hydroxy-dihydrobenzotriazinone (HODhbt, 49 mg, 0.3 mmol, 1.2 molequivalents) was added thereto, followed by addition of Et3N (51 mg, 0.5 mmol, 2 molequivalents) and 4-dimethylaminopyridine (DMAP, 15 mg, 0.125 mmol, 0.5 molequivalents). The mixture was stirred at 25° C. for 16 hours while being monitored by TLC, using a 6:4 hexane:ethyl acetate mixture as eluent, until the appearance of a less polar spot of the active ester intermediate was observed. The solvent was then evaporated under reduced pressure and the residue was dissolved in chloroform (10 ml). N,N-dimethylaminopropylamine (DMAPA, 103 mg, 1 mmol, 2 molequivalents) was then added and the active ester was consumed after additional 1 hour, as indicated by TLC. Chloroform was thereafter added and the mixture was washed three times with 5% NaHCO3, with 1 M HCl, dried (Na2SO4) and the solvent was evaporated under reduced pressure to give a red solid. Chromatography was carried out using a 88:10:2 EtOAc:MeOH:Et3N mixture as eluent to give Compound 15 (101 mg, 69% yield) as a red solid.

Workup

  1. customThe solvent was then evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in chloroform (10 ml)
  3. customthe active ester was consumed after additional 1 hour
  4. additionChloroform was thereafter added
  5. washthe mixture was washed three times with 5% NaHCO3
  6. dry with materialwith 1 M HCl, dried (Na2SO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customto give a red solid

Sources & evidence

ORD record
ord-198a88d346ff46a4aa44439804cbd749
Source dataset
uspto-grants-2010_09
Patent number
US07795255B2

Reaction notes

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