Sodium → HCID 178457607, compound

HRID 1690627Notes

Reaction equation

HRID 1690627 reaction equation
[Na].Cl.[CH2:3]([NH:6][C:7]([NH2:9])=[NH:8])[CH2:4][CH3:5].[CH3:10][O:11][CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:21]=[C:20]([C:22]([CH3:30])([CH3:29])[CH2:23][C:24]([O:26]CC)=O)[CH:19]=[CH:18][C:17]=1[C:31]1[CH:36]=[CH:35][C:34]([C:37]([N:39]2[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]2)=[O:38])=[CH:33][CH:32]=1.[Cl:46]CCl.[Cl-].[Na+].O>C(O)C.CN(C=O)C>[ClH:46].[NH:8]=[C:7]([NH:6][CH2:3][CH2:4][CH3:5])[NH:9][C:24](=[O:26])[CH2:23][C:22]([C:20]1[CH:19]=[CH:18][C:17]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([N:39]3[CH2:40][CH2:41][N:42]([CH3:45])[CH2:43][CH2:44]3)=[O:38])=[CH:33][CH:32]=2)=[C:16]([O:15][CH2:14][CH2:13][CH2:12][O:11][CH3:10])[CH:21]=1)([CH3:29])[CH3:30]

Participants

7

Reactant 4

HCID 5360545Sodium2×HCID 66906304HCID 66906304, compoundHCID 131726697Dichloromethane brineHCID 178457588Propylguanidine hydrochloride

Product 1

HCID 178457607HCID 178457607, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium (0.15 g, 6.5 mmol) was dissolved in ethanol (3.5 mL) at room temperature. Once all the sodium was dissolved, propylguanidine hydrochloride (0.65 g, 6.5 mmol) was added and the mixture was stirred for 1 h. A white precipitate formed and was filtered off. The filtrate was evaporated under reduced pressure and a solution of ethyl 3-{2-(3-methoxypropoxy)-4′-[(4-methylpiperazin-1-yl)carbonyl]biphenyl-4-yl}-3-methylbutanoate (0.51 g, 1.0 mmol) and DMF (3.5 mL) was added at room temperature. The mixture was stirred at 50° C. until reaction was completed. The mixture was then poured into dichloromethane/brine (50/50). The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was then dissolved in ethanol and HCl in diethyl ether (1N, 4 mL) was added. The mixture was evaporated and the residue was purified on reverse phase (C18) flash chromatography (H2O, HCl N/1000, acetonitrile, 100/0 to 80/20) to afford 0.20 g (35%) of the desired product as a white solid: mp=99° C.; 1H NMR (400 MHZ, d6-DMSO) δ 12.22 (bs, 1H), 11.15 (bs, 1H), 9.02 (t, 1H), 8.69 (bs, 1H), 7.58 (m, 4H), 7.30 (d, 1H), 7.15 (s, 1H), 7.09 (d, 1H), 4.08 (t, 2H), 3.38 (t, 2H), 3.21 (m, 10H), 3.18 (s, 3H), 2.81 (s, 2H), 2.73 (s, 3H), 1.86 (m, 2H), 1.49 (m, 2H), 1.41 (s, 6H), 0.87 (t, 3H).

Workup

  1. customA white precipitate formed
  2. filtrationwas filtered off
  3. customThe filtrate was evaporated under reduced pressure
  4. stirringThe mixture was stirred at 50° C. until reaction
  5. extractionThe aqueous layer was extracted three times with dichloromethane
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. dissolutionThe residue was then dissolved in ethanol
  11. additionHCl in diethyl ether (1N, 4 mL) was added
  12. customThe mixture was evaporated
  13. customthe residue was purified on reverse phase (C18) flash chromatography (H2O, HCl N/1000, acetonitrile, 100/0 to 80/20)

Sources & evidence

ORD record
ord-90b4d6ef6ad64e2691aab47ebff8929f
Source dataset
uspto-grants-2012_04
Patent number
US08153647B2

Reaction notes

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