1-Hydroxybenzotriazole → HCID 86667976, compound

HRID 2403620Notes

Reaction equation

HRID 2403620 reaction equation
[CH3:1][N:2]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:16]=1)[C:3](=[O:13])[CH2:4][NH:5][C:6](=[O:12])[O:7]C(C)(C)C.[OH:33][CH2:34][C:35]([CH3:40])([CH3:39])[C:36]([OH:38])=[O:37].CCN=C=NCCCN(C)C.Cl.C1C=CC2N([OH:62])N=NC=2C=1>ClC(Cl)C.O>[C:36]([C@@H:35]([C@H:34]([C:6]([OH:12])=[O:7])[OH:33])[OH:62])([OH:38])=[O:37].[OH:37][CH2:36][C:35]([CH3:40])([CH3:39])[C:34]([N:30]1[CH2:29][CH2:28][N:27]([C:24]2[N:23]=[CH:22][C:21]([C:17]3[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=3)[CH2:14][N:2]([CH3:1])[C:3](=[O:13])[CH2:4][NH2:5])=[CH:26][N:25]=2)[CH2:32][CH2:31]1)=[O:33]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70570767HCID 70570767, compound

Product 1

HCID 86667976HCID 86667976, compoundYield 33.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl (2-{methyl[3-(2-piperazin-1-ylpyrimidin-5-yl)benzyl]amino}-2-oxoethyl)carbamate (250 mg) was dissolved in dichloroethane (3 ml), and 3-hydroxy-2,2-dimethylpropionic acid (74 mg), WSC hydrochloride (131 mg), and HOBt (92 mg) were added thereto, followed by stirring at 60° C. for 6 hours. To the reaction mixture was added water, followed by extraction with CHCl3. After drying over Na2SO4, the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in EtOH (3 ml), and 4 M hydrogen chloride/EtOAc (1 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The product was dissolved in EtOH (3 ml), and L-tartaric acid (27 mg) was added thereto, followed by stirring at room temperature overnight. The precipitated solid was collected by filtration to obtain N-(3-{2-[4-(3-hydroxy-2,2-dimethylpropanoyl)piperazin-1-yl]pyrimidin-5-yl}benzyl)-N-methylglycinamide L-tartrate (62 mg).

Workup

  1. extractionfollowed by extraction with CHCl3
  2. dry with materialAfter drying over Na2SO4
  3. concentrationthe solvent was concentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  5. dissolutionThe product was dissolved in EtOH (3 ml)
  6. addition4 M hydrogen chloride/EtOAc (1 ml) was added
  7. stirringby stirring at room temperature overnight
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additiona saturated aqueous sodium hydrogen carbonate solution was added
  10. extractionfollowed by extraction with CHCl3
  11. dry with materialThe organic layer was dried over Na2SO4
  12. concentrationthe solvent was concentrated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  14. dissolutionThe product was dissolved in EtOH (3 ml)
  15. additionL-tartaric acid (27 mg) was added
  16. stirringby stirring at room temperature overnight
  17. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-6a8e9a2dfbc4443685bad0b5ecbeb323
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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