Dichloromethane → 2-[3-(methylamino)-3-oxopropyl]-N,N-bis(3-methylbutyl)-1-(3-piperidin-1-ylpropyl)-1H-benzimidazole-6-carboxamide hydrochloride

HRID 1516753노트

반응식

HRID 1516753 반응식
CN(C(ON1N=N[C:11]2C=CC=C[C:10]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([N:26]([CH:29](C)C)[CH2:27][CH3:28])(C)C.[NH2:32][C:33]1[CH:51]=[CH:50][C:36]([C:37]([N:39]([CH2:45][CH2:46][CH:47]([CH3:49])[CH3:48])[CH2:40][CH2:41][CH:42]([CH3:44])[CH3:43])=[O:38])=[CH:35][C:34]=1[NH:52][CH2:53][CH2:54][CH2:55][N:56]1[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]1.C(=O)([O-])[OH:63].[Na+].[Cl:67]CCl>CN(C=O)C.C(OCC)(=O)C.C(O)(=O)C>[ClH:67].[CH3:29][NH:26][C:27](=[O:63])[CH2:28][CH2:10][C:11]1[N:52]([CH2:53][CH2:54][CH2:55][N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)[C:34]2[CH:35]=[C:36]([C:37]([N:39]([CH2:45][CH2:46][CH:47]([CH3:48])[CH3:49])[CH2:40][CH2:41][CH:42]([CH3:43])[CH3:44])=[O:38])[CH:50]=[CH:51][C:33]=2[N:32]=1

참가 물질

9

반응물 5

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 684463484-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide

생성물 1

HCID 696539452-[3-(methylamino)-3-oxopropyl]-N,N-bis(3-methylbutyl)-1-(3-piperidin-1-ylpropyl)-1H-benzimidazole-6-carboxamide hydrochloride

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

TBTU (67 mg, 1 eq) and diisopropylethylamine (70 μL, 2 eq) are successively added to a solution of N-methylsuccinimic acid (26 mg, 1 eq) in DMF (1 ml). After stirring for 30 minutes at ambient temperature, a solution of 4-amino-N,N-bis(3-methylbutyl)-3-[(3-piperidin-1-ylpropyl)amino]benzamide (66 mg) in DMF (1 ml) is added to the mixture. The mixture is stirred for 15 hours at a temperature of approximately 20° C. then diluted in ethyl acetate (10 ml) and a saturated aqueous solution of sodium hydrogen carbonate (4 ml) is added. After decantation and extractions, the combined organic phases are washed with salt water, dried over Na2SO4 and concentrated under reduced pressure at 40° C. The oil thus obtained is solubilized in acetic acid (2 ml). The mixture is heated at 100° C. for 18 hours then cooled down to ambient temperature and concentrated under reduced pressure at 40° C. A saturated aqueous solution of sodium hydrogen carbonate is added to the residue obtained dissolved in dichloromethane. After decantation and extractions, the combined organic phases are washed with salt water, dried over Na2SO4 and concentrated under reduced pressure. Purification of the residue obtained by flash chromatography on silica gel (eluent: dichloromethane 100% to dichloromethane/methanol 85:15) produces the expected compound in the form of the free base. The corresponding hydrochloride salt is formed by the addition of a 1N solution of hydrochloric acid in diethyl ether. The precipitate obtained is filtered and dried in order to produce the expected monohydrochloride compound (64 mg, 54% yield).

후처리

  1. stirringThe mixture is stirred for 15 hours at a temperature of approximately 20° C.
  2. extractionAfter decantation and extractions
  3. washthe combined organic phases are washed with salt water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure at 40° C
  6. customThe oil thus obtained
  7. temperatureThe mixture is heated at 100° C. for 18 hours
  8. temperaturethen cooled down to ambient temperature
  9. concentrationconcentrated under reduced pressure at 40° C
  10. additionA saturated aqueous solution of sodium hydrogen carbonate is added to the residue
  11. customobtained
  12. extractionAfter decantation and extractions
  13. washthe combined organic phases are washed with salt water
  14. dry with materialdried over Na2SO4
  15. concentrationconcentrated under reduced pressure
  16. customPurification of the residue
  17. customobtained by flash chromatography on silica gel (eluent: dichloromethane 100% to dichloromethane/methanol 85:15)

출처 및 근거

ORD 기록
ord-c32b86ecb31d4812849ea9d4647f9dba
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227485B2

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