Sodium → 3-[4'-{[4-(dimethylamino)piperidin-1-yl]methyl}-2-(3-methoxypropoxy)biphenyl-4-yl]-N-(5,5-dimethyl-4-oxo-1,4,5,6-tetrahydropyrimidin-2-yl)propanamide hydrochloride

HRID 1690629노트

반응식

HRID 1690629 반응식
[Na].Cl.N[C:4]([NH:6][CH2:7][C:8]([CH3:13])([CH3:12])[C:9]([NH2:11])=[O:10])=[NH:5].[CH3:14][N:15]([CH3:48])[CH:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37](OCC)=[O:38])=[CH:31][C:30]=3[O:42][CH2:43][CH2:44][CH2:45][O:46][CH3:47])=[CH:25][CH:24]=2)[CH2:18][CH2:17]1.[Cl:49]CCl.[Cl-].[Na+].O>C(O)C.CN(C=O)C>[ClH:49].[CH3:48][N:15]([CH3:14])[CH:16]1[CH2:17][CH2:18][N:19]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37]([NH:5][C:4]4[NH:6][CH2:7][C:8]([CH3:12])([CH3:13])[C:9](=[O:10])[N:11]=4)=[O:38])=[CH:31][C:30]=3[O:42][CH2:43][CH2:44][CH2:45][O:46][CH3:47])=[CH:27][CH:28]=2)[CH2:20][CH2:21]1

참가 물질

7

반응물 4

HCID 5360545Sodium2회HCID 66906460Ethyl 3-[4'-{[4-(dimethylamino)piperidin-1-yl]methyl}-2-(3-methoxy-propoxy)biphenyl-4-yl]propanoateHCID 131726697Dichloromethane brineHCID 1784492223-{[Amino(imino)methyl]amino}-2,2-dimethylpropanamide hydrochloride

생성물 1

HCID 1784953603-[4'-{[4-(dimethylamino)piperidin-1-yl]methyl}-2-(3-methoxypropoxy)biphenyl-4-yl]-N-(5,5-dimethyl-4-oxo-1,4,5,6-tetrahydropyrimidin-2-yl)propanamide hydrochloride수율 19%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 6228Dimethylformamide용매

실험 절차

Sodium (0.15 g, 6.5 mmol) was dissolved in ethanol (3.5 mL) at room temperature. Once all the sodium was dissolved, 3-{[amino(imino)methyl]amino}-2,2-dimethylpropanamide hydrochloride (1.26 g, 6.5 mmol) was added and the mixture was stirred for 1 hr. A white precipitate formed and was filtered off. The filtrate was evaporated under reduced pressure and a solution of ethyl 3-[4′-{[4-(dimethylamino)piperidin-1-yl]methyl}-2-(3-methoxy-propoxy)biphenyl-4-yl]propanoate (0.50 g, 1.0 mmol) and DMF (3.5 mL) was added at room temperature. After completion of the reaction, the mixture was 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, 6 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 0.12 g (19%) of the desired product as a white solid: mp=132° C.; 1H NMR (400 MHZ, d6-DMSO) δ 7.50 (m, 4H), 7.23 (d, 1H), 7.00 (s, 1H), 6.91 (d, 1H), 4.02 (t, 2H), 3.51 (s, 2H), 3.38 (t, 2H), 3.29 (m, 4H), 3.20 (s, 3H), 3.02 (t, 2H), 2.95 (t, 2H), 2.69 (s, 6H), 2.05 (m, 5H), 1.82 (m, 2H), 1.17 (m, 2H), 1.05 (s, 6H).

후처리

  1. customA white precipitate formed
  2. filtrationwas filtered off
  3. customThe filtrate was evaporated under reduced pressure
  4. customAfter completion of the 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, 6 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)

출처 및 근거

ORD 기록
ord-e60cae582a52434681193251b08e6e5e
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08153647B2

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