Hydrochloric Acid → 6-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide

HRID 1444949노트

반응식

HRID 1444949 반응식
[BH4-].[Na+].[Cl-].[Ca+2].[Cl-].[OH:6][C@@:7]([C:40]1[CH:49]=[CH:48][C:47]2[C:42](=[CH:43][CH:44]=[C:45]([C:50]([NH:52][CH3:53])=[O:51])[CH:46]=2)[CH:41]=1)([C:16]1[N:17]=[CH:18][N:19]([C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1)[CH2:8][C:9](OC(C)(C)C)=[O:10].Cl>C(OCC)(=O)C.O.C1COCC1.C(O)C>[OH:6][C@@:7]([C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[CH:46]=[C:45]([C:50]([NH:52][CH3:53])=[O:51])[CH:44]=[CH:43]2)([C:16]1[N:17]=[CH:18][N:19]([C:21]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1)[CH2:8][CH2:9][OH:10]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57465810tert-butyl(3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

생성물 1

HCID 574658086-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide수율 61%

시약·촉매·용매 4

HCID 702Ethanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

6.5 mL of ethanol and 6.5 mL of THF were added to 0.47 g (12.5 mmol, 8 eq) of sodium borohydride. 0.7 g (6.27 mmol, 4 eq) of calcium chloride was added at 4˜5° C., and the mixture was stirred at 4˜5° C. for 35 minutes. 1 g (1.57 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate was added at 5° C. The mixture was stirred at 23˜29° C. for 6 hours. 35 mL of water was added dropwise. 12.5 mL of 1N hydrochloric acid was added dropwise, diluted with 20 mL of ethyl acetate, and the layers were separated. The aqueous layer was re-extracted with 20 mL of ethyl acetate. The organic layers were combined, and washed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution. After concentrated under reduced pressure, the concentration residue was dissolved in 1 mL of ethanol, and allowed to stand overnight. Crystals were filtered, and washed with 0.2 mL of ethanol. The filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE were added to the concentration residue, crystals were loosened, filtered, and washed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml. Vacuum drying (40° C.) to a constant weight afforded 0.5 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 61%).

후처리

  1. stirringThe mixture was stirred at 23˜29° C. for 6 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was re-extracted with 20 mL of ethyl acetate
  4. washwashed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution
  5. concentrationAfter concentrated under reduced pressure
  6. dissolutionthe concentration residue was dissolved in 1 mL of ethanol
  7. waitto stand overnight
  8. filtrationCrystals were filtered
  9. washwashed with 0.2 mL of ethanol
  10. concentrationThe filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE
  11. additionwere added to the concentration residue, crystals
  12. filtrationfiltered
  13. washwashed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml
  14. customVacuum drying (40° C.) to a constant weight

출처 및 근거

ORD 기록
ord-35bba36c6f3a45dfb1476e4b59d24c59
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07662974B2

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