Ammonium Chloride → 2-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide

HRID 579396

반응식

HRID 579396 반응식
[OH:1][C@@:2]1([C:34]([F:37])([F:36])[F:35])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:21])[CH3:20])[CH:11]=[C:10]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:33])([CH3:32])[C:29](O)=[O:30])[CH:27]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[Cl-].[NH4+].C([N:43](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C>CN(C)C=O.O>[OH:1][C@@:2]1([C:34]([F:37])([F:35])[F:36])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:21])[CH3:20])[CH:11]=[C:10]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:32])([CH3:33])[C:29]([NH2:43])=[O:30])[CH:27]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 1175991392-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acidHCID 178484293HCID 178484293, 화합물

생성물 1

HCID 783249642-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

Under a nitrogen atmosphere, 2-{4-[(9R)-9-hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acid (89 mg) was dissolved in N,N-dimethylformamide (1 ml), ammonium chloride (28 mg), N,N-diisopropylethylamine (148 μl) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridin-1-ium 3-oxide hexafluorophosphate (HATU) (99 mg) were added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate (twice). The obtained organic layer was washed successively with diluted brine (twice) and saturated brine. The obtained organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the solvent in the filtrate was evaporated. The obtained residue was purified by silica gel thin layer chromatography (a mixture of chloroform and methanol at a mixing ratio 9:1 (chloroform:methanol) was used as an elution solvent) to give the title compound (48 mg, optical purity 96.9% e.e.). The optical purity was determined under the HPLC analysis condition 2. Retention time of (R) form 13.0 min, retention time of (S) form 14.4 min.

후처리

  1. extractionthe mixture was extracted with ethyl acetate (twice)
  2. washThe obtained organic layer was washed successively with diluted brine (twice) and saturated brine
  3. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  4. filtrationthe insoluble material was filtered off
  5. customthe solvent in the filtrate was evaporated
  6. customThe obtained residue was purified by silica gel thin layer chromatography (
  7. additiona mixture of chloroform and methanol at a mixing ratio 9:1 (chloroform:methanol)

출처 및 근거

ORD 기록
ord-4956b61d6f374e4a81ae4860ba7c203c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040717B2

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