Lithium Hydroxide → (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1,4-diazepan-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride

HRID 2192452노트

반응식

HRID 2192452 반응식
[N+](C1C=CC(C([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:26][CH2:25][CH2:24][N:23]([C:27](=[O:48])[C@@H:28]([C:41]5[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=5)[CH2:29][N:30](C(OC(C)(C)C)=O)[CH:31]([CH3:33])[CH3:32])[CH2:22][CH2:21]4)[C:14]=3[C@H:13]([CH3:49])[CH2:12]2)=O)=CC=1)([O-])=O.[OH-].[Li+]>C1COCC1.O.CCOC(C)=O>[ClH:47].[ClH:47].[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([C@@H:28]([CH2:29][NH:30][CH:31]([CH3:33])[CH3:32])[C:27]([N:23]2[CH2:24][CH2:25][CH2:26][N:20]([C:19]3[C:14]4[C@H:13]([CH3:49])[CH2:12][C@@H:11]([OH:10])[C:15]=4[N:16]=[CH:17][N:18]=3)[CH2:21][CH2:22]2)=[O:48])=[CH:42][CH:43]=1

참가 물질

5

반응물 2

HCID 3939Lithium HydroxideHCID 67437824(5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

생성물 1

HCID 67438019(S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1,4-diazepan-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride수율 231.4%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 21881883Oxolane--water (1/1)용매

실험 절차

(5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (50 mg, 0.069 mmol) was dissolved in a THF/water mixture (1:1, 2 mL), and then solid lithium hydroxide (6 mg, 0.139 mmol) was added. The resultant mixture was stirred at ambient for 16 hours, at which time it was diluted with EtOAc and then washed twice with saturated sodium bicarbonate solution. The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting residue was taken up in dichloromethane (5 mL), and then HCl (4M in dioxane, 0.25 mL) was added. The mixture was stirred for 16 hours, at which time solvents were removed via rotary evaporation. The resulting residue was dissolved in dichloromethane (1 mL) and then added to diethyl ether (50 mL). The resulting precipitate was collected by filtration and dried to give (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-1,4-diazepan-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride (29 mg, 78%). LCMS (APCI+) M+=472.2, Rt=2.05 min.

후처리

  1. washwashed twice with saturated sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionHCl (4M in dioxane, 0.25 mL) was added
  6. customwere removed via rotary evaporation
  7. dissolutionThe resulting residue was dissolved in dichloromethane (1 mL)
  8. additionadded to diethyl ether (50 mL)
  9. filtrationThe resulting precipitate was collected by filtration
  10. customdried

출처 및 근거

ORD 기록
ord-ebcf7e174e674c5981cfd2cf357f75f8
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329709B2

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