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 521389ノート

反応式

HRID 521389 の反応式
[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

参加物

5

反応物 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

生成物 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 dihydrochloride収率 231.4%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 21881883Oxolane--water (1/1)溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-4822bf63b82e435fae72268355dc2add
出典データセット
uspto-grants-2016_05
特許番号
US09328091B2

反応ノート

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