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 340148Notes

Reaction equation

HRID 340148 reaction equation
[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

Participants

5

Reactant 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

Product 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 dihydrochlorideYield 231.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-140fc086771d467e976a0217406b99eb
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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