Hydrochloric Acid → (S)-2-(4-chlorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)ethanone dihydrochloride

HRID 340145Notes

Reaction equation

HRID 340145 reaction equation
[ClH:1].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([C@H:28]2[N:32](C(OC(C)(C)C)=O)[C:31]([CH3:41])([CH3:40])[CH2:30][CH2:29]2)[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH2:14][CH2:13]2)=[O:11])=[CH:5][CH:4]=1>O1CCOCC1>[ClH:2].[ClH:1].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]([C@@H:28]2[CH2:29][CH2:30][C:31]([CH3:40])([CH3:41])[NH:32]2)[C:10]([N:12]2[CH2:13][CH2:14][CH:15]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH2:16][CH2:17]2)=[O:11])=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67436379(S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

Product 1

HCID 44196954(S)-2-(4-chlorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)ethanone dihydrochlorideYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 4M HCl in 1,4-dioxane (0.344 mL) was added to a solution of (S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (26 mg, 0.046 mmol) in 1,4-dioxane (1 mL) at 0° C. The mixture was allowed to warm up and stirred at room temperature for 4 hours. The mixture was concentrated in vacuo. The resulting residue was dissolved in minimal DCM and added to the ether (5 mL) at 0° C. A solid precipitated. The mixture was decanted and dried in vacuo to give (S)-2-(4-chlorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperidin-1-yl)ethanone dihydrochloride as a solid (26 mg, 100%). MS (APCI+) [M+H]+467.3. 1H NMR (D2O, 500 MHz) δ 8.96 (s, 1H), 7.48 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H), 4.60-4.20 (m, 3H), 4.01-3.52 (m, 6H), 3.48-3.05 (m, 4H), 2.85-2.82 (m, 1H), 2.43-2.36 (m, 1H), 1.96-1.86 (m, 5H), 1.32 (s, 3H), 1.1.31 (s, 3H), 1.19 (d, J=7.5 Hz, 3H).

Workup

  1. temperatureto warm up
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in minimal DCM
  4. additionadded to the ether (5 mL) at 0° C
  5. customA solid precipitated
  6. customThe mixture was decanted
  7. customdried in vacuo

Sources & evidence

ORD record
ord-ba14be3e105748b9a651807b73b42ded
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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