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

HRID 1480584Notes

Reaction equation

HRID 1480584 reaction equation
[ClH:1].O1CCOCC1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([C@H:35]2[N:39](C(OC(C)(C)C)=O)[C:38]([CH3:48])([CH3:47])[CH2:37][CH2:36]2)[C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[C:25]4[C@H:32]([CH3:33])[CH2:31][C@@H:30]([OH:34])[C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:20][CH2:19]2)=[O:17])=[C:11]([F:49])[CH:10]=1>C(Cl)Cl>[ClH:8].[ClH:1].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([C@@H:35]2[CH2:36][CH2:37][C:38]([CH3:48])([CH3:47])[NH:39]2)[C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[C:25]4[C@H:32]([CH3:33])[CH2:31][C@@H:30]([OH:34])[C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:20][CH2:19]2)=[O:17])=[C:11]([F:49])[CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66845611(S)-tert-butyl 5-((S)-1-(4-chloro-2-fluorophenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

Product 1

HCID 66845797(S)-2-(4-chloro-2-fluorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)ethanone dihydrochlorideYield 84.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4N HCl in dioxane (3 mL, 0.191 mmol) was added to a solution of (S)-tert-butyl 5-((S)-1-(4-chloro-2-fluorophenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (0.115 g, 0.191 mmol) in dry DCM (30 mL) and stirred at room temperature for 2 hours. The reaction was concentrated to dryness to reveal (S)-2-(4-chloro-2-fluorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)ethanone dihydrochloride (0.093 g, 0.162 mmol, 84.7% yield). HPLC, 220 nM=1.93 minutes, 100% purity. LC/MS=2.22 minutes, (APCI+) m/z=502 [M+H]+. 1H NMR (400 MHz, D2O) 8.38 (s, 1H), 7.27 (d, J=10.54 Hz, 1H), 7.21-7.15 (m, 2H), 5.22 (t, J=7.81 Hz, 1H), 4.43 (d, J=8.98 Hz, 1H), 4.19 (dd, J1=8.59 Hz, J2=14.8 Hz, 1H), 4.15-4.05 (m, 1H), 3.87-3.75 (m, 2H), 3.74-3.46 (m, 5H), 3.42 (q, J=7.03 Hz, 2H), 3.39-3.25 (m, 2H), 2.19 (dd, J1=7.08 Hz, J2=13.27 Hz, 1H), 2.07-1.97 (m, 1H), 1.90-1.72 (m, 4H), 1.36 (s, 3H), 1.31 (s, 3H), 1.04 (t, J=7.03 Hz, 2H), 0.97 (d, J=7.03 Hz, 3H).

Workup

  1. concentrationThe reaction was concentrated to dryness

Sources & evidence

ORD record
ord-61374af7c8f04a858e53cc17d21ccdd4
Source dataset
uspto-grants-2016_08
Patent number
US09409886B2

Reaction notes

Loading…