Hydrochloric Acid → (S)-2-(4-bromo-3-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 1480588Notes

Reaction equation

HRID 1480588 reaction equation
[ClH:1].[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([C@H:29]2[N:33](C(OC(C)(C)C)=O)[C:32]([CH3:42])([CH3:41])[CH2:31][CH2:30]2)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][C@@H:24]([OH:28])[C:20]=4[N:21]=[CH:22][N:23]=3)[CH2:14][CH2:13]2)=[O:11])=[CH:5][C:4]=1[F:43]>C(Cl)Cl>[ClH:1].[ClH:1].[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([C@@H:29]2[CH2:30][CH2:31][C:32]([CH3:42])([CH3:41])[NH:33]2)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][C@@H:24]([OH:28])[C:20]=4[N:21]=[CH:22][N:23]=3)[CH2:14][CH2:13]2)=[O:11])=[CH:5][C:4]=1[F:43]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66846078(S)-tert-butyl 5-((S)-1-(4-bromo-3-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 66845095(S)-2-(4-bromo-3-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 31.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4.0M HCl in dioxanes (1.5 mL) was added to a solution of (S)-tert-butyl 5-((S)-1-(4-bromo-3-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 (0.012 g, 0.0186 mmol) in DCM (5 mL). This solution was stirred at room temperature overnight, and then the solvent was removed to yield (S)-2-(4-bromo-3-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 (0.00367 g, 0.00593 mmol, 31.9% yield). HPLC, 254 nm=1.99 minutes, 96.93% purity, LCMS (APCI+) 548.3 m/z [M+H]+; Retention time=2.56 minutes, 1H NMR (400 MHz, CD3OD) 8.59 (s, 1H), 7.71 (t, J=7.418 Hz, 1H), 7.39 (dd, J1=1.562 Hz, J2=9.761 Hz, 1H), 7.22 (d, J=7.418 Hz, 1H), 5.30 (t, J=7.809 Hz, 1H), 4.53 (d, J=9.371 Hz, 1H), 3.81-3.65 (m, 6H), 2.30 (dd, J1=7.809 Hz, J2=12.884 Hz, 1H), 2.21-2.15 (m, 1H), 2.02-1.85 (m, 4H), 1.55 (s, 3H), 1.45 (s, 3H), 1.19 (d, J=7.028 Hz, 3H).

Workup

  1. customthe solvent was removed

Sources & evidence

ORD record
ord-697a94eb2966416d8c9d953605a1b5e0
Source dataset
uspto-grants-2016_08
Patent number
US09409886B2

Reaction notes

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