Diisopropylethylamine → (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone hydrochloride

HRID 1916382Notes

Reaction equation

HRID 1916382 reaction equation
Cl.Cl.[F:3][C@H:4]1[C:8]2[N:9]=[CH:10][N:11]=[C:12]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:7]=2[C@H:6]([CH3:19])[CH2:5]1.C(OC([N:27]1[CH2:31][CH2:30][CH2:29][C@H:28]1[C@H:32]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:33](O)=[O:34])=O)(C)(C)C.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[ClH:42].[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([C@@H:32]([C@@H:28]2[CH2:29][CH2:30][CH2:31][NH:27]2)[C:33]([N:16]2[CH2:15][CH2:14][N:13]([C:12]3[C:7]4[C@H:6]([CH3:19])[CH2:5][C@@H:4]([F:3])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:18][CH2:17]2)=[O:34])=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564918(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acidHCID 66845507(5R,7R)-7-fluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride

Product 1

HCID 66845106(S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone hydrochlorideYield 151.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(5R,7R)-7-Fluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine di-hydrochloride (0.050 g, 0.16 mmol) was combined with (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (0.055 g, 0.16 mmol) in dichloromethane (10 mL). Diisopropylethylamine (0.1 mL, 0.57 mmol) and HBTU (0.061 g, 0.16 mmol) were added, and the mixture was stirred at ambient temperature for 1 hour. The solvent was removed by concentration in vacuo and the residue was purified by column chromatography on SiO2, eluting with 2:1 hexanes/ethyl acetate. The product was dissolved in dioxane (1 mL) and treated with a solution of 4M HCl in dioxane (2 mL). After stirring at ambient temperature for 2 hours, the mixture was concentrated in vacuo to yield (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-((S)-pyrrolidin-2-yl)ethanone hydrochloride (0.060 g, 81% yield). MS (APCI+) [M+H] 458.2.

Workup

  1. customThe solvent was removed by concentration in vacuo
  2. customthe residue was purified by column chromatography on SiO2
  3. washeluting with 2:1 hexanes/ethyl acetate
  4. dissolutionThe product was dissolved in dioxane (1 mL)
  5. additiontreated with a solution of 4M HCl in dioxane (2 mL)
  6. stirringAfter stirring at ambient temperature for 2 hours
  7. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-09f8072fda394e57890ad4fa83b7966a
Source dataset
uspto-grants-2013_12
Patent number
US08618097B2

Reaction notes

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