Diisopropylethylamine → HCID 66845106, Verbindung

HRID 1480541Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1480541
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

Komponenten

6

Edukt 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 66845507HCID 66845507, Verbindung

Produkt 1

HCID 66845106HCID 66845106, VerbindungAusbeute 151,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-331775c3c5a84fa9a798e6f4afd267a4
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409886B2

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