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Hydrochloric Acid → cis-2,6-Dimethyl-4-[4-(2-methylpropyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine hydrochloride

HRID 2278450
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2278450
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[CH:6][N:5]=[C:4]([N:15]2[CH2:20][C@H:19]([CH3:21])[O:18][C@H:17]([CH3:22])[CH2:16]2)[N:3]=1.[CH2:23]([Mg]Cl)[CH:24]([CH3:26])[CH3:25].[Cl-].[NH4+].Cl>O1CCCC1.ClCCl.[Cu]I.CO>[ClH:1].[CH3:22][C@H:17]1[O:18][C@@H:19]([CH3:21])[CH2:20][N:15]([C:4]2[N:3]=[C:2]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:7]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=3)=[CH:6][N:5]=2)[CH2:16]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 86702425cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholineHCID 178418368HCID 178418368, Verbindung

Produkt 1

HCID 86702431cis-2,6-Dimethyl-4-[4-(2-methylpropyl)-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]morpholine hydrochlorideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of cis-4-[4-chloro-5-(2-methyl-4-pyridinyl)-2-pyrimidinyl]-2,6-dimethylmorpholine (100 mg, 0.314 mmol) and copper (I) iodide (11.95 mg, 0.063 mmol) in tetrahydrofuran (1 ml) was stirred at 0° C. under argon and isobutyl magnesium chloride (2M solution in tetrahydrofuran) (0.314 ml, 0.627 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 90 minutes. Saturated ammonium chloride solution was added and the mixture was extracted with ethyl acetate. The organic extract was separated, washed with saturated ammonium chloride solution, water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 50-100% ethyl acetate in isohexanes. The product (61 mg, 0.18 mmol) was dissolved in dichloromethane (1 ml) and methanol (0.5 ml) and hydrogen chloride (1M in ether, 0.2 ml) was added. The solvent was evaporated and the residue was co-evaporated with ether. The residue was triturated with ether and the resulting solid was collected and dried to give the title compound (48 mg, 41%). LC/MS [M+H]+=341. 1H NMR (400 MHz, d6-DMSO): δ 8.74 (1H, d), 8.36 (1H, s), 7.87-7.85 (1H, m), 7.81-7.78 (1H, m), 4.62-4.58 (2H, m), 3.61-3.54 (2H, m), 2.72 (3H, s), 2.63-2.58 (4H, m), 2.15-2.08 (1H, m), 1.18 (6H, d), 0.79 (6H, d).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 0° C. for 90 minutes
  2. extractionthe mixture was extracted with ethyl acetate
  3. extractionThe organic extract
  4. customwas separated
  5. washwashed with saturated ammonium chloride solution, water and brine
  6. customdried
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 50-100% ethyl acetate in isohexanes
  10. customThe solvent was evaporated
  11. customThe residue was triturated with ether
  12. customthe resulting solid was collected
  13. customdried

Quellen und Nachweise

ORD-Eintrag
ord-a72df787267d44de92d0a562e95a9fbd
Quelldatensatz
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09133178B2

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