Diisopropylethylamine → [2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine

HRID 216153Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 216153
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=2)[N:5]=[C:4]([O:18][CH3:19])[N:3]=1.C(N(CC)C(C)C)(C)C.[CH3:29][CH:30]([NH2:39])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1.Cl>C1COCC1>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([CH2:31][CH:30]([NH:39][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=3)[N:5]=[C:4]([O:18][CH3:19])[N:3]=2)[CH3:29])=[CH:37][CH:36]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 107161p-Chloroamphetamine hydrochlorideHCID 576361174-Chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine2×

Produkt 1

HCID 11524458[2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amineAusbeute 25,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4-chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine [140 mg, 0.5 mmol, Intermediate (50)] and N,N-diisopropylethylamine (392 μL, 2.25 mmol) in THF (1.7 mL) is added DL-p-chloroamphetamine hydrochloride (154.6 mg, 0.75 mmol, Intermediate (51)]. The mixture is heated to reflux for 2 hours and quenched with water (20 mL) and extracted twice with EtOAc (20 mL). The combined extracts are concentrated and the residue is subjected to flash column chromatography on silica gel eluting with 0 to 50% EtOAc in heptane gradient to afford [2-(4-chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine [52.7 mg, 25.5%, Example 43(a)]. LCMS: RT=2.66 minutes, MS: 414 (M+H). 1H NMR (300 MHz, CDCl3): δ 7.65 (1H, d, J=0.066 Hz), 7.53 (1H, dd, J=0.066, 0.028), 7.28 (2H, d, J=0.028 Hz), 7.14 (2H, d, J=0.028 Hz), 6.93 (1H, d, J=0.028 Hz), 6.31 (1H, s), 4.72 (1H, s), 4.34 (1H, s), 4.04 (3H, s), 3.99 (3H, s), 3.95 (3H, s), 2.89 (2H, qd, J=0.045, 0.022 Hz), 1.79 (1H, s), 1.24 (3H, d, J=0.22 Hz). IC50=1726 nM

Aufarbeitung

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 2 hours
  3. customquenched with water (20 mL)
  4. extractionextracted twice with EtOAc (20 mL)
  5. concentrationThe combined extracts are concentrated

Quellen und Nachweise

ORD-Eintrag
ord-2694736abe174c43b8a97e59fd3672a4
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193183B2

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