Methylamine → Methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

HRID 1677256Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1677256
[NH2:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=2[CH:18]([CH3:20])[CH3:19])=[CH:6][N:5]=[C:4]([NH:21][C@H:22]([CH3:25])[CH2:23][OH:24])[N:3]=1.[CH3:26][NH2:27].C1[CH2:32][O:31]CC1>>[NH2:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=2[CH:18]([CH3:20])[CH3:19])=[CH:6][N:5]=[C:4]([NH:21][CH:22]([CH3:25])[CH2:23][O:24][C:32](=[O:31])[NH:27][CH3:26])[N:3]=1

Komponenten

4

Edukt 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 161191702-[4-Amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-(R)-propan-1-ol

Produkt 1

HCID 16119173Methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

Versuchsvorschrift

1,1-Carbonyldiimidazole (0.97 g, 6 mmol) was added to a solution of 2-[4-Amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-(R)-propan-1-ol from Example 4 (0.22 g, 0.6 mmol) in 20 mL of THF at room temperature. The mixture was stirred for 2 hours and methylamine (3 mL, 2M/THF, 0.6 mmol) was added. The reaction mixture was stirred overnight and concentrated under reduced pressure, diluted with water (75 mL), and extracted with EtOAc (2×75 mL). The organic phase was washed with Brine and dried with MgSO4. The solution was filtered and concentrated. The residue was purified on two Silica preparative TLC plates (20×40 cm) eluting with 5% MeOH/dichloromethane affording 143 mg of methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester: MS (M+H); 424: MP; 63.5-69.4° C.

Aufarbeitung

  1. stirringThe reaction mixture was stirred overnight
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (75 mL)
  4. extractionextracted with EtOAc (2×75 mL)
  5. washThe organic phase was washed with Brine
  6. dry with materialdried with MgSO4
  7. filtrationThe solution was filtered
  8. concentrationconcentrated
  9. customThe residue was purified on two Silica preparative TLC plates (20×40 cm)
  10. washeluting with 5% MeOH/dichloromethane affording 143 mg of methyl-carbamic acid 2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-ylamino]-propyl ester

Quellen und Nachweise

ORD-Eintrag
ord-9cdad06548494e0590a7f0f8a63bcedf
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08008313B2

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