4-(6-Methoxy-pyridin-3-ylmethoxy)-pyrimidin-2-ylamine → (1-{4-[7-(6-Methoxy-pyridin-3-ylmethoxy)-3-phenyl-imidazo[1,2-a]pyrimidin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester

HRID 872302Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 872302
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH:19](Br)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:29][O:30][C:31]1[N:36]=[CH:35][C:34]([CH2:37][O:38][C:39]2[CH:44]=[CH:43][N:42]=[C:41]([NH2:45])[N:40]=2)=[CH:33][CH:32]=1>CCO>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:45]=[C:41]4[N:40]=[C:39]([O:38][CH2:37][C:34]5[CH:35]=[N:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=5)[CH:44]=[CH:43][N:42]4[C:19]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:2])([CH3:4])[CH3:3]

Komponenten

4

Edukt 2

HCID 666649914-(6-Methoxy-pyridin-3-ylmethoxy)-pyrimidin-2-ylamine2×HCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Produkt 1

HCID 66665111(1-{4-[7-(6-Methoxy-pyridin-3-ylmethoxy)-3-phenyl-imidazo[1,2-a]pyrimidin-2-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl esterAusbeute 119,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

A mixture of crude {1-[4-(2-bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [Int-1-A] (1.2 g, 82% purity), crude 4-(6-methoxy-pyridin-3-ylmethoxy)-pyrimidin-2-ylamine (0.66 g, 65% purity) and activated 3 Å molecular sieves in EtOH (7.5 mL) was heated at reflux for 2 hours. LC-MS indicated the reaction to be incomplete. A further 0.66 g portion of 4-(6-methoxy-pyridin-3-ylmethoxy)-pyrimidin-2-ylamine was added and the mixture was heated at reflux for 3 hours. On cooling the mixture was partitioned between EtOAc and water, decanted and the separated organic phase washed with brine, dried and concentrated to give the title compound (1.86 g) as a yellow solid which was used in the next step without further purification.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customthe reaction
  4. temperaturethe mixture was heated
  5. temperatureat reflux for 3 hours
  6. temperatureOn cooling the mixture
  7. customwas partitioned between EtOAc and water
  8. customdecanted
  9. washthe separated organic phase washed with brine
  10. customdried
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1edb6466584c4b2fb2d31bc50612ff9b
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08975265B2

Notizen zur Reaktion

Wird geladen…