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 872302Notes

Reaction equation

HRID 872302 reaction equation
[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]

Participants

4

Reactant 2

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

Product 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 esterYield 119.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-1edb6466584c4b2fb2d31bc50612ff9b
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

Loading…