Cesium carbonate → [5-(Benzhydrylidene-amino)-pyridin-3-yl]-[7-bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-methanone

HRID 82301Notes

Reaction equation

HRID 82301 reaction equation
[C:1]12([N:6]3[C:10]4[N:11]=[C:12]([NH:15][CH2:16][C:17]5[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=5)[N:13]=[CH:14][C:9]=4[C:8]([C:25]([C:27]4[CH:28]=[N:29][CH:30]=[C:31](Br)[CH:32]=4)=[O:26])=[CH:7]3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.[C:34](=[NH:47])([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:34](=[N:47][C:31]1[CH:32]=[C:27]([C:25]([C:8]2[C:9]3[CH:14]=[N:13][C:12]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)=[N:11][C:10]=3[N:6]([C:1]34[CH2:2][CH:3]([CH2:5]3)[CH2:4]4)[CH:7]=2)=[O:26])[CH:28]=[N:29][CH:30]=1)([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 70817552[7-Bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-(5-bromo-pyridin-3-yl)-methanone

Product 1

HCID 86672131[5-(Benzhydrylidene-amino)-pyridin-3-yl]-[7-bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-methanoneYield 85%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of [7-Bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-(5-bromo-pyridin-3-yl)-methanone (Preparation 285, 1.18 g, 2 mmol) and benzophenoneimine (0.50 mL, 3 mmol) in dry toluene (50 mL), cesium carbonate (3.2 g, 10 mmol) was added and the reaction mixture was purged under N2 for 20 min and then Pd(OAc)2 (45 mg, 0.2 mmol) and BINAP (125 mg, 0.2 mmol) were added followed by degassing for another 10 min and refluxing overnight. The reaction mass was cooled to room temperature and filtered through a pad of Celite. The filtrate was partitioned between water (25 mL) and EtOAc (100 mL). The organic phase was washed with brine (10 mL), dried (Na2SO4) and evaporated in vacuo. Purification by column chromatography on silica gel (EtOAc:Hexane 25:75) afforded the title compound as a yellow solid in 85% yield, 1.1 g.

Workup

  1. customthe reaction mixture was purged under N2 for 20 min
  2. customby degassing for another 10 min
  3. temperaturerefluxing overnight
  4. filtrationfiltered through a pad of Celite
  5. customThe filtrate was partitioned between water (25 mL) and EtOAc (100 mL)
  6. washThe organic phase was washed with brine (10 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo
  9. customPurification by column chromatography on silica gel (EtOAc:Hexane 25:75)

Sources & evidence

ORD record
ord-68aaccad8a1b4eac9fa7b12aa1ae53c1
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

Loading…