Benzophenone imine → [1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]{4-[(diphenylmethylene)amino]pyridin-2-yl}methanone

HRID 1753046Notes

Reaction equation

HRID 1753046 reaction equation
[CH3:1]C([O-])(C)C.[Na+].[C:7]([SiH:11]([O:13][CH2:14][C:15]([N:18]1[C:26]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[C:20]([C:27]([C:29]2[CH:34]=[C:33](Cl)[CH:32]=[CH:31][N:30]=2)=[O:28])=[CH:19]1)([CH3:17])[CH3:16])[CH3:12])([CH3:10])([CH3:9])[CH3:8].[C:36](=[NH:49])([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C[C@H](P(C(C)(C)C)C(C)(C)C)[C]1[C](P(C2CCCCC2)C2CCCCC2)[CH][CH][CH]1.[CH]1[CH][CH][CH][CH]1.[Fe]>[Si:11]([O:13][CH2:14][C:15]([N:18]1[C:26]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[C:20]([C:27]([C:29]2[CH:34]=[C:33]([N:49]=[C:36]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:32]=[CH:31][N:30]=2)=[O:28])=[CH:19]1)([CH3:17])[CH3:16])([C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:1])[CH3:12]

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 137331321[1-(2-{[tert-butyl(methyl)silyl]oxyl}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl](4-chloropyridin-2-yl)methanone

Product 1

HCID 90093197[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]{4-[(diphenylmethylene)amino]pyridin-2-yl}methanoneYield 64.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 16218679(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine, >=97%CatalystHCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
80 °C

Procedure

To a suspension of NaOtBu (500 mg, 5.2 mmol) and [1-(2-{[tert-butyl(methyl)silyl]oxyl}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl](4-chloropyridin-2-yl)methanone (Preparation 44, 1.65 g, 3.71 mmol) in DME (5 mL) was added a solution of palladium acetate (41.8 mg, 0.186 mmol) and (R)-1-[(SP)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (103 mg, 0.186 mmol) in DME (2 mL) followed by a solution of benzophenone imine (808 mg, 4.46 mmol) in DME (2 mL). The reaction was degassed and heated to 80° C. for 30 minutes. The reaction was cooled, filtered through celite and partitioned between EtOAc and water. The organic layer was collected, dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 100% heptanes to 100% EtOAc to afford the title compound as a brown oil (1.4 g, 64%).

Workup

  1. customThe reaction was degassed
  2. temperatureThe reaction was cooled
  3. filtrationfiltered through celite
  4. custompartitioned between EtOAc and water
  5. customThe organic layer was collected
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified
  9. washeluting with 100% heptanes to 100% EtOAc

Sources & evidence

ORD record
ord-b9883ac6d1ad47d18e947666756dfe19
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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