Cesium carbonate → tert-butyl 3-(6-((diphenylmethylene)amino)-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylate

HRID 919646Notes

Reaction equation

HRID 919646 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[CH:9][N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[C:4]=2[CH:3]=1.[NH:24](C1C=CC=CC=1)C1C=CC=CC=1.C[C:38]1(C)[C:64]2[C:59](=[C:60](P(C3C=CC=CC=3)C3C=CC=CC=3)[CH:61]=[CH:62][CH:63]=2)O[C:40]2[C:41](P(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:42][CH:43]=[CH:44][C:39]1=2.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[C:39]1([C:38](=[N:24][C:2]2[N:7]=[CH:6][C:5]3[N:8]=[CH:9][N:10]([CH:11]4[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]4)[C:4]=3[CH:3]=2)[C:64]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11487DiphenylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 72344680tert-butyl 3-(6-bromo-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylate

Product 1

HCID 87946249tert-butyl 3-(6-((diphenylmethylene)amino)-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylateYield 519.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of tert-butyl 3-(6-bromo-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylate (0.6 g, 1.58 mmol, 1.0 eq) in DMA (5 mL) were added Ph2NH (430 mg, 2.37 mmol, 1.5 eq), Pd3(dba)2 (87 mg, 0.095 mmol, 0.06 eq), Xantphos (91 mg, 0.16 mmol, 0.1 eq) and Cs2CO3 (0.8 g, 2.5 mmol, 1.6 eq) at rt under N2. The mixture was stirred at 115° C. for 16 h, cooled to rt and the solid was filtered off and washed with EtOAc (30 mL). The organic layer was washed with H2O (20 mL×2) and brine (10 mL), separated, dried (Na2SO4) and concentration in vacuo to afford a residue which was purified by silica gel column chromatography with EtOAc in PE (1/1 v/v) to give the title compound (0.4 g, 50%) as brown solid. 1H NMR (400 MHz, CDCl3) δ: 8.80 (s, 1H), 7.89 (s, 1H), 7.82 (d, 2H), 7.52-7.48 (m, 1H), 7.44-7.40 (m, 2H), 7.27-7.24 (m, 3H), 7.24-7.17 (m, 2H), 6.68 (s, 1H), 4.13-4.09 (m, 2H), 3.95-3.92 (m, 1H), 3.18-3.14 (m, 1H), 3.01-2.94 (m, 1H), 1.95-1.90 (m, 2H), 1.79-1.76 (m, 1H), 1.63-1.60 (m, 1H), 1.53 (s, 9H). ESI-MS (M+H+): 382.0.

Workup

  1. temperaturecooled to rt
  2. filtrationthe solid was filtered off
  3. washwashed with EtOAc (30 mL)
  4. washThe organic layer was washed with H2O (20 mL×2) and brine (10 mL)
  5. customseparated
  6. customdried
  7. concentration(Na2SO4) and concentration in vacuo
  8. customto afford a residue which
  9. customwas purified by silica gel column chromatography with EtOAc in PE (1/1 v/v)

Sources & evidence

ORD record
ord-16ce8639513c4a3298d40d611f1635a4
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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