HCID 58266297, compound → HCID 58266836, compound

HRID 1888587Notes

Reaction equation

HRID 1888587 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([CH3:8])[N:3]1[CH2:9][C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][CH:11]=1.I[C:26]1[CH:39]=[N:38][C:29]2[NH:30][C:31]3[CH:36]=[N:35][C:34]([Br:37])=[CH:33][C:32]=3[C:28]=2[CH:27]=1>C(=O)([O-])[O-].[Na+].[Na+].C1COCC1.C(Cl)Cl>[Br:37][C:34]1[N:35]=[CH:36][C:31]2[NH:30][C:29]3[N:38]=[CH:39][C:26]([C:13]4[CH:12]=[CH:11][C:10]([CH2:9][N:3]5[C@H:4]([CH3:8])[CH2:5][CH2:6][CH2:7][C@@H:2]5[CH3:1])=[CH:15][CH:14]=4)=[CH:27][C:28]=3[C:32]=2[CH:33]=1

Participants

6

Reactant 2

HCID 58266297HCID 58266297, compoundHCID 58266411HCID 58266411, compound

Product 1

HCID 58266836HCID 58266836, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Procedure

A degassed mixture of (2S,6R)-2,6-dimethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]piperidine (685 mg, 2.08 mmol), 3-iodo-6-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (389 mg, 1.04 mmol), 1,1′-[bis(diphenylphosphino)ferrocene] dichloropalladium(II) (127 mg, 0.16 mmol) in saturated sodium carbonate solution (1 mL) and THF (10 mL) was heated under reflux for 18 h. The cooled reaction mixture was diluted with DCM (50 mL) and washed with water (25 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 40 g column, ISCO, 0-15% methanol in DCM) to afford the title compound as an off-white solid (181 mg, 39%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.85 (d, J=2.2 Hz, 1H), 8.72 (d, J=2.2 Hz, 1H), 8.69 (d, J=0.9 Hz, 1H), 8.29 (d, J=0.9 Hz, 1H), 7.68-7.63 (d, J=8.1 Hz, 2H), 7.56-7.50 (m, 2H), 4.00 (s, 2H), 2.65-2.51 (m, 2H), 1.72-1.56 (m, 4H), 1.46-1.30 (m, 2H), 1.25 (d, J=6.2 Hz, 6H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 18 h
  3. customThe cooled reaction mixture
  4. washwashed with water (25 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromatography (silica, 40 g column, ISCO, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-16ac996fb5ad4d45bd0ea1348625ac88
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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