4-((Morpholino)methyl)phenylboronic acid pinacol ester → 6-Bromo-3-(4-morpholin-4-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888588Notes

Reaction equation

HRID 1888588 reaction equation
B1([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)OC(C)(C)C(C)(C)O1.I[C:24]1[CH:37]=[N:36][C:27]2[NH:28][C:29]3[CH:34]=[N:33][C:32]([Br:35])=[CH:31][C:30]=3[C:26]=2[CH:25]=1>C(=O)([O-])[O-].[Na+].[Na+].CC1CCCO1.C(OCC)(=O)C>[Br:35][C:32]1[N:33]=[CH:34][C:29]2[NH:28][C:27]3[N:36]=[CH:37][C:24]([C:10]4[CH:11]=[CH:12][C:13]([CH2:16][N:17]5[CH2:18][CH2:19][O:20][CH2:21][CH2:22]5)=[CH:14][CH:15]=4)=[CH:25][C:26]=3[C:30]=2[CH:31]=1

Participants

6

Reactant 2

HCID 27955024-((Morpholino)methyl)phenylboronic acid pinacol esterHCID 58266297HCID 58266297, compound

Product 1

HCID 582667156-Bromo-3-(4-morpholin-4-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 30.2%

Reagents, catalysts & solvents 3

HCID 73012-MethyltetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

A degassed mixture of 4-(4-morpholinomethyl)phenylboronic acid pinacol ester (486 mg, 1.61 mmol), 3-iodo-6-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (400 mg, 1.07 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (131 mg, 0.16 mmol) in 2N aqueous sodium carbonate solution (8 mL) and 2-methyltetrahyrdofuran (16 mL) was heated at 85° C. for 18 h. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (75 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, 50 g column, Biotage, 0-15% methanol in DCM) to afford the title compound as an off-white solid (137 mg, 30%). 1H NMR (CDCl3, 300 MHz): 12.41 (s, 1H), 9.04 (d, J=2.3 Hz, 1H), 8.95 (d, J=2.3 Hz, 1H), 8.72 (d, J=1.0 Hz, 1H), 8.53 (s, 1H), 7.76 (d, J=8.0 Hz, 2H), 7.47 (d, J=8.0 Hz, 2H), 3.65-3.56 (m, 4H), 3.53 (s, 2H), 2.44-2.29 (m, 4H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (75 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-b6bd052773c9464c8ae9072a568ba17d
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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