Potassium Phosphate, Tribasic → methyl 2-(3-chlorophenyl)-7-(4-morpholinyl)-5H-pyrido[2',3':4,5]pyrrolo[2,3-b]pyridine-4-carboxylate

HRID 2410754Notes

Reaction equation

HRID 2410754 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[C:14]([C:31]([O:33][CH3:34])=[O:32])[C:15]2[NH:29][C:18]3=[N:19][C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[CH:21][CH:22]=[C:17]3[C:16]=2[N:30]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[C:14]([C:31]([O:33][CH3:34])=[O:32])[C:15]3[NH:29][C:18]4=[N:19][C:20]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[CH:21][CH:22]=[C:17]4[C:16]=3[N:30]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734323(3-Chlorophenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663024methyl 2-bromo-7-(4-morpholinyl)-5H-pyrido[2',3':4,5]pyrrolo[2,3-b]pyridine-4-carboxylate

Product 1

HCID 66605303methyl 2-(3-chlorophenyl)-7-(4-morpholinyl)-5H-pyrido[2',3':4,5]pyrrolo[2,3-b]pyridine-4-carboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of 3-chlorophenylboronic acid (48.0 mg, 0.307 mmol), methyl 2-bromo-7-(4-morpholinyl)-5H-pyrido[2′,3′:4,5]pyrrolo[2,3-b]pyridine-4-carboxylate (100 mg, 0.256 mmol), finely powdered potassium phosphate tribasic (130 mg, 0.613 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (21 mg, 0.051 mmol), and Pd(OAc)2 (5.7 mg, 0.026 mmol) in a microwave vial was flushed with nitrogen. THF (1.3 mL) was added, the vial was capped, and the reaction was heated in a 70° C. oil bath for 24 hr. After cooling, it was partitioned between EtOAc and water. The organic phase was extracted with brine and dried with sodium sulfate. The solvents were removed and radial chromatography (step gradient elution with DCM containing 0 to 50% EtOAc) afforded methyl 2-(3-chlorophenyl)-7-(4-morpholinyl)-5H-pyrido[2′,3′:4,5]pyrrolo[2,3-b]pyridine-4-carboxylate (55 mg, 0.130 mmol, 51% yield). MS (ESI) m/z 423.11 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.51 (1H, s), 8.43 (1H, d, J=8.55 Hz), 8.16 (1H, t, J=1.83 Hz), 8.13 (1H, s), 7.99 (1H, d, J=7.93 Hz), 7.42 (1H, t, J=7.78 Hz), 7.33-7.38 (1H, m), 6.67 (1H, d, J=8.85 Hz), 4.08 (3H, s), 3.84-3.91 (4H, m), 3.67-3.75 (4H, m).

Workup

  1. customwas flushed with nitrogen
  2. additionTHF (1.3 mL) was added
  3. customthe vial was capped
  4. temperatureAfter cooling
  5. customit was partitioned between EtOAc and water
  6. extractionThe organic phase was extracted with brine
  7. dry with materialdried with sodium sulfate
  8. customThe solvents were removed
  9. washradial chromatography (step gradient elution with DCM containing 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-eafa3da4e8234bc1ae85e95a07984cd1
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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