Potassium Phosphate, Tribasic → HCID 66605177, compound

HRID 2410795Notes

Reaction equation

HRID 2410795 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[CH:13]=[C:14]([C:35]([O:37][CH3:38])=[O:36])[C:15]2[N:16]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:17]3[CH:18]=[C:19]([Cl:25])[CH:20]=[CH:21][C:22]=3[C:23]=2[N:24]=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:25][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:24]=[C:12]([C:5]4[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=4)[CH:13]=[C:14]([C:35]([O:37][CH3:38])=[O:36])[C:15]=3[N:16]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:17]=2[CH:18]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27630812-Methylpyridine-5-boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663043HCID 86663043, compound

Product 1

HCID 66605177HCID 66605177, compoundYield 28.3%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A flask containing a mixture of 6-methylpyridin-3-ylboronic acid (0.592 g, 4.32 mmol), methyl 2-bromo-7-chloro-5-(4-methoxybenzyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.24 g, 2.70 mmol), powdered potassium phosphate tribasic (1.38 g, 6.48 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.222 g, 0.540 mmol), and Pd(OAc)2 (0.061 g, 0.270 mmol) was flushed with nitrogen. THF (10 mL) was added and the reaction was heated at 70° C. for 15 hr. This was partitioned between EtOAc and water. The organic phase was washed with water and brine, dried with sodium sulfate, and the solvent was removed. Silica gel chromatography (step gradient elution with DCM containing 0 to 3% EtOAc) afforded methyl 7-chloro-5-(4-methoxybenzyl)-2-(6-methylpyridin-3-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (360 mg, 0.763 mmol, 28% yield) as a solid. MS (ESI) m/z 472.12 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.18 (1H, s), 8.33-8.42 (2H, m), 7.98 (1H, s), 7.47 (1H, s), 7.34 (1H, d, J=8.24 Hz), 7.28 (1H, d, J=7.93 Hz), 6.86 (2H, d, J=8.24 Hz), 6.75 (2H, d, J=8.55 Hz), 5.66 (2H, s), 3.78-3.84 (3H, m), 3.69-3.74 (3H, m), 2.63 (3H, s).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen
  3. additionTHF (10 mL) was added
  4. customThis was partitioned between EtOAc and water
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvent was removed
  8. washSilica gel chromatography (step gradient elution with DCM containing 0 to 3% EtOAc)

Sources & evidence

ORD record
ord-a5567e1a5b93495696d11697fbfae99d
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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