Potassium Phosphate, Tribasic → HCID 136337375, compound

HRID 2410811Notes

Reaction equation

HRID 2410811 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[OH:8].Br[C:13]1[CH:14]=[C:15]([C:33]([O:35][CH3:36])=[O:34])[C:16]2[NH:17][C:18]3[CH:19]=[C:20]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH:21]=[CH:22][C:23]=3[C:24]=2[N:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[C:15]([C:33]([O:35][CH3:36])=[O:34])[C:16]3[NH:17][C:18]4[CH:19]=[C:20]([N:26]5[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]5)[CH:21]=[CH:22][C:23]=4[C:24]=3[N:25]=2)[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 221253733-Chloro-4-hydroxyphenylboronic AcidHCID 86663050HCID 86663050, compound

Product 1

HCID 136337375HCID 136337375, compoundYield 34.9%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

A microwave vial containing a mixture of 3-chloro-4-hydroxyphenylboronic acid (64 mg, 0.37 mmol), methyl 2-bromo-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (50 mg, 0.12 mmol), powdered potassium phosphate tribasic (116 mg, 0.546 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (12 mg, 0.025 mmol), and Pd(OAc)2 (2.8 mg, 0.012 mmol) was flushed with nitrogen. THF (0.5 mL) was added, the vial was sealed, and the reaction was heated at 80° C. for 3 hr. Preparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA; 10-60% B at 42 mL/min over 20 min) of the reaction mixture followed by SCX capture and release with 2 N NH3 in MeOH gave methyl 2-(3-chloro-4-hydroxyphenyl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (30 mg, 0.043 mmol, 34.9% yield. MS (ESI) m/z 451.10 (M+H).

Workup

  1. additionA microwave vial containing
  2. customwas flushed with nitrogen
  3. additionTHF (0.5 mL) was added
  4. customthe vial was sealed
  5. customPreparative HPLC (100×30 mm Luna C18 column, Solvent A=10% Methanol, 90% H2O, 0.1% TFA; Solvent B=90% Methanol, 10% H2O, 0.1% TFA; 10-60% B at 42 mL/min over 20 min) of the reaction mixture

Sources & evidence

ORD record
ord-b1e9bc3d278644bc8a65bb7016f8f87b
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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