Potassium Phosphate, Tribasic → HCID 66604850, compound

HRID 2410794Notes

Reaction equation

HRID 2410794 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](B(O)O)=[CH:8][CH:9]=2)[CH:4]=[N:3]1.Br[C:15]1[CH:16]=[C:17]([C:38]([O:40][CH3:41])=[O:39])[C:18]2[N:19]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[C:20]3[CH:21]=[C:22]([Cl:28])[CH:23]=[CH:24][C:25]=3[C:26]=2[N:27]=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:28][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[N:27]=[C:15]([C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[N:2]([CH3:1])[N:3]=[CH:4]5)[CH:16]=[C:17]([C:38]([O:40][CH3:41])=[O:39])[C:18]=3[N:19]([CH2:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[C:20]=2[CH:21]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 225589101-Methyl-1H-indazole-5-boronic acidHCID 86663043HCID 86663043, compound

Product 1

HCID 66604850HCID 66604850, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A flask containing a mixture of 1-methyl-1H-indazol-5-ylboronic acid (590 mg, 3.35 mmol), methyl 2-bromo-7-chloro-5-(4-methoxybenzyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.19 g, 2.58 mmol), powdered potassium phosphate tribasic (1.31 g, 6.19 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.212 g, 0.516 mmol), and Pd(OAc)2 (0.058 g, 0.258 mmol) was flushed with nitrogen. THF (10 mL) was added and the reaction was heated at 70° C. for 15 hr. The reaction 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-(1-methyl-1H-indazol-5-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (720 mg, 1.41 mmol, 55% yield) as a solid. MS (ESI) m/z 511.14 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.47 (1H, s), 8.42 (1H, d, J=8.24 Hz), 8.27 (1H, dd, J=8.55, 1.53 Hz), 8.07 (2H, d, J=2.14 Hz), 7.50 (1H, d, J=8.55 Hz), 7.46 (1H, s), 7.35 (1H, dd, J=8.24, 1.53 Hz), 6.86-6.91 (2H, m), 6.76 (2H, d, J=8.85 Hz), 5.67 (2H, s), 4.12 (3H, s), 3.82 (3H, s), 3.73 (3H, s).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen
  3. additionTHF (10 mL) was added
  4. customThe reaction 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-7f5aaf57fc9a4d84a1bf760c6c0e9065
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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