Potassium Phosphate, Tribasic → HCID 66604957, compound

HRID 2410790Notes

Reaction equation

HRID 2410790 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Br[C:14]1[CH:15]=[C:16]([C:28]([O:30][CH3:31])=[O:29])[C:17]2[NH:18][C:19]3[CH:20]=[C:21]([Cl:27])[CH:22]=[CH:23][C:24]=3[C:25]=2[N:26]=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:27][C:21]1[CH:22]=[CH:23][C:24]2[C:25]3[N:26]=[C:14]([C:4]4[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=4)[CH:15]=[C:16]([C:28]([O:30][CH3:31])=[O:29])[C:17]=3[NH:18][C:19]=2[CH:20]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27821943-Fluoro-4-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86663042HCID 86663042, compound

Product 1

HCID 66604957HCID 66604957, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A flask containing a mixture of 3-fluoro-4-methoxyphenylboronic acid (0.901 g, 5.30 mmol), methyl 2-bromo-7-chloro-5H-pyrido[3,2-b]indole-4-carboxylate (1.5 g, 4.4 mmol), powdered potassium phosphate tribasic (2.25 g, 10 6 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.363 g, 0.883 mmol), and Pd(OAc)2 (0.099 g, 0.44 mmol) was flushed with nitrogen, THF (22 mL) was added, and the reaction was heated at 70° C. for 20 hr. This was partitioned between EtOAc and water and the organic phase was washed with water and brine and then dried with sodium sulfate. Removal of the solvent followed by silica gel chromatography (step gradient elution with DCM containing 75 to 0% hexane) afforded methyl 7-chloro-2-(3-fluoro-4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.29 g, 3.35 mmol, 76% yield) as a light green solid. MS (ESI) m/z 385.13 (M+H). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.89 (1H, s), 8.19 (1H, d, J=8.24 Hz), 7.92 (1H, s), 7.76 (1H, d, J=1.53 Hz), 7.35 (1H, dd, J=8.55, 1.83 Hz), 4.04 (3H, s).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen, THF (22 mL)
  3. additionwas 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. customRemoval of the solvent
  8. washfollowed by silica gel chromatography (step gradient elution with DCM containing 75 to 0% hexane)

Sources & evidence

ORD record
ord-9603eb0d11584492a78e9d391c2e8b7a
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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