Potassium Phosphate, Tribasic → HCID 66606265, compound

HRID 2410780Notes

Reaction equation

HRID 2410780 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:32]([O:34][CH3:35])=[O:33])[C:15]2[NH:16][C:17]3[CH:18]=[C:19]([CH2:25][N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[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:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:13]=[C:14]([C:32]([O:34][CH3:35])=[O:33])[C:15]3[NH:16][C:17]4[CH:18]=[C:19]([CH2:25][N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)[CH:20]=[CH:21][C:22]=4[C:23]=3[N:24]=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 86663033HCID 86663033, compound

Product 1

HCID 66606265HCID 66606265, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A mixture of 3-chlorophenylboronic acid (34 mg, 0.22 mmol), methyl 2-bromo-7-(morpholinomethyl)-5H-pyrido[3,2-b]indole-4-carboxylate (75 mg, 0.19 mmol), powdered potassium phosphate tribasic (95 mg, 0.45 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (15 mg, 0.037 mmol), and Pd(OAc)2 (4.2 mg, 0.019 mmol) in a microwave vial was flushed with nitrogen. THF (928 μL) was added, the vial was capped, and the reaction was heated in a 70° C. oil bath for 24 hr. The reaction 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 2% MeOH) afforded methyl 2-(3-chlorophenyl)-7-(morpholinomethyl)-5H-pyrido[3,2-b]indole-4-carboxylate (59 mg, 0.14 mmol, 73% yield) as a yellow oil. MS (ESI) m/z 435.9 (M+H). 1H NMR (400 MHz, chloroform-d) δ ppm 9.54 (1H, s), 8.40 (1H, d, J=8.06 Hz), 8.26 (1H, s), 8.23 (1H, t, J=1.76 Hz), 8.06 (1H, dt, J=7.74, 1.42 Hz), 7.56 (1H, s), 7.46 (1H, t, J=7.68 Hz), 7.33-7.43 (2H, m), 4.13 (3H, s), 3.75-3.80 (4H, m), 3.73 (2H, s), 2.51-2.58 (4H, m).

Workup

  1. customwas flushed with nitrogen
  2. additionTHF (928 μL) was added
  3. customthe vial was capped
  4. customThe reaction was partitioned between EtOAc and water
  5. extractionThe organic phase was extracted with brine
  6. dry with materialdried with sodium sulfate
  7. customThe solvents were removed
  8. washradial chromatography (step gradient elution with DCM containing 0 to 2% MeOH)

Sources & evidence

ORD record
ord-2ed3a30a7774430997e620df94303c45
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…