Dabco → HCID 57750071, compound

HRID 340407Notes

Reaction equation

HRID 340407 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1I.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[CH:16][CH:15]=1.N12CCN(CC1)CC2>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:13][C:14]1[CH:15]=[CH:16][C:17]([N:20]2[CH2:25][CH2:24][C:23]3[NH:1][C:2]4[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=4[C:22]=3[CH2:21]2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 9237DabcoHCID 6062841-(4-fluorophenyl)piperidin-4-oneHCID 4104649Methyl 4-amino-3-iodobenzoate

Product 1

HCID 57750071HCID 57750071, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of methyl 4-amino-3-iodobenzoate (0.5 g, 1.8 mmol), 1-(4-fluorophenyl)piperidin-4-one (1.05 g, 5.4 mmol), 1,4-diazabicyclo[2.2.2]octane (0.61 g, 5.4 mmol) and palladium (II) acetate (20 mg, 0.09 mmol) in DMF (10.0 mL) was degassed, filled with argon (3×) and allowed to stir at 110° C. for 3.5 h. The reaction mixture was allowed to cool to room temperature and partitioned between EtOAc (40 mL) and water (40 mL), and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with water (2×20 mL), brine (1×20 mL), dried (MgSO4), filtered and concentrated. Column chromatography (25% EtOAc/hexane) provided, upon trituration with ethyl ether, methyl 2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate (23 in Scheme 1(k)) as a yellow solid (0.23 g, 39%). 1H NMR (CDCl3, 300 MHZ) 8.17 (s, 1H), 7.77 (d, J=7.2 Hz, 1H), 7.23 (d, J=8.0 Hz, 3H), 7.09 (t, J=8.1 Hz, 2H), 4.53 (s, 2H), 3.96 (s, 3H), 3.73 (t, J=5.6 Hz, 2H), 3.12 (br s, 2H) ppm; MS (ES) 325 (M+H).

Workup

  1. additionfilled with argon (3×)
  2. temperatureto cool to room temperature
  3. custompartitioned between EtOAc (40 mL) and water (40 mL)
  4. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washThe combined organic layers were washed with water (2×20 mL), brine (1×20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-042a9d21625e42b4a2303a69209b8384
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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