Methyl 4-iodobenzoate → HCID 68162189, compound

HRID 2041759Notes

Reaction equation

HRID 2041759 reaction equation
Cl.Cl.[C:3]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[CH:13][CH:14]=2)[C@H:9]([NH2:22])[CH2:8][C@@H:7]1[CH3:23])(=[O:5])[CH3:4].I[C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:3]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[CH:13][CH:14]=2)[C@H:9]([NH:22][C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=2)[CH2:8][C@@H:7]1[CH3:23])(=[O:5])[CH3:4]

Participants

6

Reactant 4

HCID 69273Methyl 4-iodobenzoateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68161466HCID 68161466, compound

Product 1

HCID 68162189HCID 68162189, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
70 °C

Procedure

A flask was charged with (cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinamine di-hydrochloride (for a preparation see Intermediate 61) (250 mg, 0.700 mmol), methyl 4-iodobenzoate (202 mg, 0.770 mmol), sodium tert-butoxide (235 mg, 2.449 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (55.0 mg, 0.140 mmol) and tris(dibenzylideneacetone)dipalladium(0) (64.1 mg, 0.070 mmol) then filled with dried degassed toluene (15 mL) and the resulting mixture was stirred at 70° C. under nitrogen for 5 h then was cooled to room temperature and filtered through celite. The insoluble were rinsed with toluene (3×30 mL) and the combined filtrate and washings were concentrated in vacuo. The residue was partitioned between AcOEt (50 mL) and water (20 mL) and the layers were separated. The organic phase was washed with brine, and the combined aqueous phases were extracted with AcOEt (30 mL). The combined organic phases were dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge (gradient:0 to 20% MeOH in DCM) gave methyl 4-{[(cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]amino}benzoate (37 mg, 0.088 mmol, 13%).

Workup

  1. additionthen filled
  2. customwith dried
  3. customdegassed toluene (15 mL)
  4. temperaturethen was cooled to room temperature
  5. filtrationfiltered through celite
  6. washThe insoluble were rinsed with toluene (3×30 mL)
  7. concentrationthe combined filtrate and washings were concentrated in vacuo
  8. customThe residue was partitioned between AcOEt (50 mL) and water (20 mL)
  9. customthe layers were separated
  10. washThe organic phase was washed with brine
  11. extractionthe combined aqueous phases were extracted with AcOEt (30 mL)
  12. dry with materialThe combined organic phases were dried over MgSO4
  13. concentrationconcentrated in vacuo
  14. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-e0b1136fccac4c5ea931074ab8eb62ed
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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