2-Bromo-5-methylpyridine → HCID 67206538, compound

HRID 2041747Notes

Reaction equation

HRID 2041747 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:25])[CH2:6][C@@H:5]1[CH3:26])(=[O:3])[CH3:2].Br[C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][N:29]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:25][C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][N:29]=2)[CH2:6][C@@H:5]1[CH3:26])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 5642162-Bromo-5-methylpyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 67205707ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Product 1

HCID 67206538HCID 67206538, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation, see Intermediate 52) (153 mg, 0.434 mmol) and 2-bromo-5-methylpyridine (224 mg, 1.302 mmol) in toluene (10 mL) were successively added sodium tert-butoxide (417 mg, 4.34 mmol), tris(dibenzylideneacetone)dipalladium(0) (398 mg, 0.434 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (342 mg, 0.868 mmol). The resulting mixture was stirred at 100° C. for 3 h then cooled to room temperature. The insoluble material was washed with 5% MeOH in DCM. The combined filtrate and washings were concentrated in vacuo and the residue was dissolved in a 1:1 MeOH/DMSO mixture and purified via MDAP (modifier: formic acid). The appropriate fractions were combined and the solvents evaporated using a blow down apparatus to give 4-{(2S,4R)-1-acetyl-2-methyl-4-[(5-methyl-2-pyridinyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}benzoic acid (27.5 mg, 0.066 mmol, 15%) as an off white solid.

Workup

  1. temperaturethen cooled to room temperature
  2. washThe insoluble material was washed with 5% MeOH in DCM
  3. concentrationThe combined filtrate and washings were concentrated in vacuo
  4. dissolutionthe residue was dissolved in a 1:1 MeOH/DMSO mixture
  5. custompurified via MDAP (modifier: formic acid)
  6. customthe solvents evaporated

Sources & evidence

ORD record
ord-09e3edf52053482ea47aeaebec53f900
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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