2-Bromo-6-methylpyridine → HCID 52936008, compound

HRID 2041744Notes

Reaction equation

HRID 2041744 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:19][CH2:20][O:21][Si](C(C)(C)C)(C)C)[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:29])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].Br[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=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[N:15]=[N:16][N:17]([CH2:19][CH2:20][OH:21])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:29][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 792052-Bromo-6-methylpyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 67205868HCID 67205868, compound

Product 1

HCID 52936008HCID 52936008, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (2S,4R)-1-acetyl-6-[1-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation, see Intermediate 44) (59 mg, 0.137 mmol) and 2-bromo-6-methylpyridine (70.9 mg, 0.412 mmol) in toluene (2.5 mL) were successively added sodium tert-butoxide (132 mg, 1.373 mmol), tris(dibenzylideneacetone)dipalladium(0) (25.2 mg, 0.027 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (21.62 mg, 0.055 mmol). The reaction mixture was stirred at 75° C. for 5 h then cooled to room temperature and filtered through Celite. The insoluble material was washed with 5% MeOH in DCM and the combined filtrate and washings were concentrated in vacuo. The residue was dissolved in a 1:1 MeOH/DMSO mixture and was purified by MDAP (modifier: formic acid). The appropriate fractions were combined and the solvents evaporated using a blow down apparatus (nitrogen inlet) to give 2-(4-{(2S,4R)-1-acetyl-2-methyl-4-[(6-methyl-2-pyridinyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}-1H-1,2,3-triazol-1-yl)ethanol (12.5 mg, 0.031 mmol, 22%) as a viscous yellow oil.

Workup

  1. temperaturethen cooled to room temperature
  2. filtrationfiltered through Celite
  3. washThe insoluble material was washed with 5% MeOH in DCM
  4. concentrationthe combined filtrate and washings were concentrated in vacuo
  5. dissolutionThe residue was dissolved in a 1:1 MeOH/DMSO mixture
  6. customwas purified by MDAP (modifier: formic acid)
  7. customthe solvents evaporated

Sources & evidence

ORD record
ord-668c4c1132ca4b00b8c7856f7e64d0cc
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

Loading…