2-Bromo-5-methylpyridine → HCID 68161807, compound

HRID 2041688Notes

Reaction equation

HRID 2041688 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:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[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][C:35]([CH3:38])=[CH:34][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][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:29][C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][N:33]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 5642162-Bromo-5-methylpyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 67205868HCID 67205868, compound

Product 1

HCID 68161807HCID 68161807, compoundYield 58%

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) (48 mg, 0.112 mmol) and 2-bromo-5-methylpyridine (57.7 mg, 0.335 mmol) in toluene (2.5 mL) were successively added sodium tert-butoxide (107 mg, 1.117 mmol), tris(dibenzylideneacetone)dipalladium(0) (20.46 mg, 0.022 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (17.59 mg, 0.045 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. The combined filtrate and washings were concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient:10 to 80% AcOEt in Hexanes) gave (2S,4R)-1-acetyl-6-[1-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-N-(5-methyl-2-pyridinyl)-1,2,3,4-tetrahydro-4-quinolinamine (34 mg, 0.065 mmol, 58%) as a colourless 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. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-8bfab34dee4e45bd9e18084da6617f38
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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