2-Bromopyridine → HCID 86669440, compound

HRID 2041702Notes

Reaction equation

HRID 2041702 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].Br[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.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]>[CH:22]([OH:28])=[O:23].[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:30][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 79732-BromopyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68162631HCID 68162631, compound

Product 1

HCID 86669440HCID 86669440, compoundYield 67.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

1,1-Dimethylethyl (2-{4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (for a preparation see intermediate 55) (159 mg, 0.372 mmol), 2-bromopyridine (0.071 mL, 0.744 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (58.5 mg, 0.149 mmol), tris(dibenzylideneacetone)dipalladium(0) (68.1 mg, 0.074 mmol) and sodium tert-butoxide (107 mg, 1.116 mmol) were dissolved in 1,4-dioxane (4 mL) and the resulting mixture was stirred at 120° C. under nitrogen for 16 h then cooled to room temperature and concentrated in vacuovacuo. The residue was partitioned between EtOAc and a saturated NaHCO3 aqueous solution and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuovacuo. The residue was dissolved in 1:1 MeOH:DMSO (0.6 mL ×3) and purified by MDAP (modifier: formic acid). The desired fractions were combined and the solvent was removed under vacuo to give 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(2-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate formate (126 mg, 0.250 mmol, 67.1% yield).

Workup

  1. temperaturethen cooled to room temperature
  2. concentrationconcentrated in vacuovacuo
  3. customThe residue was partitioned between EtOAc
  4. customa saturated NaHCO3 aqueous solution and the layers were separated
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuovacuo
  9. dissolutionThe residue was dissolved in 1:1 MeOH
  10. customDMSO (0.6 mL ×3) and purified by MDAP (modifier: formic acid)
  11. customthe solvent was removed under vacuo

Sources & evidence

ORD record
ord-f5334752f537493aa6fc8ea29880652c
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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