4-Bromopyridine → HCID 68184861, compound

HRID 2041701Notes

Reaction equation

HRID 2041701 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][N:36]=[CH:35][CH: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]>[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][N:36]=[CH:35][CH:34]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 142684-BromopyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68162631HCID 68162631, compound

Product 1

HCID 68184861HCID 68184861, compoundYield 78%

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), 4-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 partitioned between EtOAc and a saturated NaHCO3 aqueous solution. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuovacuo. Purification of the residue by SP4 using a 50 G silica cartridge (gradient:5 to 20% (2M NH3 in MeOH) in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(4-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (147 mg, 0.29 mmol, 78%).

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuovacuo
  8. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-d646e8a34e8c422489f6abf2caf7df57
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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