3-Iodopyridine → HCID 68184860, compound

HRID 2041700Notes

Reaction equation

HRID 2041700 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].I[C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=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:34]=[N:35][CH:36]=[CH:37][CH:38]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 707143-IodopyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68162631HCID 68162631, compound

Product 1

HCID 68184860HCID 68184860, compoundYield 47.4%

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) (150 mg, 0.351 mmol), 3-iodopyridine (144 mg, 0.702 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (27.6 mg, 0.070 mmol), tris(dibenzylideneacetone)dipalladium(0) (32.1 mg, 0.035 mmol) and sodium tert-butoxide (67.4 mg, 0.702 mmol) were dissolved in 1,4-dioxane (4 mL) and the resulting mixture was stirred at 100° C. under nitrogen for 20 h, at 120° C. for 16 h, then cooled to room temperature and concentrated in vacuovacuo. The residue was partitioned between DCM and a saturated NaHCO3 aqueous solution and the layers were separated using a hydrophobic frit. The organic phase was concentrated in vacuovacuo. Purification of the residue by SP4 using a 50 G silica cartridge (gradient:0.5 to 10% (2M NH3 in MeOH) in DCM) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (84 mg, 0.166 mmol, 47.4% yield).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuovacuo
  3. customThe residue was partitioned between DCM
  4. customa saturated NaHCO3 aqueous solution and the layers were separated
  5. concentrationThe organic phase was concentrated in vacuovacuo
  6. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-d267b54f5e3148bb8c9bba803856072a
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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