Iodobenzene → HCID 68184859, compound

HRID 2041696Notes

Reaction equation

HRID 2041696 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:38]=[CH:37][CH: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][CH:36]=[CH:35][CH:34]=2)[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 11575IodobenzeneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 68162631HCID 68162631, compound

Product 1

HCID 68184859HCID 68184859, compoundYield 58.9%

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), iodobenzene (0.078 mL, 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). 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 partitioned between DCM and a saturated NaHCO3 aqueous solution. The layers were separated using an hydrophobic frit and the organic phase concentrated in vacuovacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient:20 to 100% AcOEt in hexanes) gave 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (104 mg, 0.206 mmol, 58.9% yield) as a yellow oil.

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between DCM
  3. customThe layers were separated
  4. concentrationthe organic phase concentrated in vacuovacuo
  5. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-70edfc8683694e96960ef65715af2c15
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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