Dimethylacetamide → HCID 118006339, compound

HRID 926577Notes

Reaction equation

HRID 926577 reaction equation
C[C:2]([N:4](C)C)=O.Cl[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:27]3[N:31]([CH3:32])[C:30]([CH3:33])=[N:29][CH:28]=3)([C:20]3[N:24]([CH3:25])[C:23]([CH3:26])=[N:22][CH:21]=3)[OH:19])[CH:16]=2)[N:11]=[C:10]([O:34][CH3:35])[C:9]=1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.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].[Zn]>[CH3:32][N:31]1[C:27]([C:18]([C:20]2[N:24]([CH3:25])[C:23]([CH3:26])=[N:22][CH:21]=2)([OH:19])[C:15]2[CH:16]=[C:17]3[C:12](=[CH:13][CH:14]=2)[N:11]=[C:10]([O:34][CH3:35])[C:9]([CH2:36][C:37]2[CH:38]=[CH:39][C:40]([C:43]([F:44])([F:46])[F:45])=[CH:41][CH:42]=2)=[C:8]3[C:2]#[N:4])=[CH:28][N:29]=[C:30]1[CH3:33]

Participants

8

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 74221330HCID 74221330, compound2×

Product 1

HCID 118006339HCID 118006339, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

DMA (1.22 mL) was added to a mixture of (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)bis(1,2-dimethyl-1H-imidazol-5-yl)methanol (70.6 mg, 0.124 mmol, Intermediate 76), zinc cyanide (27.5 mg, 0.234 mmol), Pd2(dba)3 (18.5 mg, 0.0202 mmol), zinc nanopowder (2.5 mg, 0.0382 mmol) and X-Phos (12.9 mg, 0.0262 mmol). The mixture was stirred at 120° C. under argon for 4 hours. After cooling to room temperature, the reaction was diluted with EtOAc (2 mL), filtered through Celite®, and the filter cake washed with EtOAc (2×1 mL). The combined filtrates were washed with 0.75 M aqueous EDTA tetrasodium salt (2×1 mL), water (1×2 mL), and 5 M aqueous NaCl (1×2 mL). The organic layer was diluted with DCM/MeOH, dried (Na2SO4), filtered, and concentrated, and the residue was dry load flash chromatographed with a DCM to 10% MeOH/DCM gradient to provide the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=1.81 Hz, 1H), 7.76 (d, J=9.09 Hz, 1H), 7.55 (d, J=8.59 Hz, 2H), 7.49 (d, J=8.08 Hz, 2H), 7.41 (dd, J=2.06 Hz, 9.04 Hz, 1H), 6.16 (s, 2H), 4.39 (s, 2H), 4.10 (s, 3H), 3.42 (s, 6H), 2.27 (s, 6H); MS m/e 561.3 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered through Celite®
  3. washthe filter cake washed with EtOAc (2×1 mL)
  4. washThe combined filtrates were washed with 0.75 M aqueous EDTA tetrasodium salt (2×1 mL), water (1×2 mL), and 5 M aqueous NaCl (1×2 mL)
  5. additionThe organic layer was diluted with DCM/MeOH
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was dry load flash
  10. customchromatographed with a DCM to 10% MeOH/DCM gradient

Sources & evidence

ORD record
ord-1f2ffb52e1e64d0889590921f68ff552
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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