Dimethylacetamide → HCID 131735022, compound

HRID 926622Notes

Reaction equation

HRID 926622 reaction equation
[CH2:1]([C:8]1[C:9]([C:34]([F:37])([F:36])[F:35])=[N:10][C:11]2[C:16]([C:17]=1Cl)=[CH:15][C:14]([C:19]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)([C:21]1[N:25]([CH3:26])[CH:24]=[N:23][CH:22]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:79][N:80](C)C(=O)C>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-]#N.[Zn+2].[C-]#N.[Zn]>[CH2:1]([C:8]1[C:9]([C:34]([F:37])([F:35])[F:36])=[N:10][C:11]2[C:16]([C:17]=1[C:79]#[N:80])=[CH:15][C:14]([C:19]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)([OH:20])[C:21]1[N:25]([CH3:26])[CH:24]=[N:23][CH:22]=1)=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([OH:44])([C:40]([F:43])([F:42])[F:41])=[O:39]

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 131735023HCID 131735023, compound

Product 1

HCID 131735022HCID 131735022, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A pressure tube containing (3-benzyl-4-chloro-2-(trifluoromethyl)quinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol•TFA (167 mg, 0.220 mmol, Example 100), Pd2(dba)3 (30 mg, 0.033 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (X-Phos, 16 mg, 0.034 mmol), zinc cyanide (15 mg, 0.13 mmol) and zinc nanopowder (3.5 mg, 0.054 mmol) in N,N-dimethylacetamide (1 mL) was sparged with nitrogen for 8 minutes, and then heated at 120° C. for 4 hours. The mixture was allowed to cool to room temperature and filtered through a syringe filter. The filtrate was concentrated in vacuo, EtOAc and saturated NH4Cl aqueous solution were added. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to provide the title compound. 1H NMR (400 MHz, CD3OD) δ 9.02 (s, 1H), 8.34 (d, J=9.09 Hz, 1H), 8.31 (d, J=1.52 Hz, 1H), 8.01 (dd, J=2.02, 9.09 Hz, 1H), 7.44-7.49 (m, 4H), 7.24-7.30 (m, 2H), 7.18-7.24 (m, 1H), 7.06 (d, J=7.58 Hz, 2H), 7.03 (d, J=2.02 Hz, 1H), 4.64 (s, 2H), 3.71 (s, 3H); MS m/e 533.3 [M+H]+.

Workup

  1. customwas sparged with nitrogen for 8 minutes
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a syringe
  4. filtrationfilter
  5. concentrationThe filtrate was concentrated in vacuo, EtOAc and saturated NH4Cl aqueous solution
  6. additionwere added
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with EtOAc
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-5f3512b6878a48289a7ecffb9b07b86f
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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