Dimethylacetamide → HCID 131735021, compound

HRID 926621Notes

Reaction equation

HRID 926621 reaction equation
[CH2:1]([C:8]1[C:9]([C:33]([F:36])([F:35])[F:34])=[N:10][C:11]2[C:16]([C:17]=1Cl)=[CH:15][C:14]([C:19]([C:27]1[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[OH:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:78][N:79](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:33]([F:36])([F:35])[F:34])=[N:10][C:11]2[C:16]([C:17]=1[C:78]#[N:79])=[CH:15][C:14]([C:19]([OH:20])([C:27]1[N:31]([CH3:32])[CH:30]=[N:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 131735020HCID 131735020, compound

Product 1

HCID 131735021HCID 131735021, 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)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol•TFA (86 mg, 0.12 mmol, Example 97), Pd2(dba)3 (10 mg, 0.011 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (X-Phos, 10 mg, 0.021 mmol), zinc cyanide (12 mg, 0.10 mmol) and zinc nanopowder (2.3 mg, 0.035 mmol) in N,N-dimethylacetamide (1 mL) was sparged with nitrogen for 8 minutes, and then heated at 120° C. for 2 hours. The mixture was allowed to cool to room temperature, 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 8.98 (s, 1H), 8.62 (d, J=4.04 Hz, 1H), 8.47 (d, J=2.02 Hz, 1H), 8.32 (d, J=9.09 Hz, 1H), 8.17 (dd, J=2.02, 9.09 Hz, 1H), 7.93 (dt, J=2.02, 7.58, 1H), 7.83 (d, J=8.08 Hz, 1H), 7.40-7.45 (m, 1H), 7.24-7.31 (m, 2H), 7.18-7.24 (m, 1H), 7.15 (d, J=1.52, 1H), 7.05 (d, J=7.58 Hz, 2H), 4.64 (s, 2H), 3.63 (s, 3H); MS m/e 500.3 [M+H]+.

Workup

  1. customwas sparged with nitrogen for 8 minutes
  2. temperatureto cool to room temperature
  3. additionEtOAc and saturated NH4Cl aqueous solution were added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-51dc5966665548dbad058dca0dfd5b5e
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

Loading…