Dimethylacetamide → HCID 86716142, compound

HRID 627566Notes

Reaction equation

HRID 627566 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:24]3[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=3)([C:14]3[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([C:30]([F:33])([F:32])[F:31])[C:3]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:81][N:82](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]>[OH:13][C:12]([C:24]1[N:28]([CH3:29])[CH:27]=[N:26][CH:25]=1)([C:14]1[CH:15]=[N:16][C:17]([C:20]([F:22])([F:21])[F:23])=[CH:18][CH:19]=1)[C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([C:30]([F:31])([F:32])[F:33])[C:3]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[C:2]2[C:81]#[N:82].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86716144HCID 86716144, compound

Product 1

HCID 86716142HCID 86716142, 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 (4-chloro-3-phenyl-2-(trifluoromethyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol•TFA (101 mg, 0.128 mmol, Example 172), Pd2 dba3 (12 mg, 0.013 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (X-Phos, 6.3 mg, 0.013 mmol), zinc cyanide (10 mg, 0.085 mmol), and zinc nanopowder (2.5 mg, 0.038 mmol) in N,N-dimethylacetamide (1 mL) was purged with nitrogen for 5 min, and then heated at 120° C. for 2.5 hours. The mixture was allowed to cool to room temperature and filtered through a syringe filter. The filtrate was concentrated in vacuo, and EtOAc and NH4OH (aqueous) 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 give the title compound as a white solid. 1H NMR (400 MHz, MeOD-d4) δ 9.06 (s, 1H), 8.87 (d, J=2.02 Hz, 1H), 8.38-8.47 (m, 2H), 8.14 (dd, J=2.27, 8.34 Hz, 1H), 8.05 (dd, J=2.02, 9.09 Hz, 1H), 7.91 (d, J=8.08 Hz, 1H), 7.52-7.62 (m, 3H), 7.47 (d, J=6.06 Hz, 2H), 7.19 (s, 1H), 3.72 (s, 3H); MS m/e 554.1 [M+H]

Workup

  1. customwas purged with nitrogen for 5 min
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a syringe
  4. filtrationfilter
  5. concentrationThe filtrate was concentrated in vacuo, and EtOAc and NH4OH (aqueous)
  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-02fc1cd1300d487f99874b3a04827766
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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