Dimethylformamide → HCID 118071099, compound

HRID 920710Notes

Reaction equation

HRID 920710 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:23](I)=[C:11]3[CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:25]([C:23]1[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:11]=12)#[N:26]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 118071097HCID 118071097, compound

Product 1

HCID 118071099HCID 118071099, compoundYield 64%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of Intermediate 1H (6.0 g, 13.54 mmol) in DMF (10 mL) was added zinc cyanide (2.066 g, 17.60 mmol) and zinc (0.265 g, 4.06 mmol) to give a brown suspension. The reaction mixture was degassed under nitrogen for 15 min, added Pd2(dba)3 (0.620 g, 0.677 mmol), dppf (0.750 g, 1.354 mmol), and stirred at 90° C. for 18 h. The reaction mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (3×50 mL). Combined organic layer was washed with aqueous ammonia (2×50 mL), water, dried over Na2SO4, filtered and concentrated to afford crude Intermediate 1I as a brown gummy solid. The residue was purified by ISCO using 40 g REDISEP® silica gel column eluting with 3% MeOH in chloroform. The collected fractions were concentrated together to afford Intermediate 1I (3 g, 64%) as white solid. MS(ES): m/z=343 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.84-7.94 (m, 2H), 7.34-7.44 (m, 2H), 4.78 (s, 2H), 4.23 (t, J=5.36 Hz, 2H), 3.87 (t, J=5.45 Hz, 2H), 1.46 (s, 9H).

Workup

  1. customto give a brown suspension
  2. customThe reaction mixture was degassed under nitrogen for 15 min
  3. customThe reaction mixture was quenched with water
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washCombined organic layer was washed with aqueous ammonia (2×50 mL), water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude Intermediate 1I as a brown gummy solid
  10. customThe residue was purified by ISCO
  11. washeluting with 3% MeOH in chloroform
  12. concentrationThe collected fractions were concentrated together

Sources & evidence

ORD record
ord-4e9f4743bb8b4f988425bf2507790ce5
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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