Methanol → HCID 59393680, compound

HRID 2092137Notes

Reaction equation

HRID 2092137 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:9]=[N:10][C:11]([C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:26]=[N:27][CH:28]=[C:29]([O:31][CH3:32])[CH:30]=4)=[CH:21][CH:20]=3)([CH3:18])[CH:15]([CH3:17])[CH3:16])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1.CN([CH:36]=[O:37])C.[CH3:38][OH:39].[C]=O>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:32][O:31][C:29]1[CH:30]=[C:25]([C:22]2[CH:23]=[CH:24][C:19]([C:14]([C:11]3[N:10]=[CH:9][C:8]([C:5]4[N:4]=[N:3][C:2]([C:38]([O:37][CH3:36])=[O:39])=[CH:7][CH:6]=4)=[CH:13][CH:12]=3)([CH3:18])[CH:15]([CH3:17])[CH3:16])=[CH:20][CH:21]=2)[CH:26]=[N:27][CH:28]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 59393682HCID 59393682, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 59393680HCID 59393680, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

Palladium (II) acetate (81.0 mg, 0.360 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (401 mg, 0.720 mmol) were added to a stirred solution of 4b (1.60 g, 3.62 mmol) in triethylamine:DMF:methanol (25.0 mL of a 1:10:10 mixture, respectively) at rt. The reaction mixture was saturated with carbon monoxide and then heated to 70° C. under a carbon monoxide atmosphere (balloon) for approximately 3.5 h. After cooling to rt, the reaction mixture was filtered through a short column of CELITE®, eluting with DCM. The filtrate was partially concentrated in vacuo and diluted with EtOAc. The organic phase was washed with water and brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 40%-80% EtOAc/hexanes as eluent) afforded the title compound 4c. m/z (ES) 469 (MH)+. 1HNMR. (500 MHz, CDCl3): δ 9.31 (d, 1H, J=1.9 Hz), 8.45 (m, 2H), 8.29 (d, 2H, J=8.7 Hz), 8.03 (d, 1H, J=8.7 Hz), 7.50 (m, 6H), 4.12 (s, 3H), 3.94 (s, 3H), 3.22 (m, 1H), 1.81 (s, 3H), 0.93 (d, 3H, J=6.6 Hz), 0.89 (d, 3H, J=6.6 Hz).

Workup

  1. customat rt
  2. temperatureAfter cooling to rt
  3. filtrationthe reaction mixture was filtered through a short column of CELITE®
  4. washeluting with DCM
  5. concentrationThe filtrate was partially concentrated in vacuo
  6. additiondiluted with EtOAc
  7. washThe organic phase was washed with water and brine
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 40%-80% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-37b6f26be15d4240a163137efd74f8f0
Source dataset
uspto-grants-2013_05
Patent number
US08440672B2

Reaction notes

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