Methanol → Methyl 6-(4-{1,2-dimethyl-1-[5-(pyridin-2-ylmethoxy)pyridin-2-yl]propyl}phenyl)pyridazine-3-carboxylate

HRID 1644874Notes

Reaction equation

HRID 1644874 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([CH3:32])([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)=[CH:20][N:19]=3)[CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.CN([CH:36]=[O:37])C.[CH3:38][OH:39]>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][C:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[N:4]=[N:3][C:2]([C:38]([O:37][CH3:36])=[O:39])=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:20][N:19]=1)[CH:15]([CH3:17])[CH3:16]

Participants

7

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 57910808HCID 57910808, compound

Product 1

HCID 57910811Methyl 6-(4-{1,2-dimethyl-1-[5-(pyridin-2-ylmethoxy)pyridin-2-yl]propyl}phenyl)pyridazine-3-carboxylate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

Palladium (II) acetate (8.00 mg, 0.0350 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (39.0 mg, 0.070 mmol) were added successively to a stirred solution of 5b (155 mg, 0.349 mmol) in triethylamine:DMF:MeOH (4.00 mL of a 1:10:10 mixture, respectively) at rt. A gentle stream of the carbon monoxide gas was bubbled through the reaction mixture for approximately 15 min, after which the resulting mixture was heated to 70° C. under a carbon monoxide atmosphere (balloon) for about 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, brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 30%-100% EtOAc/hexanes as eluent) afforded the title compound 5c. m/z (ES) 469 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.62 (d, 1H, J=4.8 Hz), 8.41 (m, 1H), 8.22 (d, 1H, J=8.7 Hz), 8.08 (d, 2H, J=8.8 Hz), 7.96 (d, 1H, J=8.9 Hz), 7.75 (dt, 1H, J=1.7, 7.7 Hz), 7.56 (d, 2H, J=8.7 Hz), 7.53 (d, 1H, J=7.8 Hz), 7.26 (dd, 1H, J=5.2, 7.3 Hz), 7.19 (m, 2H), 5.23 (s, 2H), 4.10 (s, 3H), 3.11 (m, 1H, 6.6 Hz), 1.73 (s, 3H), 0.89 (d, 3H, J=6.7 Hz), 0.83 (d, 3H, J=6.8 Hz).

Workup

  1. customat rt
  2. customA gentle stream of the carbon monoxide gas was bubbled through the reaction mixture for approximately 15 min
  3. temperatureAfter cooling to rt
  4. filtrationthe reaction mixture was filtered through a short column of CELITE®
  5. washeluting with DCM
  6. concentrationThe filtrate was partially concentrated in vacuo
  7. additiondiluted with EtOAc
  8. washThe organic phase was washed with water, brine
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 30%-100% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-3edd65837f4d4152aa4158b6575f53fd
Source dataset
uspto-grants-2012_02
Patent number
US08124628B2

Reaction notes

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