Dimethylformamide → HCID 58212052, compound

HRID 1967441Notes

Reaction equation

HRID 1967441 reaction equation
[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=2)[C:9]2[C:4](=[CH:5][C:6](B3OC(C)(C)C(C)(C)O3)=[CH:7][CH:8]=2)[CH2:3]1.[NH2:31][C:32]1[N:33]=[N:34][C:35](Cl)=[CH:36][CH:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O>[CH3:1][N:2]1[CH2:11][CH:10]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=2)[C:9]2[C:4](=[CH:5][C:6]([C:35]3[N:34]=[N:33][C:32]([NH2:31])=[CH:37][CH:36]=3)=[CH:7][CH:8]=2)[CH2:3]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 216436-Amino-3-chloropyridazineHCID 44546896HCID 44546896, compound

Product 1

HCID 58212052HCID 58212052, compound

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of Compound 18 (6.0 g, 15.0 mmol), 3-amino-6-chloropyridazine (3.0 g, 22.5 mmol) and cesium carbonate (14.7 g, 45.0 mmol) were added DMF (140 mL) and water (35 mL). The reaction solution was flushed with argon for 10 min, and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (1.2 g, 1.5 mmol) was added. The resultant mixture was flushed with argon for 5 min and heated at 80° C. for 1 h. The reaction solution was then cooled to room temperature, diluted with ethyl acetate, washed with 1:1 brine and water (2×), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography (92:2:5.4:0.6 to 47:47:5.4:0.6 dichloromethane/ethyl acetate/methanol/concentrated ammonium hydroxide) to give rac-1 (3.2 g, 58%) as a light tan solid: 1H NMR (500 MHz, CDCl3) δ 7.82-7.76 (m, 4H), 7.71 (s, 1H), 7.61-7.57 (m, 2H), 7.47-7.43 (m, 2H), 7.30 (dd, J=8.0, 1.5 Hz, 1H), 6.99 (d, J=8.0 Hz, 1H), 6.80 (d, J=9.5 Hz, 1H), 4.71 (br s, 2H), 4.50 (t, J=7.0 Hz, 1H), 3.89 (d, J=15.0 Hz, 1H), 3.74 (d, J=14.5 Hz, 1H), 3.14 (dd, J=11.5, 6.0 Hz, 1H), 2.70 (dd, J=11.5, 9.0 Hz, 1H), 2.48 (s, 3H); ESI MS m/z 367 [M+H]+.

Workup

  1. customThe reaction solution was flushed with argon for 10 min
  2. customThe resultant mixture was flushed with argon for 5 min
  3. temperatureThe reaction solution was then cooled to room temperature
  4. additiondiluted with ethyl acetate
  5. washwashed with 1:1 brine and water (2×)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (92:2:5.4:0.6 to 47:47:5.4:0.6 dichloromethane/ethyl acetate/methanol/concentrated ammonium hydroxide)
  9. customto give rac-1 (3.2 g, 58%) as a light tan solid

Sources & evidence

ORD record
ord-f85f2c2d8d3e43efb01e97959301bab8
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

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