Diisopropylethylamine → HCID 71212232, compound

HRID 1752259Notes

Reaction equation

HRID 1752259 reaction equation
Cl[C:2]1[N:7]=[N:6][CH:5]=[C:4]2[O:8][CH2:9][CH2:10][CH2:11][C:3]=12.C(N(CC)C(C)C)(C)C.[CH3:21][O:22][C:23]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:24]=1[CH2:25][NH2:26]>C(O)(C)C>[CH3:21][O:22][C:23]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:24]=1[CH2:25][NH:26][C:2]1[N:7]=[N:6][CH:5]=[C:4]2[O:8][CH2:9][CH2:10][CH2:11][C:3]=12

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5972502,4-Dimethoxybenzylamine2×HCID 89375780HCID 89375780, compound

Product 1

HCID 71212232HCID 71212232, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 5-chloro-3,4-dihydro-2H-pyrano[2,3-d]pyridazine (150 mg, 0.879 mmol), N,N-diisopropylethylamine (0.154 mL, 114 mg, 0.879 mmol), and 2,4-dimethoxybenzylamine (294 mg, 1.76 mmol) in isopropanol (2 mL) was heated in a sealed tube 18 hours at 115° C. and then 4.5 hours at 145° C. before addition of excess 2,4-dimethoxybenzylamine (about 2 g, 12 mmol). The reaction was stirred at 145° C. for 18 hours. After cooling to room temperature, isopropanol was removed in vacuo. The crude was then treated with diethyl ether (30 mL). A tan solid was removed by filtration. The filtrate was washed twice with small amounts of saturated aqueous ammonium chloride. The organic layer was dried over sodium sulfate, filtered, and concentrated down. The crude was purified by silica gel chromatography with a 0 to 10% methanol/dichloromethane gradient to afford the title compound (159 mg) as an amber foamy oil. MS (ESI) [m/e, (M)+]=301.8. 1H NMR (400 MHz, chloroform-d) δ ppm 8.22 (s, 1H), 7.35 (d, J=8.08 Hz, 1H), 6.36-6.56 (m, 2H), 4.73 (d, J=5.56 Hz, 2H), 4.37-4.56 (m, 1H), 4.11-4.24 (m, 2H), 3.86 (s, 3H), 3.81 (s, 3H), 2.27-2.31 (m, 2H), 2.04-2.11 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customisopropanol was removed in vacuo
  3. additionThe crude was then treated with diethyl ether (30 mL)
  4. customA tan solid was removed by filtration
  5. washThe filtrate was washed twice with small amounts of saturated aqueous ammonium chloride
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated down
  9. customThe crude was purified by silica gel chromatography with a 0 to 10% methanol/dichloromethane gradient

Sources & evidence

ORD record
ord-752e5d075fc04e17ad8180f715d21a13
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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