Piperidine → (E)-2-(2-(4-amino-3-methoxystyryl)-6-methyl-4H-pyran-4-ylidene)malononitrile

HRID 576455Notes

Reaction equation

HRID 576455 reaction equation
[CH3:1][C:2]1[O:3][C:4]([CH3:13])=[CH:5][C:6](=[C:8]([C:11]#[N:12])[C:9]#[N:10])[CH:7]=1.[CH:14]([C:16]1[CH:21]=[CH:20][C:19]([NH:22]C(=O)OC(C)(C)C)=[C:18]([O:30][CH3:31])[CH:17]=1)=O.N1CCCCC1>CCO>[NH2:22][C:19]1[CH:20]=[CH:21][C:16](/[CH:14]=[CH:13]/[C:4]2[O:3][C:2]([CH3:1])=[CH:7][C:6](=[C:8]([C:11]#[N:12])[C:9]#[N:10])[CH:5]=2)=[CH:17][C:18]=1[O:30][CH3:31]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 1199154-(Dicyanomethylene)-2,6-dimethyl-4H-pyranHCID 84804049Tert-butyl 4-formyl-2-methoxyphenylcarbamate

Product 1

HCID 76071879(E)-2-(2-(4-amino-3-methoxystyryl)-6-methyl-4H-pyran-4-ylidene)malononitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(2,6-dimethyl-4H-pyran-4-ylidene)malononitrile (1, 20.7 mg, 0.12 mmol) and aldehyde 2c (25.1 mg, 0.1 mmol) were dissolved in anhydrous EtOH (0.67 ml) at 65° C. Piperidine (0.5 μl) was added and the mixture was stirred at 80° C. for 7 hours. The solvent was removed with a stream of N2, the crude mixture was dissolved in EtOAc at 5 mg/ml and purified by normal phase preparative HPLC using hexanes/ethyl acetate as eluent. Yield: 10.6 mg (26%). LCMS ESI+m/z 406 (M+H+) H-NMR (400 MHz, CD2Cl2): 8.16 (1H, d, J=8 Hz) 7.47 (1H, d, J=16 Hz) 7.29 (1H, s) 7.19 (1h, dd, J=8 Hz, 0.4 Hz) 7.1 (1H, d, J=0.4 Hz) 6.67-6.74 (2H, m) 6.56 (1H, m) 3.97 (3H, s) 2.43 (3H, s) 1.55 (9H, s). C-NMR (400 MHz, CD2Cl2) 163.02, 160.11, 157.01, 152.81, 148.32, 138.31, 131.33, 129.29, 122.99, 118.01, 116.81, 115.74, 108.45, 107.26, 106.77, 81.27, 56.35, 28.56, 20.31. This compound was treated with a 4N HCl solution in dioxane (4 N, 1.3 ml) for 3 hrs. The mixture was diluted with hexanes, the precipitate centrifuged, re-suspended and washed with hexanes, then dried under vacuum. LCMS ESI+ m/z: 306 (M+H+). H-NMR (400 MHz, CD2Cl2) 7.37 (1H, d, J=16 hz) 7.12 (1H, dd, J=16 Hz, 0.4 Hz) 7.02 (1H, d, J=0.4 Hz) 6.56-6.63 (3H, m) 6.12 (1H, m) 3.97 (3H, s) 2.42 (3H, s). C-NMR (400 MHz, CD2Cl2) 164.58, 156.12, 151.52, 140.90, 139.05, 129.73, 127.19, 121.74, 115.48, 110.73, 109.95, 102.81, 101.68, 100.79, 90.2, 55.89, 21.02.

Workup

  1. customThe solvent was removed with a stream of N2
  2. dissolutionthe crude mixture was dissolved in EtOAc at 5 mg/ml
  3. custompurified by normal phase preparative
  4. additionThis compound was treated with a 4N HCl solution in dioxane (4 N, 1.3 ml) for 3 hrs
  5. additionThe mixture was diluted with hexanes
  6. washwashed with hexanes
  7. customdried under vacuum

Sources & evidence

ORD record
ord-9fe17135e2fd49499bd837ee769f2728
Source dataset
uspto-grants-2015_05
Patent number
US09040019B2

Reaction notes

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