Ethyl isocyanate → HCID 11495480, compound

HRID 216149Notes

Reaction equation

HRID 216149 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([O:14][CH3:15])[N:11]=[C:10]([NH:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:27]([N:29]=[C:30]=[O:31])[CH3:28]>N1C=CC=CC=1>[CH2:27]([NH:29][C:30]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH:9]=[C:10]([NH:16][CH2:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:11]=[C:12]([O:14][CH3:15])[N:13]=2)[CH:3]=1)=[O:31])[CH3:28]

Participants

4

Reactant 2

HCID 8022Ethyl isocyanateHCID 11537596HCID 11537596, compound

Product 1

HCID 11495480HCID 11495480, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of [6-(3-amino-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine (184 mg, 0.45 mmol, Example 2) in pyridine (1.5 mL) is added ethyl isocyanate (43 μL, 0.54 mmol). The reaction mixture is stirred for 18 hours at ambient temperature, quenched with the addition of water (25 mL), and extracted four times with EtOAc (25 mL). The combined extracts and washed four times with aqueous copper sulfate solution (25 mL), with water (25 mL), with brine (25 mL), dried over magnesium sulfate, filtered and concentrated by rotary evaporator. The resulting solid is subjected to flash column chromatography on silica (4.5 g) eluting with 20 to 40% EtOAc in heptane to afford 1-ethyl-3-(3-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-urea [98.3 mg, 52%, Example 41]. LCMS: RT=2.68 minutes, MS: 422 (M+H). 1H NMR (300 MHz, CDCl3) δ 8.11 (1H, d, J=0.17 Hz), 7.88 (2H, s), 7.62 (1H, d, J=0.026 Hz), 7.49 (1H, d, J=0.026 Hz), 7.18 (4H, m), 6.81 (2H, m), 6.22 (1H, d, J=0.08 Hz), 5.83 (1H, s), 5.35 (1H, s), 3.93 (3H, d, J=0.04 Hz), 3.73 (3H, d, J=0.012 Hz), 3.55 (2H, m), 3.19 (2H, q, J=0.022 Hz), 2.81 (2H, m), 2.13 (1H, s), 1.04 (2H, t, J=0.022 Hz). IC50=7.6 nM

Workup

  1. customquenched with the addition of water (25 mL)
  2. extractionextracted four times with EtOAc (25 mL)
  3. washThe combined extracts and washed four times with aqueous copper sulfate solution (25 mL)
  4. dry with materialwith water (25 mL), with brine (25 mL), dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporator
  7. washeluting with 20 to 40% EtOAc in heptane

Sources & evidence

ORD record
ord-10672a2315854be695ce338cab46f54d
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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