1-Isocyanato-4-methoxybenzene → 1-[3-Benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-3-(4-methoxyphenyl)urea

HRID 2172946Notes

Reaction equation

HRID 2172946 reaction equation
[CH2:1]([C:8]1[C:9]([NH2:22])=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=[O:33])=[CH:27][CH:26]=1>ClCCCl>[CH2:1]([C:8]1[C:9]([NH:22][C:32]([NH:31][C:28]2[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)=[O:33])=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 794431-Isocyanato-4-methoxybenzeneHCID 113007862-Amino-3-benzyl-5-(4-methoxyphenyl)pyrazine

Product 1

HCID 575166861-[3-Benzyl-5-(4-methoxyphenyl)pyrazin-2-yl]-3-(4-methoxyphenyl)ureaYield 59.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, to a solution of 3-benzyl-5-(4-methoxyphenyl)pyrazin-2-amine (12) (synthesized by the process of M. Adamczyk, et al., Org. Prep. Proced. Int., 33, 477-485 (2001)) (306 mg, 1.05 mmol) in anhydrous 1,2-dichloroethane (10 mL) was added 4-methoxyphenyl isocyanate (13) (191 μL, 1.00 mmol) at room temperature, and the mixture was heated with stirring at 80° C. for 19 hours. After cooling to room temperature, the solid precipitated was collected by filtration and dried in vacuo to give the crude product (293 mg, <664 μmol, <63.2%) as a colorless solid. An aliquot (93.0 mg, <211 μmol) was recrystallized from methanol to give Compound 11u (54.9 mg, 125 μmol, 59.2%) as a colorless solid. Rf=0.50 (n-hexane/ethyl acetate=1/1); 1H NMR (400 MHz, DMSO-d6) δ 3.73 (s, 3H), 3.81 (s, 3H), 4.36 (s, 2H), 6.98-6.93 (AA′BB′, 2H), 7.02-7.08 (AA′BB′, 2H), 7.17-7.25 (m, 1H), 7.28-7.32 (m, 4H), 7.43-7.48 (AA′BB′, 2H), 7.95-8.01 (AA′BB′, 2H), 8.79 (s, 1H), 9.04 (s, 1H), 10.58 (s, 1H); 13C NMR (67.8 MHz, DMSO-d6) δ 38.5, 55.18, 55.24, 114.0 (2C), 114.4 (2C), 121.1 (2C), 126.3, 127.2 (2C), 128.2, 128.3 (2C), 129.0 (2C), 131.7, 134.5, 137.9, 144.4, 145.0, 145.4, 152.2, 155.1, 160.1; IR (KBr, cm−1) 704, 746, 824, 1038, 1173, 1242, 1329, 1369, 1416, 1481, 1510, 1570, 1607, 1668, 2833, 3030, 3261; Anal. Calcd. For C26H24N4O3: C, 70.89; H, 5.49; N, 12.72. Found: C, 70.66; H, 5.49; N, 12.61.

Workup

  1. temperaturethe mixture was heated
  2. temperatureAfter cooling to room temperature
  3. customthe solid precipitated
  4. filtrationwas collected by filtration
  5. customdried in vacuo
  6. customto give the crude product (293 mg, <664 μmol, <63.2%) as a colorless solid
  7. customAn aliquot (93.0 mg, <211 μmol) was recrystallized from methanol

Sources & evidence

ORD record
ord-b7dab580a4e341be8256035442b38fdb
Source dataset
uspto-grants-2015_06
Patent number
US09056840B2

Reaction notes

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