Diisopropylethylamine → 1-{4-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenyl}-3-(5-methyl-pyrazin-2-yl)-urea

HRID 1830785ノート

反応式

HRID 1830785 の反応式
C[C:2]1[N:3]=[CH:4][C:5]([C:8](O)=O)=[N:6][CH:7]=1.C([N:14]([CH:17](C)C)CC)(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.[CH2:37]([N:44]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH2:53])=[C:49]([O:54][CH3:55])[CH:48]=1)[CH3:45])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:37]([N:44]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:17]([NH:14][C:2]2[CH:7]=[N:6][C:5]([CH3:8])=[CH:4][N:3]=2)=[O:27])=[C:49]([O:54][CH3:55])[CH:48]=1)[CH3:45])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 1228315-Methyl-2-pyrazinecarboxylic acidHCID 199401P,P-Diphenylphosphinic azideHCID 220463124-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenylamine

生成物 1

HCID 220465131-{4-[(Benzyl-methyl-amino)-methyl]-2-methoxy-phenyl}-3-(5-methyl-pyrazin-2-yl)-urea収率 40.4%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

In a 50 mL round bottom flask, 5-methylpyrazine-2-carboxylic acid (250 mg, 1.8 mmol) and diisopropylethylamine (330 μL, 1.9 mmol) in 20 mL toluene, was stirred under a nitrogen atmosphere until the acid dissolved. Diphenylphosphoryl azide (523 mg, 1.9 mmol) was added and the solution was heated to 90° C. After 20 minutes, nitrogen evolution had subsided, and the solution had darkened to a caramel color. The reaction was cooled to 65° C., and 4-[(benzyl-methyl-amino)-methyl]-2-methoxy-phenylamine (486 mg, 1.9 mmol) was added as a solution in 5 mL toluene. The reaction was allowed to stir at 65° C. for 6 h, and was then cooled to room temperature, diluted with 30 mL EtOAc, and washed with 15 mL 5% NH4OH. The aqueous phase was extracted with EtOAc (2×20 mL) and the combined organics were washed with 30 mL brine, dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash chromatography to give 285 mg (40%) of the desired product, which was further purified by trituration with diethyl ether. Mp=142-143° C. 1H NMR (400 MHz, CDCl3): δ11.33 (s, 1H), 9.51 (s, 1H), 8.41 (s, 1H), 8.27 (d, J=8.61 Hz, 1H), 8.08 (s, 1H), 7.2-7.4 (m, 5H), 6.96 (d, J=7.83 Hz, 1H) 3.97 (s, 3H), 3.53 (s, 4H), 2.53 (s, 3H), 2.22 (s, 1H). 13C NMR (400 MHz, CDCl3): δ153.70, 149.03, 147.48, 147.4, 145.99, 138.73, 137.38, 134.81, 129.19, 128.42, 127.16, 121.89, 119.81, 111.05, 104.49, 94.98, 87.22, 61.81, 56.37, 42.5. MS (APCI-pos)M+1=392.0.

後処理

  1. dissolutiondissolved
  2. temperatureThe reaction was cooled to 65° C.
  3. temperaturewas then cooled to room temperature
  4. washwashed with 15 mL 5% NH4OH
  5. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  6. washthe combined organics were washed with 30 mL brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-ddad2bc15bd346e3bbe0194ead51bd5d
出典データセット
uspto-grants-2006_06
特許番号
US07067506B2

反応ノート

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