Triphosgene → 1-(4-(Trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-4-yl)urea

HRID 1505183ノート

反応式

HRID 1505183 の反応式
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1.ClC(Cl)(O[C:23](=[O:29])[O:24][C:25](Cl)(Cl)Cl)Cl.[N-:31]=[C:32]=[O:33]>CCOC(C)=O.CN(C=O)C>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:32]([NH:31][C:6]2[C:9]3[NH:10][C:23](=[O:29])[O:24][C:25]=3[CH:3]=[CH:4][CH:5]=2)=[O:33])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1

参加物

6

反応物 3

HCID 94429TriphosgeneHCID 105034IsocyanateHCID 58873623(4-(Trifluoromethyl)-2-(piperidin-1-yl)phenyl)-methanamine

生成物 1

HCID 534762451-(4-(Trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-4-yl)urea収率 14%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
80 °C

実験手順

Amine 2c (350 mg, 1.33 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (395 mg, 1.33 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1b (100 mg, 0.66 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 40 mg of a white solid. Yield=14% 1HNMR (DMSO, 400 MHz) δ 1.55 (2H, m), 1.68 (4H, m), 2.85 (4H, m), 4.43 (2H, d, J=5.6 Hz), 6.88 (1H, t), 6.98 (2H, m), 7.05 (1H, m), 7.31 (1H, s), 7.42 (1H, d), 7.52 (1H, d, J=8 Hz), 8.52 (1H, s), 11.00 (1H, bs); [M+1] 435.3 (C21H21F3N4O3 requires 434.41).

後処理

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutiondissolved in 5 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (30 ml)
  7. washwashed with water (1×20 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

出典と根拠

ORDレコード
ord-3351a5ca96c841e3afc09426fc51a9c8
出典データセット
uspto-grants-2015_12
特許番号
US09216975B2

反応ノート

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