Diisopropylethylamine → 1-(4-(2-Carbamoylpyridin-4-yloxy)-2,5-difluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea

HRID 1670321ノート

反応式

HRID 1670321 の反応式
[NH2:1][C:2]1[C:17]([F:18])=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)=[C:4]([F:19])[CH:3]=1.C(N(C(C)C)CC)(C)C.COC1C=CC(CNC2N=CN=C(OC3C=CC(N[C:51]([NH:53][C:54](=[O:63])[CH2:55][C:56]4[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=4)=[O:52])=CC=3F)C=2)=CC=1.FC1C=CC(CC(N=C=O)=O)=CC=1>C1COCC1>[C:13]([C:9]1[CH:8]=[C:7]([O:6][C:5]2[C:4]([F:19])=[CH:3][C:2]([NH:1][C:51]([NH:53][C:54](=[O:63])[CH2:55][C:56]3[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=3)=[O:52])=[C:17]([F:18])[CH:16]=2)[CH:12]=[CH:11][N:10]=1)(=[O:14])[NH2:15]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2 回HCID 231530882-(4-Fluorophenyl)acetyl isocyanate2 回HCID 247886284-(4-Amino-2,5-difluorophenoxy)pyridine-2-carboxamide

生成物 1

HCID 598528981-(4-(2-Carbamoylpyridin-4-yloxy)-2,5-difluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea収率 91%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a homogeneous mixture of 4-(4-amino-2,5-difluorophenoxy)picolinamide (0.15 g, 0.57 mmol) in THF (5 mL) was added diisopropylethylamine (0.10 mL, 0.57 mmol). The mixture was stirred for two minutes at ambient temperature before 2-(4-fluorophenyl)acetyl isocyanate (Compound D of Example 11, 0.36 M in toluene, 2.0 mL, 0.72 mmol) was added. After 3.5 hours, 2-(4-fluorophenyl)acetyl isocyanate (0.36 M in toluene, 2.0 mL, 0.72 mmol) was added to the reaction mixture. After an additional two hours, 2-(4-fluorophenyl)acetyl isocyanate (0.36 M in toluene, 2.0 mL, 0.72 mmol) was added to the reaction mixture. The mixture was then stirred for 16 hours before being concentrated in vacuo. The residue was treated with Et2O and sonication and the resultant white solid was removed by filtration. The solid was treated with Et2O and sonication two more times before vacuum filtration afforded a white solid (0.23 g, 91%). 1H NMR (DMSO-d6) δ 11.29 (s, 1H), 10.92 (s, 1H), 8.56 (d, 1H, J=5.6 Hz), 8.21-8.26 (m, 1H), 8.16 (br s, 1H), 7.76 (br s, 1H), 7.66-7.71 (m, 1H), 7.12-7.44 (m, 6H), 3.77 (s, 2H); MS (ESI+) m/z 445 (M+H)+.

後処理

  1. additionwas added
  2. waitAfter an additional two hours
  3. concentrationbefore being concentrated in vacuo
  4. additionThe residue was treated with Et2O and sonication
  5. customthe resultant white solid was removed by filtration
  6. additionThe solid was treated with Et2O and sonication two more times before vacuum filtration

出典と根拠

ORDレコード
ord-59b5fc87390b4f3181ed921ff02037fc
出典データセット
uspto-grants-2011_08
特許番号
US07989477B2

反応ノート

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