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

HRID 1670321노트

반응식

HRID 1670321 반응식
[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]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 115698931-(4-(6-(4-Methoxybenzylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea2회HCID 231530882-(4-Fluorophenyl)acetyl isocyanate2회HCID 247886284-(4-Amino-2,5-difluorophenoxy)pyridine-2-carboxamide

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-59b5fc87390b4f3181ed921ff02037fc
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989477B2

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