4-Fluorobenzylamine → HCID 57810203、化合物

HRID 445513ノート

反応式

HRID 445513 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]2([C:28]([OH:30])=O)[CH2:27][CH2:26]2)=[O:24])=[CH:18][CH:17]=1.[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[CH:34][CH:33]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:23]([C:25]2([C:28]([NH:37][CH2:36][C:35]3[CH:38]=[CH:39][C:32]([F:31])=[CH:33][CH:34]=3)=[O:30])[CH2:27][CH2:26]2)=[O:24])=[CH:20][CH:21]=1

参加物

7

反応物 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57810164849217-77-2

生成物 1

HCID 57810203HCID 57810203、化合物収率 35.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenylcarbamoyl]-cyclopropanecarboxylic acid (74.3 mg, 0.182 mmol), 4-Fluoro benzylamine (25 μL, 0.219 mmol), DIEA (90.0 μL, 0.544 mmol) in DMA (1.0 mL) was added HATU (203 mg, 0.534 mmol). The resulting solution was stirred at room temperature for 1 hour before adding dropwise to water (10 mL) with stirring. The slurry was sonicated, filtered and the solids were washed with 1 N NaOH followed by water. After air drying, the solids were further purified by prep HPLC, affording ‘N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-[(4-fluorophenyl)methyl]cyclopropane-1,1-dicarboxamide (33 mg, 35% yield, 98% pure) as a white solid. 1H NMR (DMSO, d6): 10.82 (s, 1H), 8.80 (d, 1H), 8.50 (t, 1H), 7.83 (d, 2H), 7.74 (s, 1H), 7.56 (s, 1H), 7.30-7.38 (m, 4H), 7.15 (t, 2H), 6.80 (d, 1H), 4.32 (d, 2H), 4.04 (s, 3H), 4.03 (s, 3H), 1.42 (s, 4H).

後処理

  1. stirringwith stirring
  2. customThe slurry was sonicated
  3. filtrationfiltered
  4. washthe solids were washed with 1 N NaOH
  5. customAfter air drying
  6. customthe solids were further purified by prep HPLC

出典と根拠

ORDレコード
ord-9ff74b4e6f2949bd880b19062b4f251f
出典データセット
uspto-grants-2013_07
特許番号
US08476298B2

反応ノート

読み込み中…