Hydrochloric Acid → methyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate

HRID 1402599ノート

反応式

HRID 1402599 の反応式
[F:1][C:2]1[CH:32]=[CH:31][C:30]([C:33]([NH:35][C:36]2[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=2[F:43])=[O:34])=[CH:29][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]2[NH:15][CH:14]=[C:13]([C:16]([NH:18][CH:19]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:20]([OH:22])=O)=[O:17])[CH:12]=2)[CH:6]=1.CN(C(O[N:52]1N=N[C:54]2C=CC=N[C:53]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl>O1CCCC1.O>[CH2:53]([NH:52][C:20](=[O:22])[CH:19]([NH:18][C:16]([C:13]1[CH:12]=[C:11]([C:7]2[CH:6]=[C:5]([O:4][C:3]3[CH:29]=[C:30]([C:33]([NH:35][C:36]4[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:37]=4[F:43])=[O:34])[CH:31]=[CH:32][C:2]=3[F:1])[CH:10]=[CH:9][N:8]=2)[NH:15][CH:14]=1)=[O:17])[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH3:54]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712935982-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-methoxy-5-oxopentanoic acid

生成物 1

HCID 71293549methyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

To a stirred suspension of 2-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-methoxy-5-oxopentanoic acid (260 mg, 0.44 mmol) in 20 ml of anhydrous tetrahydrofuran were added HATU (200 mg, 0.53 mmol) and N,N-diisopropylethylamine (170 mg, 1.32 mmol). The mixture was heated at 60° C. for 15 minutes and cooled to room temperature, followed by addition of 2-Methylamine solution in THF (0.44 ml, 0.88 mmol). The mixture was stirred for another 5 minutes, and poured into 100 ml of water with vigorous stirring. 1M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography eluting with 2˜5% methanol in chloroform to give methyl 5-(ethylamino)-4-[({5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]-5-oxopentanoate as white solid. Yield: 127 mg, 47%.

後処理

  1. temperaturecooled to room temperature
  2. filtrationThe precipitates were filtered
  3. washwashed with water
  4. customdried in vacuo
  5. customto give the crude, which
  6. customwas purified by silica gel chromatography
  7. washeluting with 2˜5% methanol in chloroform

出典と根拠

ORDレコード
ord-4cb63226df8f44c787955d28ac9cc3f5
出典データセット
uspto-grants-2014_12
特許番号
US08906944B2

反応ノート

読み込み中…