Dichloromethane → (R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid

HRID 1625468ノート

反応式

HRID 1625468 の反応式
C[O:2][C:3](=[O:48])[CH2:4][C@H:5]([C:25]1[S:26][C:27]([C:30]2[C:38]3[C:33](=[N:34][CH:35]=[CH:36][CH:37]=3)[N:32](S(C3C=CC=CC=3)(=O)=O)[CH:31]=2)=[CH:28][CH:29]=1)[NH:6][C:7]([C:9]1[C:10](=[O:24])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)=[O:8].C(Cl)Cl>C[O-].[Na+].CO>[F:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[F:22])[CH2:15][N:11]1[CH:12]=[CH:13][CH:14]=[C:9]([C:7]([NH:6][C@@H:5]([C:25]2[S:26][C:27]([C:30]3[C:38]4[C:33](=[N:34][CH:35]=[CH:36][CH:37]=4)[NH:32][CH:31]=3)=[CH:28][CH:29]=2)[CH2:4][C:3]([OH:48])=[O:2])=[O:8])[C:10]1=[O:24]

参加物

5

反応物 2

HCID 6344DichloromethaneHCID 68609564(R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

生成物 1

HCID 59362416(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 10942334Sodium Methoxide溶媒

実験手順

(R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester (0.050 g, 0.000072 mol;) was dissolved in 0.5 M of Sodium methoxide in methanol (3 mL) and Methylene chloride (3 g, 0.04 mol;). The reaction was heated at 75 C for 1 hour. LC-MS showed the disappearance of starting material and the appearance of product at 1.25 535.55. Some methyl ester and acid were seen but by the time it was injected on gilson only acid was present. The reaction was concentrated and dissolved in DMSO and methanol 1:1 for purification by Gilson Preparative HPLC. Pure fractions were combined and concentrated. ES (+) MS m/e=535.55; NMR (400 MHz, DMSO-d6) δ ppm 2.98 (d, 2H, J=7 Hz), 5.22 (s, 2H,), 5.66 (m, 1H), 6.66 (t, 1H, J=8 Hz), 7.03 (d, 1H, J=3 Hz), 7.14-7.20 (m, 2H), 7.22 (d, 1H, J=4 Hz), 7.38-7.49 (m, 2H), 7.81 (m, 1H), 8.2-8.25 (m, 2H), 8.29 (m, 1H), 8.4 (dd. 1H), 10.27 (d, 1H)

後処理

  1. temperatureThe reaction was heated at 75 C for 1 hour
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in DMSO
  4. custommethanol 1:1 for purification by Gilson Preparative HPLC
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-eb70e980ed36494495d639ba281a4813
出典データセット
uspto-grants-2014_07
特許番号
US08778977B2

反応ノート

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