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 1625468노트

반응식

HRID 1625468 반응식
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]

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 2

HCID 887Methanol용매HCID 10942334Sodium Methoxide용매

실험 절차

(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)

후처리

  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

출처 및 근거

ORD 기록
ord-eb70e980ed36494495d639ba281a4813
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778977B2

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