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Lithium Hydroxide → 2-Tert-butoxy-2-[6-methyl-1-[(4-methylsulfonylphenyl)methyl]-7-oxo-4-(p-tolyl)pyrrolo[2,3-c]pyridin-5-yl]acetic acid

HRID 1473215
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HRID 1473215 반응식
[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>CO.O1CCCC1>[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:33]1[CH:34]=[CH:35][C:36]([CH3:39])=[CH:37][CH:38]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

5

반응물 2

HCID 3939Lithium HydroxideHCID 89463522methyl 2-(tert-butoxy)-2-(6-methyl-1-(4-(methylsulfonyl)benzyl)-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

생성물 1

HCID 715367792-Tert-butoxy-2-[6-methyl-1-[(4-methylsulfonylphenyl)methyl]-7-oxo-4-(p-tolyl)pyrrolo[2,3-c]pyridin-5-yl]acetic acid

시약·촉매·용매 2

HCID 887Methanol용매
HCID 8028
Tetrahydrofuran
용매

반응 조건

온도
60 °C

실험 절차

A suspension of methyl 2-(tert-butoxy)-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (17 mg, 0.044 mmol) in Acetonitrile (0.4 mL) was treated with Cs2CO3 (57.9 mg, 0.178 mmol), 4-methylsulfonylbenzyl bromide (44.3 mg, 0.089 mmol), and stirred at 70° C. for 1.5 hours. The reaction was cooled to rt, diluted with water and 1N HCl, extracted with EtOAc, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane) gave methyl 2-(tert-butoxy)-2-(6-methyl-1-(4-(methylsulfonyl)benzyl)-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (22 mg, 0.040 mmol, 90% yield) as yellow oil. The ester intermediate was dissolved in Methanol (0.5 mL) and Tetrahydrofuran (THF) (0.5 mL), treated with 2M LiOH (0.120 mL, 0.24 mmol), and stirred at 60° C. for 2 hours. The reaction was concentrated and purified with reverse phase HPLC (20-100% MeCN/H2O-0.1% TFA) to give title compound (9.3 mg, 0.017 mmol, 37.6 yield) as off white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 1.00 (s, 9H), 2.44 (s, 3H), 3.02 (s, 3H), 3.64 (s, 3H), 5.47 (s, 1H), 5.81 (d, J=15.7 Hz, 1H), 6.02 (d, J=15.6 Hz, 1H), 6.10 (d, J=2.8 Hz, 1H), 7.05 (d, J=2.9 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 7.32-7.43 (m, 3H), 7.47-7.58 (m, 1H), 7.89 (d, J=8.4 Hz, 2H). LCMS (m/z) ES+=537 (M+1).

후처리

  1. concentrationThe reaction was concentrated
  2. custompurified with reverse phase HPLC (20-100% MeCN/H2O-0.1% TFA)

출처 및 근거

ORD 기록
ord-b69c9dc99fde484cad24ebfcb477fb5c
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09012642B2

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