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Cesium carbonate → 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

HRID 1473214
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HRID 1473214 반응식
[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[NH:19][CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:35][S:36]([C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1)(=[O:38])=[O:37]>C(#N)C.O.Cl>[C:1]([O:5][CH:6]([C:11]1[N:16]([CH3:17])[C:15](=[O:18])[C:14]2[N:19]([CH2:43][C:42]3[CH:41]=[CH:40][C:39]([S:36]([CH3:35])(=[O:38])=[O:37])=[CH:46][CH:45]=3)[CH:20]=[CH:21][C:13]=2[C:12]=1[C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 27335814-(Methylsulfonyl)benzyl BromideHCID 89462627methyl 2-(tert-butoxy)-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

생성물 1

HCID 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)acetate수율 90.9%

시약·촉매·용매 3

HCID 313
Hydrochloric Acid
용매
HCID 962Water용매
HCID 6342Acetonitrile용매

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온도
70 °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. temperatureThe reaction was cooled to rt
  2. extractionextracted with EtOAc
  3. washwashed with Brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification with column chromatography (0-100% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-30a74b52b8384f9eb27882869b5e0a31
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09012642B2

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