Potassium Carbonate → 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473646노트

반응식

HRID 1473646 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20]([N:23]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=4)[C:24]4[CH:29]=[CH:28][N:27]=[CH:26][N:25]=4)(=[O:22])=[O:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]=2)=[CH:4][CH:3]=1.[F:39][C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[CH:44][C:45]=1[F:46].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:39][C:40]1[CH:41]=[C:42]([C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]3[C:19]4[C:14](=[CH:15][C:16]([S:20]([N:23]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=5)[C:24]5[CH:29]=[CH:28][N:27]=[CH:26][N:25]=5)(=[O:22])=[O:21])=[CH:17][CH:18]=4)[CH:13]=[CH:12][N:11]=3)=[CH:4][CH:3]=2)[CH:43]=[CH:44][C:45]=1[F:46]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 866876341-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

생성물 1

HCID 866877181-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

시약·촉매·용매 1

HCID 178418397HCID 178418397, 화합물촉매

실험 절차

A microwave vial was charged with 1-(6-chloro-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (Intermediate EEEEE; 0.052 g, 0.095 mmol), (3,4-difluorophenyl)boronic acid (0.022 g, 0.142 mmol), potassium carbonate (0.039 g, 0.285 mmol), and Pd(Ph3P)4 (10.96 mg, 9.49 μmol). The vial was flushed with Ar (g), then Dioxane (0.712 mL) and Water (0.237 mL) were added. The reaction was microwaved at 90° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-50% EtOAc:Heptane) to afford 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred overnight at room temperature. Triflic acid (0.050 mL, 0.563 mmol) was added and the reaction was stirred for one hour. The reaction was concentrated and the material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 1-(6-(3,4-difluorophenyl)-2-methoxypyridin-3-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.78-8.71 (m, 2H), 8.59 (s, 1H), 8.33-8.28 (m, 1H), 8.28-8.23 (m, 2H), 8.13 (br. s., 1H), 8.02 (d, J=1.9 Hz, 1H), 7.98 (d, J=7.6 Hz, 2H), 7.88 (d, J=7.9 Hz, 2H), 7.62 (td, J=8.6, 10.4 Hz, 1H), 7.03 (d, J=6.0 Hz, 1H), 3.91 (s, 3H). m/z (ESI) 506.1 (M+H)+.

후처리

  1. customThe vial was flushed with Ar (g)
  2. additionDioxane (0.712 mL) and Water (0.237 mL) were added
  3. customThe reaction was microwaved at 90° C. for one hour
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-50% EtOAc:Heptane)

출처 및 근거

ORD 기록
ord-4042048b2a8b44f880bf1c0766662e41
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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