Sodium Carbonate → 2-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one

HRID 1772093노트

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HRID 1772093 반응식
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH:15]3[C:20](=[O:21])[NH:19][CH2:18][CH2:17][N:16]3[CH3:22])=[CH:11][CH:10]=2)[C:5](=[O:23])[N:4]([CH3:24])[CH:3]=1.[C:25]([C:29]1[S:36][C:35]2[C:34](=[O:37])[N:33]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40](B4OC(C)(C)C(C)(C)O4)[C:39]=3[CH3:53])[CH2:32][C:31]=2[CH:30]=1)([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[Na+].[Na+]>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.O>[C:25]([C:29]1[S:36][C:35]2[C:34](=[O:37])[N:33]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([C:2]4[N:7]=[C:6]([NH:8][C:9]5[CH:14]=[CH:13][C:12]([CH:15]6[C:20](=[O:21])[NH:19][CH2:18][CH2:17][N:16]6[CH3:22])=[CH:11][CH:10]=5)[C:5](=[O:23])[N:4]([CH3:24])[CH:3]=4)[C:39]=3[CH3:53])[CH2:32][C:31]=2[CH:30]=1)([CH3:28])([CH3:26])[CH3:27]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 666097582-(4-(6-Bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)-1-methyl-3-oxopiperazineHCID 898241832-tert-Butyl-5-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4H-thieno[3,2-c]pyrrol-6(5H)-one

생성물 1

HCID 569284422-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one수율 13%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

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온도
110 °C

실험 절차

A 5-mL reaction tube equipped with a magnetic stirrer was charged with 104d (65 mg, 0.166 mmol), 102g (68 mg, 0.166 mmol), sodium carbonate (53 mg, 0.498 mmol) dioxane (1.0 mL) and water (0.2 mL). This mixture was degassed with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (19 mg, 0.017 mmol) was added, and the tube was sealed. After heating at 110° C. (bath temperature) for 16 h, the reaction mixture was cooled to room temperature and concentrated to a residue. The resulting residue was purified by flash chromatography on silica gel. This material was further purified using a preparative HPLC to afford a 13% yield (12.5 mg) of 104 as a yellow solid: mp 174-176° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.91 (d, 2H, J=8.5 Hz), 7.82 (d, 1H, J=4.5 Hz), 7.43 (t, 2H, J=8.0 Hz), 7.34 (t, 1H, J=7.8 Hz), 7.22 (s, 1H), 7.19 (d, 2H, J=8.5 Hz), 7.14 (s, 1H), 4.78 (s, 2H), 3.55 (s, 3H), 3.52 (s, 1H), 3.40 (td, 1H, J=11.0, 3.5 Hz), 3.13 (m, 1H), 2.90 (dd, 1H, J=6.0, 3.0 Hz), 2.47 (m, 1H), 2.24 (s, 3H), 2.05 (s, 3H), 1.42 (s, 9H); MS (ESI+) m/z 597.7 (M+H).

후처리

  1. customA 5-mL reaction tube
  2. customequipped with a magnetic stirrer
  3. customThis mixture was degassed with nitrogen for 30 min
  4. customthe tube was sealed
  5. temperaturethe reaction mixture was cooled to room temperature
  6. concentrationconcentrated to a residue
  7. customThe resulting residue was purified by flash chromatography on silica gel
  8. customThis material was further purified

출처 및 근거

ORD 기록
ord-8d0aad5269094655b1f3863e83810225
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249123B2

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