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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Water → N-(4-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

HRID 2282303
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HRID 2282303 반응식
Br[C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=2)[S:5][C:6]=1[C:7]1[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=[CH:10][N:11]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[C:33]([C:45]([F:48])([F:47])[F:46])=[N:32]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[N:3]=[C:4]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=3)[S:5][C:6]=2[C:7]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=[CH:10][N:11]=2)[C:33]([C:45]([F:48])([F:47])[F:46])=[N:32]1
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참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 467380121-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)-1H-pyrazoleHCID 58095120N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

생성물 1

HCID 66855234
N-(4-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide (70.0 mg, 0.120 mmol), 1-methyl-3-trifluoromethyl-1H-pyrazole-4-boronic acid pinacol ester (0.0708 g, 0.241 mmol), [1,1′-bis(diphenylphosphino)ferrocene] palladium(II) dichloride (4.95 mg, 0.00602 mmol) and sodium carbonate (38.3 mg, 0.361 mmol) in DME (1.2 mL) was degassed with argon. Water (0.5 mL) was added to the above mixture. The mixture was irradiated in microwave at 125° C. for 30 min. At that time, LCMS showed the desired product. Reaction mixture was filtered, the filtrate was evaporated to dryness, dissolved in DCM (1.20 mL) and treated with TFA (1.20 mL). This mixture was stirred at room temperature overnight. At that time, LCMS indicated formation of the desired product. The mixture was evaporated to dryness in vacuo, the residue was taken up by DMSO and purified using preparative HPLC to give product as yellow powder (16.3 mg, 31.2%). LCMS: (AA) ES+, 434, 435. 1H NMR (400 MHz, d4-methanol) δ: 8.67 (br, 1H) 8.38 (dd, 1H) 7.87 (s, 1H) 7.63 (dd, 1H) 7.14 (d, 2H) 3.98 (s, 3H) 2.19 (s 3H).

후처리

  1. customThe mixture was irradiated in microwave at 125° C. for 30 min

출처 및 근거

ORD 기록
ord-324e447d388a4fbcbbf81424745a6c2b
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09139589B2

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