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Potassium Phosphate, Tribasic → US10023592, Example 292

HRID 575772
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HRID 575772 반응식
Br[C:2]1[CH:3]=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[F:16][C:17]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:18]=1[O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])=[CH:22][C:21]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:16][C:17]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:18]=1[O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])=[CH:22][C:21]=1[C:2]1[CH:3]=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
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참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 1180227245-Bromo-1-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-oneHCID 1239573972-[2-(2,4-Difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

생성물 1

HCID 118022018US10023592, Example 292수율 22.5%

시약·촉매·용매 3

HCID 962Water
촉매
HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매
HCID 312751,4-Dioxane용매

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온도
70 °C

실험 절차

A mixture of 5-bromo-1-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-one (50 mg, 0.18 mmol), 2-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (88 mg, 0.20 mmol), Pd(dppf)Cl2 (11 mg) and K3PO4 (85 mg, 0.40 mmol) in dioxane (5 mL) and water (5 drops) was purged with nitrogen, capped, and heated to 70° C. for 8 h. After the mixture was filtered, the filtrate was concentrated in vacuo and purified by prep-HPLC to afford the title compound (21 mg, 22%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.41 (m, 2H) 7.35 (m, 1H) 7.30 (m, 1H) 7.07-6.96 (m, 2H) 6.92-6.87 (m, 1H) 6.80 (m, 1H), 4.51 (m, 2H) 4.21 (s, 2H) 3.69 (s, 3H) 2.97 (m, 2H) 1.44 (m, 3H). LCMS (M+H)+=518.

후처리

  1. customwas purged with nitrogen
  2. customcapped
  3. filtrationAfter the mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by prep-HPLC

출처 및 근거

ORD 기록
ord-f72129b670854c9196741c065eec6036
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09034900B2

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