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Cesium carbonate → 3-{6-[2-(3-Fluoro-4-methoxy-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzonitrile

HRID 2110621
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HRID 2110621 반응식
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([F:21])[CH:14]=2)[CH:3]=1.[C:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)#[N:23].C([O-])([O-])=O.[Cs+].[Cs+]>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.COCCOC>[F:21][C:15]1[CH:14]=[C:13]([CH2:12][CH2:11][NH:10][C:4]2[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:28]3[CH:29]=[C:24]([CH:25]=[CH:26][CH:27]=3)[C:22]#[N:23])[CH:3]=2)[CH:18]=[CH:17][C:16]=1[O:19][CH3:20]
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참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 27343253-Cyanophenylboronic acid2회HCID 57636065(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(3-fluoro-4-methoxyphenyl)-ethyl]amine2회

생성물 1

HCID 115670373-{6-[2-(3-Fluoro-4-methoxy-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzonitrile수율 56.6%

시약·촉매·용매 3

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 962Water용매2회
HCID 80711,2-Dimethoxyethane용매

실험 절차

(6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(3-fluoro-4-methoxyphenyl)-ethyl]amine [1.6 g, Intermediate (5)], 3-cyano-phenylboronic acid [1.5 g, Intermediate (6)], Cs2CO3 (8.3 g) and tetrakis(triphenylphosphine)palladium (45 mg) in a solution of water (8 mL) and ethylene glycol dimethyl ether (32 mL) is heated at 90° C. for 16 hours. The solution is poured into water and extracted twice with EtOAc (200 mL). The combined extracts are dried over sodium sulfate, filtered, and evaporated. The residue is subjected to chromatography on silica gel eluting with EtOAc to give 3-{6-[2-(3-fluoro-4-methoxy-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzonitrile [1.1 g, Example 1]. MS: 379 (M+H); 1H NMR (CDCl3): δ 8.3 (1H, s); 8.2 (1H, d (J=5.1 Hz)); 7.9 (1H, d (J=5.1 Hz)); 7.6 (1H, t); 7-7.2 (4H, m); 6.4 (1H, s); 5 (1H, m); 3.95 (3H, s); 3.8 (3H, s); 3.7 (2H, t); 3 (2H, t).

후처리

  1. extractionextracted twice with EtOAc (200 mL)
  2. dry with materialThe combined extracts are dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated

출처 및 근거

ORD 기록
ord-a2de5ab150d44faca67136840a3e7c62
출처 데이터셋
uspto-grants-2009_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07517889B2

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