Cesium carbonate → 4-[6-(5-Chloro-2-fluoro-phenyl)-3-methyl-isoxazolo[5,4-d]pyrimidin-4-ylamino]-nicotinic acid methyl ester

HRID 1354313

반응식

HRID 1354313 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]2[O:16][N:17]=[C:18]([CH3:19])[C:3]=12.[CH3:20][O:21][C:22](=[O:30])[C:23]1[C:28]([NH2:29])=[CH:27][CH:26]=[N:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][O:21][C:22](=[O:30])[C:23]1[C:28]([NH:29][C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=3[F:15])[N:5]=[C:4]3[O:16][N:17]=[C:18]([CH3:19])[C:3]=23)=[CH:27][CH:26]=[N:25][CH:24]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 592353Methyl 4-aminopyridine-3-carboxylateHCID 211043424-Chloro-6-(5-chloro-2-fluoro-phenyl)-3-methyl-isoxazolo[5,4-d]pyrimidine

생성물 1

HCID 588659594-[6-(5-Chloro-2-fluoro-phenyl)-3-methyl-isoxazolo[5,4-d]pyrimidin-4-ylamino]-nicotinic acid methyl ester수율 126.9%

시약·촉매·용매 3

HCID 634876Binap, (A+-)-촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

4-Chloro-6-(5-chloro-2-fluoro-phenyl)-3-methyl-isoxazolo[5,4-d]pyrimidine (Prepared by method used for 0043) (298 mg, 1 mmole) was dissolved in dioxane (4 ml), added BINAP (4.67 mg, 0.0075), 4-Amino-nicotinic acid methyl ester (182 mg, 1.2 mmole), cesium carbonate (456 mg, 1.4 mmole), and Pd2(dba)3 (2.29 mg, 0.0025 mmole) to the mixture and heated to 90° C. overnight. Removed dioxane under vacuum and triturated residue with ethyl acetate (5 ml) and isolated product by filtration. Obtained 525 mg solid which also contained cesium carbonate as byproduct.

후처리

  1. customRemoved dioxane under vacuum and triturated residue with ethyl acetate (5 ml)
  2. customisolated product
  3. filtrationby filtration

출처 및 근거

ORD 기록
ord-c36d067062e14c268c718d1fd1340036
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07223766B2

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