Water → 2-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)pyridin-4-amine

HRID 407219

反応式

HRID 407219 の反応式
Br[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([O:9][CH:10]([F:12])[F:11])=[C:4]([NH2:13])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B2OCCCO2)=[C:17]([F:27])[C:16]=1[O:28][CH3:29].[F-].[Cs+].O>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:6]1[C:5]([O:9][CH:10]([F:12])[F:11])=[C:4]([NH2:13])[CH:3]=[C:2]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[C:16]([O:28][CH3:29])[C:17]=2[F:27])[N:7]=1

参加物

7

反応物 4

HCID 962WaterHCID 25953Cesium fluorideHCID 577824192-(4-Chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinaneHCID 866754046-Bromo-2-chloro-3-(difluoromethoxy)pyridin-4-amine

生成物 1

HCID 866754052-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)pyridin-4-amine収率 84.2%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

6-Bromo-2-chloro-3-(difluoromethoxy)pyridin-4-amine (368 mg, 1.346 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane (395 mg, 1.615 mmol), PdCl2(PPh3)2 (47.2 mg, 0.067 mmol), and CsF (409 mg, 2.69 mmol) were combined in DME (2 mL) and H2O (2 mL) and heated in a Biotage microwave reactor at 110° C. for 15 min. The cooled reaction mixture was partitioned between EtOAc and H2O. The organic phase was dried, concentrated onto silica gel, and purified by flash chromatography (SiO2, EtOAc/hexane gradient). This process yielded the title compound as a white solid (0.4 g, 84%): mp 152-154° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.63-7.50 (m, 1H), 7.42 (dd, J=8.7, 1.6, 1H), 7.16 (d, J=1.8, 1H), 7.02 (t, J=73.4, 1H), 6.70 (s, 2H), 3.93 (d, J=0.8, 3H); ESIMS m/z 354 ([M+H]+), 352 ([M−H]−).

後処理

  1. customThe cooled reaction mixture
  2. customwas partitioned between EtOAc and H2O
  3. customThe organic phase was dried
  4. concentrationconcentrated onto silica gel
  5. custompurified by flash chromatography (SiO2, EtOAc/hexane gradient)

出典と根拠

ORDレコード
ord-67c9ae402d9048d795b7fd9de05e6325
出典データセット
uspto-grants-2014_06
特許番号
US08754229B2

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