Hydrochloric Acid → 3-((2-((5-Fluoro-4-methylpyridin-2-yl)amino)-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid

HRID 629190ノート

反応式

HRID 629190 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[C:10]([O:18][CH3:19])=[C:11]([CH:15]=[CH:16][CH:17]=2)[C:12]([OH:14])=[O:13])[C:5]([C:20](=[O:23])[NH:21][CH3:22])=[CH:4][N:3]=1.[F:24][C:25]1[C:26]([CH3:32])=[CH:27][C:28]([NH2:31])=[N:29][CH:30]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl>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].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.O>[F:24][C:25]1[C:26]([CH3:32])=[CH:27][C:28]([NH:31][C:2]2[CH:7]=[C:6]([NH:8][C:9]3[C:10]([O:18][CH3:19])=[C:11]([CH:15]=[CH:16][CH:17]=3)[C:12]([OH:14])=[O:13])[C:5]([C:20](=[O:23])[NH:21][CH3:22])=[CH:4][N:3]=2)=[N:29][CH:30]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 220636705-Fluoro-4-methylpyridin-2-amineHCID 901347923-((2-Chloro-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid

生成物 1

HCID 901350173-((2-((5-Fluoro-4-methylpyridin-2-yl)amino)-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid収率 97%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 25112535Brettphos触媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

A reaction vial was charged with 3-((2-chloro-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid (600 mg, 1.787 mmol), 5-fluoro-4-methylpyridin-2-amine (316 mg, 2.502 mmol), BrettPhos (38.4 mg, 0.071 mmol) and Pd2(dba)3 (32.7 mg, 0.036 mmol) and the contents were flushed with nitrogen before adding dioxane (2 mL) and DMA (1 mL). The resulting slurry was sparged with additional nitrogen for ˜1 minutes, then LiHMDS (1 M in THF) (3.93 mL, 3.93 mmol) was added and the resulting dark amber colored solution was heated in a preheated heating block at 110° C. for 2 h, then cooled to room temperature. The reaction mixture was added to water (80 mL) and the pH was adjusted with aq. 1N HCl to ˜3 causing a solid to precipitate from solution. After stirring the slurry at room temperature for ˜4 h, the solid was collected by vacuum filtration, rinsed with water, and dried on the filter to afford 3-((2-((5-fluoro-4-methylpyridin-2-yl)amino)-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid (736 mg, 1.730 mmol, 97% yield) as a beige solid. HPLC (Method N) RT=2.45 minutes. LCMS (m+1)=426.

後処理

  1. customA reaction
  2. customthe contents were flushed with nitrogen
  3. additionbefore adding dioxane (2 mL) and DMA (1 mL)
  4. customThe resulting slurry was sparged with additional nitrogen for ˜1 minutes
  5. temperaturecooled to room temperature
  6. customto precipitate from solution
  7. filtrationthe solid was collected by vacuum filtration
  8. washrinsed with water
  9. customdried on the
  10. filtrationfilter

出典と根拠

ORDレコード
ord-da48b8c1e3f34e4ba4edf1fb986e135d
出典データセット
uspto-grants-2016_04
特許番号
US09315494B2

反応ノート

読み込み中…