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4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-fluoropyridin-3-yl)-3-chloro-5-cyanopicolinamide

HRID 930303
ノート
印刷プレビュー

反応式

HRID 930303 の反応式
[NH2:1][C:2]1[O:3][C@H:4]([C:26]([F:29])([F:28])[F:27])[CH2:5][C@:6]([C:9]2[CH:10]=[C:11]([NH:16]C(=O)C3C=CC(Cl)=CN=3)[CH:12]=[N:13][C:14]=2[F:15])([CH3:8])[N:7]=1.[Cl:30][C:31]1[C:32]([C:39]([OH:41])=O)=[N:33][CH:34]=[C:35]([C:37]#[N:38])[CH:36]=1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1.CO>[NH2:1][C:2]1[O:3][C@H:4]([C:26]([F:27])([F:29])[F:28])[CH2:5][C@:6]([C:9]2[CH:10]=[C:11]([NH:16][C:39](=[O:41])[C:32]3[C:31]([Cl:30])=[CH:36][C:35]([C:37]#[N:38])=[CH:34][N:33]=3)[CH:12]=[N:13][C:14]=2[F:15])([CH3:8])[N:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride2 回HCID 508531763-Chloro-5-cyanopyridine-2-carboxylic acid2 回HCID 78321763N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-fluoropyridin-3-yl)-5-chloropicolinamide

生成物 1

HCID 86732133N-(5-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-6-fluoropyridin-3-yl)-3-chloro-5-cyanopicolinamide
収率 22.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A flask was charged with (4S,6S)-4-(5-amino-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (6a, 0.075 g, 0.257 mmol) and 3-chloro-5-cyanopicolinic acid (Bionet Research, 0.047 g, 0.257 mmol). The solids were dissolved in a mixture of THF (2 mL)/MeOH (1 mL) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (Aldrich, 0.129 g, 0.436 mmol) was added. The reaction was stirred at RT for 25 min. Additional 0.5 equiv. chloro-5-cyanopicolinic acid and 1 equiv. 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride were added. After 1 hour, the reaction was quenched with aqueous saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was washed with brine and dried over sodium sulfate. The filtrate was concentrated and purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 80% over 20 min. The product containing fractions were combined and neutralized with aqueous sodium bicarbonate solution. The free-based product was extracted with DCM. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure to afford the title compound (0.026 g, 0.057 mmol, 22.18% yield) as white solid. MS m/z=457 [M+H]+. Calculated for C18H13ClF4N6O2: 456.8

後処理

  1. additionwas added
  2. waitAfter 1 hour
  3. customthe reaction was quenched with aqueous saturated sodium bicarbonate solution
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe filtrate was concentrated
  8. custompurified by reversed-phase preparative HPLC
  9. customover 20 min
  10. additionThe product containing fractions
  11. extractionThe free-based product was extracted with DCM
  12. dry with materialThe organic phase was dried over MgSO4
  13. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-fefad994b38c490497019103e2f5fdff
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09296734B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート