Cesium carbonate → 7-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 2401481ノート

反応式

HRID 2401481 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([Cl:10])=[CH:4][N:3]=1.[NH2:11][C:12]1[C:13]([O:26][CH3:27])=[CH:14][C:15]2[N:20]([CH3:21])[C:19](=[O:22])[C:18]([CH3:24])([CH3:23])[O:17][C:16]=2[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[Cl:10][C:5]1[C:6]([NH:8][CH3:9])=[N:7][C:2]([NH:11][C:12]2[C:13]([O:26][CH3:27])=[CH:14][C:15]3[N:20]([CH3:21])[C:19](=[O:22])[C:18]([CH3:24])([CH3:23])[O:17][C:16]=3[CH:25]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 189812472,5-dichloro-N-methylpyrimidin-4-amineHCID 866879347-Amino-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

生成物 1

HCID 715664607-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one収率 15%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2,5-dichloro-N-methylpyrimidin-4-amine (1 mmol), 7-amino-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (222 mg, 0.94 mmol), cesium carbonate (0.65 g, 2 mmol), XantPhos (17 mg, 0.03 mmol) and Pd2(dba)3 (5 mg, 0.02 mmol) in dioxane (3 mL) was sonnicated in an ultrasonic bath for 1 min. The mixture was then degassed under a stream of nitrogen for 5 min. The tube was sealed and the reaction was heated at 100° C. for 18 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL). The organic layer was washed with water and the combined aqueous extracts were further washed with ethyl acetate. The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) gave 7-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (30 mg, 15%). LCMS (10 cm_ESCI_Formic_MeCN): [MH+]=378 at 2.77 min. 1H NMR δ (ppm)(400 MHz, d6-DMSO): 8.05 (1H, s), 7.98 (1H, s), 7.54 (1H, s), 7.28 (1H, d, J=5.2), 6.85 (1H, s), 3.93 (3H, s), 3.66 (3H, s), 2.91 (3H, d, J=4.6), 1.41 (6H, s).

後処理

  1. customThe mixture was then degassed under a stream of nitrogen for 5 min
  2. customThe tube was sealed
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate (15 mL)
  5. washThe organic layer was washed with water
  6. washthe combined aqueous extracts were further washed with ethyl acetate
  7. customThe combined organics were passed through a phase separation cartridge
  8. customthe solvent removed under reduced pressure
  9. customPurification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane)

出典と根拠

ORDレコード
ord-49ef2f8eee6e4481ab56b14c356ef0f6
出典データセット
uspto-grants-2014_08
特許番号
US08796296B2

反応ノート

読み込み中…