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 2401481노트

반응식

HRID 2401481 반응식
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

참가 물질

7

반응물 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

생성물 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)-one수율 15%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-49ef2f8eee6e4481ab56b14c356ef0f6
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796296B2

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