Cesium carbonate → (4-(1-Methyl-5-(7-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

HRID 1022107ノート

反応式

HRID 1022107 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]2[N:8]=[C:9]([NH2:11])[N:10]=[C:4]2[CH2:3]1.[C:12]([O:15][CH2:16][C:17]1[C:18]([N:32]2[CH2:44][CH2:43][N:35]3[C:36]4[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[CH:42]=[C:34]3[C:33]2=[O:45])=[N:19][CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[C:27](Br)[C:26](=[O:30])[N:25]([CH3:31])[CH:24]=1)(=[O:14])[CH3:13].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>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].CN(C=O)C>[C:12]([O:15][CH2:16][C:17]1[C:18]([N:32]2[CH2:44][CH2:43][N:35]3[C:36]4[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[CH:42]=[C:34]3[C:33]2=[O:45])=[N:19][CH:20]=[CH:21][C:22]=1[C:23]1[CH:28]=[C:27]([NH:11][C:9]2[N:10]=[C:4]3[CH2:3][N:2]([CH3:1])[CH2:7][CH2:6][N:5]3[N:8]=2)[C:26](=[O:30])[N:25]([CH3:31])[CH:24]=1)(=[O:14])[CH3:13]

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 838726777-Methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-amineHCID 86684400(4-(5-Bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate

生成物 1

HCID 86684512(4-(1-Methyl-5-(7-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl Acetate収率 41%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 270f (100 mg, 0.65 mmol, 1.7 eq.), (4-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate 217a (200 mg, 0.38 mmol, 1.0 eq.), DMF (10 mL), and cesium carbonate (499 mg, 1.52 mmol, 4.0 eq.). After bubbling nitrogen through the resulting solution for 10 minutes, Xantphos (44 mg, 0.076 mmol, 0.20 eq.) and tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol, 0.10 eq.) were added. The reaction mixture was subjected to three cycles of vacuum/argon flush and heated at 100° C. for 16 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (10 mL). The aqueous layer was separated and extracted with ethyl acetate (3×20 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified on silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 270g (90 mg, 41%). MS-ESI: [M+H]+ 598.3.

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting solution for 10 minutes
  3. customflush
  4. temperatureAfter this time the reaction was cooled to room temperature
  5. filtrationfiltered
  6. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (10 mL)
  7. customThe aqueous layer was separated
  8. extractionextracted with ethyl acetate (3×20 mL)
  9. concentrationThe combined organic layer was concentrated under reduced pressure
  10. customThe residue was purified on silica-gel column chromatography
  11. washeluting with 50:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-012eecc6b8b0440d83ad16647ee9f464
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

読み込み中…