Dimethylformamide → 2-[[2-(dimethylcarbamoylamino)pyridin-4-yl]methylamino]-N-(2-methylindazol-6-yl)benzamide

HRID 600675ノート

反応式

HRID 600675 の反応式
Br[C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C:10]2[CH:28]=[CH:27][CH:26]=[CH:25][C:11]=2[C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]3[C:22]([CH:23]=2)=[N:21][N:20]([CH3:24])[CH:19]=3)=[O:13])[CH:5]=[CH:4][N:3]=1.[CH3:29][N:30]([CH3:34])[C:31]([NH2:33])=[O:32].CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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].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>[CH3:29][N:30]([CH3:34])[C:31](=[O:32])[NH:33][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C:10]2[CH:28]=[CH:27][CH:26]=[CH:25][C:11]=2[C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]3[C:22]([CH:23]=2)=[N:21][N:20]([CH3:24])[CH:19]=3)=[O:13])[CH:5]=[CH:4][N:3]=1

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 231189722-[(2-bromo-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-benzamide

生成物 1

HCID 115540512-[[2-(dimethylcarbamoylamino)pyridin-4-yl]methylamino]-N-(2-methylindazol-6-yl)benzamide収率 71.3%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

2-[(2-Bromo-pyridin-4-ylmethyl)-amino]-N-(2-methyl-2H-indazol-6-yl)-benzamide (110 mg, 0.25 mmol, prepared as detailed infra in Example 4A) and 1,1-dimethylurea (114 mg, 1.3 mmol) were suspended in dioxane (3 mL) under a nitrogen atmosphere and treated consecutively with DMF (1 mL), cesium carbonate (98 mg, 0.3 mmol), Pd2 dba3 (5 mg, 0.005 mmol) and Xantphos (9 mg, 0.015 mmol). The reaction mixture was flushed with nitrogen and heated for 5 hours at 110° C. (bath temperature). On cooling the reaction was concentrated in vacuo. The residue was partitioned between CH2Cl2 and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on Isolute® flash silica get (Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 95:5) to give 2-{[2-(3,3-dimethyl-ureido)-pyridin-4-ylmethyl]-amino}-N-(2-methyl-2H-indazol-6-yl)-benzamide (79 mg, 71%) as a solid; 1 H-NMR (300 MHz, d6-DMSO) 10.15 (1H, s), 8.80 (1H, s), 8.25 (1H, s), 8.13 (1H, d), 8.10 (1H, s), 7.95 (1H, t), 7.82 (1H, s), 7.72 (1H, d), 7.63 (1H, d), 7.22-7.32 (2H, m), 6.95 (1H, d), 6.68 (1H, t), 6.54 (1H, d), 4.45 (2H, d), 4.13 (3H, s), 2.91 (6H, s); m/z (ES+) 444 [M+H]+, 223; Mp. 184° C.

後処理

  1. customThe reaction mixture was flushed with nitrogen
  2. temperatureOn cooling the reaction
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between CH2Cl2 and water
  5. washThe organic phase was washed with brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on Isolute® flash silica
  10. customget
  11. wash(Separtis) (Gradient elution: 100% CH2Cl2 to CH2Cl2/EtOH 95:5)

出典と根拠

ORDレコード
ord-9aa0692e81b44ed48cd76252abdcead7
出典データセット
uspto-grants-2011_03
特許番号
US07902229B2

反応ノート

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