Cesium carbonate → 2-[5-Cyclopropyl-2-(2,5-dimethyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methyl-benzamide

HRID 1472556ノート

反応式

HRID 1472556 の反応式
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([CH:19]2[CH2:21][CH2:20]2)=[CH:4][N:3]=1.[CH3:22][N:23]1[C:27]([NH2:28])=[CH:26][C:25]([CH3:29])=[N:24]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>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].O1CCOCC1>[CH:19]1([C:5]2[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11]([NH:13][CH3:14])=[O:12])=[CH:7][C:2]([NH:28][C:27]3[N:23]([CH3:22])[N:24]=[C:25]([CH3:29])[CH:26]=3)=[N:3][CH:4]=2)[CH2:21][CH2:20]1

参加物

7

反応物 4

HCID 10796Cesium carbonate2 回HCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 575169032-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide

生成物 1

HCID 462152682-[5-Cyclopropyl-2-(2,5-dimethyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methyl-benzamide収率 17%

試薬・触媒・溶媒 2

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

実験手順

To a 10 mL microwave tube were added 2-(2-chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide (0.075 g, 0.25 mmol, 1 eq), 2,5-dimethyl-2H-pyrazol-3-ylamine (0.030 g, 0.27 mmol, 1.1 eq), Cs2CO3 (0.23 g, 0.70 mmol, 2.8 eq) and 1,4-dioxane (4 mL) and resulting mixture was degassed with N2 for 30 minutes. To this was added Pd2(dba)3 (0.008 g, 0.007 mmol, 0.03 eq) and xanthphos (0.009 g, 0.014 mmol, 0.06 eq) and reaction mixture was degassed again with N2 for another 15 minutes. The resulting reaction mixture was irradiated in a CEM microwave at 110° C. and 150 W for 40 min. The progress of reaction was monitored by LCMS. After completion of reaction, Cs2CO3 was removed by filtration and the filtrate was concentrated under reduced pressure to give a crude product. The crude compound was purified by column chromatography over neutral alumina using 0.1% MeOH-DCM as the eluant. Solid compound so obtained was washed with diethyl ether and pentane to give the title compound as a yellowish solid (16 mg, 17%). 1H-NMR (400 MHz, DMSO-d6): δ 0.52-0.59 (m, 2H), 0.89-0.99 (m, 2H), 1.52-1.62 (m, 1H), 2.05 (s, 3H), 2.76-2.77 (d, 3H, J=4.44 Hz), 3.52 (s, 3H), 5.96 (s, 1H), 6.69 (s, 1H), 7.01-7.05 (t, 1H, J=7.48 Hz), 7.42-7.45 (m, 1H), 7.51-7.60 (m, 1H) 7.64-7.66 (d, 1H, J=7.32 Hz), 7.72 (s, 1H), 8.37 (s, 1H), 8.55-8.65 (brs, 1H), 9.96 (s, 1H). LC-MS [M+H]+=377.2.

後処理

  1. customresulting mixture
  2. customwas degassed with N2 for 30 minutes
  3. additionTo this was added
  4. customwas degassed again with N2 for another 15 minutes
  5. customThe resulting reaction mixture
  6. customwas irradiated in a CEM microwave at 110° C.
  7. customThe progress of reaction
  8. customwas removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customto give a crude product
  11. customThe crude compound was purified by column chromatography over neutral alumina using 0.1% MeOH-DCM as the eluant
  12. customSolid compound so obtained
  13. washwas washed with diethyl ether and pentane

出典と根拠

ORDレコード
ord-31e817e1bbdb471088589164d4d94cfa
出典データセット
uspto-grants-2015_04
特許番号
US09012479B2

反応ノート

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