2-Aminothiazole → 4-methyl-N-(thiazol-2-yl)pyridine-2-amine

HRID 1800806ノート

反応式

HRID 1800806 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4](Cl)[CH:3]=1.[NH2:9][C:10]1[S:11][CH:12]=[CH:13][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.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>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:9][C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[CH:3]=1

参加物

7

反応物 3

HCID 21552-AminothiazoleHCID 10340Sodium CarbonateHCID 772482-Chloro-4-methylpyridine

生成物 1

HCID 146685484-methyl-N-(thiazol-2-yl)pyridine-2-amine収率 67.2%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒2 回HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
130 °C

実験手順

A suspension of 4-methyl-2-chloropyridine (5.10 g, 40.0 mmol), 2-aminothiazole (4.81 g, 48 mmol, 1.2 eq), sodium carbonate (5.94 g, 56.0 mmol, 1.4 eq) and XANTPHOS (0.278 g, 0.48 mmol, 0.012 eq) in THF (100 mL, bubbled with argon for 5 minutes) was bubbled again with argon for 5 additional minutes. Tris(dibenzylideneacetone)dipalladium (0) (0.146 g, 0.16 mmol, 0.004 eq) was then added to the suspension which was heated at 130° C. for 2 days. Additional quantities of XANTPHOS (0.278 g) and tris(dibenzylideneacetone)dipalladium (0) (0.146 g) were added again and the reaction was heated at 130° C. for 4 more days. The mixture was cooled to RT and filtered. The resulting solid was suspended in water and stirred for 1 hour. After filtration, the resulting solid was dried under vacuum overnight. The THF filtrate was evaporated and the residue was combined to the previously isolated solid. This was precipitated from MeOH to give the title compound (5.14 g, 67%) as a solid. The mother liquor was evaporated and the residue purified by silica gel chromatography (50% ethyl acetate/dichloromethane to 100% ethyl acetate) and afforded the title material (0.825 g, 11%) as a solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 2.36 (3H, s), 6.71 (1H, s), 6.75 (1H, br d, J=5.1 Hz), 6.84 (1H, d, J=3.5 Hz), 7.43 (1H, d, J=3.5 Hz), 8.24 (1H, d, J=5.3 Hz). LC/MS (M+H)+: 192. HPLC ret. time (Condition A): 1.285 min.

後処理

  1. customwas bubbled again with argon for 5 additional minutes
  2. temperaturethe reaction was heated at 130° C. for 4 more days
  3. temperatureThe mixture was cooled to RT
  4. filtrationfiltered
  5. filtrationAfter filtration
  6. customthe resulting solid was dried under vacuum overnight
  7. customThe THF filtrate was evaporated
  8. customThis was precipitated from MeOH

出典と根拠

ORDレコード
ord-4b66e1b5f50c4e628838b6d24b36f3ef
出典データセット
uspto-grants-2013_01
特許番号
US08343999B2

反応ノート

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