Ammonia → 3-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

HRID 1191091ノート

反応式

HRID 1191091 の反応式
[CH:1]1([CH2:4][NH:5][C:6]2[S:7][CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=3)[N:10]=2)[CH2:3][CH2:2]1.N.[H][H]>[Ni].CO>[NH2:16][CH2:15][C:14]1[CH:13]=[N:12][C:11]([C:9]2[N:10]=[C:6]([NH:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[S:7][CH:8]=2)=[CH:18][CH:17]=1

参加物

6

反応物 3

HCID 222AmmoniaHCID 59828824HCID 59828824、化合物HCID 178418361HCID 178418361、化合物

生成物 1

HCID 598288833-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine収率 51.7%

試薬・触媒・溶媒 2

HCID 935Nickel触媒HCID 887Methanol溶媒

反応条件

温度
40 °C

実験手順

Add 6-[2-(cyclopropylmethylamino)-thiazol-4-yl]-nicotinonitrile (2.0 g, 7.8 mmol), Raney Nickel (2.0 mL), and 2M ammonia in methanol (200 mL) to a pressure vessel under a nitrogen atmosphere. Pressurize the vessel to 60 psi with hydrogen, and stir the mixture for 6 h at 40° C. Filter the mixture through Celite® and concentrate in vacuo to an oil. Dissolve the oil in EtOAc (300 mL) and saturated ammonium hydroxide (50 mL). Stir the solution for 20 h in a sealed flask at room temperature. Collect the organic layer and concentrate in vacuo. Purify the crude mixture by SCX chromatography followed by chromatography on silica gel (150 g) eluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient) to obtain the title compound (1.05 g, 51%). MS (ES+) m/z: 261 (M+H)+.

後処理

  1. filtrationFilter the mixture through Celite®
  2. concentrationconcentrate in vacuo to an oil
  3. dissolutionDissolve the oil in EtOAc (300 mL)
  4. stirringStir the solution for 20 h in a sealed flask at room temperature
  5. customCollect the organic layer
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by SCX chromatography
  8. washeluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient)

出典と根拠

ORDレコード
ord-419a6b6d4fbd471097ca9e1e8522e50f
出典データセット
uspto-grants-2014_03
特許番号
US08680091B2

反応ノート

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