Pyridine → (S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1511052ノート

反応式

HRID 1511052 の反応式
[S:1]([N:5]=[C:6]=O)N=C=O.[Na].[N:9]1C=CC=C[CH:10]=1.CS(ON=C(Cl)[C@H:22]1[CH2:26][O:25][C:24]2([CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[O:23]1)(=O)=O.[Br:33][C:34]1[CH:35]=[C:36]([O:41][C:42]2[C:43]([CH3:48])=[N:44][CH:45]=[CH:46][CH:47]=2)[C:37]([NH2:40])=[N:38][CH:39]=1>C(#N)C>[Br:33][C:34]1[CH:35]=[C:36]([O:41][C:42]2[C:43]([CH3:48])=[N:44][CH:45]=[CH:46][CH:47]=2)[C:37]([NH:40][C:10]2[S:1][N:5]=[C:6]([C@H:26]3[CH2:22][O:23][C:24]4([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]4)[O:25]3)[N:9]=2)=[N:38][CH:39]=1

参加物

6

反応物 4

HCID 1049PyridineHCID 674861815-Bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chlorideHCID 86644150Sodium thioisocyanate

生成物 1

HCID 67486320(S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine収率 73%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

In 100 mL of acetonitrile was added sodium thioisocyanate (1.5 g, 20 mmol), pyridine (3.5 g, 44 mmol), followed by (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (5.2 g, 18 mmol) and the reaction was heated to 60° C. for 30 minutes. 5-Bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-amine (4.1 g, 15 mmol) was added and the reaction was heated overnight at 60° C. The reaction was concentrated to about one quarter volume, the residue was partitioned between EtOAc and the water layer was made basic with 1N NaOH. The organic layer was separated and the aqueous layer extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The material was purified on silica gel (25% EtOAc in CH2Cl2) to afford (S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (5.4 g, 73%).

後処理

  1. temperaturethe reaction was heated overnight at 60° C
  2. concentrationThe reaction was concentrated to about one quarter volume
  3. customthe residue was partitioned between EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe material was purified on silica gel (25% EtOAc in CH2Cl2)

出典と根拠

ORDレコード
ord-4a32ae14c2894cb6924c54b71fe1c497
出典データセット
uspto-grants-2012_07
特許番号
US08212045B2

反応ノート

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