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 1511034노트

반응식

HRID 1511034 반응식
[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

참가 물질

6

반응물 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

생성물 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-amine수율 73%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
60 °C

실험 절차

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 one fourth the volume and the residue partitioned between EtOAc and water 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%).

후처리

  1. temperaturethe reaction was heated overnight at 60° C
  2. concentrationThe reaction was concentrated to one fourth the volume
  3. customthe residue partitioned between EtOAc and water
  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)

출처 및 근거

ORD 기록
ord-bdeef288939645f08ff44d08afb875fa
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08212045B2

반응 노트

불러오는 중…