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 534071Notes

Reaction equation

HRID 534071 reaction equation
[S:1]([N:5]=[C:6]=O)N=C=O.[Na].[N:9]1C=CC=C[CH:10]=1.[O:15]1[C:19]2([CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[O:18][CH2:17][CH:16]1C(Cl)=N.[Br:28][C:29]1[CH:30]=[C:31]([O:36][C:37]2[C:38]([CH3:43])=[N:39][CH:40]=[CH:41][CH:42]=2)[C:32]([NH2:35])=[N:33][CH:34]=1>C(#N)C>[Br:28][C:29]1[CH:30]=[C:31]([O:36][C:37]2[C:38]([CH3:43])=[N:39][CH:40]=[CH:41][CH:42]=2)[C:32]([NH:35][C:10]2[S:1][N:5]=[C:6]([C@H:17]3[CH2:16][O:15][C:19]4([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]4)[O:18]3)[N:9]=2)=[N:33][CH:34]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 674861815-Bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-amineHCID 86644150Sodium thioisocyanateHCID 866731981,4-Dioxaspiro[4.5]decane-2-carbimidoyl chloride

Product 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-amineYield 73%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

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 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 quarter volume and the residue was partitioned between EtOAc and water made basic with 1N NaOH. The combined organic layers were 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]decane-2-yl)-1,2,4-thiadiazol-5-amine (5.4 g, 73%).

Workup

  1. temperaturethe reaction was heated overnight at 60° C
  2. concentrationThe reaction was concentrated to one quarter volume
  3. customthe residue was partitioned between EtOAc and water
  4. customThe combined organic layers were 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)

Sources & evidence

ORD record
ord-6b7d57807b844cd28cd6ef7d44400dfe
Source dataset
uspto-grants-2014_10
Patent number
US08853409B2

Reaction notes

Loading…