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 1523587Notes

Reaction equation

HRID 1523587 reaction equation
[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

Participants

6

Reactant 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

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 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%).

Workup

  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)

Sources & evidence

ORD record
ord-495afdb5d0294a1f86a00d389a268eb6
Source dataset
uspto-grants-2015_07
Patent number
US09079890B2

Reaction notes

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