Sodium Azide → Ethyl 2-(4-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}-1H-1,2,3-triazol-1-yl)propanate

HRID 729485Notes

Reaction equation

HRID 729485 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:16]=[CH:15][C:14]([C:17]#[CH:18])=[CH:13][N:12]=2)[CH2:7][CH2:6]1.[N-:24]=[N+:25]=[N-:26].[Na+].[O:28]=[C:29]1[O:35][C@H:34]([C@H:36](CO)O)[C:32]([O-])=[C:30]1O.[Na+].BrC(C)C(OCC)=O>[Cu]I.O>[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:12]=[CH:13][C:14]([C:17]3[N:24]=[N:25][N:26]([CH:30]([CH3:32])[C:29]([O:35][CH2:34][CH3:36])=[O:28])[CH:18]=3)=[CH:15][N:16]=2)[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 33557Sodium AzideHCID 79040Ethyl 2-bromopropionateHCID 23667548Sodium AscorbateHCID 866218082-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-5-ethynylpyrimidine

Product 1

HCID 68828372Ethyl 2-(4-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidin-5-yl}-1H-1,2,3-triazol-1-yl)propanate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent2×

Procedure

The title compound was prepared in a similar manner as that described for Example 10, step 4. Into a 25-mL round-bottom flask equipped with a magnetic stirbar was added 2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-5-ethynylpyrimidine (130 mg, 0.35 mmol), sodium azide (23 mg, 0.35 mmol) tert-butanol (1.5 mL), water (0.7 mL), copper(I) iodide (4 mg, 0.02 mmol) and sodium ascorbate (9 mg, 0.04 mmol). The resulting suspension was treated with dropwise addition of ethyl 2-bromopropionate (45 μL, 0.35 mmol) and stirred at room temperature for 16 h overnight. The mixture was poured into a 125 mL separatory funnel containing water (75 mL) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 5% EtOAc in hexanes to 55% EtOAc in hexanes as a gradient gave the desired product as a beige solid.

Workup

  1. customThe title compound was prepared in a similar manner as
  2. customInto a 25-mL round-bottom flask equipped with a magnetic stirbar
  3. additionThe mixture was poured into a 125 mL separatory funnel
  4. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customPurification by column chromatography through silica gel
  10. washeluting with 5% EtOAc in hexanes to 55% EtOAc in hexanes as a gradient

Sources & evidence

ORD record
ord-100efa4e37c84f99bc37875ffa497ac4
Source dataset
uspto-grants-2009_09
Patent number
US07582633B2

Reaction notes

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