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 729485ノート

反応式

HRID 729485 の反応式
[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

参加物

7

反応物 4

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

生成物 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

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-100efa4e37c84f99bc37875ffa497ac4
出典データセット
uspto-grants-2009_09
特許番号
US07582633B2

反応ノート

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