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 729485노트

반응식

HRID 729485 반응식
[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

참가 물질

7

반응물 4

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

생성물 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

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-100efa4e37c84f99bc37875ffa497ac4
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582633B2

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