Sodium Bicarbonate → [4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-methanone

HRID 349750노트

반응식

HRID 349750 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:8][CH2:7]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[F:46][C:47]1[CH:48]=[CH:49][C:50]2[N:51]([CH:53]=[C:54]([C:56](O)=[O:57])[N:55]=2)[CH:52]=1.C([O-])(O)=O.[Na+]>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:7][CH2:8][N:9]([CH:12]2[CH2:13][CH2:14][N:15]([C:56]([C:54]3[N:55]=[C:50]4[CH:49]=[CH:48][C:47]([F:46])=[CH:52][N:51]4[CH:53]=3)=[O:57])[CH2:16][CH2:17]2)[CH2:10][CH2:11]1

참가 물질

7

반응물 4

HCID 516892Sodium BicarbonateHCID 2733179PyBroPHCID 223974344-(3,4-Dichloro-phenoxy)-[1,4']bipiperidineHCID 223975086-Fluoroimidazo[1,2-a]pyridine-2-carboxylic acid

생성물 1

HCID 22397486[4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-methanone수율 34.8%

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8471Triethylamine용매

실험 절차

4-(3,4-Dichloro-phenoxy)-[1,4′]bipiperidine (0.2 g, see step b of Example 2) was dissolved in dichloromethane (5 ml), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PYBROP™; 0.425 g), 6-fluoro-imidazo[1,2-a]pyridine-2-carboxylic acid (0.126 g) and triethylamine (0.254 ml) were added. After 16 hours at room temperature dichloromethane and aqueous NaHCO3 solution were added. The product was extracted with dichloromethane, the combined organic extracts were washed with water, dried with MgSO4 and concentrated. Purification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAc aq (0.1%) to 95% MeCN//NH4OAc aq (0.1%)) (any excess NH4OAc was removed by dissolving the compound in ethyl acetate and washing with aqueous saturated NaHCO3 followed by drying of the organics with magnesium sulfate and evaporation of solvent) gave the title compound (0.104 g).

후처리

  1. extractionThe product was extracted with dichloromethane
  2. washthe combined organic extracts were washed with water
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated
  5. customPurification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAc aq (0.1%) to 95% MeCN//NH4OAc aq (0.1%)) (any excess NH4OAc
  6. customwas removed
  7. dissolutionby dissolving the compound in ethyl acetate
  8. washwashing with aqueous saturated NaHCO3
  9. customby drying of the
  10. customorganics with magnesium sulfate and evaporation of solvent)

출처 및 근거

ORD 기록
ord-27101e0571614eea80771365ec2fe8d1
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07179922B2

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