Lithium Hydroxide → 5-([1,2,4]Triazolo[4,3-a]pyridin-6-yl)-6-(4-fluorophenyl)imidazo[2,1-b]oxazole

HRID 1711794노트

반응식

HRID 1711794 반응식
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[N:19][C:20]([NH:23][NH2:24])=[CH:21][CH:22]=1)[CH:14]=[CH:13][O:12]2.F[C:26]1C=CC(C2N=C3N(C=2)C=CO3)=CC=1.C1C(=O)N(I)C(=O)C1.FC1C=CC(B(O)O)=CN=1.NN.O=CC(OCC)=O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.[Li+].[OH-]>CO.O>[N:23]1[N:24]=[CH:26][N:19]2[CH:18]=[C:17]([C:16]3[N:15]4[C:11]([O:12][CH:13]=[CH:14]4)=[N:10][C:9]=3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][CH:2]=3)[CH:22]=[CH:21][C:20]=12

참가 물질

11

반응물 8

HCID 3939Lithium HydroxideHCID 9321HydrazineHCID 70211Ethyl oxoacetateHCID 120273N-IodosuccinimideHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 12217721Iodo benzene diacetateHCID 574336106-(4-Fluorophenyl)-imidazo[2,1-b]oxazoleHCID 594578146-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole

생성물 1

HCID 594578155-([1,2,4]Triazolo[4,3-a]pyridin-6-yl)-6-(4-fluorophenyl)imidazo[2,1-b]oxazole수율 80%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

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온도
65 °C

실험 절차

The 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.20 g, 0.65 mmol; prepared using A from 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [prepared according to WO2004110990A2, Example 1, Steps 1-3] with NIS, C with 2-fluoropyridine-5-boronic acid [Asymchem], D with hydrazine) and ethyl 2-oxoacetate (0.65 mL, 9.7 mmol) were dissolved in MeOH (5.0 mL) and heated to about 65° C. for about 1 h. The MeOH was evaporated and then DCM (5 mL) was added followed by iodobenzene diacetate (0.53 g, 1.6 mmol). The reaction was stirred for about 15 min then the DCM was evaporated and the resulting solid was triturated with Et2O. The solid was dissolved in 1,4-dioxane (10 mL) and LiOH (0.060 g, 2.4 mmol) dissolved in water (2 mL) was added drop-wise followed by heating to about 50° C. for about 30 min. The 1,4-dioxane was evaporated and the pH was adjusted to about 1 with 1N HCl. The resulting precipitate was filtered and washed with water (about 10 mL) and dried in a vacuum oven to give the title compound (0.31 g, 80%): LC/MS (Table 1, Method a) Rt=1.88 min; MS m/z: 320.1 (M+H)+.

후처리

  1. customprepared
  2. customThe MeOH was evaporated
  3. additionDCM (5 mL) was added
  4. customthe DCM was evaporated
  5. customthe resulting solid was triturated with Et2O
  6. dissolutionThe solid was dissolved in 1,4-dioxane (10 mL)
  7. additionwas added drop-wise
  8. temperatureby heating to about 50° C. for about 30 min
  9. customThe 1,4-dioxane was evaporated
  10. filtrationThe resulting precipitate was filtered
  11. washwashed with water (about 10 mL)
  12. customdried in a vacuum oven

출처 및 근거

ORD 기록
ord-48949c59adad4c979d002ebc935fc6af
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07790741B2

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