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3-Aminopyridine → (2R)-2-amino-N-[5-(4,4-dimethyl-2,5-dioxo-3-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidin-1-yl)-2-(trifluoromethoxy)phenyl]-2-phenylacetamide

HRID 546570
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HRID 546570 반응식
[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23](Cl)[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4].[NH2:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1.CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C@H:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH:40][C:41]4[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=4)[CH:22]=3)[C:13]2=[O:28])[CH:9]=[CH:8][C:7]=1[O:29][C:30]([F:33])([F:32])[F:31])=[O:4]
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참가 물질

7

반응물 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)HCID 86629090(2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide

생성물 1

HCID 57625991
(2R)-2-amino-N-[5-(4,4-dimethyl-2,5-dioxo-3-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidin-1-yl)-2-(trifluoromethoxy)phenyl]-2-phenylacetamide
수율 33%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

To a solution of 33 mg of (2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide obtained in stage d) below in 1 mL of dioxane are successively added, under argon, 7 mg of 3-aminopyridine, 3 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 1.1 mg of palladium acetate and 61 mg of caesium carbonate. The reaction mixture is heated at 110° C. for 1 hour, filtered and washed with twice 10 mL of dioxane, and the filtrate is then concentrated under reduced pressure. The residue is taken up in 1 mL of dioxane, 1 mL of a 4N solution of hydrogen chloride in dioxane is then added and the reaction mixture is stirred at 40° C. for 2 hours. The reaction mixture is then treated with 30 mL of saturated sodium hydrogen carbonate solution and extracted with three times 30 mL of ethyl acetate. The combined organic phases are then washed with water, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 12 mg of (2R)-2-amino-N-[5-(4,4-dimethyl-2,5-dioxo-3-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidin-1-yl)-2-(trifluoromethoxy)phenyl]-2-phenylacetamide, the characteristics of which are as follows:

후처리

  1. filtrationfiltered
  2. washwashed with twice 10 mL of dioxane
  3. concentrationthe filtrate is then concentrated under reduced pressure
  4. addition1 mL of a 4N solution of hydrogen chloride in dioxane is then added
  5. additionThe reaction mixture is then treated with 30 mL of saturated sodium hydrogen carbonate solution
  6. extractionextracted with three times 30 mL of ethyl acetate
  7. washThe combined organic phases are then washed with water
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid)

출처 및 근거

ORD 기록
ord-e849ff23d4d94254b131dd196d4a2a13
출처 데이터셋
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07935819B2

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