HOAt → N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide

HRID 1962879

반응식

HRID 1962879 반응식
[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:18][CH3:19])[C:15]([OH:17])=O)=[CH:8][CH:7]=2)#[CH:2].ON1C2N=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:52][C:53]([CH3:58])([CH2:56][OH:57])[C:54]#[N:55]>C(#N)C.[Cl-].[Na+].O.C(OCC)(=O)C.C(N(CC)CC)C>[C:54]([C:53]([NH:52][C:15](=[O:17])[CH:14]([O:13][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:1]#[CH:2])=[CH:12]2)[S:18][CH3:19])([CH3:58])[CH2:56][OH:57])#[N:55]

참가 물질

9

반응물 4

HCID 181649HOAtHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 144057522-Amino-3-hydroxy-2-methylpropanenitrileHCID 59565474(3-Ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid

생성물 1

HCID 59565307N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide수율 38.8%

시약·촉매·용매 4

HCID 6342Acetonitrile용매2회HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

실험 절차

To a solution of (3-ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid (4.0 g) and triethylamine (6 ml) in dry acetonitrile (50 ml) at room temperature were added successively a 1-hydroxy-7-azabenzotriazole (2.39 g) and O-(1H Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (5.64 g) and a solution of 2-amino-3-hydroxy-2-methyl-propionitrile (1.76 g) in dry acetonitrile (20 ml). The reaction mixture was stirred at room temperature for 18 hrs and then poured onto a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine and then, dried over sodium sulphate. After filtration and concentration under reduced pressure, the crude residue was dissolved in 50 ml of THF/H2O (1/1) and treated with 260 mg of LiOH monohydrate at room temperature for 1 hr. The crude mixture was extracted (pH=11) thrice with ethyl acetate. The organic layers were combined, washed with water, with brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure, the crude residue was purified by flash chromatography on silica gel (hexane/ethyl acetate 1:4, 0:1) to provide 2.02 g of N-(1-cyano-2-hydroxy-1-methyl-ethyl)-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide as a white solid (m.p. 78-80° C.).

후처리

  1. customThe two layers were separated
  2. extractionthe aqueous layer was extracted thrice with ethyl acetate
  3. washwashed once with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. dissolutionthe crude residue was dissolved in 50 ml of THF/H2O (1/1)
  7. additiontreated with 260 mg of LiOH monohydrate at room temperature for 1 hr
  8. extractionThe crude mixture was extracted (pH=11) thrice with ethyl acetate
  9. washwashed with water, with brine
  10. dry with materialdried over sodium sulphate
  11. filtrationAfter filtration and concentration under reduced pressure
  12. customthe crude residue was purified by flash chromatography on silica gel (hexane/ethyl acetate 1:4, 0:1)

출처 및 근거

ORD 기록
ord-83e5b67dd8ca41aa977d80063878cfd0
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415272B2

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