2-Amino-2-methyl-1-propanol → 2-(3-bromo-quinolin-6-yloxy)-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methylsulfanyl-acetamide

HRID 1892039

반응식

HRID 1892039 반응식
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH:13]([S:17][CH3:18])[C:14]([OH:16])=O)=[CH:7][CH:6]=2.[NH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C([O-])(O)=O.[Na+]>CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH:13]([S:17][CH3:18])[C:14]([NH:19][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22])=[O:16])=[CH:7][CH:6]=2

참가 물질

9

반응물 5

HCID 118072-Amino-2-methyl-1-propanolHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66717844(3-Bromo-quinolin-6-yloxy)-methylsulfanyl-acetic acid

생성물 1

HCID 667178702-(3-bromo-quinolin-6-yloxy)-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methylsulfanyl-acetamide

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

(3-Bromo-quinolin-6-yloxy)-methylsulfanyl-acetic acid (23 g) from Example 1, Stage 1 above, 2-amino-2-methyl-1-propanol (8.06 ml), 1-hydroxy-7-azabenzotriazole (HOAT) (11.44 g), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) (16.12 g) and triethylamine (14.63 ml) in dry DMF (175 ml) were stirred at rt for 16 hours. The reaction mixture was diluted with ethyl acetate and poured into 200 ml sat. NaHCO3. The two phases were separated and the aqueous layer was extracted three times with ethyl acetate (3×200 ml). The organic layers were combined, dried over magnesium sulphate, filtered and evaporated. The residue was purified by column chromatography (heptane/ethyl acetate 7:13) to give 2-(3-bromo-quinolin-6-yloxy)-N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methylsulfanyl-acetamide as a white solid (16.94 g). 1H NMR (DMSO) δ ppm: 8.82 (1H, d); 8.57 (1H, d); 7.99 (1H, d); 7.58 (1H, dd); 7.52 (1H, s); 7.44 (1H, d); 5.94 (1H, s); 4.99 (1H, t); 3.48-3.37 (2H, m); 2.15 (3H, s); 1.28 (3H, s); 1.26 (3H, s).

후처리

  1. customThe two phases were separated
  2. extractionthe aqueous layer was extracted three times with ethyl acetate (3×200 ml)
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography (heptane/ethyl acetate 7:13)

출처 및 근거

ORD 기록
ord-451e5cb9118f45ee813d870987d19391
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507509B2

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