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

HRID 1892039

反応式

HRID 1892039 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(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).

後処理

  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)

出典と根拠

ORDレコード
ord-451e5cb9118f45ee813d870987d19391
出典データセット
uspto-grants-2013_08
特許番号
US08507509B2

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