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

HRID 1892039

Reaction equation

HRID 1892039 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-451e5cb9118f45ee813d870987d19391
Source dataset
uspto-grants-2013_08
Patent number
US08507509B2

Linked notes

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