2-Dimethylaminopyridine → 2-(3-Ethynyl-quinolin-6-yloxy)-2-methoxy-n-(2-methoxy-1,1-dimethyl-ethyl)-acetamide

HRID 1962859Notes

Reaction equation

HRID 1962859 reaction equation
[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]([O:18][CH3:19])[C:15]([OH:17])=O)=[CH:8][CH:7]=2)#[CH:2].Cl.[CH3:21][O:22][CH2:23][C:24]([NH2:27])([CH3:26])[CH3:25].CN(C1C=CC=CN=1)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.[Cl-].[Na+].O>[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]([O:18][CH3:19])[C:15]([NH:27][C:24]([CH3:26])([CH3:25])[CH2:23][O:22][CH3:21])=[O:17])=[CH:8][CH:7]=2)#[CH:2]

Participants

7

Reactant 4

HCID 218852-DimethylaminopyridineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 212557121-Methoxy-2-methylpropan-2-amine hydrochlorideHCID 59565329(3-Ethynyl-quinolin-6-yloxy)-metoxy-acetic acid

Product 1

HCID 595653012-(3-Ethynyl-quinolin-6-yloxy)-2-methoxy-n-(2-methoxy-1,1-dimethyl-ethyl)-acetamideYield 86.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (3-ethynyl-quinolin-6-yloxy)-metoxy-acetic acid (150 mg) in dry dimethylformamide (7 mL) were added 2-metoxy-1,1-dimethyl-ethylamine hydrochloride (81 mg) N-ethyldiisopropylamine (0.25 mL), dimethylaminopyridine (catalytic quantity) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (297 mg). The reaction mixture was stirred at room temperature for 18 hours. The mixture was poured over brine and extracted twice with ethyl acetate (thrice). The organic layer was washed with water then with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude was purified by chromatography eluting with cyclohexane/ethyl acetate (7:3 by volume), to give 2-(3-ethynyl-quinolin-6-yloxy)-2-methoxy-N-(2-methoxy-1,1-dimethyl-ethyl)-acetamide (172 mg) as an oil.

Workup

  1. extractionextracted twice with ethyl acetate (thrice)
  2. washThe organic layer was washed with water
  3. dry with materialwith brine, dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by chromatography
  7. washeluting with cyclohexane/ethyl acetate (7:3 by volume)

Sources & evidence

ORD record
ord-aac07bc2f04b40839bc13df906ed2bfb
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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