Dimethylformamide → 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

HRID 1962876Notes

Reaction equation

HRID 1962876 reaction equation
ON1[C:6]2N=CC=[CH:10][C:5]=2[N:4]=N1.F[B-](F)(F)F.N1([O:25][C:26](N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N([CH2:38][CH3:39])CC)C.[C:40]([C:42]1[CH:43]=[N:44][C:45]2[C:50]([CH:51]=1)=[CH:49][C:48]([O:52][CH:53]([S:57][CH3:58])[C:54]([OH:56])=O)=[CH:47][CH:46]=2)#[CH:41].CN([CH:62]=[O:63])C>[Cl-].[Na+].O.C(OCC)(=O)C>[C:40]([C:42]1[CH:43]=[N:44][C:45]2[C:50]([CH:51]=1)=[CH:49][C:48]([O:52][CH:53]([S:57][CH3:58])[C:54]([NH:4][C:5]([CH3:6])([CH2:10][O:25][CH2:26][C:38]#[CH:39])[CH2:62][OH:63])=[O:56])=[CH:47][CH:46]=2)#[CH:41]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 181649HOAtHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59565474(3-Ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid

Product 1

HCID 595654102-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-Hydroxy-7-azabenzotriazole (0.717 g), O-(1H benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium tetrafluoroborate (1.692 g) and 2-mmino-2-methyl-3-prop-2-ynyloxy-propan-1-ol hydrochloric salt (0.947 g) were added at room temperature to a solution of triethylamine (2.14 ml) and (3-ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid (1.20 g) in DMF. The reaction mixture was stirred 16 hrs at room temperature 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 with sat. sodium hydrogen carbonate, with water and brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure the crude residue was purified was dissolved in 24 ml of THF/H2O (1/1) and treated with of LiOH monohydrate at room temperature for 1 h 45 min. The crude mixture was extracted (pH=11) thrice with ethyl acetate. The organic layers were combined, washed with water and brine and after separation dried over sodium sulphate. Filtration and concentration under reduced pressure provided crude 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide as a yellow oil that was used in the next step, Stage 4, without any further purification. 1H NMR (CDCl3) δ ppm: 8.88 (1H, d); 8.22 (1H, d); 8.07 (1H, d); 7.49 (1H, dd); 7.39 (1H, s br); 7.22 (1H, m); 5.68 (1H, s); 4.22-4.16 (2H, m); 3.90 (1H, s br); 3.81-3.60 (4H, m); 3.30 (1H, s); 2.45 (1H, dt); [{2.22 (s), 2.20 (s) 3H}, isomer A and isomer B]; [{1.40 (s), 1.34 (s) 3H}, isomer A and isomer B].

Workup

  1. customThe two layers were separated
  2. extractionthe aqueous layer was extracted thrice with ethyl acetate
  3. washwashed with sat. sodium hydrogen carbonate, with water and brine
  4. dry with materialdried over sodium sulphate
  5. filtrationAfter filtration and concentration under reduced pressure the crude residue
  6. customwas purified
  7. dissolutionwas dissolved in 24 ml of THF/H2O (1/1)
  8. additiontreated with of LiOH monohydrate at room temperature for 1 h 45 min
  9. extractionThe crude mixture was extracted (pH=11) thrice with ethyl acetate
  10. washwashed with water and brine
  11. customafter separation
  12. dry with materialdried over sodium sulphate
  13. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-1bf01c3f71d54828b4d61ce6ae89c588
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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