Sodium Bicarbonate → N-(1-dimethoxymethyl-cyclobutyl)-2-(3-ethynyl-quinolin-6-yloxy)-2methylsulfanyl-acetamide

HRID 1962890Notes

Reaction equation

HRID 1962890 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]([S:24][CH3:25])[C:15]([NH:17][C:18]1([CH:22]=[O:23])[CH2:21][CH2:20][CH2:19]1)=[O:16])=[CH:8][CH:7]=2)#[CH:2].C1(C)C=CC=CC=1.C1C[O:36][CH2:35]C1.[C:38]([O-])(O)=O.[Na+]>CO>[CH3:38][O:23][CH:22]([O:36][CH3:35])[C:18]1([NH:17][C:15](=[O:16])[CH:14]([O:13][C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[CH:4][C:3]([C:1]#[CH:2])=[CH:12]3)[S:24][CH3:25])[CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 22635083Tetrahydrofuran tolueneHCID 595654712-(3-ethynyl-quinolin-6-yloxy)-N-(1-formyl-cyclobutyl)-2-methylsulfanyl-acetamide

Product 1

HCID 59565272N-(1-dimethoxymethyl-cyclobutyl)-2-(3-ethynyl-quinolin-6-yloxy)-2methylsulfanyl-acetamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-formyl-cyclobutyl)-2-methylsulfanyl-acetamide (180 mg) from Example 12f, Step 2 described above in a 10/1 mixture of toluene/THF (11 ml) p-toluene sulphonic acid (4 mg) was added followed by MeOH (1.10 ml), at room temperature. The mixture was stirred at 50° C. overnight and 60° C. during 6 hrs, then after cooling to room temperature poured into aq NaHCO3 soln and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulphate anhydrous, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give N-(1-dimethoxymethyl-cyclobutyl)-2-(3-ethynyl-quinolin-6-yloxy)-2methylsulfanyl-acetamide as white solid. 1H NMR (CDCl3) δ ppm: 8.84 (1H, d); 8.19 (1H, d); 8.05 (1H, d); 7.46 (1H, dd); 7.23 (1H, d); 6.86 (1H, br s); 5.62 (1H, s); 4.57 (1H, s); 3.51 (3H, s); 3.47 (3H, s); 3.28 (1H, s); 2.47-2.21 (4H, m); 2.21 (3H, 5); 2.01-1.73 (2H, m).

Workup

  1. additionwas added
  2. temperatureafter cooling to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulphate anhydrous
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-31751f19c05347bb8ca4b2d0b8471d98
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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