Triethylamine → (R)-3-(2-(Methoxymethyl)-7-methyl-2H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 2099795Notes

Reaction equation

HRID 2099795 reaction equation
[O:1]=[C:2]1[C:11]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH:21]([CH2:24][C:25]3[CH:33]=[C:32]([CH3:34])[C:31]4[C:27](=[CH:28][N:29]([CH2:35][O:36][CH3:37])[N:30]=4)[CH:26]=3)[CH2:22][OH:23])=[O:19])[CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C(N(CC)CC)C>CS(C)=O>[O:1]=[C:2]1[C:11]([CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C@H:21]([CH2:24][C:25]3[CH:33]=[C:32]([CH3:34])[C:31]4[C:27](=[CH:28][N:29]([CH2:35][O:36][CH3:37])[N:30]=4)[CH:26]=3)[CH:22]=[O:23])=[O:19])[CH2:16][CH2:17]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 690718601-Hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

Product 1

HCID 57794651(R)-3-(2-(Methoxymethyl)-7-methyl-2H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
5 °C

Procedure

1-Hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate (0.65 g, 1.29 mmol) was dissolved in anhydrous dimethyl sulfoxide (5.0 mL). Triethylamine (0.54 mL, 3.87 mmol) was added and the reaction mixture cooled to ca. 5° C. using an ice bath. A solution of sulfur trioxide pyridine complex (0.62 g, 3.87 mmol) in dimethyl sulfoxide (4.0 mL) was added in one portion. After 1 min, the ice bath was removed and the reaction mixture stirred at room temperature for 20 min. The reaction mixture was poured into an ice slurry and extracted with ethyl acetate (3×). The combined organic extracts were washed with 10% citric acid (2×), water (2×), 5% sodium bicarbonate (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography afforded 0.55 g (85%). 1H-NMR (DMSO. d6, 500 MHz) δ 1.90 (s, 3H), 2.48 (s, 3H), 2.51 (m, 2H), 2.71-2.95 (m, 4H), 4.51 (m, 1H), 4.72-4.84 (m, 1H), 6.31-6.46 (m, 1H), 6.91 (d, J=4.0, 1H), 8.36 (s, 1H), 11.74 (s, 1H). Mass spec.: 503.3 (MH)+.

Workup

  1. customthe ice bath was removed
  2. additionThe reaction mixture was poured into an ice slurry
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organic extracts were washed with 10% citric acid (2×), water (2×), 5% sodium bicarbonate (2×), brine (2×)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography afforded 0.55 g (85%)

Sources & evidence

ORD record
ord-71b47a99c701460dad42f09d1f470665
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

Loading…