Diisopropylethylamine → (R)-N-[5-(1-(tert-Butyl-dimethyl-silanyloxy)-2-{2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamino}-ethyl)-pyridin-2-yl]-acetamide

HRID 413312Notes

Reaction equation

HRID 413312 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:16]=[CH:15][C:10]([O:11][CH2:12][CH2:13][NH2:14])=[CH:9][CH:8]=2)[N:6]=1.[C:17]([NH:20][C:21]1[N:26]=[CH:25][C:24]([CH:27]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH2:28]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:23][CH:22]=1)(=[O:19])[CH3:18].C(N(C(C)C)CC)(C)C>CS(C)=O>[C:44]([Si:41]([CH3:43])([CH3:42])[O:40][C@H:27]([C:24]1[CH:23]=[CH:22][C:21]([NH:20][C:17](=[O:19])[CH3:18])=[N:26][CH:25]=1)[CH2:28][NH:14][CH2:13][CH2:12][O:11][C:10]1[CH:15]=[CH:16][C:7]([C:5]2[N:6]=[C:2]([CH3:1])[S:3][CH:4]=2)=[CH:8][CH:9]=1)([CH3:47])([CH3:46])[CH3:45]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 17940032Toluene-4-sulfonic acid 2-(6-acetylamino-pyridin-3-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl esterHCID 185328822-[4-(2-Methyl-thiazol-4-yl)-phenoxy]-ethylamine

Product 1

HCID 69743740(R)-N-[5-(1-(tert-Butyl-dimethyl-silanyloxy)-2-{2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamino}-ethyl)-pyridin-2-yl]-acetamideYield 45%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

In a round-bottomed flask, 2-[4-(2-methyl-thiazol-4-yl)-phenoxy]-ethylamine (175 mg, 0.747 mmol) and toluene-4-sulfonic acid 2-(6-acetylamino-pyridin-3-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethyl ester (231 mg, 0.498 mmol) were dissolved in dimethylsulfoxide (0.50 mL), and diisopropyl ethyl amine (0.105 mL, 0.600 mmol) was added in one portion. The resulting mixture was heated to about 80° C. for about sixteen hours, and was then partitioned between diethyl ether and water. The aqueous phase was extracted with diethyl ether four times, and the combined organic extracts were then washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting white solid was purified by column chromatography (methylene chloride to 10% methanol/methylene chloride) to afford 117 mg (45%) of the desired product. LRMS ([M+1]+): 527.1.

Workup

  1. customwas then partitioned between diethyl ether and water
  2. extractionThe aqueous phase was extracted with diethyl ether four times
  3. washthe combined organic extracts were then washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting white solid was purified by column chromatography (methylene chloride to 10% methanol/methylene chloride)

Sources & evidence

ORD record
ord-8bc2e1ae920d498b9a063304a2be2c80
Source dataset
uspto-grants-2003_05
Patent number
US06566377B2

Reaction notes

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