Triethylamine → methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoate

HRID 517497Notes

Reaction equation

HRID 517497 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH2:23]([O:27][C:28]1[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=1)[C:24]#[C:25][CH3:26].Cl.[NH2:38][CH2:39][C@H:40]([N:45]1[CH2:50][CH2:49][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:47][CH2:46]1)[C:41]([O:43][CH3:44])=[O:42].C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:23]([O:27][C:28]1[CH:29]=[CH:30][C:31]([C:32]([NH:38][CH2:39][C@H:40]([N:45]2[CH2:50][CH2:49][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:47][CH2:46]2)[C:41]([O:43][CH3:44])=[O:42])=[O:34])=[CH:35][CH:36]=1)[C:24]#[C:25][CH3:26]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222825564-But-2-ynyloxy-benzoic acidHCID 67057002methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride

Product 1

HCID 67056862methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoateYield 101.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

210 mg (1.5 mmol) of 1-hydroxybenzotriazole and 290 mg (1.5 mmol) of 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride are added to a solution of 260 mg (1.9 mmol) of 4-but-2-ynyloxybenzoic acid (prepared as described in example 1-5) in 10 ml of dimethylformamide. The reaction medium is stirred for 15 minutes and a mixture of 420 mg (1.4 mmol) of methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride and 390 mg (2.8 mmol) of triethylamine in 3 ml of dimethylformamide are added. The reaction medium is stirred at ambient temperature for 1 h 30 min, heated to 50° C., over 1 h 30 min then hydrolysed with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic phase is washed with an aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The crude product obtained is purified by chromatography over silica gel eluted with a 98/2 dichloromethane/methanol mixture. 620 mg (100%) of methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoate are obtained in the form of a colourless oil.

Workup

  1. additionare added
  2. stirringThe reaction medium is stirred at ambient temperature for 1 h 30 min
  3. extractionextracted with ethyl acetate
  4. washThe organic phase is washed with an aqueous solution of sodium hydrogen carbonate
  5. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product obtained
  9. customis purified by chromatography over silica gel
  10. washeluted with a 98/2 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-8725f9cc43874c6eb75a7ce6697f9bd8
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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