Hi,

If your compound is a primary or secondary amine, I suggest that you acylate it to an amide, perhaps using acetic anhydride. The extract the mixture with dilute Hcl to remove the DIPEA (which IO assume id di-isopropyl-ethyl amine). Then hydrolyse the mixture of amides to regain you amines.

If your compound is also a tertiary amine, AND it is a high boiling compound, I think you might be able to distill out the DIPEA (bp 127 deg. C). Otherwise you may have to use column chromatography.

Bill

slurry with diisipropyl ether or heptane or hexane

Dear william,

as per u rsuggestion ,my compound contains amide basically it prepared from acid functional group contains primary amine.if it hydrolysed starting material will come.and also i passed through column but did not get positive result.

Hi,

I'm not sure I understand. Is the compound you want an amide that you prepared starting with a carboxylic acid + an amine? Or is the product you want an amine? Can you tell me the reaction conditions you used, and the structure of the product you want.?

Bill

[email protected]

i used HATU,DMFand dipea at room temp.my starting material is 4-amino 5-methoxy benzoic acid coupling with methyl amine.i need amine with amide. Thanks®ards, srinivas

I think u add the cold water to ur reaction mixture and stirred it for some time, u get solid then u filter it. If u dont get the solid u add the DCM and extract ur compound, and the organic layer was washed with 10% citric acid solution

Hi,

Here are three ways:

1) MeNHCONHMe + ZrOCl2

2) make the acid chloride and treat that with MeNH2

3) Probably the best: make the methyl ester then treat that with MeNH2

NH2PhCOOH to NH2PhCONHMe

1. Zirconyl chloride: an efficient, water-tolerant, and reusable catalyst for the synthesis of N-methylamides

Talukdar, Dhrubajyoti; Saikia, Lakhinath; Thakur, Ashim Jyoti

Synlett (2011), (11), 1597-1601.

ZrOCl2•8H2O is a highly effective, water-tolerant, and reusable catalyst for the direct condensation of carboxylic acids and N,N'-dimethylurea under microwave irradn. to give the corresponding N-methylamides in moderate to excellent yields. Notably, ZrOCl2•8H2O is a potentially useful green catalyst due to its low toxicity, easy availability, low cost, ease of handling, easy recovery, good activity, and reusability.

Typical Procedure for the Synthesis of N-Methylamides 3 A 1:1 mixture of DMU (MeNHCONHMe) 2, 0.088 g, 1 mmol), carboxylic acid 1a (0.122 g, 1 mmol, R = Ph), and ZrOCl2•8H2O (0.032 g, 10 mol%)

were ground in a mortar, placed in a 50 mL conical flask and irradiated in a microwave oven. The progress of the reaction was monitored by TLC. After completion of the reaction, the contents were

extracted with EtOAc (3 × 10 mL) and filtered to remove the catalyst. To remove unreacted acid the organic layer was washed with aq NaHCO3 followed by H2O. Evaporating the organic solvent provided

the product in essentially pure form. Column chromatography was used when required. In this instance, recrystallization from EtOH afforded the pure product N-methylbenzamide (3a). White solid; mp 77 °C. MS: m/z = 225 [M+ ]. IR (KBr): nmax = 3289, 3105,

With p-aminobenzoic acid this gives a 50% yield of p-amino-N-methylbenzamide.

2. Solid-Phase Synthesis of an A-B Loop Mimetic of the Cε3 Domain of Human IgE: Macrocyclization Sonogashira Coupling

Spivey, Alan C.; McKendrick, John; Srikaran, Ratnasothy; Helm, Birgit A.

Journal of Organic Chemistry (2003), 68(5), 1843-1851.

4-Amino-3-iodo-N-methylbenzamide (13). The acid chloride of4-amino-3-iodobenzoic acid 10 was prepared as detailed in the preparation of compound 11 (below). To a solution of this crude acid chloride (750 mg, 2.80 mmol) in CH2Cl2 (10 mL) were added MeNH2-HCl (250 mg, 1.75 equiv) and Et3N (0.90 mL, 2.30 equiv). The resulting solution was stirred for 0.5 h, diluted with EtOAc (25 mL), and washed with 5% NaHCO3 (50 mL). The organic layer was then washed with brine (2 25 mL), dried (MgSO4), and concentrated in vacuo. Purification by FC (EtOAc/hexane, 4:6) gave methylbenzamide 13 as a white solid (432 mg, 56%): mp 64-67 °C; 1 H NMR (CDCl3) ä 2.90 (2 s, 3H), 4.46 (br s, 2H), 6.35 (br s, 1H), 6.63 (d, J ) 6.9…

4-Amino-3-iodobenzoic Acid 2,2,2-Tribromoethyl Ester

(11). A solution of 4-amino-3-iodobenzoic acid 10 (1.40 g, 5.32 mmol) in SOCl2 (8.0 mL, excess) was heated to reflux for 1.5 h. The solution was then concentrated in vacuo and the residue dissolved in toluene (15 mL) and then reconcentrated in vacuo to give the crude acid chloride as a yellow oil.

3a. Structure-Activity Relationship for Thiohydantoin Androgen Receptor Antagonists for Castration-Resistant Prostate Cancer (CRPC)

Jung, Michael E.; Ouk, Samedy; Yoo, Dongwon; Sawyers, Charles L.; Chen, Charlie; Tran, Chris; Wongvipat, John

Journal of Medicinal Chemistry (2010), 53(7), 2779-2796.

Synthesis of 87 and 88. 4-Aminobenzoic Acid Methyl Ester, 87a

. Concentrated sulfuric acid was slowly added to a mixture of 4-aminobenzoic acid (4 g, 29.2 mmol) in methanol cooled to 0 .C. After the addition, the mixture was stirred at 21 .C for 5 h. The mixture was washed with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over MgSO4 and concentrated under vacuum to obtain 87a (4.22 g, 27.9 mmol, 96%) as an off-white solid.

3b. Preparation of aminopyrimidine derivatives for use as antitumor agents Full Text

By Appari, Rama Devi; Chen, Xin; Chilukuri, Ramesh; Crew, Andrew P.; Dong, Hanqing; Ferraro, Caterina; Foreman, Kenneth; Gupta, Ramesh C.; Li, An-Hu; Sherman, Dan; et al

From PCT Int. Appl. (2010), WO 2010141406 A2 20101209. | Language: English, Database: CAPLUS

Compound 106A: 2-Amino-5-bromo-N-methylbenzamide A mixture of methyl 2-amino-5-bromobenzoate (Compound 106B, 65 g) and CH3NH2•H2O (1000 mL) was stirred at 80 °C overnight in a pressure tube. The mixture was diluted with H2O (1000 mL) and extracted with EtOAc (3 x 500 mL). The combined organic layers were dried over MgSO4, concentrated to afford the title compound (55 g, yield: 87 %) as a gray solid. 1H NMR (CDCl3, 400 MHz): δ = 2.93 (d, J = 5.2 Hz, 3H), 5.48 (s, br, 2H), 6.04 (s, br, 1H), 6.54 (d, J = 8.4 Hz, 1H), 7.24 (dd, J = 2.0, 8.4 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H).

Column chromatography in presence of amines are very challenging. with this condition I would recommend to leave the compound in high vacuum at 50C for a day or two, if your product is not volatile.