33322-60-0|3-Amino-N,N-dimethylbenzamide| Ambeed

CAS No. :	33322-60-0
Formula :	C₉H₁₂N₂O
M.W :	164.20
SMILES Code :	O=C(N(C)C)C1=CC=CC(N)=C1
MDL No. :	MFCD01168905
InChI Key :	LZPLRAXAVPPVSX-UHFFFAOYSA-N
Pubchem ID :	424774

Safety of [ 33322-60-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Application In Synthesis of [ 33322-60-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 33322-60-0 ]

[ 33322-60-0 ] Synthesis Path-Downstream 1~54

1
[ 75-21-8 ]
[ 33322-60-0 ]
3-[Bis-(2-hydroxy-ethyl)-amino]-N,N-dimethyl-benzamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 112 - 121.

2
[ 33322-60-0 ]
[ 14301-31-6 ]
3-([2-(3,4-Dimethoxy-phenyl)-ethylcarbamoyl]-methyl}-amino)-N,N-dimethyl-benzamide [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 2712 - 2719.

Yield	Reaction Conditions	Operation in experiment
85%	With iron; acetic acid; at 50℃; for 1h;	General procedure: (0244) General procedure for the reduction of aromatic nitro groups with iron powder. Iron powder (10.0 equiv.) was added to a solution of the relevant nitro aromatic (1.0 equiv.) in acetic acid (5 mL/mmol). The reaction mixture was stirred at 50C for 1H, before being filtered through celite. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (10 mL/mmol) and washed with saturated NaHC03 solution (2 x 10 mL/mmol). The organic phase was washed with water (10 mL/mmol) and brine (5 mL/mmol) before being dried (MgS04) and concentrated in vacuo. The material was purified via chromatography if necessary. Synthesis of AT'.AT'-dimethylbenzene-I.B-diamine. N,N-Dimethyl-3-nitroaniline (0.500 g, 3.01 mmol) and iron powder (1.68 g, 30.1 mmol) were reacted in acetic acid (15 mL) according to the described general procedure. Purification on silica gel (1 :1 (0247) Hexanes:EtOAc) afforded the target compound as a red oil (0.328 g, 2.40 mmol, 80%). Rf 0.44 (1 :1 Hexanes:EtOAc); IR (cm 1) 3343, 3220, 2878, 2800, 1606, 1579, 1501; 1H NMR (400 MHz, CDCIs) 2.94 (6H, s, N(CH3)2), 3.62 (2H, br s, NH2), 6.10-6.16 (2H, m, H-2/6), 6.24 (1 H, dd, = 8.1, 2.3 Hz, H-4), 7.07 (1 H, dd, J = 8.1, 7.9 Hz, H-5); 13C NMR (100 MHz, CDCI3) 40.6 (N(CH3)2), 99.6 (Ar-C), 103.8 (Ar-C), 104.3 (Ar-C), 129.9 (Ar-C), 147.3 (Ar-C), 151.9 (Ar-C).
	With 5%-palladium/activated carbon; hydrogen; In methanol;	General procedure: Compound 5a or 5b was reduced in the following manner to prepare compound 6c or 6d. Nitrogen-substituted compound 5a or 5b was dissolved in anhydrous MeOH, and 5% palladium carbon was added thereto under an argon atmosphere. The reaction solution was stirred overnight in a hydrogen atmosphere and filtered through a celite pad, and the filtrate was purified without additional purification to obtain a crude product. 1) 3-Amino-N-methylbenzamide (6c) was obtained as a white solid from compound 5a. 1H NMR (DMSO-d6, 400 MHz) δ = 8.13 (d, J = 4.0 Hz, 1H), 6.99-7.05 (m, 2H), 6.89 (d, J = 7.2 Hz, 1H), 6.62-6.65 (m, 1H), 5.17 (s, 2H), 2.71 (d, J = 4.8 Hz, 3H).

4
[ 861136-84-7 ]
[ 33322-60-0 ]
[ 861136-86-9 ]

References: [1]Synthesis,2005,p. 1550 - 1554.

5
[ 1027038-69-2 ]
[ 33322-60-0 ]
[ 855249-68-2 ]

Yield	Reaction Conditions	Operation in experiment
72%		3, 4-Bis- (4-fluoro-phenyl)-5-formyl-1-isopropyl-1H-pyrrole-2-carboxylic acid (3- dimethylcarbamoyl-phenyl)-amide To a mixture of 3, 4-bis- (4-fluoro-phenyl)-5-formyl-1-isopropyl-lH-pyrrole-2- carboxylic acid prepared in Step G of Example 1 (3.0 g, 8.1 mmoles) in anhydrous dichloromethane (90 mL) was added 2 drops of anhydrous DMF, followed by oxalyl chloride (0.85 mL, 9.7 mmoles). The reaction mixture was stirred at room temperature for 18 hrs and then evaporated and dried to provide 3.15 g (100% crude) of a dark green tacky solid as the acid chloride. The solid was dissolved in anhydrous dichloromethane (50 mL) and then added dropwise to a cold (0 C) mixture of 3- amino-N, N-dimethyl-benzamide (H. Wenker, JACS, 60: 1080 1938) (1.6 g, 9.7 mmoles) and diisopropylethylamine (1.8 mL, 11 mmoles) in anhydrous dichloromethane (50 mL). The reaction mixture was stirred at-5 to 0 C for 2 hrs and then at room temperature for 18 hrs. The reaction mixture was diluted with a mixture of 300 mL of dichloromethane and 50 mL of water. The aqueous layer was separated and then the organic layer was washed with 1 N HCI (3 x 50 mL), 5% sodium bicarbonate (2 x 50 mL), and with brine (50 mL). The organic layer was separated, dried (sodium sulfate), filtered, and then evaporated to give a residue, which was purified by flash chromatographed (silica gel, 60% ethyl acetate in hexane) to provide 3.03 g (72%) of the desired product as a tan solid: mp 133-135 C ; MS (APCI+) nez 516.

References: [1]Patent: WO2005/56004,2005,A1 .Location in patent: Page/Page column 177.
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4538 - 4544.

6
[ 33322-60-0 ]
[ 24813-06-7 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 112 - 121.

7
[ 5460-29-7 ]
[ 33322-60-0 ]
[ 73279-19-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In methanol; 5,5-dimethyl-1,3-cyclohexadiene; ethanol; ethyl acetate;	3-[(3-Aminopropyl)amino]-N,N-dimethylbenzamide A mixture of <strong>[33322-60-0]3-amino-N,N-dimethylbenzamide</strong> (15.4 g) and N-(3-bromopropyl)phthalimide (12 g) in dry xylene was heated under reflux during 12 hr. The precipitate that formed was dissolved in methanol and ethyl acetate added. The mixture was washed with water and the organic phase was evaporated to leave a crude oil (15 g) which was used without further purification. The oil and hydrazine hydrate (5.55 g) were heated under reflux in ethanol for 2 hr and then cooled to 25. A solid precipitate that formed was removed by filtration and the filtrate concentrated in vacuo to give the title compound (2.2 g) b.p. 170-5, (0.01 mm). TLC silica; methanol:ammonia (80:1) Rf 0.2.

References: [1]Patent: US4318913,1982,A .

8
[ 927206-91-5 ]
[ 33322-60-0 ]

Yield	Reaction Conditions	Operation in experiment
36%		The title compound from Step B above (0.36 g, 1.37 mmol) was dissolved in dichloromethane (2 mL) and treated with a 4 M solution of hydrochloric acid in 1,4-dioxane (2 mL, 8 mmol). The mixture was stirred at room temperature for 3 h and diluted with ethyl acetate (20 mL). Saturated aqueous sodium carbonate was then added until pH10. The organic phase was separated, dried over Na2SO4, filtered and the solvents were removed. The residue was purified by chromatography on silica using ethyl acetate to afford the title compound as off-white solid (0.08 g, 36%).1H-NMR (400 MHz, CDCl3): δ=3.00 (s, 3H), 3.11 (s, 3H), 6.70-6.74 (m, 2H), 6.77 (dt, 1H), 7.18 (t, 1H)
	With trifluoroacetic acid; In dichloromethane; for 1h;	Example 27A (50 mg) was treated with trifluoroacetic acid/CH2Cl2 (1 mL:1 mL) and stirred for one hour. The mixture was concentrated to dryness under reduced pressure to give the title compound. 1H NMR (300 MHz, methanol-d4) δ ppm 3.66 (d, 6H), 7.43 (d, J=1.70 Hz, 1H), 7.49 (dd, J=7.80, 2.37 Hz, 1H), 7.52-7.58 (m, 1H), 7.63 (d, J=7.80 Hz, 1H). MS (DCI) m/z 265 [M+H]+.

References: [1]Patent: US2011/280808,2011,A1 .Location in patent: Page/Page column 53.
[2]Patent: US2007/49596,2007,A1 .Location in patent: Page/Page column 35.

9
[ 928639-97-8 ]
[ 33322-60-0 ]
[ 928789-46-2 ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; at 90℃; for 15h;	A. 2-(3-Dimethylcarbamoyl-phenylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 8-Indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (20 mg, 0.048 mmol) and 3-amino-N,N-dimethyl-benzamide (8 mg, 0.05 mmol) were combined in i-PrOH (2 mL) and heated to 90 C. After 15 h, the reaction mixture was concentrated and purified by preparative HPLC (C-18 column, 32 mL/min 5-100% MeCN/H2O gradient over 15 min) and lyophilized to provide 15.6 mg of 2-(3-dimethylcarbamoyl-phenylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.31 (s, 1H), 1.13 (s, 1H), 7.46 (br s, 1H), 7.33 (d, 1H, J=7.9 Hz), 7.16-7.21 (m, 2H), 7.10 (d, 1H, J=7.6 Hz), 6.96 (br s, 2H), 4.29 (q, 2H, J=7.1 Hz), 2.97-3.04 (m, 5H), 2.85-2.93 (m, 5H), 2.14 (p, 2H, J=7.4 Hz), 1.29 (t, 3H, J=7.1 Hz)

References: [1]Patent: US2007/60577,2007,A1 .Location in patent: Page/Page column 65.

10
[ 945257-67-0 ]
[ 33322-60-0 ]
[ 945257-76-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 120℃; for 12h;	EXAMPLE 8 3-({4-[(5,5-dimethyl-2,4-dioxo-3-{4-[(trifluoro-methyl)thio]phenyl}imidazolidin-1-yl)methyl]pyridin-2-yl}amino)-N,N-dimethylbenzamide To a solution of 42.9 mg of 1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethyl-3-{4-[(trifluoromethyl)thio]phenyl}imidazolidine-2,4-dione obtained in stage d) of Example 1, and 24.4 mg of <strong>[33322-60-0]3-amino-N,N-dimethylbenzamide</strong> in 5 mL of dioxane, under an inert atmosphere of argon, are added 2.2 mg of palladium acetate, 6.9 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene and 123 mg of caesium carbonate. The reaction medium is heated at 120 C. for 12 hours, cooled to room temperature and concentrated under reduced pressure. The residue obtained is purified by preparative HPLC chromatography (reverse-phase C18 column, eluding with a water/acetonitrile gradient containing 0.1% tri-fluoroacetic acid). After evaporating off the solvents under reduced pressure, 33.2 mg of 3-({4-[(5,5-dimethyl-2,4-dioxo-3-{4-[(trifluoromethyl)thio]phenyl}imidazolidin-1-yl)methyl]pyridin-2-yl}amino)-N,N-dimethylbenzamide are obtained, the characteristics of which are as follows: LCMS: m/Z=558.23 [M+H]+; RT: 1.46 min

References: [1]Patent: US2009/82329,2009,A1 .Location in patent: Page/Page column 19.

11
[ 33322-60-0 ]
[ 3932-97-6 ]
[ 1141379-20-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6071 - 6077.

12
[ 953908-11-7 ]
[ 33322-60-0 ]
[ 1220112-63-9 ]

References: [1]Chemical Communications,2010,vol. 46,p. 1062 - 1064.

13
[ 7291-02-3 ]
[ 33322-60-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With ammonium chloride; zinc; In ethanol; water; at 20℃;	Add 3-nitro-N,N-dimethylbenzamide (660mg, 3.4mmol)Dissolved in 10mL ethanol and 2mL water,Add zinc powder (2.2g, 34.0mmol)And ammonium chloride (1.8g, 34.0mmol),Stir at room temperature overnight.The reaction solution is concentrated and diluted by adding 100 mL of water,Extract with ethyl acetate (50mL×3), dry with anhydrous magnesium sulfate,Purified by column chromatography to obtain 470 mg of the target product,The yield was 85%.
		2) 3-Amino-N,N-dimethylbenzamide (6d) was obtained as a white solid from compound 5b. 1H NMR (DMSO-d6, 400 MHz) δ=7.02 (t, J=7.6 Hz, 1H), 6.55-6.58 (m, 1H), 6.51 (s, 1H), 6.43 (d, J=7.6 Hz, 1H), 5.18 (s, 2H), 2.89 (d, J=11.6 Hz, 6H).

References: [1]ChemMedChem,2018,vol. 13,p. 1681 - 1694.
[2]Patent: CN111662242,2020,A .Location in patent: Paragraph 0585; 0591-0593.
[3]RSC Medicinal Chemistry,2020,vol. 11,p. 707 - 731.
[4]Chemical Communications,2010,vol. 46,p. 1062 - 1064.
[5]Patent: US2015/159142,2015,A1 .Location in patent: Page/Page column.

14
[ 33322-60-0 ]
[ 75-36-5 ]
[ 500160-02-1 ]

References: [1]Chemical Communications,2010,vol. 46,p. 1062 - 1064.

15
[ 945396-99-6 ]
[ 33322-60-0 ]
3-[4-(1H-indazol-4-yl-methyl-amino)pyrimidin-2-yl]-N,N-dimethyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With hydrogenchloride; In 1,4-dioxane; pentanol, 2-; at 150℃; for 0.25h;Microwave irradiation;	A mixture of N-methyl-N-(2-methylsulfonylpyrimidin-4-yl)-1H-indazol-4-amine (200 mg, 0.66 mmol), 3-amino-N,N-dimethyl-benzamide (130 mg, 0.79 mmol) and hydrogen chloride (4N in dioxane, 0.165 ml, 0.66 mmol) in 2-pentanol (3 ml) was irradiated in a Personal Chemistry EMRYS Optimizer EXP microwave synthesisor at 150 C. for 15 minutes. After cooling and evaporation of the solvents, the residue was dissolved in DMF (1.5 ml) and concentrated aqueous ammonia (50 μl) was added. The mixture was injected on an HPLC column (C18, 5 microns, 19 mm diameter, 100 mm length) of a preparative HPLC-MS system eluting with a mixture of water and acetonitrile containing 2 g/l of ammonium carbonate (gradient). Evaporation of the fractions gave the title compound (69 mg, 27%).NMR Spectrum: (500 MHz, DMSO) 2.90-2.97 (br s, 3H), 2.97 (br s, 3H), 3.55 (s, 3H), 5.74 (d, 1H), 6.86 (d, 1H), 7.10 (d, 1H), 7.22 (dd, 1H), 7.45 (dd, 1H), 7.55 (d, 1H), 7.75 (d, 1H), 7.80 (d, 1H), 7.88 (d, 1H), 7.92 (s, 1H), 9.34 (s, 1H), 13.31 (br s, 1H); Mass spectrum: MH+ 388

References: [1]Patent: US2011/46108,2011,A1 .Location in patent: Page/Page column 91.

16
[ 1333238-86-0 ]
[ 33322-60-0 ]
[ 1333239-01-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5224 - 5229.

17
[ 99-05-8 ]
[ 33322-60-0 ]

References: [1]Patent: US2011/280808,2011,A1 .

18
[ 111331-82-9 ]
[ 33322-60-0 ]

References: [1]Patent: US2011/280808,2011,A1 .

19
[ 42883-45-4 ]
[ 33322-60-0 ]
[ 1428968-35-7 ]

Yield	Reaction Conditions	Operation in experiment
19%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 200℃; for 0.5h;Microwave irradiation;	General procedure: A mixture of an a-halogenoketone, an amine and a base (DIPEA or triethylamine) in a solvent (e.g. DMF, ethanol, acetonitrile, dioxane or THF) was irradiated in a microwave oven at 100C to 200C (more in particular at 120 to 200 C) for 5 to 180 min. (more in particular for 15 to 120 min). The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel.

References: [1]Patent: WO2013/45516,2013,A1 .Location in patent: Page/Page column 129; 150.

20
[ 1374867-83-0 ]
[ 33322-60-0 ]
[ 1445787-00-7 ]

Yield	Reaction Conditions	Operation in experiment
68.6%	With acetic acid;	Example 36 7-(2,4-dimethoxypyrimidin-5-yl)-4-((3-(dimethylcarbamoyl)phenyl)amino)quinoline-3- carboxamide A mixture of <strong>[33322-60-0]3-amino-N,N-dimethylbenzamide</strong> (52.4 mg, 0.319 mmol) and 4- chloro-7-(2,4-dimethoxypyrimidin-5-yl)quinoline-3-carboxamide (100 mg, 0.290 mmol) in acetic acid (5 mL) was kept stirring overnight. The mixture was diluted with ether. The precipitate was collected, washed with ether and dried under reduced pressure to afford 7-(2,4-dimethoxypyrimidin-5-yl)-4-((3-(dimethylcarbamoyl)phenyl)am carboxamide (94 mg, 0.199 mmol, 68.6 % yield) as an yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.89 (s, 3 H) 2.95 (s, 3 H) 3.99 (s, 3 H) 4.02 (s, 3 H) 7.32 - 7.36 (m, 2 H) 7.44 (d, J=8.08 Hz, 1 H) 7.49 - 7.56 (m, 1 H) 7.82 (dd, J=8.97, 1.64 Hz, 1 H) 7.89 (br. s., 1 H) 8.09 (d, J=9.09 Hz, 1 H) 8.32 (d, J=1.52 Hz, 1 H) 8.47 (br. s., 1 H) 8.63 (s, 1 H) 9.10 (s, 1 H) 12.21 (br. s., 1 H). LCMS (ES+) m/e 473 [M+H]+.

References: [1]Patent: WO2013/96151,2013,A1 .Location in patent: Page/Page column 106; 107.

21
C₁₂H₇ClO₂ [ No CAS ]
[ 33322-60-0 ]
[ 1613439-86-3 ]