Name: 105-83-9|N1-(3-Aminopropyl)-N1-methylpropane-1,3-diamine|98%
Brand: Ambeed
SKU: A496856
Rating: 93 (30 reviews)

1
[ 50-00-0 ]
[ 105-83-9 ]
[ 3855-32-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With hydrogen; In methanol; water; at 90℃; under 22502.3 Torr;Autoclave; Green chemistry;	Compound 4 (14.5 g, 0.1 mol), methanol (150 mL), aqueous formaldehyde solution (40.6 g, 0.5 mol, 37 wt%) and W-3 Raney Ni (3 g) were added to the autoclave. The air in the autoclave was replaced with nitrogen (3 times) and then with hydrogen (3 times). The dangers of hydrogen/oxygen contact with the catalyst should always be given attention since a mixture of hydrogen and oxygen is capable to of leading to an explosion. Then the reaction mixture was stirred ata rotation speed of 500 rpm at 90 C, 3.0 MPa. The reaction was not stopped until the hydrogen pressure no longer dropped over 5 h and then the mixture was filtered. When the mixture was filtered, Raney Ni should always be kept wet with ethanol and should never directly have contact with the air since dry Raney Ni can easily burst into flames in the air which could result in significant hazards. After the filtration, volatiles were evaporated to give PMDPTA: viscous, yellow liquid; 16.28 g, 81.0 % yield; 1H NMR (CDCl3, 400 MHz) delta: 1.63 (m, J = 7.6Hz, 4H, CH2), 2.21 (s, 15H, CH3), 2.27 (t, J = 7.4 Hz, 4H, CH2), 2.35 (t, J = 7.4 Hz, 4H, CH2); 13C NMR (CD3OD, 151 MHz) delta: 57.3 (2 ×C, CH2), 55.2 (2 × C, CH2), 44.1 (4 × C, CH3), 40.9 (1 × C, CH3), 24.2 (2 × C, CH2); ESI-HRMS m/z [M + H]+: calcd 202.2239, observed 202.2287.

Reference： [1]Journal of Chemical Research,2016,vol. 40,p. 486 - 488
[2]Helvetica Chimica Acta,1951,vol. 34,p. 924,927

2
[ 1555-58-4 ]
[ 105-83-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydrogen; sodium hydroxide; In ethanol; at 90℃; under 15001.5 Torr;Autoclave; Green chemistry;	Compound 3 (30 mL), ethanol (150 mL), sodium hydroxide (0.18 g) and W-3 Raney Ni (6 g) were added into the 300 mL autoclave. The air in the autoclave was replaced with nitrogen by 3 times and then with hydrogen by 3 times. The dangers of hydrogen/oxygen contact with the catalyst should always be given attention since a mixture of hydrogen and oxygen is capable of leading to an explosion. After the reaction mixture was stirred at 90 C, 2.0 MPa, the reaction was not stopped until the hydrogen pressure no longer dropped over 6 h and then the mixture was filtered. When the mixture was filtered, Raney Ni should always be kept wet with ethanol and should never have direct contact with air since dry Raney Ni can easily burst into flames in the air, which could result in significant hazards. After the filtration, the solvent was evaporated to give 4: viscous, colourless liquid; 25.5 g, 85.0% yield; 1H NMR (CDCl3, 400 MHz) delta: 1.65 (m, J = 7.6 Hz, 4H,CH2), 2.26 (s, 3H, CH3), 2.37 (t, J = 7.4, 4H, CH2), 2.48 (t, J = 7.4 Hz,4H, CH2), 5.15 (s, 4H, NH2).

Reference： [1]Journal of Chemical Research,2016,vol. 40,p. 486 - 488
[2]Sb. Statei Obshch. Khim.,1953,p. 1162
Chem.Abstr.,1955,p. 4551
[3]Zhurnal Obshchei Khimii,1954,vol. 24,p. 157,160,161;engl.Ausg.S.157,159,161

3
[ 105-83-9 ]
[ 37942-07-7 ]
N,N′-bis(3,5-di-tert-butyl-2-hydroxybenzyliden)-1,7-diamino-4-methyl-4-azaheptane [ No CAS ]

Reference： [1]Inorganic Chemistry,2013,vol. 52,p. 660 - 670
[2]Journal of the American Chemical Society,1985,vol. 107,p. 2903 - 2907
[3]Journal of Coordination Chemistry,2016,vol. 69,p. 1695 - 1708

4
[ 105-83-9 ]
[ 98-59-9 ]
[ 95690-83-8 ]

Reference： [1]Journal of Organic Chemistry,1993,vol. 58,p. 4749 - 4753
[2]Chemistry - A European Journal,2005,vol. 11,p. 5146 - 5156

5
[ 60117-35-3 ]
[ 105-83-9 ]
N-methyl-N-<3-(5-azido-2-nitrobenzoylamino)propyl>propylene-1,3-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane for 1.5h;

Reference： [1]Dobrikov, M. I.; Prikhod'ko, T. A.; Safaronov, I. V.; Shishkin, G. V. [Russian Journal of Bioorganic Chemistry, 1994, vol. 20, # 5, p. 281 - 287][Bioorganicheskaya Khimiya, 1994, vol. 20, # 5, p. 515 - 523]

6
[ 105-83-9 ]
[ 4053-08-1 ]
2-(3-((3-aminopropyl)(methyl)amino)propyl)-6-chloro-1H-benzo[de]isoquinoline-1,3(2H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	In ethanol Reflux;	2.1.1 General procedure for the preparation of compounds L1-L14 General procedure: To a solution of 4-substituted-1,8-naphthalic anhydride (1.0 mmol) in ethanol (30 mL) was added various alkylamine (3.0 mmol). The reaction mixture was heated under reflux for 20-60 min, and cooled down to room temperature. The solution was concentrated in rotary evaporator and washed with diethyl ether, to give crude yellow solids L1-L14. The residue was purified by using chromatograph on silica gel with DCM/MeOH (50/1-30/1) to give desire compounds.
37%	In ethanol for 15h; Ambient temperature;

Reference： [1]Zhang, Meiling; Wei, Zuzhuang; Gong, Xue; Li, Xiaoya; Kang, Shuangshuang; Wang, Jing; Liu, Bobo; Huang, Zhi-Shu; Li, Ding [Bioorganic and Medicinal Chemistry, 2021, vol. 34]
[2]Brana, M. F.; Castellano, J. M.; Moran, M.; Vega, M. J. Perez de; Qian, X. D.; et al. [European Journal of Medicinal Chemistry, 1995, vol. 30, # 3, p. 235 - 240]

7
[ 21814-48-2 ]
[ 105-83-9 ]
1,1'-<(methylimino)bis(3,1-propanediylimino)>bis<7-methoxy-4-nitro-9(10H)-acridinone> [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3043 - 3052

8
[ 105-83-9 ]
[ 99009-49-1 ]
1,1'-<(methylimino)bis(3,1-propanediylimino)>bis<7-hydroxy-4-nitro-9(10H)-acridinone> [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3043 - 3052

9
[ 105-83-9 ]
[ 166756-49-6 ]
[ 166756-69-0 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3043 - 3052

10
[ 105-83-9 ]
[ 20621-51-6 ]
1,1'-<(methylimino)bis(3,1-propanediylimino)>bis<4-nitro-9(10H)-acridinone> [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3043 - 3052

11
[ 105-83-9 ]
[ 5231-87-8 ]
[ 679427-49-7 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 2302 - 2308
[2]Chemical Communications,2007,p. 963 - 965
[3]Angewandte Chemie - International Edition,2006,vol. 45,p. 6844 - 6848
[4]Chemical Communications,2001,p. 1456 - 1457
[5]Journal of Medicinal Chemistry,2014,vol. 57,p. 987 - 999

12
[ 105-83-9 ]
[ 24424-99-5 ]
[ 87530-14-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	In tetrahydrofuran;	The synthesis of the receptors 1 and 2 (scheme 1) started with the coupling of two equivalents of the mono-BOC-protected N-methyl-N,N-di(3-aminopropyl)amine 6 with the diacid chlorides of either fumaric acid (for 1) or maleic acid (for 2). The synthesis of the mono-BOC-protected species was straightforward and the excess of amine starting material was recovered from aqueous waste by drying and distillation. The resulting intermediates (9 and 10) were subsequently deprotected using gaseous HCl and isolated as hydrochloride salts after purification by preparative gel permeation chromatography (Sephadex G-10, eluent water). The degree of protonation was established by potentiometric titrations, vide infra.
27%	In tetrahydrofuran; at 0 - 20℃; for 20h;	To a stirred solution of 3,3?-diamino-N-methyldipropylamine (22.0 g, 151.46 mmol) in THF (60 mE) cooled to 00 C. was added (l3oc)20 (10.9 g, 50.0 mmol) in THF (60 mE) over 2 h. Afier stirring for 18 h at room temperature, the mixture was concentrated to dryness in vacuo and the residue was partitioned between a saturated aqueous solution of NaC1 (200 mE), and CH2C12 (400 mE). The organic phase was further washed with saturated brine (200 mE), dried over Na2SO4 and concentrated to dryness. The crude material was purified by silica gel chromatography on a Siotage HorizonTM flash chromatography system using a gradient of 5-70% methanol in 5% Et3N/CH2C12 as the eluent to give 3 (10.1 g, 27%). ?H NMR (400 MHz, CDC13) oe 1.43 (s, 9H),1.62 (m, 4H), 2.26 (s, 3H), 2.38 (t, 4H), 2.45 (bs, 3H), 2.78 (t, 3H), 3.16 (m, 2H).
1.3 g	In tetrahydrofuran; at 0 - 20℃; for 16.33h;	To a solution of N1-(3-aminopropyl)-N1-methylpropane-l,3-diamine (5 g, 38.48 mmol) in THF (10 mL) at 0 C was added Boc anhydride (1.50 g, 6.89 mmol) dropwise over a period of 20 min and the resulting reaction mixture was stirred at room temperature for 16 h. THF was removed under reduced pressure and the resulting mixture was poured in water (50 mL). The aqueous mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with water, dried using anhydrous Na2S04 and concentrated under reduced pressure to get pure 2a (1.3 g, 15.4 %) as a colorless oil. NMR (400 MHz, d6-DMSO) delta 6.80- 6.79 ppm (1H, d, J=4 Hz), 3.17 (3H, broad s) 2.94-2.89ppm (2H, dd, 7=12.4, 6 Hz), 2.51 ppm (2H, broad s), 2.28-2.21ppm (4H, m), 2.08-2.07 (2H, d, 7=4 Hz), 1.50-1.44 ppm (4H, m), 1.37 (9H, s); MS (ESI-MS): m/z calcd for Ci2H26N202 [MH]+246.21,

1.3 g

In tetrahydrofuran; at 0 - 20℃; for 16.3333h;

To a solution of N?-(3-aminopropyl)-N?-methylpropane-1,3-diamine (5 g, 38.48 mmol) in THF (10 mL) at 0 C was added Boc anhydride (1.50 g, 6.89 mmol) dropwise over a period of 20 mm and the resulting reaction mixture was stirred at room temperature for 16 h. THF was removed under reduced pressure and the resulting mixture was poured in water (50 mL). The aqueous mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with water, dried using anhydrous Na2SO4 and concentrated under reduced pressure to get pure 2a (1.3 g, 15.4%) as a colorless oil. ?HNMR (400 IVIHz, d6-DMSO) 6.80- 6.79 ppm (1H, d, J=4 Hz), 3.17 (3H, broad s) 2.94-2.89ppm (2H, dd, J=12.4, 6 Hz), 2.51 ppm (2H, broad s), 2.28-2.2lppm (4H, m), 2.08-2.07 (2H, d, J4 Hz), 1.50-1.44 ppm (4H, m), 1.37 (9H, s); MS (ESI-MS): m/z calcd for C,2H26N202 [MH]246.21, No mass response observed.

Reference： [1]Chemical Communications,2007,p. 3039 - 3041
[2]Patent: US2008/221218,2008,A1 .Location in patent: Page/Page column 6
[3]Journal of the American Chemical Society,2011,vol. 133,p. 20288 - 20300
[4]ChemBioChem,2016,vol. 17,p. 506 - 514
[5]Bioorganic and Medicinal Chemistry,2002,vol. 10,p. 19 - 29
[6]Patent: US10201587,2019,B2 .Location in patent: Page/Page column 41; 42; 43; 44
[7]Angewandte Chemie - International Edition,2011,vol. 50,p. 4675 - 4679
[8]Patent: WO2017/136450,2017,A2 .Location in patent: Paragraph 00375; 00376
[9]Patent: WO2018/6074,2018,A2 .Location in patent: Paragraph 00435; 00436

13
[ 105-83-9 ]
[ 41840-28-2 ]
[ 87530-14-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	In 1,4-dioxane at 20℃; for 9h;	2.11. Synthesis of [3-[3-(Aminopropyl)methylamino]propyl]carbamic acid tert-butyl ester (9) 9 was synthesized according to the previous report [10], N,N′ -bis(3-aminopropyl)methylamine (24.8 mL, 166 mmol) was dissolved indioxane (200 mL) and S-Boc-2-mercapto-4,6-dimethylpyrimidine (10 g,42 mmol) in dioxane (160 mL) was added dropwise to this solution. Theprecipitate that formed during the dropwise addition was taken up in asmall amount of water. After stirring for 9 h, the water was evaporatedunder reduced pressure. A saturated saline solution (140 mL) was addedto the residue, followed by extraction with ethyl acetate (50 mL). Theorganic phase was dried over anhydrous MgSO4 and evaporated underreduced pressure to give 9 as a yellow viscous oil (9.7 g, 40 mmol, 95%yield). 1H NMR (500 MHz, CDCl3): δ = 1.44 (9H, s, t-Bu), 1.60-1.65 (4H,m, CH2CH2CH2N(CH3)CH2CH2CH2), 2.19 (3H, s, CH2N(CH3)CH2),2.37-2.40 (4H, m, CH2N(CH3)CH2), 2.74 (2H, t, J = 5.9 Hz, H2NCH2),3.18 (2H, q, J = 5.9 Hz, CH2NHCO), and 5.42 (1H, br, NHCO) ppm (Fig.S16). HRMS (EI+) m/z [M]+ Calcd for C12H28N3O2 246.21815, found246.21785.
32%	In 1,4-dioxane at 20℃; for 20h;
25%	In 1,4-dioxane

In 1,4-dioxane

Reference： [1]Kaneyoshi, Shuma; Eguchi, Nao; Fujimoto, Kazuhisa; Fujii, Satoshi; Sato, Shinobu; Takenaka, Shigeori [Journal of Inorganic Biochemistry, 2022, vol. 230]
[2]Mukumoto, Kosuke; Nojima, Takahiko; Takenaka, Shigeori [Tetrahedron, 2005, vol. 61, # 49, p. 11705 - 11715]
[3]Sato, Shinobu; Fujii, Satoshi; Yamashita, Kenichi; Takagi, Makoto; Kondo, Hiroki; Takenaka, Shigeori [Journal of Organometallic Chemistry, 2001, vol. 637-639, p. 476 - 483]
[4]Takeuchi, Ryusuke; Zou, Tingting; Wakahara, Daiki; Nakano, Yoshifumi; Sato, Shinobu; Takenaka, Shigeori [Chemistry - A European Journal, 2019, vol. 25, # 37, p. 8691 - 8695]

14
[ 105-83-9 ]
1-Chloro-7-nitro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid (2-dimethylamino-ethyl)-amide [ No CAS ]
C₄₃H₅₁N₁₁O₈ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3109 - 3115

15
[ 105-83-9 ]
[ 16865-11-5 ]
N-(5,6-dichloro-1H-benzoimidazol-2-yl)-N'-[3-(5,6-dichloro-1H-benzoimidazol-2-ylamino)-propyl]-N'-methyl-propane-1,3-diamine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1669 - 1672

16
[ 67692-91-5 ]
[ 105-83-9 ]
[ 637033-04-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 48h;	2,2, 2-Trifluoro-N-[3-(methyl{3-[(1-oxido-1, 2, 4-benzotriazin-3- yl) amino] propyl} amino) propyl] acetamide [(38).] A solution of chloride 3 (2.07 g, 11.4 mmol), [NL- (3-AMINOPROPYL) NL-METHYL-1, 3-PROPANEDIAMINE (3. 31] g, 22.8 mmol) and Et3N (3.2 mL, 22.8 mmol) in DCM (200 mL) was stirred at [20 C] for 2 d. The solvent was evaporated and the residue dissolved in [MECN] (150 mL). Ethyl trifluoroacetate (5.4 mL, 45.6 mmol) and water (0.8 mL, 45.6 mmol) added and the solution heated at reflux temperature for 16 h. The solvent was evaporated, and the residue purified by chromatography, eluting with a gradient [(0-1%) OFET3N/ (0-10%)] MeOH/DCM, followed by further chromatography, eluting with 10% MeOH/DCM, to give 1-oxide 38 (1.89 g, [43%)] as a yellow solid, mp (DCM) [111-115 C ; 1H] NMR 8 9.04 (br s, 1 H, NH), 8.25 (dd, [J=] 8.7, 1.4 Hz, 1 H, H [8'),] 7.70 (ddd, [J='8.] 4,7. 1,1. 4 Hz, 1 H, H-6'), 7.57 (d, [J=8. 4HZ, LH,] H-5'), 7.29 (ddd, [J= 8.] 7,7. 1, [1.] 1 Hz, 1 H, H- 7'), 6.17 (br s, 1 H, NH), 3. [58] (dd, J= 6.6, 5.8 Hz, 2 H, CH2N), 3.49 (br t, [J =] 6.0 Hz, 2 H, CH2N), 2.52-2. 58 (m, 4 H, 2 x [CH2N),] 2.27 (s, 3 H, [NCH3),] 1. [84-1.] 90 [(M,] 2 H, CH2), 1.75-1. 82 (m, [2 H, CH2) ;"C NMR 8 158.] 9,157. 3 [(Q,] [J= 36 HZ),] 148. 8, 135.6, 130.8, 126.4, 124.9, 120.4, 116.1 [(Q,] J= [288] Hz), 57.1, 56.4, 41.3, 40.3 (2), 26.3, 24.4 ; MS (FAB+) m/z 387 (MH+, 100%), [371] (8), [338 (30)] ; HRMS (FAB+) calcd for [C16H22F3N602] 2 m/z 387.1756, found [387.] 1765. Anal. calcd for [CI6H2IF3N602'MEOH] : C, 49.2 ; H, 5. [8] ; N, 20.9 ; found: C, 49.1 ; H, 5.5 ; N, 20.7%.

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 475 - 488
[2]Patent: WO2004/26846,2004,A1 .Location in patent: Page 74; 75

17
[ 105-83-9 ]
[ 16695-22-0 ]
[ 655260-65-4 ]

Reference： [1]Heterocycles,2004,vol. 62,p. 279 - 296

18
[ 105-83-9 ]
[ 160657-05-6 ]
N-(8-chloro-pyrrolo[1,2-a]quinoxalin-4-yl)-N'-[3-(8-chloro-pyrrolo[1,2-a]quinoxalin-4-ylamino)-propyl]-N'-methyl-propane-1,3-diamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1997 - 2009

19
[ 105-83-9 ]
[ 160657-08-9 ]
N-(7-methoxy-pyrrolo[1,2-a]quinoxalin-4-yl)-N'-[3-(7-methoxy-pyrrolo[1,2-a]quinoxalin-4-ylamino)-propyl]-N'-methyl-propane-1,3-diamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1997 - 2009

20
[ 105-83-9 ]
[ 687638-14-8 ]
N-(8-methoxy-pyrrolo[1,2-a]quinoxalin-4-yl)-N'-[3-(8-methoxy-pyrrolo[1,2-a]quinoxalin-4-ylamino)-propyl]-N'-methyl-propane-1,3-diamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1997 - 2009

21
[ 105-83-9 ]
[ 6025-69-0 ]
methylbis[3-({pyrrolo[1,2-a]quinoxalin-6-yl}amino)propyl]amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1997 - 2009
[2]European Journal of Medicinal Chemistry,2012,vol. 55,p. 335 - 345,11

22
[ 75-77-4 ]
[ 105-83-9 ]
N-methyl-N'-trimethylsilanyl-N-[3-(trimethylsilanyl-amino)-propyl]-propane-1,3-diamine [ No CAS ]

Reference： [1]Chemical Communications,2005,p. 113 - 115

23
[ 105-83-9 ]
[ 576-83-0 ]
N-methyl-N'-(2,4,6-trimethyl-phenyl)-N-[3-(2,4,6-trimethyl-phenylamino)-propyl]-propane-1,3-diamine [ No CAS ]

Reference： [1]Chemical Communications,2005,p. 113 - 115

24
[ 105-83-9 ]
[ 358-23-6 ]
N,N-bis[(trifluoromethanesulfonamido)propyl]methylamine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2000,vol. 122,p. 9318 - 9319

25
[ 105-83-9 ]
[ 5651-60-5 ]
bis{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propyl}methylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	In chloroform; for 48h;Heating / reflux;	Bis{(5.6-dihydro-5,l l-diketo-l lH-indeno[l,2-c]isoquinoline)-6- propyl}methylamine (12d). 3,3 '-Diamino-N-methyl dipropylamine (1 Id) (0.1O g, 0.69 mmol) was added to a stirred solution of indenobenzopyran 4d (0.38 g, 1.52 mmol) in C?CI3 (150 mL) and the reaction mixture was stirred under reflux for 48 h. The reaction mixture was cooled to room temperature and purified by flash column chromatography (SiO2/CHCl3 to 5% MeOH in CHCl3) to provide bisindenoisoquinoline 12d (340 mg, 82%) as a red solid: mp 230-232 C. 1H NMR (CDCl3) ? 8.67 (d, J= 8.1 Hz, 2 H), 8.30 (d, J= 7.6 Hz, 2 H), 7.72-7.66 (dt, J= 8.3 and 2.8 Hz, 4 H), 7.59 (d, J= 7.1 Hz, 2 H), 7.48-7.40 (q, J= 7.5 Hz, 4 H), 7.33 (t, J =7.3 Hz, 2 H), 4.63 (t, J= 8.0 Hz, 4 H), 2.66 (t, J= 6.5 Hz, 4 H), 2.37 (s, 3 H), 2.13-2.04 (m, 4 H); ESIMS m/z (rel intensity) 606 (MH+, 100). Anal. Calcd for C39H3 ,N3O4'0.4 CHCl3: C, 72.42; H, 4.84; N, 6.43. Found: C, 72.67; H, 5.05; N, 6.32.

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 5129 - 5140
[2]Patent: WO2007/59008,2007,A2 .Location in patent: Page/Page column 50

26
[ 105-83-9 ]
[ 68282-47-3 ]
N-methyl-N'-(2-phenyl-1H-imidazol-4-ylmethylene)-N-{3-[(2-phenyl-1H-imidazol-4-ylmethylene)-amino]-propyl}-propane-1,3-diamine [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2000,vol. 342,p. 177 - 184

27
[ 105-83-9 ]
[ 49584-26-1 ]
[ 950857-70-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 5h;	4-Cyanobenzene-1-sulfonyl chloride (4.0 g, 19.8 mmol) was added to a solution of 3,3'-diamino-/V-methyldipropylamine (1.66 ml, 9.9 mmol) and triethylamine (3.0 ml, 21.6 mmol) in DMF (15 ml) at RT under nitrogen then stirred for 5 h. The mixture was poured into water (250 ml) and extracted with EtOAc (3 x 100 ml). The extracts were washed with water (2 x 100 ml) and brine (50 ml) before the organic phase was isolated, dried (MgSO4), filtered and concentrated. The crude product was triturated using cyclohexane, filtered and dried to afford the desired compound as a white solid. Yield: 2.69 g (57%)LC-MS (Method 2): Rt 2.31 min, m/z 476 [MH+]
57%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 5h;	4-Cyanobenzene-1-sulfonyl chloride (4.0 g, 19.8 mmol) was added to a solution of 3,3'-diamino-lambda/-methyldipropylamine (1.66 ml, 9.9 mmol) and triethylamine (3.0 ml, 21.6 mmol) in DMF (15 ml) at RT under nitrogen then stirred for 5 h. The mixture was poured into water (250 ml) and extracted with EtOAc (3 x 100 ml). The extracts were washed with water (2 x 100 ml) and brine (50 ml) before the organic phase was isolated, dried (MgSO4), filtered and concentrated. The crude product was triturated using cyclohexane, filtered and dried to afford Intermediate 26 as a white solid. Yield: 2.69 g (57%) LC-MS (Method 2): Rt 2.31 min, m/z 476 [MH+]

Reference： [1]Patent: WO2009/37413,2009,A1 .Location in patent: Page/Page column 19
[2]Patent: WO2007/107706,2007,A2 .Location in patent: Page/Page column 31

28
[ 956487-29-9 ]
[ 105-83-9 ]
[ 956487-30-2 ]

Yield	Reaction Conditions	Operation in experiment
43%	With sodium hydrogencarbonate; In acetonitrile; at 80℃; for 3.5h;	A solution of Intermediate 35 (467 mg, 0.751 mmol) in acetonitrile (15 ml) was treated with ?/,?/-<strong>[105-83-9]bis(3-aminopropyl)methylamine</strong> (54 mg, 0.375 mmol) and sodium hydrogen carbonate (252 mg, 3.00 mmol). The reaction was heated at 80sC for 3.5 h. After allowing the mixture to cool, it was filtered and the filtrate evaporated. Chromatography using an Isolute Si Il cartridge (10 g), and eluting with 1-20% MeOH in EtOAc, gave the pure product as a white solid. Yield: 182 mg (43%) LC-MS (Method 2): Rt = 3.22 min, m/z = 1136 [M+Hf
43%	With sodium hydrogencarbonate; In acetonitrile; at 80℃; for 3.5h;	A solution of Intermediate 35 (467 mg, 0.751 mmol) in acetonitrile (15 ml) was treated with lambda/,lambda/-<strong>[105-83-9]bis(3-aminopropyl)methylamine</strong> (54 mg, 0.375 mmol) and sodium hydrogen carbonate (252 mg, 3.00 mmol). The reaction was heated at 809C for 3.5 h. After allowing the mixture to cool, it was filtered and the filtrate evaporated. Chromatography using an Isolute Si Il cartridge (10 g), and eluting with 1-20% MeOH in EtOAc, gave the pure product as a white solid. Yield: 182 mg (43%) LC-MS (Method 2): Rt = 3.22 min, m/z = 1136 {M+H]+

Reference： [1]Patent: WO2009/13444,2009,A1 .Location in patent: Page/Page column 31
[2]Patent: WO2007/129060,2007,A1 .Location in patent: Page/Page column 31

29
[ 5900-58-3 ]
[ 124-09-4 ]
[ 5162-44-7 ]
[ 446-48-0 ]
[ 7209-38-3 ]
[ 74-96-4 ]
[ 4784-77-4 ]
[ 22288-78-4 ]
[ 542-69-8 ]
bromomethyl resin [ No CAS ]
9-fluorenyl-methoxycarbonyl-cyclohexyl alanine [ No CAS ]
[ 462-94-2 ]
[ 1458-98-6 ]
[ 78-77-3 ]
[ 1809-10-5 ]
[ 110-53-2 ]
[ 592-55-2 ]
[ 7328-91-8 ]
[ 871-76-1 ]
[ 105-83-9 ]
[ 144-48-9 ]
[ 929-59-9 ]
[ 107-59-5 ]
[ 5324-30-1 ]
[ 5428-54-6 ]
[ 27129-86-8 ]
[ 2417-72-3 ]
[ 2581-34-2 ]
[ 554-84-7 ]
[ 3385-21-5 ]
[ 126-38-5 ]
[ 636-93-1 ]
[ 88-30-2 ]
[ 620-13-3 ]
[ 823-78-9 ]
[ 5035-82-5 ]
[ 29022-11-5 ]
[ 539-48-0 ]
[ 35661-39-3 ]
[ 26759-46-6 ]
[ 20439-47-8 ]
[ 2615-25-0 ]
[ 6393-01-7 ]
[ 5372-81-6 ]
[ 35661-40-6 ]
[ 100-39-0 ]
[ 611-17-6 ]
[ 23915-07-3 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 2592-95-2 ]
[ 18880-00-7 ]
[ 88681-68-9 ]
[ 100063-22-7 ]
[ 75-03-6 ]
[ 106-94-5 ]
[ 104-81-4 ]
[ 589-10-6 ]
[ 107-15-3 ]
[ 109-76-2 ]
[ 110-60-1 ]
[ 7051-34-5 ]
[ 106-95-6 ]
[ 622-95-7 ]
[ 589-15-1 ]
[ 134-20-3 ]
[ 2550-36-9 ]
[ 89-92-9 ]
[ 456-41-7 ]
[ 766-80-3 ]
[ 459-46-1 ]
[ 874-98-6 ]
[ 402-49-3 ]
[ 870-63-3 ]
[ 85118-01-0 ]
[ 22115-41-9 ]
[ 3958-57-4 ]
[ 100-11-8 ]
[ 107-82-4 ]
[ 6482-24-2 ]
[ 3132-64-7 ]
[ 112883-41-7 ]
[ 3433-80-5 ]
[ 52727-57-8 ]
C₁₈H₁₅N₂O₃PolS [ No CAS ]
C₂₀H₂₀N₃OPolS [ No CAS ]
C₂₃H₁₉N₂O₂PolS [ No CAS ]
C₁₈H₂₃ClN₃OPolS [ No CAS ]
C₂₂H₂₆N₃OPolS [ No CAS ]
C₂₂H₂₃N₂O₅PolS [ No CAS ]
C₂₀H₂₆ClN₂O₃PolS [ No CAS ]
C₂₃H₂₂ClN₂O₃PolS [ No CAS ]
C₂₀H₂₁FN₃O₃PolS [ No CAS ]
C₂₂H₂₉N₂O₃PolS [ No CAS ]
C₂₁H₂₈N₃O₃PolS [ No CAS ]
C₁₉H₂₆N₃O₄PolS₂ [ No CAS ]
C₂₂H₃₀N₃OPolS [ No CAS ]
C₂₁H₂₈N₃O₄PolS [ No CAS ]
C₂₆H₂₆N₃OPolS [ No CAS ]
C₂₃H₁₅ClF₃N₂O₂PolS [ No CAS ]
C₂₄H₂₂N₃O₃PolS [ No CAS ]
C₂₃H₁₆ClF₂N₂O₂PolS [ No CAS ]
C₂₂H₂₂Br₂N₃OPolS [ No CAS ]
C₂₄H₂₆FN₂O₅PolS [ No CAS ]
C₂₅H₂₂FN₂O₄PolS [ No CAS ]
C₂₆H₂₂N₃O₄PolS [ No CAS ]
C₂₅H₂₅ClN₃O₃PolS [ No CAS ]
C₂₅H₁₈ClF₂N₂O₃PolS [ No CAS ]
C₂₉H₂₆N₃O₃PolS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS);	EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...

Reference： [1]Patent: US2004/102629,2004,A1 .Location in patent: Page 16-18

30
C₃₈H₃₂Cl₂N₁₂O₁₀S₂^(2-)*2Na⁽¹⁺⁾ [ No CAS ]
[ 105-83-9 ]
C₅₂H₇₀N₁₈O₁₀S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		18.8 G (0.13 mol) of N, N-bis (3-aminopropyl) METHYLAMINE in 100 ML of water and 100 ML of dioxane are introduced into a 350 ml sulfonation flask equipped with a condenser and pH meter. At 70-75C, 22.7 G (0.021 mol) of the intermediate of formula (105a) prepared according to Example 1. 6 are introduced. The yellow solution is stirred for 3 h at 86-88C. After cooling to 70C, the solution is then diluted with 120 ml of water and adjusted to pH 4.5 with 35 ml of conc. hydrochloric acid. After addition of 100 ML of acetone, the precipitate is filtered through a suction filter, washed with water and dried IN VACUO at 70C. Yield : 28.7 G

Reference： [1]Patent: WO2005/19189,2005,A1 .Location in patent: Page/Page column 17

31
[ 105-83-9 ]
[ 110-21-4 ]
[ 81779-01-3 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; water;	EXAMPLE 10 72.5 g of bis-(3-aminopropyl)-methylamine and 120 g of hydrazodicarbonamide are stirred in 300 ml of N-methyl pyrrolidone for 2 hours at 175 C. and for 3 hours at 200 C. The reaction product is concentrated in vacuo, dissolved in water and precipitated with isopropanol giving a colourless product which could not be crystallized. For characterisation and purification, the product is dissolved in water, the resulting solution is adjusted to pH 2 with concentrated HCl and subsequently concentrated in vacuo. The residue is recrystallized from ethanol, giving 112 g (65% of the theoretical) of bis-[3-(3,5-dioxo,1,2,4-triazolidin-4-yl)-propyl]-methylamine hydrochloride in the form of colourless crystals melting at 238 C. IR (KBr): 1763, 1698 cm-1 (C=O)

Reference： [1]Patent: US4386213,1983,A

32
[ 1871-76-7 ]
[ 105-83-9 ]
N-(3-{Methyl-13-(N'-cyano-N"-pyridin-4-yl-guanidino)propyl]-amino}-propyl)-2,2-diphenyl-acetamide [ No CAS ]
3-amino-3'-diphenylacetylamino-N-methyldipropylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In pyridine;	EXAMPLE 19 N-(3-{Methyl-13-(N'-cyano-N"-pyridin-4-yl-guanidino)propyl]-amino}-propyl)-2,2-diphenyl-acetamide (SBR-11-4491) was synthesised as follows To a solution of 3,3'-diamino-N-methyldipropylamine (3.05 g, 21.0 mmol, 7.0 equiv.) in 10 mL pyridine at room temperature was added slowly diphenylacetyl chloride (0.692 g, 3.0 mmol, 1.0 equiv.). The reaction mixture was stirred at room temperature overnight, diluted with 100 mL EtOAc, and washed with 3*40 mL water to wash away excess starting material. The organic layer was washed with 30 mL brine, dried over K2CO3, and concentrated to yield 3-amino-3'-diphenylacetylamino-N-methyldipropylamine as viscous yellow oil (crude 0.82 g, 80%, 2.40 mmol). [M+H] calculated: 340.24, found: 340.2.

Reference： [1]Patent: US6255323,2001,B1

33
[ 105-83-9 ]
[ 2251-50-5 ]
[ 918776-74-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; In chloroform;	EXAMPLES; Synthesis of crosslinkers:; Synthesis of I:; 3,3'-diamino-N-methyldipropylamme (0.29 mL,1.79 mmol, Aldrich) and triethylamine (0.55 mL, 3.93 mmol, Aldrich) were dissolved in 40 mL anhydrous CHCl3 and added dropwise to perfluorobenzoyl chloride (0.54 mL, 3.93 mmol, Aldrich) in another 40ml anhydrous CHCl3. The white precipitate of triethylammonium chloride by-product was filtered off, the filtrate washed with 3x25 mL of half-saturated NaCl solution, then dried with MgSO4, and evaporated to give N-methyl-N,N-dipropylene bis(pentafiuorobenzamide) as colorless liquid (yield, 75%). This was then dissolved (777 mg, 1.34 mmol) in 3.2 mL acetone and reacted with 10% excess sodium azide (192 mg, 2.95 mmol) dissolved in 1.5 mL water and 3 mL acetone, under reflux for 5-8hours. Excess acetone was added, the white precipitate of NaF was filtered off, and the yellow filtrate washed with 3x25 mL of half saturated NaCl solution, dried with MgSO4, and evaporated to give N-methyl-LambdaxiJV-dipropylene bis(4-azido-2,3,5,6-tetrafluorobenzamide) as a pale yellow solid (yield, 65%). This was then dissolved (505 mg, 0.87 mmol) in 10 mL anhydrous CHCl3, and reacted with excess iodomethane (5 mL, 80.3 mmol) overnight at room temperature. The fine pale yellow precipitate was filtered off and recrystallized twice in water to give N,N-dimethyl-izetaN-dipropylene bis(4-azido-2,3,5,6- tetrafluorobenzamide) ammonium iodide (I) as pale yellow crystals (yield, 55%). 1H NuMR (ppm, MeOD) = 4.56 (s), 3.50 (t, J=6.6Hz, 2H), 3.42 (m, 2H), 3.15 (s, 3H), 2.12 (m, 2H). 19F NuMR (ppm, MeOD) = -68.35 (d, J=25Hz), -76.97 (d, J=24Hz). FTIR (cm" l) = 3300 (NH), 3078 (NH), 3032 (NH), 2968 (CH3), 2942 (CH2), 2885 (CH2), 2157- 2129 (N3), 1658 (CO), 1549 (CONH), 1486 (N3), 1437 (CH2), 1407 (CH3, CH2), 1338 (N3), 1278 (N3), 1024, 1000, 989.

Reference： [1]Patent: WO2007/4995,2007,A1 .Location in patent: Page/Page column 25

34
[ 864228-16-0 ]
[ 105-83-9 ]
C₄₇H₄₃F₆N₉O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2.5h;	Example 5; Intermediate 4 (117 g, 0.292 mmol), 3,3'-diamino-N-methyldipropylamine (21 mg, 0.146 mmol) and DIPEA (254 mul, 1.46 mmol) were dissolved in DMF (6 ml). HATU (133 mg, 0.350 mmol) was added and the solution was allowed to stand at RT for 2.5 h. The DMF was evaporated and the residue was dissolved in EtOAc (100 ml). The organic solution was washed with aqueous NaHCO3 (60 ml), water (50 ml) and brine (40 ml). After drying (Na2SO4), the solvent was removed and the crude product was purified using HPLC (System 1). Yield: 38 mg (14%) LC-MS (Method 1): Rt 7.92 min, m/z 912.23 [MH+]

Reference： [1]Patent: WO2006/136857,2006,A1 .Location in patent: Page/Page column 34

35
[ 14220-65-6 ]
[ 105-83-9 ]
[ 15391-24-9 ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1981,p. 1504 - 1514

36
[ 105-83-9 ]
[ 6147-53-1 ]
[ 90-02-8 ]
[ 15391-24-9 ]

Reference： [1]Journal of the American Chemical Society,1980,vol. 102,p. 6014 - 6019

37
sodium hexaflorophosphate [ No CAS ]
copper(II) nitrate monohydrate [ No CAS ]
[ 105-83-9 ]
[ 68282-53-1 ]
[Cu(CH₃N(C₃H₆NCHC₃H₂N₂CH₃)2)]⁽²⁺⁾*2PF₆^(1-)=[Cu(CH₃N(C₃H₆NCHC₃H₂N₂CH₃)2)](PF₆)2 [ No CAS ]

Reference： [1]Journal of the Chemical Society. Dalton Transactions (2001),2001,p. 845 - 849

38
[ 7791-07-3 ]
copper(II) nitrate monohydrate [ No CAS ]
[ 105-83-9 ]
[ 68282-53-1 ]
[Cu(CH₃N(C₃H₆NCHC₃H₂N₂CH₃)2)]⁽²⁺⁾*2ClO₄^(1-)*H₂O=[Cu(CH₃N(C₃H₆NCHC₃H₂N₂CH₃)2)](ClO₄)2*H₂O [ No CAS ]

Reference： [1]Journal of the Chemical Society. Dalton Transactions (2001),2001,p. 845 - 849

39
copper(II) choride dihydrate [ No CAS ]
[ 105-83-9 ]
sodium perchlorate [ No CAS ]
[ 68282-47-3 ]
[Cu(N,N'-bis((2-phenylimidazol-4-yl)methylene)-3,3-diaminodipropylmethylamine)](ClO₄)2 * 0.5 H₂O [ No CAS ]

Reference： [1]Inorganic Chemistry,1999,vol. 38,p. 3513 - 3522

40
ethyl (4R)-6-(bromomethyl)-4-(4-cyanophenyl)-2-oxo-1-[3-(trifluoromethyl)-phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate [ No CAS ]
[ 105-83-9 ]
[ 956486-48-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In tetrahydrofuran; at 20℃; for 17.5h;	Intermediate 26Intermediate 5 (108.6 g, 0.217 mol) was dissolved in THF (1500 ml) and triethylamine (240 ml, 1.74 mol) was added, followed by a solution of lambda/,lambda/-bis(3- aminopropyl)methylamine (23.55 g, 0.162 mol) in THF (100 ml) dropwise over 30 min. The reaction was stirred at RT for 17 h and the volume was reduced to 300-400 ml. Water (3000 ml) was added and the mixture was stirred vigorously for 90 min. The supernatant was decanted off and a further amount of water (3000 ml) was added. Stirring was continued for 30 min. The water was decanted off and the remaining solid was dissolved in EtOAc (1500 ml). The solution was dried(Na2SO4), evaporated to a small volume, and poured into Et2O with vigorous stirring. The white precipitate was filtered off and washed with Et2O and dried in vacuo.Yield: 86.0 g (88%)Further purification was achieved by crystallization from either n-butanol or n- propanol.LC-MS (Method 4): Rt = 7.88 min, m/z = 908.44 [M+H]+
88%	With triethylamine; In tetrahydrofuran; at 20℃; for 17.5h;	Intermediate 5 (108.6 g, 0.217 mol) was dissolved in THF (1500 ml) and triethylamine (240 ml, 1.74 mol) was added, followed by a solution of /V,lambda/-bis(3- aminqpropyl)methylamine (23.55 g, 0.162 mol) in THF (100 ml) dropwise over 30 min.The reaction was stirred at RT for 17 h and the volume was reduced to 300-400 ml.Water (3000 ml) was added and the mixture was stirred vigorously for 90 min. The supernatant was decanted off and a further amount of water (3000 ml) was added. Stirring was continued for 30 min. The water was decanted off and the remaining solid was dissolved in EtOAc (1500 ml). The solution was dried (Na2SO4), evaporated to a small volume, and poured into Et2O with vigorous stirring. The white precipitate was filtered off and washed with Et2O and dried in vacuo.Yield: 86.0 g (88%) Further purification was achieved by crystallization from either n-butanol or n-propanol.LC-MS (Method 4): Rt = 7.88 min, m/z = 908.44 [M+H]+

Reference： [1]Patent: WO2009/60158,2009,A1 .Location in patent: Page/Page column 23
[2]Patent: WO2009/60206,2009,A1 .Location in patent: Page/Page column 31

41
[ 105-83-9 ]
[ 265312-60-5 ]
[ 890649-32-8 ]

Yield	Reaction Conditions	Operation in experiment
36%	In ethanol; at 60℃; for 2h;	Example 1 5.5'-[(methylimino)bis(propane-3,1-diylimino)]bis(2-methyl-1,3-benzothiazole-4,7-dione) 83.4 mg (0.57 mmol; 0.6 equivalents) of N-(3-aminopropyl)-N-methylpropane-1,3-diamine are added to 200 mg (0.95 mmol) of 5-methoxy-2-methyl-4,7-dioxobenzothiazole in solution in 15 ml of anhydrous ethanol. The reaction mixture is stirred at 60 C. for 2 hours, then the solvent is evaporated off under reduced pressure. The residue is purified on a silica column (eluent: methanol at 3% in dichloromethane) and 30 mg (yield=36%) of expected product is obtained in the form of a red powder. Melting point: 94-96 C. NMR 1H (DMSO d6, 400 MHz, delta): 7.93 (t, 2H, 2NH); 5.40 (s, 2H, 2CH); 3.20-3.15 (m, 4H); 2.72 (s, 6H, 2CH3); 2.40-2.37 (m, 4H); 2.17 (s, 3H, CH3); 1.76-1.73 (m, 4H). MS-LC: MH+=500.15; r.t.=7.49 min.

Reference： [1]Patent: US2009/275624,2009,A1 .Location in patent: Page/Page column 16-17

42
[ 105-83-9 ]
5-methoxy-1,3-benzothiazol-4,7-dione [ No CAS ]
[ 1346864-08-1 ]

Yield	Reaction Conditions	Operation in experiment
26%	In ethanol; at 85℃; for 1.5h;	25.4) 5.5'-[(methylimino)bis(propane-3,1-diylimino)]bis(1,3-benzothiazole-4,7-dione) 57 mul (0.37 mmol; 0.48 equivalent) of N-(3-aminopropyl)-N-methylpropane-1,3-diamine is added to 150 mg (0.77 mmol) of 5-methoxy-1,3-benzothiazol-4,7-dione in solution in 6 ml of ethanol. The reaction mixture is maintained under stirring at 85 C. for 90 minutes, then the solvent is evaporated off under reduced pressure and the expected product is purified by chromatography on a silica column (eluent: dichloromethane/methanol mixture 94/6) and 95 mg (yield=26%) of 5.5'-[(methylimino)bis(propane-3,1-diylimino)]bis(1,3-benzothiazole-4,7-dione) is obtained in the form of a red powder. Melting point: 223-224 C. NMR 1H (DMSO d6, 400 MHz, delta): 9.28 (s, 2H); 8.02 (t, 2H, 2NH); 5.48 (s, 2H); 3.24-3.19 (m, 4H); 2.42-2.38 (m, 4H); 2.18 (s, 3H, CH3); 1.78-1.74 (m, 4H). MS-LC: MH+=472.19; r.t.=7.32 min.

Reference： [1]Patent: US2009/275624,2009,A1 .Location in patent: Page/Page column 19-20

43
[ 20485-43-2 ]
[ 105-83-9 ]
[ 57294-38-9 ]
[ 128293-64-1 ]
[ 77716-11-1 ]
[ 1186017-44-6 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 3910 - 3913

44
[ 105-83-9 ]
[ 1234366-99-4 ]
[ 1234368-02-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With triethylamine; In dichloromethane; at 20℃; for 3h;	To a solution of Nl-(3-aminopropyl)-Nl-methyIpropane-l,3-diamme (560 mg, 3.85 mmol) dissolved in DCM (20 mL), was added triethylamine (300 mg, 2 96 mmol) and 3-(6,8-dichloro-2-5 methyl-l,2,3,4-tetrahydroisoqumolin-4-yl)benzene-l-sulfonyl chloride (300 mg, 0.77 mmol). The resulting solution was stirred for 3 h at room temperature After removing the solvent, the resulting residue was diluted with EtOAc (50 mL), washed with water (2x10 mL) and d?ed over anhydrous sodium sulfate. The crude product was purified by Flash-Prep-HPLC with H2O MeOH (1.4) to afford 300 mg (74%) of N-(3-((3-0 ammopropyl)(methyl)armno)propyl)-3-(6,8-dichloro-2-methyl-l, 2,3,4- tetrahydroisoquinolin-4-yl)benzenesulfonamide as a yellow oil.

Reference： [1]Patent: WO2010/78449,2010,A2 .Location in patent: Page/Page column 319

45
[ 881890-07-9 ]
[ 105-83-9 ]
[ 1276655-59-4 ]

Yield	Reaction Conditions	Operation in experiment
16%	With sodium carbonate; mercury dibromide; In ethanol; toluene; at 135℃; for 2h;	General procedure: To a solution of 5 (173 mg, 0.5 mmol) in anhydrous dichloromethane (5 mL) was added 4 M HCl in 1,4-dioxane (5 mL) and the resulting mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated and the crude product hydrochloride was used in the next step without further purification. Alternatively, N-Me-N-(3-propylamino)propanediamine is also commercially available. A mixture of 2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-thione 16a19 (202 mg, 1 mmol), N-Me-N-(3-propylamino) propanediamine (0.08 mL, 0.5 mmol; alternatively 0.5 mmol of the hydrochloride obtained as described above), and sodium carbonate (318 mg, 3 mmol) was refluxed in ethanol (10 mL)/toluene (10 mL) in an 135 C oil bath, and finely grinded mercury(II) bromide (0.72 g, 0.2 mmol) was added. The mixture was heated and stirred vigorously for 2 h. The mixture was then filtered and the filtrate concentrated. The crude product obtained was purified by column chromatography (chloroform/methanol/ammonia, 7:1:0.1).

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1222 - 1235

46
[ 105-83-9 ]
[ 50441-50-4 ]
[ 1276655-57-2 ]

Yield	Reaction Conditions	Operation in experiment
36%	With sodium carbonate; mercury dibromide; In ethanol; toluene; at 135℃; for 2h;	To a solution of 5 (173 mg, 0.5 mmol) in anhydrous dichloromethane (5 mL) was added 4 M HCl in 1,4-dioxane (5 mL) and the resulting mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated and the crude product hydrochloride was used in the next step without further purification. Alternatively, N-Me-N-(3-propylamino)propanediamine is also commercially available. A mixture of 2,3-dihydropyrrolo[2,1-b]quinazoline-9(1H)-thione 16a19 (202 mg, 1 mmol), N-Me-N-(3-propylamino) propanediamine (0.08 mL, 0.5 mmol; alternatively 0.5 mmol of the hydrochloride obtained as described above), and sodium carbonate (318 mg, 3 mmol) was refluxed in ethanol (10 mL)/toluene (10 mL) in an 135 C oil bath, and finely grinded mercury(II) bromide (0.72 g, 0.2 mmol) was added. The mixture was heated and stirred vigorously for 2 h. The mixture was then filtered and the filtrate concentrated. The crude product obtained was purified by column chromatography (chloroform/methanol/ammonia, 7:1:0.1). The pure compound was obtained as a yellow grease (36 %). 1H NMR (CDCl3, 400 MHz) delta: 1.83-1.88 (m, 4H, CH3N(CH2CH2CH2N)2), 2.02-2.07 (m, 4H, 2 × NCH2CH2), 2.28 (s, 3H, NCH3), 2.56 (t, 4H, J = 7.62 Hz, 2 × N(CH3)CH2), 2.93 (t, 4H, J = 7.86 Hz, 2 × CH2C), 3.80 (t, 4H, J = 6.47 Hz, 2 × CH2N), 3.88 (t, 4H, J = 7.08 Hz, 2 × NCH2), 7.06-7.12 (m, 2H, 2 × C(7)H), 7.39-7.41 (m, 4H, 2 × C(6, 8)H), 8.03 (d, 2H, J = 8.26 Hz, 2 × C(5)H) ppm. 13C NMR (CDCl3, 400 MHz) delta: 18.71, 30.77, 32.83, 42.82, 48.23, 48.61, 55.57, 119.83 (arom), 123.81 (arom), 126.78 (arom), 128.05 (arom), 131.58 (arom), 145.33 (arom), 148.85 (arom), 160.17 (arom) ppm. ESI-MS m/z 482 [M+H]+. Elem. Anal. Calcd for (C29H35N7·0.3CH2Cl2·0.6CH3OH): C, 68.23; H, 7.28; N, 18.63. Found: C, 67.88; H, 7.45; N, 18.72.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1222 - 1235

47
[ 13139-17-8 ]
[ 105-83-9 ]
[ 1307864-23-8 ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform; at 20℃; for 16h;	a) Compound 11a[0271] A solution of N,N-bis(3-aminopropyl)methyl amine (lg, 6.9 mmoles) in chloroform (40 mL) was treated with benzyloxycarbonylsuccimmide (3.78 g, 2.2 equivalents). The reaction was stirred at room temperature for 16 hours. TLC analysis on silica of the reaction mixture using 15% methanol in ethyl acetate showed the formation of a polar product in a clean reaction. The reaction mixture was diluted with chloroform (40 mL) and washed with saturated aqueous sodium bicarbonate solution. It was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford a viscous oil that solidified upon storage to a waxy solid. Yield = 3.2 g; MALDI-TOF MS 414.4 observed.
	In chloroform; at 20℃; for 16h;	Example 8[0220] Synthesis of Z-diamine, compound 8c and Z-Di-NHS, compound 8d; [0221] a) Compound 8a[0222] A solution of N,N-bis(3-aminopropyl)methyl amine (lg, 6.9 mmoles, TCI) in chloroform (40 mL) was treated with benzyloxycarbonylsuccinimide (3.78 g, 2.2 equivalents). The reaction was stirred at room temperature for 16 hours. TLC analysis on silica of the reaction mixture using 15% methanol in ethyl acetate showed the formation of a polar product in a clean reaction. The reaction mixture was diluted with chloroform (40 mL) and washed with saturated aqueous sodium bicarbonate solution. It was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford a viscous oil that solidified upon storage to a waxy solid. Yield = 3.2 g; MALDI-TOF MS 414.4 observed.

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5092 - 5103
[2]Patent: WO2011/60228,2011,A1 .Location in patent: Page/Page column 66-67
[3]Patent: WO2011/146595,2011,A2 .Location in patent: Page/Page column 57

48
[ 105-83-9 ]
[ 162758-35-2 ]
[ 1338604-44-6 ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In tetrahydrofuran; at 20℃; for 16h;	N-{3-[(3-ammopropyl)(methyl)amino]propyl}-5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4- methyl-lH-pyrazole-3-carboxamide: H NMR (300 MHz, CHLOROFORM- ) d ppm 1.53 - 1.69 (m, 2 H) 1.77 (t, J=6.62 Hz, 2 H) 2.15 - 2.23 (m, 3 H) 2.34 - 2.50 (m, 7 H) 2.66 - 2.75 (m, 2 H) 3.45 - 3.53 (m, 2 H) 7.03 - 7.09 (m, 2 H) 7.23 - 7.35 (m, 3 H) 7.43 (dd, J=2.05, 0.54 Hz, 1 H) 7.75 (t, J=5.37 Hz, 1 H).; Benzotriazole-l-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) (leq) was added to a solution of 5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4-methyl-lH-pyrazole-3- carboxylic acid (1 eq), and diamine (5 eq) in tetrahydrofuran (THF). The reaction mixture was stirred for 16 h. Ethyl acetate was added and the solution was washed with 2 N sodium hydroxide and brine. The organic layer was dried with magnesium sulfate. The solution was then filtered and concentrated in vacuo. The crude reaction material was then purified by silica gel column chromatography using 0-100% CMA 80/efhyl acetate to yield pure amino- lH-pyrazole-3- carboxamides.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5711 - 5714
[2]Patent: WO2012/174362,2012,A1 .Location in patent: Page/Page column 40

49
[ 105-83-9 ]
[ 35034-22-1 ]
[ 1432473-78-3 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 50℃; for 0.25h; Inert atmosphere;	2 2.2 Synthesis of ligand bis(N,N′-2-methylimidazol-4-yl-methylideneaminopropyl)methylamine (abbreviated as H₂L¹) To a solution of N,N′-bis(3-aminopropyl)methylamine (0.072g, 0.5mmol) in 10mL of methanol was added a solution of 2-methyl-4-formylimidazole (0.110g, 1mmol) in 10mL of methanol at room temperature. The resulting solution was warmed at 50°C under stirring for 15min and then cooled to room temperature. The ligand solution was used for the synthesis of the FeII complex without further purification.

Reference： [1]Murakami, Keishiro; Kitabayashi, Aki; Yamauchi, Suguru; Nishi, Koshiro; Fujinami, Takeshi; Matsumoto, Naohide; Iijima, Seiichiro; Kojima, Masaaki [Inorganica Chimica Acta, 2013, vol. 400, p. 244 - 249]

50
[ 105-83-9 ]
[ 1448724-50-2 ]
[ 1448724-51-3 ]

Yield	Reaction Conditions	Operation in experiment
63.9%	In methanol; at 140℃; for 0.5h;Microwave irradiation;	A mixture of methyl 2-(3-(1 -(benzyloxy)-2,2,2-trifluoroethyl)benzyl)-4-chloro-9H-pyrimido[4,5- b]indole-7-carboxylate (0.375 g, 0.695 mmol) and N1 -(3-aminopropyl)-N1 -methylpropane-1 ,3-diamine (0.784 mL, 4.86 mmol) in MeOH (9.83 mL, 243 mmol) was heated in a microwave oven to 140C for 30 minutes. Then, after concentration to dryness under reduced pressure the resulting brown oil was purified by flash chromatography to afford methyl 4-((3-((3-aminopropyl)(methyl)amino)propyl)amino)-2- (3-(1 -(benzyloxy)-2,2,2-thfluoroethyl)benzyl)-9H-pyhmido[4,5-b]indole-7-carboxylate (288 mg, 63.9% yield) as a yellow foam: H NMR (400 MHz, DMSO-d6) delta ppm 1.48 (dt, J=14.0, 6.9 Hz, 2 H) 1 .75 (quin, J=6.7 Hz, 2 H) 2.14 (s, 3 H) 2.24 - 2.42 (m, 4 H) 2.52 - 2.60 (m, 2 H) 3.61 (q, J=6.3 Hz, 2 H) 3.88 (s, 3 H) 4.10 (s, 2 H) 4.49 (s, 2 H) 5.17 (q, J=7.0 Hz, 1 H) 7.18 - 7.30 (m, 5 H) 7.31 - 7.36 (m, 1 H) 7.39 (t, J=7.6 Hz, 1 H) 7.44 - 7.53 (m, 2 H) 7.58 (t, J=5.3 Hz, 1 H) 7.84 (dd, J=8.2, 1.4 Hz, 1 H) 8.00 (d, J=1 .4 Hz, 1 H) 8.28 (d, J=8.2 Hz, 1 H); MS m/z 649.3 (M+H)+; HPLC 97.6% 220 nm and 95.5% 254 nm, RT = 1.96 minutes.

Reference： [1]Patent: WO2013/110198,2013,A1 .Location in patent: Paragraph 0194

51
[ 105-83-9 ]
[ 1448724-61-5 ]
[ 1448724-14-8 ]
[ 1448724-21-7 ]

Yield	Reaction Conditions	Operation in experiment
67.2%; 6.71%	In methanol; at 140℃; for 0.5h;Microwave irradiation;	In a 2-5 mL microwave vial was added methyl 2-benzyl-4-chloro-9H-pyrimido[4,5-b]indole-7- carboxylate (0.050 g, 0.142 mmol) and A/1 -(3-aminopropyl)-A/1 -methylpropane-1 ,3-diamine (0.115 mL, 0.711 mmol) in MeOH (2.000 mL, 49.4 mmol) to give a tan suspension. The vial was placed in the microwave and heated to 140C for 30 min. After 30 minutes, the mixture was concentrated to dryness on a rotavap. and the residue was purified by flash chromatography and lyophilized from CH3CN to afford two distinct products: Example 45 as the mono-N-alkylated product: methyl 4-((3-((3- aminopropyl)(methyl)amino)propyl)amino)-2-benzyl-9H-pyrimido[4,5-b]indole-7-carboxylate (44 mg, 67.2% yield) as a white solid; H NMR (400 MHz, DMSO-d6) delta ppm 1 .44 (dt, J=13.8, 6.6 Hz, 2 H) 1 .72 (dt, J=13.7, 6.8 Hz, 2 H) 2.11 (s, 3 H) 2.24 - 2.30 (m, 2 H) 2.33 (t, J=6.7 Hz, 2 H) 2.47 (br. s., 2 H) 3.51 - 3.61 (m, 2 H) 3.76 - 3.85 (m, 3 H) 3.97 (s, 2 H) 7.08 - 7.15 (m, 1 H) 7.17 - 7.24 (m, 2 H) 7.27 - 7.34 (m, 2 H) 7.50 (t, J=5.3 Hz, 1 H) 7.76 (dd, J=8.2, 1.6 Hz, 1 H) 7.92 (d, J=1.6 Hz, 1 H) 8.20 (d, J=8.2 Hz, 1 H); MS m/z 461.2 (M+H)+; HPLC >99%, RT = 1 .63 minutes. Example 51 as a bis-alkylated product: dimethyl 4,4'-(((methylazanediyl)bis(propane-3,1- diyl))bis(azanediyl))bis(2-benzyl-9H-pyrimido[4,5-b]indole-7-carboxylate) (3.7 mg, 6.71 % yield) as a light yellow solid: H NMR (400 MHz, DMSO-de) delta ppm 1 .18 - 1 .29 (m, 4 H) 1.79 - 1.91 (m, 4 H) 2.25 (s, 3 H) 3.58 - 3.71 (m, 4 H) 3.84 (s, 6 H) 3.97 (s, 4 H) 7.07 - 7.16 (m, 2H) 7.22 (t, J=7.4 Hz, 4 H) 7.29 - 7.34 (m, 4 H) 7.53 (t, J=5.3 Hz, 2 H) 7.77 (dd, J=8.2, 1 .4 Hz, 2 H) 7.96 (d, J=1.4 Hz, 2 H) 8.22 (d, J=8.2 Hz, 2 H) 12.01 (s, 2H); MS m/z 776.3 (M+H)+; HPLC 94.6% 220 nm and 93.8% 254 nm, RT = 2.01 minutes.

Reference： [1]Patent: WO2013/110198,2013,A1 .Location in patent: Paragraph 0184-0185

52
[ 105-83-9 ]
[ 814-68-6 ]
[ 158749-62-3 ]

Yield	Reaction Conditions	Operation in experiment
29%	With sodium hydroxide; In water; acetonitrile; at 20℃; for 6h;Cooling with ice;	Synthesis of Specific Polymerizable Compound 3- (0257) To a one-liter three-necked flask equipped with a stirrer, 50.0 g (344 mmol) of N,N-<strong>[105-83-9]bis(3-aminopropyl)methylamine</strong>, 55.0 g (1.4 mol) of sodium hydroxide, 300 mL of water, and 450 mL of acetonitrile were added. Then, while cooling in an ice bath, 65.6 g (725 mmol) of acrylic acid chloride was added thereto dropwise. After the addition was completed, the temperature of the mixture was elevated to room temperature, and the mixture was further stirred for 6 hours. Then, from the resulting reaction liquid, acetonitrile was distilled off under reduced pressure. Thereafter, the aqueous layer was extracted 3 times with ethyl acetate. The obtained organic layer was dried with magnesium sulfate, and then filtered. Thereafter, ethyl acetate was distilled off under reduced pressure, thereby obtaining 25.4 g (100 mmol, yield: 29%) of specific polymerizable compound 3.

Reference： [1]Patent: US8461228,2013,B2 .Location in patent: Page/Page column 27
[2]ACS Catalysis,2016,vol. 6,p. 5245 - 5250

53
[ 86-98-6 ]
[ 105-83-9 ]
[ 947699-89-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	at 80 - 100℃;	General procedure: A combined method, as described by Biot et al.30 and N?Da et al.31 were used. 4,7-dichloroquinoline (15.1mmol, 3g, 1equiv) and diamine (0.15mol, 10equiv) were reacted for 3-6h at 80-100C [Scheme 1, step (i)]. The reaction mixture was allowed to cool and neutralized with an aqueous solution of 1M NaOH. The product was extracted with hot ethyl acetate, washed with water, dried over MgSO4 and evaporated to dryness under reduced pressure to produce the desired pure compound in high yields (51-85%), unless stated otherwise.32 In the reaction involving piperazine and leading to 4-amino-7-chloroquinoline 9, acetonitrile was used as solvent. The yields, melting points, IR, NMR, and HRMS data are reported.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1128 - 1138
[2]ACS Medicinal Chemistry Letters,2018,vol. 9,p. 980 - 985

54
[ 105-83-9 ]
C₁₇H₁₃ClNO₂⁽¹⁺⁾*I^(1-) [ No CAS ]
[ 1587729-29-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	at 120℃; for 0.5h;	0.3mol of chloroacetic acid dissolved in 60ml of water, adjusted to pH 9 with sodium hydroxide, then add 0.2mol of p-methoxy phenol, l0 C reflux, the compound T1,Followed by addition of thionyl chloride for chlorination reaction to obtain compound T2,Steamed to the thionyl chloride solvent to brown liquid, and then with anthranilic acid condensation reaction, obtained T3,Then PPA preheated to 130 C by adding T3 for the chemical reaction,The compound T4 was obtained. The T4 was reacted with thionyl chloride at 80 C under reflux,To obtain compound T5. Then, the purified T5 was methylated with methyl iodide in the system of sulfolane as the solvent to obtain the compound T6,T6-2 was added to a one-Using ethylene glycol ether as solvent,And N, N-bis (3-aminopropyl) methylamine at 120 C for 30min, and finally adding a large number of anhydrous ether, precipitate precipitation, filter drying compounds 4T7.
1.36 g	In 2-methoxy-ethanol; at 120℃; for 0.5h;	A solution of 1c (1g, 3.52mmol) in tetramethylene sulfone (10mL) was treated with iodomethane (10mL, 159.0mmol) and was heated at 68C for 3 days. After cooling to room temperature, the mixture was poured into ether. The solution was filtered, and the filtrate was extracted with ether (3×10mL). Then the filtrate was dried under infrared light to afford crude product. The above crude product in 2-methoxyethanol (10mL) was treated with N,N-bis(3-aminopropyl) methylamine (10mL, 62.05mmol), and heated at 120C for 30min. After cooling to room temperature, the mixture was poured into ether. The solution was filtered, and extracted with ether (3×10mL). The solvent was evaporated, and the residue was dried under infrared light to afford product 7 (1.36g) as a pale yellow solid in 95% yield. mp 168-170C. 1H NMR (400MHz, DMSO-d6): delta 8.69 (d, J=8.4Hz, 1H), 8.44 (d, J=9.0Hz, 1H), 8.11 (d, J=8.0Hz, 1H), 8.03-7.97 (m, 2H), 7.83 (t, J=7.6Hz, 1H), 7.58 (dd, J=9.2, 2.3Hz, 1H), 4.59 (s, 3H), 4.17 (t, J=6.4Hz, 2H), 3.99 (s, 3H), 3.25-3.17 (m, 2H), 3.13 (dd, J=12.2, 6.6Hz, 2H), 3.03-2.93 (m, 2H), 2.70 (s, 3H), 2.25-2.14 (m, 2H), 1.84-1.70 (m, 2H). IR (KBr, cm-1): 3261, 3051, 2955, 2876, 1598, 1529, 1493, 1386, 1347, 1253, 1213, 1107, 1039, 977, 822, 774, 671. ESI-MS: m/z 407 [M-I]+. HRMS (ESI): m/z calcd for C24H31IN4O2 ([M-I] +) 407.1583; found 407.6453.

Reference： [1]Patent: CN103666452,2016,B .Location in patent: Paragraph 0076-0079
[2]Dyes and Pigments,2014,vol. 107,p. 97 - 105

55
[ 105-83-9 ]
[ 638-29-9 ]
N,N'-(methylazanediyl)bis(propan-3,1-diyl)dipentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In methanol; at 0 - 20℃;	The amine forms (Compounds 1 to 4) having no acyl groups of the compounds were prepared. 10 mL of each of the amine forms was dissolved in a solution of 200 mL of methanol and 200 mL of a 1 M sodium bicarbonate solution in a round-bottom flask. [0072] The temperature of the resulting solution was adjusted to 0 C. The acyl anhydride or acyl chloride (Compound a, b or c) having the corresponding acyl group was slowly added. 1.5 equivalents of the acyl anhydride or acyl chloride was used per equivalent of the primary and tertiary amino groups of the amine. The mixture was stirred at 0 C. for 1 h and at room temperature for additional 16-18 h. After completion of the reaction, the reaction mixture was extracted about 2-4 times with dichloromethane, followed by drying to obtain the final product. 1H NMR spectra of nBu-DETA, Val-DEEA, iBu-DEER, nBu-DAPMA, Val-DAPMA, and nBu-DIPA measured on a 300 MHz Bruker spectrometer are shown in FIGS. 3 to 8, respectively.

Reference： [1]Patent: US2014/158621,2014,A1 .Location in patent: Paragraph 0071; 0072; 0073

56
[ 106-31-0 ]
[ 105-83-9 ]
[ 17785-26-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In methanol; at 0 - 20℃;	The amine forms (Compounds 1 to 4) having no acyl groups of the compounds were prepared. 10 mL of each of the amine forms was dissolved in a solution of 200 mL of methanol and 200 mL of a 1 M sodium bicarbonate solution in a round-bottom flask. [0072] The temperature of the resulting solution was adjusted to 0 C. The acyl anhydride or acyl chloride (Compound a, b or c) having the corresponding acyl group was slowly added. 1.5 equivalents of the acyl anhydride or acyl chloride was used per equivalent of the primary and tertiary amino groups of the amine. The mixture was stirred at 0 C. for 1 h and at room temperature for additional 16-18 h. After completion of the reaction, the reaction mixture was extracted about 2-4 times with dichloromethane, followed by drying to obtain the final product. 1H NMR spectra of nBu-DETA, Val-DEEA, iBu-DEER, nBu-DAPMA, Val-DAPMA, and nBu-DIPA measured on a 300 MHz Bruker spectrometer are shown in FIGS. 3 to 8, respectively.

Reference： [1]Patent: US2014/158621,2014,A1 .Location in patent: Paragraph 0071; 0072; 0073

57
[ 105-83-9 ]
[ 446-33-3 ]
[ 1383630-25-8 ]

Yield	Reaction Conditions	Operation in experiment
78.4%	With sodium carbonate; at 60 - 100℃; for 12h;	5.1. Synthesis of N1-Methyl-N3-(3-methyl-4-nitrophenyl)-N1-{3-[(3-methyl-4-nitrophenyl)-amino]propyl}-1,3-propanediamine To 5-fluoro-2-nitrotoluene (50.0 g, 0.32 mol) was added sodium carbonate (17.1 g, 0.16 mol) at 60 C. <strong>[105-83-9]3,3'-Diamino-N-methyldipropylamine</strong> (23.7 g, 0.16 mol) was then carefully added dropwise (exothermic reaction). The resulting mixture was heated at 100 C. for 12 hours. 100 ml toluene were added to the cooled reaction mixture causing the inorganic salts to precipitate, which were filtered off. The organic phase was then concentrated down under vacuum in a rotovap to afford the product as a residue in the form of a yellow orange oil. Yield: 52.5 g (78.4%); 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=1.71 (m, 4H); 2.18 (s, 3H); 2.40 (m, 4H); 2.55 (s, 6H); 3.17 (m, 4H); 6.45 (s, 2H); 6.48 (d, 2H); 7.08 (br., 2*NH); 7.92 (d, 2H).

Reference： [1]Patent: US2014/245541,2014,A1 .Location in patent: Paragraph 0234

58
[ 105-83-9 ]
[ 100-00-5 ]
[ 1383630-17-8 ]

Yield	Reaction Conditions	Operation in experiment
78.2%	With sodium carbonate; In dimethyl sulfoxide; at 80 - 120℃; for 12h;	1.1 Synthesis of N1-methyl-N3-(4-nitrophenyl)-N1-{3-[(4-nitrophenyl)amino]propyl}-1,3-propanediamine 4-Chloronitrobenzene, 50.0 g (0.32 mol), in 100 ml dimethylsulfoxide were heated to 80 C. (clear solution). Sodium carbonate, 15.6 g (0.16 mol), was then added. N1-(3-Aminopropyl)-N1-methyl-1,3-propanediamine, 23.2 g (0.16 mol), was then added dropwise at this temperature. Following the dropwise addition the reaction mixture was then stirred for 12 h at 120 C. After cooling, water (11) was added and the aqueous phase was extracted 3 times with 200 ml ethyl acetate. The organic phase was then dried with sodium sulfate and concentrated under vacuum in a rotovap. The product remained as a residue in the form of a highly viscous oil. Yield: 48.1 g (78.2%); 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=1.71 (m, 4H); 2.17 (s, 3H); 2.40 (t, 4H); 3.18 (m, 4H); 6.61 (d, 4H); 7.27 (br., 2*NH); 7.98 (d, 4H).

Reference： [1]Patent: US2014/245541,2014,A1 .Location in patent: Paragraph 0224

59
[ 105-83-9 ]
[ 400-94-2 ]
N,N'-(3,3'-(methylazanediyl)bis(propane-3,1-diyl))bis(4-fluoro-3-nitrobenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.61 g	With triethylamine; In dichloromethane; at 20℃; for 18h;	General procedure: This solutionwas slowly added to a solution of the corresponding amine andtriethylamine in CH2Cl2 at 0 C. The mixture was stirred overnightat room temperature. After removal of solvent in vacuo the crudeproduct was dispersed in concentrated Na2CO3 solution, and extracted with CH2Cl2. The combined organic phases were driedover anhydrous Na2SO4. After filtration and removal of solvent invacuo the product was purified by column chromatography toyield the corresponding amide.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3938 - 3946

60
[ 474018-94-5 ]
[ 105-83-9 ]
4,4'-(3,3'-(methylazanediyl)bis(propane-3,1-diyl)bis(azanediyl))bis(N,N-diethyl-3-nitrobenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: The corresponding amine and triethylamine were dissolved inethanol and stirred at room temperature for 0.5-1 h. Then, a solutionof the corresponding 4-fluoro-3-nitrophenyl compound inethanol was slowly added. The mixture was stirred overnight at50-75 C. After removal of solvent in vacuo the product waspurified by column chromatography to give the corresponding4-amino-3-nitrophenyl compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3938 - 3946

61
Fmoc-β-Ala-Wang resin [ No CAS ]
[ 105-83-9 ]
[ 872679-70-4 ]
[ 1040393-13-2 ]
C₂₀H₂₅N₉O₅ [ No CAS ]
[ 195387-29-2 ]
C₁₀₃H₁₂₉N₄₁O₂₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 11546 - 11554

62
Fmoc-β-Ala-Wang resin [ No CAS ]
[ 105-83-9 ]
[ 1040393-13-2 ]
C₂₀H₂₅N₉O₅ [ No CAS ]
[ 139338-72-0 ]
[ 195387-29-2 ]
C₁₀₄H₁₃₁N₄₁O₂₁ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 11546 - 11554

63
[ 437655-95-3 ]
Fmoc-β-Ala-Wang resin [ No CAS ]
[ 105-83-9 ]
[ 1040393-13-2 ]
C₂₀H₂₅N₉O₅ [ No CAS ]
[ 195387-29-2 ]
C₁₀₆H₁₃₅N₄₁O₂₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 11546 - 11554

64
6-bromo-1-(2',4'-dichlorophenyl)-4,5-dihydro-1H-thieno[3,2-g]indazol-3-carboxylic acid [ No CAS ]
[ 105-83-9 ]
C₃₉H₃₃Br₂Cl₄N₇O₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%		mmole of 6-bromo-1-(2?,4?-dichlorophenyl)-4,5-dihydro-1H-thieno[3,2-g]indazol-3-carboxylic acid prepared in Ex. 26aand 1.1 mmoles of 1,1?-carbonyldiimidazole (CDI) in 2.5 ml of DMF were mixed under stirring at room temperature andstirring continued for 3 hours, then 0.5 mmoles of CH3N(CH2CH2CH2NH2)2 in DMF (2 ml) were added. The reactionmixture was stirred at room temperature for 48 hours. The solvent was then removed under reduced pressure and theobtained residue was purified by flash chromatography (eluent CHCl3/CH3OH 9/1 v/v) obtaining the titled compound.Yield 38%. 1H-NMR (CDCl3) delta 1.82 (q, 4H), 2.38 (s, 3H), 2.55 (t, 4H), 2.88-3.35 (m, 8H), 3.56 (q, 4H), 7. 14 (s, 2H), 7.36(dd, 2H), 7. 47 (d, 2H), 7.63 (d, 2H).
38%		0424] 1 mmole of 6-bromo-1-(2?,4?-dichlorophenyl)-4,5-dihydro-1H-thieno[3,2-g]indazol-3-carboxylic acid prepared in Ex. 26a and 1.1 mmoles of 1,1?-carbonyldiimidazole (CDI) in 2.5 ml of DMF were mixed under stirring at room temperature and stirring continued for 3 hours, then 0.5 mmoles of CH3N(CH2CH2CH2NH2)2 in DMF (2 ml) were added. The reaction mixture was stirred at room temperature for 48 hours. The solvent was then removed under reduced pressure and the obtained residue was purified by flash chromatography (eluent CHCl3/CH3OH 9/1 v/v) obtaining the titled compound. Yield 38%. 1H-NMR (CDCl3) delta 1.82 (q, 4H), 2.38 (s, 3H), 2.55 (t, 4H), 2.88-3.35 (m, 8H), 3.56 (q, 4H), 7.14 (s, 2H), 7.36 (dd, 2H), 7.47 (d, 2H), 7.63 (d, 2H)

Reference： [1]Patent: EP2789619,2014,A1 .Location in patent: Paragraph 0181
[2]Patent: US2014/343294,2014,A1 .Location in patent: Paragraph 0423; 0424

65
[ 105-83-9 ]
[ 29548-30-9 ]
{3-[(3-aminopropyl)methylamino]propyl}(3,7,11-trimethyldodeca-2,6,10-trienyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With tetrakis(triphenylphosphine) palladium(0); In ethanol; at 110℃; for 1h;	General procedure: To a solution of geranyl acetate (196 mg, 1 mmol) in ethanol (96%) (5 mL) is added tris(3-amino-propyl)amine (235 mg,1.25 mmol). This mixture is heated under air in an oil bath at 110 C.When the reflux is well established 46 mg of Pd(PPh3)4 (4 mol %) is quickly added in one portion. The reflux is maintained for 1 h. After cooling to room temperature, the solvent is removed under reduced pressure and the crude product is purified by column chromatography (silica gel; CH2Cl2/MeOH/NH4OH, 7:3:1) affordinga clear oil of Z-3 in 80% yield.

Reference： [1]Tetrahedron,2014,vol. 70,p. 9718 - 9725

66
[ 105-83-9 ]
[ 16409-44-2 ]
{3-[(3-aminopropyl)methylamino]propyl}(3,7-dimethylocta-2,6-dienyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With tetrakis(triphenylphosphine) palladium(0); In ethanol; at 110℃; for 1h;	General procedure: To a solution of geranyl acetate (196 mg, 1 mmol) in ethanol (96%) (5 mL) is added tris(3-amino-propyl)amine (235 mg,1.25 mmol). This mixture is heated under air in an oil bath at 110 C.When the reflux is well established 46 mg of Pd(PPh3)4 (4 mol %) is quickly added in one portion. The reflux is maintained for 1 h. After cooling to room temperature, the solvent is removed under reduced pressure and the crude product is purified by column chromatography (silica gel; CH2Cl2/MeOH/NH4OH, 7:3:1) affordinga clear oil of Z-3 in 80% yield.

Reference： [1]Tetrahedron,2014,vol. 70,p. 9718 - 9725

67
[ 105-83-9 ]
[ 3320-86-3 ]
C₂₁H₂₇N₇O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In dichloromethane; at 20℃; for 24h;Reflux;	L:3,3'-diamino-N-methyl-dipropylamine (417.4 mL, 2.1 mmol) was added to 2-nitrophenyl isocyanate (0.7g, 4.2 mmol) in dichloromethane (250 mL) at room temperature under constantstirring. The mixture was reuxed for 24 hours. Solvent was evaporated. Ayellow precipitate was formed and collected by filtration. The precipitate waswashed by methanol and dried under vacuum for overnight to give the neutralpropylene-based dipodal urea receptor (L). Yield: 0.7 g , 70%. 1H NMR (500 MHz, DMSO-d6): delta 9.31 (s, 2H, Ar-NH), 8.24 (d, J = 8.4 Hz, 2H, ArH), 8.02 (d, J = 7.00 Hz, 2H, ArH), delta7.61 (t, J1 = 7.15 Hz, J2 = 7.15 Hz, 2H, ArH), 7.48 (s, 2H, Ar-NH), delta 7.09 (t, J = 8.37 Hz, 2H, ArH), delta3.11 (m, 4H, NHCH2), delta2.32 (t, J = 7.02 Hz, 4H, NCH2), delta 2.13(s, 3H, NCH3), delta 1.58 (m, 4H, CH2CH2). 13C NMR (125MHz, DMSO-d6): delta 154.61 (C=O), 137.19 (Ar-C), 136.39 (Ar-C), 135.37 (Ar-CH), 125.72 (Ar-CH),122.38 (Ar-CH), 121.71 (ArCH), 55.27 (NCH2), 42.23 (NCH3),38.08 (NHCH2), 27.64 (CH2CH2). Anal. Calcd. for C21H27N7O6: C, 53.27; H, 5.75; N, 20.71. Found: C, 53.33; H, 5.68; N, 20.65.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 657 - 661

68
[ 105-83-9 ]
10-(5-carboxypentyl)acridine orange chloride salt [ No CAS ]
C₅₃H₇₅N₉O₂⁽²⁺⁾*2I^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
250 mg		Example 7 Preparation of AOAO-2 (Dye No. 7 of Table 1) (0164) Et3N (0.15 mL, 1.05 mmol) and TSTU (320 mg, 1.05 mmol) were added to a suspension of 10-(5-carboxypentyl)acridine orange chloride salt (438 mg, 1.03 mmol) in DMF (5 mL) at room temperature. The mixture was stirred at room temperature for 15 minutes, followed by the addition of Et3N (0.1 mL) and 3,3?-diamino-N-methyldipropylamine (50 mg, 0.344 mmol). After the mixture was stirred at room temperature overnight, EtOAc (20 mL) was added to precipitate the product. The crude product was re-dissolved in DMF and precipitated out again with EtOAc. The solid (250 mg) was separated by centrifugation.

Reference： [1]Patent: US9102835,2015,B2 .Location in patent: Page/Page column 80

69
[ 105-83-9 ]
[ 1314863-61-0 ]
5-[(1S,2S,5S,7R,10R,11S,14S,15R)-5-{3-[N-methyl(3-aminopropyl)amino]propylaminocarbonyloxy}-11-hydroxy-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-14-yl]-2-pyranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.4%	In dichloromethane; tert-butyl methyl ether; at 20℃; for 2h;	31.8mgs (57.44.imol) of 4-nitrophenyl carbamate-3-O-bufalin was dissolved in lmL of DCMand lmL of MTBE. 46.3.iL (287.2.imol) of 3,3?-diamino-N-methyldipropylamine was addedand stirred at room temperature. After 90 minutes 4mL of MTBE was added and stirred foran additional 30 minutes. The solvent was decanted off, leaving a yellow precipitate behind.The precipitate was washed with a minimal amount of MTBE. The MTBE was decanted offand placed with the previously decanted material. The decanted solvent was rotaryevaporated off. The material was washed 4 times with lOmL of hexanes. 5mL of H20 wasadded and the precipitate was suction filtered. The precipitate was washed 3 times with 10-l5mL of H20. To the precipitate (16.Smgs) was added lmL of MeOH. The material was centrifuged with the solvent being decanted off. The decanted material was rotary evaporatedoff. 14.2 lmgs (25.48umol) of CEN-372 was obtained for a % Yield of 44.4%.TLC: 75:25DCM:EtOAc; RfCEN-372 = 0.0; Ninhydrin positive; HPLC Analysis: C18 Column:AtlantisT3; 3um; 4.6 x 150mm; Gradient: 0-2mm = 90:10 (A:B); 2-15mm = 0:100 (A:B);Flow Rate: 1 mL/min; RtCEN-372= 11.60 mm (2max = 300nm). ?H-NMR (400 MHz,DMSO-d6): oe 7.92 (d, 1H, H21), 7.51 (s, 1H, H14), 6.95 (s, 1H, H26), 6.27 (d, 1H, H20)4.78 (s, 1H, H3), 4.15 (s, 1H, H13), 3-1.1 (multiple peaks, 39H, H1,2,4-9,11,12,15-17,27-34), 0.87 (s, 3H, H18), 0.59 (s, 3H, H19). TOF-MS (ESI): MWobs = 558.39 g/mol; MWcalc. =558.84 g/mol. RJPAC Name: 5-[(1S,2S,5S,7R, bR, 11S, 14S, 15R)-5- {3-[N-Methyl(3-aminopropyl)amino]propylaminocarbonyloxy} -11 -hydroxy-2, 15-dimethyltetracyclo [8.7.0.02,7.011,15 ]heptadec- 1 4-yl] -2-pyranone

Reference： [1]Patent: WO2015/123687,2015,A1 .Location in patent: Page/Page column 68; 69

70
[ 105-83-9 ]
[ 1448724-40-0 ]
N₁-(3-aminopropyl)-N₃-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)-N₁-methylpropane-1,3-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In methanol; at 140℃; for 0.5h;Microwave irradiation;	A mixture of 2-benzyl-4-chloro-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indole prepared as described above (0.865 g, 2.302 mmol) and 3,3'-Diamino-/V-methyldipropylamine (2.60 mL, 16.1 1 mmol) in MeOH (17.4 mL) was heated 30 minutes to 140 C in a microwave oven. After cooling and evaporation of the solvent, the residue was purified by flash chromatography to give N1-(3-aminopropyl)-N3-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H- pyrimido[4,5-b]indol-4-yl)-N1-methylpropane-1 ,3-diamine (832 mg, 74% yield) as a yellow solid; 1H NMR (400 MHz, DMSO-d6) delta ppm 1.52 (quin, J=6.85 Hz, 2 H) 1.80 (quin, J=6.85 Hz, 2 H) 2.18 (s, 3 H) 2.36 (t, J=7.24 Hz, 2 H) 2.41 (t, J=6.65 Hz, 2 H) 2.53 - 2.61 (m, 2 H) 3.64 (q, J=6.52 Hz, 2 H) 4.04 (s, 2 H) 4.43 (s, 3 H) 7.14 - 7.23 (m, 1 H) 7.28 (t, J=7.43 Hz, 2 H) 7.38 (d, J=7.43 Hz, 2 H) 7.49 (t, J=5.09 Hz, 1 H) 7.91 (d, J=8.22 Hz, 1 H) 8.08 (s, 1 H) 8.32 (d, J=8.22 Hz, 1 H); HPLC 99.4% at 254 nm, RT 1.608 minutes; HRMS m/z 485.2884 (M+H)+.

Reference： [1]Patent: WO2016/41080,2016,A1 .Location in patent: Page/Page column 71

71
[ 12093-10-6 ]
[ 105-83-9 ]
N-ferrocenyl-N-(3-aminopropyl)-N-methylpropane-1,3-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%		General procedure: A mixture of ferrocene carboxaldehyde(9.3 mmol, 2 g, 1 eq.) and the appropriate primarydiamine (46.5 mmol, 5 eq.) was stirred in anhydrousMeOH (50 ml) for 4 h at room temperature. An excess ofsodium borohydride, NaBH4 (93 mmol, 3.5 g, 10 eq.), wasadded, and stirring was continued for an additional 2 h atroom temperature (Scheme 1). Afterward, the reactionmixture was acidified with HCl (1 M, 50 ml), diluted withwater (50 ml) and extracted with EtOAc (2 9 50 ml) toremove any unreacted ferrocene carboxaldehyde. Theaqueous layer was basified to pH 10 with a solution ofsaturated NaHCO3 and extracted with EtOAc (3 9 50 ml).The combined organic layers were dried over MgSO4, andthe solvent was removed in vacuo. The residue was subjectedto column chromatography on silica gel, elutingsuccessively with DCM:MeOH (9:1, v/v) and then withCH2Cl2:MeOH:NH4OH (25 %), (4:1:0.1, v/v/v) to affordthe pure compounds 1-8 in high yields.

Reference： [1]Medicinal Chemistry Research,2016,vol. 25,p. 568 - 584

72
[ 105-83-9 ]
[ 439147-09-8 ]
1-{3-[N-(3-aminopropyl)-N-methylamino]propylamino}-4-methyl-9(10H)-acridone trihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		Preparation of derivative 2h: l-{3-[N-(3- Aminopropyl)-N-methylamino]propylamino}-4-methyl-9(10H)-acridone 'x3HCl. A mixture of 1- chloro-4-methyl-9(10H)-acridone (lb) (2.0 g, 0.0082 mol) and 3,3-diamino-N-methyldipropylamine (10 ml) were reacted using a microwave reactor. The synthesis parameters were: the efficiency of the microwave reactor was P=25%, tmin=120C, tmax=130C, the conduct time was lh. After this time, the mixture was cooled to room temperature and then poured into water (100 ml) and extracted with chloroform. The product was purified by column chromatography. The initial eluent was CHC13/MeOH (4:1 v/v) and then CHC13/MeOH/NH3 (3: 1 :0.01, v/v). Fractions containing the desired product were evaporated, and then it was dissolved in methanol (10 ml) and acidified with HC1/diethyl ether. After adding acetone the desired product was obtained. Yield 47%.

Reference： [1]Patent: WO2016/150799,2016,A1 .Location in patent: Page/Page column 12

73
[ 105-83-9 ]
[ 99009-49-1 ]
1-{3-[N-(3-aminopropyl)-N-methylamino]propylamino}-7-hydroxy-4-nitro-9(10H)-acridone dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%		Synthesis of derivative 2a: l-{ 3-fN- ( 3-Aminopropyl)-N-methylamino ]propylamino}- 7-hydroxy-4- nitro-9(10H)-acridone x2HCl. A mixture of l -chloro-7-hydroxy-4-nitro-9(10H)-acridone (la) (1.45 g, 0.005 mol), and 3,3-diamino-N-methyldipropylamine 2.90 g (0.02 mol) in DMSO (25 ml) was stirred at room temperature for 2.5 h. After this time, water was added (-200 ml) and the reaction mixture was stirred for 0.5 h. The precipitate was collected by filtration. Next, it was transferred into water, acidified with a dilute hydrochloric acid and stirred for 0.5 h. Undissolved material was filtered off, and the solution was evaporated to a small volume. The product was precipitated out using acetone (-100 ml), and then was filtered off to give 1.2 g (51 %).

Reference： [1]Patent: WO2016/150799,2016,A1 .Location in patent: Page/Page column 8

74
[ 105-83-9 ]
[ 20621-51-6 ]
1-{3-[N-(3-aminopropyl)-N-methylamino]propylamino}-4-nitro-9(10H)-acridone dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%		Preparation of derivative 2i: l-{3-[N- (3-Aminopropyl)-N-methylamino]propylamino}-4-nitro-9(10H)-acridone x2HCl. A mixture of 1- chloro-4-nitro-9(10H)-acridone (lc) (0.01 mol), 3,3-diamino-N-methyldipropylamine (0.04 mol) in DMSO (50 ml) was stirred at room temperature for 3 h. After this time, water was added (-200 ml) and then stirred for 10 min. The precipitate was collected by filtration and suspended into water (-100 ml) and then acidified with a dilute hydrochloric acid and stirred again for 15 min. The insoluble precipitate was filtered off, and the filtrate was evaporated to a smaller volume. The product was precipitated out using acetone (-100 ml), and then was filtered off. Yield 81%.

Reference： [1]Patent: WO2016/150799,2016,A1 .Location in patent: Page/Page column 13

75
[ 105-83-9 ]
[ 118-92-3 ]
N,N'-[(methylazanediyl)bis(propane-3,1-diyl)]bis(2-aminobenzamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.6%		General procedure: Compound 1 (10 mmol) and CDI (11 mmol) in DMF (100 mL) were stirred for 1 h at roomtemperature. Then the appropriate polyamine (a-d) (6 mmol) was added and stirring was continuedfor additional 2 h. At the end of the reaction, the mixture was filtered. The solvent was removed invacuum. 20 mL of H2O was added to the residue (compounds 3a,b) and left for 24 h at 5 C. Then thesolid was filtered off, washed with H2O and crystallized from DMF/H2O. The residue was purified bycolumn chromatography over silica gel (CHCl3/MeOH, 100:1-0:1, v/v) to give compounds 3c,d.