[ CAS No. 51-80-9 ]

Name: 51-80-9|N,N,N',N'-Tetramethylmethanediamine|98%
Brand: Ambeed
SKU: A852024
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Cat. No.: {[proInfo.prAm]}

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Quality Control of [ 51-80-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 51-80-9 ]

SDS Specification

Alternatived Products of [ 51-80-9 ]

Product Details of [ 51-80-9 ]

CAS No. :	51-80-9	MDL No. :	MFCD00008328
Formula :	C₅H₁₄N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VGIVLIHKENZQHQ-UHFFFAOYSA-N
M.W :	102.18	Pubchem ID :	5829
Synonyms :

Calculated chemistry of [ 51-80-9 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	31.94
TPSA :	6.48 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.64 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.93
Log Po/w (XLOGP3) :	0.4
Log Po/w (WLOGP) :	0.07
Log Po/w (MLOGP) :	0.63
Log Po/w (SILICOS-IT) :	-0.86
Consensus Log Po/w :	0.43

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.59
Solubility :	26.1 mg/ml ; 0.255 mol/l
Class :	Very soluble
Log S (Ali) :	-0.1
Solubility :	80.7 mg/ml ; 0.79 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.43
Solubility :	37.9 mg/ml ; 0.371 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.34

Safety of [ 51-80-9 ]

Signal Word:	Danger	Class:	3,8
Precautionary Statements:	P210-P280-P305+P351+P338-P310	UN#:	2733
Hazard Statements:	H225-H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 51-80-9 ]

* 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.

Upstream synthesis route of [ 51-80-9 ]
Downstream synthetic route of [ 51-80-9 ]

[ 51-80-9 ] Synthesis Path-Upstream 1~8

1
[ 108-77-0 ]
[ 51-80-9 ]
[ 645-05-6 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1998, # 9, p. 2033 - 2055

2
[ 141-30-0 ]
[ 51-80-9 ]
[ 7145-60-0 ]

Reference： [1] Synthetic Communications, 1992, vol. 22, # 5, p. 787 - 792

3
[ 592-41-6 ]
[ 51-80-9 ]
[ 5277-11-2 ]
[ 36343-05-2 ]

Reference： [1] Journal of Organic Chemistry, 1983, vol. 48, # 24, p. 4531 - 4537

4
[ 51-80-9 ]
[ 17510-47-3 ]
[ 51690-03-0 ]

Reference： [1] Chemistry Letters, 1980, p. 1213 - 1214
[2] Bulletin of the Chemical Society of Japan, 1982, vol. 55, # 2, p. 534 - 539

5
[ 51-80-9 ]
[ 78024-10-9 ]
[ 51690-03-0 ]

Reference： [1] Journal of the Chemical Society, Chemical Communications, 1990, # 21, p. 1532 - 1533
[2] Journal of the Chemical Society, Chemical Communications, 1990, # 21, p. 1532 - 1533
[3] Journal of the Chemical Society, Chemical Communications, 1990, # 21, p. 1532 - 1533
[4] Journal of the Chemical Society, Chemical Communications, 1990, # 21, p. 1532 - 1533

6
[ 74-83-9 ]
[ 51-80-9 ]
[ 64-20-0 ]
[ 16513-42-1 ]

Reference： [1] Mendeleev Communications, 2006, vol. 16, # 5, p. 258 - 259

7
[ 693-98-1 ]
[ 27387-31-1 ]
[ 51-80-9 ]
[ 99614-02-5 ]

Yield	Reaction Conditions	Operation in experiment
81.5%	With acetyl chloride In toluene; acetonitrileHeating / reflux	Example 11: Synthesis of ls239-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one To the solution of 36 ml of acetyl chloride in 50 ml of actonitrile and 750 ml of toluene, was slowly added 51 ml of N, N, N', N'- tetramethyldiaminomethane at 0°C, which was then stirred for 10min. 50 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 100 g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 150 ml of water was added to the resulting residue. The resulting solid was filtered and washed, and then dried under a reduced pressure. The resulting solid was suspended in 350 ml of methanol, and then 0.7g of active carbon was added to thereto, which was then stirred for 1 hour under reflux. The resulting mixture was filtered and washed with methanol, which was then stirred for 3 hours at room temperature. The resulting solid was filtered and dried to give 60 g of pure white title compound (yield 81.5percent).
75%	Stage #1: at 120 - 130℃; for 8 h; Stage #2: With sodium hydroxide In water	Example 8: Synthesis of 12s3 " 9-tetrahydro-9-methyl-3-[(2-methel-lH- imidazole-1-vl) methyl]-4H-carbazol-4-one At-10°C, 4 ml of N, N, N', N'-tetramethyldiaminomethane was slowly added to 46 ml of trifluoroacetic acid, which was then stirred for 30 min. 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 8 g of 2-methyl imidazole was added to the reaction mixture, which was then stirred for about 8 hours at 120-130°C. After completion of reaction, the reaction mixture was cooled at room temperature, and then IN aq. sodium hydroxide was added thereto. The resulting solid was filtered and washed with water, and then dried. The resulting solid was suspended in 80 ml of methanol, and then 0.28 g of active carbon was added thereto, which was then stirred under reflux for 1 hour. The resulting mixture was filtered and washed with methanol, and then evaporated to give 2.2 g of 1, 2,3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazol-1-yl) methyl]- 4H-carbazol-4-one (yield 75percent).
66%	With chloro-trimethyl-silane In DMF (N,N-dimethyl-formamide) at 90℃; for 10 h;	Example 2: Synthesis of 1, 23*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 20 ml of N, N-dimethylformamide, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred at 90 °C for 10 hours. 100ml of water was added to the reaction mixture. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.93 g of title compound (yield 66percent).

60%	With chloro-trimethyl-silane In acetonitrile for 10 h; Heating / reflux	Example 1 : Synthesis of 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 40 ml of water was added to the resulting residue. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.76 g of title compound (yield 60percent).
58%	With acetyl chloride In toluene for 10 h; Heating / reflux	Example 7: Synthesis of 123*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 2 ml of N, N, N', N'-tetramethyl- diaminomethane were suspended in 30 ml of toluene, and then 1.4 ml of acetyl chloride was slowly added thereto, which was then stirred for 10 min. 1.65g of 2-methyl imidazole was added to the reaction mixture, which was then stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 150ml dichloromethane and 50ml of IN aq. sodium hydroxide were added to the resulting residue. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone, which was then stirred for 3 hours, and then filtered and dried to give 1.70 g of title compound (yield 58percent).
55%	With aluminum (III) chloride In acetonitrile for 10 h; Heating / reflux	Example 4: Synthesis of 123, 9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yDmethyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 1.4 g of aluminum chloride was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. 150 ml dichloromethane and 50 ml of IN aq. sodium hydroxide were added to the reaction mixture. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.61 g of title compound (yield 55percent).

Reference： [1] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 11
[2] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 10
[3] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 7
[4] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 7
[5] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 9-10
[6] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 8

8
[ 51-80-9 ]
[ 19685-09-7 ]
[ 119413-54-6 ]

Reference： [1] Tetrahedron Letters, 1996, vol. 37, # 32, p. 5683 - 5686

[ 51-80-9 ] Synthesis Path-Downstream 1~69

1
[ 68043-53-8 ]
[ 51-80-9 ]
3-dimethylaminomethyl-6-nitro-chroman-4-one [ No CAS ]

Reference： [1]Yaoxue Xuebao/Acta pharmaceutica Sinica,1959,vol. 7,p. 189,190
Chem.Abstr.,1960,p. 5637

2
[ 51-80-9 ]
[ 67-64-1 ]
[ 2543-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	With water
	With alkali
	With water; sodium chloride; benzene

Reference： [1]Mannich [Archiv der Pharmazie, 1917, vol. 255, p. 266]
[2]Current Patent Assignee: Bayer & Co. - DE254714, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 11, p. 783,788][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 11, p. 783,788]
[3]Current Patent Assignee: Bayer & Co. - DE267347, 1800, C

3
[ 50-00-0 ]
[ 51-80-9 ]
[ 275-51-4 ]
[ 93187-51-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: formaldehyd; bis-(dimethylamino)methane With acetic acid In dichloromethane Stage #2: azulene In dichloromethane at 0 - 20℃; for 2h;
	In dichloromethane; acetic acid

Reference： [1]Moroz, Yurii S.; Binder, Wolfgang; Nygren, Patrik; Caputo, Gregory A.; Korendovych, Ivan V. [Chemical Communications, 2013, vol. 49, # 5, p. 490 - 492]
[2]Hafner,K.; Senf,W. [Justus Liebigs Annalen der Chemie, 1962, vol. 656, p. 34 - 39]
[3]Anderson,A.G. et al. [Journal of Organic Chemistry, 1962, vol. 27, p. 4535 - 4539]

4
[ 26456-59-7 ]
[ 51-80-9 ]
[ 82040-04-8 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1982,vol. 18,p. 297 - 299
Khimiya Geterotsiklicheskikh Soedinenii,1982,vol. 18,p. 393 - 396

5
[ 106-98-9 ]
[ 51-80-9 ]
[ 25419-06-1 ]
[ 2050-92-2 ]

Reference： [1]Journal of Organic Chemistry,1983,vol. 48,p. 4531 - 4537

6
[ 141-30-0 ]
[ 51-80-9 ]
[ 7145-60-0 ]

Reference： [1]Synthetic Communications,1992,vol. 22,p. 787 - 792

7
[ 592-41-6 ]
[ 51-80-9 ]
[ 5277-11-2 ]
[ 36343-05-2 ]

Reference： [1]Journal of Organic Chemistry,1983,vol. 48,p. 4531 - 4537

8
[ 1620-55-9 ]
[ 51-80-9 ]
[ 108664-37-5 ]

Reference： [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 1497 - 1502

9
[ 51-80-9 ]
[ 17510-47-3 ]
[ 51690-03-0 ]

Reference： [1]Chemistry Letters,1980,p. 1213 - 1214
[2]Bulletin of the Chemical Society of Japan,1982,vol. 55,p. 534 - 539

10
[ 51-80-9 ]
[ 6306-60-1 ]
[ 26923-38-6 ]

Reference： [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 1497 - 1502

11
[ 51-80-9 ]
[ 7295-50-3 ]
1-(4-Chloro-phenyl)-2-methylene-hexan-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 1054 - 1068

12
[ 51-80-9 ]
[ 25017-08-7 ]
[ 170917-90-5 ]

Yield	Reaction Conditions	Operation in experiment
	In acetic anhydride for 0.25h; Ambient temperature;

Reference： [1]Ogata; Matsumoto; Takahashi; Shimizu; Kida; Murabayashi; Shiro; Tawara [Journal of Medicinal Chemistry, 1987, vol. 30, # 6, p. 1054 - 1068]

13
[ 51-80-9 ]
[ 78024-10-9 ]
[ 51690-03-0 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1990,p. 1532 - 1533
[2]Journal of the Chemical Society. Chemical communications,1990,p. 1532 - 1533
[3]Journal of the Chemical Society. Chemical communications,1990,p. 1532 - 1533
[4]Journal of the Chemical Society. Chemical communications,1990,p. 1532 - 1533

14
[ 51-80-9 ]
[ 74976-31-1 ]
3-dimethylaminomethyl-6-chloro-5-azaindole dihydrochloride monohydrate [ No CAS ]

Reference： [1]Pharmaceutical Chemistry Journal,1980,vol. 14,p. 308 - 313
Khimiko-Farmatsevticheskii Zhurnal,1980,vol. 14,p. 40 - 45

15
[ 51-80-9 ]
[ 131707-24-9 ]
[ 131707-25-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	In 1,4-dioxane; for 3.5h;Reflux; Inert atmosphere;	Indole 3 (200 mg, 0.476 mmol, 1.0 eq.) andN,N,N?,N?-tetramethyldiaminomethane (195 muL, 1.43 mmol, 3.0 eq.) were dissolved in 1,4-dioxane(2 mL). The reaction was heated to reflux for 3.5 h before removing the solvent in vacuo. Thereaction was then re-dissolved in ethyl acetate and 1 M HCl was added to the solution causing thetitle product to crash out as a pale yellow solid (117 mg, 51%).
51%		Indole 3 (200 mg, 0,476 mmof, 1.0 eq.) and N, N, N'f W? etramethyldi.amtnometha.ne (1-95 pL, 1.43 mmol, 3,0 eq.) were dissolved in 1 ,4- dsoxane (2 mi.). The reaction was. heated to reflux for 3,5 h before removing the solvent in vacuo. The reaction was then re-dissolved in ethyl acetate and 1 M HCI.was added to the solution causing the title product to crash .out as a pale yellow solid (1 17 mg, 51%). NMR-: delta (500 MHz, MeOD) 7.87 (s, I N, H7), 7.39 (dd, J ~ 7.4, 2.2 Hz, 2H, Hw), 7.35 ~ 7.31 (m, 3H, Hu and ). 4,87 (s, 2H , SCtf), 4.71 (s, 2H, C^N e?), 4.33 (q, J = 7.1 Hz, 2H, C02CCB3), 3,63 (s, 3H, HCHs), 2.97 (s, 6H, U(CH3 )> 1.39 (t, J - 7.1 Hz, 3H, C02C:H2C}, Sc (150 MHz, MeOD) 169,7 C02Et), 152.7 (<}, 149.0 (C), 13.7.7 (Cf0), 136,4 (<), 136.0 (<, 132.3 (C.}), 131.3 (CH), 129.3 (C?2), 11.9.8 (C>-),. 11:3.1 (C2), 111.3 (Cs), 108.3 (0,), 64.2. (CO2CH2CH3), 57.4 (CH2NMe2), 45.4 {CH2N(CR3)2); 33.7 (CHjSPh), 32,9 (NCH3), 16.6 (CO2CH2CH3). Rf: 0.25 (0078) (EtOAc). HR S .(ESI-TOF): G22H2sBrN203S ({M+H]) requires 477.0842, found 477,0844.

Reference： [1]Pharmaceutical Chemistry Journal,1993,vol. 27,p. 75 - 76
Khimiko-Farmatsevticheskii Zhurnal,1993,vol. 27,p. 70 - 71
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3744 - 3748
[3]Patent: WO2018/112128,2018,A1 .Location in patent: Page/Page column 9-10; 12

16
[ 51-80-9 ]
[ 15574-49-9 ]
[ 88461-90-9 ]

Reference： [1]Pharmaceutical Chemistry Journal,1983,vol. 17,p. 564 - 570
Khimiko-Farmatsevticheskii Zhurnal,1983,vol. 17,p. 940 - 946

17
[ 51-80-9 ]
[ 41292-65-3 ]
[ 57050-67-6 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1985,vol. 34,p. 1705 - 1708
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1985,p. 1855 - 1858

18
[ 51-80-9 ]
[ 41292-66-4 ]
[ 101018-70-6 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1985,vol. 34,p. 1705 - 1708
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1985,p. 1855 - 1858

19
[ 51-80-9 ]
[ 75-36-5 ]
[ 36916-18-4 ]
[ 72882-78-1 ]

Reference： [1]Journal of Medicinal Chemistry,1980,vol. 23,p. 392 - 402

20
[ 61160-18-7 ]
[ 51-80-9 ]
[ 174095-91-1 ]

Reference： [1]Tetrahedron,1996,vol. 52,p. 1835 - 1840
[2]Chemistry - A European Journal,2006,vol. 12,p. 1058 - 1066

21
[ 51-80-9 ]
[ 19685-09-7 ]
[ 119413-54-6 ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 5683 - 5686

22
[ 108-77-0 ]
[ 51-80-9 ]
[ 645-05-6 ]

Reference： [1]Journal of Chemical Research, Miniprint,1998,p. 2033 - 2055

23
[ 39604-64-3 ]
[ 51-80-9 ]
[ 15236-11-0 ]

Reference： [1]Synthetic Communications,1999,vol. 29,p. 3895 - 3899

24
[ 51-80-9 ]
[ 2555-30-8 ]
8-dimethylaminomethyl-7-hydroxy-4-phenyl coumarin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	In 1,4-dioxane at 100℃;

Reference： [1]Garazd; Garazd; Shilin; Khilya [Chemistry of Natural Compounds, 2000, vol. 36, # 5, p. 485 - 492]

25
[ 51-80-9 ]
[ 17587-22-3 ]
2C₁₀H₁₀F₇O₂^(1-)*C₅H₁₄N₂*2H⁽¹⁺⁾ [ No CAS ]

Reference： [1]Journal of Fluorine Chemistry,2005,vol. 126,p. 1222 - 1229

26
[ 615-16-7 ]
[ 51-80-9 ]
[ 100801-43-2 ]

Yield	Reaction Conditions	Operation in experiment
86%	With succinic acid anhydride; potassium carbonate In dichloromethane at 20℃; for 1h;

Reference： [1]Love, Brian E. [Journal of Organic Chemistry, 2007, vol. 72, # 2, p. 630 - 632]

27
[ 583-39-1 ]
[ 51-80-9 ]
[ 100531-96-2 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 630 - 632

28
[ 27387-31-1 ]
[ 51-80-9 ]
[ 99614-64-9 ]

Yield	Reaction Conditions	Operation in experiment
90%		Example 7 To a solution of 2.2 ml of acetyl chloride in 40ml of acetonitrile was, added dropwise 4.1 ml of N, N, N', N'-tetramethyldiaminomethane at 0C, which was then stirred for 1 hour. 2 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one was added to the reaction mixture, which was then stirred under reflux for 2 hours. 2.46 g of sodium acetate was added to the reaction mixture, which was then stirred under reflux for 6.5 hours. After completion of reaction, acetonitrile was distilled off and the water was added to the resulting residue. The resulting solid was stirred for 1 hour, filtered and dried to give 1.9 g of the title compound (yield 90%).
80%		Example 1 To the solution of 10 ml of acetic anhydride and 3.93 g of acetyl chloride in 40 ml of acetonitrile, was slowly added 6.82 ml of N, N, N', N'- tetramethyldiaminomethane. 2 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one was added to the reaction mixture, which was then stirred under reflux for 1 hour. 4. 1g of sodium acetate was added to the reaction mixture, which was then stirred under reflux. After completion of reaction, ethyl acetate was added to the reaction mixture, which was consequently washed with diluted HCI, saturated aqueous sodium bicarbonate solution, water and brine. The resulting organic layer was dried over anhydrous magnesium sulfate and evaporated to give 1.69 g of the title compound, which was used for next step without purification (yield 80%).
70%	With acetic anhydride; at 100℃; for 1.5h;Product distribution / selectivity;	Example 5 2g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one was added in 20 ml of acetic anhydride, and then the reaction mixture was heated to 100C. 15 ml of N, N, N', N'-tetramethyldiaminomethane was added dropwise for 1.5 hours. After completion of reaction, excess acetic anhydride was distilled off, and then ethyl acetate was added to the resulting residue, and then successively washed with diluted HCI, saturated aqueous sodium bicarbonate solution, water and brine. The resulting organic layer was dried over anhydrous magnesium sulfate and evaporated to give 1.50 g of the title compound, which was used for next step without purification (yield 70%).

Reference： [1]Patent: WO2005/37823,2005,A1 .Location in patent: Page/Page column 11
[2]Patent: WO2005/37823,2005,A1 .Location in patent: Page/Page column 9
[3]Patent: WO2005/37823,2005,A1 .Location in patent: Page/Page column 10

29
[ 693-98-1 ]
[ 27387-31-1 ]
[ 51-80-9 ]
[ 99614-02-5 ]

Yield	Reaction Conditions	Operation in experiment
81.5%	With acetyl chloride; In toluene; acetonitrile;Heating / reflux;Product distribution / selectivity;	Example 11: Synthesis of ls239-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one To the solution of 36 ml of acetyl chloride in 50 ml of actonitrile and 750 ml of toluene, was slowly added 51 ml of N, N, N', N'- tetramethyldiaminomethane at 0C, which was then stirred for 10min. 50 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 100 g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 150 ml of water was added to the resulting residue. The resulting solid was filtered and washed, and then dried under a reduced pressure. The resulting solid was suspended in 350 ml of methanol, and then 0.7g of active carbon was added to thereto, which was then stirred for 1 hour under reflux. The resulting mixture was filtered and washed with methanol, which was then stirred for 3 hours at room temperature. The resulting solid was filtered and dried to give 60 g of pure white title compound (yield 81.5%).
75%		Example 8: Synthesis of 12s3 « 9-tetrahydro-9-methyl-3-[(2-methel-lH- imidazole-1-vl) methyl]-4H-carbazol-4-one At-10C, 4 ml of N, N, N', N'-tetramethyldiaminomethane was slowly added to 46 ml of trifluoroacetic acid, which was then stirred for 30 min. 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 8 g of 2-methyl imidazole was added to the reaction mixture, which was then stirred for about 8 hours at 120-130C. After completion of reaction, the reaction mixture was cooled at room temperature, and then IN aq. sodium hydroxide was added thereto. The resulting solid was filtered and washed with water, and then dried. The resulting solid was suspended in 80 ml of methanol, and then 0.28 g of active carbon was added thereto, which was then stirred under reflux for 1 hour. The resulting mixture was filtered and washed with methanol, and then evaporated to give 2.2 g of 1, 2,3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazol-1-yl) methyl]- 4H-carbazol-4-one (yield 75%).
66%	With chloro-trimethyl-silane; In DMF (N,N-dimethyl-formamide); at 90℃; for 10h;Product distribution / selectivity;	Example 2: Synthesis of 1, 23*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 20 ml of N, N-dimethylformamide, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred at 90 C for 10 hours. 100ml of water was added to the reaction mixture. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.93 g of title compound (yield 66%).

60%	With chloro-trimethyl-silane; In acetonitrile; for 10h;Heating / reflux;Product distribution / selectivity;	Example 1 : Synthesis of 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 40 ml of water was added to the resulting residue. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.76 g of title compound (yield 60%).
58%	With acetyl chloride; In toluene; for 10h;Heating / reflux;Product distribution / selectivity;	Example 7: Synthesis of 123*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 2 ml of N, N, N', N'-tetramethyl- diaminomethane were suspended in 30 ml of toluene, and then 1.4 ml of acetyl chloride was slowly added thereto, which was then stirred for 10 min. 1.65g of 2-methyl imidazole was added to the reaction mixture, which was then stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 150ml dichloromethane and 50ml of IN aq. sodium hydroxide were added to the resulting residue. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone, which was then stirred for 3 hours, and then filtered and dried to give 1.70 g of title compound (yield 58%).
55%	With aluminum (III) chloride; In acetonitrile; for 10h;Heating / reflux;Product distribution / selectivity;	Example 4: Synthesis of 123, 9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yDmethyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 1.4 g of aluminum chloride was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. 150 ml dichloromethane and 50 ml of IN aq. sodium hydroxide were added to the reaction mixture. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.61 g of title compound (yield 55%).

Reference： [1]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 11
[2]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 10
[3]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 7
[4]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 7
[5]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 9-10
[6]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 8

30
[ 693-98-1 ]
[ 27387-31-1 ]
[ 51-80-9 ]
[ 99614-01-4 ]

Yield	Reaction Conditions	Operation in experiment
78%		Example 13: Synthesis of 1, 2, 3, 9-tetrahydro-9-methyl-3-F (2-methyl-IH- imidazole-1-yl methyl]-4H-carbazol-4-one hydrochloride dihydrate To the solution of 11 ml of acetyl chloride in 350 ml of actonitrile, was slowly added 21 ml of N, N, N', N'-tetramethyldiaminomethane at 0C, which was then stirred for 10min. 20 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4- one and 50 g of 2-methyl imidazole was subsequently added to the reaction mixture under reflux. After completion of reaction, the resulting solid was filtered and washed with acetonitrile and water, and then dried. The resulting solid was suspended in 250 ml of ethanol, and 11 ml of cone. HCl was slowly added thereto, which was then stirred for 2 hours. The resulting solid was filtered and washed with cold ethanol, and then re-crystallized with water to give 28.3 g of pure white title compound (yield 78%).
53%		Example 3: Synthesis of 123z9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-l-yl . methyll-4H-carbazol-4-one hydrochloride dihydrate 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 5 ml of acetonitrile and 30 ml of toluene, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 50 ml of water was added to the resulting residue. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours. The resulting solid was filtered and dried under a reduced pressure, which was then suspended in acetone, and then HCl was slowly added to thereto. The resulting suspension was stirred for 3 hours and cooled at 10C and below, which was then additionally stirred for 1 hour. The resulting solid was filtered and washed with acetone. The resulting solid was suspended in dichloromethane, which was then stirred under reflux for 1 hour and cooled at room temperature. The resulting solid was filtered and recrystallized with 10% aq. isopropyl alcohol to give 1.94 g of title compound (yield 53%).

Reference： [1]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 12
[2]Patent: WO2005/37822,2005,A1 .Location in patent: Page/Page column 8

31
[ 173252-76-1 ]
[ 51-80-9 ]
[ 872178-03-5 ]

Yield	Reaction Conditions	Operation in experiment
	With acetyl chloride In acetonitrile at 0 - 50℃; for 21h;

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2005/123681, 2005, A1 Location in patent: Page/Page column 34

32
[ 4769-97-5 ]
[ 51-80-9 ]
[ 7150-46-1 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid for 4.5h;	A N, N,Λ^,Λ^-Tetramethyldiaminomethane (2.2 mL, 15.6 mol) in acetic acid (30 mL) was added dropwise over 60 min to a solution of 4-nitroindole (2.30 g, 14.2 mol) in acetic acid (30 mL). After 3.5 h, the reaction was cooled to 0 °C, and 20 % aqueous sodium hydroxide was added to adjust the pΗ to 11. The mixture was extracted with CHCl3 (3 x 300 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: mlz = 220 (M + 1).
	Stage #1: 4-nitro-1H-indoIe; bis-(dimethylamino)methane In acetic acid for 4.5h; Stage #2: With sodium hydroxide In water	41.A N^NNyV'-Tetramethyldiaminomethane (2.2 mL, 15.6 mol) in acetic acid (30 mL) was added dropwise over 60 min to a solution of 4-nitroindoIe (2.30 g, 14.2 mol) in acetic acid (30 mL).After 3.5 h, the reaction was cooled to 0 0C3 and 20 % aqueous sodium hydroxide was added to adjust the pη to 11. The mixture was extracted with CηCI3 (3 * 300 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: mlz = 220 (M +I)-
	Stage #1: 4-nitro-1H-indoIe; bis-(dimethylamino)methane In acetic acid for 3.5h; Stage #2: With sodium hydroxide In water at 0℃;	46.A NjNjNjN'-Tetramethyldiaminomethane (2.2 mL, 15.6 mol) in acetic acid (30 mL) was added dropwise over 60 min to a solution of 4-nitroindole (2.30 g, 14.2 mol) in acetic acid (30 mL). After 3.5 h, the reaction was cooled to 0 0C, and 20 % aqueous sodium hydroxide was added to adjust the pH to 11. The mixture was extracted with CHCI3 (3 x 300 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: mlz - 220 (M + 1).

	With acetic acid for 4.5h;	11.A N,N,N,N-Tetramethyldiaminomethane (2.2 ϖiL, 15.6 mol) in acetic acid (30 mL) was added dropwise over 60 rain to a solution of 4-nitroindole (2.30 g, 14.2 mol) in acetic acid (30 mL). After 3.5 h, the reaction was cooled to 0 0C, and 20 % aqueous sodium hydroxide was added to adjust the pΗ to 11. The mixture was extracted with CHCl3 (3 x 300 mL) and the combined organic extracts were dried over Νa2Sθ4, filtered, and concentrated in vacuo to give the title compound. MS: mlz = 220 (M + I)-
	Stage #1: 4-nitro-1H-indoIe; bis-(dimethylamino)methane With acetic acid for 4.5h; Stage #2: With sodium hydroxide In water at 0℃;	11.A Step A. N.N-Dimethyl-l-(4-nitro-lH-indol-3-yl)methanamineN,N,λ^λ''-Tetramethyldiaminomethane (2.2 mL, 15.6 mol) in acetic acid (30 mL) was added dropwise over 60 min to a solution of 4-nitroindole (2.30 g, 14.2 mol) in acetic acid (30 mL). After 3.5 h, the reaction was cooled to 0 °C, and 20 % aqueous sodium hydroxide was added to adjust the pH to 11. The mixture was extracted with CHCl3 (3 x 300 mL) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: mlz = 220 (M + 1).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/31676, 2006, A2 Location in patent: Page/Page column 57
[2]Current Patent Assignee: MERCK & CO INC - WO2007/61692, 2007, A2 Location in patent: Page/Page column 119
[3]Current Patent Assignee: MERCK & CO INC - WO2007/61694, 2007, A2 Location in patent: Page/Page column 116
[4]Current Patent Assignee: MERCK & CO INC - WO2006/31491, 2006, A2 Location in patent: Page/Page column 61
[5]Current Patent Assignee: MERCK & CO INC - WO2008/153852, 2008, A1 Location in patent: Page/Page column 56-57

33
[ 173252-76-1 ]
[ 51-80-9 ]
[ 75-36-5 ]
[ 872178-03-5 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile	20.3 5-Trifluoromethoxy-indan-1-one Step 3 2-Dimethylaminomethyl-5-trifluoromethoxy-indan-1-one hydrochloride 6.4 ml of bis-(dimethylamino)-methane were added to a solution of 10.1 g of the product from step 2 in 37 ml of acetonitrile; 3.3 ml of acetic acid chloride were added dropwise at from 0 to 10° C., a further 25 ml of acetonitrile were added, and stirring was carried out for 3 hours at 50° C. and then for 18 hours at room temperature. The resulting solid was filtered off with suction, washed twice with diethyl ether and dried in vacuo (yield 12.4 g).

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - US2007/203192, 2007, A1

34
[ 102-54-5 ]
[ 51-80-9 ]
[ 1271-86-9 ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 3065 - 3072
[2]Gmelin Handbuch der Anorganischen Chemie,Gmelin Handbook: Fe: Org.Verb.A1, 2.5.7.10, page 166 - 167
[3]Gmelin Handbuch der Anorganischen Chemie,Gmelin Handbook: Fe: Org.Verb.A1, 2.5.7.10, page 166 - 167
[4]Organic Syntheses,1960,vol. 40,p. 31 - 33
[5]Journal of Organic Chemistry,1957,vol. 22,p. 355 - 358
[6]Journal of Organic Chemistry,1964,vol. 29,p. 2028 - 2030
[7]Tetrahedron,1973,vol. 29,p. 1575 - 1584
[8]Tetrahedron,1973,vol. 29,p. 1575 - 1584
[9]Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1963,p. 942 - 949
    Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1963,p. 1036 - 1045
[10]Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1963,p. 942 - 949
    Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1963,p. 1036 - 1045
[11]Dissertation abstracts, Diss. Purdue Univ. 1963,1964,vol. 24,p. 2687
[12]Angewandte Chemie - International Edition,2015,vol. 54,p. 1494 - 1498
    Angew. Chem.,
[13]Patent: DE2543999,1977,A1
    C.A.,1977,vol. 87,p. 67314

35
[ 51-80-9 ]
[ 4097-89-6 ]
[ 54761-04-5 ]
ytterbium 1,9-bis(2-aminoethyl)1,4,6,9,12,14-hexaazacyclohexadecane triflate acetonitrile [ No CAS ]
lanthanum 1,9-bis(2-aminoethyl)1,4,6,9,12,14-hexaazacyclohexadecane ditriflate triflate acetonitrile [ No CAS ]

Reference： [1]Pure and Applied Chemistry,1988,vol. 60,p. 1141 - 1144

36
[ 51-80-9 ]
[ 4097-89-6 ]
[ 54761-04-5 ]
ytterbium 1,9-bis(2-aminoethyl)1,4,6,9,12,14-hexaazacyclohexadecane triflate ditriflate [ No CAS ]

Reference： [1]Pure and Applied Chemistry,1988,vol. 60,p. 1141 - 1144

37
[ 51-80-9 ]
[ 4097-89-6 ]
[ 54761-04-5 ]
[ 116841-10-2 ]

Reference： [1]Inorganic Chemistry,1988,vol. 27,p. 4154 - 4165

38
[ 1277-49-2 ]
[ 51-80-9 ]
[ 31904-34-4 ]

Reference： [1]Compt. Rend. C 269 424/6,
[2]Compt. Rend. C 269 424/6,
[3]Bulletin de la Societe Chimique de France,
Bulletin de la Societe Chimique de France,1972,p. 2838 - 2847
[4]Bulletin de la Societe Chimique de France,
Bulletin de la Societe Chimique de France,1972,p. 2838 - 2847

39
[ 51-80-9 ]
[ 4097-89-6 ]
[ 54761-04-5 ]
[ 98104-55-3 ]

Reference： [1]Inorganic Chemistry,1985,vol. 24,p. 3469 - 3477

40
[ 51-80-9 ]
[ 2945-08-6 ]
[ 28042-27-5 ]

Yield	Reaction Conditions	Operation in experiment
47%	With acetic anhydride; In dimethyl sulfoxide; at 23℃; for 2h;	Step 2: To a stirred solution of <strong>[2945-08-6]methyl 2-(4-nitrophenyl)acetate</strong> (8.0g, 40.994 mmol, 1 .0 eq) in DMSO (40 mL) was added tetramethyldiaminomethane (8.38mL, 61 .491 mmol, 1 .5 eq) followed by acetic anhydride (12.78 mL, 135.17 mmol, 3.3eq) at RT and the mixture was stirred for 2h. The reaction mixture was diluted with water (40 mL), extracted with ether (80mL x 2) and the solvent evaporated. The crude product was purified by CC using EtOAc/PE (1 :9) as eluent) to get methyl 2-(4-nitrophenyl)acrylate (4.0 g, 47%, solid; TLC system: EtOAc/PE (3:7), Rf: 0.60).
1.30 g (84%)	With acetic anhydride; In dimethyl sulfoxide;	EXAMPLE 35 2-(4-Nitro-phenyl)-acrylic acid methyl ester (compound 135) [CAS-Number: 28042-27-5] is prepared according to the following literature: Y. Todo, J. Nitta, M. Miyajima, Y. Fukuoka, Y. Yamashiro, N. Nishida, I. Saikawa, H. Narita Chem. Pharm. Bull. 1994, 42, 2063-2070. To a solution of 1.46 g (7.50 mmol) of <strong>[2945-08-6](4-nitro-phenyl)-acetic acid methyl ester</strong> (CAS-Number: 2945-08-6) in 15 ml of dimethylsulfoxide is added at room temperature 1.15 g (11.3 mmol) of N,N,N',N'-tetramethyldiaminomethane followed by 2.53 g (24.8 mmol) of acetic anhydride. The reaction mixture is stirred for 2 hours, then diluted with diethyl ether (80 ml). The organic phase is washed with 1M NaHCO3 (40 ml), brine (2*40 ml), dried over sodium sulfate and concentrated using a vacuum rotary evaporator. The solid residue is recrystallized in diethylether/hexane to give 1.30 g (84%) of compound 135, white solid, m.p. 110-111 C. (lit.: m.p. 110.5-111 C.). 1H-NMR (1H 300 MHz, CDCl3): delta=8.45-8.37 (m, 2 arom. H), 7.80-7.75 (m, 2 arom. H), 6.74 (d, J=0.6 Hz, C=CHH, 1H), 6.23 (d, J=0.6 Hz, C=CHH, 1H), 4.05 (s, OCH3, 3H).

Reference： [1]Patent: WO2013/68461,2013,A1 .Location in patent: Page/Page column 144
[2]Patent: US2008/269382,2008,A1

41
[ 51-80-9 ]
[ 3027-13-2 ]
[ 197145-37-2 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid;	In the first step, bis(dimethylamino)methane was reacted with 3-(3-methoxyphenyl)propan-2-one in a Mannich reaction to give (rac)-3-(dimethylamino)-1-(3-methoxyphenyl)-2-methylpropan-1-one, after purification by chromatography

Reference： [1]Patent: US2011/190267,2011,A1 .Location in patent: Page/Page column 67

42
[ 37951-49-8 ]
[ 51-80-9 ]
[ 197145-37-2 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid;	In the first step, bis(dimethylamino)methane was reacted with 3-(3-methoxyphenyl)propan-2-one, in the presence of trifluoroacetic acid, in a Mannich reaction, to give (rac)-3-(dimethylamino)-1-(3-methoxyphenyl)-2-methylpropan-1-one

Reference： [1]Patent: US2010/227921,2010,A1 .Location in patent: Page/Page column 10

43
[ 1191-08-8 ]
[ 51-80-9 ]
[ 1369273-08-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With samarium(III) chloride hexahydrate In chloroform at 60℃; for 1.5h; Inert atmosphere; chemoselective reaction;

Reference： [1]Location in patent: experimental part Khairullina; Akmanov; Tyumkina; Kunakova; Ibragimov [Russian Journal of Organic Chemistry, 2012, vol. 48, # 2, p. 175 - 179]

44
[ 51-80-9 ]
[ 1455091-10-7 ]
[ 1509958-19-3 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; at 55℃;	102371 A flask was charged with 3a (29.5 g) and acetic acid (44.3 g ± 5%), and then stirred. Bis5 dimethylaminomethane (12.8 g ± 2%) was slowly added. The mixture was heated to 55 ± 5 C andmaintained until reaction completion. The reaction product was evaluated by MS, HPLC and ?H NMR. ?H NMR (200 MHz, DMSO-d6) d 11.7 (S, 1 H), 8.38 (d, J = 9.0 Hz, 1 H), 7.61 (dd, J = 9.0, 2.7 Hz, 1 H), 7.49 (m, 3 H), 7.21 (m, 3 H), 5.34 (s, 2 H), 3.97 (s, 3 H), 1.98 (s, 3 H); MS-(+)-ion M+1 = 368.12.
	With acetic acid; at 55℃; for 6h;	At room temperature,N, N, N ', N'-tetramethylmethylenediamine (1.08 g, 10.60 mmol)Slowly added to4-hydroxy-7-phenoxyisoquinolyl-3-carboxylic acidMethyl ester(2.60 g.8.80 mmol)In acetic acid (4 mL)The reaction was warmed to 55 C and the reaction was stirred for 6 hours.Cooled to room temperature and used directly in the next step.
	With acetic acid; at 25 - 55℃;	Add <strong>[1455091-10-7]methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate</strong> to the reaction flask(525 mg, 1.78 mmol), acetic acid (2 mL), N,N,N',N'-tetramethylethylenediamine (360 mg, 3.52 mmol) was added dropwise at 25 C or lower. After the completion of the dropwise addition, the mixture was heated to 55 C to stir the reaction. After overnight, the reaction was monitored by thin layer chromatography and then cooled to 25 C to give the title compound (2e).

Reference： [1]Patent: WO2014/14834,2014,A1 .Location in patent: Paragraph 0237
[2]Patent: CN106083720,2016,A .Location in patent: Paragraph 0062; 0073-0074
[3]Patent: CN108341777,2018,A .Location in patent: Paragraph 0199; 0200; 0207; 0208; 0567-0570

45
[ 31366-25-3 ]
[ 51-80-9 ]
[ 138535-96-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: tetrathiafulvalene With 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex In tetrahydrofuran at 25℃; Stage #2: bis-(dimethylamino)methane With trifluoroacetic anhydride In tetrahydrofuran; dichloromethane at -30℃; for 2h;

Reference： [1]Nafe, Julia; Auras, Florian; Karaghiosoff, Konstantin; Bein, Thomas; Knochel, Paul [Organic Letters, 2015, vol. 17, # 21, p. 5356 - 5359]

46
[ 51-80-9 ]
[ 6147-11-1 ]
4-dimethylaminomethyl-1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	In benzene; at 20℃; for 0.75h;	N,N,N',N'-Tetramethylmethanediamine(27.5 muL, 0.2mmol) was added to a suspension of alpha-mangostin (1) (82.1 mg, 0.2 mmol) in benzene (3 mL). The mixture was stirredat rt for 45 min. The excess of solvent was removed at reduced pressure and thereaction mixture was purified by column chromatography (Silica gel, 70-230 mu,CHCl3-EtOH, 100:150:1).4-Dimethylaminomethyl-1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one(2). Yield 68.5 mg (73%). Yellowish powder, mp 162-164 C. TLC: Sorbfil, Rf 0.22, CHCl3-EtOH,25:1. UV-vis (EtOH, lambdamax, nm): 245, 265 (shoulder), 325 (shoulder),and 362. IR (KBr, n, cm-1):3375 (O-H), 2961, 2916, 2857, 2791, 2727, 1460 (CH3, CH2),1618, 1578 (C=O, C-H), 1175, 1161 (C-O). 1H NMR (300 MHz, CDCl3):d = 1.68 and 1.69 (both s, 3H and 3H, C14H3,C20H3), 1.82 (s, 6H, C15H3, C19H3),2.41 (s, 6H, NMe2), 3.41 (d, 2H, C16H2, J = 6.8 Hz), 3.80 (s, 3H, OCH3),3.90 (s, 2H, C21H2), 4.14 (d, 2H, C11H2,J = 6.0 Hz), 5.26 (br. t, 1H, C12H2),5.28 (br. t, 1H, C17H2), 6.82 (s, 1H, C5H),7.30 (br. s, 2H, C3-OH, C6-OH), 13.62 (br. s, 1H, C1-OH).13C NMR (75 MHz, CDCl3): d = 17.84 (C15),18.19 (C19), 21.35 (C16), 25.80 (C14, C20),26.51 (C11), 44.14 (NMe2), 54.71 (C21), 62.00(OCH3), 97.12 (C4), 101.35 (C5), 102.49 (C9a),110.82 (C2), 112.11 (C8a), 122.59 (C17),123.29 (C12), 131.77 and 131.94 (C13, C18),137.06 (C8), 142.54 (C7), 151.78 (C4a), 154.28(C6), 155.27 (C10a), 160.17 (C1), 164.30 (C3),181.83 (C9). MS-MALDI(m/z): 468.25 [MH]+. Found (%):C, 69.57; H, 6.80. Calc. for C27H33NO6 (%): C,69.36; H, 7.11.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 826 - 829

47
[ 51-80-9 ]
[ 3681-99-0 ]
3'-methylene-dimethylamine-puerarin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With pyridine; hydrogenchloride; In methanol; water; at 60℃; for 4h;	accurately weighed 0.146g <strong>[3681-99-0]puerarin</strong> placed in 100mL three-necked bottle, 10 mL of anhydrous pyridine was added to dissolve, Was added dropwise with a dropping funnel, 175 g of bis- (dimethylamine) methane and 0.8 mL of concentrated hydrochloric acid (37 wtpercent, density of about 1.19 g / cm3) were heated and refluxed at 60 ° C, TLC followed the reaction for 4 hours, The reaction was stopped and the solvent was distilled off under reduced pressure to mix the solvent (CH3C1-CH30H, 4: 1, V / V) The crystals were recrystallized to give a deep red solid (95.3 mg, yield 65percent)

Reference： [1]Patent: CN103923073,2016,B .Location in patent: Paragraph 0027-0028

48
[ 109-57-9 ]
[ 1191-08-8 ]
[ 51-80-9 ]
N,N'-(2,7-dithiaoctane-1,8-diyl)bis(N'-allylthiourea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: Allylthiourea In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

Reference： [1]Khairullina; Geniyatova; Meshcheryakova; Tyumkina; Khalilov; Ibragimov; Dzhemilev [Russian Journal of Organic Chemistry, 2017, vol. 53, # 3, p. 315 - 321][Zh. Org. Khim., 2017, vol. 53, # 3, p. 319 - 325,7]

49
[ 1191-08-8 ]
[ 51-80-9 ]
[ 103-85-5 ]
N,N'-(2,7-dithiaoctane-1,8-diyl)bis(N'-phenylthiourea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: monophenylthiourea In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

50
[ 1191-08-8 ]
[ 51-80-9 ]
[ 538-32-9 ]
N,N'-(2,7-dithiaoctane-1,8-diyl)bis(N'-benzylurea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: benzylurea In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

51
[ 1191-08-8 ]
[ 51-80-9 ]
[ 557-11-9 ]
N,N'-(2,7-dithiaoctane-1,8-diyl)bis(N'-allylurea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: allylurea In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

52
[ 51-80-9 ]
[ 64-10-8 ]
[ 540-63-6 ]
N,N'-(2,5-dithiahexane-1,6-diyl)bis(N'-phenylurea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: bis-(dimethylamino)methane; ethane-1,2-dithiol With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: phenyl carbamate In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

53
[ 109-80-8 ]
[ 51-80-9 ]
[ 64-10-8 ]
N,N'-(2,6-dithiaheptane-1,7-diyl)bis(N'-phenylurea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 1.3-propanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: phenyl carbamate In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

54
[ 1191-08-8 ]
[ 51-80-9 ]
[ 64-10-8 ]
N,N'-(2,7-dithiaoctane-1,8-diyl)bis(N'-phenylurea) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane With caesium carbonate In chloroform at 20℃; for 0.5h; Stage #2: phenyl carbamate In ethanol; chloroform at 60℃; for 6h;	Thiomethylation of substituted thioureas with N,N,N′,N′-tetramethylmethanediamine and α,ω-alkanedithiols (general procedure) General procedure: A glass reactor was charged with 10 mmol of N,N,N′,N′-tetramethyl-methanediamine and 10 mmol of the corresponding α,ω-alkanedithiol in 5 mL of chloroform, and the mixture was stirred for 30 min at room temperature. A solution of 20 mmol of N-substituted thiourea in 10 mL of ethanol and 1 mmol of cesium carbonate were then added, and the mixture was stirred for 6 h at 60 °C. Compounds 1(a-e)-5(a-e) were isolated from the reaction mixture.

55
[ 1191-08-8 ]
[ 51-80-9 ]
[ 17356-08-0 ]
1,7-dithia-3,5-diazacycloundecane-4-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane In ethanol at 20℃; for 0.0833333h; Stage #2: thiourea With caesium carbonate In ethanol at 60℃; for 8h;	4.2 Cyclothiomethylation of (thio)urea with bis-(N,N-dimethylamino)methane and α,ω-alkanedithiols. Method A General procedure: In a glass reactor placed on a magnetic stirrer bis-(N,N-dimethylamino)methane (2mmol), α,ω-alkanedithiol (1mmol) and EtOH (5mL) are charged and stirred for 5minat room temperature (∼20°C), and then, (thio)urea (1mmol) and Cs2CO3 (0.1mmol) in EtOH (5mL) are added. The reaction mixture is stirred for 8hat 60°C. The separated powder of compounds 1,7-dithia-3,5-diazacycloalkan-4-ones 2- or 1,7-dithia-3,5-diazocycloalkane-4-thiones 3- are filtered off, washed with water, and dried.

Reference： [1]Khairullina, Regina R.; Geniyatova, Alfiya R.; Tyumkina, Tatyana V.; Karamzina, Diana S.; Ibragimov, Askhat G.; Dzhemilev, Usein M. [Tetrahedron, 2017, vol. 73, # 50, p. 7079 - 7084]

56
[ 1191-08-8 ]
[ 51-80-9 ]
[ 57-13-6 ]
1,7-dithia-3,5-diazacycloundecan-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane In ethanol at 20℃; for 0.0833333h; Stage #2: urea With caesium carbonate In ethanol at 60℃; for 8h;	4.2 Cyclothiomethylation of (thio)urea with bis-(N,N-dimethylamino)methane and α,ω-alkanedithiols. Method A General procedure: In a glass reactor placed on a magnetic stirrer bis-(N,N-dimethylamino)methane (2mmol), α,ω-alkanedithiol (1mmol) and EtOH (5mL) are charged and stirred for 5minat room temperature (∼20°C), and then, (thio)urea (1mmol) and Cs2CO3 (0.1mmol) in EtOH (5mL) are added. The reaction mixture is stirred for 8hat 60°C. The separated powder of compounds 1,7-dithia-3,5-diazacycloalkan-4-ones 2- or 1,7-dithia-3,5-diazocycloalkane-4-thiones 3- are filtered off, washed with water, and dried.

57
[ 108-19-0 ]
[ 51-80-9 ]
[ 3544-24-9 ]
3-[(8-methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)amino]benzamide [ No CAS ]
3-amino-N-[(dimethylamino)methyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With samarium(III) chloride hexahydrate; In ethanol; for 12h;Heating;	General procedure: a. A mixture of 1 mmol of carbamide in 5 mL of ethanol, 2.5 mmol of bis(N,N-dimethylamino)methane and 0.2 mmol of catalyst NiCl2·6H2O or SmCl3·6H2O was stirred for 5 min, then solution of 1 mmol of aminobenzamide in 5 mL of ethanol was added. The temperature was raised to 80C, and the reaction mixture was stirred for 12 h. The target products were isolated by column chromatography on SiO2.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 204 - 211
Zh. Obshch. Khim.,2019,vol. 89,p. 202 - 210,9

58
[ 108-19-0 ]
[ 51-80-9 ]
[ 2835-68-9 ]
4-[(8-methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)amino]benzamide [ No CAS ]
4-amino-N-[(dimethylamino)methyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With samarium(III) chloride hexahydrate; In ethanol; for 12h;Heating;	General procedure: a. A mixture of 1 mmol of carbamide in 5 mL of ethanol, 2.5 mmol of bis(N,N-dimethylamino)methane and 0.2 mmol of catalyst NiCl2·6H2O or SmCl3·6H2O was stirred for 5 min, then solution of 1 mmol of aminobenzamide in 5 mL of ethanol was added. The temperature was raised to 80C, and the reaction mixture was stirred for 12 h. The target products were isolated by column chromatography on SiO2.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 204 - 211
Zh. Obshch. Khim.,2019,vol. 89,p. 202 - 210,9

59
[ 108-19-0 ]
[ 51-80-9 ]
N,N'-bis[(dimethylamino)methyl]allophanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With samarium(III) chloride hexahydrate; In ethanol; for 8h;	General procedure: A mixture of 5 mmol of bis(N,N-dimethylamino)methane, 0.1 mmol of SmCl3·6H2O and 2 mmol of carbamide dissolved in 10 mL of ethanol was stirred for 8 h at room temperature. The target products were isolated by column chromatographyon SiO2.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 204 - 211
Zh. Obshch. Khim.,2019,vol. 89,p. 202 - 210,9

60
[ 108-19-0 ]
[ 51-80-9 ]
[ 28144-70-9 ]
2-[(8-methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)amino]benzamide [ No CAS ]
2-amino-N-[(dimethylamino)methyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With samarium(III) chloride hexahydrate; In ethanol; for 12h;Heating;	General procedure: a. A mixture of 1 mmol of carbamide in 5 mL of ethanol, 2.5 mmol of bis(N,N-dimethylamino)methane and 0.2 mmol of catalyst NiCl2·6H2O or SmCl3·6H2O was stirred for 5 min, then solution of 1 mmol of aminobenzamide in 5 mL of ethanol was added. The temperature was raised to 80C, and the reaction mixture was stirred for 12 h. The target products were isolated by column chromatography on SiO2.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 204 - 211
Zh. Obshch. Khim.,2019,vol. 89,p. 202 - 210,9

61
[ 51-80-9 ]
[ 14970-87-7 ]
[ 5452-37-9 ]
6-cyclooctyl-1,11-dioxa-4,8-dithia-6-azacyclotridecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: bis-(dimethylamino)methane; 3,6-dioxa-1,8-octandithiol With samarium(III) chloride hexahydrate In chloroform at 20℃; for 0.5h; Stage #2: cyclooctylamine In ethanol; chloroform at 20℃; for 3h;	General procedure for heterocyclization of carbocyclicamines. General procedure: A mixture of N,N,N1,N1-tetramethylmethanediamine(0.27 mL, 2 mmol), 3,6-dioxa-1,8-octanedithiol (0.16 mL, 1 mmol) in 5 mL of CHCl3 and SmCl3.6H2O (0.018 g, 0.05 mmol) was stirred at room temperature for 30 min, then the corresponding cycloalkylamine (1 mmol) in 5 mL of EtOH was added dropwise.The reaction mixture was stirred for 3 h at ~20°C and then evaporated. The residue was chromatographed on a SiO2column obtaining pure heterocycles 4-8.

Reference： [1]Rakhimova; Ismagilov; Ibragimov [Russian Journal of General Chemistry, 2019, vol. 89, # 8, p. 1591 - 1594][Zh. Obshch. Khim., 2019, vol. 89, # 8, p. 1591 - 1594,4]

62
[ 51-80-9 ]
[ 3114-70-3 ]
[ 540-63-6 ]
3,3'-(cyclohexane-1,4-diyl)di-1,5,3-dithiazepane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		General procedure: A mixture of N,N,N1,N1-tetramethylmethanediamine (0.53 mL, 4 mmol), 1,2-ethanedithiol (0.17 mL,2 mmol) in 5 mL of CHCl3 and SmCl3.6H2O (0.018 g,0.05 mmol) was stirred at room temperature for 30 min,then the corresponding alpha,omega-diamine (1 mmol) in 5 mLof EtOH was added dropwise. The reaction mixture wasstirred for 3 h at ~20 and then evaporated. The residue was chromatographed on a column with SiO2 obtaining pure heterocycles 1-3.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 1591 - 1594
Zh. Obshch. Khim.,2019,vol. 89,p. 1591 - 1594,4

63
[ 51-80-9 ]
[ 497-18-7 ]
1,2,4,5-tetrazinan-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%		General procedure: Cyclothiomethylation of carbonic acid diamidesand dihydrazides with diamine and H2Sor Na2S·9H2O (general procedure). A glass reactorequipped with a magnetic stirrer and a gas-inlet tube wasloaded with diamine (2.5 mmol), carbonic acid diamideor dihydrazide (1 mmol), EtOH (5 mL), and RbNO3(0.2 mmol), and the mixture was stirred for 1 h at roomtemperature (~20C), after which gaseous H2S wasbubbled into the mixture under constant stirring for 1 huntil saturation (method a) or Na2S·9H2O (20 mmol)was added (method b). After 4-h stirring at 60C, compounds1 and 2 were fi ltered off, washed with hot water,and dried, and compounds 3 and 4 were extracted withchloroform and purifi ed by column chromatography onSiO2. 1,2,4,5-Tetrazinan-3-one (4). Yield 0.092 g(90%, method a), amorphous powder, mp 80-86C.IR spectrum, nu, cm-1: 33283253, 2924-2854, 1651,1537, 1462, 1367, 1176, 1022, 987, 745734. 1 NMRspectrum, delta, ppm: 4.30 br.s (2, CH2), 4.74 and 7.95 br.s(4, N). 13C NMR spectrum, delta, ppm: 67.27 (CH2),162.85 (C=O). MALDI TOF, m/z: 140.053 [M + K H]+, 159.073 [M + K + H2O]+.

Reference： [1]Russian Journal of Organic Chemistry,2020,vol. 56,p. 276 - 280
Zh. Org. Khim.,2020,vol. 56,p. 277 - 282,6

64
[ 51-80-9 ]
[ 2835-68-9 ]
4,4'-methylenebis(thiomethylenimino)dibenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: bis-(dimethylamino)methane; 4-aminobenzamide With samarium(III) chloride hexahydrate In ethanol at 20℃; for 1h; Stage #2: With sodiumsulfide nonahydrate In ethanol at 60℃; for 4h;	Catalytic thiomethylation of 2-, 3-, and 4-aminobenzamides with diamine, Na₂S•9H₂O, NaHS, or H₂S (general procedure). General procedure: Aminobenzamide (1 mmol), diamine (2.5 mmol), EtOH (5 mL), and catalyst (0.1 mmol (method A), 0.2 mmol (method B)) were placed into a glass reactor equipped with a magnetic stirrer and a gas inlet adapter and the mixture was stirred for 1 h at room temperature (~20 °). Then Na2S•9H2O (method A) or NaHS (20 mmol) (method B) was added, or the reaction mixture was saturated with hydrogen sulfide by bubbling with constant stirring for 1 h (method C). The reaction mixture was stirred for 4 h at 60 °C. The target products were isolated using column chromatography on SiO2.

Reference： [1]Khairullina; Tyumkina; Akhmetshina; Abdullin; Ibragimov [Russian Chemical Bulletin, 2021, vol. 70, # 1, p. 152 - 157][Izv. Akad. Nauk, Ser. Khim., 2021, # 1, p. 152 - 157,6]

65
[ 1191-08-8 ]
[ 51-80-9 ]
[ 28144-70-9 ]
2-[({4-[([2-(aminocarbonyl)phenyl]amino}methyl)thio]butyl}thio)methyl]amino}benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: 1,4-Butanedithiol; bis-(dimethylamino)methane In ethanol; chloroform for 0.5h; Stage #2: anthranilic acid amide With samarium(III) chloride hexahydrate In ethanol; chloroform at 70℃; for 24h;	Thiomethylation of 2-aminobenzamide (1) using bis(N,N-dimethylamino)methane (4) and α,ω-dithiols 5a-d (general procedure).Method A. General procedure: A two-neck fl ask was charged with α,ω-alkanedithiol5a-d (1 mmol; 0.083 mL of 1,2-ethanedithiol (5a), 0.100 mL of 1,3-propanedithiol (5b), 0.117 mL of 1,4-butanedithiol(5c) or 0.134 mL of 1,5-pentanedithiol (5d)), bis(N,Ndimethylamino)methane (4) (0.300 mL, 2 mmol), and solvent(10 mL, a 1 : 1 mixture of EtOH-CHCl3). The resulting mixturewas stirred for 30 min, then catalyst SmCl3•6H2O (0.04 g, 0.1 mmol)and a solution of 2-aminobenzamide (1) (0.272 g, 2 mmol) inEtOH (5 mL) were added. The reaction mixture was stirred for24 h. Acyclic products 7a-d were isolated by silica gel columnchromatography (eluent hexane-ethyl acetate, 1 : 1).