[ CAS No. 1186-73-8 ]

Name: 1186-73-8|Trimethyl methanetricarboxylate|98%
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Quality Control of [ 1186-73-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1186-73-8 ]

Product Details of [ 1186-73-8 ]

CAS No. :	1186-73-8	MDL No. :	MFCD02178862
Formula :	C₇H₁₀O₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BNOIMFITGLLJTH-UHFFFAOYSA-N
M.W :	190.15 g/mol	Pubchem ID :	136922
Synonyms :

Calculated chemistry of [ 1186-73-8 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.57
Num. rotatable bonds :	6
Num. H-bond acceptors :	6.0
Num. H-bond donors :	0.0
Molar Refractivity :	39.62
TPSA :	78.9 Å²

Pharmacokinetics

GI absorption :	High
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) :	-7.28 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.11
Log Po/w (XLOGP3) :	0.26
Log Po/w (WLOGP) :	-0.88
Log Po/w (MLOGP) :	-0.33
Log Po/w (SILICOS-IT) :	-0.13
Consensus Log Po/w :	0.21

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.79
Solubility :	31.1 mg/ml ; 0.163 mol/l
Class :	Very soluble
Log S (Ali) :	-1.48
Solubility :	6.33 mg/ml ; 0.0333 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.16
Solubility :	131.0 mg/ml ; 0.69 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.53

Safety of [ 1186-73-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1186-73-8 ]

* 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 [ 1186-73-8 ]
Downstream synthetic route of [ 1186-73-8 ]

[ 1186-73-8 ] Synthesis Path-Upstream 1~13

1
[ 79-22-1 ]
[ 108-59-8 ]
[ 1186-73-8 ]

Reference： [1] European Journal of Organic Chemistry, 2010, # 6, p. 1037 - 1045
[2] Liebigs Annalen, 1995, # 8, p. 1483 - 1494
[3] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363
[4] Journal of Physical Organic Chemistry, 2010, vol. 23, # 3, p. 255 - 265

2
[ 39000-70-9 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363
[2] Journal of the American Chemical Society, 1926, vol. 48, p. 3195

3
[ 360-54-3 ]
[ 1186-73-8 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1977, vol. 26, p. 1023 - 1027[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1977, vol. 26, p. 1117 - 1121

4
[ 67-56-1 ]
[ 17094-36-9 ]
[ 36797-93-0 ]
[ 1186-73-8 ]

Reference： [1] Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4404 - 4405
[2] Journal of Organic Chemistry, 1985, vol. 50, # 22, p. 4404 - 4405

5
[ 5538-05-6 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363

6
[ 108-59-8 ]
[ 1186-73-8 ]

Reference： [1] Organic Syntheses, 1933, vol. 13, p. 100

7
[ 75-44-5 ]
[ 18424-76-5 ]
[ 1186-73-8 ]

Reference： [1] Chemische Berichte, 1926, vol. 59, p. 990[2] Chemische Berichte, 1916, vol. 49, p. 2716

8
[ 5838-00-6 ]
[ 127-08-2 ]
[ 1186-73-8 ]

9
[ 18424-76-5 ]
[ 79-22-1 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1932, vol. 499, p. 228,283
[2] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 1234,1246

10
[ 59681-94-6 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1932, vol. 499, p. 228,283

11
[ 67-56-1 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363

12
[ 5485-76-7 ]
[ 64-19-7 ]
[ 1186-73-8 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 1234,1246

13
[ 18424-76-5 ]
[ 79-22-1 ]
[ 1186-73-8 ]

Reference： [1] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363

[ 1186-73-8 ] Synthesis Path-Downstream 1~59

1
[ 59681-94-6 ]
[ 1186-73-8 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1932,vol. 499,p. 228,283

2
[ 5485-76-7 ]
[ 64-19-7 ]
[ 1186-73-8 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1938,vol. 57,p. 1234,1246

3
[ 5538-05-6 ]
[ 1186-73-8 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1913,vol. 397,p. 363

4
[ 39000-70-9 ]
[ 1186-73-8 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1913,vol. 397,p. 363

5
[ 5838-00-6 ]
[ 127-08-2 ]
[ 1186-73-8 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1977,vol. 26,p. 1023 - 1027
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1977,vol. 26,p. 1117 - 1121

6
[ 50-00-0 ]
[ 1186-73-8 ]
[ 5491-07-6 ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

7
[ 75-77-4 ]
[ 1186-73-8 ]
[ 32364-57-1 ]

Reference： [1]Journal of Organometallic Chemistry,1972,vol. 46,p. 59 - 71

8
[ 3377-21-7 ]
[ 1186-73-8 ]
[ 5564-28-3 ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

9
[ 111-66-0 ]
[ 1186-73-8 ]
Trimethyl-nonan-1,1,1-tricarboxylat [ No CAS ]

Reference： [1]Synthesis,1970,p. 99 - 140

10
[ 111-81-9 ]
[ 1186-73-8 ]
[ 1472-87-3 ]

Reference： [1]Synthesis,1970,p. 99 - 140

11
[ 67-56-1 ]
[ 17094-36-9 ]
[ 36797-93-0 ]
[ 1186-73-8 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 4404 - 4405
[2]Journal of Organic Chemistry,1985,vol. 50,p. 4404 - 4405

12
[ 768-03-6 ]
[ 1186-73-8 ]
[ 97427-61-7 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1985,vol. 39,p. 7 - 14

13
[ 75-77-4 ]
[ 90484-46-1 ]
[ 1186-73-8 ]
[ 97427-57-1 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1985,vol. 39,p. 7 - 14

14
[ 2684-02-8 ]
[ 1186-73-8 ]
[ 119471-92-0 ]

Reference： [1]Tetrahedron Letters,1988,vol. 29,p. 3379 - 3382

15
[ 1186-73-8 ]
2C₇H₉O₆^(1-)*Ba⁽²⁺⁾ [ No CAS ]

Reference： [1]New Journal of Chemistry,2001,vol. 25,p. 400 - 407

16
[ 1186-73-8 ]
5-amino-2-oxo-2,3-dihydro-benzo[<i>e</i>]indole-1,1-dicarboxylic acid dimethyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1998,vol. 63,p. 9414 - 9420

17
[ 1186-73-8 ]
[ 213181-23-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1998,vol. 35,p. 627 - 636

18
[ 1186-73-8 ]
[ 213181-32-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1998,vol. 35,p. 627 - 636

19
[ 1186-73-8 ]
1,1,1-Tris(methoxycarbonyl)pentane [ No CAS ]

Reference： [1]Liebigs Annales,1995,p. 1483 - 1494

20
[ 1186-73-8 ]
1,1,1-Tris(methoxycarbonyl)-2,2-diphenylethane [ No CAS ]

Reference： [1]Liebigs Annales,1995,p. 1483 - 1494

21
[ 1186-73-8 ]
9-Fluorenyltris(methoxycarbonyl)methane [ No CAS ]

Reference： [1]Liebigs Annales,1995,p. 1483 - 1494

22
[ 1186-73-8 ]
[ 97427-58-2 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1985,vol. 39,p. 7 - 14

23
[ 360-54-3 ]
[ 1186-73-8 ]

24
[ 1186-73-8 ]
[ 5101-91-7 ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

25
[ 1186-73-8 ]
1-Benzylamino-aethan-tricarbonsaeure-(2,2,2)-trimethylester [ No CAS ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

26
[ 1186-73-8 ]
[ 5564-30-7 ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

27
[ 1186-73-8 ]
[ 5491-02-1 ]

Reference： [1]Chemische Berichte,1966,vol. 99,p. 281 - 290

28
[ 16872-09-6 ]
[ 1186-73-8 ]
[ 16872-10-9 ]
[ 20505-38-8 ]
[ 20505-39-9 ]

Reference： [1]Inorganic Chemistry,1986,vol. 25,p. 129 - 130

29
[ 109-99-9 ]
[ 1184-54-9 ]
[ 1186-73-8 ]
copper(II) dicarbomethoxymethanate [ No CAS ]
[ 342805-80-5 ]

Reference： [1]New Journal of Chemistry,2001,vol. 25,p. 400 - 407

30
[ 342805-80-5 ]
[ 1186-73-8 ]
copper(II) dicarbomethoxymethanate [ No CAS ]

Reference： [1]New Journal of Chemistry,2001,vol. 25,p. 400 - 407

31
C₇₃H₂₁F₁₇O₆ [ No CAS ]
[ 1186-73-8 ]
C₈₇H₃₉F₁₅O₁₈ [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2010,p. 1037 - 1045

32
C₈₆H₄₂F₁₆O₁₂ [ No CAS ]
[ 1186-73-8 ]
C₉₃H₅₁F₁₅O₁₈ [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2010,p. 1037 - 1045

33
[ 185912-87-2 ]
[ 1186-73-8 ]
[ 1199940-07-2 ]

Reference： [1]Russian Chemical Bulletin,2012,vol. 61,p. 264 - 279
[2]European Journal of Organic Chemistry,2010,p. 1037 - 1045

34
[ 1186-73-8 ]
[ 28791-16-4 ]

Reference： [1]Journal of Physical Organic Chemistry,2010,vol. 23,p. 255 - 265

35
C₂₄H₂₉N₂OS⁽¹⁺⁾*Cl^(1-) [ No CAS ]
[ 1186-73-8 ]
(3aS,4S,6aR)-1,3-dibenzyl-4-(ω,ω,ω-tri-methoxycarbonylbutyl)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)-ketone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.6%		Embodiment 3; A. Synthesis of (3aS,4S,6aR)-1,3-dibenzyl-4-(omega,omega,omega-methoxycarbonyl buty)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)-ketone; Put 300 ml methylbenzene and 60% sodium hydride 3.3 g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8 g (0.085 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80 C. and protected for 2 h by heat preservation; add 33.3 g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 70 C. for a 10 h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-1.0 g tri-ester dibenzyl biotin (96.6% of the theoretical value), and the HPLC measured content is 98.4% with no impurity 5 (hereinafter to be referred as dicarboxylic ester).

Reference： [1]Patent: US2012/65406,2012,A1 .Location in patent: Page/Page column 4

36
Br^(1-)*C₂₄H₂₉N₂OS⁽¹⁺⁾ [ No CAS ]
[ 1186-73-8 ]
(3aS,4S,6aR)-1,3-dibenzyl-4-(ω,ω,ω-tri-methoxycarbonylbutyl)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)-ketone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.3%		Embodiment 2; A. Synthesis of (3aS,4S,6aR)-1,3-dibenzyl-4-(omega,omega,omega-3-methoxycarbonyl butyl)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)- ketone; Put 300 ml methylbenzene and 60% sodium hydride 3.3 g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8 g (0.083 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80 C. and protected for 2 h by heat preservation; add 33.3 g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 80 C. for a 15 h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-0.2 g tri-ester dibenzyl biotin (95.3% of the theoretical value), and the HPLC measured content is 98.0% with no impurity 5 (hereinafter to be referred as dicarboxylic ester).

Reference： [1]Patent: US2012/65406,2012,A1 .Location in patent: Page/Page column 4

37
[ 33719-11-8 ]
[ 1186-73-8 ]
[ 1250271-03-4 ]

Yield	Reaction Conditions	Operation in experiment
95.3%		Put 300 ml methylbenzene and 60% sodium hydride 3.3g (0.0825 mol) into the 500 ml four-neck flask with reflux condenser pipe, dropping pipette, stirrer and thermometric instrument which is protected by dry nitrogen; and then add 15.8g(0.083 mol) methane tricarboxylic acid triethyl ester into the flask at the temperature of below 80C and protected for 2h by heat preservation; add 33.3g (0.075 mol) bromine sulfonium salts into the flask and then raise the temperature and control the temperature of the entire flask at 80C for a 15h reaction; cool it to the normal temperature and use 5% sulfuric acid to adjust the pH to pH=3; separate the organic layer and extract the water layer by 100 ml methylbenzene for two times; use 40 ml 5% sodium bicarbonate water solution wash the organic layer for two times; dry the oil layer by anhydrous sodium sulfate, filtrate and reduce pressure to recycle faint yellow fluid, finally get the target object-0.2g tri-ssterdibanzyl biotin (95.3% of the theoretical value), and the HPLC measured content is 98.0% with no impurity 5 (hereinafter to be referred as dicarboxylic ester).

Reference： [1]Patent: EP2433942,2012,A1 .Location in patent: Page/Page column 5

38
N-(9-(tert-butyldimethylsilyloxy)-2-chloro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 7-((tert-butyldimethylsilyl)oxy)-9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.13 g	In diphenylether; at 230℃; for 0.166667h;	Step 9; methyl 7-((tert-butyldimethylsilyl)oxy)-9-chloro-l-(2,4-dimethoxybenzyl)-4- hydroxy-2-oxo-2,5,6,7-tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3- carboxylate To a suspension of the intermediate obtained above in Ph20 (10 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.6 g, 8.4 mmol, 1.7 eq) at room temperature. A short-path distillation apparatus was attached to the flask and the reaction mixture was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature and then purified by flash column chromatography (0- 25% EtOAc in CH2C12) to give the product (1.13 g, 1.9 mmol, 37%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm -0.13 (s, 3 H) -0.03 (s, 3 H) 0.90 (s, 9 H) 1.51 (td, J=13.87, 7.25 Hz, 1 H) 1.66 - 1.77 (m, 1 H) 2.36 (tdd, J=13.28, 13.28, 7.49, 6.31 Hz, 1 H) 2.94 (dd, J=14.50, 5.36 Hz, 1 H) 3.56 (s, 3 H) 3.73 (s, 3 H) 4.01 (s, 3 H) 4.31 - 4.40 (m, 1 H) 5.10 (d, J=16.08 Hz, 1 H) 5.25 (d, J=16.08 Hz, 1 H) 6.28 (d, J=2.21 Hz, 1 H) 6.34 (dd, J=8.51, 2.21 Hz, 1 H) 6.73 (d, J=8.51 Hz, 1 H) 7.1 1 (d, .7=8.51 Hz, 1 H) 7.25 (dd, J=8.20, 2.21 Hz, 3 H) 7.64 (d, J=2.21 Hz, 1 H) 13.78 (s, 1 H). LC-MS 598.5/600.4 [M-H]", 600.4 [M+H]+, RT 1.95 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 114

39
N-(1-methyl-6,7-dihydrocyclohepta[f]indol-5(1H)-ylidene)prop-2-en-1-amine [ No CAS ]
[ 1186-73-8 ]
methyl 1-allyl-4-hydroxy-9-methyl-2-oxo-1,2,5,9-tetrahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.15 g	In diphenylether; for 0.166667h;Heating;	The intermediate N-(l-methyl-6,7-dihydrocyclohepta[fJindol-5(lH)-ylidene)prop-2-en- 1 -amine obtained above (ca. 8.46 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (2.75 g, 14.46 mmol) were mixed together in PI12O (17 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-80% gradient) to provide the product as a yellow solid (2.15 g, 56% overall). ^ MR ^OO MHz, CHCl3-i/) 8 ppm 2.1 1 (ddd, J=14.1, 5.8, 2.0 Hz, 1 H) 3.51 (dd, J=14.1, 8.0 Hz, 1 H) 3.86 (s, 3 H) 4.01 (s, 3 H) 4.38 (dd, J=15.1, 5.9 Hz, 1 H) 4.53 (ddt, J=15.1, 4.6, 2.1 Hz, 1 H) 4.75 (dd, J=17.2, 1.1 Hz, 1 H) 5.05 (dd, J=10.4, 1.1 Hz, 1 H) 5.90 (dddd, J=17.2, 10.4, 5.9, 4.6 Hz, 1 H) 6.37 (ddd, J=9.8, 8.0, 5.8 Hz, 1 H) 6.53 (dd, J=3.2, 0.9 Hz, 1 H) 6.76 (dd, J=9.8, 2.0 Hz, 1 H) 7.20 (d, J=3.2 Hz, 1 H) 7.29 (s, 1 H) 7.85 (s, 1 H) 13.72 (br. s., 1 H). LC-MS 375.3 [M+H]+, 377.3 [M+H]+, RT 1.40 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 119

40
N-(10-fluoro-1-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(1H)-ylidene)-2-methylpropan-2-amine [ No CAS ]
[ 1186-73-8 ]
C₁₉H₁₇FN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diphenylether; at 230℃; for 0.166667h;	Step 11; 8-fluoro-4-hvdroxv-9-methyl-2-oxo-l,2,5,6,7,9- hexahydropyrido [3',2' :6,7] cyclohepta [l,2-f]indole-3-carboxylic acid The N-(10-fluoro-l-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(lH)-ylidene)-2- methylpropan-2-amine obtained above (ca. 2.22 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.72 g, 3.79 mmol) were mixed together in Ph20 (5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min. The reaction mixture was cooled to room temperature. The precipitate was filtered, then washed with ether, to give a crude product (22 mg, 3%) which was used directly in the next step without further purification. LC-MS 357.1 [M+H]+, RT 1.38 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 124

41
N-(2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-6,7-dihydrocyclopenta[f]indol-5(1H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2,4-dimethoxybenzyl)-8-hydroxy-1-methyl-6-oxo-1,5,6,9-tetrahydropyrido[3',2':4,5]cyclopenta[1,2-f]indole-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
404 mg	In diphenylether; for 0.166667h;Heating;	Step 12; methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-5-(2,4-dimethoxybenzyl)-8- hydroxy-l-methyl-6-oxo-l,5,6,9-tetrahydropyrido[3',2':4,5]cyclopenta[l,2- f] indole-7-carboxylate The crude product obtained above (1.09 g, ca. 2.04 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.68 g, 3.58 mmol) were mixed together in Pl^O (6.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature) under a blanket of Argon. The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 25-60% gradient ) to yield the product as a yellow foam (404 mg, 33% 2 steps). LC-MS 605.3 [M+H]+, RT 1.80 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 129
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

42
N-(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-7,8-dihydro-1H-benzo[f]indol-5(6H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-8-methyl-2-oxo-2,5,6,8-tetrahydro-1H-indolo[6,5-h]quinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.158 g	In diphenylether; for 0.166667h;Heating;	Step 5; methyl 9-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-8-methyl-2-oxo-2,5,6,8-tetrahydro-lH-indolo[6,5-h]quinoline-3- carboxylate The N-(2-(((tert-butyldimethylsilyl)oxy)methyl)- 1 -methyl-7,8-dihydro- 1H- benzo[f]indol-5(6H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (1.40 g, 2.84 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.95 g, 5.00 mmol) were mixed together in PI12O (7.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature) under a blanket of Argon. The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 25-60% gradient) to yield the product as a yellow foam (1.158 g, 63% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.06 (s, 6 H) 0.90 (s, 9 H) 2.58 - 2.72 (m, 2 H) 2.89 (t, J=6.6 Hz, 2 H) 3.62 (s, 3 H) 3.78 (s, 3 H) 3.80 (s, 3 H) 3.97 (s, 3 H) 4.77 (s, 2 H) 5.37 (s, 2 H) 6.19 (s, 1 H) 6.42 (d, J=2.4 Hz, 1 H) 6.46 (dd, J=8.4, 2.4 Hz, 1 H) 7.14 (d, J=8.4 Hz, 1 H) 7.18 (s, 1 H) 7.63 (s, 1 H) 13.60 (s, 1 H). LC-MS 619.6 [M+H]+, RT 1.76 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 132-133
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

43
N-(2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(1H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-9-methyl-2-oxo-1,2,5,6,7,9-hexahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7.44 g	In diphenylether; for 0.166667h;Heating;	Step 6; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-9-methyl-2-oxo-l,2,5,6,7,9-hexahydropyrido[3',2':6,7]cyclohepta[l,2- f] indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)-l-methyl-6,7,8,9- tetrahydrocyclohepta[fJindol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (10.6 g, 20.91 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (6.80 g, 35.76 mmol) were mixed together in PI12O (40 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (7.44 g, 56%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.08 (s, 3 H) 0.09 (s, 3 H) 0.90 (s, 9 H) 1.45 - 1.55 (m, 1 H) 1.85 - 1.95 (m, 1 H) 1.96 - 2.05 (m, 1 H) 2.32 - 2.44 (m, 1 H) 2.58 (dd, J=13.4, 6.1 Hz, 1 H) 2.96 (dd, J=13.4, 5.4 Hz, 1 H) 3.33 (s, 3 H) 3.76 (s, 3 H) 3.78 (s, 3 H) 4.00 (s, 3 H) 4.80 (s, 2 H) 5.13 - 5.37 (m, 2 H) 6.22 (d, J=2.2 Hz, 1 H) 6.28 (s, 1 H) 6.34 (dd, J=8.4, 2.2 Hz, 1 H) 6.81 (d, J=8.4 Hz, 1 H) 7.06 (s, 1 H) 7.32 (s, 1 H) 13.66 (br. s, 1 H). LC-MS 633.5 [M+H]+, RT 1.85 min.
7.44 g	With diphenylether; at 230℃; for 0.166667h;	Step 2: Methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)- l-(2,4-dimethoxybenzyl)-4-hydroxy-9-methyl-2-oxo- 1,2,5, 6,7, 9-hexahydropyrido[3',2':6,7]cyclohepta[l,2-f]indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)- l-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (10.6 g, 20.91 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (6.80 g, 35.76 mmol) were mixed together in Ph20 (40 mL). The stirred mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after initial bubbling of MeOH was observed (occurs at approx. 160 C internal reaction temperature). The reaction mixture was cooled to room temperature, loaded directly on a silica column, eluted first with hexanes to separate Ph20 and then anEtOAc/hexanes gradient (0-80%) to yield the product as a yellow foam (7.44 g, 56% 2 steps). LC-MS: 633.5 [M+H]+, RT 1.85 min. 1H NMR (500 MHz, CDC13) 5 ppm 0.08 (s, 3H), 0.09 (s, 3H), 0.90 (s, 9H), 1.45 - 1.55 (m, IH), 1.85 - 1.95 (m, IH), 1.96 - 2.05 (m, IH), 2.32 -2.44 (m, IH), 2.58 (dd, J=13.4, 6.1 Hz, IH), 2.96 (dd, J=13.4, 5.4 Hz, IH), 3.33 (s, 3H), 3.76 (s, 3H), 3.78 (s, 3H), 4.00 (s, 3H), 4.80 (s, 2H), 5.13 - 5.37 (m, 2H), 6.22 (d, J=2.2 Hz, IH), 6.28 (s, IH), 6.34 (dd, J=8.4, 2.2 Hz, IH), 6.81 (d, J=8.4 Hz, IH), 7.06 (s, IH), 7.32 (s, IH), 13.66 (br. s, IH)

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 137-138
[2]Patent: WO2016/25932,2016,A1 .Location in patent: Page/Page column 161
[3]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

44
5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-amine [ No CAS ]
[ 1186-73-8 ]
methyl 1-(2,4-dimethoxybenzyl)-9-(dimethylamino)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	In diphenylether; for 0.25h;Heating;	Step 1; methyl l-(2,4-dimethoxybenzyl)-9-(dimethylamino)-4-hydroxy-2-oxo-2,5,6,7- tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate The previously obtained product 5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl-6,7,8,9- tetrahydro-5H-benzo[7]annulen-2-amine (Example 1, step 6, 0.85 g, 2.41 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.87 g, 4.58 mmol) were mixed together in PI12O (5.5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 220 C and heated for 15 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 40-90% gradient) to provide the product as a yellow foam (0.525 g, 45% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 1.58 (td, J=13.6, 6.9 Hz, 1 H) 1.86 - 2.08 (m, 2 H) 2.33 (td, J=12.7, 7.7 Hz, 1 H) 2.45 (dd, J=13.1, 6.1 Hz, 1 H) 2.97 - 3.01 (m, 1 H) 3.00 (s, 6 H) 3.61 (s, 3 H) 3.76 (s, 3 H) 3.97 (s, 3 H) 5.14 (br. s., 2 H) 6.33 (d, J=2.2 Hz, 1 H) 6.36 (dd, J=8.4, 2.2 Hz, 1 H) 6.50 (br. s., 2 H) 6.79 (d, J=8.4 Hz, 1 H) 7.00 (d, J=8.4 Hz, 1 H) 13.65 (s, 1 H). LC-MS 477.4 [M-H]", 479.4 [M+H]+, RT 1.46 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 97

45
N-(2-((tert-butyldimethylsilyloxy)methyl)-1-methyl-7,8,9,10-tetrahydro-1H-cycloocta[f]indol-5(6H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 11-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-10-methyl-2-oxo-2,5,6,7,8,10-hexahydro-1H-pyrido[3',2':7,8]cycloocta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.375 g	In diphenylether; for 0.166667h;Heating;	Step 9; methyl ll-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-10-methyl-2-oxo-2,5,6,7,8,10-hexahydro-lH- pyrido [3 ',2' : 7,8] cycloocta [1,2-f] indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)- 1 -methyl-7,8,9, 10-tetrahydro- 1 H- cycloocta[f]indol-5(6H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (-0.60 g, 1.17 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.37 g, 1.95 mmol) were mixed together in Ph 0 (2.5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-60% gradient) to yield the product as a yellow foam (0.3750 g, 51%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.10 (s, 3 H) 0.11 (s, 3 H) 0.91 (s, 9 H) 1.33 - 1.51 (m, 3 H) 1.80 - 1.90 (m, 1 H) 2.02 (t, J=7.7 Hz, 1 H) 2.13 (t, J=12.0 Hz, 1 H) 2.55 (dd, J=13.6, 7.3 Hz, 1 H) 2.82 (dd, J=13.2, 7.6 Hz, 1 H) 3.10 (s, 3 H) 3.76 (s, 3 H) 3.77 (s, 3 H) 4.03 (s, 3 H) 4.80 (d, J=13.2 Hz, 1 H) 4.82 (d, J=13.2 Hz, 1 H) 4.96 - 5.26 (m, 2 H) 6.12 (d, J=2.5 Hz, 1 H) 6.24 (s, 1 H) 6.32 (dd, J=8.5, 2.2 Hz, 1 H) 6.81 (d, J=8.5 Hz, 1 H) 7.04 (s, 1 H) 7.11 (s, 1 H) 13.73 (s, 1 H). LC-MS 647.5 [M+H]+, RT 1.90 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 169-170
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

46
N-(2-((tert-butyldimethylsilyloxy)methyl)-3-methyl-7,8,9,10-tetrahydrocyclohepta[e]indol-6(3H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-10-(2,4-dimethoxybenzyl)-7-hydroxy-1-methyl-9-oxo-1,4,5,6,9,10-hexahydropyrido[2’,3’:3,4]cyclohepta[1,2-e]indole-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	In diphenylether; at 230℃; for 0.166667h;	2-(((tert-Butyldimethylsilyl)oxy)methyl)-N-(2,4-dimethoxybenzyl)-3-methyl-7, 8,9,10- tetrahydrocyclohepta[e]indol-6(3H)-imine was divided into two batches for the annulation reaction. The crude imine (2.6 g, 5.12 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.66 g, 8.73 mmol) were mixed together in Ph20 (10 mL). The stirred mixture was placed onto a heat block pre-heated to 230 C and heated for 10 minutes. Initial bubbling of MeOH was observed (occuring at approx.. 160 C internal reaction temperature). The reaction mixture was cooled to room temperature, loaded directly on a column, eluted first with hexanes to separate Ph20 and then an EtOAc/hexanes gradient (0-50%) to yield the title compound as a yellow foam (3.093 g, 48% 2 steps). LC-MS 633.5 [M+H]+, RT 1.85 min. 1H NMR (500 MHz, CDC13 delta ppm 0.09 (s, 3H), 0.12 (s, 3H), 0.92 (s, 9H), 1.49 (td, J=13.6, 7.3 Hz, IH), 1.97 - 2.17 (m, 2H), 2.41 (td, J=12.9, 7.9 Hz, IH), 2.99 (dd, J=13.9, 6.0 Hz, 2H), 3.48 (s, 3H), 3.75 (s, 3H), 3.78 (s, 3H), 3.99 (s, 3H), 4.84 (d, J=13.2 Hz, IH), 4.84 (d, J=13.2 Hz, IH), 5.18 (br. s, 2H), 6.27 (d, J=2.4 Hz, IH), 6.35 (dd, J=8.2, 2.4 Hz, IH), 6.45 (s, IH), 6.82 (d, J=8.2 Hz, IH), 7.00 (d, J=8.8 Hz, IH), 7.11 (d, J=8.8 Hz, IH), 13.68 (s, IH).
0.5425 g	In diphenylether; for 0.166667h;Heating;	Step 13; methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-10-(2,4-dimethoxybenzyl)-7- hydroxy-l-methyl-9-oxo-l,4,5,6,9,10- hexahydropyrido [2',3' :3,4] cyclohepta [l,2-e]indole-8-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)-3-methyl-7,8,9, 10- tetrahydrocyclohepta[e]indol-6(3H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (0.858 g, 1.69 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.55 g, 2.89 mmol) were mixed together in Rho12theta (4 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (0.5425 g, 50%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.09 (s, 3 H) 0.12 (s, 3 H) 0.92 (s, 9 H) 1.49 (td, J=13.6, 7.3 Hz, 1 H) 1.97 - 2.17 (m, 2 H) 2.41 (td, J=12.9, 7.9 Hz, 1 H) 2.99 (dd, J=13.9, 6.0 Hz, 2 H) 3.48 (s, 3 H) 3.75 (s, 3 H) 3.78 (s, 3 H) 3.99 (s, 3 H) 4.84 (d, J=13.2 Hz, 1 H) 4.84 (d, J=13.2 Hz, 1 H) 5.18 (br. s., 2 H) 6.27 (d, J=2.4 Hz, 1 H) 6.35 (dd, J=8.2, 2.4 Hz, 1 H) 6.45 (s, 1 H) 6.82 (d, J=8.2 Hz, 1 H) 7.00 (d, J=8.8 Hz, 1 H) 7.11 (d, J=8.8 Hz, 1 H) 13.68 (s, 1 H). LC-MS 633.5 [M+H]+, RT 1.85 min.

Reference： [1]Patent: WO2016/25933,2016,A2 .Location in patent: Page/Page column 192; 193
[2]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 177
[3]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

47
N-(2-(((tert-butyldimethylsilyl)oxy)methyl)-1,9-dimethyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(1H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-7,9-dimethyl-2-oxo-1,2,5,6,7,9-hexahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.41 g	In diphenylether;Heating;	Step 7; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-7,9-dimethyl-2-oxo-l,2,5,6,7,9- hexahydropyrido[3',2':6,7]cyclohepta[l,2-f\|indole-3-carboxylate Crude N-(2-(((tert-butyldimethylsilyl)oxy)methyl)-l,9-dimethyl-6,7,8,9- tetrahydrocyclohepta[fJindol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (ca 3.63 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.20 g, 6.31 mmol) were mixed together in Pl^O (7 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (1.41 g, 60% 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.09 (s, 3 H) 0.10 (s, 3 H) 0.91 (s, 9 H) 1.23 (d, J=6.9 Hz, 3 H) 1.37 - 1.52 (m, 2 H) 2.00 - 2.12 (m, 1 H) 2.33 - 2.47 (m, 1 H) 2.89 (dd, J=13.4, 5.5 Hz, 1 H) 3.21 (s, 3 H) 3.74 (s, 3 H) 3.80 (s, 3 H) 4.02 (s, 3 H) 4.82 (s, 2 H) 5.09 (d, J=15.4 Hz, 1 H) 5.39 - 5.58 (m, 1 H) 6.14 (d, J=1.9 Hz, 1 H) 6.27 (dd, J=8.4, 1.9 Hz, 1 H) 6.31 (s, 1 H) 6.69 (d, J=8.4 Hz, 1 H) 7.04 (s, 1 H) 7.35 (s, 1 H) 13.64 (s, 1 H) LC-MS 647.4 [M+H]+, RT 1.92 min

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 183

48
N-(2-((tert-butyldimethylsilyloxy)methyl)-1,7-dimethyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(1H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-5,9-dimethyl-2-oxo-1,2,5,6,7,9-hexahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
210 mg	In diphenylether; for 0.166667h;Heating;	Step 7; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-5,9-dimethyl-2-oxo-l,2,5,6,7,9- hexahydropyrido[3',2':6,7]cyclohepta[l,2-f\|indole-3-carboxylate The crude product obtained above (450 mg, ca. 0.88 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (380 mg, 2.0 mmol) were mixed together in Ph20 (2 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (210 mg, 37% 2 steps) LC-MS 645.3 [M-H]", 647.3 [M+H]+, RT 1.87 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 190

49
C₃₀H₄₀N₂O₃Si [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-9-methyl-2-oxo-1,2,5,9-tetrahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.4 g	In diphenylether; for 0.166667h;Heating;	The crude product obtained above (ca. 16.31 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (5.20 g, 27.35 mmol) were mixed together in Pl^O (32 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (5.40 g, 52% overall). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.10 (s, 3 H) 0.10 (s, 3 H) 0.91 (s, 9 H) 2.09 (ddd, J=14.1, 5.9, 2.0 Hz, 1 H) 3.35 (s, 3 H) 3.50 (dd, J=14.1, 7.9 Hz, 1 H) 3.74 (s, 3 H) 3.79 (s, 3 H) 3.99 (s, 3 H) 4.82 (s, 2 H) 4.91 (d, J=15.4 Hz, 1 H) 5.20 (br. s., 1 H) 6.19 (d, J=2.2 Hz, 1 H) 6.24 - 6.36 (m, 3 H) 6.60 - 6.68 (m, 2 H) 7.14 (s, 1 H) 7.57 (s, 1 H) 13.72 (br. s., 1 H). LC- MS 629.3 [M+H]+, 631.3 [M+H]+, RT 1.84 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 193

50
C₃₁H₄₂N₂O₃Si [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-7,9-dimethyl-2-oxo-1,2,5,9-tetrahydropyrido[3',2':6,7]cyclohepta[1,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.322 g	In diphenylether; for 0.166667h;Heating;	The crude product obtained above (ca. 1.47 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.50 g, 2.63 mmol) were mixed together in Pl^O (3 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-70% gradient) to yield the product as a yellow foam (0.322 g, 34% overall). LC-MS 645.6 [M+H]+, RT 2.04 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 196

51
N-(8-chloro-3,4-dihydrobenzo[b]oxepin-5(2H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydrobenzo[2,3]oxepino[4,5-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6 g	In diphenylether; at 230℃; for 0.25h;	Step 5; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-l,2,5,6- tetrahydrobenzo [2,3] oxepino [4,5-b] pyridine-3-carboxylate A solution of N-(8-chloro-3 ,4-dihydrobenzo [b] oxepin-5 (2H)-ylidene)- 1 -(2,4- dimethoxyphenyl)methanamine (4.4 g crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (4.9 g, 25.6 mmol) in Pl^O (13 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature, and purified on silica gel using EtO Ac/Hex (0-60% gradient) to afford the product (2.6 g, 43%) as a yellow foam. XH NMR (500 MHz, CHCl3-i/) delta ppm 2.06 - 2.17 (m, 1 H) 3.18 (dd, J=15.09, 3.90 Hz, 1 H) 3.63 - 3.68 (m, 3 H) 3.75 - 3.79 (m, 3 H) 3.99 (s, 3 H) 4.37 (dd, J=9.81, 6.34 Hz, 1 H) 4.41 - 4.50 (m, 1 H) 4.93 - 5.04 (m, 1 H) 5.15 (d, J=15.76 Hz, 1 H) 6.32 - 6.44 (m, 2 H) 6.94 (d, J=8.35 Hz, 1 H) 7.06 - 7.12 (m, 2 H) 7.17 (s, 1 H) 13.80 (s, 1 H). LC-MS: 470.1 [M-H]", RT 1.45 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 206

52
N-(8-bromo-3-methyl-3,4-dihydrobenzo[b]oxepin-5(2H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-bromo-1-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-1,2,5,6-tetrahydrobenzo[2,3]oxepino [4,5-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6 g	In diphenylether; at 230℃; for 0.25h;	Step 7; methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-l,2,5,6- tetrahydrobenzo [2,3] oxepino [4,5-b] pyridine-3-carboxylate A solution of N-(8-bromo-3-methyl-3,4-dihydrobenzo[b]oxepin-5(2H)-ylidene)-l-(2,4- dimethoxyphenyl)methanamine (3.7 g, crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (3.4 g, 18 mmol) in PI12O (10 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature and purified on silica gel using EtOAc/Hex (0-60% gradient) to afford the product methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-l, 2,5,6- tetrahydrobenzo[2,3]oxepino[4,5-b]pyridine-3-carboxylate (2.6 g, 43%) as a brown foam. XH NMR (500 MHz, DMSO-i) delta ppm 0.56 (d, J=7.72 Hz, 3 H) 3.57 - 3.66 (m, 4 H) 3.68 - 3.72 (m, 3 H) 3.85 (s, 3 H) 4.14 (d, J=10.96 Hz, 1 H) 4.60 (dd, J=11.07, 6.66 Hz, 1 H) 4.90 (d, J=15.68 Hz, 1 H) 5.13 (br. s., 1 H) 6.35 - 6.46 (m, 2 H) 6.74 (d, J=8.43 Hz, 1 H) 7.31 - 7.51 (m, 3 H) 13.51 (br. s, 1 H).LC-MS: 530.2 [M-H]", RT 0.92 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 212

53
C₁₇H₂₂N₂O [ No CAS ]
[ 1186-73-8 ]
methyl 4-hydroxy-9-methyl-2-oxo-2,5,6,9-tetrahydro-1H-pyrido[2',3':4,5]oxepino[3,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
480 mg	In diphenylether; at 230℃; for 0.25h;	A solution of the crude product obtained above and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.0 g, 5.6 mmol) in Pl^O (5 mL) was heated at 230 C for 15 min. The reaction mixture was then cooled to room temperature at which point the product precipitates. The solid was filtered and rinsed with Et20 (20 mL) to afford the title compound as a brown solid (480 mg, 38%). XH NMR (500 MHz, DMSO-i) delta ppm 2.56 (t, J=6.46 Hz, 2 H) 3.79 (s, 3 H) 4.38 (t, J=6.34 Hz, 2 H) 6.52 (dd, J=3.1 1, 0.75 Hz, 1 H) 7.29 (s, 1 H) 7.37 - 7.39 (m, 1 H) 7.74 (s, 1 H) 11.72 (br. s., 1 H) 13.59 (br. s., 1 H). LC-MS: 341.3 [M+H]+, 0.68 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 216

54
N-(8-((tert-butyldimethylsilyloxy)methyl)-9-methyl-3,4-dihydro-2H-oxepino[3,2-f]indol-5(9H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-1-(2,4-dimethoxybenzyl)-4-hydroxy-9-methyl-2-oxo-2,5,6,9-tetrahydro-1H-pyrido[2',3':4,5]oxepino[3,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2 g	In diphenylether; at 230℃; for 0.25h;	Step 13; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-9-methyl-2-oxo-2,5,6,9-tetrahydro-lH-pyrido[2',3':4,5]oxepino[3,2- f] indole-3-carboxylate A solution of N-(8-((tert-butyldimethylsilyloxy)methyl)-9-methyl-3,4-dihydro-2H- oxepino[3,2-f]indol-5(9H)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (3.81 g crude) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (2.9 g, 15.0 mmol) in Ph20 (15 mL) was heated at 230 C for 15 min. The reaction mixture was cooled to room temperature and purified on silica gel using EtO Ac/Hex (0-60% gradient) to afford the product (2.0 g, 43%) as a yellow foam. XH NMR (500 MHz, DMSO-i) delta ppm 0.00 (d, J=0.95 Hz, 6 H) 0.77 - 0.83 (m, 9 H) 1.87 - 1.96 (m, 2 H) 2.88 - 2.96 (m, 1 H) 3.48 (s, 3 H) 3.64 (d, J=1.89 Hz, 6 H) 3.77 (s, 3 H) 4.21 (br. s., 2 H) 4.74 (s, 2 H) 4.98 - 5.07 (m, 1 H) 6.24 (s, 1 H) 6.37 (s, 2 H) 6.61 - 6.68 (m, 1 H) 7.21 (s, 1 H) 7.31 - 7.40 (m, 1 H) 13.28 - 13.36 (m, 1 H). LC-MS: 633.2 [M-H]", RT 1.80 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 220-221
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4456 - 4475

55
N-(8-chloro-1-methyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-7-methyl-2-oxo-2,5,6,7-tetrahydro-1H-benzo[b]pyrido[2,3-d]azepine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
289 mg	In diphenylether; at 210℃; for 0.166667h;Inert atmosphere;	Step 3; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-7-methyl-2-oxo-2,5,6,7- tetrahydro-lH-benzo [b] pyrido [2,3-d] azepine-3-carboxylate Crude N-(8-chloro-l-methyl-3,4-dihydro-lH-benzo[b]azepin-5(2H)-ylidene)-l-(2,4- dimethoxyphenyl)methanamine (690 mg, 1.95 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (631 mg, 3.32 mmol) were mixed together in Pl^O (4.0 mL). With stirring, the mixture was placed into a pre-heated heat block at 210 C and heated for 10 minutes under a blanket of Argon. The reaction mixture was cooled to room temperature and was filtered directly on a silica cartridge. The product was purified by column chromatography (100% hexanes followed by EtOAc in hexanes 0 to 85% gradient) to provide the desired product (289 mg, 31%, two steps) as an off-white foam which was used directly in the next step. LC-MS 483.9 [M-H]", 485.8 [M+H]+, RT 1.53 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 228

56
benzyl 8-chloro-5-((2,4-dimethoxybenzyl)imino)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate [ No CAS ]
[ 1186-73-8 ]
7-benzyl 3-methyl 9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-5,6-dihydro-1H-benzo[b]pyrido[2,3-d]azepine-3,7(2H)-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.13 g	In diphenylether; at 210℃; for 0.166667h;Inert atmosphere;	Step 3; 7-benzyl 3-methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-5,6- dihydro-lH-benzo [b] pyrido [2,3-d] azepine-3,7(2H)-dicarboxylate The crude benzyl 8-chloro-5-((2,4-dimethoxybenzyl)imino)-2,3,4,5-tetrahydro-lH- benzo[b]azepine-l-carboxylate (2.75 g, 5.75 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.85 g, 9.78 mmol) were mixed together in Rho12theta (12.0 mL). With stirring, the mixture was placed into a pre-heated heat block at 210 C and heated for 10 minutes under a blanket of Argon. The reaction mixture was cooled to room temperature and filtered directly on a silica cartridge. The product was purified by column chromatography (100% hexanes followed by EtOAc in hexanes 0 to 85% gradient) to give the desired product (1.13 g, 32%, two steps) as an off-white foam which was used directly in the next step.. LC-MS 603.4 [M-H]", 605.4 [M+H]+, RT 0.94 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 229-230

57
5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl-5,6,7,8,9,10-hexahydrobenzo[8]annulen-2-amine [ No CAS ]
[ 1186-73-8 ]
methyl 1-(2,4-dimethoxybenzyl)-10-(dimethylamino)-4-hydroxy-2-oxo-1,2,5,6,7,8-hexahydrobenzo[7,8]cycloocta[1,2-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.2%	In diphenylether; for 0.25h;Heating;	Step 1; methyl l-(2,4-dimethoxybenzyl)-10-(dimethylamino)-4-hydroxy-2-oxo- l,2,5,6,7,8-hexahydrobenzo[7,8]cycloocta[l,2-b]pyridine-3-carboxylate The previously obtained product 5-((2,4-dimethoxybenzyl)imino)-N,N-dimethyl- 5,6,7,8,9, 10-hexahydrobenzo[8]annulen-2-amine (Example 4, step 7, 0.30 g, 0.82 mmol) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (0.28 g, 1.47 mmol) were mixed together in PI12O (2.0 mL). With stirring, the mixture was placed onto a pre-heated heat block at 220 C and heated for 15 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes, followed by EtOAc/hexanes 0-70% gradient) to provide the product as a yellow foam (0.178 g, 44% 2 steps) XH NMR (500 MHz, CHCh-d) delta ppm 1.29 - 1.44 (m, 2 H) 1.50 (dd, J=13.4, 1 1.2 Hz, 1 H) 1.84 - 2.03 (m, 3 H) 2.41 (dd, J=13.1, 7.7 Hz, 1 H) 2.86 (dd, J=13.7, 7.7 Hz, 1 H) 2.98 (s, 6 H) 3.51 (s, 3 H) 3.75 (s, 3 H) 4.00 (s, 3 H) 5.01 (d, J=15.8 Hz, 1 H) 5.17 (d, J=15.8 Hz, 1 H) 6.25 (d, J=2.4 Hz, 1 H) 6.33 (dd, J=8.5, 2.4 Hz, 1 H) 6.41 - 6.53 (m, 2 H) 6.74 (d, J=8.5 Hz, 1 H) 6.85 (d, J=8.5 Hz, 1 H) 13.71 (s, 1 H). LC-MS 491.4 [M-H]", 493.4 [M+H]+, RT 1.57 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 102

58
N-(2-chloro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.57 g	In diphenylether; at 230℃; for 0.166667h;	Step 3; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-2,5,6,7-tetrahydro- lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate To a suspension of the crude product obtained above (4.75 g, ca. 13.8 mmol) in Ph20 (20 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (4.7 g, 24.7 mmol, 1.8 eq). A short-path distillation apparatus was attached to the flask containing the reaction mixture. The reaction mixture was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature, then purified by flash column chromatography (0-25% EtOAc in CH2CI2) to afford the title compound (3.57 g, 7.60 mmol, 52%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 1.46 (td, J=13.69, 6.90 Hz, 1 H) 1.83 - 1.96 (m, 1 H) 2.01 (dq, J=13.36, 6.71 Hz, 1 H) 2.15 (td, J=12.69, 7.88 Hz, 1 H) 2.40 (dd, J=13.20, 6.27 Hz, 1 H) 2.99 (dd, J=14.19, 5.20 Hz, 1 H) 3.54 (s, 3 H) 3.75 (s, 3 H) 4.01 (s, 3 H) 5.03 (d, J=15.68 Hz, 1 H) 5.29 (d, J=15.68 Hz, 1 H) 6.26 (d, J=2.29 Hz, 1 H) 6.30 - 6.37 (m, 1 H) 6.78 (d, J=8.43 Hz, 1 H) 7.06 - 7.17 (m, 2 H) 7.17 - 7.25 (m, 1 H) 13.74 (s, 1 H). LC-MS 468.3/470.3 [M-H]", 470.3 [M+H]+, RT 1.57 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 104

59
N-(2-chloro-7-methyl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-ylidene)-1-(2,4-dimethoxyphenyl)methanamine [ No CAS ]
[ 1186-73-8 ]
methyl 9-chloro-1-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-2,5,6,7-tetrahydro-1H-benzo[6,7]cyclohepta[1,2-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.4 g	In diphenylether; at 230℃; for 0.166667h;	Step 7; methyl 9-chloro-l-(2,4-dimethoxybenzyl)-4-hydroxy-5-methyl-2-oxo-2,5,6,7- tetrahydro-lH-benzo[6,7]cyclohepta[l,2-b]pyridine-3-carboxylate To a suspension of the crude product obtained above (2.68 g, ca. 7.5 mmol) in Rho12theta (15 mL) was added <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (3.23 g, 17.0 mmol, 2.3 eq). A short-path distillation apparatus was attached to the flask containing the reaction mixture. The reaction was heated to 230 C for 10 min. The heat was removed after methanol distillation ceased. The mixture was allowed to cool to room temperature, then purified by flash column chromatography (0-25% EtOAc in CH2C12) to give the product (2.40 g, 4.96 mmol, 55%, two steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.38 (d, J=7.09 Hz, 3 H) 1.62 - 1.75 (m, 1 H) 1.75 - 2.15 (m, 1 H) 2.18 - 2.27 (m, 1 H) 2.27 - 2.39 (m, 2 H) 3.52 (s, 3 H) 3.75 (s, 3 H) 4.02 (m, 3 H) 4.96 - 5.02 (m, 1 H) 5.39 (d, J=15.45 Hz, 1 H) 6.20 - 6.28 (m, 1 H) 6.28 - 6.38 (m, 1 H) 6.77 (d, J=8.35 Hz, 1 H) 7.06 - 7.13 (m, 1 H) 7.13 - 7.18 (m, 1 H) 7.18 - 7.25 (m, 1 H) 13.96 (br. s., 1 H). LC-MS 482.9/484.9 [M-H]", 484.8 [M+H]+, RT 1.60 min.

Reference： [1]Patent: WO2013/33228,2013,A1 .Location in patent: Page/Page column 109-110

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P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1186-73-8 ]

Quality Control of [ 1186-73-8 ]

Related Doc. of [ 1186-73-8 ]

Product Details of [ 1186-73-8 ]

Calculated chemistry of [ 1186-73-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1186-73-8 ]

Application In Synthesis of [ 1186-73-8 ]

[ 1186-73-8 ] Synthesis Path-Upstream 1~13

[ 1186-73-8 ] Synthesis Path-Downstream 1~59

Related Functional Groups of [ 1186-73-8 ]

Aliphatic Chain Hydrocarbons

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1186-73-8 ]