[ CAS No. 876-72-2 ]

Name: 876-72-2|4-Chloro-1H-indole-3-carbaldehyde|98%
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Quality Control of [ 876-72-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 876-72-2 ]

Product Details of [ 876-72-2 ]

CAS No. :	876-72-2	MDL No. :	MFCD05864704
Formula :	C₉H₆ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MSYJFNQAVTYKOP-UHFFFAOYSA-N
M.W :	179.60	Pubchem ID :	13499089
Synonyms :

Calculated chemistry of [ 876-72-2 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	48.7
TPSA :	32.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.88 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.45
Log Po/w (XLOGP3) :	2.14
Log Po/w (WLOGP) :	2.63
Log Po/w (MLOGP) :	1.45
Log Po/w (SILICOS-IT) :	3.29
Consensus Log Po/w :	2.19

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.79
Solubility :	0.291 mg/ml ; 0.00162 mol/l
Class :	Soluble
Log S (Ali) :	-2.46
Solubility :	0.62 mg/ml ; 0.00345 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.85
Solubility :	0.0256 mg/ml ; 0.000143 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.26

Safety of [ 876-72-2 ]

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

Application In Synthesis of [ 876-72-2 ]

* 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 [ 876-72-2 ]
Downstream synthetic route of [ 876-72-2 ]

[ 876-72-2 ] Synthesis Path-Upstream 1~8

1
[ 25235-85-2 ]
[ 68-12-2 ]
[ 876-72-2 ]

Yield	Reaction Conditions	Operation in experiment
44%	at 10 - 37℃; for 0.75 h;	To a stirring DMF (10.63 mL) was added dropwise POC13 (3.55 mL) at 10-20 °C followed by addition of a solution of SM1 (2 g,13.19 mmol) at 20-30 °C. Thereaction mixture was stirred at 35-37 °C for 45 minutes and finally poured into stirred ice(28 g) and water (21 mL). Sodium hydroxide (6.86 g) in water (36 mL) was added at 20-30°C and made the solution pH=8. The mixture was boiled for 5 minutes and cooled to roomtemperature, extracted with EtOAc, washed with brine. Combined organic extracts were dried over anhydrous Na2504 and concentrated under reduced pressure to obtain crude product, which was purified by silica gel column chromatography eluting with 60percent PE/EtOAc to afford compound 1 (1.037 g, 44percent) as an off-white solid. LC-MS: m/z =180[(M+1)].

Reference： [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 23, p. 9179 - 9195
[2] Organic Letters, 2013, vol. 15, # 17, p. 4330 - 4333
[3] Patent: WO2016/44777, 2016, A1, . Location in patent: Page/Page column 72; 73
[4] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[5] Organic and Biomolecular Chemistry, 2018, vol. 16, # 36, p. 6647 - 6651

2
[ 25235-85-2 ]
[ 876-72-2 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 9, p. 3696 - 3708
[2] Patent: US6433175, 2002, B1,
[3] Patent: US2007, 2001, H1,

3
[ 942-24-5 ]
[ 876-72-2 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 9, p. 3696 - 3708

4
[ 101909-42-6 ]
[ 876-72-2 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 9, p. 3696 - 3708

5
[ 43142-77-4 ]
[ 876-72-2 ]

Reference： [1] Helvetica Chimica Acta, 1955, vol. 38, p. 468,470

6
[ 487-89-8 ]
[ 876-72-2 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 9, p. 3696 - 3708

7
[ 53590-46-8 ]
[ 876-72-2 ]

Reference： [1] Helvetica Chimica Acta, 1955, vol. 38, p. 468,470

8
[ 876-72-2 ]
[ 24424-99-5 ]
[ 914349-00-1 ]

Yield	Reaction Conditions	Operation in experiment
0.431 g	With dmap In acetonitrile at 20℃;	General procedure: To a solution of an appropriate indole, azaindole or alternative heterocycles (1.0 eq) and di-ferf-butyl dicarbonate (1eq. to 2 eq., more in particular 1.2 eq) in acetonitrile was added DMAP (0.1 to 0.5 eq. more in particular 0.1 eq). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with a saturated sodium bicarbonate solution. The phases were separated. The aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with a saturated ammonium chloride solution, water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The BOC-protected compound was used in the next step without further purification.

Reference： [1] Journal of Medicinal Chemistry, 2015, vol. 58, # 23, p. 9179 - 9195
[2] Patent: WO2013/45516, 2013, A1, . Location in patent: Page/Page column 129; 151

[ 876-72-2 ] Synthesis Path-Downstream 1~58

1
[ 43142-77-4 ]
[ 876-72-2 ]

Reference： [1]Helvetica Chimica Acta,1955,vol. 38,p. 468,470

2
[ 487-89-8 ]
[ 876-72-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 3696 - 3708

3
[ 25235-85-2 ]
[ 876-72-2 ]

Yield	Reaction Conditions	Operation in experiment
7.8 g (100%)		4-Chloroindole-3-carboxaldehyde 4-Chloroindole-3-carboxaldehyde was prepared from 4-chloroindole according to the method described in Example 1 to give 7.8 g (100%) of the product which was used without further purification.
	With sodium hydroxide; trichlorophosphate; In water; ethyl acetate; N,N-dimethyl-formamide;	Step A Synthesis of 4-chloro-3-formylindole as an intermediate During a period of five minutes 2.3 grams (0.015 mole) of phosphorus oxychloride was added dropwise to 10 mL of N,N-dimethylformamide. The solution was stirred for 30 minutes and then cooled in an ice bath. To this was added dropwise a solution of 2.0 grams (0.013 mole) of 4-chloroindole in 3 mL of N,N-dimethylformamide. Upon completion of the addition the ice bath was removed, and the reaction mixture was warmed to ambient tempeature, where it stirred for 1.5 hours. After this time the reaction mixture was warmed to 40 C., where it was stirred for 30 minutes, and then poured onto 50 grams of ice. A solution of 5.9 grams (0.146 mole) of sodium hydroxide in 20 mL of water was added during a 2-3 minute period, after which the mixture was heated to reflux and then cooled to ambient temperature. The cooled mixture was poured into 500 mL of water, stirred at ambient temperature for about 18 hours, and then filtered to collect a solid that had precipitated. The solid was washed with three portions of water and then dissolved in ethyl acetate. The ethyl acetate solution was subjected to column chromatography on silica gel with 1:1 ethyl acetate:hexane as eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 1.4 grams of 4-chloro-3-formylindole. The NMR spectrum was consistent with the proposed structure.

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 3696 - 3708
[2]Patent: US6433175,2002,B1
[3]Patent: US2007,2001,H1

4
[ 876-72-2 ]
[ 23872-36-8 ]

Reference： [1]Heterocycles,1987,vol. 26,p. 1173 - 1176

Yield	Reaction Conditions	Operation in experiment
90%	With trichlorophosphate; at 45℃; for 2h;	General procedure: Phosphoryl chloride ( 1.5 equiv.) was added dropwise to anhydrous DMF ( 10 mL) at 0 C and left to stir for 10 min. To this, a solution of 4-fluoroindole ( 1 equiv.) in anhydrous DMF (5 mL) was added dropwise and the resultant mixture was heated to 45 C and left to stir for 2 h. The reaction mixture was cooled to room temperature and pH was adjusted to 9- 10 with 1 M NaOH. The resultant suspension was then heated to 60 C and left to cool to room temperature. Deionised water was added to the cooled mixture and the resultant precipitate was filtered and washed with excess deionised water. The precipitate was air dried overnight to yield the title compound. 4-Fluoro-lH-indole-3-carbaldehyde (intermediate 2a) Synthesis was carried out using the general procedure, using phosphoryl chloride (2. 1 mL, 22.2 mmol), 4-fluoroindole (2.0 g, 14.8 mmol) and DMF (10 mL) to yield the title compound as beige solid (1.76 g, 77% yield); m.p. 170- 172 C (Lit. m.p. 182- 187 C); Rf = 0.2 (hexane/EtOAc 2: 1); -NuMRho (400 MHz, (CD3)2CO): delta = 7.02 (td, J = 9.5, 3 Hz, 1H, H-6), 7.29 (td, J = 8, 5 Hz, H-7), 7.45 (d, J = 8 Hz, 1H, H-5), 8.23 (s, 1H, H-2), 10.21 (d, J = 2 Hz, 1H, CHO) ppm; 1 C-NMR (100 MHz, (CD3)2CO): delta = 108.8 (d, J = 20 Hz), 1 15.5 (d, J = 20 Hz), 1 19.4 (d, J = 5 Hz), 125.6 (d, J = 8 Hz), 135.1, 141.5, 157.2, 159.6, 185.2 ppm; MS : m/z (+ESI) calcd. for C9H7FNO+ 164.0506, found 163.7540 [MH+].

6
[ 6843-45-4 ]
[ 876-72-2 ]
5-[1-(4-Chloro-1H-indol-3-yl)-meth-(Z)-ylidene]-3-methyl-imidazolidine-2,4-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5039 - 5044

7
[ 25235-85-2 ]
[ 68-12-2 ]
[ 876-72-2 ]

Yield	Reaction Conditions	Operation in experiment
44%	With trichlorophosphate; at 10 - 37℃; for 0.75h;	To a stirring DMF (10.63 mL) was added dropwise POC13 (3.55 mL) at 10-20 C followed by addition of a solution of SM1 (2 g,13.19 mmol) at 20-30 C. Thereaction mixture was stirred at 35-37 C for 45 minutes and finally poured into stirred ice(28 g) and water (21 mL). Sodium hydroxide (6.86 g) in water (36 mL) was added at 20-30C and made the solution pH=8. The mixture was boiled for 5 minutes and cooled to roomtemperature, extracted with EtOAc, washed with brine. Combined organic extracts were dried over anhydrous Na2504 and concentrated under reduced pressure to obtain crude product, which was purified by silica gel column chromatography eluting with 60% PE/EtOAc to afford compound 1 (1.037 g, 44%) as an off-white solid. LC-MS: m/z =180[(M+1)].
		General procedure: POCl3 (13.09 g, 85.36 mmol) was slowly added dropwise to DMF(10 mL) under ice bath. The mixture was stirred at ice bath for30 min. Then, DMF (6.24 g, 85.36 mmol) solution of indole (5 g,42.68 mmol) was added dropwise to the reaction system. Keepingthe reaction at room temperature for 3 h, ice water and 10% NaOHaq. were added into the reaction system to pH of 7-8 and continue to stir to a lot of white solid precipitation. The solid was recrystallizedfrom ethyl acetate and petroleum ether to obtain compound3 in yields of 97.6%.

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 9179 - 9195
[2]Organic Letters,2013,vol. 15,p. 4330 - 4333
[3]Patent: WO2016/44777,2016,A1 .Location in patent: Page/Page column 72; 73
[4]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798
[5]Organic and Biomolecular Chemistry,2018,vol. 16,p. 6647 - 6651
[6]European Journal of Medicinal Chemistry,2019,vol. 175,p. 357 - 372

8
[ 876-72-2 ]
[ 74-88-4 ]
[ 338760-69-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798

9
[ 876-72-2 ]
4-(4-chloro-1-methyl-1H-indol-3-ylmethylene)-5-[1,2,3]thiadiazol-5-yl-2,4-dihydro-pyrazol-3-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798

10
[ 876-72-2 ]
4-(4-chloro-1-methyl-1H-indol-3-ylmethylene)-5-(4-methyl-[1,2,3]thiadiazol-5-yl)-2,4-dihydro-pyrazol-3-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1793 - 1798

11
[ 876-72-2 ]
5-(4-chloro-1H-indol-3-ylmethyl)-3-methyl-imidazolidine-2,4-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 5039 - 5044

12
[ 876-72-2 ]
[ 101909-42-6 ]

Reference： [1]Heterocycles,1987,vol. 26,p. 1173 - 1176

13
[ 942-24-5 ]
[ 876-72-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 3696 - 3708

14
[ 101909-42-6 ]
[ 876-72-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 3696 - 3708

15
[ 53590-46-8 ]
[ 876-72-2 ]

Reference： [1]Helvetica Chimica Acta,1955,vol. 38,p. 468,470

16
[ 876-72-2 ]
[ 260267-19-4 ]

Yield	Reaction Conditions	Operation in experiment
3.8 g (45%, from 4-chloroindole)		4-Chloro-1-(3-chloropropyl)indole-3-carboxaldehyde 4-Chloro-1-(3-chloropropyl)indole-3-carboxaldehyde was prepared from <strong>[876-72-2]4-chloroindole-3-carboxaldehyde</strong> according to the method described in Example 1 to give 3.8 g (45%, from 4-chloroindole) of the product as a white solid: mp 89 C.; Found: C, 56.16; H, 4.23; N, 5.40%. C12H11Cl2NO requires: C, 56.27; H, 4.33; N, 5.47%.

Reference： [1]Patent: US6433175,2002,B1

17
[ 876-72-2 ]
[ 6419-36-9 ]
[ 1316694-62-8 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5320 - 5334

18
[ 123-75-1 ]
[ 876-72-2 ]
C₁₃H₁₃ClN₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

19
[ 876-72-2 ]
[ 1422432-71-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

20
[ 876-72-2 ]
[ 1422432-87-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

21
[ 876-72-2 ]
[ 1428648-07-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

22
[ 876-72-2 ]
[ 1428648-59-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

23
[ 876-72-2 ]
[ 1422433-20-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

24
[ 876-72-2 ]
[ 1422432-57-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 944 - 948

25
[ 876-72-2 ]
[ 1428968-37-9 ]

Reference： [1]Patent: WO2013/45516,2013,A1

26
[ 876-72-2 ]
[ 24424-99-5 ]
[ 914349-00-1 ]

Yield	Reaction Conditions	Operation in experiment
0.431 g	With dmap; In acetonitrile; at 20℃;	General procedure: To a solution of an appropriate indole, azaindole or alternative heterocycles (1.0 eq) and di-ferf-butyl dicarbonate (1eq. to 2 eq., more in particular 1.2 eq) in acetonitrile was added DMAP (0.1 to 0.5 eq. more in particular 0.1 eq). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with a saturated sodium bicarbonate solution. The phases were separated. The aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with a saturated ammonium chloride solution, water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The BOC-protected compound was used in the next step without further purification.

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 9179 - 9195
[2]Patent: WO2013/45516,2013,A1 .Location in patent: Page/Page column 129; 151

27
[ 876-72-2 ]
[ 75-52-5 ]
[ 1452838-23-1 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4330 - 4333
[2]Patent: WO2015/129926,2015,A1 .Location in patent: Page/Page column 154

28
[ 876-72-2 ]
[ 2447-16-7 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4330 - 4333
[2]Patent: WO2015/129926,2015,A1

29
[ 876-72-2 ]
[ 1452838-25-3 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4330 - 4333

30
[ 876-72-2 ]
[ 1452838-36-6 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4330 - 4333

31
[ 876-72-2 ]
[ 1452838-47-9 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4330 - 4333

32
[ 876-72-2 ]
[ 889942-73-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 1840 - 1840
[2]Organic and Biomolecular Chemistry,2015,vol. 13,p. 8322 - 8329

33
[ 876-72-2 ]
[ 24424-99-5 ]
tert-butyl 3-((4-(2-((tert-butyldimethylsilyl)oxy)ethyl)piperazin-1-yl)methyl)-4-chloro-1H-indole-1-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 9179 - 9195

34
[ 876-72-2 ]
N-benzyl-2-(4-(4-chloro-1H-indol-3-yl)-2,5-dioxoimidazolidin-1-yl)-N-(1-cyclopropylethyl)acetamide [ No CAS ]

Reference： [1]Patent: WO2016/44777,2016,A1

35
[ 876-72-2 ]
[ 506-87-6 ]
C₁₁H₈ClN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium cyanide; In ethanol; water; at 95℃;Sealed tube;	To a stirring solution of compound 1(0.5 g, 2.78 mmol) in EtOH (6 mL), H20 (6 mL) was added (NH4)2C03 (1.334 g, 13.9 mmol) followed by potassium cyanide (0.272 g, 4.17 mmol) at room temperature in a sealed tube. The reaction mixture was heated to 95 C overnight. After consumption of the starting material (by TLC), thereaction mixture was diluted with water and extracted with EtOAc. Combined organic extracts were dried over anhydrous Na2504 and concentrated under reduced pressure to obtain crude product, which was purified by silica gel column chromatography eluting with 66% PE/EtOAc to afford compound 2 (0.344 g, 50%) as a yellow solid. LC-MS: m/z =250[(M+1)].

Reference： [1]Patent: WO2016/44777,2016,A1 .Location in patent: Page/Page column 72; 73

36
[ 876-72-2 ]
[ 75-52-5 ]
3-(2-nitrovinyl)-4-chloro-1H-indole [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2018,vol. 360,p. 2959 - 2965

37
[ 876-72-2 ]
[ 73874-95-0 ]
C₁₉H₂₆ClN₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 6002 - 6017

38
[ 876-72-2 ]
C₁₄H₁₈ClN₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 6002 - 6017

39
[ 876-72-2 ]
C₃₀H₃₆ClN₅O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 6002 - 6017

40
[ 876-72-2 ]
(S)-2-amino-N-(1-((4-chloro-1H-indol-3-yl)methyl)piperidin-4-yl)-3-(1H-indol-3-yl)propanamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 6002 - 6017

41
[ 59-48-3 ]
[ 876-72-2 ]
C₁₇H₁₃ClN₂O [ No CAS ]