[ CAS No. 688357-19-9 ] {[proInfo.proName]}

Name: 688357-19-9|Methyl 4-Chloro-5-azaindole-2-carboxylate|98%
Brand: Ambeed
SKU: A144915
Price: 25.0 USD
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Quality Control of [ 688357-19-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 688357-19-9 ]

SDS Specification

Alternatived Products of [ 688357-19-9 ]

Product Details of [ 688357-19-9 ]

CAS No. :	688357-19-9	MDL No. :	MFCD09870065
Formula :	C₉H₇ClN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NFEOJQQNFBVATP-UHFFFAOYSA-N
M.W :	210.62	Pubchem ID :	26599236
Synonyms :

Calculated chemistry of [ 688357-19-9 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.11
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	52.38
TPSA :	54.98 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) :	-6.07 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.88
Log Po/w (XLOGP3) :	2.13
Log Po/w (WLOGP) :	2.0
Log Po/w (MLOGP) :	1.07
Log Po/w (SILICOS-IT) :	2.47
Consensus Log Po/w :	1.91

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.83
Solubility :	0.31 mg/ml ; 0.00147 mol/l
Class :	Soluble
Log S (Ali) :	-2.92
Solubility :	0.256 mg/ml ; 0.00121 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.61
Solubility :	0.0517 mg/ml ; 0.000245 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.78

Safety of [ 688357-19-9 ]

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

Application In Synthesis of [ 688357-19-9 ]

* 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 [ 688357-19-9 ]
Downstream synthetic route of [ 688357-19-9 ]

[ 688357-19-9 ] Synthesis Path-Upstream 1~4

1
[ 1418287-33-8 ]
[ 688357-19-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With copper(l) iodide; potassium carbonate; <i>L</i>-proline In 1,4-dioxaneInert atmosphere; Reflux	To a solution of (racemic)-benzyloxycarbonyl-a-phosphonoglycine trimethyl ester (12.08 g, 36.5 mmole) in 80 mL C¾C1₂ was added DBU (6.34 mL, 42.1 mmole) slowly at RT. After 30 minutes a solution of 2-chloro-3-formyl-4-iodopyridine (7.5 g, 28.0 mmole) in 20 mL CH₂C1₂ was added slowly at RT. During the addition the reaction became slightly exothermic and was cooled via a cold water bath. After 4 hr the mixture was diluted with CH₂C1₂and washed with IN aqueous HC1 (2 x) and H₂0 (1 x). The organic layer was dried (MgS0₄), filtered, and concentrated. Flash column (ISCO Redi-Sep 330g Si0₂, 20percent EtOAc hexanes) gave methyl (2Z)-2-[(benzyloxy)carbonyl]amino}-3-(2-chloro-4-iodopyridin-3-yl)prop-2-enoate (11.46 g, 86percent) as a white solid. 1H NMR (399 MHz, CDCI3): δ 7.89 (d, J = 5.1 Hz, 1 H); 7.70 (d, J = 5.1 Hz, 1 H); 7.33 (m, 3 H); 7.24 (m, 2 H); 7.06 (s, 1 H); 6.96 (s, 1 H); 4.97 (s, 2 H); 3.91 (s, 3 H).Methyl (2Z)-2-[(benzyloxy)carbonyl]amino}-3-(2-chloro-4-iodopyridin-3-yl)prop-2-enoate (11.46 g, 24.25 mmole), K₂C0₃ (10.05 g, 72.7 mmole), Cul (0.462 g, 2.425 mmole), and L- proline (0.558 g, 4.85 mmole) were combined in 1,4-dioxane (120 mL). The mixture was degassed (3 x pump/N₂) then heated to reflux. After stirring at reflux overnight the mixture was cooled to RT, diluted with saturated aqueous NH₄CI, and extracted with CH₂C1₂ (3 x). The combined organic layers were dried (MgS0₄), filtered through a pad of Celite, and concentrated. The resulting solid was triturated with Et₂0/hexanes to give the title compound (4.6 g, 90percent) as an off-white solid. Ή NMR (399 MHz, CDC1₃): δ 9.25 (s, 1 H); 8.18 (d, J = 5.8 Hz, 1 H); 7.35 (d, J = 2.1 Hz, 1 H); 7.29 (d, J = 5.9 Hz, 1 H); 3.99 (s, 3 H).

Reference： [1] Patent: WO2013/9582, 2013, A1, . Location in patent: Page/Page column 29; 30
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5800 - 5816

2
[ 688357-18-8 ]
[ 688357-19-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	for 6.5 h; Reflux	A solution of 2-2 (3.8 g, 12.1 mmol) in xylene (35 mL) was added dropwise to boiling xylene (250 mL) over a period of 30 minutes, and the mixture was stirred at - the same temperature for 6 hours. The reaction mixture was allowed to cool to room temperature, and then stirred at 0°C for additional 1 hour. The resulting solid was collected by filtration, and dried under vacuum to give the desired product 2-3 as a yellow solid (1.7 g, 56percent); LCMS: m/z 211 (M+ 1).
56%	for 6 h; Reflux	Step II: methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (2-3) A solution of 2-2 (3.8 g, 12.1 mmol) in xylene (35 mL) was added dropwise to boiling xylene (250 mL) over a period of 30 minutes, and the mixture was stirred at the same temperature for 6 hours. The reaction mixture was allowed to cool to room temperature, and then stirred at 0° C. for additional 1 hour. The resulting solid was collected by filtration, and dried under vacuum to give the desired product 2-3 as a yellow solid (1.7 g, 56percent); LCMS: m/z 211 (M⁺+1).

Reference： [1] Synthesis, 2005, # 16, p. 2751 - 2757
[2] Organic Syntheses, 2007, vol. 84, p. 262 - 271
[3] Patent: WO2015/88045, 2015, A1, . Location in patent: Paragraph 0286
[4] Patent: US2017/8885, 2017, A1, . Location in patent: Paragraph 0693; 0696
[5] Patent: WO2006/89309, 2006, A2, . Location in patent: Page/Page column 50
[6] Patent: WO2006/26273, 2006, A2, . Location in patent: Page/Page column 32
[7] Patent: WO2006/57922, 2006, A2, . Location in patent: Page/Page column 82
[8] Patent: US2007/299122, 2007, A1, . Location in patent: Page/Page column 16
[9] Patent: WO2006/52555, 2006, A2, . Location in patent: Page/Page column 104
[10] Patent: WO2006/113150, 2006, A1, . Location in patent: Page/Page column 65

3
[ 36404-88-3 ]
[ 688357-19-9 ]

Reference： [1] Synthesis, 2005, # 16, p. 2751 - 2757
[2] Patent: WO2015/88045, 2015, A1,
[3] Patent: US2017/8885, 2017, A1,
[4] Patent: WO2006/113150, 2006, A1,

4
[ 153034-90-3 ]
[ 688357-19-9 ]

Reference： [1] Patent: WO2013/9582, 2013, A1,
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5800 - 5816

[ 688357-19-9 ] Synthesis Path-Downstream 1~88

1
[ 688357-18-8 ]
[ 688357-19-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	In 5,5-dimethyl-1,3-cyclohexadiene; for 6.5h;Reflux;	A solution of 2-2 (3.8 g, 12.1 mmol) in xylene (35 mL) was added dropwise to boiling xylene (250 mL) over a period of 30 minutes, and the mixture was stirred at - the same temperature for 6 hours. The reaction mixture was allowed to cool to room temperature, and then stirred at 0C for additional 1 hour. The resulting solid was collected by filtration, and dried under vacuum to give the desired product 2-3 as a yellow solid (1.7 g, 56%); LCMS: m/z 211 (M+ 1).
56%	In 5,5-dimethyl-1,3-cyclohexadiene; for 6h;Reflux;	Step II: methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (2-3) A solution of 2-2 (3.8 g, 12.1 mmol) in xylene (35 mL) was added dropwise to boiling xylene (250 mL) over a period of 30 minutes, and the mixture was stirred at the same temperature for 6 hours. The reaction mixture was allowed to cool to room temperature, and then stirred at 0 C. for additional 1 hour. The resulting solid was collected by filtration, and dried under vacuum to give the desired product 2-3 as a yellow solid (1.7 g, 56%); LCMS: m/z 211 (M++1).
	In 1,3,5-trimethyl-benzene; for 1h;Heating / reflux;	Step 3 Methyl 4-chloro- lH-pyrroloD ,2-c1pyridine-2-carboxylateA solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]rhorop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 0C, and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1 :20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid (13.2 g).

	In 1,3,5-trimethyl-benzene; at 0 - 20℃; for 1h;Heating / reflux;	A solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 0C, and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1:20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid.
	In 1,3,5-trimethyl-benzene; for 1h;Heating / reflux;	Step 3; Methyl 4-chloro-lH-pyrrolor3,2-c1pyridine-2-carboxylateA solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 niL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 0C, and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1 :20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid (13.2 g).
	In 1,3,5-trimethyl-benzene; at 0 - 20℃; for 1h;Heating / reflux;	A solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 C., and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1:20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid (13.2 g).
	In 1,3,5-trimethyl-benzene; for 1h;Heating / reflux;	A solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 0C, and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1 :20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid (13.2 g).
	In 1,3,5-trimethyl-benzene; for 1h;Heating / reflux;	Step 3 Methyl 4-chloro-lH-pyttauolo[3,2-clpyridine-2-carboxylateA solution of methyl (2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 C, and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1 :20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid.

Reference： [1]Synthesis,2005,p. 2751 - 2757
[2]Organic Syntheses,2007,vol. 84,p. 262 - 271
[3]Patent: WO2015/88045,2015,A1 .Location in patent: Paragraph 0286
[4]Patent: US2017/8885,2017,A1 .Location in patent: Paragraph 0693; 0696
[5]Patent: WO2006/89309,2006,A2 .Location in patent: Page/Page column 50
[6]Patent: WO2006/26273,2006,A2 .Location in patent: Page/Page column 32
[7]Patent: WO2006/57922,2006,A2 .Location in patent: Page/Page column 82
[8]Patent: US2007/299122,2007,A1 .Location in patent: Page/Page column 16
[9]Patent: WO2006/52555,2006,A2 .Location in patent: Page/Page column 104
[10]Patent: WO2006/113150,2006,A1 .Location in patent: Page/Page column 65

2
[ 36404-88-3 ]
[ 688357-19-9 ]

Reference： [1]Synthesis,2005,p. 2751 - 2757
[2]Patent: WO2015/88045,2015,A1
[3]Patent: US2017/8885,2017,A1
[4]Patent: WO2006/113150,2006,A1

Yield	Reaction Conditions	Operation in experiment
		Step 3 Methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate A solution of methyl(2Z)-2-azido-3-[2-chloropyridin-3-yl]prop-2-enoate (21 g, 88 mmol) in mesitylene (880 mL) was heated at reflux for a period of 1 h. The reaction mixture was cooled to room temperature then to 0 C., and the precipitate was filtered and washed with cold hexane. The material was stirred overnight in 1:20 EtOAc/hexane to give, after filtration, the title product as a pale yellow solid (13.2 g).

4
[ 688357-19-9 ]
[ 292638-85-8 ]
[ 688357-20-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	To a suspension of <strong>[688357-19-9]methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate</strong> (12.5 g, 59 mmol) in THF (116 ml ) - toluene (460 ml ) were added a 1.0 M THF solution of potassium tert-butoxide (64 rnL, 64 mrnol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 100C. for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	Step 4 Methyl 1 -chloro-delta-oxo-y^-dihydro-betaH-pyridofS^-^ipyrrolizine-?- carboxylate To a suspension of methyl 4-chloro-lH-pyrrolo[3,2-c]pyridine-2-carboxylate (12.5 g, 59 mmol) in TEtaF (116 mL) - toluene (460 mL) were added a 1.0 M TEtaF solution of potassium tert- butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 1000C for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound
	With potassium tert-butylate; In tetrahydrofuran; THF (116 mL)-toluene; ammonium chloride;	Step 4 Methyl 1-chloro-8-oxo-7,8-dihydro-6H-pyrido[3,4-b]pyrrolizine-7-carboxylate To a suspension of <strong>[688357-19-9]methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate</strong> (12.5 g, 59 mmol) in THF (116 mL)-toluene (460 mL) were added a 1.0 M THF solution of potassium tert-butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 100 C. for 18 h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.

	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	To a suspension of methyl 4-chloro-lH-pyrrolo[3,2-c]pyridine-2-carboxylate (12.5 g, 59 mmol) in TKF (116 mL) - toluene (460 mL) were added a 1.0 M TEtaF solution of potassium tert- butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 100C for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	Step 4; Methyl l-chloro-8-oxo-7,8-dihvdro-6H-pwidor3,4-Zphiyrrolizine-7- carboxylateTo a suspension of methyl 4-chloro-lH-pyrrolo[3,2-c]pyridine-2-carboxylate (12.5 g, 59 mmol) in TEtaF (116 mL) - toluene (460 mL) were added a 1.0 M TEtaF solution of potassium tert- butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 1000C for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	To a suspension of <strong>[688357-19-9]methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate</strong> (12.5 g, 59 mmol) in THF (116 mL)-toluene (460 mL) were added a 1.0 M THF solution of potassium tert-butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 100 C. for 18 h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	To a suspension of methyl 4-chloro-lH-pyrrolo[3,2-c]pyridine-2-carboxylate (12.5 g, 59 mmol) in TEtaF (116 mL) - toluene (460 mL) were added a 1.0 M TEtaF solution of potassium tert- butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated EPO <DP n="106"/>at 1000C for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.
	With potassium tert-butylate; In tetrahydrofuran; toluene; at 100℃; for 18h;	Step 4 Methyl l-chloro-8-oxo-7,8-dihvdro-6H-pyrido[3,4-61pyrrolizine-7- carboxylateTo a suspension of methyl 4-chloro-lH-pyrrolo[3,2-c]pyridine-2-carboxylate (12.5 g, 59 mmol) in TEtaF (116 mL) - toluene (460 mL) were added a 1.0 M TEtaF solution of potassium tert- butoxide (64 mL, 64 mmol) and methyl acrylate (55 mL, 611 mmol). The resulting mixture was heated at 1000C for 18h. After this time, the suspension was cooled to room temperature and it was poured into a mixture of saturated aqueous NH4Cl (400 mL) and hexanes (400 mL). The solids were decanted, filtered and washed with H2O and hexanes to provide the title compound.

Reference： [1]Patent: WO2004/39807,2004,A1 .Location in patent: Page 49
[2]Patent: WO2006/89309,2006,A2 .Location in patent: Page/Page column 50
[3]Patent: US2004/229844,2004,A1
[4]Patent: WO2006/26273,2006,A2 .Location in patent: Page/Page column 33
[5]Patent: WO2006/57922,2006,A2 .Location in patent: Page/Page column 82
[6]Patent: US2007/299122,2007,A1 .Location in patent: Page/Page column 16
[7]Patent: WO2006/52555,2006,A2 .Location in patent: Page/Page column 104-105
[8]Patent: WO2006/113150,2006,A1 .Location in patent: Page/Page column 66

5
[ 688357-19-9 ]
[ 916326-10-8 ]
C₁₇H₁₅N₃O₄ [ No CAS ]

Reference： [1]Synthetic Communications,2008,vol. 38,p. 2775 - 2781

6
[ 688357-19-9 ]
[ 292638-85-8 ]
C₁₂H₉ClN₂O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 2125 - 2128

7
[ 688357-19-9 ]
4-(3-ethoxyphenyl)-1-[(1-phenylpyrrolidin-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid trifluoroacetate [ No CAS ]