[ CAS No. 10242-00-9 ] {[proInfo.proName]}

Name: 10242-00-9|6-Nitro-1H-indole-2-carboxylic acid|95%
Brand: Ambeed
SKU: A556066
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Quality Control of [ 10242-00-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 10242-00-9 ]

CAS No. :	10242-00-9	MDL No. :	MFCD02664466
Formula :	C₉H₆N₂O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JIXJNWVLWQQNDB-UHFFFAOYSA-N
M.W :	206.15	Pubchem ID :	4714997
Synonyms :

Calculated chemistry of [ 10242-00-9 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	54.08
TPSA :	98.91 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) :	-6.04 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.82
Log Po/w (XLOGP3) :	2.14
Log Po/w (WLOGP) :	1.77
Log Po/w (MLOGP) :	0.06
Log Po/w (SILICOS-IT) :	-0.3
Consensus Log Po/w :	0.9

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.78
Solubility :	0.343 mg/ml ; 0.00167 mol/l
Class :	Soluble
Log S (Ali) :	-3.85
Solubility :	0.0292 mg/ml ; 0.000142 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.04
Solubility :	1.86 mg/ml ; 0.00904 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.74

Safety of [ 10242-00-9 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 10242-00-9 ]

* 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 [ 10242-00-9 ]
Downstream synthetic route of [ 10242-00-9 ]

[ 10242-00-9 ] Synthesis Path-Upstream 1~1

1
[ 10242-00-9 ]
[ 4769-96-4 ]

Reference： [1] Journal of the American Chemical Society, 1958, vol. 80, p. 4621

[ 10242-00-9 ] Synthesis Path-Downstream 1~50

1
[ 10242-00-9 ]
[ 4769-96-4 ]

Yield	Reaction Conditions	Operation in experiment
	With quinoline; copper(II) oxide

Reference： [1]Parmerter et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 4621]

2
[ 16792-45-3 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide

Reference： [1]Parmerter et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 4621]

3
[ 10242-00-9 ]
5-hydroxy-(1S)-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole hydrochloride [ No CAS ]
3-(6-nitroindole-2-carbonyl)-1-(S)-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.60 mg	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 14h;

Reference： [1]Parrish, Jay P.; Kastrinsky, David B.; Stauffer, Frederic; Hedrick, Michael P.; Hwang, Inkyu; Boger, Dale L. [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 17, p. 3815 - 3838]

4
[ 31252-42-3 ]
[ 10242-00-9 ]
[ 933474-56-7 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 20℃; for 6h;

Reference： [1]Borza, István; Bozó, Éva; Barta-Szalai, Gizella; Kiss, Csilla; Tárkányi, Gábor; Demeter, Ádám; Gáti, Tamás; Háda, Viktor; Kolok, Sándor; Gere, Anikó; Fodor, László; Nagy, József; Galgóczy, Kornél; Magdó, Ildikó; Ágai, Béla; Fetter, József; Bertha, Ferenc; Keserü, György M.; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György [Journal of Medicinal Chemistry, 2007, vol. 50, # 5, p. 901 - 914]

5
[ 10242-00-9 ]
[ 933474-57-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine; HBTU / dimethylformamide / 6 h / 20 °C 2: H₂ / Pd/C / methanol / 3 h

6
[ 10242-00-9 ]
C₂₂H₂₅N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine; HBTU / dimethylformamide / 6 h / 20 °C 2: H₂ / Pd/C / methanol / 3 h 3: triethylamine / CHCl₃ / 10 h / 20 °C

7
[ 134747-25-4 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: polyphosphoric acid 2: aq.-ethanolic KOH

Reference： [1]Parmerter et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 4621]

8
[ 136818-66-1 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: 6-Nitro-1H-indole-2-carboxylic acid methyl ester With sodium hydroxide; water In methanol at 55℃; Stage #2: With hydrogenchloride In water	138 6-Nitro-1H-indole-2-carboxylic Acid 191 4.4 g (20 mmol) 6-Nitro-1H-indole-2-carboxylic acid methyl ester (190) was dissolved in 80 mL methanol and was treated with 30 mL 1M NaOH overnight at 55 Co. The methanol was evaporated, the remaining aqueous solution was diluted to 100 mL and was acidified to pH 2 using concentrated HCl. The precipitate was filtered off, washed three times with water then dried to give 3.92 g (95%) 191 as yellow powder. The NMR was consistent with the structure. 191 was used without further purification
		62 6-Nitroindole-2-carboxylic acid (I) PREPARATION 62 6-Nitroindole-2-carboxylic acid (I) Following the general procedure of PREPARATION 59 and making non-critical variations but starting with methyl 6nitroindole-2-carboxylate (PREPARATION 61), the title compound is obtained.
		95 6-Nitroindole-2-carboxylic acid (I) PREPARATION 95 6-Nitroindole-2-carboxylic acid (I) Following the general procedure of PREPARATION 63 and making non-critical variations but starting with methyl-6-nitroindole-2-carboxylate (PREPARATION 94), the title compound is obtained.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2004/63645, 2004, A1 Location in patent: Page/Page column 46; 65
[2]Current Patent Assignee: PFIZER INC - US5599930, 1997, A
[3]Current Patent Assignee: PFIZER INC - US5489593, 1996, A

9
[ 16792-45-3 ]
[ 4993-93-5 ]
[ 16732-60-8 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6-nitro-1H-indole-2-carboxylic acid ethyl ester; 4-nitro-1H-indole-2-carboxylic acid ethyl ester With sodium hydroxide; water Heating / reflux; Stage #2: With hydrogenchloride In water at 20℃;	49 A mixture of ethyl 6-nitro-1H-indole-2-carboxylate (0.5 g) and 10% NaOH (20 mL) was heated at reflux overnight and then was cooled to room temperature. The mixture was extracted with ether and the aqueous phase was acidified with HCl to pH 1-2. The insoluble solid was isolated by filtration to give a crude mixture that was taken on to the next step without purification (0.3 g, 68%).

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2007/244159, 2007, A1 Location in patent: Page/Page column 139

10
[ 16732-60-8 ]
[ 10242-00-9 ]
[ 873055-05-1 ]
[ 120975-29-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-nitro-1H-indole-2-carboxylic acid; 6-Nitro-1H-indole-2-carboxylic Acid With thionyl chloride In benzene for 2h; Heating / reflux; Stage #2: With ammonia In dichloromethane; water at 0 - 20℃; for 1h;	49 A mixture of 6-nitro-1H-indole-2-carboxylic acid (12 g, 58 mmol) and SOCl2 (50 mL, 64 mmol) in benzene (150 mL) was heated at reflux for 2 h. The benzene and excess SOCl2 was removed under reduced pressure. The residue was dissolved in anhydrous CH2Cl2 (250 mL) and NH3.H2O (22 g, 0.32 mol) was added dropwise at 0° C. The mixture was stirred at room temperature for 1 h. The insoluble solid was isolated by filtration to obtain crude mixture (9.0 g, 68%), which was used directly in the next step.

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2007/244159, 2007, A1 Location in patent: Page/Page column 139

11
[ 10242-00-9 ]
[ 90886-84-3 ]
[ 1221418-66-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With trichlorophosphate for 6h; Reflux;

Reference： [1]Narayana; Ashalatha; Vijaya Raj; Sarojini [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 12, p. 1794 - 1805]

12
6-nitro-1H-indole-2-carboxylic acid ethyl ester (B-4-b) [ No CAS ]
[ 4993-93-5 ]
[ 16732-60-8 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	In NaOH	2 6-Nitro-1H-indole-2-carboxylic acid and 4-Nitro-1H-indole-2-carboxylic acid Example 2 6-Nitro-1H-indole-2-carboxylic acid and 4-Nitro-1H-indole-2-carboxylic acid A mixture of 4-nitro-1H-indole-2-carboxylic acid ethyl ester and 6-nitro-1H-indole-2-carboxylic acid ethyl ester (B-4-b) (0.5 g, 2.13 mmol) in 10% NaOH (20 mL) was heated at reflux overnight and then cooled to room temperature. The mixture was extracted with ether. The aqueous phase was separated and acidified with HCl to pH 1-2. The resulting solid was isolated via filtration to give a mixture of 6-nitro-1H-indole-2-carboxylic acid and 4-nitro-1H-indole-2-carboxylic acid (0.3 g, 68%).

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2011/98311, 2011, A1

13
[ 10242-00-9 ]
[ 120975-30-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ammonium hydroxide; thionyl chloride / dichloromethane; benzene 2: (CF₃CO)2O; triethylamine / dichloromethane

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2011/98311, 2011, A1

14
[ 16732-60-8 ]
[ 10242-00-9 ]
[ 873055-05-1 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; thionyl chloride In dichloromethane; benzene	2 6-Nitro-1H-indole-2-carboxylic acid amide and 4-Nitro-1H-indole-2-carboxylic acid amide A mixture of 6-nitro-1H-indole-2-carboxylic acid and 4-nitro-1H-indole-2-carboxylic acid (12 g, 58 mmol) and SOCl2 (50 mL, 64 mmol) in benzene (150 mL) was refluxed for 2 h. The benzene and excessive SOCl2 was removed under reduced pressure. The residue was dissolved in CH2Cl2 (250 mL). NH4OH (21.76 g, 0.32 mol) was added dropwise at 0° C. The mixture was stirred at room temperature for 1 h. The resulting solid was isolated via filtration to give a crude mixture of 6-nitro-1H-indole-2-carboxylic acid amide and 4-nitro-1H-indole-2-carboxylic acid amide (9 g, 68%), which was used directly in the next step.

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2011/98311, 2011, A1

15
[ 109-01-3 ]
[ 10242-00-9 ]
[ 1394078-38-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 6-Nitro-1H-indole-2-carboxylic Acid With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 1-methyl-piperazine In N,N-dimethyl-formamide at 20℃; for 16h;	4.2.3.1. (5-Chloro-7-fluoro-1H-indole-2-yl)-(4-methyl-piperazine-1-yl)-methanone (49) General procedure: (5-Chloro-7-fluoro-1H-indole-2-yl)-carboxylic acid (5a) (50 mg, 0.23 mmol), N,N-diisopropylethylamine (82 μl, 0.47 mmol) and 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (89 mg, 0.23 mmol) were dissolved in 550 μl N,N-dimethylformamide. After stirring for 10 min 4-methyl-piperazin 6a (26 μl, 0.23 mmol) was added and the reaction mixture was stirred for 16 h at 20 °C. The solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P1, yielding 37 mg (53%) of the title compound.

Reference： [1]Location in patent: experimental part Engelhardt, Harald; De Esch, Iwan J.P.; Kuhn, Daniel; Smits, Rogier A.; Zuiderveld, Obbe P.; Dobler, Julia; Mayer, Moriz; Lips, Sebastian; Arnhof, Heribert; Scharn, Dirk; Haaksma, Eric E.J.; Leurs, Rob [European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668]

16
[ 109-01-3 ]
[ 10242-00-9 ]
[ 1394078-39-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 0.17 h / 20 °C 1.2: 16 h / 20 °C 2.1: hydrogen / methanol / 2 h / 3750.38 Torr

Reference： [1]Engelhardt, Harald; De Esch, Iwan J.P.; Kuhn, Daniel; Smits, Rogier A.; Zuiderveld, Obbe P.; Dobler, Julia; Mayer, Moriz; Lips, Sebastian; Arnhof, Heribert; Scharn, Dirk; Haaksma, Eric E.J.; Leurs, Rob [European Journal of Medicinal Chemistry, 2012, vol. 54, p. 660 - 668]

17
[ 99-09-2 ]
[ 16732-60-8 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: hydrogenchloride; sodium nitrite; tin(II) chloride dihdyrate / water / 0.5 h / 0 °C 2.1: ethanol / 4 h / 20 °C 3.1: PPA / toluene / Reflux 3.2: Reflux 3.3: pH 1 - 2

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2012/309758, 2012, A1

18
[ 51516-96-2 ]
[ 16732-60-8 ]
[ 10242-00-9 ]

Reference： [1]Patent: US2012/309758,2012,A1

19
[ 134747-25-4 ]
[ 16732-60-8 ]
[ 10242-00-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl 2-[2-(3-nitrophenyl)hydrazinylidene]propanoate In toluene Reflux; Stage #2: With water; sodium hydroxide Reflux; Stage #3: With hydrogenchloride In water	2 2-[(3-Nitro-phenyl)-hydrazono]-propionic acid ethyl ester from the preceding step was dissolved in toluene (300 mL). PPA (30 g) was added. The mixture was heated at reflux overnight and then cooled to room temperature. The solvent was removed to give a mixture of 4-nitro-1H-indole-2-carboxylic acid ethyl ester and 6-nitro-1H-indole-2-carboxylic acid ethyl ester (B-4-b) (15 g, 40%).; A mixture of 4-nitro-1H-indole-2-carboxylic acid ethyl ester and 6-nitro-1H-indole-2-carboxylic acid ethyl ester (B-4-b) (0.5 g, 2.13 mmol) in 10% NaOH (20 mL) was heated at reflux overnight and then cooled to room temperature. The mixture was extracted with ether. The aqueous phase was separated and acidified with HCl to pH 1-2. The resulting solid was isolated via filtration to give a mixture of 6-nitro-1H-indole-2-carboxylic acid and 4-nitro-1H-indole-2-carboxylic acid (0.3 g, 68%).

Reference： [1]Current Patent Assignee: VERTEX PHARMACEUTICALS (OLD) - US2012/309758, 2012, A1 Location in patent: Page/Page column 68

20
[ 10242-00-9 ]
[ 167027-30-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: thionyl chloride / 4 h / Reflux 2: ammonium chloride; zinc / tetrahydrofuran; methanol; water / 1 h / 40 °C / Sonication

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1
[2]Current Patent Assignee: JW PHARMACEUTICAL CO LTD - WO2014/196793, 2014, A1

21
[ 10242-00-9 ]
[ 541522-65-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: triethylamine / dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

22
[ 10242-00-9 ]
[ 1093261-18-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

23
[ 10242-00-9 ]
[ 1049677-82-8 ]

Reference： [1]Patent: WO2008/154271,2008,A1

24
[ 10242-00-9 ]
[ 1093261-21-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: triethylamine / dichloromethane / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

25
[ 10242-00-9 ]
[ 1093261-23-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: triethylamine / dichloromethane / 0.5 h / 20 °C 5: water; lithium hydroxide / tetrahydrofuran; methanol / 1 h / 50 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

26
[ 10242-00-9 ]
[ 1093255-82-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: triethylamine / dichloromethane / 0.5 h / 20 °C 5: water; lithium hydroxide / tetrahydrofuran; methanol / 1 h / 50 °C 6: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 2 h / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

27
[ 10242-00-9 ]
[ 1093261-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: triethylamine / dichloromethane / 1 h / 20 °C 6: water; lithium hydroxide / tetrahydrofuran; methanol / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

28
[ 10242-00-9 ]
[ 1093261-29-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: triethylamine / dichloromethane / 1 h / 20 °C 6: water; lithium hydroxide / tetrahydrofuran; methanol / 20 °C 7: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 1.5 h / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

29
[ 10242-00-9 ]
[ 1093255-84-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: sulfuric acid / 2 h / Reflux 2: dmap / dichloromethane / 1 h / 20 °C 3: hydrogen / platinum(IV) oxide / ethanol / 1 h / 20 °C / 2585.81 Torr / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 5: triethylamine / dichloromethane / 1 h / 20 °C 6: water; lithium hydroxide / tetrahydrofuran; methanol / 20 °C 7: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 1.5 h / 20 °C 8: trifluoroacetic acid / dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1

30
[ 67-56-1 ]
[ 10242-00-9 ]
[ 136818-66-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride for 4h; Reflux;	(a) Synthesis of methyl 6-nitro-1H-indole-2-carboxylate 6-Nitro-1H-indole-2-carboxylic acid (100.0 mg, 0.49 mmol) was dissolved in MeOH (2.4 mL), and SOCl2 (100.0 μ) was slowly added. The reaction mixture was refluxed for 4 hours and concentrated under reduced pressure, and the residue was purified by flash column chromatography (amine silica gel, CH2C12 : MeOH = 30 : 1) to obtain methyl 6-nitro-1H-indole-2-carboxylate (107.0 mg, 100%) as a yellow solid. -NMR (300MHz, DMSO-1H-NMR (300MHz, DMSO-d6: δ 12.64 (brs, 1H), 8.34 (s, 1H), 7.92 (m, 2H), 7.33 (s, 1H), 3.93 (s, 3H)
81%	With sulfuric acid for 2h; Reflux;	122.A Sulfuric acid (1 ml_, 18.76 mmol) was added to a suspension of 6-nitro-1 H-indole-2- carboxylic acid (0.5 g, 2.425 mmol) in methanol (5 ml_). The mixture was heated to reflux for 2 h. The reaction mixture was cooled to RT, poured into ice/water, neutralized with sodium bicarbonate, and extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, and concentrated to give the title compound (0.433 g, 81%) as a yellow solid. 1H NMR (400 MHz, CDCI3): δ ppm 9.31 (s, 1 H), 8.41 (s, 1 H), 8.05 (dd, 1 H), 7.79 (d, 1 H), 7.29 (s, 1 H), 3.70 - 4.24 (m, 3 H). MS: m/z 221 (M+1 ).

Reference： [1]Current Patent Assignee: JW PHARMACEUTICAL CO LTD - WO2014/196793, 2014, A1 Location in patent: Page/Page column 49
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2008/154271, 2008, A1 Location in patent: Page/Page column 133

31
[ 10242-00-9 ]
N-(3-(2-(4-fluorophenyl)propan-2-yl)phenyl)-6-(methylsulfonamido)-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: thionyl chloride / 4 h / Reflux 2: ammonium chloride; zinc / tetrahydrofuran; methanol; water / 1 h / 40 °C / Sonication 3: pyridine / 3 h / 0 - 20 °C 4: lithium hydroxide monohydrate / tetrahydrofuran; methanol; water / 10 h / 20 °C 5: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 15 h / 20 °C