[ CAS No. 1031417-41-0 ] {[proInfo.proName]}

Name: 1031417-41-0|7-Methyl-1H-indazole-5-carboxylic acid|96%
Brand: Ambeed
SKU: A313129
Price: 24.0 USD
Availability: InStock
Rating: 91 (35 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 1031417-41-0

Structure of 1031417-41-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1031417-41-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1031417-41-0 ]

SDS Specification

Alternatived Products of [ 1031417-41-0 ]

Product Details of [ 1031417-41-0 ]

CAS No. :	1031417-41-0	MDL No. :	MFCD14585353
Formula :	C₉H₈N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XMVNTKZCEKCKQD-UHFFFAOYSA-N
M.W :	176.17	Pubchem ID :	53408503
Synonyms :

Calculated chemistry of [ 1031417-41-0 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.11
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	48.02
TPSA :	65.98 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.83
Log Po/w (XLOGP3) :	1.44
Log Po/w (WLOGP) :	1.57
Log Po/w (MLOGP) :	1.04
Log Po/w (SILICOS-IT) :	1.82
Consensus Log Po/w :	1.34

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.29
Solubility :	0.912 mg/ml ; 0.00518 mol/l
Class :	Soluble
Log S (Ali) :	-2.43
Solubility :	0.653 mg/ml ; 0.00371 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.67
Solubility :	0.378 mg/ml ; 0.00214 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.47

Safety of [ 1031417-41-0 ]

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 [ 1031417-41-0 ]

* 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 [ 1031417-41-0 ]
Downstream synthetic route of [ 1031417-41-0 ]

[ 1031417-41-0 ] Synthesis Path-Upstream 1~1

1
[ 124-38-9 ]
[ 156454-43-2 ]
[ 1031417-41-0 ]

Yield	Reaction Conditions	Operation in experiment
86.6%	Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.333333 h; Stage #2: With sec.-butyllithium In tetrahydrofuran; cyclohexane; mineral oil at -78℃; for 4 h;	To a solution of 5-bromo-7-methylindazole, (purchased from PharmaLab, Morrisville, PA) (2.00 g, 9.47 mmol) in anhydrous THF (50 ml) was added NaH (570 mg, 14.25 mmol; 60percent suspension in mineral oil) at room temperature. After 20 minutes the mixture was cooled to -78 ⁰C and sec-butyllithium (1.4 M in cyclohexane, 17 ml; 23.8 mmol) was added drop wise and the resulting mixture was stirred for 4 hours. Dry CO₂ was then bubbled through the reaction mixture for 1 hour while allowing warming to room temperature. It was then stirred at room temperature overnight. 1 N HCI was added and the solution extracted with EtOAc. The organic layer was washed with saturated aqueous NaCI, dried (MgSO₄), then filtered and concentrated. The residue was re-dissolved in MeOH, filtered, then concentrated to provide the product as a brown solid (1.445 g, 86.6percent). ¹H NMR (DMSO-d₆) δ 8.23 (s, 1H), 8.17 (s, 1H), 7.65 (s, 1H), 2.46 (s, 3H). LC/MS ES+ 177 (MH+).

Reference： [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 2, p. 935 - 942
[2] Patent: WO2008/65508, 2008, A1, . Location in patent: Page/Page column 27
[3] Synthetic Communications, 2012, vol. 42, # 13, p. 1914 - 1921

[ 1031417-41-0 ] Synthesis Path-Downstream 1~42

1
[ 124-38-9 ]
[ 156454-43-2 ]
[ 1031417-41-0 ]

Yield	Reaction Conditions	Operation in experiment
86.6%		To a solution of 5-bromo-7-methylindazole, (purchased from PharmaLab, Morrisville, PA) (2.00 g, 9.47 mmol) in anhydrous THF (50 ml) was added NaH (570 mg, 14.25 mmol; 60% suspension in mineral oil) at room temperature. After 20 minutes the mixture was cooled to -78 0C and sec-butyllithium (1.4 M in cyclohexane, 17 ml; 23.8 mmol) was added drop wise and the resulting mixture was stirred for 4 hours. Dry CO2 was then bubbled through the reaction mixture for 1 hour while allowing warming to room temperature. It was then stirred at room temperature overnight. 1 N HCI was added and the solution extracted with EtOAc. The organic layer was washed with saturated aqueous NaCI, dried (MgSO4), then filtered and concentrated. The residue was re-dissolved in MeOH, filtered, then concentrated to provide the product as a brown solid (1.445 g, 86.6%). 1H NMR (DMSO-d6) delta 8.23 (s, 1H), 8.17 (s, 1H), 7.65 (s, 1H), 2.46 (s, 3H). LC/MS ES+ 177 (MH+).

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 935 - 942
[2]Patent: WO2008/65508,2008,A1 .Location in patent: Page/Page column 27
[3]Synthetic Communications,2012,vol. 42,p. 1914 - 1921

2
[ 1031417-41-0 ]
[ 927978-38-9 ]
[ 1031411-94-5 ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine; HATU; In dichloromethane; at 20℃; for 6h;	Method B: To a flask was added the appropriate amine or amine hydrochloride (1 equivalents), DMF or CH2CI2 (about 0.1 M), carboxylic acid, N,N-diisopropylethylamine (DIEA) (4-6 equivalents) or triethylamine (TEA) (4-6 equivalents) and HATU (1-1.3 equivalents). The mixture was stirred at room temperature until the reaction was complete as determined by LC/MS. The mixture was diluted with ethyl acetate and washed with saturated aqueous NaHCO3 (2x) and then saturated aqueous NaCI. The organic extract was dried over MgSO4, filtered and concentrated. The crude material was purified by liquid chromatography to afford product. Alternately, (hereinafter, "Method B1"), the crude reaction mixture was concentrated and d1rectiy~purifled by chromatography as ^described in Method A1; Ex. A1 : Method B1 was used to form 6,7-dimethyl-1'-[(7-rnethyl-1H-indazol-5-yl)carbonyl]spiro- [chromene-2,4'-piperidin]-4(3H)-one as follows. A solution of 6,7-dimethylspiro[chromene-2,4 -piperidin]- 4(3H)-one (300 mg, 0.83 mmol) in CH2CI2 (5 ml_) was treated with triethylamine (0.70 ml_, 5.0 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate ("HATU") (317 mg, 0.84 mmol). The mixture was stirred at room temperature for 6 hours before removing the solvents under reduced pressured and purified by chromatography to afford the titled compound (50 mg, 48,%). 1H NMR (CDCI3) delta 8.24 (br s, 1H), 7.71 (s, 1H), 7.59 (s, 1H), 7.33 (s, 1H), 6.80 (s, 1H), 2.66 (m, 3H), 2.26 (s, 3H), 2.20 (s, 3H).
	With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 16h;	Method A: To 10x75 mm culture tubes was added 500 muL (1 equivalent ("eq")) of a 0.2 M solution of the appropriate carboxylic acid in anhydrous DMF. To this was added 500 muL (0.10 mmol) of a 0.2 M solution of spirocyclic amine 6,7-dimethylspiro[chromene-2,4'-piperidin]-4(3H)-one in anhydrous dimethylformamide (DMF). To this was added 200 muL (1 eq) of a 0.5 M solution of triethylamine in anhydrous DMF. To this was added 200 muL (1 eq) of a 0.5 M O-^-azabenzotriazoM-yO-N.N.N'.N1- tetramethyluronium hexafluorophosphate (HATU) solution in anhydrous DMF. The tubes were capped and the reaction mixtures were stirred for 16 hours at room temperature. The vlatiles from the tubes were removed using a rotary evaporator system at 55 0C for 4 hours. Dimethylsulfoxide (1540 muL containing 0.01% 2,6-di-t-butyl-4-methylphenol (BHT)) was added to each tube (final theoretical concentration 0.05 M). The tubes were covered with cellophane and agitated for 5 minutes or until the product in each tube was dissolved. Product was analyzed by LC/MS.Alternately in Method A, the following analysis and purification method was used (hereinafter, "Method A1"). Throughout Method A1 , the solvents used were: A: water, B: acetonitrile and C: 1% aqueous trifluoroacetic acid., [percent by volume]; Method A was used to form 6,7-dimethyl-1'-[(7-methyl-1H-indazol-5-yl)carbonyl]spiro- [chromene-2,4'-piperidin]-4(3H)-one trifluoroacetic acid salt as follows. To 10x75 mm culture tubes was added 400 muL (0.08 mmol) of a 0.2 M solution of 6,7-dimethylspiro[chromene-2,4'-piperidin]-4(3H)-one in anhydrous dimethylformamide (DMF) followed by a stir bar. To this was added 400 muL (1 eq) of a 0.2 M solution of the appropriate carboxylic acid in anhydrous DMF. To this was added 160 muL (1 eq) of a 0.5 M solution of triethylamine in anhydrous DMF. To this was added 160 muL (1 eq) of a 0.5 M HATU solution in anhydrous DMF. The tubes were covered with cellophane and the reaction mixtures were stirred for 16 hours. The volatiles from the tubes were removed using a rotary evaporator system with medium heating. Dimethylsulfoxide (1540 muL containing 0.01% 2,6-di-t-butyl-4-methylphenol (BHT)) was added to each tube (final theoretical concentration 0.05 M). The tubes were covered with cellophane and agitated for 5 minutes or until the product in each tube was dissolved. MS(ACPI) m/z 404 (M+H)+, HPLC RT 1.56 minutes, 1H NMR (CDCI3) delta 8.24 (br s, 1H), 7.71 (s, 1H), 7.59 (s, 1H), 7.33 (s, 1H), 6.80 (s, 1H), 2.66 (m, 3H), 2.26 (s, 3H), 2.20 (s, 3H).

Reference： [1]Patent: WO2008/65508,2008,A1 .Location in patent: Page/Page column 43; 44
[2]Patent: WO2008/65508,2008,A1 .Location in patent: Page/Page column 41; 43; 44

3
[ 1031417-41-0 ]
[ 74-88-4 ]
[ 1197943-91-1 ]
[ 1197943-93-3 ]

Yield	Reaction Conditions	Operation in experiment
22%; 35%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 50℃;	Acid Preparation 12; 2,7-Dimethvl-2H-indazole-5-carboxvlic acid; To a solution of 7-methyl-1 H-indazole-5-carboxylic acid (356 mg, 2.0 mmol) in DMF (6 mL) was added K2CO3 (0.85 g, 6.2 mmol) and iodomethane (0.45 mL, 7.2 mmol). The mixture was stirred at room temperature for 4 hours and then heated at 50 3C overnight. The reaction was cooled to room temperature, diluted with EtOAc and washed with saturated <n="50"/>aqueous NaCI. The organic extract was concentrated and purified by Biotage chromatography (40 S column, 25-50% EtOAc/heptane) to afford methyl 1 ,7-dimethyl-i H- indazole-5-carboxylate (91 mg, 22%) and methyl 2,7-dimethyl-2H-indazole-5-carboxylate (141 mg, 35%).

Reference： [1]Patent: WO2009/144554,2009,A1 .Location in patent: Page/Page column 48-49

4
[ 1031417-41-0 ]
6-methylspiro-[2H-1,3-benzoxazin-2,4'-piperidin]-4-(3H)-one trifluoroacetate [ No CAS ]
[ 1204345-05-0 ]

Yield	Reaction Conditions	Operation in experiment
56%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 3h;	Example 1046-Methyl-1'-[(7-methyl-1H-indazol-5-yl)carbonyl]spiro[2H-1,3-benzoxazin-2,4'-piperidin]-4-(3H)-one (Compound 123)To a solution of 32 mg (0.18 mmol) of <strong>[1031417-41-0]7-methyl-1H-indazole-5-carboxylic acid</strong> (see WO2008/065508), 70 mg (0.18 mmol) of HATU, and 0.067 mL (0.39 mmol) of diisopropylethylamine in 1.0 mL of DMF is added 62 mg (0.18 mmol) of the trifluoroacetic acid salt of 6-methylspiro-[2H-1,3-benzoxazin-2,4'-piperidin]-4-(3H)-one (from TFA cleavage of 6-methyl-1'-(tert-butyloxycarbonyl)spiro[1,3-benzoxazine-2,4'-piperidine]-4(3H)-one, purchased from Apollo Scientific). The mixture is stirred at room temperature for 3 hr., and then diluted with ethyl acetate. The ethyl acetate solution is washed with aqueous sodium bicarbonate, then brine, and is finally dried over Na2SO4. After solvent removal by rotoevaporation, the crude product is purified by preparative TLC to give to give 38 mg (0.10 mmol. 56% yield) 6-methyl-1'-[(7-methyl-1H-indazol-5-yl)carbonyl]spiro[2H-1,3-benzoxazin-2,4'-piperidin]-4-(3H)-one (Compound 123): MS m/z: 391.0 (M+H)+, 413.0 (M+Na)+.

Reference： [1]Patent: US2010/9982,2010,A1 .Location in patent: Page/Page column 70

5
[ 1031417-41-0 ]
[ 1038399-45-9 ]
[ 79099-07-3 ]
[ 1224198-48-4 ]