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Chemistry
Heterocyclic Building Blocks
Indazoles
Indazole Derivatives
4-Bromo-6-chloro-1H-indazole
Chemistry
Heterocyclic Building Blocks
Organic Building Blocks
Indazoles
Bromides Chlorides
Indazole Derivatives
6-chloro-1H-indazole

[ CAS No. 885519-03-9 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 885519-03-9
Chemical Structure| 885519-03-9
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Quality Control of [ 885519-03-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification
Alternatived Products of [ 885519-03-9 ]

Product Details of [ 885519-03-9 ]

CAS No. :885519-03-9 MDL No. :MFCD07781352
Formula : C7H4BrClN2 Boiling Point : -
Linear Structure Formula :- InChI Key :KCDKINCUTSIQAF-UHFFFAOYSA-N
M.W : 231.48 Pubchem ID :24728100
Synonyms :

Calculated chemistry of [ 885519-03-9 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 48.8
TPSA : 28.68 Ų

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) : -5.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.52
Log Po/w (XLOGP3) : 2.87
Log Po/w (WLOGP) : 2.98
Log Po/w (MLOGP) : 2.46
Log Po/w (SILICOS-IT) : 3.35
Consensus Log Po/w : 2.63

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.69
Solubility : 0.0474 mg/ml ; 0.000205 mol/l
Class : Soluble
Log S (Ali) : -3.13
Solubility : 0.171 mg/ml ; 0.000738 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.39
Solubility : 0.00952 mg/ml ; 0.0000411 mol/l
Class : Moderately soluble

Medicinal Chemistry

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

Safety of [ 885519-03-9 ]

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 [ 885519-03-9 ]

* 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.

  • Downstream synthetic route of [ 885519-03-9 ]

[ 885519-03-9 ] Synthesis Path-Downstream   1~69

  • 1
  • [ 885519-03-9 ]
  • 4-benzyloxy-3-fluorophenylboronic acid [ No CAS ]
  • [ 1056263-84-3 ]
  • C20H13BrClFN2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine;copper diacetate; In dichloromethane; for 40h;Molecular sieve; Description 10; 4-Bromo-6-chloro-1 -{3-fluoro-4-[(phenyl methyl )oxy]phenyl}-1H-indazole (D10)4-Bromo-6-chloro-1 H-indazole (413 mg, 1.78 mmol), {3-fluoro-4-[(phenylmethyl)oxy]phenyl}boronic acid (876 mg, 3.56 mmol), copper (II) acetate (483 mg, 2.67 mmol) and pyridine (0.29 ml_, 3.56 mmol) in DCM (30 ml.) were stirred in the presence of molecular sieves (4A, 790 mg) in air. After 40 hours the mixture was filtered through a pad of celite and concentrated to afford 1.24 g of crude material. This was purified by flash chromatography (Biotage SP4, 40 + M silica column) with a gradient of Et2O (0 to 30%) in hexane to afford 410 mg of desired compound (D10) containing a small amount of the N2- aryl regioisomer. LC-MS: MH+ = 432 (C20H13BrCIFN2O = 431 )
Reference： [1]Patent: WO2008/107455,2008,A1 .Location in patent: Page/Page column 20
  • 2
  • zinc cyanide [ No CAS ]
  • [ 885519-03-9 ]
  • [ 1425932-59-7 ]
YieldReaction ConditionsOperation in experiment
86.9% With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 120℃; for 16h;Inert atmosphere; Referential Example 24 (6-Chloro-3-methyl-l-(tetrahydro-2H-pyran-2-yl)-lH-indazol-4-yl)methanamine (123) step 1 : A mixture of 4-bromo-6-chloro-lH-indazole (3.0g, 12.9 mmol), Pd(PPh3)4 (2.24 g, 1.94 mmol), and Zn(CN)2 (9.22 g, 25.8 mmol) in DMF (50 mL) under nitrogen was heated at 120 C for 16 h. The reaction mixture was quenched with water and extracted with EtOAc (50 mL chi 5). The combined extracts were washed with brine (100 mL), dried (MgS04), filtered, and concentrated in vacuo to afford 6-chloro-lH-indazole-4-carbonitrile as white solid (2.0 g, 86.9%).
Reference： [1]Patent: WO2013/26914,2013,A1 .Location in patent: Page/Page column 120
  • 3
  • [ 885519-03-9 ]
  • [ 1425932-60-0 ]
Reference： [1]Patent: WO2013/26914,2013,A1
  • 4
  • [ 885519-03-9 ]
  • [ 1425932-61-1 ]
Reference： [1]Patent: WO2013/26914,2013,A1
  • 5
  • [ 885519-03-9 ]
  • [ 1425932-62-2 ]
Reference： [1]Patent: WO2013/26914,2013,A1
  • 6
  • [ 885519-03-9 ]
  • [ 1425932-63-3 ]
Reference： [1]Patent: WO2013/26914,2013,A1
  • 7
  • [ 885519-03-9 ]
  • tert-butyl 4-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)-2,2,-dimethylpiperazine-1-carboxylate [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 8
  • [ 885519-03-9 ]
  • tert-butyl 4-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-yl)-5,6-dihydropyridine-1 (2H)-carboxylate [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 9
  • [ 885519-03-9 ]
  • tert-butyl 4-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-yl)piperidine-1-carboxylate [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 10
  • [ 885519-03-9 ]
  • 6-chloro-4-(piperidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole trifluoroacetate [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 11
  • [ 885519-03-9 ]
  • 6-chloro-4-(1-(methylsulfonyl)piperidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 12
  • [ 885519-03-9 ]
  • 6-chloro-4-(1-(methylsulfonyl)piperidin-4-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 13
  • [ 885519-03-9 ]
  • 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 14
  • [ 885519-03-9 ]
  • C23H30ClN3O3 [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 15
  • [ 885519-03-9 ]
  • tert-butyl (4-(6-chloro-1H-indazol-4-yl)cyclohexyl)carbamate [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 16
  • [ 885519-03-9 ]
  • 6-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 17
  • [ 885519-03-9 ]
  • 6-chloro-4-(1-isobutyl-1H-pyrazol-4-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 18
  • [ 885519-03-9 ]
  • 6-chloro-4-(4-(methylsulfonyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 19
  • [ 885519-03-9 ]
  • 6-chloro-4-(4-(methylsulfonyl)phenyl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2016/71293,2016,A2
  • 20
  • [ 885519-03-9 ]
  • [ 108-94-1 ]
  • 1-(6-chloro-1H-indazol-4-yl)cyclohexanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
16% To a solution of 1001 (200 mg, 869 mmol) in THF (30 ml) was added nbutyl lithium (2.5 M sam. in hexane, 0.87 ml, 2.17 mmol) at -78C. After being stirred for 15 mm., cyclohexanone 1027 (426 mg, 4.34 mmol) was added and stirred at the same temperature for 3 h. The reaction was quenched with saturated ammonium chloride solution and extracted with EtOAc (2 x SOml). The organic phase was separated, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford crude residue. The crude residue purified by Combiflash chromatography using 4 g redisep coloumn (hexanes/EtOAc, 7:3) to afford 273 (35 mg, 16%) as a white solid,MS (MM) m/z 251.1 [M+H].HPLC: 97.02%, Eclipse XDBC?18 column, 220 mm?H NMR (400 MHz, DMSOd6): 13.20 (s, 1H), 8.33 (s, 1H), 7.45 (s, 1H), 7.14 (s, 1H), 5.06 (s, 1H), 1.99- 1.90 (m, 2H), 1.85 - 1.67 (m, 5H), 1.56- 1.37 (m, 3H).
Reference： [1]Patent: WO2016/71293,2016,A2 .Location in patent: Page/Page column 302
  • 21
  • [ 110-87-2 ]
  • [ 885519-03-9 ]
  • 4-bromo-6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With (R)-10-camphorsulfonic acid; In tetrahydrofuran; at 55℃; for 2h;Inert atmosphere; Compound 527 <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> 63a (2 g, 8.68 mmol) was dissolved in 34 THF (40 mL), added with 528 3,4-dihydro-2H-pyran (2.2 g, 26 mmol) and 529 L-camphorsulfonic acid (0.2 g, 0.87 mmol), heated to 55 C. and stirred for 2 h. After cooled to room temperature, the mixture was basified with triethylamine to pH=7 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=10/1) to give the target 530 product 4-bromo-6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 63b (2.5 g, orange solid). Yield: 92% MS m/z (ESI): 231/233[M+1]
81% With toluene-4-sulfonic acid; In tetrahydrofuran; at 50℃; for 16h; A solution of 1001 (50 g, 205 mrnol) in THF (50 mL) was treated with dihydropyran (25 g, 308 mmol),ptou1enesulphonic acid (0M3 g, 0A8 mmoi). After stirring at 50C for 16 h, the reaction mixture was concentrated in vacuo. This crude residue was purified by chromatography (silica; hexanes/EtOAc, 8,5:1,5) to afford 1003 (5.5 g, 81%) as an off white solid.MS (MM) m/z 316 [M+H].?H NMR (400 MHz, CDC13): 797 (d, J= L2 Hz, IH), 757 (dd, J= L6, L2 Hz, 1H), 732 (d, J= 1,6 Hz, 1H), 564 (dd, J= 9,2, 28 Hz, 1H), 4,01 197 (m, 1H), 176 173 (m, 1H), 253 243 (m, 1H), 2,142,06 (m, 2H), L78 L67 (m, 3H).
80% With toluene-4-sulfonic acid; In tetrahydrofuran; at 20℃; Step 1: 4-Bromo-6-chloro-1H-indazole (3.5 g, 15.2 mmol) and 3,4-dihydro-2H-pyran(2.73 g, 32.5 mol) were added to tetrahydrofuran (80 mL). Add p-toluenesulfonic acidhydrate (200 mg, 0.80 mmol) and stir at room temperature overnight. The solvent wasdistilled off under reduced pressure, and the resulting residue was purified by silicagel column chromatography (petroleum ether/ethyl acetate = 5/1) to give compound 10.1(3.8 g, yield: 80%) as a white solid.
Reference： [1]Patent: US2019/185472,2019,A1 .Location in patent: Paragraph 0246; 0846-0849
[2]Patent: WO2016/71293,2016,A2 .Location in patent: Page/Page column 310
[3]Patent: CN107556244,2018,A .Location in patent: Paragraph 0460-0462
  • 22
  • [ 885519-03-9 ]
  • [ 98-80-6 ]
  • C13H9ClN2 [ No CAS ]
Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 2774 - 2778
  • 23
  • [ 885519-03-9 ]
  • (2R)-8-fluoro-6-[4-(methanesulfonyl)-1H-indazol-6-yl]-2-methyl-4-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one [ No CAS ]
Reference： [1]Patent: WO2016/198400,2016,A1
  • 24
  • [ 885519-03-9 ]
  • [ 20277-69-4 ]
  • 6-chloro-4-(methanesulfonyl)-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In dimethyl sulfoxide; at 100 - 160℃; for 25.5h; To a solution of 4-bromo-6-chloro-lH-indazole (100 mg, 0.43 mmol) in DMSO (7 mL) were added sodium methanesulfmate (165 mg, 1.62 mmol), Cul (8.2 mg, 0.04 mmol), N,N'-dimethylethylenediamine (0.01 mL, 0.09 mmol) and K2CO3 (119.41 mg, 0.86 mmol). The reaction mixture was heated at 100C for 3.75 h, then at 140C for 16.25 h, then at 160C for 3.5 h. The reaction mixture was retreated with another portion of sodium methanesulfmate (165 mg, 1.62 mmol), Cul (24.68 mg, 0.13 mmol) and Nu,Nu'- dimethylethylenediamine (0.03 mL, 0.26 mmol) and the resulting mixture was heated at 160C for 2 h. The reaction mixture was extracted with EtOAc (2 x 15 mL), washed with water (10 mL) and brine (10 mL), and dried over MgS04, then concentrated in vacuo. The resulting crude product was purified by column chromatography, using a heptane/ EtOAc gradient followed by a DCM/MeOH gradient, to give the title compound (24.6 mg, 19%). deltaEta (500 MHz, DMSO-de) 13.85 (s, 1H), 8.40 (s, 1H), 8.08 (s, 1H), 7.65 (s, 1H), 3.38 (s, 3H). Method B HPLC-MS: MH+ mlz 231, RT 1.42 minutes (81%)
Reference： [1]Patent: WO2016/198400,2016,A1 .Location in patent: Page/Page column 102
  • 25
  • [ 885519-03-9 ]
  • spiro[adamantane-2,2'-[1,3]dioxolane]-5-carbaldehyde [ No CAS ]
  • C20H23ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% Step 1: To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (500 mg, 2.16 mmol) inanhydrous tetrahydrofuran (10 mL) at -78C, a solution of n-butyllithium in n-hexane (3mL) was slowly added dropwise. 2.5M) The system was stirred at -78C for 20 minutes.The spiro [adamantane-2,2 '- [1,3] dioxolane] 5-carbaldehyde (959mg, 4.32mmol) inanhydrous tetrahydrofuran (2.0 mL) was slowly added dropwise to the reaction mixture, inthe system It was stirred at -78C for 1.5 hours, quenched with saturated aqueousammonium chloride (20 mL), diluted with ethyl acetate (80 mL) and the organic phaseseparated. The organic phase was washed with saturated brine, filtered, and the filtratewas concentrated under reduced pressure. The residue was purified by flash columnchromatography (petroleum ether/ethyl acetate = 1/1) to give compound 4.1 (530 mg,yield: 66%) as a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0388-0390
  • 26
  • [ 20098-14-0 ]
  • [ 885519-03-9 ]
  • [ 67-64-1 ]
  • C18H21ClN2O2 [ No CAS ]
  • C18H21ClN2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.7%; 5.5% Step 1: 4-Bromo-6-chloro-lH-indazole (500 mg, 3.04 mmol) was dissolved inacetone (10 mL) and potassium carbonate (839 mg, 6.08 mmol) was added on an ice bath.The reaction was stirred at room temperature for 5 hours. The reaction solution wasconcentrated under reduced pressure, and the concentrate was purified by flash columnchromatography (petroleum ether/ethyl acetate = 1/1) to give 4-bromo-6-chloro-2-methyl-2H-indazole and 4-bromo- A mixture of 6-chloro-1-methyl-1H-carbazole (300 mg, yield:56%) was a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0453-0455
  • 27
  • [ 885519-03-9 ]
  • [ 67-64-1 ]
  • 4-bromo-6-chloro-2-methyl-2H-indazole [ No CAS ]
  • 4-bromo-6-chloro-1-methyl-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; at 20℃; for 5h;Cooling with ice; Step 1: 4-Bromo-6-chloro-lH-indazole (500 mg, 3.04 mmol) was dissolved inacetone (10 mL) and potassium carbonate (839 mg, 6.08 mmol) was added on an ice bath.The reaction was stirred at room temperature for 5 hours. The reaction solution wasconcentrated under reduced pressure, and the concentrate was purified by flash columnchromatography (petroleum ether/ethyl acetate = 1/1) to give 4-bromo-6-chloro-2-methyl-2H-indazole and 4-bromo- A mixture of 6-chloro-1-methyl-1H-carbazole (300 mg, yield:56%) was a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0453-0455
  • 28
  • [ 885519-03-9 ]
  • 5-((tetrahydro-2H-pyran-2-yl)oxy)-2-adamantanone [ No CAS ]
  • C22H27ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Step 1: To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (295 mg, 1.27 mmol) in tetrahydrofuran (100 mL) at -78C, a solution of n-butyllithium in n-hexane (1.8 mL,3.5 mmol) was added dropwise. ). The system was stirred at -78 C for 20 minutes. Then,a solution of 5-((tetrahydro-2H-pyran-2-yl)oxy)-2-adamantanone (1.6 g, 6.39 mmol) intetrahydrofuran (10 mL) was dropped into the above reaction solution. Stir at -78C for1 hour. The reaction was quenched with saturated aqueous ammonium chloride, the organicphase was separated, the organic phase was washed with saturated brine and concentrated.The residue was purified by silica gel column chromatography (petroleum ether/ethylacetate = 1/1) to give compound 1.2a (70 mg, less polar) and 1.2b (150 mg, more polar)as white solids.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0331-0333
  • 29
  • [ 700-58-3 ]
  • [ 885519-03-9 ]
  • C17H19ClN2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (200 mg, 0.86 mmol) in anhydroustetrahydrofuran (10 mL) at -78C, a solution of n-butyllithium in n-hexane (1.2 mL, 2.5M) was slowly added dropwise. ) The system was stirred at -78 C for 20 minutes. Asolution of 2-adamantanone (325 mg, 2.16 mmol) dissolved in dry tetrahydrofuran (2.0 mL)was slowly added dropwise to the above reaction solution, and the system was stirred at-78C for 1.5 hours. The reaction was quenched with saturated aqueous ammonium chloride(20 mL), diluted with ethyl acetate (30 mL) and the organic phase separated. The organicphase was washed with saturated brine, filtered, and the filtrate was concentrated underreduced pressure. The residue was purified by flash chromatography(dichloromethane/methanol = 95/5) to give compound 1-1 (38.4 mg, yield: 15%) as a whitesolid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0302-0304
  • 30
  • [ 885519-03-9 ]
  • [ 39750-93-1 ]
  • C18H21ClN2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
12% To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (80 mg, 0.35 mmol) in anhydroustetrahydrofuran (10 mL) at -78C, a solution of n-butyllithium in n-hexane (0.49 mL,2.5M) was slowly added dropwise. ) The system was stirred at -78 C for 20 minutes. Asolution of adamantane-2-carbaldehyde (115 mg, 0.7 mmol) in dry tetrahydrofuran (2.0 mL)was slowly added dropwise to the above reaction solution, and the system was stirred at-78C for 1.0 hour, and quenched with saturated aqueous ammonium chloride solution. Thereaction was quenched (20 mL), diluted with ethyl acetate (30 mL) and the organic phaseseparated. The organic phase was washed with saturated brine, filtered, and the filtratewas concentrated under reduced pressure. The residue was purified by flashchromatography (petroleum ether/ethyl acetate = 3/1) to give compound 2-1 (12 mg, yield:12%) as a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0365-0367
  • 31
  • [ 885519-03-9 ]
  • 5-((tetrahydro-2H-pyran-2-yl)oxy)adamantane-2-carboxaldehyde [ No CAS ]
  • C23H29ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% Step 1: To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (500 mg, 2.16 mmol) inanhydrous tetrahydrofuran (10 mL) at -78C, a solution of n-butyllithium in n-hexane (3mL) was slowly added dropwise. 2.5M) The system was stirred at -78C for 20 minutes. Asolution of 5-((tetrahydro-2H-pyran-2-yl)oxy)adamantane-2-carbaldehyde (1.14 g, 4.32mmol) in anhydrous tetrahydrofuran (2.0 mL) was slowly added dropwise to the reactionsolution. The system was stirred at -78C for 1.5 hours, quenched with saturatedaqueous ammonium chloride (20 mL), diluted with ethyl acetate (80 mL), and the organicphase separated. The organic phase was washed with saturated brine, filtered, and thefiltrate was concentrated under reduced pressure. The residue was purified by flashchromatography (petroleum ether/ethyl acetate = 1/1) to give compound 2.1 (530 mg,yield: 59%) as a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0370-0372
  • 32
  • [ 885519-03-9 ]
  • 3-((tetrahydro-2H-pyran-2-yl)oxy)adamantane-1-carboxaldehyde [ No CAS ]
  • C23H29ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% Step 1: A solution of n-butyllithium in n-hexane (0.66 mL) was slowly addeddropwise to a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (110 mg, 0.47 mmol) in drytetrahydrofuran (10 mL) at -78C. 2.5M) The system was stirred at -78C for 20minutes. A solution of 3-((tetrahydro-2H-pyran-2-yl)oxy)adamantane-1-carbaldehyde (216mg, 0.82 mmol) in anhydrous tetrahydrofuran (2.0 mL) was slowly added dropwise to theabove reaction solution. The system was stirred at -78 C for 1 hour. Quench with asaturated aqueous ammonium chloride solution (10 mL), dilute with ethyl acetate (30 mL)and separate the organic phase. The organic phase was washed with saturated brine,filtered, and the filtrate was concentrated under reduced pressure. The residue waspurified by flash column chromatography (dichloromethane/methanol = 10/1) to givecompound 3.1 (30 mg, yield: 15%) as a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0388-0390
  • 33
  • [ 885519-03-9 ]
  • 2-(5-hydroxyadamantan-2-yl)acetaldehyde [ No CAS ]
  • C19H23ClN2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (173 mg, 0.75 mmol) in anhydroustetrahydrofuran (10 mL) at -78C, a solution of n-butyllithium in n-hexane (2.1 mL, 2.5M) was slowly added dropwise. ) The system was stirred at -78 C for 20 minutes. Asolution of 2-(5-hydroxyadamantan-2-yl)acetaldehyde (291 mg, 1.50 mmol) in drytetrahydrofuran (5.0 mL) was slowly added dropwise to the above reaction solution, andthe system was stirred at -78C for 1 hour. . Quench with a saturated aqueous ammoniumchloride solution (10 mL), dilute with ethyl acetate (30 mL), and separate the organicphase. The organic phase was washed with saturated brine, filtered, and the filtrate wasconcentrated under reduced pressure. The residue was purified by flash columnchromatography (dichloromethane/methanol = 10/1) to give compound 6-1a (13 mg, yield:5%, less polar) and compound 6-1b (10 mg, yield: 4 %, more polar), all white solids.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0425-0427
  • 34
  • [ 885519-03-9 ]
  • C16H19NO2 [ No CAS ]
  • C23H24ClN3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% Step 1: Compound 11.5 (100 mg, 0.43 mmol) was added to tetrahydrofuran (10 mL),cooled to -78 C and a solution of n-butyllithium (0.6 mL, 1.5 mmol) in n-hexane wasadded dropwise. The system was stirred at -78 C for 10 mins. A tetrahydrofuran solution in which 4-bromo-6-chloro-1H-carbazole (134 mg, 0.52 mmol) was dissolved wasdropped into the reaction solution, and the system was stirred at -78C for 3.0 hours.The saturated aqueous ammonium chloride solution was quenched and the organic phase wasseparated. The aqueous phase was extracted with ethyl acetate (10 mL×3). The organicphases were combined and washed once with saturated brine. The crude product wasconcentrated and purified by column chromatography (dichloromethane/methanol=100 /1 to10:/1) Compound 11-1 (60 mg, yield: 34%) was obtained as a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0479-0481
  • 35
  • [ 885519-03-9 ]
  • C16H19NO2 [ No CAS ]
  • C16H18ClN3O2 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 36
  • [ 885519-03-9 ]
  • C16H19NO [ No CAS ]
  • C23H24ClN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% Step 1: Compound 13.4 (360 mg, 1.57 mmol) was dissolved in tetrahydrofuran (15mL), cooled to -70C, n-butyllithium (2.5 M, 2.2 mL, 5.48 mmol) was added dropwise, andstirring was continued at -70C. In minutes, <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (387 mg, 1.60mmol) was then dissolved in 2 mL of tetrahydrofuran and added to the reaction system.The dry ice acetone bath was removed and the reaction was continued for 2 hours withstirring. Add water and extract with dichloromethane (100 mL x 3). It was dried overanhydrous sodium sulfate, filtered, and the filtrate was distilled off under reducedpressure to remove the solvent. The resulting residue was purified by silica gel columnchromatography (petroleum ether/ethyl acetate = 4/1) to give Compound 13-1 (240 mg,yield: 39%). ) is a white solid.
Reference： [1]Patent: CN107556244,2018,A .Location in patent: Paragraph 0494-0496
  • 37
  • [ 885519-03-9 ]
  • C18H19ClN2O2 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 38
  • [ 885519-03-9 ]
  • C18H21ClN2O2 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 39
  • [ 885519-03-9 ]
  • C13H13ClN2O3 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 40
  • [ 885519-03-9 ]
  • C13H15ClN2O2 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 41
  • [ 885519-03-9 ]
  • C13H14BrClN2O [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 42
  • [ 885519-03-9 ]
  • C17H24ClN2O4P [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 43
  • [ 885519-03-9 ]
  • C28H35ClN2O3 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 44
  • [ 885519-03-9 ]
  • C28H37ClN2O3 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 45
  • [ 885519-03-9 ]
  • C18H21ClN2O [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 46
  • [ 885519-03-9 ]
  • C18H19ClN2O2 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 47
  • [ 885519-03-9 ]
  • C18H21ClN2O3 [ No CAS ]
Reference： [1]Patent: CN107556244,2018,A
  • 48
  • [ 885519-03-9 ]
  • [ 2043-61-0 ]
  • (6-chloro-1H-indazol-4-yl)(cyclohexyl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (78, 0.37 g, 1.62 mmol) in THF (6 ml) was added sodium hydride (60% dispersion in mineral oil, 0.08 g, 2.12 mmol). The mixture was allowed to stir at room temperature for 30 min and then was cooled to -78 C. Then, 2.5 M n- butyllithium in hexane (0.65 ml) was added dropwise over 5 min period. The mixture was allowed to stir at -78 C for 30 min followed by the addition of cyclohexanecarbaldehyde (0.08 g, 0.67 mmol). The reaction mixture was allowed to stir for 1h at -78C and then for 20 min while warming to room temperature. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate and water. The organic phase was washed with brine (3x), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting crude material was purified by silica gel column chromatography to provide product (P-0173). [M+H+]+ = 265.0.
[0432] To a solution of 4-bromo-6-chloro-lH-indazole (78, 0.37 g, 1.62 mmol) in THF (6 ml) was added sodium hydride (60% dispersion in mineral oil, 0.08 g, 2.12 mmol). The mixture was allowed to stir at room temperature for 30 min and then was cooled to -78 C. Then, 2.5 M n- butyllithium in hexane (0.65 ml) was added dropwise over 5 min period. The mixture was allowed to stir at -78 C for 30 min followed by the addition of cyclohexanecarbaldehyde (0.08 g, 0.67 mmol). The reaction mixture was allowed to stir for lh at -78C and then for 20 min while warming to room temperature. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate and water. The organic phase was washed with brine (3x), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting crude material was purified by silica gel column chromatography to provide product (P-0173). [M+H+]+ = 265.0.
Reference： [1]Patent: WO2018/57973,2018,A1 .Location in patent: Paragraph 0567
[2]Patent: WO2019/183145,2019,A1 .Location in patent: Paragraph 0432
  • 49
  • [ 885519-03-9 ]
  • [ 1056262-14-6 ]
Reference： [1]Patent: WO2008/107455,2008,A1
  • 50
  • [ 885519-03-9 ]
  • [ 1056263-92-3 ]
Reference： [1]Patent: WO2008/107455,2008,A1
  • 51
  • [ 885519-03-9 ]
  • di-tert-butyl ((3a'R,5'r,6a'S)-5,5-dimethylhexahydro-1'H-spiro[[1,3]dioxane-2,2'-pentalen]-5'-yl)iminodicarboxylate [ No CAS ]
  • tert-butyl ((2r,3aR,5r,6aS)-5-(6-chloro-1H-indazol-4-yl)-5-hydroxyoctahydropentalen-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (552 mg, 2.39 mmol) in THF (20 mL) , cooled to -78 under N2, was added n-BuLi/THF (2.5M, 3.16 mL, 7.89 mmol) dropwise, maintaining the inner temperature below -78 . After the addition was complete, the reaction mixture was stirred at -78 for 0.5 h and the product of Step 4 above (810 mg) in THF (2 mL) was added dropwise, maintaining the inner temperature below -78 . After the addition was complete, the reaction mixture was stirred at -78 for 1 h before quenching with NH4Cl (sat. aq, 50 mL) . The reaction mixture was extracted with EtOAc (80 mL) . The organic phase was washed with H2O (40 mL) and brine (40 mL) , dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel flash column chromatography (PE: EtOAc = 5: 11: 2) to give the title compound (320 mg) as a yellow solid.
Reference： [1]Patent: WO2019/76358,2019,A1 .Location in patent: Page/Page column 71
  • 52
  • [ 885519-03-9 ]
  • (1R,5S,6s)-6-(bis(boc-aminomethyl))bicyclo[3.1.0]hexan-3-one [ No CAS ]
  • (1R,3r,5S,6s)-6-(bis-boc-aminomethyl)-3-(6-chloro-1H-indazol-4-yl)bicyclo[3.1.0]hexan-3-ol to a solution of 4-bromo-6-chloro-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (855 mg, 3.69 mmol) in THF (18 mL) was added slowly n-BuLi (2.5 N in hexane, 4.87 mL, 12.2 mmol) at -78 C under N 2. After stirring at -78 C for 0.5 h, the product of Step 5 above (1.2 g, 3.69 mmol) in THF (8 mL) was added slowly at -78 C. The resulting mixture was stirred at -78 C for 1h, quenched with saturated NH 4Cl (10 mL), extracted by EtOAc (120 mL), washed by water (20 mL) and brine (20 mL), dried over anhydrous Na 2SO 4, and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (PE: EtOAc = 6: 1 to 2: 1) to give the title compound (350 mg, yield: 20%).
Reference： [1]Patent: WO2019/76358,2019,A1 .Location in patent: Page/Page column 131
  • 53
  • [ 885519-03-9 ]
  • (3aR,5r,6aS)-5-(6-chloro-1H-indazol-4-yl)octahydrocyclopenta[c]pyrrol-5-ol hydrochloride [ No CAS ]
Reference： [1]Patent: WO2019/76358,2019,A1
  • 54
  • [ 885519-03-9 ]
  • (3aR,5r,6aS)-5-(6-chloro-1H-indazol-4-yl)-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-ol [ No CAS ]
Reference： [1]Patent: WO2019/76358,2019,A1
  • 55
  • [ 885519-03-9 ]
  • rac-6-chloro-4-((3aR,6aS)-2-(methylsulfonyl)-1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: WO2019/76358,2019,A1
  • 56
  • [ 885519-03-9 ]
  • (1R,3r,5S,6r)-6-amino-3-(6-chloro-1H-indazol-4-yl)bicyclo[3.1.0]hexan-3-ol hydrochloride [ No CAS ]
Reference： [1]Patent: WO2019/76358,2019,A1
  • 57
  • [ 885519-03-9 ]
  • N'-methyl-N-((1R,3r,5S,6r)-3-(6-chloro-1H-indazol-4-yl)-3-hydroxybicyclo[3.1.0]hexan-6-yl)sulfuric diamide [ No CAS ]
Reference： [1]Patent: WO2019/76358,2019,A1
  • 58
  • [ 885519-03-9 ]
  • [ 146231-54-1 ]
  • (3aR,5r,6aS)-tert-butyl 5-(6-chloro-1H-indazol-4-yl)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (2.31 g, 10 mmol) in THF (60 mL) cooled at -78 C, BuLi in hexane (1.6 M, 12.5 mL, 20 mmol) was added slowly. After the addition, the mixture was stirred at -78 C for 0.5 h, and a solution of (3aR,6aS)-tert-butyl 5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (2.5 g, 11.1 mmol) in THF (5 mL) was added dropwise. The reaction mixture was quenched with saturated aqueous NH4Cl (20 mL). The mixture was extracted with EtOAc (100 mL x 2). The combined organi layers were washed with brine (50 mL x 2), dried over anhydrous Na 2SO 4, filtered off and and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (PE: EA = 10: 1 to 2: 1) to give the title compound (1.055 g, yield: 27%).
Reference： [1]Patent: WO2019/76358,2019,A1 .Location in patent: Page/Page column 68
  • 59
  • [ 504438-04-4 ]
  • [ 885519-03-9 ]
  • tert-butyl ((1R,3r,5S,6r)-3-(6-chloro-1H-indazol-4-yl)-3-hydroxybicyclo[3.1.0]hexan-6-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
21.3% To a solution of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (25 g, 108 mmol) in THF (250 mL) cooled to -78 C in a liquid nitrogen/acetone bath was added dropwise n-BuLi (2.5M in THF, 143 mL, 356 mmol), maintaining the inner temperature below -75 C. After stirring at -78 C for 0.5 h, a solution of tert-butyl ((1R,5S, 6r)-3-oxobicyclo[3.1.0]hexan-6-yl)carbamate (23 g, 108 mmol) in THF (150 mL) was added dropwise to the reaction mixture, maintaining the inner temperature below -75 C. After the addition, the reaction mixture was stirred at -78 C for 2 h before quenching with NH 4Cl (sat. aq, 150 mL) at -20 C and allowed to warm up to rt gradually. EtOAc (400 mL) was added to the reaction mixture, and the organic layer waw separated, which was washed with H 2O (200 mL) and brine (150 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel flash column chromatography (PE: EtOAc = 5: 1 DCM: MeOH = 20: 1) to give the title compound (8.35 g, yield: 21.3%).
Reference： [1]Patent: WO2019/76358,2019,A1 .Location in patent: Page/Page column 79-80
  • 60
  • [ 885519-03-9 ]
  • [ 74-88-4 ]
  • 4-bromo-6-chloro-2-methyl-2H-indazole [ No CAS ]
  • 4-bromo-6-chloro-1-methyl-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In tetrahydrofuran; N,N-dimethyl-formamide; at 10 - 35℃; for 1h; a) 4-(benzylthio)-6-chloro-1-methyl-1H-indazole A mixture of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (740 mg), iodomethane (0.23 mL), cesium carbonate (1.34 g), THF (12 mL) and DMF (3 mL) was stirred at room temperature for 1 hr. The reaction mixture was filtered to remove an insoluble material and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a mixture (735 mg) of 4-bromo-6-chloro-1-methyl-1H-indazole and 4-bromo-6-chloro-2-methyl-2H-indazole.
Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1246; 1247
  • 61
  • [ 885519-03-9 ]
  • 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-4-((trimethylsilyl)ethynyl)-1H-indazole [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 62
  • [ 885519-03-9 ]
  • 6-chloro-4-ethynyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 63
  • [ 885519-03-9 ]
  • methyl 2-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)acetate [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 64
  • [ 885519-03-9 ]
  • 2-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)acetic acid [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 65
  • [ 885519-03-9 ]
  • 2-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)-N-(4-cyanophenyl)acetamide [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 66
  • [ 885519-03-9 ]
  • 2-(6-chloro-1H-indazol-4-yl)-N-(4-cyanophenyl)acetamide [ No CAS ]
Reference： [1]Patent: US2019/185472,2019,A1
  • 67
  • [ 885519-03-9 ]
  • [ 100-53-8 ]
  • [ 74-88-4 ]
  • 4-(benzylthio)-6-chloro-1-methyl-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
592 mg A mixture of <strong>[885519-03-9]4-bromo-6-chloro-1H-indazole</strong> (740 mg), iodomethane (0.23 mL), cesium carbonate (1.34 g), THF (12 mL) and DMF (3 mL) was stirred at room temperature for 1 hr. The reaction mixture was filtered to remove an insoluble material and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a mixture (735 mg) of 4-bromo-6-chloro-1-methyl-1H-indazole and 4-bromo-6-chloro-2-methyl-2H-indazole. A mixture of this mixture (730 mg), benzylmercaptan (0.40 mL), tris(dibenzylideneacetone)dipalladium(0) (68 mg), 1,1?-bis(diphenylphosphino)ferrocene (83 mg), DIPEA (1.10 mL) and toluene (10 mL) was stirred under a nitrogen atmosphere at 100 C. for 1 hr. The reaction mixture was filtered to remove an insoluble material and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (592 mg). (1247) 1H NMR (300 MHz, DMSO-d6) delta 4.01 (3H, s), 4.44 (2H, s), 7.08 (1H, d, J=1.5 Hz), 7.21-7.37 (3H, m), 7.37-7.46 (2H, m), 7.63-7.68 (1H, m), 8.03 (1H, d, J=1.0 Hz).
Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1246; 1247
  • 68
  • [ 885519-03-9 ]
  • 6-chloro-1-methyl-1H-indazole-4-sulfonyl chloride [ No CAS ]
Reference： [1]Patent: US2019/169166,2019,A1
  • 69
  • [ 885519-03-9 ]
  • N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-6-chloro-1-methyl-1H-indazole-4-sulfonamide [ No CAS ]
Reference： [1]Patent: US2019/169166,2019,A1

Tags: 885519-03-9 synthesis path| 885519-03-9 SDS| 885519-03-9 COA| 885519-03-9 purity| 885519-03-9 application| 885519-03-9 NMR| 885519-03-9 COA| 885519-03-9 structure

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Chemical Structure| 1260382-77-1

[ 1260382-77-1 ]

5-Bromo-6-chloro-1H-indazole

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Chemical Structure| 1056264-74-4

[ 1056264-74-4 ]

4-Bromo-5-chloro-1H-indazole

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Related Parent Nucleus of
[ 885519-03-9 ]

Indazoles

Chemical Structure| 885518-99-0

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6-Bromo-4-chloro-1H-indazole

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4-Bromo-1H-indazole

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Chemical Structure| 926922-40-9

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4-Bromo-5-methyl-1H-indazole

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Chemical Structure| 1305208-02-9

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6-Bromo-5-chloro-1H-indazole

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Chemical Structure| 79762-54-2

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6-Bromo-1H-indazole

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