Name: 141290-59-7|1H-Indazole-6-carbonitrile|98%
Brand: Ambeed
SKU: A210599
Price: 10.0 USD
Availability: InStock
Rating: 99 (28 reviews)

1
[ 141290-59-7 ]
[ 501-53-1 ]
[ 903557-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In tetrahydrofuran	A; 2059.A A solution of commercially available 1H-Indazole-6-carbonitrile (503 mg), chloro benzylformate (560 μL) and potassium carbonate (650 mg) in aqueous tetrahydrofurane was stirred overnight. The mixture was concentrated to dryness, ethyl acetate was added and the resulting solution was washed with a aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate and brine, dried (MgSO4), filtered and concentrated to afford the title compound (490 mg) as colourless solid.

Reference： [1]Current Patent Assignee: AMGEN INC - US2006/173183, 2006, A1 Location in patent: Page/Page column 109-110

2
[ 267413-32-1 ]
[ 141290-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; sodium nitrite; In hydrogenchloride; 1,2-dimethoxyethane; water;	Step A 6-Cyanoindazole A solution of sodium nitrite (218 mg, 3.16 mmol) in water (1 mL) was added dropwise over 2 min to a stirred suspension of <strong>[267413-32-1]3-amino-6-cyanoindazole</strong> (250 mg, 1.58 mmol) in water (1 mL) and acetic acid (2 mL) at 0 C. The resulting thick suspension was warmed to rt. After 16 h the mixture was cooled to 0 C. and the solids were collected by filtration, washing with cold water. The solids were suspended in 0.1 M HCl (4 mL), DME (3 mL) was added and the resulting mixture was stirred and heated to 80 C. for 1.5 h. The reaction was cooled and concentrated to 1/3 the volume. The residue was neutralised with sodium bicarbonate and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by chromatography on silica (5:1 chloroform/ethyl acetate) to give the title compound as a yellow solid: LRMS=143.1 (M)+; 1H NMR (CDCl3) delta 7.39 (dd, J=1.1 and 8.3 Hz, 1H), 7.87 (dd, J=0.9 and 8.3 Hz, 1H), 7.94 (dd, J=0.9 and 2.1 Hz, 1H), 8.21 (d, J=0.9 Hz, 1H).
		To a suspension of <strong>[267413-32-1]3-amino-1H-indazole-6-carbonitrile</strong> (345 mg) in AcOH was slowly added an aqueous NaNO2 solution (301 mg) at 0C. It was stirred at room temperature for 2.5 days, and the residue was collected by filtration, and washed with cool water. To the residue were added 0.1M HCl and DME, followed by stirring at 80C for 2 hours. The reaction mixture was neutralized with a saturated aqueous NaHCO3 solution, and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4 and concentrated. The residue was purified by silica gel column chromatography (n-hexane:EtOAc=80:20 to 50:50) to obtain 1H-indazole-6-carbonitrile (175 mg) as a yellow solid.

Reference： [1]Patent: US6376499,2002,B1
[2]Patent: EP2003132,2008,A1 .Location in patent: Page/Page column 24

3
[ 141290-59-7 ]
[ 704-91-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; water; In ethanol; at 80℃; for 4h;	A mixture of 1H-indazole-6-carbonitrile (1-3, 1.50 g, 10.5 mmol, 1.00 equiv), and sodium hydroxide ( 1.26 g, 31.4 mmol, 3 equiv) in a 1 : 1 mixture of ethanol and IN aqueous sodium hydroxide (5 mL) was heated to 80 °C for 4 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (4 x 50 mL). The organic layer was discarded and the aqueous layer was acidified to pH 5 and washed with ethyl acetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated to give 1H-indazole-6-carboxylic acid (4- 1) as an off-white solid. The LRMS m/z (M+H ) 163.1 found, 163.0 required.
	With sodium hydroxide; In ethanol; water; at 80℃; for 4h;	A mixture of lH-indazole-6-carbonitrile (1-3, 1.50 g, 10.5 mmol, 1.00 equiv), and sodium hydroxide (1.26 g, 31.4 mmol, 3 equiv) in a 1:1 mixture of ethanol and IN aqueous sodium hydroxide (5 mL) was heated to 80 0C for 4 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (4 x 50 mL). The organic layer was discarded and the aqueous layer was acidified to pH 5 and washed with ethyl acetate (2 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated to give lH-indazole-6-carboxylic acid (4-1) as an off-white solid. The LRMS m/z (M+H ) 163.1 found, 163.0 required.

Reference： [1]Patent: WO2006/86255,2006,A2 .Location in patent: Page/Page column 62
[2]Patent: WO2007/88400,2007,A1 .Location in patent: Page/Page column 19

4
[ 141290-59-7 ]
[ 906000-39-3 ]

Yield	Reaction Conditions	Operation in experiment
47%	With iodine; potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 4h;	4.1.2 General procedure for the synthesis of 3-iodo-1H-indazoles (5a-c) General procedure: KOH (31.10g, 0.555mol) was added in portions at 0°C to a solution of 4a (15.80g, 0.134mol) and I2 (85.40g, 0.336mol) in DMF (263.40mL). The mixture was stirred for 4h at room temperature, quenched with saturated Na2S2O3 solution (50mL), diluted with H2O (150mL), and extracted with EtOAc (70mL×3). The organic phase was washed with brine (50mL×3), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=15:1, v/v) to give an orange solid (16.78g).
18%	With iodine; potassium hydroxide In N,N-dimethyl-formamide at 0 - 15℃; for 6h; Inert atmosphere;	81.1 [558] Step 1: 3-iodo-1H-indazole-6-carbonitrile To a solution of 1H-indazole-6-carbonitrile (8.00 g, 55.9 mmol, 1.00 eq) and I2 (35.5 g, 140 mmol, 28 mL, 2.50 eq) in DMF (56 mL) was added KOH (12.5 g, 224 mmol, 4.00 eq) at 0C. The mixture was stirred at 15C for 6 hrs under N2. TLC (Petroleum ether: EtOAc = 5:1, Rf = 0.43) indicated one major new spot with larger polarity was detected. The reaction mixture was quenched with saturated Na2S2O3 solution (80 mL), and filtered to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether: EtOAc = 3:1). 3-iodo-1H-indazole-6-carbonitrile (2.70 g, 18% yield) was obtained as a white solid.
	With potassium hydroxide; iodine In N,N-dimethyl-formamide at 23℃; for 5h;	1 A mixture of 1H-indazole-6-carbonitrile (1-3, 4.7 g, 32.8 mmol, 1 equiv), iodine (18.3 g, 72.2 mmol, 2.20 equiv) and potassium hydroxide (4.42 g, 78.8 mmol, 2.40 equiv) in DMF (75 mL) was stirred at 23 °C for 5 h. The reaction mixture was partitioned between a 1: 1 aqueous mixture of saturated sodium chloride solution and saturated sodium thiosulfate solution and ethyl acetate (2 x 300 mL). The combined organic layers were washed with water then brine, dried over sodium sulfate and concentrated to give 3-iodo-1H-indazole-6-carbonitrile (1-4) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 13.29 (br s, 1H), 7.90 (s, 1H), 7.59 (d, 1H, J= 8.2 Hz), 7.38 (dd, 1H, J= 8.5, 0.9 Hz). LRMS m/z (M+H + CH3CN) 311.1 found, 311.0 required.

	With potassium hydroxide; iodine In N,N-dimethyl-formamide at 23℃; for 5h;	1.3 A mixture of lH-indazole-6-carbonitrile (1-3, 4.7 g, 32.8 mmol, 1 equiv), iodine (18.3 g, 72.2 mmol, 2.20 equiv) and potassium hydroxide (4.42 g, 78.8 mmol, 2.40 equiv) in DMF (75 mL) was stirred at 23 0C for 5 h. The reaction mixture was partitioned between a 1: 1 aqueous mixture of saturated sodium chloride solution and saturated sodium thiosulfate solution and ethyl acetate (2 x 300 mL). The combined organic layers were washed with water then brine, dried over sodium sulfate and concentrated to give 3-iodo-lH- indazole-6-carbonitrile (1-4) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 13.29 (br s, IH), 7.90 (s, IH), 7.59 (d, IH, J= 8.2 Hz), 7.38 (dd, IH, J= 8.5, 0.9 Hz). LRMS m/z (M+H + CH3CN) 311.1 found, 311.0 required.
	With iodine; potassium hydroxide In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h; regioselective reaction;
	With iodine; potassium hydroxide In N,N-dimethyl-formamide at 20℃;
	With iodine; potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 2.5h;	LLLL.2 Step 2: Synthesis of 3-iodo- 1 H-indazole-6-carbonitrile To a solution of 1H-indazole-6-carbonitrile (450.00 mg, 3.14 mmol, 1.00 equiv) in N,N-dimethylformamide (10.00 mL, 129.22 mmol, 41.10 equiv) was added iodine (1595.78 mg, 6.29 mmol, 2.00 equiv) and potassium hydroxide (440.94 mg, 7.86 mmol, 2.50 equiv) at room temperature. After being stirred for 2.5 h at room temperature, the reaction was quenched by 10 mL of brine, extracted with ethyl acetate, washed with sat. aq. sodium thiosulfate and brine, driedover anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 500 mg (59%) of the title compound as a brown solid. LC-MS (ES, m/z): 270 [M+H].

Reference： [1]Song, Pinrao; Chen, Ming; Ma, Xiaodong; Xu, Lei; Liu, Tao; Zhou, Yubo; Hu, Yongzhou [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 8, p. 1858 - 1868]
[2]Current Patent Assignee: SYROS PHARMACEUTICALS INC - WO2018/13867, 2018, A1 Location in patent: Paragraph 558
[3]Current Patent Assignee: MERCK & CO INC - WO2006/86255, 2006, A2 Location in patent: Page/Page column 39-40
[4]Current Patent Assignee: MERCK & CO INC - WO2007/88400, 2007, A1 Location in patent: Page/Page column 13
[5]Location in patent: scheme or table Herdemann, Matthias; Heit, Isabelle; Bosch, Frank-Uwe; Quintini, Gianluca; Scheipers, Claudia; Weber, Alexander [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 23, p. 6998 - 7003]
[6]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]
[7]Current Patent Assignee: ROCHE HOLDING AG - WO2015/25025, 2015, A1 Location in patent: Page/Page column 231

5
[ 141290-59-7 ]
[ 906000-44-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; water; In ethanol; at 80.0℃; for 51.0h;	A solution of 1H-indazole-6-carbonitrile (1-3, 1.0Og, 6.99 mmol, 1.00 equiv) in a 1:1 mixture of ethanol and IN aqueous sodium hydroxide solution (5 mL) was heated at 80 C for 3 h. Excess sodium hydroxide (200 mg, 5.00 mmol, 0.716 equiv) was added and heating was continued for 48 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (4 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated to a yellow solid. The solid was then triturated with acetonitrile to give 1H-indazole-6-carboxamide (3-1) as a light yellow solid. LRMS m/z (M+H ) 162.1 found, 162.1 required.

Reference： [1]Patent: WO2006/86255,2006,A2 .Location in patent: Page/Page column 59

6
[ 141290-59-7 ]
[ 141-43-5 ]
[ 906000-63-3 ]

Yield	Reaction Conditions	Operation in experiment
	at 140℃; for 2h; Neat liquid(s);	9 A mixture of 1H-indazole-6-carbonitrile (1-3, 100 mg, 0.70 mmol, 1 equiv), ethanolamine (0.21 mL, 3.5 mmol, 5.00 equiv) and cadmium acetate dehydrate (5 mg, 0.02 mmol, 0.03 equiv) was heated neat at 140 °C for 2 h. The reaction mixture was partitioned between water and ethyl acetate aided by vigorous stirring and heating. The organic layer was washed with brine, dried over sodium sulfate and concentrated to give 6-(4,5-dihydro-l,3-oxazol-2-yl)-1H-indazole (9-1) as a brown solid. 1H NMR (300 MHz, CD3OD) δ 8.11 (br s, 2H), 7.83 (d, 1H, J = 8.5 Hz), 7.70 (br d, 1H, J = 8.8 Hz), 4.54 (t, 2H, J = 9.8 Hz), 4.06 (t, 2H, / = 9.8 Hz). LRMS m/z (M+H + CH3CN) 188.2 found, 188.1 required.
	With cadmium(II) acetate at 140℃; for 2h; Neat (no solvent);	15 6-(4,5-dihvdro-l,3-oxazol-2-yl)-3-r5-(morpholin-4-ylmetfayl)-lH-indol-2-yl1-lH-indazole A mixture of lH-indazole-6-carbonitrile (1-3, 100 mg, 0.70 mmol, 1 equiv), ethanolamine (0.21 mL, 3.5 mmol, 5.00 equiv) and cadmium acetate dehydrate (5 mg, 0.02 mmol, 0.03 equiv) was heated neat at 140 0C for 2 h. The reaction mixture was partitioned between water and ethyl acetate aided by vigorous stirring and heating. The organic layer was washed with brine, dried over sodium sulfate and concentrated to give 6-(4,5-dihydro-l,3-oxazol-2-yl)-lH-indazole (9-1) as a brown solid. 1H NMR (300 MHz, CD3OD) δ 8.11 (br s, 2H), 7.83 (d, IH, J= 8.5 Hz), 7.70 (br d, IH, J= 8.8 Hz), 4.54 (t, 2H, J= 9.8 Hz), 4.06 (t, 2H, J= 9.8 Hz). LRMS m/z (M+H + CH3CN) 188.2 found, 188.1 required.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/86255, 2006, A2 Location in patent: Page/Page column 81
[2]Current Patent Assignee: MERCK & CO INC - WO2007/88400, 2007, A1 Location in patent: Page/Page column 20

7
5-cyano-2-methylbenzenediazonium tetrafluoroborate [ No CAS ]
[ 141290-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate In chloroform at 23℃; for 20h;	1 A solution of sodium nitrite (4.14 g, 59.9 mmol, 1.10 equiv) in water (20 mL) was added slowly to a pre-cooled (-10 °C) mixture of 3-amino-4-methylbenzonitrile (1-2, 7.2 g, 54.5 mmol, 1 equiv) and concentrated aqueous hydrochloric acid solution (12 M, 13.6 mL, 163 mmol, 3.00 equiv) in water (50 mL) at a rate that kept the reaction mixture temperature below 0 °C. Following the addition, the reaction mixture was stirred at -5 °C for 30 min, then filtered. A solution of sodium tetrafluoroborate (17.9 g, 163 mmol, 3.00 equiv) in water (100 mL) was immediately added to the cold filtrate. The precipitate was filtered and washed with ice-cold water (30 mL). The remaining solid was air-dried to give 5-cyano-2- methylbenzenediazonium tetrafluoroborate as a white solid. A suspension of this product (11.7 g, 50.7 mmol, 1 equiv), potassium acetate (12.4 g, 127 mmol, 2.50 equiv) and 18-crown-6 (1.34 g, 5.07 mmol, 0.100 equiv) in chloroform (150 mL) was stirred at 23 °C for 20 h. The reaction mixture was filtered and concentrated. The residue was partitioned between water and EtOAc (300 mL). The organic layer was washed with brine, dried over sodium sulfate and cocnetrated to give 1H-indazole-6-carbonitrile (1-3) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 10.37 (br s, 1H), 8.19 (d, 1H, J = 0.9 Hz), 7.90 (d, 1H, J = 1.5 Hz), 7.88 (dd, 1H, J = 8.5, 0.9 Hz), 7.42 (dd, 1H, J = 8.3, 1.5 Hz). LRMS m/z (M+H + CH3CN) 185.1 found, 185.0 required.
	With 18-crown-6 ether; potassium acetate In chloroform at 23℃; for 20h;	1.2 A solution of sodium nitrite (4.14 g, 59.9 mmol, 1.10 equiv) in water (20 mL) was added slowly to a pre- cooled (-10 0C) mixture of 3-amino-4-methylbenzonitrile (1-2, 7.2 g, 54.5 mmol, 1 equiv) and concentrated aqueous hydrochloric acid solution (12 M, 13.6 mL, 163 mmol, 3.00 equiv) in water (50 mL) at a rate that kept the reaction mixture temperature below 0 0C. Following the addition, the reaction mixture was stirred at -5 0C for 30 min, then filtered. A solution of sodium tetrafluoroborate (17.9 g, 163 mmol, 3.00 equiv) in water (100 mL) was immediately added to the cold filtrate. The precipitate was filtered and washed with ice-cold water (30 mL). The remaining solid was air-dried to give 5-cyano-2-methylbenzenediazonium tetrafluoroborate as a white solid. A suspension of this product (11.7 g, 50.7 mmol, 1 equiv), potassium acetate (12.4 g, 127 mmol, 2.50 equiv) and 18-crown-6 (1.34 g, 5.07 mmol, 0.100 equiv) in chloroform (150 mL) was stirred at 23 0C for 20 h. The reaction mixture was filtered and concentrated. The residue was partitioned between water and EtOAc (300 mL). The organic layer was washed with brine, dried over sodium sulfate and cocnetrated to give lH-indazole-6-carbonitrile (1-3) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 10.37 (br s, IH), 8.19 (d, IH, J= 0.9 Hz), 7.90 (d, IH, J= 1.5 Hz), 7.88 (dd, IH, J = 8.5, 0.9 Hz), 7.42 (dd, IH, J= 8.3, 1.5 Hz). LRMS m/z (M+H + CH3CN) 185.1 found, 185.0 required.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/86255, 2006, A2 Location in patent: Page/Page column 39-40
[2]Current Patent Assignee: MERCK & CO INC - WO2007/88400, 2007, A1 Location in patent: Page/Page column 13

8
[ 141290-59-7 ]
[ 76513-69-4 ]
[ 1361332-18-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: tetrabutylammomium bromide; sodium hydroxide / dichloromethane; water / 3 h / Inert atmosphere 2.1: 2,2,6,6-tetramethylpiperidinylmagnesium chloride; zinc(II) chloride / tetrahydrofuran / 2 h / 25 °C / Inert atmosphere 2.2: 10 h / 50 °C / Inert atmosphere

Reference： [1]Unsinn, Andreas; Knochel, Paul [Chemical Communications, 2012, vol. 48, # 21, p. 2680 - 2682]

9
[ 141290-59-7 ]
[ 76513-69-4 ]
[ 1361331-71-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With tetrabutylammomium bromide; sodium hydroxide In dichloromethane; water for 3h; Inert atmosphere;

Reference： [1]Unsinn, Andreas; Knochel, Paul [Chemical Communications, 2012, vol. 48, # 21, p. 2680 - 2682]

10
[ 141290-59-7 ]
[ 875900-08-6 ]
[ 1044598-73-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; (S,S)-1,2-diaminocyclohexane In 1,4-dioxane at 110℃; for 24h;

Reference： [1]Location in patent: scheme or table Fuchi, Nobuhiro; Iura, Yosuke; Kaneko, Hiroaki; Nitta, Aiko; Suyama, Kazuharu; Ueda, Hiroshi; Yamaguchi, Shinichi; Nishimura, Kazumi; Fujii, Shigeo; Sekiya, Yumiko; Yamada, Masateru; Takahashi, Toshiya [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 13, p. 4358 - 4361]

11
[ 141290-59-7 ]
[ 3993-78-0 ]
[ 1394117-29-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1H-indazole-6-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: 2-amino-4-chloropyrimidine In N,N-dimethyl-formamide at 20 - 50℃; for 19h; Sealed tube;	8 Preparation of 1-(2-aminopyrimidin-4-yl)-1H-indazole-6-carbonitrile Example 8 Preparation of 1-(2-aminopyrimidin-4-yl)-1H-indazole-6-carbonitrile To a solution of 1H-indazole-6-carbonitrile (200 mg, 1.40 mmol) in DMF (2 mL), was added NaH (60% oil dispersion) (89.4 mg, 2.24 mmol). The reaction mixture was stirred for 10 min at RT before addition of 4-chloropyrimidin-2-amine (362 mg, 2.79 mmol). The reaction mixture was stirred at RT for 1 hr then heated at 50° C. in a sealed tube for 18 hr. LC-MS (Method B) indicated a mixture of desired product and a regiosiomer by-product [21%, Retention time=1.65 min, m/z=237.4 (M+H)+] and [29%, Retention time=1.43 min, m/z=237.4 (M+H)+]. The reaction was quenched by addition of water (1 mL) and EtOAc (3 mL). The precipitated solid was collected by suction filtration: LC-MS (Method B): Retention time=1.65 min. LC-MS (Method B) of the filtrate showed Retention time=1.43 min as the major peak. Further trituration with EtOAc gave a second crop of solid, which was the title compound: 1H NMR (500 MHz, MeOD) δ 7.29 (1H, d, J=5.65 Hz), 7.63 (1H, dd, J=8.24, 1.22 Hz), 8.03 (1H, dd, J=8.24, 0.46 Hz), 8.29 (1H, d, J=5.80 Hz), 8.45 (1H, s), 9.45 (1H, s); LC-MS: m/z=+236.90 (M+H)+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2012/214762, 2012, A1 Location in patent: Page/Page column 79

12
[ 141290-59-7 ]
[ 1394119-46-0 ]
[ 1394117-48-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2.16667h;	11.2 Step 2-Synthesis of 1-{4-[(2-methoxypyridin-3-yl)amino]-1,3,5-triazin-2-yl}-1H-indazole-6-carbonitrile Step 2-Synthesis of 1-{4-[(2-methoxypyridin-3-yl)amino]-1,3,5-triazin-2-yl}-1H-indazole-6-carbonitrile To a solution of 1H-indazole-6-carbonitrile (70 mg, 0.49 mmol) in DMF (5 mL) was added NaH (60% oil dispersion, 39.12 mg, 0.98 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 10 minutes before the addition of 4-chloro-N-(2-methoxypyridin-3-yl)-1,3,5-triazin-2-amine (139.45 mg, 0.59 mmol). Stirring at RT was continued for 2 hr. The reaction mixture was then quenched with water and EtOAc was added. Precipitate formed was collected by suction filtration, then redissolved in DCM and washed with water. Further trituration (9:1 mixture of heptane/Et2O) gave the title compound: 1H (250 MHz, CDCl3, VT 323K) δ 4.10 (3H, s), 7.06 (1H, br. s.), 7.60 (1H, dd, J=8.22, 1.37 Hz), 7.91 (1H, dd, J=8.22, 0.76 Hz), 7.97 (2H, d), 8.42 (1H, d, J=0.76 Hz), 8.74 (1H, dd, J=7.84, 1.60 Hz), 8.86 (1H, s), 9.20 (1H, s); m/z=+345.0 (M+H)+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2012/214762, 2012, A1 Location in patent: Page/Page column 82

13
[ 141290-59-7 ]
[ 160948-35-6 ]
[ 1394117-33-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 18.1667h;	9.3 Step 3-Synthesis of 1-(2-amino-5-nitro-3,4-dihydropyrimidin-4-yl)-1H-indazole-6-carbonitrile Step 3-Synthesis of 1-(2-amino-5-nitro-3,4-dihydropyrimidin-4-yl)-1H-indazole-6-carbonitrile To a solution of 6-chloro-5-nitro-1,6-dihydropyrimidin-2-amine (538.5 mg, 60% purity, 2.00 mmol) in DMF (10 mL) was added NaH (60% oil suspension, 172 mg, 4.30 mmol) at 0° C. Mixture was stirred at RT for 10 min before addition of 1H-indazole-6-carbonitrile (410 mg, 2.87 mmol). Stirring was continued at RT for 18 hr. The reaction mixture was quenched with water (25 mL) cooled in an ice bath and extracted with EtOAc (3*20 mL). Insoluble solid formed during extraction was separated out. Combined EtOAc extract was washed with water (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. A portion (70 mg) of the crude product was purified by reverse phase preparative HPLC to give the title compound: 1H NMR (250 MHz, DMSO) δ 7.79 (1 H, dd, J=8.22, 1.07 Hz), 8.14 (1H, d, J=8.22 Hz), 8.20 (1H, br. s.), 8.33 (1H, br. s.), 8.65 (1H, s), 8.91 (1H, s), 9.03 (1H, s); LC-MS: m/z=+281.95 (M+H)+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2012/214762, 2012, A1 Location in patent: Page/Page column 80

14
[ 141290-59-7 ]
C₃₀H₃₄N₈O₃Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: iodine; potassium hydroxide / N,N-dimethyl-formamide / 20 °C 2: potassium <i>tert</i>-butylate / 0 - 20 °C 3: isopropyl magnesium chloride / tetrahydrofuran / -10 °C 4: tetrahydrofuran / -10 - 20 °C 5: copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 2 h / 85 °C

Reference： [1]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]

15
[ 141290-59-7 ]
C₂₄H₂₀N₈O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: iodine; potassium hydroxide / N,N-dimethyl-formamide / 20 °C 2: potassium <i>tert</i>-butylate / 0 - 20 °C 3: isopropyl magnesium chloride / tetrahydrofuran / -10 °C 4: tetrahydrofuran / -10 - 20 °C 5: copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / N,N-dimethyl-formamide / 2 h / 85 °C 6: trifluoroacetic acid / dichloromethane

Reference： [1]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]

16
[ 141290-59-7 ]
[ 1426425-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: iodine; potassium hydroxide / N,N-dimethyl-formamide / 20 °C 2: potassium <i>tert</i>-butylate / 0 - 20 °C

Reference： [1]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]

17
[ 141290-59-7 ]
[ 1426426-96-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: iodine; potassium hydroxide / N,N-dimethyl-formamide / 20 °C 2: potassium <i>tert</i>-butylate / 0 - 20 °C 3: isopropyl magnesium chloride / tetrahydrofuran / -10 °C 4: tetrahydrofuran / -10 - 20 °C

Reference： [1]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]

18
[ 141290-59-7 ]
C₉H₆MgN₃⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: iodine; potassium hydroxide / N,N-dimethyl-formamide / 20 °C 2: potassium <i>tert</i>-butylate / 0 - 20 °C 3: isopropyl magnesium chloride / tetrahydrofuran / -10 °C

Reference： [1]Lynch, Stephen M.; Devicente, Javier; Hermann, Johannes C.; Jaime-Figueroa, Saul; Jin, Sue; Kuglstatter, Andreas; Li, Hongju; Lovey, Allen; Menke, John; Niu, Linghao; Patel, Vaishali; Roy, Douglas; Soth, Michael; Steiner, Sandra; Tivitmahaisoon, Parcharee; Vu, Minh Diem; Yee, Calvin [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 9, p. 2793 - 2800]

19
[ 141290-59-7 ]
[ 1620816-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 1 h / 0 °C 1.2: 18 h / 0 - 20 °C 2.1: potassium carbonate; 1,10-Phenanthroline; palladium diacetate; potassium phosphate / N,N-dimethyl acetamide / 18 h / Inert atmosphere; Reflux

Reference： [1]Naas, Mohammed; El Kazzouli, Saïd; Essassi, El Mokhtar; Bousmina, Mosto; Guillaumet, Gérald [Journal of Organic Chemistry, 2014, vol. 79, # 16, p. 7286 - 7293]

20
[ 141290-59-7 ]
[ 74-88-4 ]
[ 267413-29-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 1H-indazole-6-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 0℃; for 1h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃; for 18h;

Reference： [1]Naas, Mohammed; El Kazzouli, Saïd; Essassi, El Mokhtar; Bousmina, Mosto; Guillaumet, Gérald [Journal of Organic Chemistry, 2014, vol. 79, # 16, p. 7286 - 7293]

21
[ 60710-80-7 ]
[ 141290-59-7 ]

Yield	Reaction Conditions	Operation in experiment
53%		General procedure: NaNO2 aqueous solution (13.80g, 0.2mol, 32.20mL) was added dropwise to a mixture of 3a (21.40g, 0.2mol), H2O (190mL), and 12N HCl aqueous solution (50mL, 0.6mol) at 0C. The mixture was stirred at 0C for 30min and then was filtered. The precooled NaBF4 (24.20g, 0.22mol) dissolved in H2O (90mL) was added to the filtrate and kept stirring at 0C for an additional 40min. The precipitate was collected by filtration, washed with cold ethanol (50mL×3), cold ethylether (50mL×3), and concentrated in vacuo to deliver diazonium salt (19.19g) as a yellow solid. To a solution of diazonium salt (19.19g, 0.093mol) in CHCl3 (231mL), KOAc (15.15g, 0.155mol) was added. The mixture was stirred at room temperature for 4h. Afterwards, the reaction was quenched with water (200mL) and extracted with CH2Cl2 (70mL×3). The organic phase was washed with brine (50mL×3), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The obtained crude residue was purified by recrystallization to give the title compound 7.51g.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 1858 - 1868

22
[ 141290-59-7 ]
tert-butyl 3-(1-(tert-butoxycarbonyl)-5-((tert-butoxycarbonyl)(methyl)amino)-1H-pyrrolo[3,2-b]pyridin-2-yl)-6-cyano-1H-indazole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 4 h / 20 °C 2.1: iodine; ethyl bromide; magnesium / diethyl ether; tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 0.67 h / 0 °C / Inert atmosphere 3.1: dmap / tetrahydrofuran / 0.5 h / 20 °C 4.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; copper(l) iodide / toluene / 24 h / 95 °C / Inert atmosphere