Name: 1301214-72-1|Methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate|98%
Brand: Ambeed
SKU: A876585
Rating: 92 (40 reviews)

1
[ 911434-04-3 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; water / 18 h / Reflux 1.2: 0 °C 2.1: hydrogenchloride; iron / ethanol; water / 40 °C / Reflux 3.1: triethylamine / dichloromethane / 0 - 20 °C 4.1: acetic anhydride; potassium acetate; acetic acid / chloroform / 0.25 h / 20 °C 4.2: 40 - 60 °C 4.3: 0 - 20 °C 5.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 5 steps 1.1: hydrogenchloride; water / 18 h / Reflux 1.2: 0 °C 2.1: hydrogenchloride; iron / water; industrial methylated spirit / 2 h / Reflux 3.1: triethylamine / dichloromethane / 90 h / 20 °C 4.1: acetic anhydride; potassium acetate; isopentyl nitrite / chloroform; acetic acid / 20 - 60 °C 5.1: triethylamine / (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 5 steps 1.1: hydrogenchloride / water / 18 h / Reflux 1.2: 0 °C 2.1: hydrogenchloride; iron / methanol; water / 2 h / Reflux 3.1: triethylamine / dichloromethane / 0 - 20 °C 4.1: potassium acetate; acetic anhydride; acetic acid / chloroform / 48.25 h / 20 - 60 °C 4.2: 0 - 20 °C 5.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr

Reference： [1]Current Patent Assignee: PFIZER INC - US2011/111046, 2011, A1
[2]Current Patent Assignee: PFIZER INC - WO2011/58473, 2011, A1
[3]Current Patent Assignee: PFIZER INC - US2012/108619, 2012, A1

2
[ 911434-05-4 ]
[ 1301214-72-1 ]

Reference： [1]Patent: US2011/111046,2011,A1
[2]Patent: WO2011/58473,2011,A1
[3]Patent: WO2013/127266,2013,A1
[4]Patent: WO2013/127267,2013,A1
[5]Patent: WO2013/130935,2013,A1
[6]Patent: WO2013/130943,2013,A1
[7]Patent: WO2014/26327,2014,A1
[8]Patent: WO2014/28589,2014,A2
[9]Patent: US2012/108619,2012,A1

3
[ 914358-73-9 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: acetic anhydride; potassium acetate; acetic acid / chloroform / 0.25 h / 20 °C 2.2: 40 - 60 °C 2.3: 0 - 20 °C 3.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 90 h / 20 °C 2: acetic anhydride; potassium acetate; isopentyl nitrite / chloroform; acetic acid / 20 - 60 °C 3: triethylamine / (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 3 steps 1: acetic acid / 20 °C 2: acetic anhydride; isopentyl nitrite; potassium acetate / toluene / 90 °C / Inert atmosphere 3: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr

	Multi-step reaction with 3 steps 1: acetic acid / 20 °C 2: acetic anhydride; isopentyl nitrite; potassium acetate / toluene / 90 °C / Inert atmosphere 3: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr / Sealed tube
	Multi-step reaction with 3 steps 1: acetic acid / 20 °C 2: isopentyl nitrite; potassium acetate; acetic anhydride / toluene / 90 °C / Inert atmosphere 3: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr
	Multi-step reaction with 3 steps 1: acetic acid / 20 °C 2: potassium acetate; isopentyl nitrite / toluene / 90 °C / Inert atmosphere 3: bis-triphenylphosphine-palladium(II) chloride; methanol; triethylamine / 100 °C / 7600.51 Torr
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: acetic anhydride; acetic acid; potassium acetate / chloroform / 20 - 40 °C 2.2: 48 h / 60 °C 2.3: 0 - 20 °C 3.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; triethylamine / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 36 h / 0 - 20 °C 2.1: potassium acetate; acetic acid; acetic anhydride / chloroform / 0.25 h / 20 °C 2.2: 48 h / 40 - 60 °C 3.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; triethylamine / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: potassium acetate; acetic anhydride; acetic acid / chloroform / 48.25 h / 20 - 60 °C 2.2: 0 - 20 °C 3.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr

Reference： [1]Current Patent Assignee: PFIZER INC - US2011/111046, 2011, A1
[2]Current Patent Assignee: PFIZER INC - WO2011/58473, 2011, A1
[3]Current Patent Assignee: VALO HEALTH INC - WO2013/127266, 2013, A1
[4]Current Patent Assignee: VALO HEALTH INC - WO2013/127267, 2013, A1
[5]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130935, 2013, A1
[6]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130943, 2013, A1
[7]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[8]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2
[9]Current Patent Assignee: PFIZER INC - US2012/108619, 2012, A1

4
[ 1301214-71-0 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: acetic anhydride; potassium acetate; acetic acid / chloroform / 0.25 h / 20 °C 1.2: 40 - 60 °C 1.3: 0 - 20 °C 2.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 2 steps 1: acetic anhydride; potassium acetate; isopentyl nitrite / chloroform; acetic acid / 20 - 60 °C 2: triethylamine / (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 2 steps 1: acetic anhydride; isopentyl nitrite; potassium acetate / toluene / 90 °C / Inert atmosphere 2: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr

	Multi-step reaction with 2 steps 1: acetic anhydride; isopentyl nitrite; potassium acetate / toluene / 90 °C / Inert atmosphere 2: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr / Sealed tube
	Multi-step reaction with 2 steps 1: isopentyl nitrite; potassium acetate; acetic anhydride / toluene / 90 °C / Inert atmosphere 2: triethylamine; bis-triphenylphosphine-palladium(II) chloride / 100 °C / 7600.51 Torr
	Multi-step reaction with 2 steps 1: potassium acetate; isopentyl nitrite / toluene / 90 °C / Inert atmosphere 2: bis-triphenylphosphine-palladium(II) chloride; methanol; triethylamine / 100 °C / 7600.51 Torr
	Multi-step reaction with 2 steps 1.1: acetic anhydride; acetic acid; potassium acetate / chloroform / 20 - 40 °C 1.2: 48 h / 60 °C 1.3: 0 - 20 °C 2.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; triethylamine / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 2 steps 1.1: potassium acetate; acetic acid; acetic anhydride / chloroform / 0.25 h / 20 °C 1.2: 48 h / 40 - 60 °C 2.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; triethylamine / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 2 steps 1.1: potassium acetate; acetic anhydride; acetic acid / chloroform / 48.25 h / 20 - 60 °C 1.2: 0 - 20 °C 2.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr

Reference： [1]Current Patent Assignee: PFIZER INC - US2011/111046, 2011, A1
[2]Current Patent Assignee: PFIZER INC - WO2011/58473, 2011, A1
[3]Current Patent Assignee: VALO HEALTH INC - WO2013/127266, 2013, A1
[4]Current Patent Assignee: VALO HEALTH INC - WO2013/127267, 2013, A1
[5]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130935, 2013, A1
[6]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130943, 2013, A1
[7]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[8]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2
[9]Current Patent Assignee: PFIZER INC - US2012/108619, 2012, A1

5
[ 67443-38-3 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0 - 20 °C 1.2: 2 h / 100 °C 2.1: hydrogenchloride; water / 18 h / Reflux 2.2: 0 °C 3.1: hydrogenchloride; iron / ethanol; water / 40 °C / Reflux 4.1: triethylamine / dichloromethane / 0 - 20 °C 5.1: acetic anhydride; potassium acetate; acetic acid / chloroform / 0.25 h / 20 °C 5.2: 40 - 60 °C 5.3: 0 - 20 °C 6.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 6 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 20 °C 1.2: 2 h / 100 °C 2.1: hydrogenchloride; water / 18 h / Reflux 2.2: 0 °C 3.1: hydrogenchloride; iron / water; industrial methylated spirit / 2 h / Reflux 4.1: triethylamine / dichloromethane / 90 h / 20 °C 5.1: acetic anhydride; potassium acetate; isopentyl nitrite / chloroform; acetic acid / 20 - 60 °C 6.1: triethylamine / (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr
	Multi-step reaction with 6 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0 - 20 °C 1.2: 2 h / 100 °C 2.1: hydrogenchloride / water / 18 h / Reflux 2.2: 0 °C 3.1: hydrogenchloride; iron / methanol; water / 2 h / Reflux 4.1: triethylamine / dichloromethane / 0 - 20 °C 5.1: potassium acetate; acetic anhydride; acetic acid / chloroform / 48.25 h / 20 - 60 °C 5.2: 0 - 20 °C 6.1: triethylamine / 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride / acetonitrile / 18 h / 100 °C / 15001.5 Torr

Reference： [1]Current Patent Assignee: PFIZER INC - US2011/111046, 2011, A1
[2]Current Patent Assignee: PFIZER INC - WO2011/58473, 2011, A1
[3]Current Patent Assignee: PFIZER INC - US2012/108619, 2012, A1

6
[ 67-56-1 ]
[ 201230-82-2 ]
[ 1150617-54-1 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; In acetonitrile; at 100℃; under 15001.5 Torr; for 18h;	To a solution of <strong>[1150617-54-1]6-bromo-1H-pyrazolo[4,3-b]pyridine</strong> (5.5 g, 27.9 mmol) in methanol (125 mL) and acetonitrile (75 mL) was added triethylamine (22 mL, 156 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1.98 g, 3.07 mmol), palladium dichloride (1.23 g, 6.98 mmol). The mixture was placed under 20 bar of carbon monoxide, heated to 100 C., and stirred vigorously for 18 hours. The reaction mixture was cooled to ambient temperature and filtered through Celite before the solvent was removed in vacuo to yield a brown oil. This crude oil was then purified by flash column chromatography (1:1, ethyl acetate:hexane) to give methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate as a pale yellow solid (4.52 g, 92% yield). 1HNMR (400, CDCl3) delta ppm 10.56 (s, 1H), 9.23 (s, 1H), 8.35 (s, 1H), 8.40 (s, 1H), 4.01 (s, 3H).
92%	With triethylamine;(S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine); palladium dichloride; In acetonitrile; at 100℃; under 15001.5 Torr; for 18h;	To a solution of <strong>[1150617-54-1]6-bromo-1H-pyrazolo[4,3-b]pyridine</strong> (5.5 g, 27.9 mmol) in methanol (125 mL) and acetonitrile (75 mL) was added triethylamine (22 mL, 156 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1 .98 g, 3.07 mmol), palladium dichloride (1.23 g, 6.98 mmol). The mixture was placed under 20 bar of carbon monoxide, heated to 100 C, and stirred vigorously for 18 hours. The reaction mixture was cooled to ambient temperature and filtered through Celite before the solvent was removed in vacuo to yield a brown oil. This crude oil was then purified by flash column chromatography (1:1, ethyl acetate : hexane) to give methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate as a pale yellow solid (4.52 g, 92 % yield). 1HNMR (400, CDCIs) ppm 10.56 (s, 1 H), 9.23 (s, 1 H), 8.35 (s, 1 H), 8.40 (s, 1 H), 4.01 (s, 3H).
92%	With triethylamine;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; palladium dichloride; In acetonitrile; at 100℃; under 15001.5 Torr; for 18h;	To a solution of <strong>[1150617-54-1]6-bromo-1H-pyrazolo[4,3-b]pyridine</strong> (5.5 g, 27.9 mmol) in methanol (125 mL) and acetonitrile (75 mL) was added triethylamine (22 mL, 156 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1.98 g, 3.07 mmol), and palladium dichloride (1.23 g, 6.98 mmol). The mixture was placed under 20 bar of carbon monoxide, heated to 100 C., and stirred vigorously for 18 hours. The reaction mixture was cooled to ambient temperature and filtered through Celite before the solvent was removed in vacuo to yield a brown oil. This crude oil was then purified by flash column chromatography (50% ethyl acetate/hexanes) to give methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate as a pale yellow solid (4.52 g, 92%). 1HNMR (400 MHz, CDCl3, delta): 10.56 (s, 1H), 9.23 (s, 1H), 8.35 (s, 1H), 8.40 (s, 1H), 4.01 (s, 3H).

69%	With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; triethylamine; palladium dichloride; In acetonitrile; at 100℃; under 15001.5 Torr; for 18h;	To a solution of 6-bromo-lH-pyrazolo[4,3-b]pyridine (M-4) ( 0.5 g, 2.5 mmol) in methanol ( 15 ml) and acetonitrile ( 7 ml) was added Et3N ( 2.2 ml, 5.6 mmol ), Binap ( 0.17 g, 0.63 mmol) and palladium dichloride ( 0.17 g, 0.27 mmol). The mixture was placed under 20 bar of carbon monoxide, stirred at 100 C for 18 h. The mixture was cooled, filtered and purified by Pre-TLC to give 310 mg white solid. ( 69 % ). LCMS (ESI) calc'd for [M+H]+: 178.1, found: 178.1.
69%	With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; triethylamine; palladium dichloride; In acetonitrile; at 100℃; under 15001.5 Torr; for 18h;	To a solution of <strong>[1150617-54-1]6-bromo-1H-pyrazolo[4,3-b]pyridine</strong> (M-4) (0.5 g, 2.5 mmol) in methanol (15 ml) and acetonitrile (7 ml) was added Et3N (2.2 ml, 5.6 mmol), Binap (0.17 g, 0.63 mmol) and palladium dichloride (0.17 g, 0.27 mmol). The mixture was placed under 20 bar of carbonmonoxide, and stirred at 100 C for 18 h. The mixture was cooled, filtered and purified by Prep-TLC to give 310mg of a white solid. (69 %). LCMS (ESI) calc?d for [M+H]: 178.1, found: 178.1.

Reference： [1]Patent: US2011/111046,2011,A1 .Location in patent: Page/Page column 16; 17
[2]Patent: WO2011/58473,2011,A1 .Location in patent: Page/Page column 34
[3]Patent: US2012/108619,2012,A1 .Location in patent: Page/Page column 30
[4]Synthetic Communications,2012,vol. 42,p. 1914 - 1921
[5]Patent: WO2014/26327,2014,A1 .Location in patent: Page/Page column 89-90
[6]Patent: WO2014/28589,2014,A2 .Location in patent: Page/Page column 108; 109; 110

7
[ 1301214-72-1 ]
[ 1256807-59-6 ]

Yield	Reaction Conditions	Operation in experiment
21%	Stage #1: 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester With water; sodium hydroxide In methanol at 0 - 20℃; Stage #2: With hydrogenchloride In water	11 To a solution of methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate (3.52 g, 20 mmol) in methanol (250 mL) and water (190 mL) at 0° C. was added aqueous sodium hydroxide (2M, 64 mL, 128 mmol), dropwise. The suspension was then allowed to warm to ambient temperature and stirred for 18 hours. The methanol was then removed in vacuo and the aqueous mixture extracted with ethyl acetate (250 mL) before being acidified (to pH 5-6) with aqueous hydrochloric acid (2 M, 70 mL). The cream solid which had precipitated out was then filtered off and dried in a desiccator to yield the title compound (0.675 g, 4.16 mmol, 21% yield). 1HNMR (400 MHz, DMSO-d6): δ ppm 8.97 (s, 1H), 8.45 (s, 1H), 8.39 (s, 1H).
21%	Stage #1: 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester With water; sodium hydroxide In methanol at 20℃; for 18h; Stage #2: With hydrogenchloride In water	11 To a solution of methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate (3.52 g, 20 mmol) in methanol (250 mL) and water (190 mL) at 0 °C was added aqueous sodium hydroxide (2M, 64 mL, 128 mmol), dropwise. The suspension was then allowed to warm to ambient temperature and stirred for 18 hours. The methanol was then removed in vacuo and the aqueous mixture extracted with ethyl acetate (250 mL) before being acidified (to pH 5-6) with aqueous hydrochloric acid (2 M, 70 mL). The cream solid which had precipitated out was then filtered off and dried in a desiccator to yield the title compound (0.675 g, 4.16 mmol, 21 % yield). 1HNMR (400 MHz, DMSO-c/e): ppm 8.97 (s, 1 H), 8.45 (s, 1 H), 8.39 (s, 1 H).
	Stage #1: 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester With water; sodium hydroxide In methanol at 0 - 20℃; Stage #2: With hydrogenchloride In water	8.7 To a solution of methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate (3.52 g, 20 mmol) in methanol (250 mL) and water (190 mL) at 0° C. was added aqueous sodium hydroxide (2M, 64 mL, 128 mmol), dropwise. The suspension was then allowed to warm to ambient temperature and stirred for 18 hours. The methanol was then removed in vacuo and the aqueous mixture extracted with ethyl acetate (250 mL). The aqueous layer was acidified (to pH 5-6) with 2 N aqueous hydrochloric acid (70 mL). The cream solid which had precipitated out was then filtered off and dried in a desiccator to yield the title compound (0.675 g, 21%). 1HNMR (400 MHz, DMSO-d6, δ): 8.97 (s, 1H), 8.45 (s, 1H), 8.39 (s, 1H).

	With water; sodium hydroxide at 20℃;	9.5 Intermediate 9: 1H-Pyrazolo[4,3-b]pyridine-6-carboxylic acid Step 5. A solution 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester (200 mg, 1 . 13 mmol, 1 .00 equiv) and sodium hydroxide (200 mg, 5.00 mmol, 4.43 equiv) in water ( 1 0 mL) was stirred overnight at rt. After the reaction was complete, the pH value of the solution was adjusted to 3 with concentrated HC1 The resulting mixture was concentrated under vacuum to give 1 g of crude title product as a light yellow solid. LC/ S (Method I, ES I): RT= 0.91 min, z = 164.0; 242.0 [M+H]"
	With water; sodium hydroxide at 20℃;	9.5 Intermediate 9: 1H-Pyrazolo[4,3-b]pyridine-6-carboxylic acid Step 5. A solution 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester (200 mg, 1 . 13 mmol, 1 .00 equiv) and sodium hydroxide (200 mg, 5.00 mmol, 4.43 equiv) in water ( 1 0 mL) was stirred overnight at rt. After the reaction was complete, the pH value of the solution was adjusted to 3 with concentrated HC1 The resulting mixture was concentrated under vacuum to give 1 g of crude title product as a light yellow solid. LC/ S (Method I, ES I): RT= 0.91 min, z = 164.0; 242.0 [M+H]"
	With water; sodium hydroxide at 20℃;	9.5 Intermediate 9: 1 H-Pyrazolo[4,3-bl pyridine-6-carboxylic acid Intermediate 9: 1 H-Pyrazolo[4,3-bl pyridine-6-carboxylic acid[0204] Step 5. A solution 1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester (200 mg, 1.13 mmol, 1.00 equiv) and sodium hydroxide (200 mg, 5.00 mmol, 4.43 equiv) in water (10 mL) was stirred overnight at rt. After the reaction was complete, the pH value of the solution was adjusted to 3 with concentrated HC1. The resulting mixture was concentrated under vacuum to give 1 g of crude title product as a light yellow solid. LC/MS (Method I, ESI): RT= 0.91 mi m/z = 164.0; 242.0 [M+H].
	With sodium hydroxide at 20℃;	Intermediate 9: lH-Pyrazolor4,3-blpyridine-6-carboxylic acid Step 5. A solution lH-pyrazolo[4,3-b]pyridine-6-carboxylic acid methyl ester (200 mg, 1.13 mmol, 1.00 equiv) and sodium hydroxide (200 mg, 5.00 mmol, 4.43 equiv) in water (10 mL) was stirred overnight at rt. After the reaction was complete, the pH value of the solution was adjusted to 3 with concentrated HC1. The resulting mixture was concentrated under vacuum to give 1 g of crude title product as a light yellow solid. LC/MS (Method I, ESI): RT= 0.91 min, m/z = 164.0; 242.0 [M+H]+. Intermediate 10: r 2,41Triazolor 5-alpyridine-6-carboxyric acid

Reference： [1]Current Patent Assignee: PFIZER INC - US2011/111046, 2011, A1 Location in patent: Page/Page column 17
[2]Current Patent Assignee: PFIZER INC - WO2011/58473, 2011, A1 Location in patent: Page/Page column 34
[3]Current Patent Assignee: PFIZER INC - US2012/108619, 2012, A1 Location in patent: Page/Page column 30
[4]Current Patent Assignee: VALO HEALTH INC - WO2013/127266, 2013, A1 Location in patent: Page/Page column 139; 140
[5]Current Patent Assignee: VALO HEALTH INC - WO2013/127267, 2013, A1 Location in patent: Page/Page column 90; 92
[6]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130935, 2013, A1 Location in patent: Paragraph 0204
[7]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130943, 2013, A1 Location in patent: Paragraph 0212

8
[ 67-56-1 ]
[ 201230-82-2 ]
[ 1383735-65-6 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
54%	With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 100℃;	9.4 Step 4. 1H-Pyrazolo[4.3-b]pyridine-6-carboxylic acid methyl ester. A mixture of 1-(6-bromo-pyrazolo[4,3-b]pyridin- 1-yl)-ethanone (2 g, 8.33 mmol, 1 .00 equiv), bis(triphenylphosphine)palladium(II) dichloride ( 1 g, 1 42 mmol, 0.1 7 equiv), and triethylamine (2.5 mL) in methanol (70 mL) was stirred overn ight under carbon monoxide ( 10 atmospheres) at 100 "C in a 1 00 mL pressure reactor The reaction mixture was cooled to rt and the solid material was removed by filtration. The filtrate was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to afford 0.8 g (54%) of the title compound as a light yellow solid. TLC: 1 : 1 ethyl acetate/petroleum ether, Rf= 0.2.
54%	With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 100℃; Sealed tube;	9.4 Step 4. 1H-Pyrazolo[4.3-b]pyridine-6-carboxylic acid methyl ester. A mixture of l -(6-bromo-pyrazolo[4,3 -b]pyridin- l -yl)-ethanone (2 g, 8.33 mmol, 1 .00 equiv), bis(triphenylphosphine)palladium(II) dichloride ( 1 g, 1 42 mmol, 0.1 7 equiv), and triethylamine (2.5 mL) in methanol (70 mL) was stirred overn ight under carbon monoxide ( 10 atmospheres) at 100 "C in a 1 00 mL pressure reactor The reaction mixture was cooled to rt and the solid material was removed by filtration. The filtrate was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1 :5) to afford 0.8 g (54%) of the title compound as a light yellow solid. TLC: 1 : 1 ethyl acetate/petroleum ether, Rf= 0.2.
	With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 100℃;	9.4 Step 4. 1H-Pyrazolo[4,3-blpyridine-6-carboxylic acid methyl ester. [0203] Step 4. 1H-Pyrazolo[4,3-blpyridine-6-carboxylic acid methyl ester. A mixture of 1-(6-bromo-pyrazolo[4,3-b]pyridin-1-yl)-ethanone (2 g, 8.33 mmol, 1.00 equiv), bis(triphenylphosphine)palladium(II) dichloride (1 g, 1.42 mmol, 0.17 equiv), and triethylamine (2.5 mL) in methanol (70 mL) was stirred overnight under carbon monoxide (10 atmospheres) at 100 °C in a 100 mL pressure reactor. The reaction mixture was cooled to rt and the solid material was removed by filtration. The filtrate was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethylacetate/petroleum ether (1:5) to afford 0.8 g (54%) of the title compound as a light yellow solid. TLC: 1:1 ethyl acetate/petroleum ether, Rf = 0.2.

Reference： [1]Current Patent Assignee: VALO HEALTH INC - WO2013/127266, 2013, A1 Location in patent: Page/Page column 140
[2]Current Patent Assignee: VALO HEALTH INC - WO2013/127267, 2013, A1 Location in patent: Page/Page column 90; 91
[3]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130935, 2013, A1 Location in patent: Paragraph 0203

9
[ 1301214-72-1 ]
[ 1453174-09-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: water; sodium hydroxide / 20 °C 2: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C

Reference： [1]Current Patent Assignee: VALO HEALTH INC - WO2013/127266, 2013, A1

10
[ 201230-82-2 ]
[ 1383735-65-6 ]
[ 1301214-72-1 ]

Yield	Reaction Conditions	Operation in experiment
54%	With methanol; bis-triphenylphosphine-palladium(II) chloride; triethylamine at 100℃;	Step 4. lH-Pyrazolor4,3-blpyridine-6-carboxylic acid methyl ester [0211] Step 4. lH-Pyrazolor4,3-blpyridine-6-carboxylic acid methyl ester. A mixture of l-(6-bromo-pyrazolo[4,3-b]pyridin-l-yl)-ethanone (2 g, 8.33 mmol, 1.00 equiv), bis(triphenylphosphine)palladium(II) dichloride (1 g, 1.42 mmol, 0.17 equiv), and triethylamine (2.5 mL) in methanol (70 mL) was stirred overnight under carbon monoxide (10 atmospheres) at 100 °C in a 100 mL pressure reactor. The reaction mixture was cooled to rt and the solid material was removed by filtration. The filtrate was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1:5) to afford 0.8 g (54%) of the title compound as a light yellow solid. TLC: 1: 1 ethyl acetate/petroleum ether, Rf = 0.2

Reference： [1]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/130943, 2013, A1 Location in patent: Paragraph 0211

11
[ 1301214-72-1 ]
[ 1352396-12-3 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; potassium hydroxide In N,N-dimethyl acetamide for 1.08333h;	7A.5 Preparation of methyl 3-iodo-lH-pyrazolo[4,3-b]pyridine-6-carboxyl- ate (M-6). To a solution of methyl lH-pyrazolo[4,3-b]pyridine- 6-carboxylate (M-5) ( 316 mg, 1.8 mmol ) in DMAC ( 30 ml ) was added KOH ( 40 mg, 7.18 mmol ). The vigorously stirred mixture was treated with iodine (550 mg, 2.15 mmol) and added portionwise over 5 minutes then stirred for 60 minutes. The reaction was quenched with 20 ml of 20% citric acid solution, followed by 16 ml of saturated NaHS03 solution, then adjusted to pH = 8 with solid NaHC03 and partitioned between ethyl acetate and water. The organic extract was dried and concentrated to a dark-red oil contain DMAC for next step directly. LCMS (ESI) calc'd for [M+H]+: 304.1, found: 304.1.
	With iodine; potassium hydroxide In N,N-dimethyl acetamide for 1h;	7A.5 Step 5. Preparation of methyl 3-iodo-1H-pyrazolo[4,3-b]pyridine-6-carboxylate (M-6). To a solution of methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate (M-5) (316 mg, 1.8mmol) in DMAC (30 ml) was added KOH (40 mg, 7.18 mmol). The vigorously stirred mixture was treated with iodine (550 mg, 2.15 mmol) and added portionwise over 5 minutes then stirred for 60 minutes. The reaction was quenched with 20 ml of 20% citric acid solution, followed by 16 ml of saturated NaHSO3 solution, then adjusted to pH = 8 with solidNaHCO3 and partitioned between ethyl acetate and water. The organic extract was dried and concentrated to a dark-red oil containing DMAC for use in the next step directly. LCMS (ESI) calc’d for [M+H]: 304.1, found: 304.1.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1 Location in patent: Page/Page column 90
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2 Location in patent: Page/Page column 108; 110

12
[ 1301214-72-1 ]
[ 1562454-17-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1.08 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

13
[ 1301214-72-1 ]
[ 1562454-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1.08 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C
	Multi-step reaction with 3 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

14
[ 1301214-72-1 ]
C₂₇H₂₀ClF₃N₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1.08 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C 4: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 100 °C / Microwave irradiation 5: ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V); triethylamine / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1

15
[ 1301214-72-1 ]
C₂₆H₁₈ClF₃N₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1.08 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C 4: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 100 °C / Microwave irradiation 5: ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V); triethylamine / dichloromethane / 2 h / 20 °C 6: water; lithium hydroxide / tetrahydrofuran / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1

16
[ 1301214-72-1 ]
[ 1352398-55-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With N-Bromosuccinimide In tetrahydrofuran at 20℃;	8A.1 Preparation of methyl 3-bromo-lH-pyrazolo[4,3-b]pyridine -6-carboxylat e (0-2). To a solution of methyl lH-pyrazolo[4,3-b]pyridine -6-carboxylate (O-l) (2 g, 11.3 mmol) in THF (50 mL) was added BS (3 g, 16.9 mmoL), the reaction mixture was stirred overnight at rt, then methanol was added to quench the reaction, concentrated to give a crude product, triturated with EtOAc, filtered and collected the solid to give 2.5 g (87%) of title compound as a white solid. LCMS (ESI): calc'd for C8H6BrN302 [M+H]+: 256, found: 256.
	With N-Bromosuccinimide In tetrahydrofuran at 20℃;	8A.1 Preparation of methyl 3-bromo-1H-pyrazolo [4,3-bj pyridine -6-carboxylate (O-2). To a solution of methyl 1H-pyrazolo[4,3-b]pyridine-6-carboxylate (0-1) (2 g, 11.3 mmol) in THF (50 mL) was added NBS (3 g, 16.9 mmoL). The reaction mixture was stirredovernight at room temperature, then methanol was added to quench the reaction. The reaction mixture was concentrated to give a crude product, triturated with EtOAc, and filtered, and 2.5 g (87%) of title compound as a white solid was collected. LCMS (ESI):calc’d for C8H6BrN3O2 [M+H]: 256, found: 256.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1 Location in patent: Page/Page column 94
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2 Location in patent: Page/Page column 115

17
[ 1301214-72-1 ]
[ 1562454-37-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1 Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

18
[ 1301214-72-1 ]
[ 1562454-41-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C
	Multi-step reaction with 3 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

19
[ 1301214-72-1 ]
[ 1562454-45-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C
	Multi-step reaction with 4 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

20
[ 1301214-72-1 ]
[ 1562454-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 5 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5: Dess-Martin periodane / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

21
[ 1301214-72-1 ]
[ 1562454-52-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6.1: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

22
[ 1301214-72-1 ]
[ 1562451-04-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6.1: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 20 °C
	Multi-step reaction with 7 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

23
[ 1301214-72-1 ]
[ 1562454-57-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6.1: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C
	Multi-step reaction with 7 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7: Dess-Martin periodane / dichloromethane / 3 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

24
[ 1301214-72-1 ]
[ 1562451-06-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3.1: diisobutylaluminium hydride / tetrahydrofuran / -40 - 20 °C 3.2: 0.5 h / 0 °C 4.1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5.1: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6.1: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7.1: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 8.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 20 °C
	Multi-step reaction with 8 steps 1: N-Bromosuccinimide / tetrahydrofuran / 20 °C 2: dmap; triethylamine / dichloromethane / 3 h / 20 °C 3: diisobutylaluminium hydride / tetrahydrofuran / 3 h / -40 - 20 °C 4: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 10 °C 5: Dess-Martin periodane / dichloromethane / 2 h / 20 °C 6: tetrahydrofuran / 4 h / -78 - 20 °C / Inert atmosphere 7: Dess-Martin periodane / dichloromethane / 3 h / 20 °C 8: lithium hydroxide monohydrate / tetrahydrofuran; water / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/28589, 2014, A2

25
[ 1301214-72-1 ]
1-(2-chloro-6-(trifluoromethyl)benzoyl)-3-(4-(methoxycarbonyl)phenyl)-1H-pyrazolo[4,3-b]pyridine-6-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1.08 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C 4: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; 1,4-dioxane / 1 h / 100 °C / Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/26327, 2014, A1

26
[ 1301214-72-1 ]
[ 1562454-24-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium hydroxide; iodine / N,N-dimethyl acetamide / 1 h 2: dmap; triethylamine / dichloromethane / 20 h / 20 °C / Inert atmosphere 3: water; lithium hydroxide / tetrahydrofuran / 24 h / 20 °C 4: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate / water; 1,4-dioxane / 1 h / 100 °C / Microwave irradiation