[ CAS No. 271-34-1 ] {[proInfo.proName]}

Name: 271-34-1|5-Azaindole|98%
Brand: Ambeed
SKU: A143044
Price: 5.0 USD
Availability: InStock
Rating: 94 (40 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 271-34-1

Structure of 271-34-1 * Storage: {[proInfo.prStorage]}

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

Search after Editing

* Storage: {[proInfo.prStorage]}

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

Quality Control of [ 271-34-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 271-34-1 ]

SDS Specification

Alternatived Products of [ 271-34-1 ]

Product Details of [ 271-34-1 ]

CAS No. :	271-34-1	MDL No. :	MFCD00955936
Formula :	C₇H₆N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SRSKXJVMVSSSHB-UHFFFAOYSA-N
M.W :	118.14	Pubchem ID :	9220
Synonyms :

Calculated chemistry of [ 271-34-1 ]

Physicochemical Properties

Num. heavy atoms :	9
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 :	36.09
TPSA :	28.68 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.32 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.11
Log Po/w (XLOGP3) :	0.98
Log Po/w (WLOGP) :	1.56
Log Po/w (MLOGP) :	0.31
Log Po/w (SILICOS-IT) :	2.15
Consensus Log Po/w :	1.22

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.93
Solubility :	1.39 mg/ml ; 0.0118 mol/l
Class :	Very soluble
Log S (Ali) :	-1.17
Solubility :	7.98 mg/ml ; 0.0675 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.86
Solubility :	0.163 mg/ml ; 0.00138 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 271-34-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P280-P271-P302+P352-P312-P304+P340-P305+P351+P338-P362+P364-P403+P233-P501	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 271-34-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 271-34-1 ]
Downstream synthetic route of [ 271-34-1 ]

[ 271-34-1 ] Synthesis Path-Upstream 1~10

1
[ 271-34-1 ]
[ 60290-21-3 ]

Reference： [1] Patent: WO2017/23987, 2017, A1,
[2] Patent: WO2017/24003, 2017, A1,
[3] Patent: WO2017/24010, 2017, A1,
[4] Patent: WO2017/23984, 2017, A1,

2
[ 271-34-1 ]
[ 23612-36-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: With copper(ll) bromide In acetonitrile at 17 - 20℃; for 1 - 2 h; Stage #2: With ammonia In methanol; acetonitrile at 10℃;	Example 1 3-bromo-5-azaindole[00145] Referring now to the Scheme 1 as shown in Fig. 1 , a solution of 3.0128g(25.51 mmol) of 5-azaindole (Atlantic SciTech Group) in 50 ml. of acetonitrile was placed in a 250 ml. three-neck round-bottom flask equipped with a magnetic stirrer, thermocouple, nitrogen bleed, and cooling ice bath. A total of 17.1Og (76.53 mmol, 3 eg.) of solid CuBr2 was added portion-wise to the flask at 17°C in 10 min. The resulting green suspension was stirred at room temperature until no starting material was observed by TLC (approximately 1-2 hours, Rf = 0.23 for 5-azaindole and 0.49 for 3- bromo-5-azaindole in EtOAc/MeOH=9:1 ). The reaction mixture was cooled to 10°C and then was slowly quenched by addition of IN ammonia in methanol solution (1 1OmL). The resulting blue solution was concentrated on rotavap at room temperature, and the residue was extracted with ethyl acetate (3 x 80 ml_). The organic extract was dried over Na₂SO₄, filtered, and concentrated to residual volume of about 50 ml_. The temperature of the residue was brought to reflux resulting in the dissolving of all solids, and then hexane was added to the hot mixture until crystallization occured. The resulting suspension was cooled on an ice bath, the product was filtered, washed with cold EtOAc/hexane = 1 :3 and then hexane, and dried. The 3-bromo-5-azaindole was an off- white solid, yield 3.52 g (70percent yield).
32%	With copper(ll) bromide In acetonitrile for 1.5 h;	5-Azaindole (118 mg, 1.00 mmol) and copper(II) bromide (669 mg, 3.00 mmol) were mixed with MeCN (10 mL) and stirred for 1.5 h. To the mixture was added 2 M ammonia in MeOH (12 mL) and the resulting suspension was added to water (40 mL) and extracted with EtOAc (2 x 60 mL). The organic layers were combined and washed with brine and evaporated to yield the title compound (190 mg, 32percent). MS (ESI+) m/z = 197, 199 (M+H)⁺.
32%	With copper(ll) bromide In acetonitrile at 20℃; for 1.5 h;	5-Azaindole (118 mg, 1.00 mmol) and copper(II) bromide (669 mg, 3.00 mmol) were mixed with MeCN (10 mL) and stirred for 1.5 h. To the mixture was added 2 M ammonia in MeOH (12 mL) and the resulting suspension was added to water (40 mL) and extracted with EtOAc (2*60 mL). The organic layers were combined and washed with brine and evaporated to yield the title compound (190 mg, 32percent). MS (ESI+) m/z=197, 199 (M+H)⁺.

Reference： [1] Synlett, 2007, # 2, p. 211 - 214
[2] Patent: WO2010/33981, 2010, A2, . Location in patent: Page/Page column 27-28
[3] Patent: WO2011/113798, 2011, A2, . Location in patent: Page/Page column 35
[4] Patent: US2013/102587, 2013, A1, . Location in patent: Paragraph 0181; 0182
[5] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2430 - 2433

3
[ 271-34-1 ]
[ 1778-74-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4752 - 4772

4
[ 271-34-1 ]
[ 98-09-9 ]
[ 109113-39-5 ]

Yield	Reaction Conditions	Operation in experiment
69.4%	Stage #1: With sodium hydride In mineral oil at 0℃; for 0.5 h; Stage #2: at 0 - 20℃; for 1 h;	To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60percent in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0°C. The mixture was stirred at 0°C for 0.5 h. PhS0₂Cl (LXXV) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0°C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCCb (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na₂SC>4. Removal solvents under reduced pressure gave l -(phenylsulfonyl)- lH- pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4percent yield) . NMR (CDCI₃, 400 MHz) δ ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C₁₃H₁₀N₂O₂S mlz 259.1 (M+H).
69.4%	Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5 h; Stage #2: at 0 - 20℃; for 1 h;	To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60percent in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0°C. The mixture was stirred at 0°C for 0.5 h. PhS0₂Cl (LXXV) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0°C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na2SC>4. Removal solvents under reduced pressure gave 1 - (phenylsulfonyl)-lH-pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4percent yield). NMR (CDCI3, 400 MHz) δ ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for Ci₃HioN₂02S mlz 259.1 (M+H).
69.4%	Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5 h; Stage #2: at 0 - 20℃; for 1 h;	To a solution of lH-pyrrolo[3,2-c]pyridine (XCI) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60percent in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0°C. The mixture was stirred at 0°C for 0.5 h. PhS0₂Cl (XCII) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0°C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC>3 (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na₂SC>₄. Removal solvents under reduced pressure gave l-(phenylsulfonyl)-lH- pyrrolo[3,2-c]pyridine (XCIII) as a yellow solid. (1.52 g, 5.88 mmol, 69.4percent yield). NMR (CDC , 400 MHz) δ ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C₁3H₁0N₂O₂S mlz 259.1 (M+H).

69.4%

Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5 h;

Step 1 [0675] To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60percent in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0°C. The mixture was stirred at 0°C for 0.5 h. PhS0₂Cl (LXXV) ( 1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0°C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC^ (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na₂SC>4. Removal solvents under reduced pressure gave 1 - (phenylsulfonyl)-lH-pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4percent yield). NMR (CDC1₃, 400 MHz) δ ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C₁3H₁0N₂O₂S mlz 259.1 (M+H).

Reference： [1] Synthesis, 2005, # 20, p. 3581 - 3588
[2] Patent: WO2017/23987, 2017, A1, . Location in patent: Paragraph 0675; 0676
[3] Patent: WO2017/24003, 2017, A1, . Location in patent: Paragraph 0675; 0676
[4] Patent: WO2017/24010, 2017, A1, . Location in patent: Paragraph 0622; 0623
[5] Patent: WO2017/23984, 2017, A1, . Location in patent: Paragraph 0675
[6] Tetrahedron, 1993, vol. 49, # 14, p. 2885 - 2914
[7] Patent: WO2015/88045, 2015, A1, . Location in patent: Paragraph 0339; 0340
[8] Patent: US2017/8885, 2017, A1, . Location in patent: Paragraph 0741-0742

5
[ 271-34-1 ]
[ 24424-99-5 ]
[ 148760-75-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap In acetonitrile at 20℃; for 18 h;	Step A: Preparation of tert-butyl 1H-pyrrolo[3,2-c]pyridine-1-carboxylate: To a stirred mixture of 1H-pyrrolo[3,2-c]pyridine (2.3 g, 20 mmol) and N,N-dimethylpyridin-4-amine (2.4 g, 20 mmol) in CH₃CN (20 mL) was added Boc-anhydride (3.9 g, 18 mmol). The mixture was stirred for 18 hours at ambient temperature. The reaction was concentrated in vacuo, and then purified by Biotage Flash 40S, eluding with 1:1 EtOAc/hexanes. The product was obtained as a colorless oil (4.0 g, 101percent).
98.2%	With triethylamine In dichloromethane at 25℃; for 12 h; Inert atmosphere	To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)₂0 (48.8 g, 223.5 mmol) in portions at 25°C under N2. The mixture was stirred at 25°C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf= 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine-l- carboxylate (C) (43.5 g, 199.3 mmol, 98.2percent yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
98.2%	With triethylamine In dichloromethane at 25℃; for 12 h; Inert atmosphere	To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)₂0 (48.8 g, 223.5 mmol) in portions at 25°C under N2. The mixture was stirred at 25°C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give tert-buty\ lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (C) (43.5 g, 199.3 mmol, 98.2percent yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).

98.2%	With triethylamine In dichloromethane at 25℃; for 12 h; Inert atmosphere	To the solution of lH-pyrrolo[3,2-c]pyridine (XCI) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)₂0 (48.8 g, 223.5 mmol) in portions at 25°C under N2. The mixture was stirred at 25°C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (CXVII) (43.5 g, 199.3 mmol, 98.2percent yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
98.2%	With triethylamine In dichloromethane at 25℃; for 12 h;	Step 1 [0703] To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)₂0 (48.8 g, 223.5 mmol) in portions at 25°C under N2. The mixture was stirred at 25°C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (C) (43.5 g, 199.3 mmol, 98.2percent yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
97%	at 0℃; for 6 h;	To a solution of 5-azaindole (5.00 g) and Et₃N (12 mL) was added (Boc)₂0 ( 14 mL) dropwise at 0°C. The mixture was stirred for 6 h, then diluted with water and extracted with EtOAc. The organic layer was dried over Na₂S0₄ for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 3: 1 (v/v) PE/EA) to give the title compound as transparent liquid (9.00 g, 97.00 percent). The compound was characterized by the following spectroscopic data: ? NMR (400 MHz, CDC1₃) ?: 1.65 (s, 9H), 6.62 (d, J = 3.6 Hz, 1H), 7.25 (d, J = 5.3 Hz, 1 H), 7.50 (d, J = 3.5 Hz, 1H), 8.42 (d, J= 5.3 Hz, 1 H), 9.43 (s, lH) ppm.
97%	at 0℃; for 6 h;	To a solution of 5-azaindole (5.00 g) and Et₃N (12 mL) was added (Boc)₂O (14 mL) dropwise at 0° C. The mixture was stirred for 6 h, then diluted with water and extracted with EtOAc. The organic layer was dried over Na₂SO₄for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to give the title compound as transparent liquid (9.00 g, 97.00percent). The compound was characterized by the following spectroscopic data: ¹H NMR (400 MHz, CDCl₃) δ: 1.65 (s, 9H), 6.62 (d, J=3.6 Hz, 1H), 7.25 (d, J=5.3 Hz, 1H), 7.50 (d, J=3.5 Hz, 1H), 8.42 (d, J=5.3 Hz, 1H), 9.43 (s, 1H) ppm.
92.4%	With dmap In acetonitrile at 20℃; for 2.5 h;	Dimethylaminopyridine (DMAP) (2.08 g, 16.9 mmol) in acetonitrile (20 mL) was added drop wise to 5-azaindole (2.0 g, 16.9 mmol) in acetonitrile (70 mL) at room temperature. After stirring for 2 hours, di-ieri-butyldicarbonate (3.68 g, 16.9 mmol) was added in portion at same temperature. After 2.5 hours, the solvent was evaporated under reduced pressure and the residue (5.4 g) was purified by column chromatography (silica gel, ethyl acetate/heptane 1/10 to 1/2) to provide pyrrolo[3,2-c]pyridine-l- carboxylic acid tert-butyl ester (2.72 g, 92.4percent yield) as a bright yellow oil. ¹H NMR (Field: 300 MHz, Solvent: CD₃OD/TMS) δ (ppm): 8.87 (s, 1H), 8.48 (d, 1H, J= 5.7 Hz), 7.98 (d, 1H, J = 5.1 Hz), 7.60 (d, 1H, J = 3.3 Hz), 6.63 (d, lH, J = 3.0 Hz), 1.68 (s, 9H). ¹³C NMR (Field: 75 MHz, Solvent: CDCI₃/TMS) δ (ppm): 148.82, 143.75, 143.51 , 139.50, 126.69, 109.83, 105.46, 84.60, 28.05.

Reference： [1] Patent: US2007/238726, 2007, A1, . Location in patent: Page/Page column 114
[2] Patent: WO2017/23987, 2017, A1, . Location in patent: Paragraph 0703; 0704
[3] Patent: WO2017/24003, 2017, A1, . Location in patent: Paragraph 0703; 0704
[4] Patent: WO2017/24010, 2017, A1, . Location in patent: Paragraph 0650; 0651
[5] Patent: WO2017/23984, 2017, A1, . Location in patent: Paragraph 0703
[6] Patent: WO2013/71697, 2013, A1, . Location in patent: Paragraph 00275
[7] Patent: US2014/228361, 2014, A1, . Location in patent: Paragraph 0416-0417
[8] Patent: WO2012/54535, 2012, A2, . Location in patent: Page/Page column 172
[9] Tetrahedron, 1993, vol. 49, # 14, p. 2885 - 2914
[10] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 4, p. 977 - 982
[11] Patent: US4831144, 1989, A,
[12] Patent: WO2007/147874, 2007, A1, . Location in patent: Page/Page column 165-166

6
[ 271-34-1 ]
[ 192189-16-5 ]

Reference： [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 15, p. 2430 - 2433
[2] Patent: WO2011/113798, 2011, A2,
[3] Patent: US2013/102587, 2013, A1,

7
[ 271-34-1 ]
[ 877060-47-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.25 h; Stage #2: With iodine In N,N-dimethyl-formamide at 0 - 20℃; for 0.25 h;	To a solution of lH-pyrrolo[3,2-c]pyridine (5.76 g, 48.8 mmol , 1.0 eq) in DMF (30 mL) was added KOH (10.39 g, 185.5 mmol , 3.8 eq). The reaction mixture was stirred at rt for 15 min. The reaction mixture was cooled to 0 °C and a solution of 12 (12.4 g, 48.8 mmol, 1.0 eq ) in DMF ( 15 mL ) was added. After stirring for 15 min at rt, the reaction mixture was poured into water. The mixture was filtered and the solid was rinsed with water. The yellow solid was dried in vacuo to give 3-iodo-lH-pyrrolo[3,2-c]pyridine (9.9 g , 83percent).

Reference： [1] Synthesis, 2005, # 20, p. 3581 - 3588
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 7, p. 2056 - 2060
[3] Patent: WO2018/11628, 2018, A1, . Location in patent: Paragraph 00308
[4] Organic and Biomolecular Chemistry, 2011, vol. 9, # 14, p. 5129 - 5136

8
[ 271-34-1 ]
[ 877060-48-5 ]

Reference： [1] Synthesis, 2005, # 20, p. 3581 - 3588
[2] Organic and Biomolecular Chemistry, 2011, vol. 9, # 14, p. 5129 - 5136

9
[ 271-34-1 ]
[ 1147422-00-1 ]

Reference： [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,

10
[ 271-34-1 ]
[ 4885-02-3 ]
[ 933717-10-3 ]

Yield	Reaction Conditions	Operation in experiment
0.333 g	With aluminum (III) chloride In nitromethane; 1,2-dichloro-ethane at 0℃; for 1 h; Inert atmosphere	To a solution of 1 /-/-pyrrolo[3,2-c]pyridine (0.400 g; 3.386 mmol) in a mixture of 1 ,2- dichloroethane (10 mL) and nitromethane (10 mL) cooled at 0 °C under an argon atmosphere were added dichloro(methoxy)methane (1 .544 mL; 16.92 mmol) and aluminum trichloride ( 1 .500 g; 1 1 .25 mmol) over 1 h. After the addition, the reaction was quenched by addition of water and of a saturated sodium bicarbonate solution. The reaction mixture was extracted with a solution of dichloromethane and ethanol (9/1 , 6x100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 0.333 g (67percent) of 1 H-pyrrolo[3,2-c]pyridine-3-carbaldehyde which was used without further purification. ESI/APCI(+): 147 (M+H). ESI/APCI(-): 145 (M-H). ¹ H NMR (DMSO- d₆) 10.00 (1 H, s); 9.29 (1 H, s); 8.42 ( 1 H, s); 8.35 (1 H, d); 7.53 (1 H, d).

Reference： [1] Patent: WO2013/45516, 2013, A1, . Location in patent: Page/Page column 201

[ 271-34-1 ] Synthesis Path-Downstream 1~88

1
[ 119248-43-0 ]
[ 271-34-1 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1958,vol. 612,p. 153,157

2
[ 271-34-1 ]
[ 24424-99-5 ]
[ 148760-75-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; In acetonitrile; at 20℃; for 18h;	Step A: Preparation of tert-butyl 1H-pyrrolo[3,2-c]pyridine-1-carboxylate: To a stirred mixture of 1H-pyrrolo[3,2-c]pyridine (2.3 g, 20 mmol) and N,N-dimethylpyridin-4-amine (2.4 g, 20 mmol) in CH3CN (20 mL) was added Boc-anhydride (3.9 g, 18 mmol). The mixture was stirred for 18 hours at ambient temperature. The reaction was concentrated in vacuo, and then purified by Biotage Flash 40S, eluding with 1:1 EtOAc/hexanes. The product was obtained as a colorless oil (4.0 g, 101%).
98.2%	With triethylamine; In dichloromethane; at 25℃; for 12h;Inert atmosphere;	To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)20 (48.8 g, 223.5 mmol) in portions at 25C under N2. The mixture was stirred at 25C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf= 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine-l- carboxylate (C) (43.5 g, 199.3 mmol, 98.2% yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
98.2%	With triethylamine; In dichloromethane; at 25℃; for 12h;Inert atmosphere;	To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)20 (48.8 g, 223.5 mmol) in portions at 25C under N2. The mixture was stirred at 25C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give tert-buty lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (C) (43.5 g, 199.3 mmol, 98.2% yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).

98.2%	With triethylamine; In dichloromethane; at 25℃; for 12h;Inert atmosphere;	To the solution of lH-pyrrolo[3,2-c]pyridine (XCI) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)20 (48.8 g, 223.5 mmol) in portions at 25C under N2. The mixture was stirred at 25C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (CXVII) (43.5 g, 199.3 mmol, 98.2% yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
98.2%	With triethylamine; In dichloromethane; at 25℃; for 12h;	Step 1 [0703] To the solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (24 g, 203 mmol) and TEA (62 g, 609 mmol) in DCM (200 mL) was added (Boc)20 (48.8 g, 223.5 mmol) in portions at 25C under N2. The mixture was stirred at 25C for 12 h. The reaction mixture was then diluted with DCM and dried to give the crude product. The residue was purified by column chromatography (S1O2, PE/EtOAc = 2/1, Rf = 0.40) to give fert-butyl lH-pyrrolo[3,2-c]pyridine- 1-carboxylate (C) (43.5 g, 199.3 mmol, 98.2% yield) as a light yellow oil. ESIMS found for C12H14N2O2 mlz 219.1 (M+H).
97%	With triethylamine; at 0℃; for 6h;	To a solution of 5-azaindole (5.00 g) and Et3N (12 mL) was added (Boc)20 ( 14 mL) dropwise at 0C. The mixture was stirred for 6 h, then diluted with water and extracted with EtOAc. The organic layer was dried over Na2S04 for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 3: 1 (v/v) PE/EA) to give the title compound as transparent liquid (9.00 g, 97.00 %). The compound was characterized by the following spectroscopic data: ? NMR (400 MHz, CDC13) ?: 1.65 (s, 9H), 6.62 (d, J = 3.6 Hz, 1H), 7.25 (d, J = 5.3 Hz, 1 H), 7.50 (d, J = 3.5 Hz, 1H), 8.42 (d, J= 5.3 Hz, 1 H), 9.43 (s, lH) ppm.
97%	With triethylamine; at 0℃; for 6h;	To a solution of 5-azaindole (5.00 g) and Et3N (12 mL) was added (Boc)2O (14 mL) dropwise at 0 C. The mixture was stirred for 6 h, then diluted with water and extracted with EtOAc. The organic layer was dried over Na2SO4 for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to give the title compound as transparent liquid (9.00 g, 97.00%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) delta: 1.65 (s, 9H), 6.62 (d, J=3.6 Hz, 1H), 7.25 (d, J=5.3 Hz, 1H), 7.50 (d, J=3.5 Hz, 1H), 8.42 (d, J=5.3 Hz, 1H), 9.43 (s, 1H) ppm.
92.4%	With dmap; In acetonitrile; at 20℃; for 2.5h;	Dimethylaminopyridine (DMAP) (2.08 g, 16.9 mmol) in acetonitrile (20 mL) was added drop wise to 5-azaindole (2.0 g, 16.9 mmol) in acetonitrile (70 mL) at room temperature. After stirring for 2 hours, di-ieri-butyldicarbonate (3.68 g, 16.9 mmol) was added in portion at same temperature. After 2.5 hours, the solvent was evaporated under reduced pressure and the residue (5.4 g) was purified by column chromatography (silica gel, ethyl acetate/heptane 1/10 to 1/2) to provide pyrrolo[3,2-c]pyridine-l- carboxylic acid tert-butyl ester (2.72 g, 92.4% yield) as a bright yellow oil. 1H NMR (Field: 300 MHz, Solvent: CD3OD/TMS) delta (ppm): 8.87 (s, 1H), 8.48 (d, 1H, J= 5.7 Hz), 7.98 (d, 1H, J = 5.1 Hz), 7.60 (d, 1H, J = 3.3 Hz), 6.63 (d, lH, J = 3.0 Hz), 1.68 (s, 9H). 13C NMR (Field: 75 MHz, Solvent: CDCI3/TMS) delta (ppm): 148.82, 143.75, 143.51 , 139.50, 126.69, 109.83, 105.46, 84.60, 28.05.
		EXAMPLE 10 Preparation of 1-tert-butoxycarbonyl-1H-pyrrolo[3,2-c]pyridine Following the same method as that described in Example 1 but starting from 22.6 g (0.2 mol) of 1H-pyrrolo[3,2-c]pyridine and 55 ml (0.24 mol) of tert-butyl dicarbonate, there were obtained 42.5 g of a brown oil which crystallized in the refrigerator. By chromatographic purification of an analytical sample, 1-tert-butoxycarbonyl-1H-pyrrolo[3,2-c]pyridine was obtained in the form of a cream-coloured powder. M.P.: 65 C.
	With dmap; In dichloromethane; for 1.25h;	To lH-pyrrolo[3,2-c]pyridine (500 mg, 4.2 mmol) in dry DCM (2 mL) were added DMAP (569 mg, 4.7 mmol, in 2 mL dry DCM ) and di-tert-butyl carbonate ( 1.02 g, 4.7 mmol, in 2 mL dry DCM). The mixture was stirred over night and extracted with IM aq HCl (20 mL) and DCM (3x 20 mL). The organic lay- ers were combined, dried (Na2Stheta4), filtered and concentrated to give 333 mg of a white solid, tert-butyl lH-pyrrolo[3,2-c]pyridine- l-carboxylate. MS (ESI+) for C12H 14N2O2 m/z 219 (M+H)+. Part of the material (163 mg, 0.75 mmol) was suspended in dry THF (5 mL) and triisopropyl borate (0.21 mL, 0.90 mmol) was added and the mixture was cooled on ice. 1.8 M LDA (0.50 mL, 0.90 mmol) was added dropwise over 20 minutes. Additional LDA (0.85 mL, 1.52 mmol, 2 additions) was added over 45 minutes to complete the reaction. An aliquot of 0.9 mL was added to a mixture of 6-chloro-N-(4-[(3R)-3- (dimethylamino)pyrrolidin- l-yl]carbonyl}-2-methoxyphenyl)pyrazin-2-amine (20 mg, 0.05 mmol), K2CO3 (1 1 mg, 0.13 mmol) and Pd(PPh3J4 (6 mg, 0.05 mmol) in MeCN/water (7:3, 4 mL). The mixture was irradiated in a microwave oven at 120 0C for 10 minutes. This was performed twice, using a total of 40 mg of 6-chloro-N-(4-[(3R)-3-(dimethylamino)pyrrolidin- l-yl]carbonyl}-2- methoxyphenyl)pyrazin-2-amine. The reactions were combined, the solvent was evaporated and the residue was extracted with DCM (2x 10 mL) and satu- rated aq Na2CO3 ( 10 mL). The organic layers were combined, dried (Na2Stheta4), filtered and concentrated. The material was purified twice by preparative HPLC <n="167"/>(XTerra C18, 50 mM NH4HCO3 pH 10, MeCN). The title compound was obtained as a light yellow solid (7 mg) . HPLC 99%(System A), 100%(System B).IH NMR (400 MHz, MeOD). Dppm 1.75 - 1.95 (m, 1 H) 2.12 - 2.24 (m, 1 H) 2.25 (s, 3 H) 2.34 (s, 3 H) 2.75 - 2.96 (m, 1 H) 3.41 - 3.54 (m, 1 H) 3.57 - 3.91 (m, 3 H) 3.98 (s, 3 H) 7.22 (d, J= 1.76 Hz, 1 H) 7.25 - 7.31 (m, 1 H) 7.33 (s, 1 H) 7.48 - 7.52 (m, 1 H) 8.17 (d, J=5.77 Hz, 1 H) 8.27 (s, 1 H) 8.51 (s, 1 H) 8.58 - 8.68 (m, 1 H) 8.84 (d, J=LOO Hz, 1 H). MS (ESI+) calcd for C2SH27N7O2 457.2226, found 457.2222.
	With dmap; In dichloromethane; at 20℃; for 12h;Inert atmosphere;	Step C: 5-Azaindole (10.00g, 84.65mmol, 1.00eq), Boc2O (19.40g, 88.88mmol, 20.42mL, 1.05eq) and 200mLdichloromethane were added to a single-neck round bottom flask, followed by addition of DMAP (1.03g, 8.47mmol,0.10eq) under nitrogen atmosphere. The reaction solution was stirred at 20C for 12 hours, then concentrated andpurified by silica gel column chromatography (EA/PE=0%-40%) to give 95. 1H NMR (400MHz, CHLOROFORM-d) delta8.89 (s, 1H), 8.47 (d, J=6.0 Hz, 1H), 7.98 (d, J=5.6 Hz, 1H), 7.61 (d, J=3.6 Hz, 1H), 6.65 (d, J=3.6 Hz, 1H), 1.69 (s, 9H).
1.76 g	With triethylamine; In acetonitrile; at 0 - 20℃;Inert atmosphere;	To a solution of triethylamine (0.65 ml, 4.66 mmol) and 5-azaindole (1.00 g, 8.46 mmol) in MeCN (20 ml) stirring at 0 00 was added di-teit-butyl dicarbonate (0.97 ml,4.23 mmol) dropwise under nitrogen with stirring. The reaction was allowed to warm to room temperature and left to stir over the weekend. Further di-teit-butyl dicarbonate (0.97 ml, 4.23 mmol) was added and stirring continued for 6 hours. The reaction mixture was concentrated under reduced pressure and the oil obtained taken up in DCM and washed with water. The mixture was passed through a hydrophobic frit and solvent removed under reduced pressure to afford teit-butyl pyrrolo[3,2-c]pyridine-1-carboxylate (P62) (1.76 g), LCMS ES 219 [M+H], Rt = 1.19 mins (Generic Basic Method).

Reference： [1]Patent: US2007/238726,2007,A1 .Location in patent: Page/Page column 114
[2]Patent: WO2017/23987,2017,A1 .Location in patent: Paragraph 0703; 0704
[3]Patent: WO2017/24003,2017,A1 .Location in patent: Paragraph 0703; 0704
[4]Patent: WO2017/24010,2017,A1 .Location in patent: Paragraph 0650; 0651
[5]Patent: WO2017/23984,2017,A1 .Location in patent: Paragraph 0703
[6]Patent: WO2013/71697,2013,A1 .Location in patent: Paragraph 00275
[7]Patent: US2014/228361,2014,A1 .Location in patent: Paragraph 0416-0417
[8]Patent: WO2012/54535,2012,A2 .Location in patent: Page/Page column 172
[9]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[10]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 977 - 982
[11]Patent: US4831144,1989,A
[12]Patent: WO2007/147874,2007,A1 .Location in patent: Page/Page column 165-166
[13]Patent: EP3434668,2019,A1 .Location in patent: Paragraph 0229
[14]Patent: WO2019/34890,2019,A1 .Location in patent: Paragraph 00153; 00207

3
[ 271-34-1 ]
[ 98-09-9 ]
[ 109113-39-5 ]

Yield	Reaction Conditions	Operation in experiment
69.4%		To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60% in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0C. The mixture was stirred at 0C for 0.5 h. PhS02Cl (LXXV) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCCb (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na2SC>4. Removal solvents under reduced pressure gave l -(phenylsulfonyl)- lH- pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4% yield) . NMR (CDCI3, 400 MHz) delta ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C13H10N2O2S mlz 259.1 (M+H).
69.4%		To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60% in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0C. The mixture was stirred at 0C for 0.5 h. PhS02Cl (LXXV) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na2SC>4. Removal solvents under reduced pressure gave 1 - (phenylsulfonyl)-lH-pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4% yield). NMR (CDCI3, 400 MHz) delta ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for Ci3HioN202S mlz 259.1 (M+H).
69.4%		To a solution of lH-pyrrolo[3,2-c]pyridine (XCI) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60% in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0C. The mixture was stirred at 0C for 0.5 h. PhS02Cl (XCII) (1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC>3 (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na2SC>4. Removal solvents under reduced pressure gave l-(phenylsulfonyl)-lH- pyrrolo[3,2-c]pyridine (XCIII) as a yellow solid. (1.52 g, 5.88 mmol, 69.4% yield). NMR (CDC , 400 MHz) delta ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C13H10N2O2S mlz 259.1 (M+H).

69.4%		Step 1 [0675] To a solution of lH-pyrrolo[3,2-c]pyridine (LXXIV) (1 g, 8.47 mmol, 1.0 eq) in THF (10 mL) was added NaH (60% in mineral oil) (0.24 g, 10.2 mmol, 1.2 eq) at 0C. The mixture was stirred at 0C for 0.5 h. PhS02Cl (LXXV) ( 1.80 g, 10.2 mmol, 1.2 eq) was then added to the solution at 0C. The reaction was warmed to room temperature and stirred for 1 h. Aqueous NaHCC^ (30 mL) was added and then extracted with EtOAc (x 3). The organic phase was combined and dried over Na2SC>4. Removal solvents under reduced pressure gave 1 - (phenylsulfonyl)-lH-pyrrolo[3,2-c]pyridine (LXXVI) as a yellow solid. (1.52 g, 5.88 mmol, 69.4% yield). NMR (CDC13, 400 MHz) delta ppm 6.75 (d, J=3.6Hz, 1H), 7.48 (t, J=8Hz, 2H), 7.55 - 7.61 (m, 2H), 7.89 - 7.93 (m, 3H), 8.49 (d, J=6Hz, 1H), 8.88 (s, 1H); ESIMS found for C13H10N2O2S mlz 259.1 (M+H).
		A solution of 5-azaindole 3-1 (5 g, 42.3 mmol) in THF (50 mL) was added to a suspension of NaH (60% in mineral oil, 2 g, 50.8 mmol) in THF (50 mL) at 0C over 30 minutes. The resulting reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The reaction mixture was again cooled to 0C, and benzenesulfonyl chloride (6.5 mL, 50.8 mmol) was added thereto over a period of 10 minutes, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with saturated NH4C1 solution (25 mL) and ethyl acetate (50 mL) . The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (25 mL x 3) . The combined organic layers were washed with brine (50 mL) , dried over anhydrous Na2SC>4, and concentrated under reduced pressure to give the crude product 3-2 (10.5 g, 96%) which was used for next step without purification; LCMS: m/z 259.1 [M + 1] .
		Step I: 1-(benzenesulfonyl)pyrrolo[3,2-c]pyridine (3-2) A solution of 5-azaindole 3-1 (5 g, 42.3 mmol) in THF (50 mL) was added to a suspension of NaH (60% in mineral oil, 2 g, 50.8 mmol) in THF (50 mL) at 0 C. over 30 minutes. The resulting reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. The reaction mixture was again cooled to 0 C., and benzenesulfonyl chloride (6.5 mL, 50.8 mmol) was added thereto over a period of 10 minutes, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with saturated NH4Cl solution (25 mL) and ethyl acetate (50 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (25 mL*3). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude product 3-2 (10.5 g, 96%) which was used for next step without purification; LCMS: m/z 259.1 [M++1].

Reference： [1]Synthesis,2005,p. 3581 - 3588
[2]Patent: WO2017/23987,2017,A1 .Location in patent: Paragraph 0675; 0676
[3]Patent: WO2017/24003,2017,A1 .Location in patent: Paragraph 0675; 0676
[4]Patent: WO2017/24010,2017,A1 .Location in patent: Paragraph 0622; 0623
[5]Patent: WO2017/23984,2017,A1 .Location in patent: Paragraph 0675
[6]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[7]Patent: WO2015/88045,2015,A1 .Location in patent: Paragraph 0339; 0340
[8]Patent: US2017/8885,2017,A1 .Location in patent: Paragraph 0741-0742

4
[ 271-34-1 ]
[ 134682-57-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With bromine; tert-butyl alcohol; In water; at 20℃; for 0.333333h;pH Ca.1;	Step 1: synthesis of 3,3,7-tribromo- 1 ,3-dihydro-2H-pyrrolo [3,2-cj pyridin-2-one(intermediate 1 la)Br2 (26m1, 5O7mmol, 4eq.) was added dropwise to a solution of 1H-pyrrolo[3,2-c]pyridine (15g, l27mmol, leq.) in H20 (500m1) and t-BuOH (500m1) at roomtemperature over a period of 20 mm. Following addition of Br2, the pH of the mixturewas approximately 1. Saturated NaHCO3 solution (800 ml) was added slowly and carefully over 30 mm, and the pH of the mixture was adjusted to 6.5-7. The mixture was stirred for 1 h, then filtered off. The resulting solid was further washed with water and co-evaporated with ethanol to give 28.5 g (61% yield) of 3,3,7-tribromo-1,3-dihydro-2H-pyrrolo [3 ,2-c]pyridin-2-one 11 a.

Reference： [1]Heterocycles,2014,vol. 89,p. 1923 - 1932
[2]Journal of Organic Chemistry,1991,vol. 56,p. 4805 - 4806
[3]Patent: WO2014/60411,2014,A1 .Location in patent: Page/Page column 45; 46

5
[ 148760-47-8 ]
[ 271-34-1 ]

Reference： [1]Tetrahedron,1993,vol. 49,p. 2885 - 2914

6
[ 123367-22-6 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrogen;Raney nickel; In ethanol; water; at 20 - 40℃; under 750.075 Torr; for 5.25h;	Step 2: 1H-pyrrole[3,2-c]pyridine 2.1 g (10 mmol) (E)-3-(2-(dimethylamino)vinyl)-4-nitropyridine-1-oxide in 25 mL EtOH were mixed with 3.2 g Raney nickel (50% in water) and hydrogenated in a 1 bar hydrogen atmosphere first of all for 3 h 15 min at RT and then for 2 h at 40 C. The catalyst was removed by suction filtering and the filtrate was purified with activated charcoal. Further purification was carried out by flash chromatography. Yield: 0.90 g (76% of theoretical) EI-MS: m/z=118 (M)+ Rf: 0.5 (silica gel, DCM/MeOH 2:3)
44%	With hydrogen;palladium 10% on activated carbon; In methanol; for 2h;	Step d: Synthesis of 1H-pyrrolo[3,2-c]pyridineTo a suspension of (E)-/V,/V-dimethyl-2-(4-nitro-1 -oxidopyridin-3- yl)ethenamine (400 mg, Step c) in methanol was added palladium on carbon (50 mg, 10% wet) and the reaction mixture was stirred under hydrogen atmosphere for 2 hours. The reaction mixture was filtered through celite and the filtrate was concentrated to get 1 /-/-pyrrolo[3,2-c]pyridine (98 mg, 44%) as off-white solid.1H NMR (400 MHz, DMSO-c/6): δ 8.83 (s, 1 H) and 1 1 .50 (br. s., 1 H), 8.15 (d, J=5.71 Hz, 1 H), 7.29-7.56 (m, 2H), 6.55-6.59 (m, 1 H).
44%	With palladium on activated charcoal; hydrogen; In methanol; for 2h;	To a suspension of (E)-N,N-dimethyl-2-(4-nitro-1-oxidopyridin-3-yl)ethenamine (400 mg, Step c) in methanol was added palladium on carbon (50 mg, 10% wet) and the reaction mixture was stirred under hydrogen atmosphere for 2 hours. The reaction mixture was filtered through celite and the filtrate was concentrated to get 1H-pyrrolo[3,2-c]pyridine (98 mg, 44%) as off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.83 (s, 1H) and 11.50 (br. s., 1H), 8.15 (d, J=5.71 Hz, 1H), 7.29-7.56 (m, 2H), 6.55-6.59 (m, 1H).

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 6369 - 6381
[2]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[3]Patent: US2011/21500,2011,A1 .Location in patent: Page/Page column 47-48
[4]Organic Letters,2009,vol. 11,p. 1357 - 1360
[5]Patent: WO2012/160464,2012,A1 .Location in patent: Page/Page column 72
[6]Patent: US2014/155398,2014,A1 .Location in patent: Paragraph 0435
[7]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 977 - 982
[8]Heterocycles,2014,vol. 89,p. 1923 - 1932

7
[ 148760-46-7 ]
[ 271-34-1 ]

Reference： [1]Tetrahedron,1993,vol. 49,p. 2885 - 2914

8
[ 146336-80-3 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
1.9 g	With hydrogenchloride; In methanol; water; for 5h;Inert atmosphere; Reflux;	Step 1. A solution of 45 (5.18 g, 24.09 mmol), (Z)-tributyl(2-ethoxyvinyl)stannane (9.65 mL, 28.90 mmol) and TBAC (6.69 g, 24.09 mmol) were degassed in CH3CN (100 mL) for 2 h. Hereafter, Pd(PPh3)2Cl2 (0.51 g, 0.72 mmol) was added and the mixture was heated to reflux temperature. After 2.5 h, the crude mixture was concentrated in vacuo, dissolved in CH2Cl2 and magnetically stirred for 2 h in the presence of a 10% KF solution. The resulting suspension was successively filtered over Hyflo Super Cel medium (calcined), extracted with CH2Cl2, concentrated in vacuo and purified using column chromatography (CH2Cl2/MeOH/NH4OH, 960:37.5:2.5) giving 6.20 g (∼80% purity) of intermediate (Z)-N-(3-(2-ethoxyvinyl)pyridin-4-yl)acetamide, which was immediately used in the next step.CommentStep 2. Intermediate (Z)-N-(3-(2-ethoxyvinyl)pyridin-4-yl)acetamide (6.20 g, 24.05 mmol) was dissolved in MeOH (50 mL), 5 mL concentrated HCl was added and the resulting mixture was heated to reflux temperature for 5 h. Hereafter, the crude mixture was concentrated in vacuo, basified with K2CO3 (15 g in 100 mL H2O) and extracted with CH2Cl2. Column chromatography (CH2Cl2/MeOH/NH4OH, 920:75.5:5) afforded 38 (1.90 g, 67% yield). 1H NMR (400 MHz, CDCl3) δ 11.07 (br s, 1H), 8.99 (d, J = 0.8 Hz, 1H), 8.30 (d, J = 5.8 Hz, 1H), 7.35 (dd, J = 9.2, 4.5 Hz, 2H), 6.67 (dd, J = 3.2, 0.8 Hz, 1H).

Reference： [1]Heterocycles,1992,vol. 34,p. 2379 - 2384
[2]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5086 - 5098

9
[ 60290-21-3 ]
[ 271-34-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,1992,vol. 29,p. 359 - 367

10
[ 271-34-1 ]
[ 23612-36-4 ]

Yield	Reaction Conditions	Operation in experiment
70%		Example 1 3-bromo-5-azaindole[00145] Referring now to the Scheme 1 as shown in Fig. 1 , a solution of 3.0128g(25.51 mmol) of 5-azaindole (Atlantic SciTech Group) in 50 ml. of acetonitrile was placed in a 250 ml. three-neck round-bottom flask equipped with a magnetic stirrer, thermocouple, nitrogen bleed, and cooling ice bath. A total of 17.1Og (76.53 mmol, 3 eg.) of solid CuBr2 was added portion-wise to the flask at 17C in 10 min. The resulting green suspension was stirred at room temperature until no starting material was observed by TLC (approximately 1-2 hours, Rf = 0.23 for 5-azaindole and 0.49 for 3- bromo-5-azaindole in EtOAc/MeOH=9:1 ). The reaction mixture was cooled to 10C and then was slowly quenched by addition of IN ammonia in methanol solution (1 1OmL). The resulting blue solution was concentrated on rotavap at room temperature, and the residue was extracted with ethyl acetate (3 x 80 ml_). The organic extract was dried over Na2SO4, filtered, and concentrated to residual volume of about 50 ml_. The temperature of the residue was brought to reflux resulting in the dissolving of all solids, and then hexane was added to the hot mixture until crystallization occured. The resulting suspension was cooled on an ice bath, the product was filtered, washed with cold EtOAc/hexane = 1 :3 and then hexane, and dried. The 3-bromo-5-azaindole was an off- white solid, yield 3.52 g (70% yield).
32%	With copper(ll) bromide; In acetonitrile; for 1.5h;	5-Azaindole (118 mg, 1.00 mmol) and copper(II) bromide (669 mg, 3.00 mmol) were mixed with MeCN (10 mL) and stirred for 1.5 h. To the mixture was added 2 M ammonia in MeOH (12 mL) and the resulting suspension was added to water (40 mL) and extracted with EtOAc (2 x 60 mL). The organic layers were combined and washed with brine and evaporated to yield the title compound (190 mg, 32%). MS (ESI+) m/z = 197, 199 (M+H)+.
32%	With copper(ll) bromide; In acetonitrile; at 20℃; for 1.5h;	5-Azaindole (118 mg, 1.00 mmol) and copper(II) bromide (669 mg, 3.00 mmol) were mixed with MeCN (10 mL) and stirred for 1.5 h. To the mixture was added 2 M ammonia in MeOH (12 mL) and the resulting suspension was added to water (40 mL) and extracted with EtOAc (2*60 mL). The organic layers were combined and washed with brine and evaporated to yield the title compound (190 mg, 32%). MS (ESI+) m/z=197, 199 (M+H)+.

Reference： [1]Synlett,2007,p. 211 - 214
[2]Patent: WO2010/33981,2010,A2 .Location in patent: Page/Page column 27-28
[3]Patent: WO2011/113798,2011,A2 .Location in patent: Page/Page column 35
[4]Patent: US2013/102587,2013,A1 .Location in patent: Paragraph 0181; 0182
[5]Journal of Medicinal Chemistry,1997,vol. 40,p. 2430 - 2433

11
[ 271-34-1 ]
[ 877060-47-4 ]

Yield	Reaction Conditions	Operation in experiment
83%		To a solution of lH-pyrrolo[3,2-c]pyridine (5.76 g, 48.8 mmol , 1.0 eq) in DMF (30 mL) was added KOH (10.39 g, 185.5 mmol , 3.8 eq). The reaction mixture was stirred at rt for 15 min. The reaction mixture was cooled to 0 C and a solution of 12 (12.4 g, 48.8 mmol, 1.0 eq ) in DMF ( 15 mL ) was added. After stirring for 15 min at rt, the reaction mixture was poured into water. The mixture was filtered and the solid was rinsed with water. The yellow solid was dried in vacuo to give 3-iodo-lH-pyrrolo[3,2-c]pyridine (9.9 g , 83%).

Reference： [1]Synthesis,2005,p. 3581 - 3588
[2]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2056 - 2060
[3]Patent: WO2018/11628,2018,A1 .Location in patent: Paragraph 00308
[4]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5129 - 5136

12
[ 109-04-6 ]
[ 271-34-1 ]
C₁₂H₉N₃ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4831 - 4833

13
[ 271-34-1 ]
[ 5332-24-1 ]
C₁₆H₁₁N₃ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4831 - 4833

14
[ 271-34-1 ]
[ 696-62-8 ]
1-(4-methoxyphenyl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In toluene; at 115℃; for 22h;Inert atmosphere; Sealed tube;	Step (a): lH-pyrrolo[3,2-c]pyridine (500 mg, 4.23 mmol), 2.1 eq Potassium phosphate (1887 mg, 8.89 mmol), Copper(I) iodide (161.20 mg, 0.85 mmol), N, N'-dimethyl ethylenediamine (0.90 mg, 8.46 mmol) and 4-iodoanisole (1485.77 mg, 6.35 mmol) were mixed in toluene (10 ml). The vial was flushed with N2 and sealed. The mixture was stirred at 115 C for 22 h. The reaction mixture was cooled to rt, water was added and the mixture was extracted with EtOAc. The combined organic layers were washed with NH4C1 (sat. aq). The crude product was filtered through a plug of silica to give l-(4-methoxyphenyl)-lH- pyrrolo[3,2-c]pyridine (820 mg).

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4831 - 4833
[2]Patent: WO2011/42474,2011,A1 .Location in patent: Page/Page column 33

15
[ 271-34-1 ]
[ 637-87-6 ]
C₁₃H₉ClN₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4831 - 4833

16
[ 271-34-1 ]
[ 1829-28-3 ]
C₁₆H₁₄N₂O₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 4831 - 4833

17
[ 271-34-1 ]
[ 79099-07-3 ]
tert-butyl 4-(1H-pyrrolo[3,2-c]pyridin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
350 mg	With potassium hydroxide; In methanol;Reflux;	To a mixture of lH-pyrrolo[3,2-c]pyridine (CAS 271-34-1) (180 mg, 1.5 mmol) and tert- butyl 4-oxopiperidine-l-carboxylate (607 mg, 3 mmol) in MeOH (5 ml) was added potassium hydroxide (342 mg, 6.1 mmol) and the mixture was heated to reflux overnight. More tert-butyl 4-oxopiperidine-l-carboxylate (155 mg) was added and the reaction mixture was again heated to reflux overnight. The reaction mixture was poured on ice water and was extracted with DCM. The combined extracts were dried with Na2S04 and evaporated. The remaining residue was triturated with MeOH and filtered. The filtrate was evaporated and the remaining oil was purified by column chromatography (50 g silica gel; DCM / MeOH 98:2 - 90: 10) to obtain tert-butyl 4-(lH-pyrrolo[3,2-c]pyridin-3-yl)-3,6- dihydro-2H-pyridine-l-carboxylate (350 mg) as light orange solid. MS (ESI): 298.5 (M-H)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5525 - 5528
[2]Patent: WO2016/87352,2016,A1 .Location in patent: Page/Page column 68-69

18
[ 271-34-1 ]
[ 877060-48-5 ]

Reference： [1]Synthesis,2005,p. 3581 - 3588
[2]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5129 - 5136

19
[ 1074-98-2 ]
[ 271-34-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 977 - 982
[2]Chemistry - A European Journal,2011,vol. 17,p. 6369 - 6381
[3]Journal of Medicinal Chemistry,2012,vol. 55,p. 9531 - 9540
[4]Patent: WO2012/160464,2012,A1
[5]Patent: US2014/155398,2014,A1
[6]Heterocycles,2014,vol. 89,p. 1923 - 1932

20
[ 271-34-1 ]
[ 192189-16-5 ]

Reference： [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 2430 - 2433
[2]Patent: WO2011/113798,2011,A2
[3]Patent: US2013/102587,2013,A1

21
[ 1678-53-1 ]
[ 271-34-1 ]

Reference： [1]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[2]Journal of Organic Chemistry,1959,vol. 24,p. 1008,1010

22
[ 1074-98-2 ]
zinc [ No CAS ]
[ 271-34-1 ]

Reference： [1]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[2]Tetrahedron,1993,vol. 49,p. 2885 - 2914
[3]Tetrahedron,1993,vol. 49,p. 2885 - 2914

23
[ 271-34-1 ]
[ 134682-54-5 ]

Reference： [1]Journal of Organic Chemistry,1991,vol. 56,p. 4805 - 4806
[2]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5970 - 5977
[3]Heterocycles,2014,vol. 89,p. 1923 - 1932

24
[ 1990-90-5 ]
[ 271-34-1 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 1008,1010
[2]Patent: CN109456322,2019,A

25
[ 271-34-1 ]
[ 610276-37-4 ]
2-(2-fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 100℃; for 0.5h;	4-CHLORO-2- (2-FLUORO-PHENYL)-QUINAZOLINE from Step C (0. LG, 0.38mmol) was dissolved in N, N- , DIMETHYLFORMAMIDE (1ML) and to it was added lH-pyrrolo [3,2- c] pyridine (0.046g, 0.38mmol) followed by cesium carbonate (0.134g, 0.41mmol). The mixture was magnetically stirred and heated TOLO0C for 0.5hr. The solvent was removed and title compound was obtained pure after column purification on a HPLC reverse phase column, using a water and acetonitrile gradient containing 0. 1% trifluoroacetic acid to yield (0.072g, 56%). MS (ES) 340.1 (M+H) +

Reference： [1]Patent: WO2004/81009,2004,A1 .Location in patent: Page 45

26
[ 271-34-1 ]
[ 760947-12-4 ]
[ 760946-13-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h;	6-Bromo-4-chloro-2-(2-fluoro-phenyl)-quinazoline from Step D (LG, 2.9mmol) was dissolved in N., N-dimethyl formamide (3ML) and to it was added 1H-Pyrrolo [3,2- c] pyridine (0.346g, 2.9mmol) followed by cesium carbonate (0.961g, 2.9mmol). The mixture was magnetically stirred at room temperature for lhr. Water was added and the product filtered to yield title compound (1.236g, 98%). MS (ES) 420 (M+H) +

Reference： [1]Patent: WO2004/81009,2004,A1 .Location in patent: Page 48-49

27
[ 148760-75-2 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With trifluoroacetic acid; In dichloromethane; at 20℃; for 1.5h;	To a solution of 4-aminopyridine (1a, 37.65 g, 0.4 mole) in HOAc (200 mL) was added iodine monchloride (130 g, 0.8 mole) portionwise. The reaction mixture was stirred at 45 C. for 20 h, then diluted with water (500 mL). The mixture was cooled to 0 C., and basified 30% NaOH to pH=9-10. The solution was extracted with EtOAc (1 L×2) and the combined extracts were washed with 15% Na2S2O3 (400 mL×2), water, brine, dried over Na2SO4, and evaporated in vacuo to give 1b (62 g) as a light yellow solid. ES-MS m/z 221 (MH+). [0185] Into a pressure flask was added 1b (4.4 g, 20 mmol), cupric iodide (228 mg, 1.2 mmol), (trimethylsilyl)acetylene (7.08 g, 72 mmol), triethylamine (200 mL) and DMF (80 mL). The mixture was stirred under nitrogen for 10 min, followed by addition of Pd(PPh3)2Cl2 (0.84 g, 1.2 mmol). The mixture was then stirred to 70 C. for 5 h, and then diluted with ethyl acetate (600 mL). The solution was washed with H2O (250 mL×2), brine (250 mL), dried over Na2SO4, and evaporated in vacuo to give crude product which was purified by flash chromatography (100% CH2Cl2 to 2% MeOH in CH2Cl2) to afford Compound 1c (2. 97 g, 78%) as a light brown solid. 1H NMR (CDCl3) delta 8.37 (s, 1H), 8.13 (d, J=5.7 Hz, 1H), 6.53 (d, J=5.6 Hz, 1H), 4.67 (bs, 2H), 0.27 (s, 9H). ES-MS m/z 191 (MH+). [0186] Into an ice-cold solution of 1c (1.35 g, 7.1 mmol) in THF (50 mL) was added 95% NaH (1.86 g, 8.5 mmol). The mixture was stirred at 0 C. for 10 min, rt for 10 min, then cooled back to 0 C. (Boc)2O (1.86 g, 8.5 mmol) was added and the mixture was stirred at 0 C. for 30 min and then rt for 2 h. Additional 95% NaH (0.08 g, 3.5 mmol) and (Boc)2O (0.2 g, 0.92 mmol) were added and the mixture was stirred at rt for another 2 h. The reaction was then quenched slowly with saturated NaHCO3 (10 mL), extracted with ethyl acetate (200 mL×2). The organic layer was washed with brine, dried over Na2SO4, and evaporated in vacuo. The crude product was purified by flash chromatography (EtOAc/hexane; 1:3) to give 1d (0.67 g). ES-MS m/z 219 (MH+). [0187] To a solution of 1d (1.3 g, 4.5 mmol) in DMF (20 mL) was added cupric iodide (0.85 g, 4.5 mmol). The mixture was stirred at 80 C. for 6 h and then filtered. The filtrate was extracted with ethyl acetate (100 mL×3), and the organic layer was washed with H2O, brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (Ethyl acetate/hexane; 1:3) to give Compound 1e (0.25 g, 26%). 1H NMR (CDCl3) delta 8.89 (s, 1H), 8.47 (d, J=5.8 Hz, 1H), 7.98 (d, J=5.7 Hz, 1H), 7.62 (d, J=3.7 Hz, 1H), 6.66 (d, J=3.7 Hz, 1H), 1.69 (s, 9H). ES-MS m/z 219 (MH+). [0188] To a solution of 1e (0.178 g, 0.82 mmol) in methylene chloride (5 mL) was added TFA (1.0 mL) slowly. The mixture was stirred at rt for 1.5 h, and The solvent was evaporated to obtain 5-azaindole 1f as a white solid (0.18 g, 95%). 1H NMR (CDCl3) delta 8.97 (s, 1H), 8.31 (d, J=5.7 Hz, 1H), 7.35 (d, J=5.7 Hz, 1H), 7.29 (m, 1H), 6.68 (d, J=3.3 Hz, 1H). ES-MS m/z 119 (MH+). [0189] A mixture of Compound 1f (0.26 g, 2.2 mmol) and cesium carbonate (1.43 g, 4.4 mmol) in DMF (10 mL) was stirred at rt for 10 min, and then 3-methoxypropylbromide (0.40 g, 2.64 mmol) was added. The reaction mixture was stirred at 60 C. for 3 h. The solvent was evaporated and the residue was partitioned between EtOAc (150 mL) and water (100 mL). The organic layer was washed with water (3×50 mL), brine (2×50 mL), then dried (Na2SO4) and evaporated in vacuo to give a brown oil. The crude product was purified by flash column chromatography (from 100% DCM to DCM/MeOH/NH4OH; 97:3:0.3) to afford Compound 1g (0.26 g, 62%) as light brown oil. 1H NMR (CDCl3) delta 8.91 (s, 1H), 8.31 (d, J=5.8 Hz, 1H), 7.27 (s, 1H), 7.11 (d, J=3.2 Hz, 1H), 6.60 (d, J=3.3 Hz, 1H), 4.25 (t, J=6.7 Hz, 2H), 3.32 (s, 3H), 3.25 (t, J=5.7 Hz, 2H), 2.05 (m, 2H). ES-MS m/z 191(MH+). [0190] Oxalyl chloride (3 mL) was added slowly to a solution of compound 1g (0.22 g, 1.14 mmol) in ether (5 mL). The mixture was heated to 48 C. in a pressure tube overnight. TLC shown that some starting materials were still present. Additional 0.5 mL of oxalyl chloride was added and stirring was continuted at 48 C. for another night. The mixture was then cooled down to rt, to which methanol (3 mL) was added. The mixture was heated to 48 C. and stirred for 2 h. The volatiles removed under vacuo and the residue was purified by flash chromatography (from 100% DCM to DCM/MeOH/NH4OH; 97:3:0.3) to afford Compound 1h (0.15 g, 48%) as a white solid. 1H NMR (CDCl3) delta 8.51 (d, J=5.8 Hz, 1H), 8.44 (s, 1H), 7.37 (m, 1H), 4.34 (t, J=6.8 Hz, 2H), 3.97 (s, 3H), 3.35 (s, 3H), 3.30 (t, J=5.7 Hz, 2H), 2.12 (m, 2H). ES-MS m/z 277 (MH+). [0191] The alpha-ketoester Compound 1h (53.8 mg, 0.20 mmol) and amide Compound 1i (23 mg, 0.14 mmol) were combined in dry THF (3 mL) under argon and cooled with an ice bath as a solution of 1.0 M potassium t-butoxide in THF (1 mL, 1 mmol) was added dropwise. The mixture was stirred at 0 C. for 30 ...

Reference： [1]Patent: US2004/192718,2004,A1 .Location in patent: Page 15-17

28
[ 271-34-1 ]
[ 275359-69-8 ]
[ 325975-32-4 ]

Yield	Reaction Conditions	Operation in experiment
51.6%	With pyrrolidine; In ethanol; for 6h;Heating / reflux;	Example 1 3-(1,2,3,5,8,8a-Hexahydro-7-indolizinyl)-1H-<strong>[271-34-1]5-azaindole</strong> A mixture of <strong>[271-34-1]5-azaindole</strong> (0.5 g, 4.23 mmol), 1,2,3,5,6,8,8a-heptahydrohydro-7-oxo-indolizine (589 mg, 4.23 mmol) and pyrrolidine (3.0 g, 42.3 mmol) in ethanol (4 ML) were heated to reflux for 6 hrs.. The reaction mixture was cooled, filtered, and the collected solid washed with ether to give 3-(1,2,3,5,8,8a-hexahydro-7-indolizinyl)-1H-5-Azaindole (0.521 g, 51.6%).

Reference： [1]Patent: US6686374,2004,B1 .Location in patent: Page column 17-18

29
[ 271-34-1 ]
[ 234108-65-7 ]
[ 234099-14-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	The reactin mixture is partitioned between water and methylene chloride; the organic layer is concentrated and the residue is chromatographed (15% EtOAc/methylene chloride) to give 4-(benzyloxycarbonyl)-1-(2-iodoethyl)-piperazin-2-one (0.24 g, 0.62 mmol). pyrrolo[3,2-c]pyridine (0.073 g, g, 0.62 mmol) is dissolved in DMF (3 ML) and treated with 60% sodium hydride (0.03 g, 0.74 mmol) and all of the 4-(benzyloxycarbonyl)-1-(2-iodoethyl)-piperazin-2-one from the previous step; the reaction mixture is stirred at r.t. for 16 g.The reaction mixture is concentrated to dryness and the residue is partitioned between water and methylene chloride.The organic layer is concentrated and subjected to chromatography (2-5% MeOH/methylene chloride) to yield the title compound (0.028 g, 0.074 mmol) Ion Spray MS m/z: 379, [M+1]+.

Reference： [1]Patent: US2004/102450,2004,A1 .Location in patent: Page/Page column 92

30
[ 271-34-1 ]
[ 506-59-2 ]
N,N-dimethyl-1-(1H-pyrrolo[3,2-c]pyridin-3-yl)methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With paraformaldehyde; In butan-1-ol;	Step 3. Preparation of N,N-Dimethyl-(1H-pyrrolo[3,2-c]-pyridin-3-yl)methylamine A solution of <strong>[271-34-1]5-azaindole</strong>(1.19 g, 10.0 mmol), dimethylamine hydrochloride (0.98 g, 12.0 mmol) and paraformaldehyde (0.36 g, 12.0 mmol-equivalents) in 1-butanol is heated at reflux temperature for 5 h and concentrated in vacuo. The concentrate is diluted with saturated aqueous NaHCO3 and extracted with 4:1 CH2Cl2:ethanol. The combined extracts are dried over MgSO4, concentrated in vacuo and filtered. The filtercake is air-dried to afford the title compound as a yellow solid, 0.680 g (39% yield), identified by NMR analysis.

Reference： [1]Patent: US2003/171395,2003,A1

31
[ 765307-12-8 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(I) iodide; In N,N-dimethyl-formamide;	Step 5. Preparation of 5-Azaindole A solution of [(3-trimethylsilanyl)ethynyl]pyridin-4-yl}amine in DMF is treated with cuprous iodide (2 eq.), stirred at reflux temperature for 2 h, cooled to room temperature, diluted with EtOAc, filtered through celite and concentrated in vacuo. The residue is purified by flash chromatography (silica gel, EtOAc/hexane as eluent) to afford the title 5-azaindole compound.

Reference： [1]Patent: US2003/171395,2003,A1

32
[ 1074-98-2 ]
[ 1188-33-6 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; ammonium formate;palladium; In ethanol; water; N,N-dimethyl-formamide; toluene; benzene;	3-Methyl-4-nitro-pyridine-N-oxide (5.34 g, 34.7 mmol, 1 equiv.) and N,N-dimethylformamide diethyl acetal (10.5 mL, 61.4 mmol, 1.8 equiv.) were combined in 50 mL anhydrous DMF and heated to 120 C. for 3 h. The reaction was allowed to cool back to room temperature and the DMF solvent was removed in vacuo. The residue was treated with ~80 mL toluene, which was then removed in vacuo as well. Finally the residue was mixed with benzene and filtered. The desired vinyl amine was obtained as a dark purple solid (6.74 g, 32.2 mmol, 93%), which was used as is in the next step. The vinyl amine from above (3.37 g, 16.1 mmol, 1 equiv.) and 1.75 mL of water were mixed in 50 mL EtOH. Ammonium formate (4.56 g, 72.5 mmol) and 10% palladium-on-carbon (600 mg) were added and the mixture was heated to a gentle reflux for 1 h. TLC and MS (ES+) revealed no starting material but showed the presence of two major components, the desired 5-aza-indole and its N-oxide. The reaction was left stirring for a further 2 h after more ammonium formate and more palladium catalyst were added. Finally the reaction was cooled to room temperature, filtered and solvents removed in vacuo. 5% NaOH aqueous solution was added and the mixture was extracted with EtOAc. The combined organics were dried (MgSO4), filtered, and the solvent was removed in vacuo, providing 0.555 g of desired 5-aza-indole (4.70 mmol, 29% yield).

Reference： [1]Patent: US2003/162968,2003,A1

33
[ 271-34-1 ]
1,5-diazainden-2-one hydrobromide [ No CAS ]
[ 1678-49-5 ]
[ 36805-97-7 ]
3-dimethylamino-methylene-1,5-diazainden-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	a 3-Dimethylamino-methylene-1,5-diazainden-2-one 3-Bromo-4-nitropyridine-1-oxide was prepared according to the procedure of Daisley and Hanbali (Org. Prep. Proced. Int. 1983, 15, 280) and converted to 1,5-diazaindene via the method of Sakamoto et. al. (Heterocycles 1992, 34, 2379). 1,5-Diazaindene was subsequently converted to 1,5-diazainden-2-one hydrobromide via the procedure out lined by Robinson and Donahue (J. Org. Chem. 1991, 56, 4805) and reaction of this with N,N-dimethylformamide-di-t-butyl acetal in DMF gave 3-dimethylamino-methylene-1,5-diazainden-2-one (as described for the preparation of 3-dimethylamino-methylene-1,6-diazainden-2-one): 1H NMR (DMSO-d6): δ3.35 (s, 6H), 7.13 (d, J=6.1 Hz, 1H), 8.09 (s, 1H), 8.20 (d, J=6.1 Hz, 1H), 8.57 (s, 1H), 11.50 (s, 1H); C10H11N3O: APES+MS: m/z 190 (M+H).

Reference： [1]Patent: US6369086,2002,B1

34
[ 271-34-1 ]
[ 13360-57-1 ]
sodium chloride [ No CAS ]
[ 125362-24-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogen sulfate; In dichloromethane;	(a) 1-dimethylaminosulfonyl 5-aza indole 3.84 g (0.032 mole) of 5-aza indole, 3.2 g (0.08 mole) of powdered sodium hydroxide and 0.12 g (3.6*10 mole) of tetrabutylammonium hydrogen sulfate as phase transfer catalyst are placed in 100 ml of dichloromethane and then the solution is stirred vigorously. 5 ml (0.048 mole) of dimethylaminosulfonyl chloride are then added and a rise in temperature from 20 to 40 C. is recorded. Stirring is continued for 1 hour after the end of the addition. Excess sodium hydroxide and the sodium chloride formed are then filtered off and the filtrate is washed with water until the pH=7-8. After drying over magnesium sulfate and partial decolorization with active charcoal, the solvent is removed under reduced pressure. A brown residue is thus obtained which is purified by chromatography on silica to give 6.1 g of 1-dimethylaminosulfonyl 5-aza indole in the form of a pale yellow solid. Yield: 83%. M.p.: 87 C. NMR spectrum (CDCl3): 2.8 ppm (s,6H); 6.7 ppm (d,1H); 7.45 ppm (d,1H); 7.8 ppm (d,1H); 8.4 ppm (d,1H); 8.9 ppm (s,1H).

Reference： [1]Patent: US5079363,1992,A

35
raney's nickel [ No CAS ]
3-(β-dimethylaminovinyl)-4-nitro-pyridine-1-oxide [ No CAS ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol; water;	(b) 1H-Pyrrolo-[3,2-c]-pyridine In a PARR apparatus, working at atmospheric pressure were placed 2.1 g (0.01 mol) of 3-(β-dimethylaminovinyl)-4-nitro-pyridine-1-oxide, 3.15 g of Raney's nickel (at 50% in water) and 25 ml of ethanol. The mixture was vigorously stirred at room-temperature for 14 h and then at 60 C. until absorption of hydrogen ceased. The catalyst was suction-filtered on Celite (a commercially available diatomaceous product, the word Celite being a registered Trade Mark) and washed several times with ethanol. The ethanol solution was discoloured by means of active charcoal, concentrated under vacuum and rapidly filtered on silica. After evaporating the solvent, 0.98 g of 1H-pyrrolo-[3,2-c]-pyridine was obtained in the form of yellowish white crystals. Yield: 84%. M.P.: 110-122 C.

Reference： [1]Patent: US4625033,1986,A

36
[ 123-75-1 ]
[ 271-34-1 ]
[ 275359-69-8 ]
[ 325975-32-4 ]

Yield	Reaction Conditions	Operation in experiment
51.6%	In ethanol;	Example 1 3-(1,2,3,5,8,8a-Hexahydro-7-indolizinyl)-1H-<strong>[271-34-1]5-azaindole</strong> A mixture of <strong>[271-34-1]5-azaindole</strong> (0.5 g, 4.23 mmol), 1,2,3,5,6,8,8a-heptahydrohydro-7-oxo-indolizine (589 mg, 4.23 mmol) and pyrrolidine (3.0 g, 42.3 mmol) in ethanol (4 mL) were heated to reflux for 6 hrs. The reaction mixture was cooled, filtered, and the collected solid washed with ether to give 3-(1,2,3,5,8,8a-hexahydro-7-indolizinyl)-1H-5-Azaindole (0.521 g, 51.6%).

Reference： [1]Patent: US6191141,2001,B1

37
[ 271-34-1 ]
[ 610-14-0 ]
[ 1056249-03-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4344 - 4347

38
[ 271-34-1 ]
[ 77-78-1 ]
[ 24331-97-3 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 1357 - 1360

39
[ 271-34-1 ]
[ 591-50-4 ]
[ 23596-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;copper(l) iodide; (S,S)-1,2-diaminocyclohexane; In 1,4-dioxane; at 110℃;	To a mixture of <strong>[271-34-1]5-azaindole</strong> (780 mg, 6.60 mmol), copper(l) iodide (25.1 mg, 132 μmol), (1S,2S)-(+)-1 ,2-diaminocyclohexane (162 μl, 1.35 mmol) and potassium phosphate (2.52 g, 11.9 mmol) in dioxane (24 ml) was added iodobenzene (739 μl, 6.60 mmol). The reaction mixture was stirred overnight at 110 0C. The mixture was then cooled to room temperature, filtered through silica gel, and the silica gel washed with EA. The combined filtrates was evaporated under reduced pressure, and the resulting solid was purified by preparative HPLC. The fractions containing the title compound were combined and lyophilized overnight. Yield: 1.28 g. LC/MS (method LC4): m/z = 195

Reference： [1]Patent: WO2009/95162,2009,A1 .Location in patent: Page/Page column 76
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5487 - 5492

40
[ 271-34-1 ]
[ 119139-17-2 ]
[ 480434-44-4 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution, maintained at ambient temperature, of <strong>[271-34-1]5-azaindole</strong> (7.89 mmol), dissolved in 15 ml of dry toluene, there is added, dropwise, a solution of LiHMDS (1M in hexane) (6.25 mmol). After stirring for 1 hour 15 minutes at ambient temperature, a solution of the product obtained in Step B of Preparation E (3.77 mmol), dissolved in 10 ml of toluene and 15 ml of dichloromethane, is added at ambient temperature. After stirring for 12 hours at ambient temperature, the mixture is extracted with ethyl acetate. The organic phases are combined, dried over magnesium sulphate and filtered. After purification by chromatography on silica gel (petroleum ether/ethyl acetate/triethylamine : 1/1/1% and then ethyl acetate/triethylamine : 9/1), the expected product is isolated. [0184] Melting point: 218 C. decomposition Infra-red (KBr), νCO=1703, 1735 cm-1; νNH=3200-3300 cm1.

Reference： [1]Patent: US2004/152721,2004,A1 .Location in patent: Page 12

41
[ 1239605-12-9 ]
[ 271-34-1 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 7169 - 7178

42
[ 271-34-1 ]
[ 23596-28-3 ]

Yield	Reaction Conditions	Operation in experiment
41%	With hydrogen;Raney nickel; In ethanol; at 70℃; under 2250.23 Torr; for 72h;	Step 3: 2,3-dihydro-1H-pyrrole[3,2-c]pyridine 1.5 g (12.7 mmol) 1H-pyrrole[3,2-c]pyridine in 70 mL EtOH were combined with 0.75 g Raney nickel and hydrogenated for 3 days at 70 C. in a 3 bar hydrogen atmosphere. The catalyst was removed by suction filtering and the filtrate was evaporated down. The residue was purified by flash chromatography. The product-containing fractions were combined and evaporated down. Yield: 0.62 g (41% of theoretical) ESI-MS: m/z=121 (M+H)+ Rf: 0.12 (silica gel, DCM/MeOH/NH4OH 80:20:2)
41%	With hydrogen; In ethanol; at 70℃; under 2250.23 Torr; for 72h;	2,3-dihydro-1H-pyrrolo[3,2-c]pyridine 1.50 g (12.7 mmol) <strong>[271-34-1]5-azaindole</strong> and 0.75 g Raney nickel in 70 mL ethanol were hydrogenated in a hydrogen atmosphere at 3 bar hydrogen pressure for 3 days at 70 C. Then the catalyst was suction filtered and the solution was evaporated down i. vac. The residue was purified through a silica gel column. The product fractions were combined and evaporated down using the rotary evaporator. Yield: 620 mg (41% of theoretical) ESI-MS: m/z=121 (M+H)+

Reference： [1]Patent: US2011/21500,2011,A1 .Location in patent: Page/Page column 48
[2]Patent: US2011/195954,2011,A1 .Location in patent: Page/Page column 90

43
[ 271-34-1 ]
[ 1276040-07-3 ]
[ 1276034-53-7 ]
[ 1276034-70-8 ]

Yield	Reaction Conditions	Operation in experiment
		To NaH (60% dispersion in mineral oil, 7.5 mg, 0.11 mmol) in DMF (2 mL) is added 4- azaindole (6 mg, 0.09 mmol). After stirring for 5 min, 29a1 (40 mg, 0.07 mmol) is added and the resulting solution is stirred 0.5 h at RT. The mixture is acidified with TFA before being injected directly onto a prep. HPLC to separate and isolate 2008 and 2025.

Reference： [1]Patent: WO2011/32277,2011,A1 .Location in patent: Page/Page column 60

44
[ 1003-73-2 ]
[ 271-34-1 ]

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 6369 - 6381
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 9531 - 9540
[3]Patent: WO2012/160464,2012,A1
[4]Patent: US2014/155398,2014,A1
[5]Heterocycles,2014,vol. 89,p. 1923 - 1932

45
[ 271-34-1 ]
[ 1778-74-1 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4752 - 4772

46
[ 271-34-1 ]
[ 50-00-0 ]
[ 506-59-2 ]
N,N-dimethyl-1-(1H-pyrrolo[3,2-c]pyridin-3-yl)methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In butan-1-ol; at 20 - 120℃;	1 /-/-pyrrolo[3,2-c]pyridine (302 mg; 2.56 mmol) in 5 mL of n-butanol was treated with dimethylamine hydrochloride (230 mg; 2.82 mmol) followed by paraformaldehyde (87 mg; 2.90 mmol formaldehyde). The mixture was stirred and heated at 120 C for 3 hr then allowed to cool to room temperature overnight. The resulting mixture was filtered, and the residue was washed with EtOH. The combined filtrates were concentated in vacuo to give a viscous amber liquid that was partitioned between 1.0 M NaOH and DCM. The aqueous phase was further extracted 6 times with DCM. The combined organic extracts were dried (MgS04), filtered, and concentrated in vacuo to give the crude product as a clear nearly colorless resin. The crude product was purified by silica gel column chromatography (ISCO Combiflash Rf, eluted with 0-30% methanol (1 % aq. NH4OH) / DCM) to give 267 mg (60% yield) of A/,//-dimethyl-1-(1/-/-pyrrolo[3,2-c]pyridin-3-yl)methanamine as a clear colorless resin. H NMR (500 MHz, CDCI3): δ 2.32 (s, 6H), 3.70 (s, 2H), 7.19 (s, 1 H), 7.28 (d, J = 6.1 , 1 H), 8.31 (d, J = 6.1 , 1 H), 8.77 (s, br, 1 H), 9.04 (s, 1 H); LCMS calculated for Ci0Hi3N3: m/z = 175; found: m/z = 176 (M+H).

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4752 - 4772
[2]Patent: WO2018/106907,2018,A1 .Location in patent: Paragraph 0211-0213

47
[ 271-34-1 ]
[ 879-18-5 ]
[ 1338925-22-6 ]

Yield	Reaction Conditions	Operation in experiment
11%	With aluminum (III) chloride; In dichloromethane; at 20℃; for 16h;Inert atmosphere;	To a solution of aluminum chloride (0.79 g, 5.93 mmol) in 50 mL CH2Cl2 was added 1-naphthoyl chloride (1.13 g, 5.93 mmol) in 10 mL CH2Cl2 at ambient temperature. After 10 min, intermediate 38 (0.70 g, 5.93 mmol) was added and the mixture was stirred for 16 h at ambient temperature. Hereafter, MeOH was added dropwise, followed by NaOH (2 N). The resulting mixture was extracted with CH2Cl2 ( × 2). The combined organic fractions were concentrated in vacuo and purified by flash column chromatography (CH2Cl2/MeOH/NH4OH, 960:37.5:2.5), giving pure 41 (0.17 g, 11% yield). 1H NMR (400 MHz, CDCl3) δ 11.15 (br s, 1H), 9.81 (d, J = 0.9 Hz, 1H), 8.45 (d, J = 5.8 Hz, 1H), 8.24-8.18 (m, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.89 (dd, J = 7.2, 2.1 Hz, 1H), 7.72 (dd, J = 7.0, 1.0 Hz, 1H), 7.64 (s, 1H), 7.55-7.40 (m, 4H).

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5086 - 5098

48
[ 271-34-1 ]
[ 134682-56-7 ]

Yield	Reaction Conditions	Operation in experiment
65%	With water; bromine; In tert-butyl alcohol; at 20℃; for 1.33333h;	General procedure: To a stirred solution of azaindole (10a or 10b, 12.7 mmol) in tert-butyl alcohol (100 mL) and H2O (100 mL) at room temperature, Br2 (2.6 mL, 50.5 mmol) was added dropwise over 20 min. The mixture was stirred for 1 h and the yellow precipitate (10b, or 11b) was collected by filtration. The dried precipitate (10b, or 11b, 4.8 mmol) was refluxed with 5% Pd-C (1.0 g) in 60 mL of 8.8% HCOOH/CH3OH for 12 h under nitrogen. The catalyst was removed by filtration through a pad of celite. After removal of the solvent, the residual was adjusted to pH 8-9 by addition of saturated K2CO3 solution. The solution was stored in the refrigerator overnight and the precipitate was filtered to give 5-azaindolin-2-one (10) or 7-azaindolin-2-one (11).

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5970 - 5977

49
[ 271-34-1 ]
[ 98-59-9 ]
[ 1279863-30-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide; In water; toluene; at 0 - 10℃; for 2h;Inert atmosphere;	Step 1: Synthesis of l-tosyl-lH-pyrrolo[3,2-c]pyridine (6-b)To a mixture of compound 6-a (CAS 271-34-1) (30 g, 253 mmol), Tos-CI (CAS 98-59- 9) (55.5 g, 291 mmol) and Bu4 HS04 (CAS 2472-88-0) (0.63 g, 1.9 mmol) in toluene(690 mL), a solution of NaOH (CAS 1310-73-2) (132 g, 3300 mmol) in water (690 mL) was added at 0C. The reaction mixture was stirred under nitrogen at 10C for 2 hours. Water (1000 mL) was added, then the mixture was extracted with ethyl acetate(2000 mL x 2). The combined organic layer was washed with brine, dried over Na2S04.The solvent was evaporated under vacuum and the residue was washed with tert- butylmethyl ether. Product 6-b was obtained as an off- white powder (64 g, 93%)

Reference： [1]Patent: WO2012/80450,2012,A1 .Location in patent: Page/Page column 20
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 8859 - 8874

50
[ 271-34-1 ]
[ 1398057-29-8 ]
[ 1398057-10-7 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane;	The reaction can be performed similar to a literature procedure: J. Yin, S. L Buchwald, J. Am. Chem. Soc. 2002, 124, 6043-6048.

Reference： [1]Patent: WO2012/119690,2012,A1 .Location in patent: Page/Page column 59

51
[ 104118-88-9 ]
[ 271-34-1 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 9531 - 9540

52
[ 271-34-1 ]
[ 501-53-1 ]
[ 1426255-11-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	Step a: Synthesis of benzyl 1H-pyrrolo[3,2-c]pyridine-1 -carboxylateTo a stirred solution of i/-/-pyrrolo[3,2-c]pyridine (500 mg, 4.2 mmol) in dichloromethane (6 ml_), triethylamine (1 .2 ml_, 8.4 mmol) was added. The mixture was cooled to 0 C and benzyl chloroformate (1 .6 ml_, 50% solution in dichloromethane, 4.6 mmol) was added drop wise. After complete addition, the reaction mixture was stirred at room temperature for about 1 hour. On completion, the reaction was quenched by addition of saturated aqueous sodium bicarbonate solution and the organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford benzyl 4-amino- 1 /-/-pyrrolo[3,2-c]pyridine-1 -carboxylate (1 g, 100%) as viscous liquid.1H NMR (400 MHz, DMSO-c/6): δ 8.93 (d, J=1 .00 Hz, 1 H), 8.45 (d, J=5.77 Hz, 1 H), 7.56 (dd, J=8.06, 1 .47 Hz, 1 H), 7.97 (d, J=5.71 Hz, 1 H), 7.82 (d, J=3.76 Hz, 1 H), 7.32-7.48 (m, 4H), 6.89 (dd, J=3.76, 0.82 Hz, 1 H), 5.51 (s, 2H).
100%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	To a stirred solution of 1H-pyrrolo[3,2-c]pyridine (500 mg, 4.2 mmol) in dichloromethane (6 mL), triethylamine (1.2 mL, 8.4 mmol) was added. The mixture was cooled to 0 C. and benzyl chloroformate (1.6 mL, 50% solution in dichloromethane, 4.6 mmol) was added drop wise. After complete addition, the reaction mixture was stirred at room temperature for about 1 hour. On completion, the reaction was quenched by addition of saturated aqueous sodium bicarbonate solution and the organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford benzyl 4-amino-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (1 g, 100%) as viscous liquid. 1H NMR (400 MHz, DMSO-d6): δ 8.93 (d, J=1.00 Hz, 1H), 8.45 (d, J=5.77 Hz, 1H), 7.56 (dd, J=8.06, 1.47 Hz, 1H), 7.97 (d, J=5.71 Hz, 1H), 7.82 (d, J=3.76 Hz, 1H), 7.32-7.48 (m, 4H), 6.89 (dd, J=3.76, 0.82 Hz, 1H), 5.51 (s, 2H).

Reference： [1]Patent: WO2012/160464,2012,A1 .Location in patent: Page/Page column 72
[2]Patent: US2014/155398,2014,A1 .Location in patent: Paragraph 0437

53
[ 271-34-1 ]
[ 434-75-3 ]
[ 1415125-05-1 ]

Yield	Reaction Conditions	Operation in experiment
39.5%		Step a: (2-chloro-6-fluorophenyl)( 1H-pyrrolo[3,2-c]pyridin-1 -yl)methanoneTo a stirred solution of <strong>[434-75-3]2-chloro-6-fluorobenzoic acid</strong> (2.5 g, 14.32 mmol) in dichloromethane (20 ml_), oxalyl chloride (3.029 ml, 28.64 mmol) was added at 0 C. After stirring at the same temperature for 15 min, dimethylfromamide (2-3 drops) was added, and the reaction was allowed to stir at room temperature for 1 .5 hours. The reaction mixture was cooled and concentrated on rotary evaporator. The residue was taken up in dichloromethane (20 ml_) and treated with 5-azaindole (1 .72 g, 14.51 mmol) and triethylamine (6.1 ml_, 43.52 mmol). The resulting reaction mixture was allowed to stir at room temperature for 20 hours. The reaction mixture was concentrated under vacuum, diluted with water (50 ml_) and extracted with ethyl acetate (2 x 100 ml_). The combined organic layer was washed with saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was removed under rotary evaporator. The product was isolated by silica gel column chromatography using ethyl acetate (25%) in hexanes as eluent to yield (2-chloro-6-fluorophenyl)(1 H- pyrrolo[3,2-c]pyridin-1 -yl)methanone (1 .56 g, 39.5%).MS (m/z): 274.68 (M+)
39.5%		To a stirred solution of <strong>[434-75-3]2-chloro-6-fluorobenzoic acid</strong> (2.5 g, 14.32 mmol) in dichloromethane (20 mL), oxalyl chloride (3.029 ml, 28.64 mmol) was added at 0 C. After stirring at the same temperature for 15 min, dimethylfromamide (2-3 drops) was added, and the reaction was allowed to stir at room temperature for 1.5 hours. The reaction mixture was cooled and concentrated on rotary evaporator. The residue was taken up in dichloromethane (20 mL) and treated with 5-azaindole (1.72 g, 14.51 mmol) and triethylamine (6.1 mL, 43.52 mmol). The resulting reaction mixture was allowed to stir at room temperature for 20 hours. The reaction mixture was concentrated under vacuum, diluted with water (50 mL) and extracted with ethyl acetate (2*100 mL). The combined organic layer was washed with saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was removed under rotary evaporator. The product was isolated by silica gel column chromatography using ethyl acetate (25%) in hexanes as eluent to yield (2-chloro-6-fluorophenyl)(1H-pyrrolo[3,2-c]pyridin-1-yl)methanone (1.56 g, 39.5%). MS (m/z): 274.68 (M+)

Reference： [1]Patent: WO2012/160464,2012,A1 .Location in patent: Page/Page column 124-125
[2]Patent: US2014/155398,2014,A1 .Location in patent: Paragraph 0757

54
[ 271-34-1 ]
[ 1000342-65-3 ]

Yield	Reaction Conditions	Operation in experiment
40%		Intermediate 44: Synthesis of 3-chloro-1 /-/-pyrrolo[3,2-c]pyridineA solution of 1 /-/-pyrrolo[3,2-c]pyridine (200 mg, 1 .69 mmol) in dichloromethane (10 ml) was treated with /V-chlorosuccinimide (339 mg, 2.5 mmol) and stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane and washed with aqueous sodium hydrogen carbonate solution, brine, dried over anhydrous sodium sulfate and concentrated. Purification from silica gel column chromatography using methanol and dichloromethane gradient afforded 3-chloro-1 H-pyrrolo[3,2-c]pyridine (98 mg, 40%).1H NMR (400 MHz, MeOH-d4): δ 8.75-8.80 (m, 1 H), 8.19-8.24 (m, 1 H), 7.42-7.47 (m, 2H). MS: 152.28 (M+).
40%	With N-chloro-succinimide; In dichloromethane; at 20℃; for 5h;	A solution of 1H-pyrrolo[3,2-c]pyridine (200 mg, 1.69 mmol) in dichloromethane (10 ml) was treated with N-chlorosuccinimide (339 mg, 2.5 mmol) and stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane and washed with aqueous sodium hydrogen carbonate solution, brine, dried over anhydrous sodium sulfate and concentrated. Purification from silica gel column chromatography using methanol and dichloromethane gradient afforded 3-chloro-1H-pyrrolo[3,2-c]pyridine (98 mg, 40%). 1H NMR (400 MHz, MeOH-d4): δ 8.75-8.80 (m, 1H), 8.19-8.24 (m, 1H), 7.42-7.47 (m, 2H). MS: 152.28 (M+).

Reference： [1]Patent: WO2012/160464,2012,A1 .Location in patent: Page/Page column 81
[2]Patent: US2014/155398,2014,A1 .Location in patent: Paragraph 0484; 0486

55
[ 271-34-1 ]
[ 773-64-8 ]
[ 1417718-51-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium hydride; at 0 - 20℃; for 16h;	To a solution of lH-Pyrrolo[3,2-c]pyridine (35 mg, 0.3 mmol) and mesitylsulfonyl chloride (66 mg, 0.3 mmol) in 4 mL of THF was added 60% NaH (16 mg, 0.4 mmol) at 0 C. The resulting mixture was stirred at r.t. for 16 h. The solution was dilutedwith EtOAc (50 mL), washed with 1 N HC1 (aq.) (10 niL) and brine (10 mL). The organic layer was dried over anhydrous Na2S04 and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hexane/EtOAc = 1/1) to give the desired product as a white solid (76 mg, 84%). H NMR (600 MHz, CDC13) δ 8.88 (s, 1H), 8.33 (d, 1H, J = 6.0 Hz), 7.54 (d, 1H, J= 3.6 Hz), 7.29 (d, 1H, J = 5.4 Hz), 6.95 (s, 2H), 6.68 (d, 1H, J = 3.6 Hz), 2.50 (s, 6H), 2.26 (s, 3H). 13C NMR (150 MHz, CDC13) δ 144.8, 144.3, 143.6, 140.4, 139.0, 132.6, 132.3, 127.2, 126.4, 107.6, 105.1, 22.6, 21.1.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 952 - 962
[2]Patent: WO2013/119931,2013,A1 .Location in patent: Paragraph 0194

56
[ 271-34-1 ]
[ 4885-02-3 ]
[ 933717-10-3 ]

Yield	Reaction Conditions	Operation in experiment
0.333 g	With aluminum (III) chloride; In nitromethane; 1,2-dichloro-ethane; at 0℃; for 1h;Inert atmosphere;	To a solution of 1 /-/-pyrrolo[3,2-c]pyridine (0.400 g; 3.386 mmol) in a mixture of 1 ,2- dichloroethane (10 mL) and nitromethane (10 mL) cooled at 0 C under an argon atmosphere were added dichloro(methoxy)methane (1 .544 mL; 16.92 mmol) and aluminum trichloride ( 1 .500 g; 1 1 .25 mmol) over 1 h. After the addition, the reaction was quenched by addition of water and of a saturated sodium bicarbonate solution. The reaction mixture was extracted with a solution of dichloromethane and ethanol (9/1 , 6x100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 0.333 g (67%) of 1 H-pyrrolo[3,2-c]pyridine-3-carbaldehyde which was used without further purification. ESI/APCI(+): 147 (M+H). ESI/APCI(-): 145 (M-H). 1 H NMR (DMSO- d6) 10.00 (1 H, s); 9.29 (1 H, s); 8.42 ( 1 H, s); 8.35 (1 H, d); 7.53 (1 H, d).

Reference： [1]Patent: WO2013/45516,2013,A1 .Location in patent: Page/Page column 201

57
[ 271-34-1 ]
[ 1147422-00-1 ]

Reference： [1]Patent: WO2013/71697,2013,A1
[2]Patent: US2014/228361,2014,A1

58
[ 271-34-1 ]
[ 375345-98-5 ]
propane-2-sulfonic acid [2-(4-pyrrolo[3,2-c]pyridin-1-ylphenyl)propyl]amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With copper(l) iodide; trans-1,2-Diaminocyclohexane; potassium carbonate; In N,N-dimethyl-formamide; at 115℃; for 18h;Inert atmosphere;	To a solution of HJC-1-2 (184 mg, 0.5 mmol) and <strong>[271-34-1]5-azaindole</strong> (59 mg, 0.5 mmol) in DMF (5 mL) was added K2C03 (138 mg, 1.0 mmol), trans- 1 ,2-diaminocyclohexane (11 mg, 0.1 mmol) and then Cul (10 mg, 0.05 mmol). The resulting mixture was deoxygenated via five vacuum/N2-refill cycles. The mixture was stirred at 115 C for 18 h, was then partitioned between EtOAc (100 mL) and H20 (30 mL). The organic layer was separated and washed with brine (10 mL), dried over anhydrous Na2S04, filtered and concentrated to give an oil residue. This residue was purified with silica gel column (Hexane/EtOAc = 1/1 to 1/3) to obtain HJC-2-31 (120 mg, 67%) as a pale yellow oil. 1H NMR (600 MHz, CDC13) δ 8.93 (s, 1H), 8.22 (d, 1H, J = 5.4 Hz), 7.38 (t, 4H, J = 8.4 Hz), 7.35 (d, 1H, J = 7.8 Hz), 7.31 (d, 1H, J= 2.4 Hz), 6.74 (d, 1H, J = 2.4 Hz), 5.10-5.14 (m, 1H), 3.39 (t, 1H, J= 7.2 Hz), 3.31 (t, 1H, J= 7.2 Hz), 3.07-3.12 (m, 2H), 1.23-1.36 (m, 9H). 13C NMR (150 MHz, CDC13) δ 144.2, 142.8, 141.4, 139.4, 137.4, 129.1, 128.9, 126.0, 124.5, 105.8, 103.1, 53.6, 50.4, 40.8, 19.2, 16.8, 16.7.

Reference： [1]Patent: WO2013/130501,2013,A1 .Location in patent: Paragraph 089

59
[ 271-34-1 ]
[ 609-73-4 ]
[ 1542750-13-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium phosphate; copper; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere;	General procedure: An oven dried two-necked round bottom flask was charged with aryl halide (1mmol) and K3PO4 (2mmol), evacuated, and backfilled with argon. The azole compound (1mmol) and 2mL of DMSO were added under argon. After that Cu-NP (1.6mmol) was added and the flask was again backfilled with argon. The flask was then immersed in a preheated oil bath at 80C until the conversion was completed (detected by TLC). The cooled mixture was partitioned between ethyl acetate (10mL) and saturated NH4Cl (10mL). The aqueous layer was extracted with ethyl acetate (2×10mL), the organic layer was washed with brine (20mL), dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate in hexane (1.5-10%) as eluent to afford the desired product. All the products have been characterized by 1H NMR, 13C NMR, and mass spectroscopy. For new products, FTIR data were also recorded.
	With potassium phosphate; In dimethyl sulfoxide; at 80℃; for 2h;Inert atmosphere;	General procedure: An oven dried two-necked round bottom flask was charged with aryl halide (1mmol) and K3PO4 (2mmol), evacuated, and backfilled with argon. The azole compound (1mmol) and 2mL of DMSO were added under argon. After that Cu-NP (1.6mmol) was added and the flask was again backfilled with argon. The flask was then immersed in a preheated oil bath at 80C until the conversion was completed (detected by TLC). The cooled mixture was partitioned between ethyl acetate (10mL) and saturated NH4Cl (10mL). The aqueous layer was extracted with ethyl acetate (2×10mL), the organic layer was washed with brine (20mL), dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate in hexane (1.5-10%) as eluent to afford the desired product. All the products have been characterized by 1H NMR, 13C NMR, and mass spectroscopy. For new products, FTIR data were also recorded.Analytical data of compound 3a: 1H NMR (CDCl3, 500MHz): δ 7.94 (d, J=8.5Hz, 2H), 7.87 (d, J=8.5Hz, 2H), 7.78 (d, J=8.5Hz, 1H), 7.70-7.68 (m, 2H), 7.27-7.24 (m, 1H), 7.20-7.17 (m, 1H), 6.79 (d, J=3.5Hz, 1H); 13C NMR (CDCl3, 125MHz): δ 142.8, 135.5, 129.7, 128.3, 127.4, 126.9 (q, J=59Hz), 125.4 (q, J=362Hz), 123.9, 122.9, 121.4, 121.0, 110.3, 104.9; MS(EI) 262.4 (M+). Anal. Calcd for C15H10F3N: C, 68.96, H, 3.86, N, 5.36. Found: C, 68.89, H, 3.88, N, 5.33.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 941 - 944
[2]Tetrahedron Letters,2014,vol. 55,p. 941 - 944

60
[ 271-34-1 ]
[ 15854-87-2 ]
[ 1542750-10-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium phosphate; In dimethyl sulfoxide; at 80℃; for 5h;Inert atmosphere;	General procedure: An oven dried two-necked round bottom flask was charged with aryl halide (1mmol) and K3PO4 (2mmol), evacuated, and backfilled with argon. The azole compound (1mmol) and 2mL of DMSO were added under argon. After that Cu-NP (1.6mmol) was added and the flask was again backfilled with argon. The flask was then immersed in a preheated oil bath at 80C until the conversion was completed (detected by TLC). The cooled mixture was partitioned between ethyl acetate (10mL) and saturated NH4Cl (10mL). The aqueous layer was extracted with ethyl acetate (2×10mL), the organic layer was washed with brine (20mL), dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate in hexane (1.5-10%) as eluent to afford the desired product. All the products have been characterized by 1H NMR, 13C NMR, and mass spectroscopy. For new products, FTIR data were also recorded.Analytical data of compound 3a: 1H NMR (CDCl3, 500MHz): δ 7.94 (d, J=8.5Hz, 2H), 7.87 (d, J=8.5Hz, 2H), 7.78 (d, J=8.5Hz, 1H), 7.70-7.68 (m, 2H), 7.27-7.24 (m, 1H), 7.20-7.17 (m, 1H), 6.79 (d, J=3.5Hz, 1H); 13C NMR (CDCl3, 125MHz): δ 142.8, 135.5, 129.7, 128.3, 127.4, 126.9 (q, J=59Hz), 125.4 (q, J=362Hz), 123.9, 122.9, 121.4, 121.0, 110.3, 104.9; MS(EI) 262.4 (M+). Anal. Calcd for C15H10F3N: C, 68.96, H, 3.86, N, 5.36. Found: C, 68.89, H, 3.88, N, 5.33.
90%	With potassium phosphate; copper; In dimethyl sulfoxide; at 80℃; for 5h;Inert atmosphere;	General procedure: An oven dried two-necked round bottom flask was charged with aryl halide (1mmol) and K3PO4 (2mmol), evacuated, and backfilled with argon. The azole compound (1mmol) and 2mL of DMSO were added under argon. After that Cu-NP (1.6mmol) was added and the flask was again backfilled with argon. The flask was then immersed in a preheated oil bath at 80C until the conversion was completed (detected by TLC). The cooled mixture was partitioned between ethyl acetate (10mL) and saturated NH4Cl (10mL). The aqueous layer was extracted with ethyl acetate (2×10mL), the organic layer was washed with brine (20mL), dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate in hexane (1.5-10%) as eluent to afford the desired product. All the products have been characterized by 1H NMR, 13C NMR, and mass spectroscopy. For new products, FTIR data were also recorded.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 941 - 944
[2]Tetrahedron Letters,2014,vol. 55,p. 941 - 944

61
[ 271-34-1 ]
[ 913000-15-4 ]
[ 1609699-98-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; In toluene; at 110℃; for 24h;Microwave irradiation; Inert atmosphere; Sealed tube;	General procedure: To a microwave vial was added 18(100mg,0.194mmol),CuI(2mg,0.01mmol), the 4-azaindole (28mg,0.23 mmol), andK3PO4(83mg,0.39 mmol), and the reaction vessel was fitted with arubber septum. The vessel was evacuated and back-filledwith argon and thisevacuation/back-fill procedure was repeated one additional time. Toluene (3 mL) and (1R,2R)-N,N'-Dimethyl-1,2-cyclohexanediamine (6μL,0.039mmol) were then successively added under a stream of argon. Thereaction tube was quickly sealed and the contents were stirredwhile heating in an oil bath at110C for 24h. The reaction mixture was cooled toambient temperature, diluted with ethyl acetate, and filtered through a plug ofsilica gel, eluting with additional ethyl acetate. The filtrate was concentrated and the resultingresidue was purified by column chromatography(20:1 DCM/MeOH) to provide the product (2,4-bis(benzyloxy)-5-(1H-pyrrolo[3,2-b]pyridin-1-yl)ph-enyl)(isoindolin-2-yl)methanoneS18 as a light yellow oil(38mg,35.4%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2525 - 2529

62
[ 271-34-1 ]
C₁₃H₉ClN₂O₂ [ No CAS ]
[ 1654013-89-4 ]

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 4399 - 4404

63
[ 271-34-1 ]
C₁₄H₁₁ClN₂O₂ [ No CAS ]
[ 1654013-93-0 ]

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 4399 - 4404

64
[ 271-34-1 ]
4-bromo-6-(bromomethyl)isoquinoline [ No CAS ]
4-bromo-6-(pyrrolo[3,2-c]pyridin-1-ylmethyl)isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 0.05 g of <strong>[271-34-1]5-azaindole</strong> (CAS: 271-34-1, 0.420 mmol) in 1 mL of THF is added 0.05 g ofNaH (60%) (1.27 mmol). The reaction mixture is stirred at 25 C for 2h. Then 0.13 g of 4-bromo-6-(bromomethyl)isoquinoline(0.42Ommol) is added, and the reaction mixture was stirred at 25C for 16 h. The reaction mixture is quenched with brine and extracted with EA. The combined organic layers are washed with water and brine, and dried over Na2SO4. After filtration, the filtrate is concentrated in vacuum to give the crude product as light yellow solid. The residue is purified by columnchromatography on silica gel eluting with (DCM/MeOH=20/1) to afford the desired product as a yellow solid.MS (ESI+): 338.0, 340.0 [M+H].‘H NMR (400 MHz, DMSO-d6) ppm: 9.28 (s, 1H), 8.88 (d, J= 1.2 Hz, 1H), 8.74 (s, 1H), 8.27 - 8.08 (m, 2H), 7.92 - 7.78 (m, 1H), 7.71 (d, J= 3.2 Hz, 1H), 7.61 - 7.50 (m, 2H), 6.74 (dd, J= 3.2, 0.8 Hz,1H), 5.79 (d, J= 16.2 Hz, 2H).

Reference： [1]Patent: WO2016/128465,2016,A1 .Location in patent: Page/Page column 150

65
[ 271-34-1 ]
[ 106-54-7 ]
3-((4-chlorophenyl)thio)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 2487 - 2491
Angew. Chem.,2017,vol. 129,p. 2527 - 2531

66
[ 271-34-1 ]
[ 60290-21-3 ]

Reference： [1]Patent: WO2017/23987,2017,A1
[2]Patent: WO2017/24003,2017,A1
[3]Patent: WO2017/24010,2017,A1
[4]Patent: WO2017/23984,2017,A1

67
[ 271-34-1 ]
[ 918538-05-3 ]
2-chloro-4-(1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolo[2,1-f][1,2,4]triazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	In tetrahydrofuran; at 20℃; for 1h;	To a solution of compound 1A (200 mg, 1.064 mmol) in THF (2 mL), 1H- pyrrolo[3,2-c]pyridine (126 mg, 1.064 mmol) was added and the yellow suspension formed was stirred at room temperature for 1 h. The reaction mixture was concentrated and the residue was basified using 10% sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated. The resulting crude residue was purified by silica gel chromatography to get 2-chloro-4-(lH-pyrrolo[3,2-c]pyridin-l-yl)pyrrolo[2,l- (140 mg, 0.519 mmol, 49 % yield) as a yellow solid. . LCMS: RT = 0.62 min; MS(ES): m/z observed = 269.9, 271.9 (Injection conditions: Column: Waters Acquity UPLC ΒΕΗ CI 8, 2.1 x 50 mm, 1.7-μτη particles; Mobile Phase A: 100% water with 0.05% TFA; Mobile Phase B: 100% MeCN with 0.05% TFA; Gradient: 2-98% B over 1 minute, then a 0.5-minute hold at 98% B; Flow: 0.8 mL/min; Detection: UV at 220 nm).

Reference： [1]Patent: WO2017/40448,2017,A1 .Location in patent: Page/Page column 50

68
[ 1990-90-5 ]
[ 4637-24-5 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
		1) 3-Methyl-4-aminopyridine was added to a chloroform solution, to which was added acetic anhydride and the catalystMethyl dithiocarbamate, <strong>[1990-90-5]3-methyl-4-aminopyridine</strong> and acetic anhydride at a ratio of 2: 1, stirred and stirred at 60 C for 1 hour.Pure to give compound I;(2) mixing the compound I with pyrrolidine and DMF-DMA, wherein the molar ratio of compound I, pyrrolidine and DMF-DMA is 1: 2: 1.5, adding N-fluorobisbenzenesulfonamide, 80 C The reaction was carried out for 2 hours and purified to give the final product5'-azaindole The prepared 5 - aza indole purity is 91.1%, yield of 92.5%.

Reference： [1]Patent: CN106279157,2017,A .Location in patent: Paragraph 0016; 0017; 0018; 0019; 0020; 0021-0039

69
[ 271-34-1 ]
6-(4-methoxybenzyl)-2-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one [ No CAS ]
6-(4-methoxybenzyl)-2-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	In acetonitrile; at 0℃; for 1h;	To a solution of 6-(4-methoxybenzyl)-2-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one (4, 0.2 g, 0.60 mmol) in acetonitrile (5 mL), was added at 0 C. 1H-pyrrolo[3,2-c]pyridine (5, 0.049 g, 0.42 mmol) and the reaction mixture was stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, the reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography to afford 6-(4-methoxybenzyl)-2-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one (6). Yield: 0.1 g, 22%; MS (ESI) m/z 372[M+1]+

Reference： [1]Patent: US2017/121339,2017,A1 .Location in patent: Paragraph 0239

70
[ 271-34-1 ]
[ 1440519-73-2 ]
6-(4-methoxybenzyl)-2-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With tris-(dibenzylideneacetone)dipalladium(0); potassium tert-butylate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 12.0h;Inert atmosphere;	General procedure: Procedure A: To a solution of 5-bromo-2-(4-methoxybenzyl)isoindolin-1-one (1, 0.5 g, 1.5 mmol) in dioxane (10 mL) was added 7H-pyrrolo[2,3-d]pyrimidine (2, 0.27 g, 2.25 mmol) and potassium tert-butoxide (0.51 g, 4.52 mmol) followed by the addition of XantPhos (0.087 g, 0.15 mmol). The reaction mixture was degassed with argon for 15 min. Tris(dibenzylideneacetone)dipalladium(0) (0.14 g, 0.15 mmol) was then added and the reaction mixture was heated at 90 C. and maintained at that temperature for 12 h. (0193) Following heating, the reaction mixture was cooled and concentrated under reduced pressure. The concentrated reaction mixture was extracted in ethyl acetate. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue obtained was purified by silica gel (100-200 mesh) column chromatography using 5% methanol in dichloromethane as eluent so as to afford 2-(4-methoxybenzyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)isoindolin-1-one (3). Yield: 0.21 g, 38%;

Reference： [1]Patent: US2017/121339,2017,A1 .Location in patent: Paragraph 0192-0193; 0205

71
[ 271-34-1 ]
[ 1440519-73-2 ]
2-(4-methoxybenzyl)-6-(1H-pyrrolo[3,2-c]pyridin-1-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; ruphos; In 1,4-dioxane; at 150℃; for 12.0h;Inert atmosphere;	General procedure: Procedure A: To a solution of 5-bromo-2-(4-methoxybenzyl)isoindolin-1-one (1, 0.5 g, 1.5 mmol) in dioxane (10 mL) was added 7H-pyrrolo[2,3-d]pyrimidine (2, 0.27 g, 2.25 mmol) and potassium tert-butoxide (0.51 g, 4.52 mmol) followed by the addition of XantPhos (0.087 g, 0.15 mmol). The reaction mixture was degassed with argon for 15 min. Tris(dibenzylideneacetone)dipalladium(0) (0.14 g, 0.15 mmol) was then added and the reaction mixture was heated at 90 C. and maintained at that temperature for 12 h. (0193) Following heating, the reaction mixture was cooled and concentrated under reduced pressure. The concentrated reaction mixture was extracted in ethyl acetate. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue obtained was purified by silica gel (100-200 mesh) column chromatography using 5% methanol in dichloromethane as eluent so as to afford 2-(4-methoxybenzyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)isoindolin-1-one (3). Yield: 0.21 g, 38%;

Reference： [1]Patent: US2017/121339,2017,A1 .Location in patent: Paragraph 0192-0193; 0227

72
[ 271-34-1 ]
[ 107-14-2 ]
5-(cyanomethyl)-1H-pyrrolo[3,2-c]pyridin-5-ium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In acetonitrile; for 6h;Reflux;	To a solution of <strong>[271-34-1]5-azaindole</strong> (1 g, 8.5 mmol) in MeCN (5 mL) was added chloroacetonitrile (0.8 mL, 12.75 mmol). The reaction mixture was stirred under reflux for 6 h. The precipitate was collected by filtration, washed with MeCN (3 × 5 mL) and dried under air to give a gray solid; yield: 1.31 g (80%); mp 212-214 C. IR (KBr): 3203-2541, 1893, 1778, 1636, 1602, 1523, 1484, 1417,1361, 1334, 1276, 1240, 1139, 924, 816, 729 cm-1. 1H NMR (600 MHz, DMSO-d6): δ = 6.10 (s, 2 H), 7.11 (d, J = 3.3 Hz, 1H), 8.03 (d, J = 3.3 Hz, 1 H), 8.13 (d, J = 7.0 Hz, 1 H), 8.67 (d, J = 7.0 Hz, 1 H), 9.60 (s, 1 H), 13.62 (br s, 1 H). 13C NMR (150 MHz, DMSO-d6): δ = 46.2, 104.6, 110.3, 115.3, 124.8, 133.8, 134.3, 139.7, 141.3. ESI-MS: m/z = 158 [M - Cl]+. Anal. Calcd for C9H8ClN3 (193.63): C, 55.83; H, 4.16; N, 21.70. Found: C, 55.97; H, 4.08; N, 21.80.

Reference： [1]Synthesis,2017,vol. 49,p. 2753 - 2760

73
[ 271-34-1 ]
[ 186552-10-3 ]
5-(1H-pyrrolo[3,2-c]pyridin-1-ylmethyl)thiophene-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		To a solution of 1H-pyrrolo[3,2-c]pyridine (1.77 g, 15.00 mmol) in anhydrous dimethylformamide (75 mL) was added sodium hydride (60% suspension in mineral oil, 0.75 g, 18.75 mmol) at 0 C in small portions under nitrogen. After the addition, reaction mixture was stirred for 15 minutes at 0 C and then at room temperature for 10 minutes. Cooled to 0 C, 5- (bromomethyl)thiophene-3-carbonitrile (from step 3, 3.79 g, 18.75 mmol) was added in small portions. After the addition, reaction mixture was stirred for 10 minutes at 0 C and then at room temperature for 1 h. Quenched with water (10 mL), solvent was evaporated under reduced pressure. Residue was partitioned between ethyl acetate (150 mL) and water (100 mL). Organic phase was separated, washed with brine and dried over Na2SO4. The crude compound was purified by flash chromatography using RediSep silica 80 g flash column (0-3% methanol in methylene chloride as eluent) to give 5 -( 1H-pyrrolo[3 ,2-c]pyridin- 1 -ylmethyl)thiophene-3 - carbonitrile (2.17 g, 60%) as a brown solid.‘HNMR (400 1VIHz, CDC13): 5.47 (s, 2H), 6.68 (d, 1H, J = 3.1 Hz), 7.10 (s, 1H), 7.15 (d, 1H, J = 3.5 Hz), 7.23 (d, 1H, J = 5.8 Hz), 7.83 (s, 1H), 8.35 (d, 1H, J = 5.9 Hz).Mass: ES 240.01

Reference： [1]Patent: WO2017/96472,2017,A1 .Location in patent: Paragraph 066

74
[ 271-34-1 ]
5-(bromomethyl)furan-3-carbonitrile [ No CAS ]
5-(1H-pyrrolo[3,2-c]pyridin-1-ylmethyl)furan-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		To a solution of 1H-pyrrolo[3,2-c]pyridine (0.77 g, 6.50 mmol) in anhydrous dimethylformamide (30 mL) was added sodium hydride (60% suspension in mineral oil, 0.26 g, 6.50 mmol) at 0 C in small portions under nitrogen. After the addition, the reaction mixture was stirred for 15 minutes at 0 C and then at room temperature for 10 minutes then cooled to 0 C and 5-(bromomethyl)furan-3-carbonitrile (from step 3, 1.10 g, 5.91 mmol) was added in small portions. After the addition, the reaction mixture was stirred for 10 minutes at 0 C then at room temperature for 1 h. The mixture was quenched with water (5 mL). Solvent was evaporated under reduced pressure. Residue was partitioned between ethyl acetate (100 mL) and water (50 mL). The organic phase was separated, washed with brine and dried over Na2 SO4. The crude compound was purified by flash chromatography using RediSep silica 40 g flash column (0-3% methanol in methylene chloride as eluent) to give 5-(1H-pyrrolo[3,2-c]pyridin-1-ylmethyl)furan- 3-carbonitrile (1.065 g, 80%) as an off-white solid.‘HNMR (400 1VIHz, CDC13): 5.29 (s, 2H), 6.46 (s, 1H), 6.66 (d, 1H, J = 2.3 Hz), 7.15 (d, 1H, J = 3.5 Hz), 7.27 (s, 1H), 7.88 (s, 1H), 8.37 (d, 1H, J = 5.9 Hz), 8.94 (s, 1H).Mass: ES 224.10.

Reference： [1]Patent: WO2017/96472,2017,A1 .Location in patent: Paragraph 067

75
[ 271-34-1 ]
4-(bromomethyl)-3-chloro-5-fluorobenzonitrile [ No CAS ]
3-chloro-5-fluoro-4-(1H-pyrrolo[3,2-c]pyridin-1-ylmethyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		An ice-cold mixture of <strong>[271-34-1]5-azaindole</strong> (0.34 g, 2.88 mmol) in N,N-dimethylformamide (10 mL) was treated with sodium hydride (60 % in mineral oil, 0.172 g, 4.32 mmol) in portions, then stirred at room temperature for 15 minutes. The mixture was cooled to 0 C, and then treated with 4- (bromomethyl)-3-chloro-5-fluorobenzonitrile (from step 3, 0.73 g, 2.93 mmol) in tetrahydrofuran (10 mL). The resulting mixture was stirred at 0 C for 1 hour then quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate, and the extracts were washed with brine, dried (sodium sulphate), filtered and concentrated in vacuo to brown oil, which was purified by column chromatography (silica gel) eluting with 5:3:2 dichloromethane/ethyl acetate/methanol as eluent to afford 3-chloro-5-fluoro-4-(1H-pyrrolo[3,2- c]pyridin-1-ylmethyl)benzonitrile (0.53 g, 65 %) as a white solid.‘HNMR (400 1VIHz, CDC13): 5.49 (d, 2H, J= 1.9 Hz), 6.62 (d, 1H, J 3.2 Hz), 7.19 (d, 1H, J = 2.8 Hz), 7.37-7.41 (m,2H), 7.59 (s, 1H), 8.35 (d, 1H, J= 6.0 Hz), 8.91 (s, 1H).

Reference： [1]Patent: WO2017/96472,2017,A1 .Location in patent: Paragraph 106

76
[ 271-34-1 ]
4-(bromomethyl)-3-chloro-5-fluorobenzonitrile [ No CAS ]
3-chloro-5-fluoro-4-(1H-pyrrolo[3,2-b]pyridin-1-ylmethyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		An ice-cold mixture of 4-azaindole (0.47 g, 3.98 mmol) in N,N-dimethylformamide (10 mL) was treated with sodium hydride (60 % in mineral oil, 0.23 g, 6.0 mmol) in portions, then stirred at room temperature for 15 minutes. The mixture was cooled to 0 C, then treated with 4- (bromomethyl)-3-chloro-5-fluorobenzonitrile (1.00 g, 4.00 mmol) in tetrahydrofuran (10 mL). The resulting mixture was stirred at 0 C for 1 hour then quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate and the extracts were washed with brine, dried (sodium sulphate), filtered and concentrated in vacuo to brown oil, which was purified by column chromatography (silica gel) eluting with 5:3:2 dichloromethane/ethyl acetate/methanol as eluent to afford 3 -chloro-5 -fluoro-4-( 1H-pyrrolo[3 ,2-b]pyridin- 1- ylmethyl)benzonitrile (0.62 g, 54 %) as brown solid.‘HNMR (400 1VIHz, CDC13): 5.49 (d, 2H, J= 1.9 Hz), 6.72 (d, 1H, J 3.4 Hz), 7.14 (dd, 1H, J= 8.2, 4.7 Hz), 7.37 (d, 1H, J=8.7 Hz), 7.41 (d, 1H, J= 3.4 Hz), 7.58 (br s, 1H,) 7.78 (d, 1H, J8.4 Hz), 8.47 (d, 1H, J 4.7 Hz).

Reference： [1]Patent: WO2017/96472,2017,A1 .Location in patent: Paragraph 112

77
[ 271-34-1 ]
[ 17201-43-3 ]
4-((1H-pyrrolo[3,2-c]pyridin-1-yl)methyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		To a solution of 1H-pyrrolo[3,2-c]pyridine (1.0 g, 8.5 mmol) in DMF (40 mL) under nitrogen at 0C was added NaH (60% in mineral oil, 0.51 g, 12.8 mmol) in portions and after stirring for 15 mm was added 4-(bromomethyl)benzonitrile (2.5 g, 12.8 mmol) in portions. The reaction mixture was stirred at 0 C for 2 h then at room temperature for 1 h and quenched with saturated ammonium chloride solution then diluted with ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, washed with brine (3 x 100 mL), dried (Na2504) and concentrated. The crude product was purified by silica gel column chromatography using methylene chloride:ethyl acetate: methanol (5:3 :2) to afford 4-( 1H-pyrrolo[3 ,2-c]pyridin- 1 -ylmethyl)benzonitrile (1.2 g, 60%) as a solid. ‘HNIVII{ (400 MHz, CDC13): 5.38 (s, 2H), 6.68 (d, 1H, J = 3.2 Hz), 7.11-7.17 (m, 4H), 7.54 (d, 2H, J = 8.0 Hz), 8.27 (d, 1H, J = 5.6 Hz), 8.94 (s, 1H).

Reference： [1]Patent: WO2017/96472,2017,A1 .Location in patent: Paragraph 062
[2]Patent: WO2020/212479,2020,A1 .Location in patent: Page/Page column 37

78
[ 271-34-1 ]
[ 3934-20-1 ]
2-chloro-4-(pyrrolo[3,2-c]pyrid-1-yl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of pyrrolo[3.2-c]pyridine (2.54 g, 21.5 mmol) in DMF (60 mL) is added NaH (60% in mineral oil,1.03 g, 25.78 mmol) portionwise at 0 C. After stirring at 0 C for 30 min.2,4-dichloropyrimidine (3.20 g, 21.5 mmol) is added, and the mixture is allowed to stir at 15 C for 12 hrs. The resulting mixture is quenched with water (200 mL) and the mixture is extracted with EtOAc (100 mL x 3), and washed with water (100 mL x 4), dried with Na2SO4 and concentrated in vacuo. The residue is purified by silica gel chromatography (petroleum ether: EtOAc =10:1), to give 2-chloro-4-(pyrrolo[3.2-c]pyrid-1-ylpyrimidine.

Reference： [1]Patent: WO2017/120429,2017,A1 .Location in patent: Page/Page column 311

79
[ 271-34-1 ]
[ 1178564-34-5 ]
[ 1654013-89-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With caesium carbonate; In N,N-dimethyl-formamide; toluene; at 90℃; for 0.333333h;Microwave irradiation;	0.15 mmol of 3-chloro-4- (1-methyl-1H-indol-3-yl) -1-phenyl-1H-pyrrole-2,5-dione 1a was added to a 10 mL microwave reaction tube,0.18 mmol <strong>[271-34-1]5-azaindole</strong>,0.3 mmol Cs2CO3,1 mL of toluene and 2 mL of DMF,Heat at 90 C for 20 minutes in a microwave reactor.After the reaction was completed, the reaction solution was washed with water (20 mL) and then extracted with ethyl acetate (3 × 20 mL). The organic phases were combined and the organic phase was washed with saturated brine (3 × 60 mL) and dried.Purification by column chromatography (ethyl acetate: petroleum ether = 1: 2) gave an orange solid 3a in 80% yield,

Reference： [1]Patent: CN106831762,2017,A .Location in patent: Paragraph 0015

80
[ 19798-77-7 ]
[ 74-86-2 ]
[ 271-34-1 ]

Yield	Reaction Conditions	Operation in experiment
90.4%	With Ni(1,5-cyclooctadiene)2; In tetrahydrofuran; diethyl ether; at 110℃; for 4.5h;Microwave irradiation;	The <strong>[19798-77-7]3-chloro-4-aminopyridine</strong> was mixed with tetrahydrofuran and added to the reactor. The mixture was heated to 110 C., and diethyl ether and Ni(COD) 2 were added. The catalyst was added. Under stirring, acetylene was added to perform microwave irradiation for 30 minutes.Afterwards, refluxing reaction was continued for 4 hours. After the reaction was completed, filtration was performed. The filtrate was evaporated off to tetrahydrofuran, extracted with ethyl acetate, recrystallized with water, suction filtered and dried to obtain 5-azaindole;The catalyst is a molybdenum trioxide-alumina composite. The catalyst is prepared by dissolving ammonium molybdate in water, adding alumina particles, ultrasonically dispersing, adding urea, and adding hydrochloric acid dropwise under stirring conditions.After completion of the dropwise addition, the precipitate was filtered, washed, dried and calcined at 400 C. to obtain a molybdenum trioxide-alumina composite.The molar ratio of ammonium molybdate and urea is 1:0.5;The molar ratio of hydrochloric acid to ammonium molybdate is 1:1;The molar ratio of molybdenum trioxide to alumina in the molybdenum trioxide-alumina composite is 1:3. The <strong>[19798-77-7]3-chloro-4-aminopyridine</strong> and ether molar ratio of 2:1.5;The molar ratio of <strong>[19798-77-7]3-chloro-4-aminopyridine</strong> to Ni(COD)2 is 7:2;The molar ratio of <strong>[19798-77-7]3-chloro-4-aminopyridine</strong> to acetylene is 1:1.5;The mass ratio of <strong>[19798-77-7]3-chloro-4-aminopyridine</strong> to the catalyst is 12:11;The microwave radiation power is 300W.The yield of the obtained 5-azaindole was 90.4% and the purity was 99.1%.

Reference： [1]Patent: CN107903262,2018,A .Location in patent: Paragraph 0020-0031; 0032-0037; 0038-0043; 0044-0049

81
[ 271-34-1 ]
6-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-sulfonyl chloride [ No CAS ]
C₂₀H₁₃FN₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: NaH (10.3 mg, 0.258 mmol) was first dissolved in 1 mL of anhydrous DMF. Imidazole (10.5mg, 0.155 mmol) dissolved in 1 mL of anhydrous DMF was slowly added dropwise, and the mixture was stirred for 30 min. Compound 35 (40 mg, 0.129 mmol) dissolved in 1 mL of anhydrous DMF was slowly added dropwise, and the mixture was stirred for 3 h at room temperature. The reaction solution was poured into 0.1 mol/L hydrochloric acid, which was then turned basic using an aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was collected, and distilled under reduced pressure. The residue was purified by flash chromatography to afford compound 5 (26 mg, 60%).

Reference： [1]Acta Pharmacologica Sinica,2016,vol. 37,p. 698 - 707

82
[ 271-34-1 ]
(6-bromo-imidazo[1,2-a]pyridine)-3-sulfonyl chloride [ No CAS ]
3-((1H-pyrrolo[3,2-c]pyridin-1-yl)sulfonyl)-6-bromoimidazo[1,2-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		NaH (0.88 g, 22 mmol) was suspended in 10 mL of anhydrous DMF and cooled to 0 C in an ice bath. 1H-pyrrolo[3,2-c]pyridine (1.3 g, 11 mmol) dissolved in 10 mL of anhydrous DMF was slowly added dropwise, and the mixture was stirred for 30 min at 0 C. Compound 36(3.9 g, 13.2 mmol) dissolved in 15 mL of anhydrous DMF was added in dropwise, and the reaction mixture was stirred for 4h at room temperature. The reaction was monitored by TLC. The reaction solution was poured into 0.1 mol/L hydrochloric acid, which was then turned basic using an aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was collected and distilled under reduced pressure.The remaining substance was purified by column chromatography to give purified compound 37 (2.5 g, 60%). MSm/z (ESI) found 377 (M+H)+; 1H NMR (400 MHz, chloroformd)δ 8.91 (d, J=1.0 Hz, 1H), 8.77 (dd, J=1.8, 0.9 Hz, 1H), 8.53 (d,J=5.8 Hz, 1H), 8.35 (s, 1H), 7.84 (d, J=5.8 Hz, 1H), 7.67 (d, J=3.7Hz, 1H), 7.63 (dd, J=9.5, 0.9 Hz, 1H), 7.53 (dd, J=9.5, 1.8 Hz,1H), 6.80 (dd, J=3.7, 0.9 Hz, 1H).

Reference： [1]Acta Pharmacologica Sinica,2016,vol. 37,p. 698 - 707

83
[ 271-34-1 ]
[ 76513-69-4 ]
C₁₃H₂₀N₂OSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		<strong>[271-34-1]5-azaindole</strong> (2 g, 17 mmol) was added portionwise to a suspension of sodium hydride (744 mg, 18.6 mmol, 60% dispersion in mineral oil) in DMF (40 mL) at 0C. The mixture was stirred at rt for 10 min. Then the mixture was cooled to 0 C and (0468) 2-(trimethylsilyl)ethoxymethyl chloride (18.6 mmol) was added. The reaction mixture was further stirred at rt for 16 h. NH4CI (aq. Sat. soltn.) was added and the mixture was extracted with EtOAc. The organic layer was separated, dried over Na2S04, filtered and the volatiles were evaporated in vacuo. The resultant residue was purified by flash column chromatography (silica; EtOAc in heptane 0/100 to 50/50) and the desired fractions were concentrated in vacuo to yield intermediate 60 as brown oil (2.1 g, 50% yield).

Reference： [1]Patent: WO2018/109198,2018,A1 .Location in patent: Page/Page column 58

84
[ 271-34-1 ]
C₁₃H₁₃BrN₂ [ No CAS ]
1-(pyrrolidin-yl)-7-(1H-5-azaindol-yl)-isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With copper(I) oxide; caesium carbonate; In N,N-dimethyl acetamide; for 1h;Microwave irradiation; Sealed tube; Heating;	General procedure: 7-Bromo-1-(4-Morpholin-yl)isoquinoline ((0.17 mmol, 50 mg), indole (0.25 mmol),Cs2CO3 (0.17 mmol), Cu2O (10 mol %), and DMA (3 mL) were added to a 5 mL vial. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. After irradiation at 200 oC for 1 h and subsequent cooling, the reaction mixture was diluted with saturated aqueous ammonium chloride. Products were isolated by extraction into ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Products were purified by silica gel column chromatography using a hexane: ethyl acetate solvent. 1-(4-Morpholin-yl)-7-(1H-indol-yl)-isoquinoline was obtained (73 % yield) as a red oil. 1H NMR (300 MHz, CDCl3) δ 8.22 (d, J = 5.7 Hz, 1H), 8.19 (d, J = 1.7 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.79 (dd, J = 8.7, 2.1Hz, 1H), 7.73 (dd, J = 6.9, 1.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 3.3 Hz, 1H), 7.34 (d, J = 5.7 Hz, 1H), 7.30 - 7.18 (m, 7H), 6.76 (d, J = 3.2 Hz, 1H), 3.93 (t, J = 4.5 Hz, 4H), 3.43 (t, J = 4.5 Hz, 4H); 13C NMR (75 MHz, CDCl3) δ 161.1, 141.0, 137.6, 136.5, 135.9, 129.5, 129.0, 127.9, 127.0, 122.8, 122.3, 121.5, 120.8, 119.6, 116.0, 110.1, 104.4, 67.0, 51.9; MS(m/z) : 329.41 (M+1). The compounds (6b-6h) were prepared general procedure for microwave promoted copper-catalyzed N-arylation.

Reference： [1]Bulletin of the Korean Chemical Society,2018,vol. 39,p. 1259 - 1265

85
[ 271-34-1 ]
[ 40400-13-3 ]
1-(2-iodobenzyl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7898 - 7901

86
[ 271-34-1 ]
[ 82386-91-2 ]
8-chloro-6H-pyrido[3',4':4,5]pyrrolo[2,1-a]isoindole [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7898 - 7901

87
[ 271-34-1 ]
[ 82386-91-2 ]
1-(5-chloro-2-iodobenzyl)-1H-pyrrolo[3,2-c]pyridine [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7898 - 7901

88
[ 271-34-1 ]
[ 1236145-31-5 ]
12-(1H-pyrrolo[3,2-c]pyridin-3-yl)-12H-chromeno[2',3':4,5]imidazo[1,2-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
204 mg	With potassium permanganate; triethylamine; In 2,2,2-trifluoroethanol; for 1h;Reflux;	General procedure: To the solution of 1 mmol of salt in 2 mL of TFE and 1 mmol (1 equiv.) of the aldehyde 0.2 mmol(28μL, 0.2 equiv.) of Et3N was added at 0C (ice bath). The reaction was stirred at 0C for an hour.Then 3 mmol (3 equiv.) of the nucleophile, 0.8 mmol (111μL, 0.8 equiv.) Et3N and 1 mmol (158mg, 1 equiv.) KMnO4 were added, and the reaction mixture was refluxed for 1 hour. Upon thecompletion reaction mixture was concentrated in vacuo. Products were isolated by columnchromatography on silica gel, eluent DCM-MeOH (1-100) for compounds 6a, c-k, DCM-MeOH(1-20) for 9, (1-15) for 10, ethyl acetate-hexane (1-1), ethyl acetate for compound 8.

Reference： [1]Beilstein Journal of Organic Chemistry,2018,vol. 14,p. 3078 - 3087

Same Skeleton Products

Related Products

Historical Records

Related Parent Nucleus of
[ 271-34-1 ]

Other Aromatic Heterocycles

[ 183586-34-7 ]

6-Methyl-1H-pyrrolo[3,2-c]pyridine

Similarity: 0.92

[ 860362-26-1 ]

4-Methyl-1H-pyrrolo[3,2-c]pyridine

Similarity: 0.88

[ 630395-95-8 ]

1H-Pyrrolo[3,2-c]pyridine-2-carbaldehyde

Similarity: 0.87

[ 1778-74-1 ]

2-(1H-Pyrrolo[3,2-c]pyridin-3-yl)ethanamine

Similarity: 0.85

[ 1082040-98-9 ]

1H-Pyrrolo[3,2-c]pyridine-6-carbonitrile

Similarity: 0.82

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 271-34-1 ] {[proInfo.proName]}

Quality Control of [ 271-34-1 ]

Related Doc. of [ 271-34-1 ]

Product Details of [ 271-34-1 ]

Calculated chemistry of [ 271-34-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 271-34-1 ]

Application In Synthesis of [ 271-34-1 ]

[ 271-34-1 ] Synthesis Path-Upstream 1~10

[ 271-34-1 ] Synthesis Path-Downstream 1~88

Related Parent Nucleus of [ 271-34-1 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Parent Nucleus of
[ 271-34-1 ]