[ CAS No. 104619-51-4 ] {[proInfo.proName]}

Name: 104619-51-4|Di(1H-imidazol-1-yl)methanimine|95%
Brand: Ambeed
SKU: A110025
Rating: 91 (22 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 104619-51-4

Structure of 104619-51-4 * 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 [ 104619-51-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 104619-51-4 ]

SDS Specification

Alternatived Products of [ 104619-51-4 ]

Product Details of [ 104619-51-4 ]

CAS No. :	104619-51-4	MDL No. :	MFCD10699388
Formula :	C₇H₇N₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FKGQRXQOODICAT-UHFFFAOYSA-N
M.W :	161.16	Pubchem ID :	11355654
Synonyms :

Calculated chemistry of [ 104619-51-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.65
TPSA :	59.49 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.16 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.86
Log Po/w (XLOGP3) :	0.17
Log Po/w (WLOGP) :	0.41
Log Po/w (MLOGP) :	-0.44
Log Po/w (SILICOS-IT) :	-0.44
Consensus Log Po/w :	0.11

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.43
Solubility :	5.97 mg/ml ; 0.0371 mol/l
Class :	Very soluble
Log S (Ali) :	-0.98
Solubility :	17.0 mg/ml ; 0.105 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.02
Solubility :	15.3 mg/ml ; 0.0951 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.32

Safety of [ 104619-51-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 104619-51-4 ]

* 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 [ 104619-51-4 ]
Downstream synthetic route of [ 104619-51-4 ]

[ 104619-51-4 ] Synthesis Path-Upstream 1~6

1
[ 99-57-0 ]
[ 104619-51-4 ]
[ 64037-16-7 ]

Reference： [1] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 1, p. 191 - 193
[2] Patent: WO2010/111483, 2010, A1, . Location in patent: Page/Page column 149

2
[ 288-32-4 ]
[ 506-68-3 ]
[ 104619-51-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	for 0.5 h; Inert atmosphere; Reflux	Step 1: To a solution of imidazole (6.8 g, 100 mmol) in CH₂Cl₂ (500 mL) was added cyanogen bromide (11 mL of 3M in CH₂Cl₂, 33 mmol) and the resultant mixture was heated under nitrogen at reflux for 30 minutes. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to 50 mL and crystallized in the freezer for 2 days. The solid was collected by filtration, washed with cold CH₂Cl₂ and dried under vacuum to afford (di-imidazol-1-yl)-methyleneamine (5.3 g, 99percent).
72%	for 0.5 h; Reflux	To a stirred solution of imidazole (6.80 g, 100 mmol) in anhydrous dichloromethane (500 mL) was added BrCN (3.70 g, 33 mmol) and stirring was continued at reflux for 30 min. The mixture was cooled to room temperature and concentrated to afford di(imidazole-1-yl)methanimine (4.05 g, 72 percent) as a pale yellow solid which was used without further purification.H NMR (DMSO-d₆): 10.21 (br s, 1 H, NH), 8.09 (s, 2 H, 2 * CH), 7.57 (s, 2 H, 2 * CH), 7.12 (s, 2 H, 2 * CH).
8%	for 0.5 h; Reflux	To a solution of 1H-imidazole (42 g, 617 mmol) in dichloromethane (1 L) was added cyanogen bromide (22.5,212 mmol) and the mixture was heated to reflux for 30 minutes,allowed to cool to room temperature and the white solid was filtered off. The filtrate was concentrated to 100 ml andstored in the refrigerator for 3 days. The precipitated solid wasfiltered off to obtain 8 g di(1H-imidazol-l-yl)methanimine(49.6mmol, 8percent).

Reference： [1] Patent: US2012/149718, 2012, A1, . Location in patent: Page/Page column 35
[2] Journal of Organic Chemistry, 2002, vol. 67, # 21, p. 7553 - 7556
[3] Journal of Heterocyclic Chemistry, 2003, vol. 40, # 1, p. 191 - 193
[4] Chemical Communications, 2014, vol. 50, # 91, p. 14257 - 14260
[5] Patent: WO2012/85586, 2012, A1, . Location in patent: Page/Page column 66; 68
[6] Journal of Organic Chemistry, 2008, vol. 73, # 3, p. 1077 - 1087
[7] Journal of Organic Chemistry, 2016, vol. 81, # 11, p. 4516 - 4529
[8] Patent: JP5714745, 2015, B2, . Location in patent: Paragraph 0507; 0508
[9] Patent: WO2007/123936, 2007, A1, . Location in patent: Page/Page column 38
[10] Patent: WO2009/11880, 2009, A2, . Location in patent: Page/Page column 91-92
[11] Patent: WO2010/111483, 2010, A1, . Location in patent: Page/Page column 149
[12] Chemical Communications, 2017, vol. 54, # 5, p. 511 - 514
[13] Patent: WO2018/152405, 2018, A1, . Location in patent: Paragraph 00208

3
[ 288-32-4 ]
[ 590-17-0 ]
[ 104619-51-4 ]

Reference： [1] Patent: US2007/105866, 2007, A1, . Location in patent: Page/Page column 65

4
[ 288-32-4 ]
[ 773837-37-9 ]
[ 104619-51-4 ]

Reference： [1] Chemical Communications, 2017, vol. 54, # 5, p. 511 - 514

5
[ 288-32-4 ]
[ 773837-37-9 ]
[ 36289-36-8 ]
[ 104619-51-4 ]

Reference： [1] Chemical Communications, 2017, vol. 54, # 5, p. 511 - 514

6
[ 288-32-4 ]
[ 36289-36-8 ]
[ 104619-51-4 ]

Reference： [1] Chemical Communications, 2017, vol. 54, # 5, p. 511 - 514

[ 104619-51-4 ] Synthesis Path-Downstream 1~88

1
[ 110-89-4 ]
[ 104619-51-4 ]
[ 477482-01-2 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 7553 - 7556

2
[ 288-32-4 ]
[ 506-68-3 ]
[ 104619-51-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	In dichloromethane; for 0.5h;Inert atmosphere; Reflux;	Step 1: To a solution of imidazole (6.8 g, 100 mmol) in CH2Cl2 (500 mL) was added cyanogen bromide (11 mL of 3M in CH2Cl2, 33 mmol) and the resultant mixture was heated under nitrogen at reflux for 30 minutes. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to 50 mL and crystallized in the freezer for 2 days. The solid was collected by filtration, washed with cold CH2Cl2 and dried under vacuum to afford (di-imidazol-1-yl)-methyleneamine (5.3 g, 99%).
72%	In dichloromethane; for 0.5h;Reflux;	To a stirred solution of imidazole (6.80 g, 100 mmol) in anhydrous dichloromethane (500 mL) was added BrCN (3.70 g, 33 mmol) and stirring was continued at reflux for 30 min. The mixture was cooled to room temperature and concentrated to afford di(imidazole-1-yl)methanimine (4.05 g, 72 %) as a pale yellow solid which was used without further purification.H NMR (DMSO-d6): 10.21 (br s, 1 H, NH), 8.09 (s, 2 H, 2 * CH), 7.57 (s, 2 H, 2 * CH), 7.12 (s, 2 H, 2 * CH).
8%	In dichloromethane; for 0.5h;Reflux;	To a solution of 1H-imidazole (42 g, 617 mmol) in dichloromethane (1 L) was added cyanogen bromide (22.5,212 mmol) and the mixture was heated to reflux for 30 minutes,allowed to cool to room temperature and the white solid was filtered off. The filtrate was concentrated to 100 ml andstored in the refrigerator for 3 days. The precipitated solid wasfiltered off to obtain 8 g di(1H-imidazol-l-yl)methanimine(49.6mmol, 8%).

	In dichloromethane; at 40℃; for 0.5h;	Synthesis of 1.1 -di-1 H-imidazol-1-yl-methyleneamine; To a solution of 1 H-imidazole (3.52g, 51.6mmol), in DCM (25OmL) cyanic bromide was added (1.82g, 17.2mmol). The reaction mixture was stirred at 400C for 30min. Part of the solvent was evaporated, leaving around 3OmL, then cooled at 0C for 1h resulting in a white precipitate which was filtered to afford the expected product 3.3g.
	In dichloromethane; for 0.5h;Heating / reflux;	[00192] 5-(Isoquinolin-6-yl)-l,3,4-oxadiazol-2-amine: A 3 M DCM solution of bromoformonitrile (0.2 mL, 0.6 mmol)(commercially available from Aldrich) was mixed with imidazole (0.157 g, 2.3 mmol)(commercialry available from Aldrich) in 10 mL DCM. The mixture was heated and maintained to reflux for 30 minutes in a round bottom flask. After the DCM was removed under a reduced pressure, isoquinoline-6- carbohydrazide (0.1 g, 0.53 mmol) suspended in 50 mL THF was added into the flask. The mixture was heated and maintained at reflux for 3 hours. After removing the THF, the remaining residue was mixed with 10 mL water and filtered. After washing with water and air drying, a white solid was obtained as the desired product (0.107 g, 96%) LCMS (API-ES) m/z (%): 213.0 (100%, M++H).
	In dichloromethane; for 0.5h;Reflux;	To a solution of imidazole (13.6 g, 0.2 mol) in IL of DCM was added BrCN (7.4 g, 66 mmol), and the mixture was heated at reflux for 30 minutes. The mixture was cooled to RT, and the white precipitate removed by filtration, and the filtrate concentrated to 100 mL then cooled to 0C for 2 days. The crystallized solid was filtered and washed with cold DCM, then dried in vacuo to give the desired product (8.8 g) as a white solid.
	In dichloromethane; for 0.5h;Reflux;	To imidazole (0.41 g, 6.0 mmol) in CH2CI2 was added bromoacetonitrile (0.21 g, 2.0 mmol), and the reaction was refluxed for 30 minutes. The mixture was cooled to room temperature and filtered, and the filtrate was concentrated to give the desired product.
8.8 g	In dichloromethane; for 0.5h;Reflux;	To a solution of imidazole (13.6 g, 0.2 mol) in 1 L of DCM was added BrCN (7.4 g, 66 mmol), and the mixture was heated at reflux for 30 minutes. The mixture was cooled to RT, and the white precipitate removed by filtration, and the filtrate concentrated to 100 mL then cooled to 0 C. for 2 days. The crystallized solid was filtered and washed with cold DCM, then dried in vacuo to give the desired product (8.8 g) as a white solid.

Reference： [1]Patent: US2012/149718,2012,A1 .Location in patent: Page/Page column 35
[2]Journal of Organic Chemistry,2002,vol. 67,p. 7553 - 7556
[3]Chemical Communications,2014,vol. 50,p. 14257 - 14260
[4]Patent: WO2012/85586,2012,A1 .Location in patent: Page/Page column 66; 68
[5]Journal of Organic Chemistry,2008,vol. 73,p. 1077 - 1087
[6]Journal of Organic Chemistry,2016,vol. 81,p. 4516 - 4529
[7]Patent: JP5714745,2015,B2 .Location in patent: Paragraph 0507; 0508
[8]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 38
[9]Patent: WO2009/11880,2009,A2 .Location in patent: Page/Page column 91-92
[10]Patent: WO2010/111483,2010,A1 .Location in patent: Page/Page column 149
[11]Chemical Communications,2018,vol. 54,p. 511 - 514
[12]Patent: WO2018/152405,2018,A1 .Location in patent: Paragraph 00208
[13]Patent: US2019/127365,2019,A1 .Location in patent: Paragraph 0910-0911

3
[ 506-68-3 ]
[ 104619-51-4 ]
[ 477482-07-8 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 7553 - 7556

4
[ 885588-69-2 ]
[ 104619-51-4 ]
[ 955372-13-1 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 18h;	Example 2: r4-(5-Amino-M ,3,41oxadiazol-2-yl)-pyridin-3-v?-(2-fluoro-4-iodo- phenvD-amine; To a solution of 3-(2-Fluoro-4-iodo-phenylamino)-isoniotacotiniotac acid hydrazide (1g, 2.68mmol) in DMSO (6mL) were added 1 ,1 -di-1 H-imidazol-1-yl-methyleneamine (864mg, 5.36mmol). The reaction mixture was stirred at RT for 18h. Quenching of the reaction by adding water (6OmL). A solid precipitated out. The solid was filtered, washed with water and cold methanol. Yield: white solid 1.Og. LC-MS (Method A) [4.66min; 398(M+1)].

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 38

5
[ 955373-08-7 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(2,4-dibromo-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 14: r4-(5-Amino- Pl .3.41 oxadiazol-2-yl)-pyridin-3-yll-(2,4-dibromo- phenvP-amine; To a solution of 3-(2,4-Dibromo-phenylamino)-isonicotinic acid hydrazide (200mg, 0.52 mmol) in DMSO (2ml_) C- (Di-imidazol-i-yl)-methyleneamine (167mg, 1.04 mmol) was added. The reaction mixture was stirred at RT under Argon overnight, then poured into water. A solid precipitated out, which was filtered, and washed with methanol to afford the desired product (100mg). LC/MS (Method A) [5.23min; 412(M+1)].

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 44

6
[ 955373-13-4 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(2-chloro-4-iodo-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 24: [4-(5-AmJnO- Pl, 3,41 oxadiazot-2-yl)-pyridin-3-yl1-(2-chloro-4-iodo- phenvh-amine; To a solution of 3-(2-Chloro-4-iodo-phenylamino)-isonicotinic acid hydrazide (150mg, 0.39mmol, 1 eq), in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (124mg, 0.77mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight and then poured into water. The product was isolated by filtration (135 mg). LC/MS (Method A) [5.22min; 414(M+1 )]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 49

7
[ 955373-14-5 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(2-fluoro-4-methoxy-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 2S: r4-(5-Amno- M .3.41 oxadiazol-2-vO-pyridin-3-ylH2-fluoro-4-methoxy- phenvD-amine; To a solution of 3-(2-Fluoro-4-methoxy-phenylamino)-isonicotinic acid hydrazide (150mg, 0.54mmol, 1eq) in DMSO (2ml_) C- (Di-imidazol-i-yl)-methyleneamine (175mg, 1.09mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight and then poured into water. The product was isolated by filtration (89 mg). LC/MS (Method A) [0.52mi?; 302(M+1)]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 50

8
[ 955373-15-6 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-1-oxy-pyridin-3-yl]-(2-fluoro-4-iodo-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 27: r4-(5-Amino- H .3.41 oxadiazol-2-yl)-1-oxy-pyiotadin-3-v?-(2-fluoro-4- iodo-phenvh-amine; To a solution of 3-(2-Fluoro-4-iodo-phenylamino)-1-oxy-isonicotinic acid hydrazide (150mg, 0.39mmol, 1eq) in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (124mg, 0.78mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight and then poured into water. The product was isolated by filtration (80 mg) . LC/MS (Method A) [4.68min; 414(M+1 )]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 51

9
[ 955373-16-7 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-6-ethynyl-pyridin-3-yl]-(2-fluoro-4-iodo-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 28: r4-(5-Amino- H .3.41 oxadiazol-2-yl)-6-ethvnyl-pyridin-3-v?-(2-fluoro-; To a solution of 2-Ethynyl-5- (2-fluoro-4-iodo-phenylamino)-isonicotinic acid hydrazide (124mg, 0.31 mmol, 1eq) in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (101mg, 0.63mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight, and then poured into water. The solid fomed was isolated by filtration and washed with methanol to afford the product (30 mg). LC/MS (Method A) [5.15min; 422(M+1 )]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 51

10
[ 955373-17-8 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(4-iodo-2-methyl-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 29: r4-(5-Amino- Pl.3,41 oxadiazol-2-vO-pyridin-3-vn-(4-iodo-2-methyl- phenvD-atnine; To a solution of 3-(4-lodo-2-methyl-phenylamino)-isonicotinic acid hydrazide (200mg, 0.54mmol, 1eq) in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (175mg, 1.09mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight, and then poured into water. The solid fomed was isolated by filtration and washed with methanol to afford the product 1 (45 mg). LC/MS (Method A) [4.90min; 394(M+1)]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 51-52

11
[ 885589-47-9 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(4-bromo-2-fluoro-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 34: r4-(5-Amino- PI ,3,4] oxadiazol-2-yl)-pyridin-3-v?-(4-bromo-2-fluoro- phenvD-amine; To a solution of 3-(4-Brorno-2-fluoro-phenylamino)-isonicotinic acid hydrazide (200mg, 0.62mmol, 1eq) in DMSO (2ml_) C- (Di-imidazol-i-yl)-methyleneamine (198mg, 1.23mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight. It was then poured into water and the solid that precipitated out was filtered and washed with methanol to afford the desired product (195 mg). LC/MS (Method A) [0.62min; 351(M+1>]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 54

12
[ 955373-19-0 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-pyridin-3-yl]-(4-bromo-2-chloro-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 35: r4-(5-Amino- Pl .3.41 oxadiazol-2-yl)-pyridin-3-vn-f4-bromo-2-chloro- phenvU-amine; To a solution of 3-(4-Bromo-2-chloro-phe?ylamino)-iso?icotinic acid hydrazide (200mg, 0.59mmol, 1eq) in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (188mg, 1.17mmol, 2eq) was added. The reaction mixture was stirred at RT under argon overnight and then poured into water. A solid precipitated out that was filtered and washed with methanol to give the desired product (125 mg). LC/MS (Method A) [4.77min; 367(M+1)]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 54-55

13
[ 955373-22-5 ]
[ 104619-51-4 ]
[4-(5-amino-[1,3,4]oxadiazol-2-yl)-5-fluoro-pyridin-3-yl]-(2-fluoro-4-iodo-phenyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃;	Example 48: r4-(5-Amino- M.3,41 oxadiazot-2-yl>-5-fluoro-pyridin-3-v?-(2-fluoro-4- iodo-phenvD-amine; To a solution of 3-Fluoro-5- (2-fluoro-4-iodo-phenylamino)-isonicotinic acid hydrazide (100mg0.26mmol, 1eq) in DMSO (2mL) C- (Di-imidazol-i-yl)-methyleneamine (123mg, 0.77mmol, 3eq) was added. The reaction mixture was stirred at RT under argon overnight and then poured- into water. A solid precipitated out that was filtered out and washed with methanol to afford the desired product (65 mg). LC/MS (Method A) [5.19min; 416(M-H)]

Reference： [1]Patent: WO2007/123936,2007,A1 .Location in patent: Page/Page column 62

14
[ 1007232-84-9 ]
[ 104619-51-4 ]
[ 1007232-56-5 ]

Yield	Reaction Conditions	Operation in experiment
19%	In tetrahydrofuran; for 72h;Heating / reflux;	Example 63 4-[2-(2-imino-4,4-dimethyl-1,3-oxazolidin-3-yl)-1,3-thiazol-4-yl]benzonitrile A mixture of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (2.00 g, 7.31 mmol), prepared in the same manner as described in step 3 of Example 52, and replacing 3-(2-bromoacetyl)benzonitrile with 4-(2-bromoacetyl)benzonitrile, and C-(di-imidazol-1-yl)-methyleneamine (1.30 g, 8.07 mmol) in 35 mL of tetrahydrofuran was refluxed under nitrogen for three days. The reaction was concentrated under reduced pressure to remove the tetrahydrofuran. The residue was partitioned between methylene chloride and water. The organic layer was separated, dried (MgSO4), filtered and the solvent removed under reduced pressure. Purification of the residue on a Horizon Flash Collector (the Biotage FLASH 40+ cartridge) using a linear gradient of hexane in methylene chloride as the eluent gave the title compound (417.2 mg, 19%) as an off-white solid, mp 158-161 C.; MS (ES) m/z 299.0 [M+H]+. Anal. Calcd for C15H14N4OS: C, 60.38; H, 4.73; N, 18.78. Found: C, 60.38; H, 4.82; N, 18.67.
19%	In tetrahydrofuran; for 72h;Heating / reflux;	Example 4 4-[2-(2-imino-4,4-dimethyl-1,3-oxazolidin-3-yl)-1,3-thiazol-4-yl]benzonitrile A mixture of 4-{2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (2.00 g, 7.31 mmol), prepared in the same manner as described in step 3 of Example 3, and replacing 3-(2-bromoacetyl)benzonitrile with 4-(2-bromoacetyl)benzonitrile, and C-(di-imidazol-1-yl)-methyleneamine (1.30 g, 8.07 mmol) in 35 mL of tetrahydrofuran was refluxed under nitrogen for three days. The reaction was concentrated under reduced pressure to remove the tetrahydrofuran. The residue was partitioned between methylene chloride and water. The organic layer was separated, dried (MgSO4), filtered and the solvent removed under reduced pressure. Purification of the residue on a Horizon Flash Collector (the Biotage FLASH 40+ cartridge) using a linear gradient of hexane in methylene chloride as the eluent gave the title compound (417.2 mg, 19%) as an off-white solid, mp 158-161 C.; MS (ES) m/z 299.0 [M+H]+. Anal. Calcd for C15H14N4OS: C, 60.38; H, 4.73; N, 18.78. Found: C, 60.38; H, 4.82; N, 18.67.

Reference： [1]Patent: US2008/45556,2008,A1 .Location in patent: Page/Page column 28
[2]Patent: US2008/45579,2008,A1 .Location in patent: Page/Page column 16

15
[ 388574-70-7 ]
[ 104619-51-4 ]
2'-(1H-imidazol-1-yl)-8'-methyl-7',8'-dihydro-6'H,10H-spiro[acridin-9,4'-imidazo[1,2-a][1,3,5]triazine] [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 5387 - 5390

16
[ 938051-29-7 ]
[ 104619-51-4 ]
MCL-453 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 4106 - 4112

17
[ 938051-30-0 ]
[ 104619-51-4 ]
MCL-454 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 4106 - 4112

18
C₃₃H₃₅N₇O₂ [ No CAS ]
[ 104619-51-4 ]
3-cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid {1-[6-(5-amino-1,3,4-oxadiazol-2-yl)-1-methyl-1H-benzimidazol-2-yl]cyclobutyl}amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	In tetrahydrofuran; at 70℃; for 16h;	EXAMPLE 36; 3-Cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid {1- [6- (5- amino-1,3, 4-oxadiazol-2-yl)-1-methyl-1 H-benzimidazol-2-yl] cyclobutyl} amide; C- (Di-imidazol-1-yl)-methyleneamine (25 mg, 0.16 mmol) was added in a single portion to a solution of compound 35-3 (Example 35) (80 mg, 0.14 mmol) in THF (4 mL). The resulting solution was heated to 70 C for 16 h, after which time a white precipitate was observed. The reaction was then concentrated under reduced pressure, dissolved in 4 mL DMSO and directly purified on a reversed phase Cis, semi-preparative HPLC column (using a solvent gradient from 5% H20 in MeCN to 100% MeCN) to isolate compound 36-1 (compound 1129, Table 1) as a yellow amorphous solid in >95% homogeneity (19 mg, 23% yield). 'H NMR (400 MHz, DMSO): 5 1.54-1. 67 (m, 2H), 1.79-1. 94 (m, 6H), 1.95-2. 06 (m, 1H), 2.11-2. 23 (m, 1H), 2.74-2. 84 (m, 2H), 3.19-3. 05 (m, 3H), 3.69 (s, 3H), 3.91 (s, 3H), 7.49 (dd, J = 1.8 & 5.7 Hz, 1 H), 7.59-7. 71 (m, 3H), 7.86-7. 92 (m, 2H) 7. 96-8. 01 (m, 1H), 8.06-8. 10 (m, 1H), 8. 10 (s, 1H), 8.78 (d, J = 4.3 Hz, 1H), 9.51 (s, 1H).

Reference： [1]Patent: WO2005/80388,2005,A1 .Location in patent: Page/Page column 97

19
[ 917363-81-6 ]
[ 104619-51-4 ]
9-phenyl-8-(4-[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3-amine trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 80 - 85℃; for 3 - 4h;	To 5-hydrazino-3-phenyl-2-(4-{ [4-(5-pyridin-2-yl-lH-l,2,4-triazol-3-yl)piperidm-l- yl]methyl}phenyl)-l,6-naphthyridine (1-3) (70 mg, 0.126 mmol) in DMF (1.5 mL) was added literature known 1,1-di-lH-imidazol-l-ylmethanimine (102 mg, 0.633 mmol). The reaction mixture was stirred at 85C for 4 hours, concentrated in vacuo, and chromatographed to furnish the desired 9-phenyl-8-(4- { [40(5-pyridin-2-yl-lH-l,2,4-triazol-3-yl)piperidin-l-yl]emthyl}phenyl}[l,2,4]triazolo[3,4-f]-l,6- naphthyridin-3-amine (1-4) (46 mg) as its trifluoroacetic acid salt. 1H NMR: (500MHz, CDCl3) delta 8.76 (s, IH), 8.74 (d, J= 4.3 Hz, IH), 8.29-8.27 (m, 2 H), 8.19 (m, IH), 7.67 (m, IH), 7.54-7.53 (m, 2H), 7.48- 7.46 (m, 2H), 7.47 (d, J= 7.7 Hz , IH), 7.34-7.26 (m, 5H), 4.43 (s, 2H), 3.65 (br d, J= 10.9 Hz, 2H), 3.46 (br s, 1 H), 3.27-3.19 (m, 2H), 2.50-2.42 (m, 2H), 2.10-2.06 (m, 2H).

Reference： [1]Patent: WO2006/135627,2006,A2 .Location in patent: Page/Page column 76

20
[ 927388-83-8 ]
[ 104619-51-4 ]
[ 927390-92-9 ]

Reference： [1]Patent: WO2007/20936,2007,A1 .Location in patent: Page/Page column 196-197
[2]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 7593 - 7606

21
[ 288-32-4 ]
[ 590-17-0 ]
[ 104619-51-4 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; for 0.5h;Heating / reflux;	Route 8: Step 1: Alkylation (Int-5) To imidazole (0.41 g, 6.0 mmol) in CH2Cl2 was added bromoacetonitrile (0.21 g, 2.0 mmol), and the reaction was refluxed for 30 minutes. The mixture was cooled to room temperature and filtered, and the filtrate was concentrated to give the desired product.

Reference： [1]Patent: US2007/105866,2007,A1 .Location in patent: Page/Page column 65

22
4-[3-tert-butylsulfanyl-2-(2,2-dimethyl-propyl)-5-(pyridin-2-ylmethoxy)-indol-1-ylmethyl]-benzoic acid hydrazide [ No CAS ]
[ 104619-51-4 ]
5-{4-[3-tert-butylsulfanyl-2-(2,2-dimethyl-propyl)-5-(pyridin-2-ylmethoxy)-indol-1-ylmethyl]-phenyl}-[1,3,4]oxadiazol-2-ylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 85℃; for 3h;	Step 4: 3-{3-tert-Butylsulfanyl-5-(6-fluoro-quinolin-2-ylmethoxy)-1-[4-(6-methoxy-pyridin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid F-3 (0.22 g, 0.31 mmol) was dissolved in MeOH (1.5 mL), THF (3 mL), and water (1.5 mL). Lithium hydroxide (0.08 g, 1.9 mmol) was added, and the reaction was heated at 60 C. for 3.5 hours until no starting material was seen by TLC analysis. The reaction was diluted with water, acidified to pH 5 with citric acid, and extracted with EtOAc. The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated to give the desired product (F-4).
	In N,N-dimethyl-formamide; at 85℃; for 3h;	To 4-[3-tert-Butylsulfanyl-2-(2,2-dimethyl-propyl)-5-(pyridin-2-ylmethoxy)-indol-l- ylmethylj-benzoic acid hydrazide (0.05g, O. lOmmol) in DMF (lmL) was added C-(Di-imidazol-l- yl)-methyleneamine (0.08g, 0.50mmol), and the reaction was heated at 85C for 3 hours. The mixture was cooled to room temperature and partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgS04, filtered, and concentrated. The residue was purified on silica gel (EtOAc:hexane gradient) to give the desired product.

Reference： [1]Patent: US2007/105866,2007,A1 .Location in patent: Page/Page column 78
[2]Patent: WO2018/152405,2018,A1 .Location in patent: Paragraph 00269

23
[ 127542-03-4 ]
[ 104619-51-4 ]
[ 1007629-94-8 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 1077 - 1087

24
[ 20662-53-7 ]
(S)-N,N-dibenzylpropane-1,2-diamine [ No CAS ]
[ 104619-51-4 ]
[ 1089275-53-5 ]

Yield	Reaction Conditions	Operation in experiment
4%		27) Guanidine derivative preparation; Preparation of N-((S)-2-(dibenzylamino)propyl)-4-(1,2-dihydro-2-oxobenzo[d]intidazol-3-yl)piperidine-1-carboxamidine (Compound n95):; [Show Image] To a stirred solution of the 4-(2-keto-1-benzimidazolinyl)-pipehdine (48 mg, 0.22 mmol) in THF/DMF 4:1 (0.6 mL) was added <strong>[104619-51-4]di(1H-imidazol-1-yl)methanimine</strong> (58 mg, 0.36 mmol) under N2 atmosphere. The reaction mixture was stirred for 72h at room temperature. Water (1 mL) was introduced and the mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. To the crude material was added a solution of (S)-N,N-dibenzylpropane-1,2-diamine in THF (0.4 mL). The solution was refluxed for 72h and the solvent was removed on vacuo. The residue was purified with preparative HPLC to obtain a colorless oil (4 mg, 4%). 1H NMR (400 MHz, CDCl3) delta 10.88 (bs, 1H, NH), 7.29 (m, 6H, Ar), 7.15 (m, 5H, Ar), 7.00 (m, 3H, Ar), 5.97 (s, 1H, NH), 4.21 (m, 1H, CHCH2CH2Npip), 3.86 (m, 1H, CH2N), 3.74 (d, J = 13.2 Hz, 2H, NCH2Ph), 3.46 (m, 1H, m, CH2N), 3.33 (d, J = 13.2 Hz, 2H, NCH2Ph), 3.29-3.05 (m, 2H, CHCH2CH2Npip), 3.00-2.91 (m, 3H, CHMe, CHCH2CH2Npip), 2.58 (m, 1H, CHCH2CH2Npip), 2.25 (m, 1H, CHCH2CH2Npip), 1.86 (bd, J = 10.4 Hz, 1H, CHCH2CH2Npip), 1.75 (bd, J= 10.8 Hz, 1H, CHCH2CH2Npip), 1.19 (d, J= 5.6 Hz, 3H, Me). LC/MS (ES+) m/z 497.3 (M+H)+

Reference： [1]Patent: EP1997805,2008,A1 .Location in patent: Page/Page column 85-86

25
[ 1015068-44-6 ]
[ 104619-51-4 ]
[ 1105709-91-8 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; for 3h;Heating / reflux;	[00192] 5-(Isoquinolin-6-yl)-l,3,4-oxadiazol-2-amine: A 3 M DCM solution of bromoformonitrile (0.2 mL, 0.6 mmol)(commercially available from Aldrich) was mixed with imidazole (0.157 g, 2.3 mmol)(commercialry available from Aldrich) in 10 mL DCM. The mixture was heated and maintained to reflux for 30 minutes in a round bottom flask. After the DCM was removed under a reduced pressure, isoquinoline-6- carbohydrazide (0.1 g, 0.53 mmol) suspended in 50 mL THF was added into the flask. The mixture was heated and maintained at reflux for 3 hours. After removing the THF, the remaining residue was mixed with 10 mL water and filtered. After washing with water and air drying, a white solid was obtained as the desired product (0.107 g, 96%) LCMS (API-ES) m/z (%): 213.0 (100%, M++H).

Reference： [1]Patent: WO2009/11880,2009,A2 .Location in patent: Page/Page column 91-92

26
[ 917363-81-6 ]
[ 104619-51-4 ]
C₃₄H₃₀N₁₀ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 834 - 836

27
[ 16867-03-1 ]
[ 104619-51-4 ]
[ 40926-66-7 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; for 1h;Reflux; Inert atmosphere;	An oven dried round bottom flask was charged withdi(IH-imidazol-l-yl)methanimine (500 mg, 3.10 mmol),2-aminopyridin-3-01 (171 mg, 1.551 mmol) and anhydrousTHF (20 ml) at room temperature. The resulting suspensionwas refluxed under N2 for I hr. LC/MS indicated completeconsumption ofstarting material. The solvent was removed invacuo and the residue was used in the next step withoutfurther purification.

Reference： [1]Patent: JP5714745,2015,B2 .Location in patent: Paragraph 0582; 0583

28
[ 6850-57-3 ]
[ 2536-91-6 ]
[ 104619-51-4 ]
N-(2-methoxybenzyl)-N'-(6-methyl-1,3-benzothiazol-2-yl)guanidine fumarate [ No CAS ]

Reference： [1]Patent: WO2005/82871,2005,A2 .Location in patent: Page/Page column 104

29
[ 1007113-32-7 ]
[ 104619-51-4 ]
[ 1007112-96-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 6538 - 6541

30
[ 63435-16-5 ]
[ 104619-51-4 ]
2-amino-6-hydroxymethylbenzoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%		Step 2: A mixture of methyl 4-amino-3-hydroxybenzoate (883 mg, 5.3 mmol) and (diimidazol-1-yl)-methyleneamine (851 mg, 5.3 mmol) in dry THF (40 mL) was warmed at 65 C. overnight. Additional (di-imidazol-1-yl)-methyleneamine (450 mg, 2.8 mmol) was added and the reaction was warmed at 75 C. for 3 days. The reaction mixture was poured onto H2O and ethyl acetate and extracted 2 times with ethyl acetate. The organic phase was washed with saturated aqueous NH4Cl, washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated in vacuo to give a dark solid. This dark solid was dissolved in dry THF (30 mL) and the resulting solution was placed under argon and cooled to 0 C. A solution of LAH (5.2 mL of 2M in THF) was added. The reaction mixture was stirred at room temperature overnight, then quenched by sequential addition of H2O (0.178 mL), a 15% aqueous solution of NaOH (0.178 mL) and H2O (0.53 mL). After stirring at room temperature for 10 minutes, the mixture was poured onto 0.01% NaOH and CH2Cl2 (containing 0.5% methanol) and the mixture was extracted 4 times with CH2Cl2 (containing 0.5% methanol). The combined organic phase was washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated in vacuo. The residue was slurried in approximately 1-5% methanol in CH2Cl2. The solid was collected, washed several times with CH2Cl2 to afford (2-aminobenzooxazol-6-yl)-methanol. (118 mg) as a yellow solid and the filtrate was purified by chromatography (silica, 4% methanol in CH2Cl2) to afford an additional 23 mg (16% overall yield): 1H NMR (300 MHz, DMSO-d6) delta ppm 4.50 (d, J=5.84 Hz, 2H) 5.13 (t, J=5.75 Hz, 1H) 7.00-7.18 (m, 2H) 7.26 (d, J=0.75 Hz, 1H) 7.32 (s, 2 H).

Reference： [1]Patent: US2012/149718,2012,A1 .Location in patent: Page/Page column 35

31
[ 53981-24-1 ]
[ 104619-51-4 ]
6-fluorobenzo[d]oxazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In acetonitrile; for 6h;Inert atmosphere; Reflux;	To a of solution 5-fluoro-2-nitrophenol (4.77 mmol, 0.75 g) in methanol (50 mL), PtO2 (0.24 mmol, 0.06 g) was added. The reaction was flushed with argon followed by hydrogen for fifteen minutes each with constant magnetic stirring. The reaction was then maintained under hydrogen atmosphere at ordinary pressure (balloon) for fifteen hours. Argon was again flushed through the reaction vessel for 15 minutes. Then the reaction contents were filtered quickly over a thin pad of celite which was then immediately washed with methanol (25 mL). The filtrate was concentrated in vacuo yielding an orange residue. The residue was quickly re-dissolved in acetonitrile (50 mL) and <strong>[104619-51-4]di(imidazole-1-yl)methanimine</strong> (11.92 mmol, 1.92 g) was added with constant magnetic stirring. The reaction was then placed under argon atmosphere and gently refluxed for six hours. The reaction was concentrated under reduced pressure and silica gel column chromatography (2:1 hexanes/ethyl acetate) provided a crystalline white solid in a 71% yield. The product of the reduction (2-amino-5-fluorophenol) is air unstable and appropriate measures should be taken to minimize air exposure.
57%	In tetrahydrofuran; at 60℃; for 72h;	Step 1: To a solution of 2-amino-5-fluorophenol (127 mg, 1 mmol) in anhydrous THF (5 mL) was added (di-imidazol-1-yl)-methyleneamine (prepared in example 20, 161 mg, 1 mmol) and the resulting solution was heated at 60 C. for 3 days. The reaction was diluted with ethyl acetate (20 mL) and washed with H2O, saturated aqueous NH4Cl and saturated aqueous NaCl and dried over Na2SO4. The mixture was concentrated in vacuo. Purification by chromatography (silica, 50% ethyl acetate/hexanes) afforded 6-fluorobenzooxazol-2-ylamine (87 mg, 57%): 1H NMR (300 MHz, MeOH) delta ppm 3.29 (s, 2H) 6.01 (ddd, J=9.89, 8.57, 2.45 Hz, 1H) 6.12 (dd, J=8.01, 2.54 Hz, 1H) 6.29 (dd, J=8.57, 4.80 Hz, 1H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3521 - 3525
[2]Patent: US2012/149718,2012,A1 .Location in patent: Page/Page column 43

32
[ 51006-03-2 ]
[ 104619-51-4 ]
2'-amino-1',3'-oxazolo-(4',5':2,3)-3-deoxymorphine [ No CAS ]

Reference： [1]Monatshefte fur Chemie,2010,vol. 141,p. 1135 - 1143

33
[ 1383778-48-0 ]
[ 104619-51-4 ]
[ 1383778-49-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	In tetrahydrofuran; at 20℃;	To a stirred solution of <strong>[104619-51-4]di(imidazole-1-yl)methanimine</strong> (0.50 g, 3.25 mmol) in anhydrous tetrahydrofuran (15 mL) was added mexiletine [A/-Boc-(S)-ornithine] amide (1.28 g, 3.25 mmol) and stirring was continued at room temperature overnight. The mixture was evaporated to dryness. Dichloromethane (100 mL) and water (100 mL) were added and the organic layer was separated, washed with saturated aqueous ammonium chloride (5 * 100 mL), saturated brine (100 mL), dried (MgS04) and concentrated. The residue was triturated with diethyl ether, collected by suction filtration and dried in vacuo to afford mexiletine [A/"-Boc-A/5-imidazole-1-yl-(S)-arginine] amide (0.63 g, 40 %) as a white solid.

Reference： [1]Patent: WO2012/85586,2012,A1 .Location in patent: Page/Page column 67; 68

34
[ 52334-79-9 ]
[ 104619-51-4 ]
5-methyloxazolo[5,4-b]pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In tetrahydrofuran; at 65℃; for 16h;	Step A: 5-Methyloxazolo[5,4-b] A round-bottomed flask was charged with 3-amino-6-methylpyridin-2(lH)- one (3.91 g, 31.5 mmol) and di(lH-imidazol-l-yl)methanimine (7.62 g, 47.3 mmol). THF (63.0 mL) was added to the reaction flask at ambient temperature. The flask was then placed into a preheated oil-bath at 65 C and stirred at that temperature. After 16 h, the reaction vessel was removed from the oil-bath and allowed to cool to ambient temperature. The volatiles were removed to 1/3 original volume under reduced pressure before the solids were filtered and washed with THF (100 mL) to afford 5 -methyloxazolo [5, 4-b]pyridin-2-amine (3.17 g, 21.2 mmol, 67 % yield) as a tan solid. MS (LC/MS) R.T. = 0.88; [M+H]+ = 150.27

Reference： [1]Patent: WO2013/177024,2013,A1 .Location in patent: Page/Page column 94; 95

35
[ 2835-98-5 ]
[ 104619-51-4 ]
6-methyl-1,3-benzoxazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In tetrahydrofuran; for 2h;Inert atmosphere; Reflux;	Step A: 6-Methylbenzojdjoxazol-2-amine An oven-dried, round-bottomed flask was charged with <strong>[104619-51-4]di(1H-imidazol-1-yl)methanimine</strong> (1.40 g, 8.69 mmol), 2-amino-5-methylphenol (713 mg, 5.79 mmol) and anhydrous THF (20m1) at ambient temperature. The resulting suspension was refluxed under N2 (g) for 2 h to give complete conversion based on LC/MS. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (0-30 % 9:1 methanol: ammonium hydroxide-chloroform) to affordthe expected product, benzo[d]oxazol-2-amine (792 mg, 5.35 mmol, 92 % yield), as agrey solid. ?H NMR (400 MHz, CHLOROFORM-cl) ppm 7.19 - 7.34 (1 H, m), 7.11(1 H, s), 7.01 (1 H, d, J=7.8 Hz), 5.60 (2 H, br. s.), 2.43 (3 H, s). MS (LC/MS) R.T.= 0.89; [M-I-H] = 149.09.
92%	In tetrahydrofuran; for 2h;Inert atmosphere; Reflux;	An oven-dried, round-bottomed flask was chargedwith di(lH-imidazoI-I-yl)methanimine (1.40 g, 8.69 mmol),2-amino-5-methylphenol (713 mg, 5.79 mmol) and anhydrous THF (20 ml) at ambient temperature. The resulting suspension was refluxed underN2 (g) for 2 h. The solvent wasremoved in vacuo and the residue was purified by silica gelchromatography (0-30% 9: I methanol:annnonium hydroxide-chloroform) to afford benzo[d]oxazol-2-amine (792 mg,5.35 mmol, 92% yield), as a grey solid.

Reference： [1]Patent: WO2013/177024,2013,A1 .Location in patent: Page/Page column 64
[2]Patent: JP5714745,2015,B2 .Location in patent: Paragraph 0663; 0664

36
2-amino-5-(trifluoromethoxy)phenol [ No CAS ]
[ 104619-51-4 ]
2-amino-6-(trifluoromethoxy)benzoxazole [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2013,vol. 22,p. 6089 - 6095

37
[ 106-47-8 ]
[ 104619-51-4 ]
[ 1610839-78-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	In tetrahydrofuran; at 20℃;	To a solution of 22 (200 mg, 1.24 mmol) in freshly distilled THF (8 ml), was added 4-chloro-aniline(208 mg, 1.64 mmol). The mixture was stirred at room temperature for 24 h. The solvent was thenremoved under vacuum and the residue was purified on silica with 10% MeOH/DCM to yield theproduct as a white solid (240 mg, 1.09 mmol) in 88% yield.
35%	In tetrahydrofuran; at 20℃; for 16h;	N-( 4-Chlorophenyl)-lH-imidazole-l-carboximidamide : To a solution of 4- chloroaniline (500 mg, 3.92 mmol) in THF (8 mL) was added di(lH-imidazol-l-yl)methanimine (757 mg, 4.7 mmol) at RT and stirred for 16 h. The reaction suspension was concentrated and purified by silica gel chromatography eluting with EtOAc to give N-(4-chlorophenyl)-lH- imidazole-l-carboximidamide (300 mg, yield: 35%) as a white solid.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3083 - 3090
[2]Patent: WO2020/37155,2020,A1 .Location in patent: Paragraph 0243-0245

38
[ 43115-41-9 ]
[ 104619-51-4 ]
[ 1421232-29-2 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6128 - 6140

39
[ 53981-25-2 ]
[ 104619-51-4 ]
7-fluorobenzo[d]oxazol-2-amine [ No CAS ]