[ CAS No. 1232431-75-2 ] {[proInfo.proName]}

Name: 1232431-75-2|4-Bromopyridine-2,3-diamine|98%
Brand: Ambeed
SKU: A363155
Price: 11.0 USD
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Quality Control of [ 1232431-75-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1232431-75-2 ]

CAS No. :	1232431-75-2	MDL No. :	MFCD15143394
Formula :	C₅H₆BrN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VDWHUTJUOZXVQW-UHFFFAOYSA-N
M.W :	188.03	Pubchem ID :	53407909
Synonyms :

Calculated chemistry of [ 1232431-75-2 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	2.0
Molar Refractivity :	40.75
TPSA :	64.93 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) :	-7.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.24
Log Po/w (XLOGP3) :	0.51
Log Po/w (WLOGP) :	1.02
Log Po/w (MLOGP) :	0.37
Log Po/w (SILICOS-IT) :	0.67
Consensus Log Po/w :	0.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.82
Solubility :	2.84 mg/ml ; 0.0151 mol/l
Class :	Very soluble
Log S (Ali) :	-1.44
Solubility :	6.76 mg/ml ; 0.036 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.16
Solubility :	1.3 mg/ml ; 0.0069 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.92

Safety of [ 1232431-75-2 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3259
Hazard Statements:	H314	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 1232431-75-2 ]

* 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 [ 1232431-75-2 ]
Downstream synthetic route of [ 1232431-75-2 ]

[ 1232431-75-2 ] Synthesis Path-Upstream 1~2

1
[ 1305317-30-9 ]
[ 1232431-75-2 ]

Yield	Reaction Conditions	Operation in experiment
53%	With tin(IV) chloride In ethanol; water at 90℃; for 2.01667 h;	To a stirred solution of 4-bromo-2-nitropyridin-3-amine (1 g, 4.59 mmol) in a mixture of EtOH (20 mL) and water (5 mL) was added tin(IV) chloride (3.00 g, 11.52 mmol) over a period of 1 mm. The reaction mixture was heated to 90 °C and stirred for 2 h. The reaction mixture was allowed to cool to room temperature, thenpoured into saturated aq. sodium bicarbonate solution (50 mL) and extracted with DCM (2 x 100 mL). The combined organic extracts were washed with water (100 mL), brine (100 mL), organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 4-bromopyridine-2,3-diamine (460 mg, 2.446 mmol, 53percent yield) as a pale brown solid. The compound was taken to thenext step without further purification. LCMS (ESI) m/e 187.9 [(M+H), calcd for C5H7BrN3, 187.91; LC/MS retention time (Method C) tR = 0.52 mm.

Reference： [1] Synthesis, 2011, # 5, p. 794 - 806
[2] Patent: WO2017/59080, 2017, A1, . Location in patent: Page/Page column 35; 111; 112

2
[ 13269-19-7 ]
[ 1232431-75-2 ]

Reference： [1] Synthesis, 2011, # 5, p. 794 - 806
[2] Patent: WO2017/59080, 2017, A1,

[ 1232431-75-2 ] Synthesis Path-Downstream 1~88

1
[ 13269-19-7 ]
[ 1232431-75-2 ]

Reference： [1]Synthesis,2011,p. 794 - 806
[2]Patent: WO2017/59080,2017,A1

2
[ 1305317-30-9 ]
[ 1232431-75-2 ]

Yield	Reaction Conditions	Operation in experiment
53%	With tin(IV) chloride; In ethanol; water; at 90℃; for 2.01667h;	To a stirred solution of 4-bromo-2-nitropyridin-3-amine (1 g, 4.59 mmol) in a mixture of EtOH (20 mL) and water (5 mL) was added tin(IV) chloride (3.00 g, 11.52 mmol) over a period of 1 mm. The reaction mixture was heated to 90 C and stirred for 2 h. The reaction mixture was allowed to cool to room temperature, thenpoured into saturated aq. sodium bicarbonate solution (50 mL) and extracted with DCM (2 x 100 mL). The combined organic extracts were washed with water (100 mL), brine (100 mL), organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 4-bromopyridine-2,3-diamine (460 mg, 2.446 mmol, 53% yield) as a pale brown solid. The compound was taken to thenext step without further purification. LCMS (ESI) m/e 187.9 [(M+H), calcd for C5H7BrN3, 187.91; LC/MS retention time (Method C) tR = 0.52 mm.

Reference： [1]Synthesis,2011,p. 794 - 806
[2]Patent: WO2017/59080,2017,A1 .Location in patent: Page/Page column 35; 111; 112

3
[ 1232431-75-2 ]
[ 1305317-33-2 ]

Reference： [1]Synthesis,2011,p. 794 - 806

4
[ 1232431-75-2 ]
[ 1305317-34-3 ]

Reference： [1]Synthesis,2011,p. 794 - 806

5
[ 1232431-75-2 ]
[ 1305317-35-4 ]

Reference： [1]Synthesis,2011,p. 794 - 806

6
[ 1232431-75-2 ]
[ 1305317-36-5 ]

Reference： [1]Synthesis,2011,p. 794 - 806

7
[ 1232431-75-2 ]
[ 1305317-37-6 ]

Reference： [1]Synthesis,2011,p. 794 - 806

8
[ 1232431-75-2 ]
[ 1305317-38-7 ]

Reference： [1]Synthesis,2011,p. 794 - 806

9
[ 1232431-75-2 ]
[ 1305317-39-8 ]

Reference： [1]Synthesis,2011,p. 794 - 806

10
[ 1232431-75-2 ]
[ 1305317-40-1 ]

Reference： [1]Synthesis,2011,p. 794 - 806

11
[ 1232431-75-2 ]
[ 1305317-41-2 ]

Reference： [1]Synthesis,2011,p. 794 - 806

12
[ 1232431-75-2 ]
[ 1305317-42-3 ]

Reference： [1]Synthesis,2011,p. 794 - 806

13
[ 1232431-75-2 ]
[ 1305317-43-4 ]

Reference： [1]Synthesis,2011,p. 794 - 806

14
[ 1232431-75-2 ]
[ 1226-42-2 ]
[ 1305317-32-1 ]

Reference： [1]Synthesis,2011,p. 794 - 806

15
[ 1232431-75-2 ]
[ 134-81-6 ]
[ 1305317-31-0 ]

Reference： [1]Synthesis,2011,p. 794 - 806

16
[ 1232431-75-2 ]
[ 7470-38-4 ]
4-(4-(7-chloro-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)morpholine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; trichlorophosphate; at 150℃; for 0.75h;Microwave irradiation;	<strong>[1232431-75-2]4-bromopyridine-2,3-diamine</strong> (143 mg, 1.0 mmol) and 4- morpholinobenzoic acid (1.0-1.1 mmol) were dissolved in phosphoryl chloride (10 ml.) in a 20 ml. microwave vial. The reaction mixture was stirred at 150 C for 45 min in a microwave reactor. After cooling down to room temperature the mixture was poured slowly into water under vigorous stirring, and extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under reduced pressure to yield 4-(4-(7-chloro-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)morpholine that was used for next step without further purification. LCMS-ESI+ (m/z): [M+H]+ calcd for C16H15CIN40: 315.7; found 315.1.

Reference： [1]Patent: WO2015/187684,2015,A1 .Location in patent: Page/Page column 172

17
[ 1232431-75-2 ]
2-(cyclopropylmethoxy)-5-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)benzonitrile [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

18
[ 1232431-75-2 ]
(R)-tert-butyl 3-(2-cyano-4-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

19
[ 1232431-75-2 ]
(R)-2-((1-(2-cyanoacetyl)pyrrolidin-3-yl)oxy)-5-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)benzonitrile [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

20
[ 1232431-75-2 ]
6-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-3-((tetrahydro-2H-pyran-4-yl)oxy)picolinonitrile [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

21
[ 1232431-75-2 ]
4-(4-(7-chloro-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)morpholine [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

22
[ 1232431-75-2 ]
(R)-5-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-2-(pyrrolidin-3-yloxy)benzonitrile [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

23
[ 1232431-75-2 ]
(R)-2-((1-(2-hydroxyacetyl)pyrrolidin-3-yl)oxy)-5-(2-(4-morpholinophenyl)-3H-imidazo[4,5-b]pyridin-7-yl)benzonitrile [ No CAS ]

Reference： [1]Patent: WO2015/187684,2015,A1

24
[ 25016-11-9 ]
[ 1232431-75-2 ]
7-bromo-2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 85℃; for 12h;	7-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine To a 10 mL reaction tube charged with a stir bar was added a solution of <strong>[1232431-75-2]2,3-diamino-4-bromopyridine</strong> (75.00 mg; 0.40 mmol; 1.00 eq.) and 1-methyl-1h-pyrazole-4-carbaldehyde (41.93 mul; 0.42 mmol; 1.05 eq.) in DMF (2.00 ml; 25.94 mmol; 65.03 eq.). The reaction mixture was then treated with p-toluenesulfonic acid monohydrate (7.59 mg; 0.04 mmol; 0.10 eq.) and heated to 85 C. for 12 h. Upon completion of the reaction, the mixture was poured into saturated aq. NaHCO3 (20 mL) and transferred to a separatory funnel. The product was extracted with ethyl acetate (3*10 mL), washed with saturated aq. NaHCO3 and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was loaded onto a 10 g KP-NH samplet and purified on a Biotage system by flash chromatography (KP-NH column; 2-10% MeOH/CH2Cl2 over 15 column volumes). The product fractions were concentrated to afford 7-bromo-2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine as a beige solid (68% yield). HPLC: 99% purity. MS: 279 [M+H]+

Reference： [1]Patent: US2016/96834,2016,A1 .Location in patent: Paragraph 0258

25
[ 1232431-75-2 ]
3-(tert-butyl)-N-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)isoxazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

26
[ 1232431-75-2 ]
5-tert-butyl-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)pyridine-2-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

27
[ 1232431-75-2 ]
4-tert-butyl-N-{2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-benzyl}-benzamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

28
[ 1232431-75-2 ]
4-tert-butyl-N-{2-methyl-3-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}benzamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

29
[ 1232431-75-2 ]
3-fluoro-5-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]pyridine-2-carbonitrile [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

30
[ 1232431-75-2 ]
{3-fluoro-5-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-pyridin-2-yl}methylamine [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

31
[ 1232431-75-2 ]
2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]benzylamine [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

32
[ 1232431-75-2 ]
3-(tert-butoxy)-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)azetidine-1-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

33
[ 1232431-75-2 ]
6-cyclopropyl-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)pyridine-3-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

34
[ 1232431-75-2 ]
tert-butyl N-(2-[3-[([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)carbamoyl]-1,2,4-oxadiazol-5-yl]propan-2-yl)carbamate [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

35
[ 1232431-75-2 ]
3-(tert-butoxy)-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)cyclobutane-1-carboxamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

36
[ 1232431-75-2 ]
5-tert-butyl-[1,3,4]oxadiazole-2-carboxylic acid (1-{4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-phenyl}-cyclopropyl)amide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

37
[ 1232431-75-2 ]
N-{2-methyl-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-benzyl}-oxalamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

38
[ 1232431-75-2 ]
3-tert-butyl-[1,2,4]oxadiazole-5-carboxylic acid 3-hydroxymethyl-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-benzylamide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

39
[ 1232431-75-2 ]
[ 58287-80-2 ]
[4-(7-bromo-3H-imidazo[4,5-b]pyridin-2-yl)-phenyl]-morpholin-4-yl-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 85℃; for 12h;	[4-(7-Bromo-3H-imidazo[4,5-b]pyridin-2-yl)-phenyl]-morpholin-4-yl-methanone To a 20 mL reaction tube with stirbar was added a solution of <strong>[1232431-75-2]2,3-diamino-4-bromopyridine</strong> (500.00 mg; 2.66 mmol; 1.00 eq.) and 4-(morpholine-4-carbonyl)-benzaldehyde (612.15 mg; 2.79 mmol; 1.05 eq.) in DMF (10.00 ml; 129.70 mmol; 48.77 eq.). To this was added p-toluenesulfonic acid monohydrate (50.58 mg; 0.27 mmol; 0.10 eq.) and the reaction mixture was heated at 85 C. for 12 h. The reaction was allowed to cool to RT and was then poured into 20 mL sat. aq. NaHCO3 and transferred to a sep funnel. Extracted with ethyl acetate (3*10 mL). The combined organics were washed with sat. aq. NaHCO3 (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purified by flash chromatography (50 g KP-NH column; 2-10% MeOH/CH2Cl2 15 CV). Concentrated product containing fractions and dried to afford 240 mg (23%) of the title compound as a beige solid. HPLC: 99% purity. MS: 388 [M+H]+. 1H NMR (500 MHz, DMSO-d6) delta 14.01 (s, 1H), 8.32 (d, J=7.9 Hz, 2H), 8.21 (d, J=5.3 Hz, 1H), 7.62 (d, J=8.0 Hz, 2H), 7.56 (d, J=5.3 Hz, 1H), 3.73-3.53 (m, 6H), 3.49-3.34 (m, 2H).

Reference： [1]Patent: US2016/96834,2016,A1 .Location in patent: Paragraph 0599

40
[ 1232431-75-2 ]
[ 95-92-1 ]
8-bromo-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
334 mg	for 4h;Reflux;	General procedure: A mixture of 2,3-diaminopyridine in diethyl oxalate (10 mL/1 mmol phenyldiamine) was heated to reflux for 4 h before cooled to room temperature. The resulted solid was filtered,washed with ethyl acetate and 95% ethanol, decolorized with activated charcoal and recrystallized in water and DMF or DMSO to give 5-azaquinoxalinediones as white solid. 5.2.2.17 8-Bromo-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione (17) The title compound was prepared from 2-amino-4-bromopyridine according to the general procedure as white solid (334 mg, 13.8%). IR (KBr) nu 3126, 3087, 3040, 2728, 1714, 1697, 1589, 1384, 1275 cm-1; 1H NMR (400 MHz, DMSO-d6) delta 7.43 (1H, d, J = 5.2 Hz, H-7), 7.92 (1H, d, J = 5.2 Hz, H-6), 11.37 (1H, s, NH-1), 12.46 (1H, s, NH-4); 13C NMR (100 MHz, DMSO-d6) delta 116.87, 121.20, 122.46, 139.86, 142.16, 155.17, 155.50; HRMS-EI C7H4BrN3O2 calcd [M+H]+ 241.9565, found 241.9561.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 117,p. 19 - 32

41
[ 1232431-75-2 ]
5-{2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-benzylamino}-2,3-dihydropyrido[3,4-b][1,4]oxazine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

42
[ 1232431-75-2 ]
5-tert-butyl-[1,2,4]oxadiazole-3-carboxylic acid {3-fluoro-5-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]-pyridin-2-ylmethyl}-amide [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

43
[ 1232431-75-2 ]
5-(dimethylamino)-N-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)benzyl)-1,2,4-oxadiazole-3-carboxamide 2,2,2-trifluoroacetate [ No CAS ]

Reference： [1]Patent: US2016/96834,2016,A1

44
[ 1232431-75-2 ]
[4-[[(3-tert-butyl-1,2,4-oxadiazole-5-carbonyl)amino]methyl]-3-fluoro-phenyl]boronic acid [ No CAS ]
3-tert-butyl-N-[4-(2,3-diaminopyridin-4-yl)-2-fluorophenyl]methyl}-1,2,4-oxadiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In tetrahydrofuran; water; at 120℃; for 1h;Sealed tube; Inert atmosphere; Microwave irradiation;	(0694) 4-Bromo-pyridine-2,3-diamine (1.60 g; 8.51 mmol; 1.00 eq.), [4-[[(3-tert-butyl-1,2,4-oxadiazole-5-carbonyl)amino]methyl]-3-fluoro-phenyl]boronic acid (3.28 g; 10.21 mmol; 1.20 eq.), 1,1?-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (694.92 mg; 0.85 mmol; 0.10 eq.), and potassium carbonate (4.70 g; 34.04 mmol; 4.00 eq.) were combined in a microwave tube. The tube was sealed and then evacuated/N2-backfilled (3×). Then THF/water (5:1, 24 mL) was then added. The tube was evacuated/N2-backfilled (3×) again and irradiated in a microwave at 120 degrees C. for 1 hr. LC-MS indicated product as the major UV peak (MSES+: 385) and no starting material. The reaction was diluted with water (100 mL) and ethyl acetate (100 mL), filtered through Celite, and partially concentrated. The black solution was diluted with ethyl acetate (50 mL) and then filtered through Celite again. The resulting layers were separated and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined ethyl acetate layer was concentrated on SiO2 and purified on a 100 g Biotage column using 80-100% ethyl acetate/hexane over 10 min at a flow rate of 50 mL/min. The product fractions were combined, concentrated, and dried to yield 2.08 g (64%) of 3-(tert-butyl)-N-(4-(2,3-diaminopyridin-4-yl)-2-fluorobenzyl)-1,2,4-oxadiazole-5-carboxamide as a tan brittle foam. HPLC: 98% purity. MS: 385 [M+H]+.

Reference： [1]Patent: US2016/96834,2016,A1 .Location in patent: Paragraph 0694

45
[ 1232431-75-2 ]
3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide [ No CAS ]
[ 824-94-2 ]
[ 104619-51-4 ]
3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide [ No CAS ]
3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step I: 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (0386) Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide (230 g, 618.08 mmol, 1.00 equiv), potassium carbonate (276 g, 2.00 mol, 3.23 equiv), NaI (18.4 g), Bu4NCl (34.0 g, 122 mmol, 0.20 equiv), chloroform (3800 mL, 1.00 equiv), 1-(chloromethyl)-4-methoxybenzene (380 g, 2.43 mol, 3.93 equiv), water (2550 mL). The resulting solution was stirred for 12 hr at 55 C. The aqueous phase was extracted with 2×1000 mL of DCM. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/ hexane (1:10). Purification afforded 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide. (0387) LC-MS: (ES, m/z): 732 [M+H]+. (0388) H-NMR: (CDCl3, 300 Hz, ppm): delta 3.763 (9H, s), 3.820-3.872 (2H, d, J=15.6), 4.402-4.454 (2H, d, J=15.6), 5.154-5.203 (1H, d, J=14.7), 5.560-5.609 (1H, d, J=14.7), 6.702-6.763 (6H, m), 6.912-6.941 (4H, m), 7.109-7.138 (2H, m), 7.839-7.854 (2H, m). Reference Example 25 (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid Into a 1 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (REFERENCE EXAMPLE 24, 120 g, 163.81 mmol, 1.00 equiv), 1,4-dioxane (360 mL), 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane (111 g, 491 mmol, 3.00 equiv), KOAc (80.3 g, 818 mmol, 5.00 equiv), 2-2-[chloro(triphenyl-5-phosphanylidene)palladio]phenylaniline (9.4 g, 16.42 mmol, 0.10 equiv). The resulting solution was stirred for 6 hr at 60 C. The resulting solution was diluted with 500 mL of CH3CN. The solids were filtered out. The filtrate was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1): Column, C18 silica gel; mobile phase, CH3CN/H2O=1:2 increasing to CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=1:0 within 10 min; Detector, UV 210 nm. This afforded (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid. (0391) LC-MS: (ES, m/z): 698 [M+H]+ (0392) H-NMR: (300 MHz, DMSO, ppm): delta 3.616-3.860 (11H, m), 3.860 (0.855H, s), 4.459-4.511 (1.492H, m), 5.172 (1.335H, s), 5.877 (0.403H, s), 6.733-6.827 (10H, m), 7.199-7.306 (2H, m), 8.456 (1.2H, m). Step A: 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide and 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide (1111) To a 10 mL RBF was added cesium carbonate (280 mg, 0.860 mmol), 2-bromopyridine-3,4-diamine (53.9 mg, 0.287 mmol), (3-(N,N-bis(4-methoxybenzyl)sulfamoyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (200 mg, 0.287 mmol) and Xphos Pd G2 (22.56 mg, 0.029 mmol). The vial was sealed, degassed, and filled with dioxane (2.4 ml) and water (0.6 ml). The resulting mixture was heated at 80 C. for 2 hr. The reaction mixture was filtered through a celite pad. The filtrate was diluted with EtOAc and washed with water. The organic layer was dried over anhydrous MgSO4, filtered, concentrated and purified by silica gel column chromatography (ISCO RediSep gold column, 24 g) using 0-10% MeOH/DCM as mobile phase (3% and 6% isostatic) to afford the title compound. LC/MS (M+H)+: 761.37. Step B: 3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide and 3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2...

Reference： [1]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0386; 0387; 0388; 0390; 0391; 0392; 1111; 1112

46
[ 1232431-75-2 ]
3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide [ No CAS ]
[ 824-94-2 ]
3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide [ No CAS ]
3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step I: 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (0386) Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide (230 g, 618.08 mmol, 1.00 equiv), potassium carbonate (276 g, 2.00 mol, 3.23 equiv), NaI (18.4 g), Bu4NCl (34.0 g, 122 mmol, 0.20 equiv), chloroform (3800 mL, 1.00 equiv), 1-(chloromethyl)-4-methoxybenzene (380 g, 2.43 mol, 3.93 equiv), water (2550 mL). The resulting solution was stirred for 12 hr at 55 C. The aqueous phase was extracted with 2×1000 mL of DCM. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/ hexane (1:10). Purification afforded 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide. (0387) LC-MS: (ES, m/z): 732 [M+H]+. (0388) H-NMR: (CDCl3, 300 Hz, ppm): delta 3.763 (9H, s), 3.820-3.872 (2H, d, J=15.6), 4.402-4.454 (2H, d, J=15.6), 5.154-5.203 (1H, d, J=14.7), 5.560-5.609 (1H, d, J=14.7), 6.702-6.763 (6H, m), 6.912-6.941 (4H, m), 7.109-7.138 (2H, m), 7.839-7.854 (2H, m). Reference Example 25 (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid Into a 1 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (REFERENCE EXAMPLE 24, 120 g, 163.81 mmol, 1.00 equiv), 1,4-dioxane (360 mL), 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane (111 g, 491 mmol, 3.00 equiv), KOAc (80.3 g, 818 mmol, 5.00 equiv), 2-2-[chloro(triphenyl-5-phosphanylidene)palladio]phenylaniline (9.4 g, 16.42 mmol, 0.10 equiv). The resulting solution was stirred for 6 hr at 60 C. The resulting solution was diluted with 500 mL of CH3CN. The solids were filtered out. The filtrate was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1): Column, C18 silica gel; mobile phase, CH3CN/H2O=1:2 increasing to CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=1:0 within 10 min; Detector, UV 210 nm. This afforded (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid. (0391) LC-MS: (ES, m/z): 698 [M+H]+ (0392) H-NMR: (300 MHz, DMSO, ppm): delta 3.616-3.860 (11H, m), 3.860 (0.855H, s), 4.459-4.511 (1.492H, m), 5.172 (1.335H, s), 5.877 (0.403H, s), 6.733-6.827 (10H, m), 7.199-7.306 (2H, m), 8.456 (1.2H, m). Step A: 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide and 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide (1111) To a 10 mL RBF was added cesium carbonate (280 mg, 0.860 mmol), 2-bromopyridine-3,4-diamine (53.9 mg, 0.287 mmol), (3-(N,N-bis(4-methoxybenzyl)sulfamoyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (200 mg, 0.287 mmol) and Xphos Pd G2 (22.56 mg, 0.029 mmol). The vial was sealed, degassed, and filled with dioxane (2.4 ml) and water (0.6 ml). The resulting mixture was heated at 80 C. for 2 hr. The reaction mixture was filtered through a celite pad. The filtrate was diluted with EtOAc and washed with water. The organic layer was dried over anhydrous MgSO4, filtered, concentrated and purified by silica gel column chromatography (ISCO RediSep gold column, 24 g) using 0-10% MeOH/DCM as mobile phase (3% and 6% isostatic) to afford the title compound. LC/MS (M+H)+: 761.37.

Reference： [1]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0386; 0387; 0388; 0390; 0391; 0392; 1111

47
[ 1232431-75-2 ]
3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide [ No CAS ]
[ 104619-51-4 ]
3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-2-(1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step I: 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (0386) Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 3-bromo-2-(1H-1,2,3,4-tetrazol-5-yl)-6-(trifluoromethyl)benzene-1-sulfonamide (230 g, 618.08 mmol, 1.00 equiv), potassium carbonate (276 g, 2.00 mol, 3.23 equiv), NaI (18.4 g), Bu4NCl (34.0 g, 122 mmol, 0.20 equiv), chloroform (3800 mL, 1.00 equiv), 1-(chloromethyl)-4-methoxybenzene (380 g, 2.43 mol, 3.93 equiv), water (2550 mL). The resulting solution was stirred for 12 hr at 55 C. The aqueous phase was extracted with 2×1000 mL of DCM. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/ hexane (1:10). Purification afforded 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide, and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide. (0387) LC-MS: (ES, m/z): 732 [M+H]+. (0388) H-NMR: (CDCl3, 300 Hz, ppm): delta 3.763 (9H, s), 3.820-3.872 (2H, d, J=15.6), 4.402-4.454 (2H, d, J=15.6), 5.154-5.203 (1H, d, J=14.7), 5.560-5.609 (1H, d, J=14.7), 6.702-6.763 (6H, m), 6.912-6.941 (4H, m), 7.109-7.138 (2H, m), 7.839-7.854 (2H, m). Reference Example 25 (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid Into a 1 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide and 3-bromo-N,N-bis[(4-methoxyphenyl)methyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-6-(trifluoromethyl)benzene-1-sulfonamide (REFERENCE EXAMPLE 24, 120 g, 163.81 mmol, 1.00 equiv), 1,4-dioxane (360 mL), 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane (111 g, 491 mmol, 3.00 equiv), KOAc (80.3 g, 818 mmol, 5.00 equiv), 2-2-[chloro(triphenyl-5-phosphanylidene)palladio]phenylaniline (9.4 g, 16.42 mmol, 0.10 equiv). The resulting solution was stirred for 6 hr at 60 C. The resulting solution was diluted with 500 mL of CH3CN. The solids were filtered out. The filtrate was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1): Column, C18 silica gel; mobile phase, CH3CN/H2O=1:2 increasing to CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=2:1 within 25 min, and then CH3CN/H2O=1:0 within 10 min; Detector, UV 210 nm. This afforded (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[1-[(4-methoxyphenyl)methyl]-1H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid and (3-[bis[(4-methoxyphenyl)methyl]sulfamoyl]-2-[2-[(4-methoxyphenyl)methyl]-2H-1,2,3,4-tetrazol-5-yl]-4-(trifluoromethyl)phenyl)boronic acid. (0391) LC-MS: (ES, m/z): 698 [M+H]+ (0392) H-NMR: (300 MHz, DMSO, ppm): delta 3.616-3.860 (11H, m), 3.860 (0.855H, s), 4.459-4.511 (1.492H, m), 5.172 (1.335H, s), 5.877 (0.403H, s), 6.733-6.827 (10H, m), 7.199-7.306 (2H, m), 8.456 (1.2H, m). Step A: 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide and 3-(2,3-diaminopyridin-4-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide (1111) To a 10 mL RBF was added cesium carbonate (280 mg, 0.860 mmol), 2-bromopyridine-3,4-diamine (53.9 mg, 0.287 mmol), (3-(N,N-bis(4-methoxybenzyl)sulfamoyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (200 mg, 0.287 mmol) and Xphos Pd G2 (22.56 mg, 0.029 mmol). The vial was sealed, degassed, and filled with dioxane (2.4 ml) and water (0.6 ml). The resulting mixture was heated at 80 C. for 2 hr. The reaction mixture was filtered through a celite pad. The filtrate was diluted with EtOAc and washed with water. The organic layer was dried over anhydrous MgSO4, filtered, concentrated and purified by silica gel column chromatography (ISCO RediSep gold column, 24 g) using 0-10% MeOH/DCM as mobile phase (3% and 6% isostatic) to afford the title compound. LC/MS (M+H)+: 761.37. Step B: 3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)-6-(trifluoromethyl)benzenesulfonamide and 3-(2-amino-1H-imidazo[4,5-b]pyridin-7-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2...

Reference： [1]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0386; 0387; 0388; 0390; 0391; 0392; 1111; 1112; 11

48
[ 1232431-75-2 ]
[ 73183-34-3 ]
(2,3-diaminopyridin-4-yl)boronic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro[(tricyclohexylphosphine)-2-(2'-aminobiphenyl)]palladium(II) second generation; potassium acetate; In 1,4-dioxane; at 80℃; for 17h;	To a 25 mL RBF was added <strong>[1232431-75-2]4-bromopyridine-2,3-diamine</strong> (0.564 g, 3.0 mmol), 4,4,4?,4?,5 ,5 ,5?,S ?-octamethyl-2,2?-bi( 1,3 ,2-dioxaborolane) (2.285 g, 9.0 mmol), chloro [(tricyclohexylphosphine)-2-(2 ?-aminobiphenyl)]Pd(II) (0.354 g, 0.6 mmol) and potassium acetate (0.883 g, 9.0 mmol) in dioxane (25 ml). The reaction mixture was degassed and heated at 80C for 17 hr. The mixture was filtered and to the filtrate was added 50 ml 2N HC1, followed by addition of 50 mL of EtOAc. The aqueous was separated and concentrated in vacuo. The residue was dissolved in 10 ml of methanol. The inorganic salt was filtered off and the filtrate was concentrated. The crude solid was chromatographed over C 18 column (80g, Acetonitrile in H20 0-100%) to give the desired product (2,3-diaminopyridin-4-yl)boronic acid. LCMS: 154.12.

Reference： [1]Patent: WO2016/206101,2016,A1 .Location in patent: Page/Page column 75

49
[ 1232431-75-2 ]
C₄₅H₄₈N₁₀O₉S₂ [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

50
[ 1232431-75-2 ]
tert-butyl 3-((2-(N,N-bis(4-methoxybenzyl)sulfamoyl)-4-(2,3-diaminopyridin-4-yl)-3-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)phenyl)sulfonyl)azetidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/206101,2016,A1

51
[ 1232431-75-2 ]
(S)-tert-butyl (1-(2-cyano-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate [ No CAS ]
(S)-tert-butyl (1-(2-cyano-4-(2,3-diaminopyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92 mg	With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 95℃; for 2h;Inert atmosphere;	To a stirred solution of (5)-tert-butyl (1 -(2-cyano-4-(4,4,5 ,5-tetramethyl-1,3 ,2-dioxaborolan-2-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate (100 mg,0.218 mmol), <strong>[1232431-75-2]4-bromopyridine-2,3-diamine</strong> (41.0 mg, 0.218 mmol) and cesiumcarbonate (142 mg, 0.43 6 mmol) in a mixture of 1,4-dioxane (5 mL) and water (0.5mL) was added XPhos generation precatalyst (17.16 mg, 0.022 mmol) under anitrogen atmosphere. The reaction mixture was heated at 95 C for 2 h. The solution was concentrated under reduced pressure, water (20 mL) was added and the solution extracted with EtOAc (2 x 20 mL). The combined organic extracts were washed with water (50 mL) and brine (20 mL) The organic layer was dried over sodium sulfate,filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (EtOAc in hexanes) to afford (5)-tert-butyl (1-(2-cyano-4-(2,3- diaminopyridin-4-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate (92 mg, 0.180 mmol, 83% yield). The product was carried forward without further purification. LCMS (ESI) m/e 384.2 [(M+H), calcd for C24H34N503, 440.31; LC/MS retentiontime (method B) tR = 0.91 mm.

Reference： [1]Patent: WO2017/59080,2017,A1 .Location in patent: Page/Page column 36; 37

52
[ 1232431-75-2 ]
7-bromo-2-methyl-3H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With acetic acid; at 150℃; for 2h;	A mixture of <strong>[1232431-75-2]4-bromopyridine-2,3-diamine</strong> (0. i 5 g, 0.798 mmol), AcOH (0.069 mL, i.i97 mmol), and PPA (0.340 mL, 0.798 mmol) was heated at iSO C for2 h. The reaction mixture was diluted with water and the pH was adjusted to i3 with aqueous NaOH (iO%). The solution was extracted with ethyl acetate (2xiOO mL). The ethyl acetate layers were washed with water, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 7-bromo-2-methyl-3H- imidazo[4,5-bjpyridine (0.i30 g, 0.460 mmol, 58% yield). LCMS (ESI) m/e 2i2.0[(M+H), calcd for C7H7BrN3 2i2.Oj; LC/MS retention time (method B): tR = 0.49 mm.

Reference： [1]Patent: WO2017/59080,2017,A1 .Location in patent: Page/Page column 92

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[ 1232431-75-2 ]
(S)-tert-butyl (1-(2-chloro-4-(2-methyl-3H-imidazo[4,5-b]pyridin-7-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate [ No CAS ]