[ CAS No. 1445-39-2 ] {[proInfo.proName]}

Name: 1445-39-2|2-Amino-5-iodopyrimidine|97%
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Quality Control of [ 1445-39-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1445-39-2 ]

SDS Specification

Alternatived Products of [ 1445-39-2 ]

Product Details of [ 1445-39-2 ]

CAS No. :	1445-39-2	MDL No. :	MFCD01075666
Formula :	C₄H₄IN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HAFKCGZQRIIADX-UHFFFAOYSA-N
M.W :	221.00	Pubchem ID :	241102
Synonyms :

Calculated chemistry of [ 1445-39-2 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	39.15
TPSA :	51.8 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) :	-7.29 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.24
Log Po/w (XLOGP3) :	0.51
Log Po/w (WLOGP) :	0.67
Log Po/w (MLOGP) :	0.33
Log Po/w (SILICOS-IT) :	1.31
Consensus Log Po/w :	0.81

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.09
Solubility :	1.81 mg/ml ; 0.00819 mol/l
Class :	Soluble
Log S (Ali) :	-1.17
Solubility :	15.0 mg/ml ; 0.0679 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.25
Solubility :	1.24 mg/ml ; 0.00561 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.91

Safety of [ 1445-39-2 ]

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 [ 1445-39-2 ]

* 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 [ 1445-39-2 ]
Downstream synthetic route of [ 1445-39-2 ]

[ 1445-39-2 ] Synthesis Path-Upstream 1~5

1
[ 109-12-6 ]
[ 1445-39-2 ]

Yield	Reaction Conditions	Operation in experiment
22.2%	With sulfuric acid; iodine; acetic acid; periodic acid In water at 80℃; for 24 h; Inert atmosphere	Mixture of 2-aminopyrimidine (2.4 g, 25 mmol, 1.0 eq.) and elemental iodine (2.7 g, 10.7 mmol, 0.43eq.) was added to 60 ml of glacial acetic acid, and then added periodic acid (0.86 g, 3.76 mmol, 0.15 eq.) and 0.5 ml concentrated sulfuric acid dissolved in sulfuric acid solution 3 ml of water. Place reactions in a nitrogen atmosphere , the reaction was heated to 80 °C for 24 hours. The reaction was then poured into a saturated aqueous solution of sodium thiosulfate in until a clear solution, (200 ml × 3) and extracted with dichloromethane, the combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, after column chromatography silica gel to give a white solid 2-amino-5-iodopyrimidine (1.4 g, yield 22.2percent).
0.4 g	With iodine In dimethyl sulfoxide at 120℃; for 1 h;	To a solution of pyrimidin-2-amine (1.0 g, 0.010 mol) in DMSO (10 mL) was added iodine (3.2 g, 0.012 mol). The reaction mixture was stirred at 120°C for 1 h. The reaction mass was quenched in water and excess of iodine was neutralised with sodium metabisulphate. The reaction mass was extracted with ethyl acetate and concentrated to afford 0.400 g of the desired product.

Reference： [1] Heterocycles, 1984, vol. 22, # 5, p. 1195 - 1210
[2] Journal of Organic Chemistry, 2000, vol. 65, # 22, p. 7468 - 7474
[3] Journal of Organic Chemistry, 2008, vol. 73, # 23, p. 9326 - 9333
[4] Synthesis, 1984, # 3, p. 252 - 254
[5] Patent: CN105622638, 2016, A, . Location in patent: Paragraph 0362
[6] Journal of the American Chemical Society, 1948, vol. 70, p. 157,158
[7] Patent: WO2013/186692, 2013, A1, . Location in patent: Page/Page column 62

2
[ 109-12-6 ]
[ 1600-27-7 ]
[ 7732-18-5 ]
[ 1445-39-2 ]

Reference： [1] Journal of the American Chemical Society, 1948, vol. 70, p. 157,158

3
[ 1445-39-2 ]
[ 32779-38-7 ]

Yield	Reaction Conditions	Operation in experiment
31%	With tert.-butylnitrite; copper dichloride In acetonitrile at 20 - 60℃; Inert atmosphere	Step A. Preparation of 2-chloro-5-iodopyrimidine [00166] To a stirring solution of 5-iodopyrimidin-2-amine (2.21 g, 10.0 mmol) in CH₃CN (20 ml) at room temperature under argon was added copper (II) chloride (2.02 g, 15 mmol) and tert-butyi nitrite (1.55 g, 15 mmol). The reaction mixture was placed in a preheated oil bath (60 ⁰C) under Argon. The reaction mixture was cooled to room temperature and 20 ml of ether was added. The resulting insoluble material was filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM (~2 ml) and loaded onto an 80 g ISCO silica gel column which was eluted with a 20 min gradient from 0percent to 100percent EtOAc/Hexanes. 778 mg (31percent) of 2-chloro-5-iodopyrimidine was obtained as an off- white solid. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.79 (s, 2 H).
28%	With sodium hydroxide; sodium nitrate In hydrogenchloride; water	(d) A suspension of 2-amino-5-iodopyrimidine (40 g) in concentrated hydrochloric acid (150 ml) was treated dropwise at a temperature of 25° to 30° C. with a solution of sodium nitrate (40 g) in water (70 ml). The reaction mixture was stirred at a temperature of 25° to 30° C. for a further 2 hr and then neutralised by the addition of aqueous 20percent sodium hydroxide, the temperature of the reaction mixture being maintained at 10° to 20° C. during the neutralisation by external cooling. The neutralised reaction mixture was filtered to remove solids and the solids were washed several times with chloroform. The filtrate was extracted with chloroform and the combined chloroform washings and extracts were dried and the chloroform was removed by distillation under reduced pressure to give crude 2-chloro-5-iodopyrimidine as a pale brown solid (12 g, 28percent) with m.p. 125° C. (Reference m.p. 129°-130° C. J. Chem. Soc. (C), 1971, 1889).
1.7 g	With tert.-butylnitrite; copper dichloride In acetonitrile at 70℃;	To a solution of 5-iodopyrimidin-2-amine (10.0 g, 0.045 mol) in acetonitrile (150 mL) was added CuCl₂ (11.57 g, 0.067 mol) and teri-butyl nitrite (6.99 g, 0.067 mol). The reaction mass was heated at 70°C for 5-6 h. The reaction mass was diluted with ether and the solid obtained was filtered off. The obtained product was purified with column chromatography on silica gel eluting with DCM to afford 1.700 g of the desired product

Reference： [1] Journal of Organic Chemistry, 2008, vol. 73, # 23, p. 9326 - 9333
[2] Patent: WO2010/9183, 2010, A1, . Location in patent: Page/Page column 79
[3] Patent: US4248618, 1981, A,
[4] Patent: WO2013/186692, 2013, A1, . Location in patent: Page/Page column 62

4
[ 1445-39-2 ]
[ 25015-63-8 ]
[ 402960-38-7 ]

Reference： [1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 9, p. 3139 - 3141

5
[ 1445-39-2 ]
[ 905856-70-4 ]

Reference： [1] Journal of Organic Chemistry, 2008, vol. 73, # 23, p. 9326 - 9333

[ 1445-39-2 ] Synthesis Path-Downstream 1~88

1
[ 109-12-6 ]
[ 1445-39-2 ]

Yield	Reaction Conditions	Operation in experiment
22.2%	With sulfuric acid; iodine; acetic acid; periodic acid; In water; at 80℃; for 24h;Inert atmosphere;	Mixture of 2-aminopyrimidine (2.4 g, 25 mmol, 1.0 eq.) and elemental iodine (2.7 g, 10.7 mmol, 0.43eq.) was added to 60 ml of glacial acetic acid, and then added periodic acid (0.86 g, 3.76 mmol, 0.15 eq.) and 0.5 ml concentrated sulfuric acid dissolved in sulfuric acid solution 3 ml of water. Place reactions in a nitrogen atmosphere , the reaction was heated to 80 C for 24 hours. The reaction was then poured into a saturated aqueous solution of sodium thiosulfate in until a clear solution, (200 ml × 3) and extracted with dichloromethane, the combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, after column chromatography silica gel to give a white solid 2-amino-5-iodopyrimidine (1.4 g, yield 22.2%).
0.4 g	With iodine; In dimethyl sulfoxide; at 120℃; for 1h;	To a solution of pyrimidin-2-amine (1.0 g, 0.010 mol) in DMSO (10 mL) was added iodine (3.2 g, 0.012 mol). The reaction mixture was stirred at 120C for 1 h. The reaction mass was quenched in water and excess of iodine was neutralised with sodium metabisulphate. The reaction mass was extracted with ethyl acetate and concentrated to afford 0.400 g of the desired product.

Reference： [1]Heterocycles,1984,vol. 22,p. 1195 - 1210
[2]Journal of Organic Chemistry,2000,vol. 65,p. 7468 - 7474
[3]Journal of Organic Chemistry,2008,vol. 73,p. 9326 - 9333
[4]Synthesis,1984,p. 252 - 254
[5]Patent: CN105622638,2016,A .Location in patent: Paragraph 0362
[6]Journal of the American Chemical Society,1948,vol. 70,p. 157,158
[7]Patent: WO2013/186692,2013,A1 .Location in patent: Page/Page column 62

2
[ 1445-39-2 ]
[ 153400-52-3 ]
exo-2-(2-aminopyrimidin-5-yl)-7-carbomethoxy-7-azabicyclo<2.2.1>heptane [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 2103 - 2110

3
[ 109-12-6 ]
[ 1600-27-7 ]
[ 7732-18-5 ]
[ 1445-39-2 ]

Reference： [1]Journal of the American Chemical Society,1948,vol. 70,p. 157,158

4
[ 1445-39-2 ]
[ 103-63-9 ]
5-phenethyl-pyrimidin-2-ylamine [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 341 - 344

5
[ 142-08-5 ]
[ 1445-39-2 ]
1-(2-amino-pyrimidin-5-yl)-1<i>H</i>-pyridin-2-one [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 7677 - 7680

6
[ 1445-39-2 ]
[ 1066-54-2 ]
[ 857265-74-8 ]

Yield	Reaction Conditions	Operation in experiment
		Example 3Synthesis of 5-ethynylpyrimidin-2-amine A flask was charged with <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (25.0 g, 110 mmol), acetonitrile (900 ml, 110 mmol), trimethylsilylacetylene (35 ml, 241 mmol), triethylami?e (93 ml, 658 mmol), Pd(PPh3)4CI2 (3.9 g, 5.5 mmol) and finally copper(l) iodide (1.1 g, 5.5 mmol). The flask was put under vacuum then filled with argon and stirred at RT overnight using a mechanical stirrer. The solvent was removed under vacuum, the residue taken up in methanol (600ml) and potassium carbonate (152 g, 1097 mmol) was added. The mixture was stirred at RT using mechanical stirring for 2 hrs. Activated carbon (~50ml_) was added to the reaction and stirring continued for 15min. The reaction mixture was then filtered through a plug of celite and the filtrate was concentrated to a volume of ~400mL and the precipitate was filtered. The filtrate was concentrated down to a thick paste which was slurried in ~150mL of 10%MeOH/H2O for 20 min at RT. The solids were then filtered off to afford 5-ethynylpyrimidin-2-amine.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 627 - 640
[2]Patent: WO2008/8493,2008,A2 .Location in patent: Page/Page column 33

7
[ 1445-39-2 ]
[ 108-24-7 ]
[ 849236-67-5 ]

Yield	Reaction Conditions	Operation in experiment
23%	With pyridine; at 110℃; for 48h;	Step 1: N- (5-LODOPYRIMIDIN-2-YL) acetamide (248) [0400] 5-lodo-pyrimidin-2-ylamine (17,1. 1 g, 4.98 MMOL) and acetic anhydride (14.94 MMOL, 1.41 mL) were dissolved in pyridine (20 mL) and stirred at 110C for 48 hours. The reaction mixture was cooled and quenched with water (50 mL). Ethyl acetate (100 mL) was added and the resulting white precipitate was collected by filtration to afford title compound 248 as a white solid (300 mg, 23% yield NMR: (DMSO) 8 10.67 (s, 1H), 8.85 (s, 2H), 2.18 (s, 3H).

Reference： [1]Patent: WO2005/30704,2005,A1 .Location in patent: Page/Page column 228-229

8
[ 1445-39-2 ]
[ 1066-54-2 ]
[ 857265-75-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h;	Intermediate 5; o 5-[(Trimethylsilyl)ethynyl]pyrimidin-2-aminePdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), CuI (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at -20C under an inert atmosphere. The reaction was allowed to warm to ambient s temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%); 1H NMR (CDCl3) 0.26 (s, 9H), 5.19 (bs, 2H)3 8.39 (s, 2H); MS m/e M^+MeCN 233. o
100%	With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h;	5-[(Trimethylsilyl)ethynyl]pyrimidin-2-amine PdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), CuI (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at -20 C. under an inert atmosphere. The reaction was allowed to warm to ambient temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%); 1H NMR (CDCl3) 0.26 (s, 9H), 5.19 (bs, 2H), 8.39 (s, 2H);
100%	With N-ethyl-N,N-diisopropylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ethyl acetate; at -20 - 20℃; for 6h;	PdCl2dppf (146 mg) was added to a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (221 mg), trimethylsilylacetylene (491 mg), Cul (57 mg) and DIPEA (259 mg) in EtOAc (5 mL) at - 20C under an inert atmosphere. The reaction was allowed to warm to ambient temperature and stirred for 6 hours. The reaction mixture was diluted with water (10 mL). The organic layer was separated, dried (MgS04), filtered and concentrated. The crude product was used directly without further purification (191 mg, 100%) ; 'H NMR (CDCl3) ; 0.26 (s, 9H), 5.19 (bs, 2H), 8.39 (s, 2H); MS m/e MH++MeCN 233.

With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In acetonitrile; at 20℃; for 3h;

Into a IL round bottom flask was placed the 2-amino-5- iodopyrimidine (8.0 g, 36.2 mmol) , acetonitrile (30OmL), triethylamine (3OmL), TMS acetylene (7.68g, 78.2 mmol), palladium dichloro-bis-triphenylphosphine (1.26g, 1.8 mmol), and copper(I) iodide (0.342g, 1.8 mmol) . The vessel was filled with argon gas and allowed to stir at room temperature for 3 hours. The solvent was evaporated and the crude was taken up in methanol (40OmL) . Then excess potassium carbonate (10eq) was added, and the mixture was stirred at room temperature for 1.5 hours. Activated charcoal was added and the mixture was filtered through celite. The filtrate was concentrated under reduced pressure to afford a tan solid, which was added to a solution of 10% methanol in water (20OmL) . The resulting precipitate was isolated by filtration, dried in a vacuum oven to constant mass and afforded the title compound as a tan solid. MS m/z = 120 [M+H]+. CaIc'd for C6H5N3: 119.

Reference： [1]Patent: WO2006/82373,2006,A1 .Location in patent: Page/Page column 93
[2]Patent: US2008/194552,2008,A1 .Location in patent: Page/Page column 28
[3]Patent: WO2005/60970,2005,A1 .Location in patent: Page/Page column 118
[4]Patent: WO2006/44823,2006,A2 .Location in patent: Page/Page column 196

9
[ 1445-39-2 ]
[ 857266-55-8 ]
[ 857266-56-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In DMF (N,N-dimethyl-formamide); at 60℃; for 4h;	Triethylamine (1.0 mL) was added to a degassed solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (275 mg), tert-butyl 3-ethynylphenyl (methyl) carbamate (Intermediate 42) (298 mg) PdCl2 (PPh3) 2 (17 mg) and cuprous iodide (1.25 mg) in DMF (5.0 mL). The mixture was heated to 60C for 4 hours and concentrated in vacuo. Purification by flash chromatography on silica using 0- 10% MeOH in DCM as eluent gave the title compound as a yellow solid (344 mg, 86%). lH NMR (CDCl3) 1.47 (s, 9H), 3.27 (s, 1H), 5.22 (s, br, 2H), 7.23-7. 31 (m, 3H), 7. 39 (s, 1H), 8.45 (s, 2H); MS m/e MH+ 325.

Reference： [1]Patent: WO2005/60970,2005,A1 .Location in patent: Page/Page column 149

10
[ 1445-39-2 ]
[ 14235-81-5 ]
5-[(4-aminophenyl)ethynyl]pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With N,N,N',N'-tetramethylguanidine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 60℃; for 2.5h;	A mixture of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (1.10 g), 4-ethynylaniline (0.82 g), 1,1, 3,3- tetramethylguanidine (0.81 g), and copper (I) iodide (9.5 mg) in dry DMF (3.0 mL) was stirred and degassed with nitrogen. Tetrakis (triphenylphosphine) palladium (0) (115 mg) was added and the mixture heated at 60 C for 2.5 hours. The solvent was evaporated and the residue was triturated with DCM. The solid formed was filtered off and washed with water then dissolved in 1: 1 DCM/MeOH, filtered then evaporated. The solid obtained was triturated with ether and dried to give the title compound (0.67 g, 63%) ; 'HNMR (DMSO-d6) 5.50 (s, 2H), 6.55 (d, 2H), 6.95 (s, 2H), 7.15 (d, 2H), 8.35 (s, 2H) ; MS m/e MH+ 211.

Reference： [1]Patent: WO2005/60970,2005,A1 .Location in patent: Page/Page column 122-123

11
[ 1445-39-2 ]
[ 149507-26-6 ]
[ 890021-33-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 38; 5-(4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-N- phenylpyrimidin-2-amine; Step 1: Preparation of 5- (3-fluoro-4-methoxgammaphengammal) pyrimidin-2- amine; In a 500 mL round bottom flask under N2, 3-fluoro-4- methoxyphenylboronic acid (5.0 g, 29.4 mmol) and 5-iodopyrimidin- 2-amine (5.5 g, 24.9 mmol) were mixed. Toluene (100 mL) , EtOH (40 mL) and H2O (20 mL) were added, followed by the addition of Na2CO3 (3.0 g, 24.2 mmol). A stream of N2 was bubbled through the mixture for 5 min before the catalyst Pd(PPh)4 (0.30 g, 0.26 mmol) was added. The mixture was heated at 80 C under N2 for 20 h whereby it was cooled to RT. A solution of NaOH (5 N, 10 mL) was added to the mixture and stirring was continued for 10 min. The mixture was filtered and the solid was washed with H2O (3 x 10 mL) , followed by a mixture of hexanes - EtOAc (1:1, 30 mL) . The solid was dried in the air to give the title compound. MS (ESI pos. ion) m/z: 220. CaIc'd for C11H10FN3O: 219.08.

Reference： [1]Patent: WO2006/60318,2006,A2 .Location in patent: Page/Page column 122

12
[ 1445-39-2 ]
[ 32779-38-7 ]

Yield	Reaction Conditions	Operation in experiment
31%	With tert.-butylnitrite; copper dichloride; In acetonitrile; at 20 - 60℃;Inert atmosphere;	Step A. Preparation of 2-chloro-5-iodopyrimidine [00166] To a stirring solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (2.21 g, 10.0 mmol) in CH3CN (20 ml) at room temperature under argon was added copper (II) chloride (2.02 g, 15 mmol) and tert-butyi nitrite (1.55 g, 15 mmol). The reaction mixture was placed in a preheated oil bath (60 0C) under Argon. The reaction mixture was cooled to room temperature and 20 ml of ether was added. The resulting insoluble material was filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM (~2 ml) and loaded onto an 80 g ISCO silica gel column which was eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes. 778 mg (31%) of 2-chloro-5-iodopyrimidine was obtained as an off- white solid. 1H NMR (400 MHz, CDCl3) delta ppm 8.79 (s, 2 H).
28%	With sodium hydroxide; sodium nitrate; In hydrogenchloride; water;	(d) A suspension of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (40 g) in concentrated hydrochloric acid (150 ml) was treated dropwise at a temperature of 25 to 30 C. with a solution of sodium nitrate (40 g) in water (70 ml). The reaction mixture was stirred at a temperature of 25 to 30 C. for a further 2 hr and then neutralised by the addition of aqueous 20% sodium hydroxide, the temperature of the reaction mixture being maintained at 10 to 20 C. during the neutralisation by external cooling. The neutralised reaction mixture was filtered to remove solids and the solids were washed several times with chloroform. The filtrate was extracted with chloroform and the combined chloroform washings and extracts were dried and the chloroform was removed by distillation under reduced pressure to give crude 2-chloro-5-iodopyrimidine as a pale brown solid (12 g, 28%) with m.p. 125 C. (Reference m.p. 129-130 C. J. Chem. Soc. (C), 1971, 1889).
1.7 g	With tert.-butylnitrite; copper dichloride; In acetonitrile; at 70℃;	To a solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (10.0 g, 0.045 mol) in acetonitrile (150 mL) was added CuCl2 (11.57 g, 0.067 mol) and teri-butyl nitrite (6.99 g, 0.067 mol). The reaction mass was heated at 70C for 5-6 h. The reaction mass was diluted with ether and the solid obtained was filtered off. The obtained product was purified with column chromatography on silica gel eluting with DCM to afford 1.700 g of the desired product

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 9326 - 9333
[2]Patent: WO2010/9183,2010,A1 .Location in patent: Page/Page column 79
[3]Patent: US4248618,1981,A
[4]Patent: WO2013/186692,2013,A1 .Location in patent: Page/Page column 62

13
[ 1445-39-2 ]
(4-chloro-3-nitrophenyl)boronic acid [ No CAS ]
[ 742700-78-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 150℃; for 0.166667h;Microwave heating;	A mixture of 4-chloro-3-nitrophenylboronic acid (600 mg, 3.0 mmoles), <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (680 mg, 3.0 mmoles), sodium carbonate (900 mg, 8.5 mmoles) and tetrakis(triphenylphosphine)palladium(0) (80 mg, 0.07 mmoles) in 3:1 dimethylformamide-water (10 ml_) was sealed in a pressure tube and heated at 1500C for 10 minutes in a microwave reactor. The mixture was diluted with water and extracted with ethyl acetate (x2). Combined extracts were washed with brine, dried and evaporated. Flash chromatography (0-5% methanol-dichloromethane) gave the title compound (525 mg, 70%). 1 H NMR(400 MHz, DMSO-alphafe) delta ppm 7.04 (s, 2 H) 7.81 (d, J=8.59 Hz, 1 H) 8.00 (dd, J=8.59, 2.27 Hz, 1 H) 8.36 (d, J=2.27 Hz, 1 H) 8.70 (s, 2 H).

Reference： [1]Patent: WO2006/127458,2006,A2 .Location in patent: Page/Page column 93

14
[ 1445-39-2 ]
[ 816-40-0 ]
2-ethyl-6-iodo-imidazo[1,2-a]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;Heating / reflux;	755 mg of 1-bromo-2-butanone was dissolved in 15 ml of ethanol, 1.0 g of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> was added and the mixture was stirred all night by heating under reflux. After cooling down to room temperature, the solvents were distilled outunder reflux, ethyl acetate followed by saturated sodium bicarbonate aqueous solution were added. Organic layer was dried with anhydrous sodium sulfate, and the solvents were distilled outunder reduced pressure. The obtained residues were purified by silicagel column chromatography (ethyl acetate) to obtain 110 mg of the above compound as a white solid. 1HNMR(300MHz,CDCl3.)delta:1.38(3H,t,J=7.0Hz), 2.88(2H,q,J=7.0Hz), 7.25(1H,s), 8.52(1H,d,J=2.4Hz), 8.58(1H,d,J=2.4Hz) ESI-MS Found:m/z 274.0[M+H]+

Reference： [1]Patent: EP1726585,2006,A1 .Location in patent: Page/Page column 102

15
[ 1445-39-2 ]
[ 54060-30-9 ]
[ 857264-92-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 95℃; for 2h;	5-[(3-aminophenyl)ethynyl]pyrimidin-2-amine <strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (2.21 g), bis(triphenylphosphine)palladium dichloride (350 mg) and copper(I) iodide (40 mg) were stirred in DMF (100 mL)-triethylamine (20 mL) and degassed with nitrogen for 10 min. 3-Ethynyl aniline (1.29 g) was added and the mixture heated to 95 C. for 2 hours. The solvent was evaporated and the residue was purified by trituration with DCM (20 mL) to give the title compound as a brown solid (1.25 g, 60%); 1H NMR (DMSO-d6) 5.21 (bs, 2H), 6.58-6.70 (m, 3H), 7.03-7.07 (m, 3H), 8.40 (s, 2H); MS m/e MH+211.
60%		<strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (2.21 g), bis (triphenylphosphine) palladium dichloride (350 mg) and copper (I) iodide (40 mg) were stirred in DMF (100 mL)- triethylamine (20 mL) and degassed with nitrogen for 10 min. 3-Ethynyl aniline (1.29 g) was added and the mixture heated to 95 C for 2 hours. The solvent was evaporated and the residue was purified by trituration with DCM (20 mL) to give the title compound as a brown solid (1.25 g, 60%); 'H NMR (DMSO-d6) 5.21 (bs, 2H), 6.58-6. 70 (m, 3H), 7.03-7. 07 (m, 3H), 8.40 (s, 2H); MS m/e MH+ 211.

Reference： [1]Patent: US2008/194552,2008,A1 .Location in patent: Page/Page column 34
[2]Patent: WO2005/60970,2005,A1 .Location in patent: Page/Page column 93-94

16
[ 1445-39-2 ]
[ 2491-38-5 ]
[ 956499-77-7 ]

Yield	Reaction Conditions	Operation in experiment
		646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 1-8, Step 2).
		646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 4, Step 2). The NMR measurement results of the resulting 2-(4'-hydroxyphanyl)-6-iodoimidazo[1,2-a]pyrimidine (internal standard: dimethylformamide) are shown below. NMR apparatus employed: JNM-ECP-500 (manufactured by Japan Electron Optics Laboratory Co., Ltd. (JEOL)) 1H-NMR (solvent: dimethylformamide-d7, resonance frequency: 500 MHz): delta 9.80 (br. s, 1H), 9.35 (d, J = 2.3 Hz, 1H), 8.60 (d, J = 2.3 Hz, 1H), 8.23 (s, 1H), 7.94-7.90 (m, 2H), 6.98-6.94 (m, 2H). 13C-NMR (solvent: dimethylformamide-d7, resonance frequency: 125 MHz): delta 158.87, 154.00, 147.18, 146.77, 139.07, 127.68, 124.50, 115.85, 106.10, 73.46.
	With sodium hydrogencarbonate; In methanol; water; acetonitrile;	, Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (

With sodium hydrogencarbonate; In methanol; water; acetonitrile;

, Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (

Reference： [1]Patent: EP2019103,2009,A1 .Location in patent: Page/Page column 17
[2]Patent: EP2022792,2009,A1 .Location in patent: Page/Page column 10; 28
[3]Patent: EP2216051,2010,A1
[4]Patent: EP2218463,2010,A1

17
[ 1445-39-2 ]
[ 905856-70-4 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 9326 - 9333

18
[ 1445-39-2 ]
[ 110-13-4 ]
[ 1139875-13-0 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 9326 - 9333

19
[ 1445-39-2 ]
[ 74-88-4 ]
[ 1083329-41-2 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 9326 - 9333
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 2462 - 2471

20
[ 1445-39-2 ]
[ 1147938-59-7 ]
[ 1147938-92-8 ]

Yield	Reaction Conditions	Operation in experiment
32%	With potassium phosphate;copper(l) iodide; cis-[2-(dimethylamino)cyclohexyl]amine; In N,N-dimethyl-formamide; at 100℃; for 24h;	Example 21 N-(3-(7-(4-((DIMETHYLAMINO)METHYL)PHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHENYL)-3-(TRIFLUOROMETHYL)BENZAMIDE (COMPOUND NO. 111) A mixture of N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)-3-(trifluoromethyl)-benzamide (0.12 g, 0.31 mmol), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (67 mg, 0.0.31 mmol), copper (I) iodide (24 mg, 0.13 mmol), potassium phosphate (140 mg, 0.66 mmol), and N,N-dimethylcyclohexane-1,2-diamine (31 mg, 0.22 mmol) in DMF (0.5 mL) were stirred for 24 hours at 100 C. The reaction mixture was filtered and purified by reverse phase chromatography to give N-(3-(7-(4-((dimethylamino)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)-3-(trifluoromethyl)benzamide (63 mg, 32% yield). MS: m/z 516.4 [M+H].

Reference： [1]Patent: US2009/118276,2009,A1 .Location in patent: Page/Page column 21

21
[ 1445-39-2 ]
[ 1663-39-4 ]
[ 1058661-99-6 ]

Reference： [1]Organic Letters,2008,vol. 10,p. 3949 - 3952
[2]Organic and Biomolecular Chemistry,2009,vol. 7,p. 2110 - 2119

22
[ 1445-39-2 ]
[ 929278-54-6 ]
5-[5-(2-aminopyrimidin-5-yl)-1H-benzimidazol-1-yl]-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)thiophene-2-carboxamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 1399 - 1402

23
[ 1445-39-2 ]
[ 1181621-18-0 ]
[ 1181621-08-8 ]

Yield	Reaction Conditions	Operation in experiment
57%	With copper(l) iodide; triethylamine;tetrakis(triphenylphosphine) palladium(0); In acetonitrile; at 82℃; for 3h;Inert atmosphere;	A mixture of alkyne 7 (710 mg, 2.224 mmol), iodopyrimidine 4 (676 mg, 3.06 mmol), palladiumtetrakistriphenylphosphine (290 mg, 0.251 mmol) and copper (I) iodide (103 mg, 0.541 mmol) was suspended in degassed mixture of acetonitrile (15 mL) and triethylamine (5 mL, 35.9 mmol). The thick mixture was then stirred under argon at 82C for 3h; cooled down to room temperature and diluted with DCM, washed with saturated NH4C1, dried over MgSO4, filtered and concentrated. The purification was performed by flash column chromatography on silica gel (eluent EtOAc) to afford compound 8 (526 mg, 57% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 8.97 (s, IH), 8.46-8.41 (m, 2H), 8.19 (s, IH), 7.79 (s, IH), 7.50 (d, J = 8.0 <n="92"/>Hz, IH), 7.41 (t, J = 7.8 Hz, IH), 7.26 (t, J = 8.0 Hz, IH), 7.14 (s, 2H), 7.08-7.02 (m, 3H). MS (m/z): 413.1 (M+H).

Reference： [1]Patent: WO2009/100536,2009,A1 .Location in patent: Page/Page column 90-91

24
[ 1445-39-2 ]
[ 1181621-20-4 ]
[ 1181621-11-3 ]

Yield	Reaction Conditions	Operation in experiment
57%	With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 40℃; for 3h;	To a suspension of compound 13 (600 mg, 1.879 mmol) in acetonitrile (4.70 niL) was added Et3N (1.572 mL, 11.28 mmol) and <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (4, 415 mg, 1.879 mmol). Then copper (I) iodide (17.89 mg, 0.094 mmol), and bis(triphenylphosphine)palladium(II) chloride (33.0 mg, 0.047 mmol), were successively added degassing the reaction mixture between and after each addition of catalysts. The mixture was stirred at 40C over 3h., diluted with DCM and quenched with sat NH4C1 and cone. NH4OH. The resulting emulsion was allowed to sit for 2h, the aqueous layer was then removed to render an organic paste which was partitioned between EtOAc and IM HCl. The layers were separated and the organic layer was concentrated to a volume of 20 mL. The resulting solid was filtered through a Buchner funnel and rinsed with EtOAc to afford title compound 14 (441 mg, 57% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 9.29 (bs, IH), 8.48 (s, IH), 8.46 (s, 2H), 8.05 (s, IH), 7.82 (bs, IH), 7.45 (t, J = 8.0 Hz, IH), 7.26 (d, J = 8.0 Hz, IH), 7.22 (t, J = 7.6 Hz, IH), 6.89 (d, J = 7.4 Hz, IH), 6.85 (s, IH), 6.81 (d, J = 8.4 Hz, IH). MS (m/z): 413.3 (M+H).

Reference： [1]Patent: WO2009/100536,2009,A1 .Location in patent: Page/Page column 92; 93

25
[ 1445-39-2 ]
[ 1181621-17-9 ]
[ 1181621-07-7 ]

Yield	Reaction Conditions	Operation in experiment
17%	With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In acetonitrile; at 81℃; for 3h;Inert atmosphere;	A mixture of compound 3 (530 mg, 1.968 mmol), iodide 4 (221 mg, 1.000 mmol), CuI (92 mg, 0.48 mmol) and PdC12(dppf) (139 mg, 0.19 mmol) was dissolved in a mixture acetonitrile (12 mL) and TEA (4 mL, 28.7 mmol), degassed under vacuum and stirred under argon at 81C for 3h. The reaction mixture was diluted with DCM, washed with sat. NH4C1, sat NaHCO3 and water, then dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (eluent EtOAc) to afford compound 5 (16 mg, 17% yield). IH NMR (400 MHz, DMSO-d6) delta (ppm): 8.92 (s, IH), 8.41 (s, 2H), 8.36 (s, IH), 8.03 (s, IH), 7.79 (s, IH), 7.50 (d, J = 8.4 Hz, IH), 7.26 (t, J = 8.0 Hz, IH), 7.22-7.17 (m, IH), 7.14 (s, 2H), 7.07 (dt, J = 6.4, 1.2 Hz, IH), 6.60 (dd, J = 8.4, 1.4 Hz, IH), 6.55-6.47 (m, IH). MS (m/z): 363.2 (M+H).

Reference： [1]Patent: WO2009/100536,2009,A1 .Location in patent: Page/Page column 89

26
[ 1445-39-2 ]
[ 629-05-0 ]
[ 1186087-76-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561
[2]Organic Letters,2009,vol. 11,p. 4342 - 4345

27
[ 1445-39-2 ]
[ 942070-47-5 ]
[ 1309365-20-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3139 - 3141

28
[ 1445-39-2 ]
[ 25015-63-8 ]
[ 402960-38-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3139 - 3141

29
[ 1445-39-2 ]
[ 2923-28-6 ]
[Ag(2-amino-5-iodopyrimidine)2](trifluoromethanesulfonate) [ No CAS ]
[Ag(2-amino-5-iodopyrimidine)(trifluoromethanesulfonate)]n*H₂O [ No CAS ]

Reference： [1]Polyhedron,2011,vol. 30,p. 2260 - 2267

30
[ 1445-39-2 ]
[ 2923-28-6 ]
[Ag(2-amino-5-iodopyrimidine)]6(trifluoromethanesulfonate)6 [ No CAS ]

Reference： [1]Polyhedron,2011,vol. 30,p. 2260 - 2267

31
[ 1445-39-2 ]
[ 100-51-6 ]
[ 42783-58-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 1868 - 1897

32
[ 1445-39-2 ]
[ 7377-26-6 ]
[ 1316221-26-7 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 4121 - 4130

33
[ 1445-39-2 ]
[ 6165-69-1 ]
[ 870096-73-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

34
[ 1445-39-2 ]
[ 16520-62-0 ]
[ 1361537-64-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

35
[ 1445-39-2 ]
[ 55552-70-0 ]
[ 1111101-87-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

36
[ 1445-39-2 ]
[ 628-71-7 ]
[ 1361537-65-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

37
[ 1445-39-2 ]
[ 3452-09-3 ]
[ 1361537-66-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

38
[ 1445-39-2 ]
[ 931-48-6 ]
[ 1361537-61-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

39
[ 1445-39-2 ]
[ 930-51-8 ]
[ 1361537-63-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

40
[ 1445-39-2 ]
[ 17715-00-3 ]
[ 1361537-60-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

41
[ 1445-39-2 ]
[ 24424-99-5 ]
[ 1361537-47-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	With dmap; In tetrahydrofuran; for 24h;Reflux;	<strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (1.0 g, 4.52 mmol, 1.0 eq.), di-tert-butyldicarbonate (2.39 g, 10.9 mmol,2.4 eq.) and 4-dimethylaminopyridine (0.14 g, 1.15 mmol, 0.26 eq.) were dissolved in THF (50 mL)and refluxed for 24 h. The solvent was removed under reduced pressure and the brown solid waspurified via column chromatography (hexane/ethyl acetate, 3:1, Rf = 0.60) to give N, N-di-tertbutoxycarbonyl-<strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> 2b (1.85 g, 97%) as a colorless solid (m.p.: 147 C).

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 4526 - 4528
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 2462 - 2471
[3]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

42
[ 1445-39-2 ]
[ 116279-08-4 ]
[ 1361537-62-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

43
[ 1445-39-2 ]
[ 32316-92-0 ]
[ 157924-74-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

44
[ 1445-39-2 ]
[ 13922-41-3 ]
[ 157924-58-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

45
[ 1445-39-2 ]
[ 13331-27-6 ]
[ 1111104-92-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

46
[ 1445-39-2 ]
[ 693-02-7 ]
[ 948560-21-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

47
[ 1445-39-2 ]
[ 145240-28-4 ]
[ 1361537-67-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2552 - 2561

48
[ 1445-39-2 ]
[ 128796-39-4 ]
[ 69816-52-0 ]

Yield	Reaction Conditions	Operation in experiment
		5-(4-(trifluoromethyl)phenyl)pyrazin-2-amine A 100 mL round bottom flask was charged with <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (3.66 g, 21.1 mmol), (4-(trifluoromethyl)phenyl)boronic acid (4.00 g, 21.1 mmol) and MeCN (84 mL). Stirred 15 minutes at room temperature until a nice clear solution is obtained. The resulting solution is then treated with 1,1'-Bis(diphenylphosphino)ferrocene-palladium(11)dichloride dichloromethane complex (508 mg, 695 mumol) was added followed by the sodium carbonate 1M aq. (52.7 mL, 52.7 mmol). Reaction refluxed for 2 hours. Reaction cooled down to room temperature and dissolved with ammonium chloride solution (aq. sat.). Aqueous layer extracted with ethyl acetate (3). Combined organic layers washed with brine (1), dried over sodium sulfate, filtered and concentrated to give the crude material. Purification by silica gel flash chromatography (Ethyl Acetate/DCM) provide the title compound as a light yellow solid (4.4 g, 87%). 1H NMR (400 MHz, DMSO-d6) delta 6.76 (s, 2H) 7.76 (d, J=8.41 Hz, 2H) 7.99 (d, J=1.57 Hz, 1H) 8.14 (d, J=8.22 Hz, 2H) 8.62 (d, J=1.37 Hz, 1H). MS (M+1): 240.2.

Reference： [1]Patent: US2012/165343,2012,A1 .Location in patent: Page/Page column 57-58

49
[ 1445-39-2 ]
[ 100-39-0 ]
[ 1448459-81-1 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 20℃; for 19.5h;Inert atmosphere;	Under nitrogen atmosphere sodium hydride (0.03 g, 0.73 mmol, 3.2 eq., 60% NaH in oil) was addedto a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (0.05 g, 0.23 mmol, 1.0 eq.) in dry THF (1 mL) at 0 C.Benzyl bromide (0.07 mL, 0.58 mmol, 2.5 eq.) was added at 0 C after 30 min. and the reactionmixture was then allowed to warm up to room temperature. After 19 h water (3 mL) and ethyl acetate(2 mL) were added and the water phase was washed with ethyl acetate (3 mL). The combined organicphase was washed with brine (5 mL), dried over Na2SO4, filtered and the solvent was removed underreduced pressure. The crude product was purified by column chromatography (hexane to hexane/ethylacetate, 10:1, Rf = 0.57) to give N, N-dibenzyl-<strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> 2a (0.07 g, 78%) as acolorless solid (m.p.: 117 C). Crystals suitable for X-ray analysis were obtained from a hexane/ethylacetate solution.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 4526 - 4528

50
[ 1445-39-2 ]
[ 824-94-2 ]
[ 1448459-82-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydride; In tetrahydrofuran; mineral oil; at 0 - 30℃; for 23h;	<strong>[1445-39-2]2-Amino-5-iodopyrimidine</strong> (1.00 g, 4.5 mmol, 1.0 eq.) and sodium hydride (0.54 g, 13.8 mmol,3.0 eq., 60% NaH in oil) were mixed with dry THF (40 mL). 4-Methoxybenzyl chloride (3.1 mL,22.8 mmol, 5.0 eq.) was added at 0 C and the reaction mixture was then stirred at 30 C for 23 h. Thereaction was quenched with water (20 mL) and ethyl acetate (20 mL). The water layer was washedwith ethyl acetate (2 × 10 mL) and the combined org. layer was dried over MgSO4 and filtered. Thecrude product was purified via column chromatography (hexane/ethyl acetate, 20:1 to 10:1, Rf = 0.33for 10:1) to give 5-iodo-N, N-bis(4-methoxybenzyl)pyrimidin-2-amine 2c (1.90 g, 91%) as a colorlesssolid (m.p.: 80-81 C).

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 4526 - 4528

51
[ 1445-39-2 ]
[ 1456506-69-6 ]
[ 1456505-32-0 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; at 130℃; for 2h;	from Sigma-Aldrich, Milwaukee, WI), sodium carbonate (2M, 254 muEpsilon, 0.509 mmol), (S)-5,5-dimethyl-4-phenyl-3-(4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2- yl)phenyl)oxazolidin-2-one (100 mg, 0.254 mmol), and dichloro(l, l- bis(diphenylphosphinoferrocene))palladium (II) (20.76 mg, 0.025 mmol, commercially available from Sigma-Aldrich, Milwaukee, WI) were combined in dioxane (848 mu) and stirred at 130C for 2 hours. LC-MS indicated complete conversion to the desired product. The reaction mixture was passed through a syringe filter, and the material thus obtained was purified by reverse-phase preparative HPLC using 0.1% TFA in ACN/H20, gradient 15% to 90% over 20 minutes to provide (S)-3-(4-(2- aminopyrimidin-5-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one as a tan solid. lH NMR (500 MHz, DMSO-d6) delta 8.50 (s, 2H), 7.53 (s, 4H), 7.34 - 7.41 (m, 2H), 7.22 - 7.33 (m, 3H), 6.70 (s, 2H), 5.47 (s, 1H), 1.64 (s, 3H), 0.91 (s, 3H). m/z (ESI) 361.2 (M+H)+.

Reference： [1]Patent: WO2013/134079,2013,A1 .Location in patent: Paragraph 0586-0587

52
[ 1445-39-2 ]
[ 1453211-49-8 ]
[ 1453211-53-4 ]

Yield	Reaction Conditions	Operation in experiment
1.07 g	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃; for 1h;Inert atmosphere;	Preparation Example 7 To a mixture of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (1 g), 3-ethynyl-2,4-difluoro-1,5-dimethoxybenzene (897 mg), tetrakistriphenylphosphine palladium (261 mg), copper iodide (43 mg), and N,N-dimethylformamide (20 mL), N,N-diisopropylethylamine (1.55 mL) was added under an argon atmosphere followed by stirring at 80 C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and to the obtained residue were added chloroform and water, and insoluble materials were removed by filtration through celite. After the filtrate was extracted with chloroform, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then filtered. After the filtrate was concentrated under reduced pressure, the resulting residue was purified by silica gel column chromatography (chloroform/methanol) to give 5-[(2,6-difluoro-3,5-dimethoxyphenyl)ethynyl]pyrimidin-2-amine (1.07 g).

Reference： [1]Patent: US2014/142084,2014,A1 .Location in patent: Paragraph 0266

53
[ 1445-39-2 ]
[ 124-40-3 ]
[ 73418-85-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2015,vol. 357,p. 714 - 718

54
[ 1445-39-2 ]
[ 24424-99-5 ]
[ 1578264-17-1 ]

Yield	Reaction Conditions	Operation in experiment
51%	With dmap; triethylamine; In tetrahydrofuran; at 60℃; for 12h;	The resulting <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (1.4 g, 6.33 mmol, 1.0 eq) and triethylamine (1.9 g, 19 mmol, 3.0 eq.) 2as dissolved in 25 ml of tetrahydrofuran, followed by addition of 4-dimethylaminopyridine (DMAP) (0.3 g, 3.2 mmol, 0.5 eq) and dicarbonate di-tert-butyl ester (2.77 g, 12.7 mmol, 2.0 equiv). The reaction was heated to 60 C for 12 hours. After the reaction solution was concentrated under reduced pressure, silica after gel column chromatography to give a brown solid 2-iodo-5-(t-butoxycarbonyl)aminopyrimidine (1.35 g, yield: 51%).

Reference： [1]Patent: CN105622638,2016,A .Location in patent: Paragraph 0363

55
[ 1445-39-2 ]
[ 437-86-5 ]
5-iodo-N-(2-methyl-6-nitrophenyl)pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%		NaH (0.7 lg, 17.9mmol) was added to a solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (2g, 8.9mmol) at 0 °C and stirred the reaction mixture for 15min. Added 2-fluoro-l-methyl-3-nitrobenzene (1.52g, 9.8mmol) and stirred the reaction mass at room temperature. Cooled the reaction mass to 0 °C and quenched with ice cold water and ethyl acetate. Separated ethyl acetate layer washed with water followed by brine, dried over Na2S04, filtered and concentrated. The residue was purified by 60-120 silica gel column chromatography to afford desired title compound (3g, 90percent). LCMS: m/z = 357.0 (M+H)+.

Reference： [1]Patent: WO2016/164703,2016,A1 .Location in patent: Page/Page column 88

56
[ 1445-39-2 ]
5-bromo-2-fluoro-1-methyl-3-nitrobenzene [ No CAS ]
N-(4-bromo-2-methyl-6-nitrophenyl)-5-iodopyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.5%		NaH (O.lg, 4.27mmol) was added to a solution of <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (0.5g, 2.13mmol) in DMF (5mL) and stirred the reaction mixture for lOmin at room temperature. Added 5-bromo-2- fluoro-l-methyl-3 -nitrobenzene (0.5g, 2.13mmol) and stirred the reaction mass for 4h at room temperature. Cooled the reaction mass to 0 C and quenched with ice cold water and ethyl acetate. Separated ethyl acetate layer washed with water followed by brine, dried over Na2S04, filtered and concentrated. The residue was purified by combiflash by eluting with 10-13% ethylacetate - hexane system to afford desired title compound (0.6g, 64.5%). LCMS: m/z = 436.0 (M+H)+.

Reference： [1]Patent: WO2016/164703,2016,A1 .Location in patent: Page/Page column 116

57
[ 1445-39-2 ]
[ 7732-18-5 ]
[ 10035-10-6 ]
[ 7787-70-4 ]
C₄H₄IN₃*Cu⁽¹⁺⁾*Br^(1-)*H₂O*BrH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	at 20℃; for 24h;	General procedure: Prepared as described for 1 except CuBr (0.29g, 2.0mmol) and HBr (47%) were used. Yield: 0.25g (27%). Anal. Calcd for C4H7N3IOCuBr2 (MW=463.48): C, 10.37; H, 1.52; N, 9.07. Found: C, 10.28; H, 1.66; N, 8.91. FT-IR (cm-1): 3163(w), 2348(m), 1673(m), 1604(m), 1363(w), 1220(s), 868(s), 664(s). The color of crystal is purple.

Reference： [1]Journal of Molecular Structure,2017,vol. 1144,p. 173 - 180

58
[ 7647-01-0 ]
[ 1445-39-2 ]
[ 7732-18-5 ]
copper(l) chloride [ No CAS ]
C₄H₄IN₃*Cu⁽¹⁺⁾*Cl^(1-)*H₂O*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	at 20℃; for 24h;	CuCl (0.1g, 1.0mmol) in 2.5ml of H2O was added to the solution of L-I (0.22g, 1.0mmol) in 2.5ml of HCl (36.5%). It can be observed that CuCl dissolved in the acidic solution slowly. Slow evaporation of the aqueous solution at room temperature for 1 day gave red crystals. The crystals were filtered, washed with diethyl ether, and then dried under vacuum. Yield: 0.045g (12%). Anal. Calcd for C4H7N3IOCuCl2 (MW=374.48): C, 12.83; H, 1.88; N, 11.22. Found: C, 12.71; H, 1.98; N, 11.35%. FT-IR(cm-1): 3308(w), 2360(s), 1653(m), 1616(m), 1375(w), 668(w).

Reference： [1]Journal of Molecular Structure,2017,vol. 1144,p. 173 - 180

59
[ 1445-39-2 ]
[ 62673-31-8 ]
5-benzylpyrimidin-2-amine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 8473 - 8477
Angew. Chem.,2018,vol. 130,p. 8609 - 8613,5

60
[ 1445-39-2 ]
[ 100-39-0 ]
5-benzylpyrimidin-2-amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 4748 - 4753

61
[ 1445-39-2 ]
[ 70-23-5 ]
ethyl 6-iodoimidazo[1,2-a]pyrimidine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%		Ethyl bromopyruvate (1.51mL, 10.86mmol) was added dropwise to a solution of 32 2-amino-4-iodopyrimidine (0.80g, 3.62mmol) in dry 33 THF (40mL). The mixture was stirred at rt for 2h after which it was filtered. This solid was then dissolved in 34 ethanol (20mL) and refluxed for 1h. The reaction mixture was cooled down, concentrated in vacuo and partitioned between CH2Cl2 (20mL) and saturated aqueous NaHCO3 (20mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by flash column chromatography (eluent 30-40C petrol/EtOAc, 3:1 to 1:6) afforded 35 1 as a white solid (0.59g, 52%): mp 209-211C; numax (cm-1) 1721 (C=O); 1H NMR (400MHz, CDCl3) 8.77 (d, J=2.0Hz, 1H), 8.69 (d, J=2.0Hz, 1H), 8.10 (s,1H), 4.45 (q, J=7.0Hz, 2H), 1.42 (t, J=7.0Hz, 3H); 13C NMR (100MHz, CDCl3) 162.6, 157.0, 146.1, 138.3, 114.8, 75.6, 61.7, 14.5; HRMS (ESI+) C9H9O2N3127I+ [M+H]+ requires 317.9734; found 317.9725.

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

62
[ 1445-39-2 ]
[ 98-80-6 ]
[ 31408-23-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium phosphate; palladium diacetate; In ethylene glycol; at 80℃; for 2h;	Based on a literature method [34] 16 <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (2.00g, 9.05mmol), 68 phenylboronic acid (1.66mg, 13.57mmol), 69 Pd(OAc)2 (20mg, 0.09mmol) and K3PO4·7H2O (3.84mg, 18.1mmol) in 70 ethylene glycol (36mL) were heated at 80C for 120min. The reaction was then allowed to cool to rt, and it was added to brine, extracted with Et2O (3×50mL), dried over Na2SO4 and concentrated in vacuo. Then 71 NaOH (3.6g) was added and stirred for 2h. The mixture was added to brine and extracted with Et2O (3×100mL) to give 17 6 as a light yellow solid (1.40g, 90%). mp 161-163C (lit. 158-159C [35]), 1H NMR (400MHz, MeOH-d4) delta 8.53 (s, 2H), 7.56-7.49 (m, 2H), 7.47-7.39 (m, 2H), 7.37-7.30 (m, 1H).

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288
[2]ACS Chemical Neuroscience,2018

63
[ 1445-39-2 ]
[ 63503-60-6 ]
[ 947592-43-0 ]

Reference： [1]ACS Chemical Neuroscience,2018

64
[ 1445-39-2 ]
[ 1679-18-1 ]
[ 31408-28-3 ]

Reference： [1]ACS Chemical Neuroscience,2018

65
[ 1445-39-2 ]
[ 5720-07-0 ]
[ 31408-47-6 ]

Reference： [1]ACS Chemical Neuroscience,2018

66
[ 1445-39-2 ]
[ 151169-75-4 ]
C₁₀H₇Cl₂N₃ [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2018

67
[ 1445-39-2 ]
5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-(trifluoromethyl)benzenesulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(trifluoromethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
142 mg	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 1.5h;Microwave irradiation;	c) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(trifluoromethyl)benzenesulfonamide A mixture of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (172 mg), 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-(trifluoromethyl)benzenesulfonamide (212 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (30 mg), cesium carbonate (656 mg) and DMSO (4 mL) was stirred under microwave irradiation at 120 C. for 1.5 hr. The reaction mixture was purified by silica gel column chromatography (ethyl acetate/hexane) and further separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). To the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate and concentrated. The residue was washed with ethyl acetate/IPE to give the title compound (142 mg). 1H NMR (300 MHz, DMSO-d6) delta 7.05-7.36 (4H, m), 7.87-7.95 (1H, m), 7.95-8.02 (1H, m), 8.03 (1H, d, J=2.1 Hz), 8.43 (2H, s), 10.72 (1H, brs).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0913; 0914

68
[ 1445-39-2 ]
5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide [ No CAS ]
[ 64-19-7 ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide acetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.53 g		b) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide acetate A mixture of 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide (1.24 g), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (1.15 g), dichlorobis(tricyclohexylphosphine)palladium(II) (170 mg), cesium carbonate (4.51 g) and DMSO (16.5 mL) was stirred under a nitrogen atmosphere at 120 C. for 3 hr. After cooling to room temperature, the mixture was diluted with water/saturated brine and extracted three times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude purified product in a free form. The obtained title compound as a crude purified product in a free form was dissolved in DMF/toluene and subjected to silica gel column chromatography (NH, methanol/ethyl acetate) to elute a byproduct. Silica gel supporting a free form of the title compound was added to ethyl acetate (100 mL), acetic acid (18 mL) and water (100 mL), and the mixture was stirred at room temperature for 10 min. The mixture was filtered and silica gel on the filter was treated 4 times with ethyl acetate/acetic acid (30 mL/6 mL) to elute the object product. The organic layer was collected from the filtrate, and the organic layer was washed with water and saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was dissolved in an ethyl acetate/THF/saturated aqueous sodium hydrogen carbonate solution, and the obtained organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and washed with ethyl acetate to give the title compound as a crude purified product in a free form. The same reaction was performed at 4.05-fold amount and 4.12-fold amount. The obtained title compounds as crude purified products in a free form were collected, acetic acid (24.8 mL) was added and the mixture was heated to 50 C. To the mixture was added DMSO (66 mL) at 50 C. and dissolved therein. The mixture was filtered, and a trace amount of an insoluble material on the filter was washed with acetic acid (24.8 mL). The filtrate was heated to 50 C. and water (50 mL) was added dropwise. The mixture was cooled to room temperature over 30 min. The precipitate was collected by filtration, washed three times with ethanol/water (1/10, 33 mL) and dried at 50 C. under reduced pressure to give the title compound (5.53 g). 1H NMR (300 MHz, DMSO-d6) delta 1.91 (3H, s), 3.94 (3H, s), 7.14-7.37 (4H, m), 8.07 (1H, d, J=2.6 Hz), 8.43 (2H, s), 8.52 (1H, d, J=2.6 Hz), 10.46 (1H, s), 11.94 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0917; 0918
[2]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1498 - 1503

69
[ 1445-39-2 ]
2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)benzenesulfonamide [ No CAS ]
[ 76-05-1 ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.5 mg		Example 13 N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide TFA Salt A mixture of 2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)benzenesulfonamide (29 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (35 mg), cesium carbonate (104 mg), bis(tricyclohexylphosphine)palladium(II) dichloride (5.6 mg) and DMSO (0.5 mL) was stirred under microwave irradiation at 120 C. for 2 hr. After cooling to room temperature, the precipitate was removed by filtration, and the filtrate was purified by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). Fractions containing the object product were collected and concentrated by blowing air at 60 C. to give the title compound (10.5 mg).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0935

70
[ 1445-39-2 ]
2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)benzenesulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.52 g	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 2h;Microwave irradiation;	Example 17 N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichlorobenzenesulfonamide A mixture of 2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)benzenesulfonamide (0.65 g), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (0.60 g), cesium carbonate (2.34 g), bis(tricyclohexylphosphine)palladium(II) dichloride (0.088 g) and DMSO (20 mL) was stirred under microwave irradiation at 120 C. for 2 hr. The same reaction using the same amounts was performed 2 times in total. The reaction mixtures were combined, an insoluble material was filtered off, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane). The obtained crude purified product of the title compound was subjected to a recrystallization operation with ethanol/water at 60 C. to give the title compound (0.52 g). 1H NMR (300 MHz, DMSO-d6) delta 7.10-7.23 (1H, m), 7.24-7.41 (3H, m), 7.76 (2H, s), 7.83-7.94 (1H, m), 8.43 (2H, s), 10.76 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0941; 0942

71
[ 1445-39-2 ]
5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methylbenzenesulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40 mg	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 2h;Microwave irradiation;	b) N-(3-((2-aminopyrimidin-5-yl) ethynyl)-2,4-difluorophenyl)-5-chloro-2-methylbenzenesulfonamide A mixture of 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-methylbenzenesulfonamide (100 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (78 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (14 mg), cesium carbonate (381 mg) and DMSO (2 mL) was stirred under microwave irradiation at 120 C. for 2 hr. After cooling to room temperature, the reaction mixture was filtered through celite, and the filtrate was diluted with water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and washed with ethyl acetate/hexane to give the title compound (40 mg). 1H NMR (300 MHz, DMSO-d6) delta 2.57 (3H, s), 7.15-7.23 (1H, m), 7.23-7.34 (3H, m), 7.48 (1H, d, J=8.0 Hz), 7.60-7.70 (2H, m), 8.43 (2H, s), 10.55 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0947; 0948

72
[ 1445-39-2 ]
2-chloro-N-(3-ethynyl-2,4-difluorophenyl)-5-(trifluoromethyl)benzenesulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2-chloro-5-(trifluoromethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60 mg	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 1.5h;Microwave irradiation;	c) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2-chloro-5-(trifluoromethyl)benzenesulfonamide A mixture of 2-chloro-N-(3-ethynyl-2,4-difluorophenyl)-5-(trifluoromethyl)benzenesulfonamide (198 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (166 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (24.6 mg), DMSO (3.16 mL) and cesium carbonate (652 mg) was stirred under microwave irradiation at 120 C. for 1.5 hr. The reaction mixture was diluted with ethyl acetate, and an insoluble material was removed by filtration. The filtrate was concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and subjected to ethyl acetate. The precipitate was collected by filtration and washed with ethyl acetate to give the title compound (60 mg). 1H NMR (300 MHz, DMSO-d6) delta 7.13-7.23 (1H, m), 7.25-7.36 (3H, m), 7.96-8.01 (1H, m), 8.06-8.11 (2H, m), 8.42 (2H, s), 10.86 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0984; 0985

73
[ 1445-39-2 ]
5-chloro-N-(3-ethynyl-2-fluorophenyl)-2-methoxypyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
121 mg	With copper(l) iodide; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); triethylamine; In dimethyl sulfoxide; at 100℃; for 1h;Microwave irradiation;	d) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide A mixture of 5-chloro-N-(3-ethynyl-2-fluorophenyl)-2-methoxypyridine-3-sulfonamide (225 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (190 mg), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (22.2 mg), copper(I) iodide (12.6 mg), triethylamine (0.92 mL) and DMSO (2.34 mL) was stirred under microwave irradiation at 100 C. for 1 hr. After cooling to room temperature, the mixture was diluted with water/saturated brine and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and subjected to ethyl acetate. The precipitate was collected by filtration and dried under reduced pressure to give the title compound (121 mg). 1H NMR (300 MHz, DMSO-d6) delta 3.93 (3H, s), 7.12-7.32 (4H, m), 7.39 (1H, t, J=6.9 Hz), 8.08 (1H, d, J=2.4 Hz), 8.42 (2H, s), 8.51 (1H, d, J=2.4 Hz), 10.48 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1019; 1020

74
[ 1445-39-2 ]
5-chloro-N-(4-chloro-3-ethynyl-2-fluorophenyl)-2-methoxypyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-4-chloro-2-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55 mg	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 130℃; for 0.5h;Microwave irradiation;	f) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-4-chloro-2-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide A mixture of 5-chloro-N-(4-chloro-3-ethynyl-2-fluorophenyl)-2-methoxypyridine-3-sulfonamide (88 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (67 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (12 mg), cesium carbonate (233 mg) and DMSO (2 mL) was stirred under microwave irradiation at 130 C. for 30 min. After cooling to room temperature, the reaction mixture was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude purified product. The obtained crude purified product of the title compound was subjected to silica gel column chromatography (NH, methanol/ethyl acetate) to elute a byproduct. Silica gel supporting the title compound was added to ethyl acetate (10 mL), acetic acid (2 mL) and water (10 mL), and the mixture was stirred at room temperature for 10 min. The mixture was filtered and silica gel on the filter was treated 4 times with ethyl acetate/acetic acid (4 mL/1 mL) to elute the object product. The filtrate was diluted with water and extracted 2 times with ethyl acetate. To the obtained residue was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted 2 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated. The obtained residue was washed with ethyl acetate to give the title compound (55 mg). 1H NMR (300 MHz, DMSO-d6) delta 3.92 (3H, s), 7.26-7.36 (3H, m), 7.37-7.44 (1H, m), 8.10 (1H, d, J=2.6 Hz), 8.44 (2H, s), 8.52 (1H, d, J=2.5 Hz), 10.61 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1030; 1031

75
[ 1445-39-2 ]
5-chloro-N-(2-chloro-3-ethynyl-4-fluorophenyl)-2-methoxypyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-chloro-4-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60 mg	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 130℃; for 0.5h;Microwave irradiation;	f) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-chloro-4-fluorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide A mixture of 5-chloro-N-(2-chloro-3-ethynyl-4-fluorophenyl)-2-methoxypyridine-3-sulfonamide (146 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (140 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (21 mg), cesium carbonate (546 mg) and DMSO (4 mL) was stirred under microwave irradiation at 130 C. for 30 min. After cooling to room temperature, the reaction mixture was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude purified product. The obtained crude purified product of the title compound was subjected to silica gel column chromatography (NH, methanol/ethyl acetate) to elute a byproduct. Silica gel supporting the title compound was added to ethyl acetate (10 mL), acetic acid (2 mL) and water (10 mL), and the mixture was stirred at room temperature for 10 min. The mixture was filtered and silica gel on the filter was treated 4 times with ethyl acetate/acetic acid (4 mL/1 mL) to elute the object product. The filtrate was diluted with water and extracted 2 times with ethyl acetate. To the obtained residue was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted 2 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated. The obtained residue was washed with ethyl acetate to give the title compound (60 mg). 1H NMR (300 MHz, DMSO-d6) delta 3.90 (3H, s), 7.25-7.44 (4H, m), 8.03 (1H, d, J=2.6 Hz), 8.43 (2H, s), 8.52 (1H, d, J=2.5 Hz), 10.44 (1H, brs).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1040; 1041

76
[ 1445-39-2 ]
5-chloro-N-(2-chloro-3-ethynylphenyl)-2-methoxypyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-chlorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	With copper(l) iodide; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); triethylamine; In dimethyl sulfoxide; at 100℃; for 1h;Microwave irradiation;	g) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2-chlorophenyl)-5-chloro-2-methoxypyridine-3-sulfonamide A mixture of 5-chloro-N-(2-chloro-3-ethynylphenyl)-2-methoxypyridine-3-sulfonamide (185 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (149 mg), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (17.4 mg), copper(I) iodide (9.9 mg), triethylamine (0.72 mL) and DMSO (1.83 mL) was stirred under microwave irradiation at 100 C. for 1 hr. After cooling to room temperature, the mixture was diluted with water/saturated brine and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude purified product. The obtained crude purified product of the title compound was subjected to silica gel column chromatography (NH, methanol/ethyl acetate) to elute a byproduct. Silica gel supporting the title compound was added to ethyl acetate (20 mL), acetic acid (4 mL) and water (20 mL), and the mixture was stirred at room temperature for 10 min. The mixture was filtered and silica gel on the filter was treated 4 times with ethyl acetate/acetic acid (6 mL/1.2 mL) to elute the object product. The organic layer was collected from the filtrate, and the organic layer was washed with water and saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and subjected to ethyl acetate/hexane and the precipitate was collected by filtration to give the title compound (31 mg). 1H NMR (300 MHz, DMSO-d6) delta 3.88 (3H, s), 7.24 (2H, brs), 7.31-7.38 (2H, m), 7.44-7.52 (1H, m), 8.03 (1H, d, J=2.6 Hz), 8.42 (2H, s), 8.48-8.52 (1H, m), 10.37 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1054; 1055

77
[ 1445-39-2 ]
5-chloro-3-(N-(3-ethynyl-2,4-difluorophenyl)sulfamoyl)-2-methoxybenzyl acetate [ No CAS ]
3-((3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)sulfamoyl)-5-chloro-2-methoxybenzyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
258 mg	With copper(l) iodide; (bis(tricyclohexyl)phosphine)palladium(II) dichloride; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; for 1h;Microwave irradiation;	g) 3-((3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)sulfamoyl)-5-chloro-2-methoxybenzyl acetate A mixture of 5-chloro-3-(N-(3-ethynyl-2,4-difluorophenyl)sulfamoyl)-2-methoxybenzyl acetate (300 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (51.5 mg), DIPEA (2 mL), copper(I) iodide (26.6 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (201 mg) and DMSO (3 mL) was stirred under microwave irradiation at 100 C. for 1 hr. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give a residue. The obtained residue was washed with ethyl acetate/IPE to give the title compound (258 mg). 1H NMR (300 MHz, DMSO-d6) delta 2.09 (3H, s), 3.83 (3H, s), 5.15 (2H, s), 7.12-7.28 (2H, m), 7.30 (2H, s), 7.66 (1H, d, J=2.7 Hz), 7.78 (1H, d, J=2.7 Hz), 8.43 (2H, s), 10.34 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1068; 1069

78
[ 1445-39-2 ]
5-chloro-7-(N-(3-ethynyl-2,4-difluorophenyl)sulfamoyl)-2,3-dihydrobenzofuran-3-yl acetate [ No CAS ]
7-(N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)sulfamoyl)-5-chloro-2,3-dihydrobenzofuran-3-yl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
254 mg	With copper(l) iodide; (bis(tricyclohexyl)phosphine)palladium(II) dichloride; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 100℃; for 1h;Microwave irradiation;	h) 7-(N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl) sulfamoyl)-5-chloro-2,3-dihydrobenzofuran-3-yl Acetate A mixture of 5-chloro-7-(N-(3-ethynyl-2,4-difluorophenyl)sulfamoyl)-2,3-dihydrobenzofuran-3-yl acetate (290 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (50.0 mg), DIPEA (2 mL), copper(I) iodide (25.8 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (195 mg) and DMSO (3 mL) was stirred under microwave irradiation at 100 C. for 1 hr. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (254 mg). MS: [M-H]- 519.1.

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1114; 1115

79
[ 1445-39-2 ]
5-chloro-2-(difluoromethoxy)-N-(3-ethynyl-2,4-difluorophenyl)pyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(difluoromethoxy)pyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26.8 mg	With copper(l) iodide; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); triethylamine; In dimethyl sulfoxide; at 100℃; for 1h;Microwave irradiation;	h) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(difluoromethoxy)pyridine-3-sulfonamide A mixture of bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (4.5 mg), 5-chloro-2-(difluoromethoxy)-N-(3-ethynyl-2,4-difluorophenyl)pyridine-3-sulfonamide (53 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (39 mg), triethylamine (0.19 mL) and copper(I) iodide (2.6 mg) in DMSO (0.48 mL) was stirred under microwave irradiation at 100 C. for 1 hr. The reaction mixture was diluted with ethyl acetate and washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine. The obtained organic layer was dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound as a crude purified product. The obtained crude purified product of the title compound was subjected to silica gel column chromatography (NH, methanol/ethyl acetate) to elute a byproduct. Silica gel supporting the title compound was added to ethyl acetate (20 mL), acetic acid (4 mL) and water (20 mL), and the mixture was stirred at room temperature for 10 min. The mixture was filtered and silica gel on the filter was treated 4 times with ethyl acetate/acetic acid (6 mL/1.2 mL) to elute the object product. The filtrate was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated. The obtained crude purified product of the title compound was separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). To the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (26.8 mg). 1H NMR (300 MHz, DMSO-d6) delta 7.13-7.22 (1H, m), 7.26-7.40 (3H, m), 7.49-8.00 (1H, m), 8.29 (1H, d, J=2.4 Hz), 8.43 (2H, s), 8.62 (1H, d, J=2.1 Hz), 10.75 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1133; 1134

80
[ 1445-39-2 ]
5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-(methylamino)pyridine-3-sulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(methylamino)pyridine-3-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46.9 mg	With copper(l) iodide; bis(di-tert-?butyl(4-?dimethylaminophenyl)?phosphine)?dichloropalladium(II); triethylamine; In dimethyl sulfoxide; at 100℃; for 1h;	d) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-5-chloro-2-(methylamino)pyridine-3-sulfonamide A mixture of 5-chloro-N-(3-ethynyl-2,4-difluorophenyl)-2-(methylamino)pyridine-3-sulfonamide (114 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (92 mg), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (11 mg), copper(I) iodide (6.0 mg), triethylamine (0.45 mL) and DMSO (1.14 mL) was stirred at 100 C. for 1 hr. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and subjected to DMSO/methanol. The precipitate was collected by filtration and washed with methanol to give the title compound (46.9 mg). 1H NMR (300 MHz, DMSO-d6) delta 2.91 (3H, d, J=4.7 Hz), 6.61-6.69 (1H, m), 7.16-7.35 (4H, m), 7.70 (1H, d, J=2.6 Hz), 8.34 (1H, d, J=2.4 Hz), 8.44 (2H, s), 10.54 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 1162; 1163

81
[ 1445-39-2 ]
2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)-3-(hydroxymethyl)benzenesulfonamide [ No CAS ]
N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichloro-3-(hydroxymethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.25 g	With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; caesium carbonate; In dimethyl sulfoxide; at 120℃; for 1.5h;Microwave irradiation;	c) N-(3-((2-aminopyrimidin-5-yl)ethynyl)-2,4-difluorophenyl)-2,5-dichloro-3-(hydroxymethyl)benzenesulfonamide A mixture of 2,5-dichloro-N-(3-ethynyl-2,4-difluorophenyl)-3-(hydroxymethyl)benzenesulfonamide (900 mg), <strong>[1445-39-2]5-iodopyrimidin-2-amine</strong> (761 mg), dichlorobis(tricyclohexylphosphine)palladium(II) (113 mg), cesium carbonate (2.99 g) and DMSO (14.5 mL) was stirred under microwave irradiation at 120 C. for 1.5 hr. The same reaction was performed two more times at 1.3-fold amount. After cooling to room temperature, the reaction mixtures were combined, diluted with water/saturated aqueous ammonium chloride solution, and extracted 3 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and subjected to ethyl acetate/hexane, and the precipitate was collected by filtration to give the title compound as a crude purified product. The filtrate was concentrated to give a residue. The crude purified product of the title compound and the obtained residue were combined, and further purified by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA-containing system)). Fractions containing the object product were collected, neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated to give a residue. The residue was dissolved in ethanol/water (90 mL/9 mL) at 60 C., and the mixture was filtered, and a trace amount of insoluble material was washed with ethanol (10 mL). The filtrate was heated to 60 C., and water (191 mL) was added dropwise over 15 min. The mixture was cooled to room temperature over 2 hr. The precipitate was collected by filtration, washed 3 times with ethanol/water (1/1, 5 mL) and dried at 50 C. under reduced pressure to give the title compound (1.25 g). 1H NMR (300 MHz, DMSO-d6) delta 4.63 (2H, d, J=5.7 Hz), 5.75 (1H, t, J=5.7 Hz), 7.12-7.36 (4H, m), 7.76-7.86 (2H, m), 8.43 (2H, s), 10.73 (1H, s).

Reference： [1]Patent: US2019/169166,2019,A1 .Location in patent: Paragraph 0900; 0901
[2]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1498 - 1503

82
[ 1445-39-2 ]
[ 866545-91-7 ]
C₁₈H₁₅N₅O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; triethylamine; In 1,4-dioxane; methanol; at 100℃; for 18h;Schlenk technique; Inert atmosphere;	General procedure: The 7-azaindole 1 (1.00 mmol) and tetrakis(triphenylphosphane)palladium(0) (35.0 mg, 0.03 mmol)were placed in a dry screw-cap vessel with a magnetic stir bar. After evacuating and refilling with argonfor three times dry 1,4-dioxan (5.0 mL) was added and the resulting mixtures was degassed with argonfor 10 min. Dry triethylamine (1.40 mL, 10.0 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.25mL, 1.70 mmol) were successively added. Then the reaction mixture was stirred in a preheated oil bathat 80 C for 4 h. The mixture was cooled down to room temp (water bath). Dry methanol (5.0 mL) wasadded and the mixture was stirred at room temp for 10 min. After the addition of (hetero)aryl halide 2and cesium carbonate (823 mg, 2.50 mmol) the mixture was stirred in a preheated oil bath at 100 C for18 h. After the Suzuki coupling was completed the mixture was cooled to room temp (water bath).Sodium hydroxide (100 mg, 2.50 mmol) was added and the reaction was stirred at 100 C for 4 h. Then,after cooling to room temp (water bath), the solvents were removed in vacuo and the residue wasabsorbed onto Celite. After purification by chromatography on silica gel (dichloromethane-methanol aqueous ammonia, see Table 1) and after drying in vacuo at 80 C for 18 h the desired compounds 3 could be obtained (see Table 1).

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 3463 - 3468

83
[ 1445-39-2 ]
ethyl 1-methyl-7-((trimethylsilyl)ethynyl)-1H-indole-2-carboxylate [ No CAS ]
ethyl 7-((2-aminopyrimidin-5-yl)ethynyl)-1-methyl-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With copper(l) iodide; tetrabutyl ammonium fluoride; triethylamine; In N,N-dimethyl-d6-formamide;Heating;	Ethyl 1-methyl-7-((trimethylsilyl)ethynyl)- 1H-indole-2-carboxylate (3.0 g, 10 mmol),<strong>[1445-39-2]5-iodopyrimidine-2-amine</strong> (3.3 g, 15 mmol), cuprous iodide (0.19 g, 1 mmol), tetrabutylammonium fluoride (2.6 g, 10 mmol),Soluble in a mixed solvent of triethylamine and dimethylformamide,Stirring with heating until the reaction is completed, ethyl acetate is extracted with water, and the organic phase is concentrated.Column chromatography gave 1.6 g of a yellow solid product in 50% yield.

Reference： [1]Patent: CN109988151,2019,A .Location in patent: Paragraph 0213; 0218-0220

84
[ 1445-39-2 ]
[ 813-19-4 ]
5-(tributylstannyl)pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; In N,N-dimethyl-formamide; at 65℃;Inert atmosphere;	To a solution of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> (0.50 g, 2.26 mmol)in anh. DMF (100 mL) under direct nitrogen bubbling was added bis(tributyltin) (1.37 mL, 2.71 mmol)and Pd2dba3*CHCl3 (0.23 g, 0.23 mmol). Then, the reaction was heated to 65 C with stirring for3 h under direct nitrogen bubbling. After completion, the solvent was removed in vacuo to give ablack thick oil. The crude mixture was resuspended in EtOAc and filtered over a celite pad; then,the filtrate was concentrated in vacuo to give a dark liquid. Purification was performed using flashcolumn chromatography on silica (0-100% EtOAc in hexanes) to give the pure product as a yellowoil (0.75 g, 86%); Rf = 0.76 (1:1 EtOAc: Hex); 1H NMR (500 MHz, CDCl3)delta 8.17 (s, 2H), 6.08 (br, 2H),1.45-1.51 (m, 6H), 1.39-1.44 (m, 6H), 1.21-1.29 (m, 6H), 0.83-1.06 (m, 9H); 13C NMR (126 MHz, CDCl3) delta164.32, 163.16, 119.22, 28.84, 27.44, 13.57, 8.09; MS (ESI+) m/z calcd for C16H31N3Sn [M + H]+ 386.15,found: 386.19.

Reference： [1]Molecules,2019,vol. 24

85
[ 1445-39-2 ]
[ 3132-99-8 ]
[ 94-02-0 ]
ethyl 2-benzoyl-3-(3-bromophenyl)-3-((5-iodopyrimidin-2-yl)amino)propanoate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9001 - 9007

86
[ 1445-39-2 ]
[ 104-88-1 ]
[ 94-02-0 ]
ethyl 2-benzoyl-3-(4-chlorophenyl)-3-((5-iodopyrimidin-2-yl)amino)propanoate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9001 - 9007

87
[ 455-19-6 ]
[ 1445-39-2 ]
[ 94-02-0 ]
ethyl 2-benzoyl-3-(5-iodopyrimidin-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propanoate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9001 - 9007

88
[ 1445-39-2 ]
[ 401-95-6 ]
[ 94-02-0 ]
ethyl 2-benzoyl-3-(3,5-bis(trifluoromethyl)phenyl)-3-((5-iodopyrimidin-2-yl)amino)propanoate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 9001 - 9007

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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. 1445-39-2 ] {[proInfo.proName]}

Quality Control of [ 1445-39-2 ]

Related Doc. of [ 1445-39-2 ]

Product Details of [ 1445-39-2 ]

Calculated chemistry of [ 1445-39-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1445-39-2 ]

Application In Synthesis of [ 1445-39-2 ]

[ 1445-39-2 ] Synthesis Path-Upstream 1~5

[ 1445-39-2 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 1445-39-2 ]

Amines

Related Parent Nucleus of [ 1445-39-2 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 1445-39-2 ]

Related Parent Nucleus of
[ 1445-39-2 ]