[ CAS No. 591-55-9 ] {[proInfo.proName]}

Name: 591-55-9|5-Aminopyrimidine|98%
Brand: Ambeed
SKU: A392008
Price: 9.0 USD
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Quality Control of [ 591-55-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 591-55-9 ]

SDS Specification

Alternatived Products of [ 591-55-9 ]

Product Details of [ 591-55-9 ]

CAS No. :	591-55-9	MDL No. :	MFCD01529870
Formula :	C₄H₅N₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FVLAYJRLBLHIPV-UHFFFAOYSA-N
M.W :	95.10	Pubchem ID :	344373
Synonyms :

Calculated chemistry of [ 591-55-9 ]

Physicochemical Properties

Num. heavy atoms :	7
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 :	26.44
TPSA :	51.8 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.46 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.99
Log Po/w (XLOGP3) :	-0.81
Log Po/w (WLOGP) :	0.07
Log Po/w (MLOGP) :	-1.13
Log Po/w (SILICOS-IT) :	0.38
Consensus Log Po/w :	-0.1

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.55
Solubility :	26.6 mg/ml ; 0.279 mol/l
Class :	Very soluble
Log S (Ali) :	0.2
Solubility :	151.0 mg/ml ; 1.59 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-1.21
Solubility :	5.93 mg/ml ; 0.0624 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.06

Safety of [ 591-55-9 ]

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 [ 591-55-9 ]

* 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 [ 591-55-9 ]
Downstream synthetic route of [ 591-55-9 ]

[ 591-55-9 ] Synthesis Path-Upstream 1~9

1
[ 53180-76-0 ]
[ 591-55-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide; hydrogen In diethyl ether; water at 20℃; for 20 h;	A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10percent on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95percent yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35percent yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10percent on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67percent). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51percent) was obtained, which was used without further purification.
67%	With ammonium formate In methanol at 0℃;	A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10percent on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95percent yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35percent yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10percent on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67percent). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51percent) was obtained, which was used without further purification.

Reference： [1] Patent: WO2005/30213, 2005, A1, . Location in patent: Page/Page column 176
[2] Patent: WO2005/30213, 2005, A1, . Location in patent: Page/Page column 176-177

2
[ 5413-85-4 ]
[ 591-55-9 ]

Yield	Reaction Conditions	Operation in experiment
31.9%	With sodium hydroxide; hydrogen In diethyl ether; water at 20℃; for 72 h;	Example 142; 4-(3-Phenyl-1,2,4-thiadiazol-5-yl)-N-pyrimidin-5-ylpiperazine-1-carboxamide; (1) Pyrimidine-5-amine; A mixture of 5-amino-4,6-dichloropyrimidine (2.00 g, 12.2 mmol), ether (240 ml), sodium hydroxide (8 g), water (32 ml) and 10percent palladium-carbon (160 mg) was stirred under a hydrogen atmosphere at room temperature for 3 days, insolubles were filtered off and an organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to obtain the desired product (370 mg, 31.9percent) as a solid. ¹H-NMR (CDCl₃) δ; 3.75 (2H, br s), 8.21 (2H, s), 8.66 (1H, s).

Reference： [1] Canadian Journal of Chemistry, 1999, vol. 77, # 2, p. 216 - 222
[2] Patent: EP1813606, 2007, A1, . Location in patent: Page/Page column 79
[3] Journal of the Chemical Society, 1956, p. 3311,3313

3
[ 4316-93-2 ]
[ 591-55-9 ]

Reference： [1] Journal of Labelled Compounds and Radiopharmaceuticals, 2008, vol. 51, # 1, p. 54 - 58

4
[ 4595-59-9 ]
[ 591-55-9 ]

Reference： [1] Journal of Organic Chemistry, 2012, vol. 77, # 16, p. 6908 - 6916

5
[ 4595-59-9 ]
[ 591-55-9 ]
[ 1298134-92-5 ]

Reference： [1] Organometallics, 2017, vol. 36, # 2, p. 251 - 254

6
[ 88317-72-0 ]
[ 591-55-9 ]
[ 6311-79-1 ]

Reference： [1] Australian Journal of Chemistry, 1983, vol. 36, # 7, p. 1477 - 1482

7
[ 5177-27-5 ]
[ 591-55-9 ]

Reference： [1] Journal of the Chemical Society, 1951, p. 1565,1568[2] Journal of the Chemical Society, 1953, p. 1646
[3] Journal of Organic Chemistry, 1955, vol. 20, p. 829,833,835

8
[ 14001-70-8 ]
[ 591-55-9 ]

Reference： [1] Journal of the Chemical Society, 1951, p. 1218,1221

9
[ 591-55-9 ]
[ 849353-34-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: With benzyltrimethylazanium tribroman-2-uide In methanol; dichloromethane at 0℃; for 0.416667 h; Stage #2: at 20℃; for 1.5 h;	A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10percent on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95percent yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35percent yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10percent on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67percent). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51percent) was obtained, which was used without further purification.

Reference： [1] Patent: WO2005/30213, 2005, A1, . Location in patent: Page/Page column 177
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 4, p. 1583 - 1598
[3] Patent: WO2013/117649, 2013, A1, . Location in patent: Paragraph 0053

[ 591-55-9 ] Synthesis Path-Downstream 1~88

1
[ 591-55-9 ]
[ 108-24-7 ]
[ 45810-14-8 ]

Reference： [1]Journal of the Chemical Society,1951,p. 1565,1568
Journal of the Chemical Society,1953,p. 1646

2
[ 591-55-9 ]
[ 555-16-8 ]
(4-nitro-benzylidene)-pyrimidin-5-yl-amine [ No CAS ]

Reference： [1]Journal of the Chemical Society,1951,p. 1565,1568
Journal of the Chemical Society,1953,p. 1646

3
[ 591-55-9 ]
[ 98-88-4 ]
[ 103854-65-5 ]

Reference： [1]Journal of the Chemical Society,1951,p. 1565,1568
Journal of the Chemical Society,1953,p. 1646

4
[ 591-55-9 ]
[ 586-96-9 ]
(E)-5-(phenyldiazenyl)pyrimidine [ No CAS ]

Reference： [1]Journal of the Chemical Society,1951,p. 1565,1568
Journal of the Chemical Society,1953,p. 1646

5
[ 5177-27-5 ]
[ 591-55-9 ]

Reference： [1]Journal of the Chemical Society,1951,p. 1565,1568
Journal of the Chemical Society,1953,p. 1646

7
[ 14001-70-8 ]
[ 591-55-9 ]

Reference： [1]Journal of the Chemical Society,1951,p. 1218,1221

8
[ 591-55-9 ]
[ 5448-49-7 ]
2-(Pyrimidin-5-ylamino)-N-thiazol-2-yl-acetamide [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1982,vol. 59,p. 1097 - 1099

9
[ 591-55-9 ]
[ 84587-80-4 ]
N-(1H-Benzoimidazol-2-yl)-2-(pyrimidin-5-ylamino)-acetamide [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1982,vol. 59,p. 1097 - 1099

10
[ 591-55-9 ]
[ 874-69-1 ]
[ 75378-62-0 ]
[ 75378-58-4 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 608 - 610

11
[ 591-55-9 ]
[ 39887-75-7 ]
[ 75378-59-5 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 608 - 610

12
[ 591-55-9 ]
[ 106-49-0 ]
[ 81541-87-9 ]
[ 81541-88-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1639 - 1641

13
[ 591-55-9 ]
[ 4903-36-0 ]
[ 75378-61-9 ]
[ 75378-57-3 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 608 - 610

14
[ 591-55-9 ]
[ 62-53-3 ]
C₁₀H₉N₅ [ No CAS ]
[ 81541-85-7 ]
[ 81541-86-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1639 - 1641

15
[ 591-55-9 ]
[ 106-40-1 ]
[ 81541-89-1 ]
[ 81557-49-5 ]
[ 81541-90-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1639 - 1641

16
[ 591-55-9 ]
[ 6780-49-0 ]
[ 75378-60-8 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 608 - 610

17
[ 88317-72-0 ]
[ 591-55-9 ]
[ 6311-79-1 ]

Reference： [1]Australian Journal of Chemistry,1983,vol. 36,p. 1477 - 1482

18
[ 591-55-9 ]
[ 402-44-8 ]
[ 157911-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In ice-water; dimethyl sulfoxide;	REFERENCE EXAMPLE 10 To 5 ml of dimethyl sulfoxide (DMSO) containing 0.34 g of potassium tert-butoxide was added 0.29 g of 5-aminopyrimidine, followed by stirring at room temperature for about 15 minutes. To the reaction mixture was added dropwise 1 ml of a DMSO solution containing 0.33 g of p-fluorobenzotrifluoride, followed by heating at 60° C. for about 40 minutes. The reaction mixture was allowed to cool and poured into 150 ml of ice-water. The thus formed white crystals were collected by filtration and dried to obtain 0.17 g of 5-(4-trifluoromethylphenyl)aminopyrimidine. Mass Spectrum (m/z): 239 (M+) NMR Spectrum (DMSO-d6, TMS internal standard) delta: 7.25 (2 H, d, J=8 Hz), 7.59 (2 H, d, J=8 Hz), 8.68 (2 H, s), 8.77 (1 H, s), 9.02 (1 H, s)

Reference： [1]Chemical and Pharmaceutical Bulletin,1997,vol. 45,p. 1293 - 1299
[2]Patent: US5538976,1996,A

19
[ 591-55-9 ]
[ 1885-14-9 ]
phenyl pyrimidin-5-ylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With pyridine; In acetonitrile; at 0℃; for 12h;	To a solution of pimidin-5-amine (0.500 g, 5.260 mmol) and pidine (0.630 g, 12.500 mmol) in acetonitrile (10 mL) was added phenylchloroformate (0.720 mL, 5.790 mmol) at 0 C. The reaction mixture was stirred for 12 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was dried over sodium sulfate and evaporated under reduced pressure to give a residue.The residue was purified by column chromatography (ethyl acetate/hexanes = 60/40) to give the titled compound (0.100 g, 10 %) as a solid. LCMS: m/z 216.2 [M+ H] .

Reference： [1]Patent: WO2014/111871,2014,A1 .Location in patent: Page/Page column 74
[2]Journal of Medicinal Chemistry,2006,vol. 49,p. 716 - 726

20
[ 591-55-9 ]
[ 1001013-59-7 ]
[ 1001013-63-3 ]

Yield	Reaction Conditions	Operation in experiment
13.5%	With sodium hydride; In dimethyl sulfoxide; at 50 - 60℃; for 4 - 6h;	Preparation 4A; N'-(Dyrimidin-5-ylV4-MH-pyiToloF2.3-b1pyridin-1-yl)benzamidine; Sodium hydride oil dispersion (6.85 g of 60%) was added to a solution of 4-(1H- pyrrolo[2,3-b]pyridin-1-yl)benzonitrile (25.0 g, 114 mmol) and <strong>[591-55-9]5-aminopyrimidine</strong> (10.8 g, 114 mmol, prepared as described by Philips et al., Can. J. Chem 1999, 77, 216-222) in anhydrous dimethylsulfoxide (200 mL), and the resulting suspension was heated at 50-60 0C for 4-6 h. The cooled mixture was poured onto ice (1 kg), and the yellow suspension stirred with 150 mL EtOAc and 150 mL hexanes for 15 min and filtered. The solid was washed with water (1L in 3 portions), and dried at 780C in vacuo overnight. The dried solid (30.0 g) was suspended in 400 mL 1N HCI and the resulting aqueous solution extracted with EtOAc (5 x 125 mL). DCM (100 mL) and aqueous NaOH (110 mL of 6N were added to the aqueous layer giving a flocculent suspension which was filtered and the solid washed with water (2 x 200 mL) and dried at 78 0C and 0.1 mm giving the title substance (22.7 g). 1H NMR (CDCI3) delta 8.78 (br, 1H), 8.33 (m, 3H), 8.2-8.0 (m, 6H), 7.21 (dd, 1H, J = 4.6, 7.9), 6.95 (br, 2H), 6.75 (d, 1H1 J = 3.7). MS (AP+) m/e 315 (MH+).

Reference： [1]Patent: WO2008/4117,2008,A1 .Location in patent: Page/Page column 85

21
[ 591-55-9 ]
[ 58656-98-7 ]
[ 881402-02-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5447 - 5454

22
[ 53180-76-0 ]
[ 591-55-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydroxide; hydrogen;palladium 10% on activated carbon; In diethyl ether; water; at 20℃; under 2585.81 Torr; for 20h;	A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10% on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95% yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35% yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10% on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67%). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51%) was obtained, which was used without further purification.
67%	With ammonium formate;palladium 10% on activated carbon; In methanol; at 0℃;	A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10% on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95% yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35% yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10% on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67%). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51%) was obtained, which was used without further purification.

Reference： [1]Patent: WO2005/30213,2005,A1 .Location in patent: Page/Page column 176
[2]Patent: WO2005/30213,2005,A1 .Location in patent: Page/Page column 176-177

23
[ 591-55-9 ]
[ 849353-34-0 ]

Yield	Reaction Conditions	Operation in experiment
51%		A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10% on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95% yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35% yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4,6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10% on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67%). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51%) was obtained, which was used without further purification.
	With benzyltrimethylazanium tribroman-2-uide; In methanol; dichloromethane; at 0 - 20℃;	Benzyltrimethylammonium tribromide (1.1 eq, 4.5 g) was added portionwised to a stirred solution of 5-aminopyrimidine (1 eq, 1 g) in DCM (50 mL) and MeOH (10 mL) at 0C. The mixture was warmed up to room temperature and stirred for 90 min. Aq. sat. NaHCC>3 solution was added (pH ~8), the organic was separated and the aqueous extracted with EtOAc (3x). The combined organics were dried and concentrated. Purification by silica chromatography (EtOAc/cyclohexane; 0:100 to 50:50) gave the desired compound

Reference： [1]Patent: WO2005/30213,2005,A1 .Location in patent: Page/Page column 177
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 1583 - 1598
[3]Patent: WO2013/117649,2013,A1 .Location in patent: Paragraph 0053

24
[ 591-55-9 ]
5-ethyl-6-oxo-6,7-dihydro-5H-1-oxa-5-aza-s-indacene-7-carboxylic acid pyrrimidin-5-ylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	In benzene; for 1h;Heating / reflux;	A mixture of 5-ethyl-6-oxo-6, 7-dihydro-5H-1-oxa-s-indacene-7-carboxylic acid ethyl ester (150 mg. 0.6 mmol) and <strong>[591-55-9]5-aminopyrimidine</strong> (52 mg, 0.6 mmol.) in benzene (40 ml) was refluxed over a Dean-Stark trap for 1 hour. The mixture was cooled to room temperature, diluted with hexanes and the resulting precipitate filtered. The filtrant was dissolved in ethyl acetate (75 ml) and methanol (3 mi) and washed with 1N hydrochloric acid (1 X 5 ml), brine (1 X 5 ml), dried (sodium sulfate) then concentrated in vacuo. The residue was dissolved in methylene chloride (2 ml), diluted with diethyl ether (5 mi) and triturated with hexanes to give 54 mg 5-ethyl-6- oxo-6, 7-dihydro-5H-1-oxa-5-aza-s-indacene-7-carboxylic acid pyrimidin-5-ylamide (31%) as an orange solid, mp 100-3 C.'H-NMR (CDCI3) : No. 8.9 (s, 1H), 8.6 (d, 1H), 8.1 (d, 1H), 7.9 (s, 1H), 7.7 (s, 1H), 7.1 (s, 1H), 6.8 (s, 1H), 4.5 (s, 1H), 3.9 (q, 2H), 1.3 (t, 3H). MS (m/z, %): 321 (M+-1, 100).

Reference： [1]Patent: WO2005/41957,2005,A1 .Location in patent: Page/Page column 22

25
[ 591-55-9 ]
[ 904685-29-6 ]
{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-pyrimidin-5-yl-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 120℃;sealed tube;	A mixture of 11 (0.269 g, 0.613 mmol) and cesium carbonate (0.200 g, 0.613 mmol) in toluene (40 mL) was degassed and treated with <strong>[591-55-9]5-aminopyrimidine</strong> (0.058 g, 0.613 mmol), palladium(II) acetate (0.014 g, 0.061 mmol), and racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.057 g, 0.092 mmol). The reaction was degassed again and heated at 120 C. in a sealed tube overnight. The reaction was then cooled to room temperature and concentrated. Purification of the residue by flash chromatography (silica, 96:4 methylene chloride/methanol) and then by preparative HPLC (Method 3) afforded the title compound 0.060 g (22%) as an off-white solid: Rf 0.32 (95:5 methylene chloride/methanol); mp 88-90 C.; 1H NMR (300 MHz, CD3OD) delta 8.56 (s, 1H), 8.52 (s, 2H), 7.46-7.13 (m, 9H), 6.32 (d, J=3.6 Hz, 1H), 6.25 (d, J=7.1 Hz, 1H), 6.24 (d, J=3.6 Hz, 1H), 5.65 (d, J=7.1 Hz, 1H), 4.94 (s, 2H); IR (ATR) 3472, 3316, 3041, 1611, 1571, 1528, 1460, 1417, 1315, 1159, 754, 718 cm-1; ESI MS m/z 453 [C26H21ClN6+H]+; HPLC (Method 1)>99% (AUC), tR=11.96 min. Anal. Calcd for C26H21ClN6.1.5H2O: C, 65.06; H, 5.04; N, 17.51. Found: C, 64.83; H, 4.32; N, 16.97

Reference： [1]Patent: US2006/173049,2006,A1 .Location in patent: Page/Page column 28

Yield	Reaction Conditions	Operation in experiment
		To a suspension of the resulting acid chloride compound and 5-aminopyrimidine (84.0 mg) in methylene chloride (5 ml) is added dimethylaminopyridine (144 mg) at room temperature, and the mixture is stirred at room temperature. To the mixture is poured water, and the mixture is extracted with ethyl acetate. The extract is washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine, dried over sodium sulfate, and concentrated. The residue is triturated with a mixture of ethyl acetate and n-hexane to give 4-(3-chloro-4-methoxybenzylamino)-5-(5-pyrimidinylaminocarbonyl)-2-methylthiopyrimidine (216 mg) as pale yellow needles, m.p. 238-240 C., IR (Nujol): 3251, 1666 cm-1, MS (m/z): 416 (M+).

27
[ 591-55-9 ]
[ 136528-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	With carbon disulfide; triethylamine; In ethanol;	1. PREPARATION EXAMPLES 2-(5-Pyrimidylimino)-1,3-dithietane (Compound 1.1) 23.4 g (0.232 mol) of triethylamine are added dropwise to a ready-prepared solution of 20 g (0.211 mol) of <strong>[591-55-9]5-aminopyrimidine</strong> and 12.7 ml (0.211 mol) of carbon disulfide in 50 ml of ethyl alcohol. The reaction mixture is then stirred for 15 hours at 70 C. and the resulting suspension is filtered off. Drying yields 10 g of carbon disulfide adduct. The filtrate is concentrated by evaporation, yielding a further 27 g of the intermediate as the residue.

Reference： [1]Patent: US5190945,1993,A

28
[ 591-55-9 ]
[ 503-38-8 ]
[ 190592-48-4 ]

Yield	Reaction Conditions	Operation in experiment
	With trimethylsilylazide; In methanol; ethyl acetate;	STR21 An ethyl acetate (60 ml) solution of <strong>[591-55-9]5-aminopyrimidine</strong> (2.85 g) was added dropwise to a mixture of diphosgene (6.0 g) and ethyl acetate (100 ml) under cooling with ice. After heating under refluxing for 6 hours, the solvent was distilled off under reduced pressure. The obtained residue and trimethylsilyl azide (11 g) were mixed and the mixture was heated under refluxing for 30 hours. The excess trimethylsilyl azide was distilled off under reduced pressure. Methanol was then added to the residue and the mixture was stirred. Thereafter, methanol was distilled off and the residue was subjected to silica gel column chromatography (eluant: chloroform/ethanol=15/1) to obtain 1-(5-pyrimidyl)-5(4H)-tetrazolinone (3.2 g). mp. 211-213 C.

Reference： [1]Patent: US5776858,1998,A

29
[ 591-55-9 ]
[ 104-88-1 ]
N-(4-chlorobenzylidene)-5-aminopyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	Example 1(c) Preparation of N-(4 -chlorobenzylidene)-<strong>[591-55-9]5-aminopyrimidine</strong> (compound 3.001) 5.71 g (60 mmol) of <strong>[591-55-9]5-aminopyrimidine</strong> and 9.84 g (70 mmol) of 4-chlorobenzaldehyde are mixed in 75 ml of methanol and the reaction mixture is heated to boiling point. The crystalline solid precipitated from the solution on cooling weighs 6.22 g (47.6% of theory) and melts at 138-139 C. A further two fractions of the product--2.69 g (20.6% of theory, m.p.: 138-139 C.) and 3.0 g (23.7% of theory, m.p.: 137-138 C.)--can be isolated by recrystallising the distillation residue of the mother liquor from ethanol.

Reference： [1]Patent: US4718934,1988,A

30
[ 591-55-9 ]
[ 874-42-0 ]
N-(2,4-dichlorobenzylidene)-5-aminopyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	Example 2(c) Preparation of N-(2,4-dichlorobenzylidene)-<strong>[591-55-9]5-aminopyrimidine</strong> (compound 3.002) A solution of 5.71 g (60 mmol) of <strong>[591-55-9]5-aminopyrimidine</strong> in 30 ml of methanol is stirred at room temperature in a solution of 11.55 g (66 mmol) of 2,4-dichlorobenzaldehyde in 30 ml of methanol and the solution thus formed is heated with stirring to boiling point, whereupon the resultant product crystallises. The crystalline product is filtered with suction at room temperature and dried. The N-(2,4-dichlorobenzylidene)-<strong>[591-55-9]5-aminopyrimidine</strong> with a melting point of 189-191 C. weighs 14.51 g (95.9% of theory).

Reference： [1]Patent: US4718934,1988,A

31
[ 591-55-9 ]
[ 104-88-1 ]
N-[(4-chlorophenyl)methyl]-(5-pyrimidyl)imine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	toluene-4-sulfonic acid; In toluene;	A. N-[(4-Chlorophenyl)methyl]-(5-pyrimidyl)imine To a solution of 7 g of 4-chlorobenzaldehyde and 5 g of <strong>[591-55-9]5-aminopyrimidine</strong> dissolved in 250 ml of toluene was added a catalytic amount of p-toluenesulfonic acid. The reaction mixture was refluxed for approximately 16 hours and the water formed as a by-product of the reaction was collected with a Dean Stark trap. The solution was filtered hot and the filtrate was concentrated under vacuum. The residue was washed with deithyl ether and Skellysolve B and the solids were dried to afford 9 g of N-[(4-chlorophenyl)methyl]-(5-pyrimidyl)imine. mp=140-141 C. Analysis calculated for C11 H8 ClN3: Theory: C, 60.70; H, 3.70; N, 19.31; Found: C, 60.97; H, 3.55; N, 19.07.

Reference： [1]Patent: US4552960,1985,A

32
[ 591-55-9 ]
[ 394-47-8 ]
5-[N-(2-cyanophenyl)-amino]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; dimethyl sulfoxide; In acetone;	REFERENCE EXAMPLE 9 To 10 ml of dimethyl sulfoxide was added 1.40 g (12.5 mmol) of potassium tert-butoxide, and to the solution was added 951 mg (10.0 mmol) of <strong>[591-55-9]5-aminopyrimidine</strong> while cooling with water. After stirring at room temperature for 1 hour, 0.54 ml (5.0 mmol) of 2-fluorobenzonitrile was added thereto while cooling with water, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into ice-water, and the mixture was adjusted to pH 7.0 with 1 N hydrochloric acid, and filtered. The filter residue was dissolved in 200 ml of acetone, and the acetone solution was filtered. The filtrate was dried over magnesium sulfate, and the solvent was removed by distillation under reduced pressure to obtain 0.53 g (2.70 mmol) of 5-[N-(2cyanophenyl)amino]pyrimidine. Mass Spectrum (m/z): 196 (M+) NMR Spectrum (DMSO-d6, TMS internal standard) delta: 7.12 (1 H, t, J=7 Hz), 7.35 (1 H, d, J=8 Hz), 7.57-7.60 (1 H, m), 7.76 (1 H, dd, J=8 Hz, 1 Hz), 8.61 (2 H, s), 8.78 (1 H, s), 8.84 (1 H, s)

Reference： [1]Patent: US5538976,1996,A

33
[ 591-55-9 ]
[ 4487-59-6 ]
5-[N-(5-nitro-pyridin-2-yl)amino]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; dimethyl sulfoxide;	REFERENCE EXAMPLE 8 To 7 ml of dimethyl sulfoxide was added 0.69 g (6.15 mmol) of potassium tert-butoxide, and 468 mg (4.92 mmol) of <strong>[591-55-9]5-aminopyrimidine</strong> was added to the solution while cooling with water. After stirring at room temperature for 1 hour, 500 mg (2.46 mmol) of 2-bromo-5-nitropyridine was added thereto under cooling with water, followed by further stirring at room temperature for 30 minutes. The reaction solution was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with 1 N hydrochloric acid, and the washing was adjusted to pH 8.5 with a 1 N sodium hydroxide aqueous solution and again extracted with ethyl acetate. The organic layer was combined with the above obtained organic layer, washed successively with water and a saturated sodium chloride aqueous solution, and dried over magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography (eluding solvent: chloroform-methanol). The resulting crude crystals were washed with ethyl ether to obtain 0.32 g (1.47 mmol) of 5-[N-(5-nitro-2-pyridyl)amino]pyrimidine. Mass Spectrum (m/z): 216 (M-H)+ NMR Spectrum (DMSO-d6, TMS internal standard) delta: 7.00 (1 H, d, J=9 Hz), 8.39 (1 H, dd, J=9 Hz, 3 Hz), 8.87 (1 H, s), 9.09 (1 H, d, J=3 Hz), 9.17 (2 H, s), 10.41 (1 H, s)

Reference： [1]Patent: US5538976,1996,A

34
[ 591-55-9 ]
[ 17341-93-4 ]
[ 887624-72-8 ]

Yield	Reaction Conditions	Operation in experiment
35.2%	With pyridine; In tetrahydrofuran; at 0℃; for 0.5h;	(2) 2,2,2-Trichloroethyl pyrimidin-5-ylcarbamate; To a solution of <strong>[591-55-9]pyrimidine-5-amine</strong> (100 mg, 1.05 mmol) and pyridine (0.255 ml, 3.15 mmol) in tetrahydrofuran (3 ml) was added 2,2,2-trichloroethyl chloroformate (0.217 ml, 1.58 mmol) with ice-cooling, the mixture was stirred for 30 minutes with ice-cooling, the reaction mixture was poured into ice-water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane : ethyl acetate = 1 : 1) to obtain the desired product (100 mg, 35.2%) as a solid. 1H-NMR (CDCl3) delta; 4.87 (2H, s), 7.60 (1H, br s), 8.95 (2H, s), 9.02 (1H, s).

Reference： [1]Patent: EP1813606,2007,A1 .Location in patent: Page/Page column 79

35
[ 4316-93-2 ]
[ 591-55-9 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2008,vol. 51,p. 54 - 58

36
[ 591-55-9 ]
[ 1002106-14-0 ]
[ 1002106-08-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; HATU; In N,N-dimethyl-formamide; at 50℃;	Step 8: 6-Chloro-3-(4-ethylphenylamino)-N-(pyrimidin-5-yl)benzo[d]isoxazole-7-carboxamide 6-Chloro-3-(4-ethylphenylamino)benzo[d]isoxazole-7-carboxylic acid (0.195 g, 0.615 mmol) was dissolved in DMF, followed by TEA (0.223 ml, 1.61 mmol) and HATU (0.285 g, 0.749 mmol). The mixture was allowed to stir for 5 min before adding <strong>[591-55-9]pyrimidin-5-amine</strong> (0.0509 g, 0.535 mmol) and the mixture was heated to 50 C. overnight. The mixture was then cooled to RT, partitioned between EtOAc/brine, the layers were separated, and the aqueous was extracted with EtOAc (3*). The combined organics were washed with H2O and brine, filtered and concentrated. The crude material was purified by silica gel chromatography using 20:1 DCM/MeOH to give 6-Chloro-3-(4-ethylphenylamino)-N-(pyrimidin-5-yl)benzo[d]isoxazole-7-carboxamide as a light brown solid. MS calculated 393.8, found M+H+=394.1.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5115 - 5117
[2]Patent: US2008/227779,2008,A1 .Location in patent: Page/Page column 15; 16

37
[ 591-55-9 ]
[ 6307-70-6 ]
2-methyl-5-nitro-N-(pyrimidin-5-yl)benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 1681 - 1694

38
[ 591-55-9 ]
[ 1018069-85-6 ]
4-methyl-N₃-5-pyrimidinyl-N₁-(3-(trifluoromethyl)phenyl)-1,3-benzenedicarboxamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4137 - 4141

39
[ 591-55-9 ]
[ 1067998-15-5 ]
[ 1002106-31-1 ]