[ CAS No. 31519-62-7 ] {[proInfo.proName]}

Name: 31519-62-7|2-Pyrimidinecarboxylic acid|97%
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Quality Control of [ 31519-62-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 31519-62-7 ]

CAS No. :	31519-62-7	MDL No. :	MFCD00856161
Formula :	C₅H₄N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZFCHNZDUMIOWFV-UHFFFAOYSA-N
M.W :	124.10	Pubchem ID :	12626245
Synonyms :

Calculated chemistry of [ 31519-62-7 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	28.99
TPSA :	63.08 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) :	-7.45 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.58
Log Po/w (XLOGP3) :	-0.55
Log Po/w (WLOGP) :	0.17
Log Po/w (MLOGP) :	-0.85
Log Po/w (SILICOS-IT) :	0.32
Consensus Log Po/w :	-0.06

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.69
Solubility :	25.3 mg/ml ; 0.204 mol/l
Class :	Very soluble
Log S (Ali) :	-0.31
Solubility :	61.5 mg/ml ; 0.495 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.98
Solubility :	12.9 mg/ml ; 0.104 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.18

Safety of [ 31519-62-7 ]

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

Application In Synthesis of [ 31519-62-7 ]

* 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 [ 31519-62-7 ]
Downstream synthetic route of [ 31519-62-7 ]

[ 31519-62-7 ] Synthesis Path-Upstream 1~9

1
[ 14080-23-0 ]
[ 31519-62-7 ]

Yield	Reaction Conditions	Operation in experiment
35.4%	Stage #1: With potassium hydroxide In water for 3 h; Reflux Stage #2: With hydrogenchloride In water at 20℃;	Pyrimidine-2-carboxylic acid (11):To a stirred solution of pyrimidine-2-carbonitrile (10) (201 mg, 1.914 mmol) in water (5 mL), KOH (214.3 mg, 3.83 mmol) was added and the reaction was refluxed for 3 h. After consumption of the starting material (by TLC), the reaction was slowly brought to RT, neutralized with 2N HC1 and water was removed from the reaction mixture to give the crude residue which was extracted with EtOAc. The combined organic extracts were filtered through a pad of celite and the filtrate was concentrated under reduced pressure to provide compound 11 (84 mg, 35.4percent) which was carried for the next step without any purification.TLC: 80percent EtOAc/Hexane (R_f: 0.05)1H NMR (400MHz, CD₃OD-d₄): δ 8.83 (br s, 2H), 7.47 (t, J = 4.8 Hz, 1H).
0.10 g	at 70℃; for 0.5 h;	To the flask was added 0.10g of 2cyanopyrimidine,12percent by mass aqueous sodium hydroxide solution 13mL was stirred at 70 30 minutes. Of 1N dilutehydrochloric acid to pH ~ 3 by adding little by little and, by concentration of the resulting organic layer was extracted three times with 10mL of ethyl acetate, to give0.10g of Compound A218

Reference： [1] Dalton Transactions, 2011, vol. 40, # 20, p. 5476 - 5482
[2] Journal of Organic Chemistry, 2015, vol. 80, # 5, p. 2676 - 2699
[3] Chemical Communications, 2016, vol. 52, # 54, p. 8459 - 8462
[4] Patent: WO2013/13238, 2013, A2, . Location in patent: Page/Page column 49
[5] Patent: KR2015/128789, 2015, A, . Location in patent: Paragraph 0818; 0820; 0821
[6] Inorganic Chemistry, 2018, vol. 57, # 11, p. 6266 - 6282

2
[ 35782-30-0 ]
[ 31519-62-7 ]

Reference： [1] Chemistry and Industry (London, United Kingdom), 1954, p. 786

3
[ 5053-43-0 ]
[ 31519-62-7 ]

Reference： [1] Chemistry and Industry (London, United Kingdom), 1954, p. 1203

4
[ 89166-80-3 ]
[ 31519-62-7 ]

Reference： [1] Chemistry and Industry (London, United Kingdom), 1954, p. 1203

5
[ 37131-87-6 ]
[ 31519-62-7 ]

Reference： [1] Chemistry and Industry (London, United Kingdom), 1954, p. 1203

6
[ 31519-62-7 ]
[ 34253-03-7 ]

Reference： [1] Chemistry and Industry (London, United Kingdom), 1954, p. 786

7
[ 31519-62-7 ]
[ 64-17-5 ]
[ 62846-82-6 ]

Reference： [1] Yakugaku Zasshi, 1953, vol. 73, p. 598,600[2] Chem.Abstr., 1954, p. 9362

8
[ 31519-62-7 ]
[ 42839-08-7 ]

Reference： [1] Journal of Organic Chemistry, 2015, vol. 80, # 5, p. 2676 - 2699

9
[ 31519-62-7 ]
[ 64-17-5 ]
[ 42839-08-7 ]

Reference： [1] Inorganic Chemistry, 2018, vol. 57, # 11, p. 6266 - 6282

[ 31519-62-7 ] Synthesis Path-Downstream 1~88

1
[ 37131-87-6 ]
[ 31519-62-7 ]

Reference： [1]Chemistry and industry,1954,p. 1203

2
C₂₁H₂₀F₆N₂O [ No CAS ]
[ 31519-62-7 ]
C₂₆H₂₂F₆N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5310 - 5315

3
[ 31519-62-7 ]
C₂₃H₂₆N₃O₃F₃*CF₃COOH [ No CAS ]
C₂₈H₂₈N₅O₄F₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6172 - 6177

4
[ 5053-43-0 ]
[ 31519-62-7 ]

Reference： [1]Chemistry and industry,1954,p. 1203

5
[ 89166-80-3 ]
[ 31519-62-7 ]

Reference： [1]Chemistry and industry,1954,p. 1203

6
[ 31519-62-7 ]
[ 320780-86-7 ]
[ 320781-51-9 ]

Reference： [1]Patent: US6350757,2002,B1 .Location in patent: Page column 26

7
[ 31519-62-7 ]
[ 220769-83-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With thionyl chloride; In dichloromethane; at 40℃; for 1h;	A flask was charged with <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (63.2 mg, 0.509 mmol, 1.00 equiv), DCM (5 mL), and thionyl chloride (121 mg, 1.02 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at 40 C. The resulting mixture was concentrated under reduced pressure to provide 72.0 mg (99% yield) of pyrimidine-2-carbonyl chloride.
	With thionyl chloride; at 110℃; for 1.5h;	2-Pyrimidinecarboxylic acid (350mg) in thionyl chloride (3ml_) was stirred at 1 10C under nitrogen for 1.5h. The solvent was removed under vacuum to give the 2-pyrimidinecarbonyl chloride as a grey solid (403mg). (4-Bromo-2-fluorophenyl)(iodo)zinc in 25 tetrahydrofuran (0.5M, 5.65mL) was added slowly to a stirred mixture of the acid chloride (403mg) and tetrakis(triphenylphosphine)palladium(0) (163mg) in tetrahydrofuran (3rnl_) at room temperature under nitrogen. The reaction mixture was stirred at room temperature under nitrogen for 1h and aqueous ammonium chloride (1M, 6ml_) was added. The mixture was absorbed onto silica and purified by chromatography on a silica column, eluting with a cyclohexane/ethyl acetate gradient to give the title compound (257mg). LC-MS: Rt 2.95min.
	With thionyl chloride; at 110℃; for 1.5h;	Pyrimidine-2-carboxylic acid 3 (0.3 lOg, 2.5 mmol) was charged to a vial. Thionyl chloride (3ml, 41.1 mmol) was added while the mixture was stirred. After addition, the reaction was heated to 1 10 C for 1.5hr to afford a green-colored solution. At this time the heat was removed and the reaction mixture was concentrated in vacuo. The reaction was diluted with 10 ml of toluene and azeotroped twice before drying under high vacuum. After lhr, the resulting green/gray residue, pyrimidine-2-carbonyl chloride 4, was carried forward to the dione formation step without any further purification.

	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h;	Preparation of Intermediate 25 2211 Intermediate 25 2212 [0255] Oxalyl chloride (2.36 mL, 24.2 mmol, 1.5 eq) and a catalytic quantity of DMF were 2213 added to a solution of <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (2 g, 16.1 mmol) in dry DCM (30 mL) at 2214 0 C. The resulting mixture was allowed to warm to RT and stir for 3 h. The volatiles were 2215 removed in vacuo and the residue was thoroughly dried to afford pyrimidine-2-carboxylic 2216 acid chloride (2.1 g, 14.8 mmol) as a black solid. The crude material was added portion- wise 2217 to a solution of aminogaunidine sulfate (5.5 g, 22.2 mmol, 1.5 eq) in pyridine (20 mL) at 2218 0 C. The resulting mixture was allowed to warm to RT and stir for 14 h. The mixture was 2219 then neutralized with saturated aqueous NaHCOs, extracted with t-BuOH (5 x 50 mL), dried 2220 over Na2S04, filtered and concentrated in vacuo. The crude material was dissolved in water 2221 (45 mL) and the resulting solution was heated to 100 C for 24 h. The reaction mixture was 2222 then cooled to RT, extracted with t-BuOH (5 x 30 mL), dried over Na2S04, filtered and 2223 concentrated in vacuo to afford Intermediate 25 (650 mg, 25 %) as off-white solid. TLC: 30% 2224 MeOH in CHC13: Rf: 0.20.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h;	Oxalyl chloride (2.36 mL, 24.2 mmol, 1.5 eq) and a catalytic quantity of DMF were added to a solution of <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (2 g, 16.1 mmol) in dry DCM (30 mL) at 0C. The resulting mixture was allowed to warm to RT and stir for 3 h. The volatiles were removed in vacuo and the residue was thoroughly dried to afford <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> chloride (2.1 g, 14.8 mmol) as a black solid.

Reference： [1]Patent: WO2019/46318,2019,A1 .Location in patent: Paragraph 00225
[2]Patent: WO2005/73189,2005,A1 .Location in patent: Page/Page column 55-56
[3]Patent: WO2011/115804,2011,A1 .Location in patent: Page/Page column 101; 102
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606
[5]Patent: WO2014/145986,2014,A1 .Location in patent: Paragraph 0254; 0255
[6]Journal of Organic Chemistry,2015,vol. 80,p. 2676 - 2699
[7]Patent: US2017/326125,2017,A1 .Location in patent: Paragraph 0380-0381
[8]Journal of the American Chemical Society,2018,vol. 140,p. 11487 - 11494

8
[ 31519-62-7 ]
(Z)-1-(1H-benzo[d]imidazol-2-ylsulfonyl)-N'2-hydroxy-2-piperidinecarboximidamide [ No CAS ]
[ 242460-04-4 ]

Yield	Reaction Conditions	Operation in experiment
		PREPARATION 105 1-(1H-Benzo[d]imidazol-2-ylsulfonyl)-N'2-[(2-pyrimidinylcarbonyl)oxy]-2-piperidinecarboximidamide The title compound was prepared by a similar method to Preparation 20 from (Z)-1-(1H-benzo[d]imidazol-2-ylsulfonyl)-N'2-hydroxy-2-piperidinecarboximidamide [see Preparation 19] and <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (see Chem. Ind. (London), 1954, 786) to afford 1-(1H-benzo[d]imidazol-2-ylsulfonyl)-N'2-[(2-pyrimidinylcarbonyl)oxy]-2-piperidinecarboximidamide as a gum.

Reference： [1]Patent: US6610707,2003,B1

9
[ 31519-62-7 ]
[ 155957-33-8 ]
[ 155957-34-9 ]

Yield	Reaction Conditions	Operation in experiment
	In methanolic hydrogen chloride; ethyl acetate;	EXAMPLE 5E This example illustrates the esterification of a pyrimidine carboxylic acid to the corresponding carboxylic ester. Compound No. 82 (see Example 5D) (0.19 g) was added in methanolic hydrogen chloride (5 cm3 of a saturated solution) and the flask was stoppered and left to stand for 72 hours. All the solid starting material had dissolved. The solution was evaporated to dryness at reduced pressure and the residue was dissolved in ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate and dried over magnesium sulfate. Evaporation of solvent under reduced pressure gave an oil which was chromatographed on silica gel, eluding with 1:4 ethyl acetate:hexane to give methyl 2-[(4,4-difluoro-3-butenyl)thio]-4-pyrimidinecarboxylate (Compound No. 83) (0.154 g). M+ =260; 1 H NMR (CDCl3): delta2.40-2.54(2H m); 3.24(2H,t); 4.00(3H,s); 4.22-4.40(1H,m); 7.64(1H,d); 8.74(1H,d).

Reference： [1]Patent: US5684011,1997,A

10
[ 31519-62-7 ]
tert-butyl {2-[4-(5-hydrazino-3-phenyl-1,6-naphthyridin-2-yl)phenyl]-5,8-dioxaspiro[3.4]oct-2-yl}carbamate [ No CAS ]
C₃₆H₃₅N₇O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (10.46 g, 46.8 mmol) in DMA (200 mL) was added EDC (8.98 g, 46.8 mmol) and HOBt (7.17 g, 46.8 mmol) and the reaction mixture was stirred at 60C for 1 hour. Then tert-butyl {2-[4-(5-hydrazino-3-phenyl-l,6- naphthyridin-2-yl)phenyl]-5,8-dioxaspiro[3.4]oct-2-yl}carbamate (1-10) (25.27 g, 46.8 mmol) was added and the reaction stirred at 60C for an additional 2 hours at which time acetic acid (20.8 g, 460 mmol) was added and the reaction was stirred overnight at 80C. The reaction mixture was cooled to rt, quenched with IN NaOH, poured into saturated sodium bicarbonate, extracted with chloroform, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by column chromatography eluting with 10% methanol in DCM. The appropriate fractions were concentrated and the resulting solid was recrystallized from methanol to give tert-butyl {2-[4-(9-phenyl-3-pyrimidin-2-yl[l,2,4]triazolo[3,4-/]-l,6-naphthyridin-8- yl)phenyl]-5,8-dioxaspiro[3.4]oct-2-yl}carbamate (3-1) as a white solid. MS (M+H+): 628

Reference： [1]Patent: WO2008/70134,2008,A1 .Location in patent: Page/Page column 56-57

11
[ 31519-62-7 ]
[ 1032350-00-7 ]
[ 1032350-08-5 ]

Yield	Reaction Conditions	Operation in experiment
		tert-butyl{1-[4-(9-phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (1-6d) To a round bottom flask was added tert-butyl{1-[4-(5-hydrazino-3-phenyl-1,6-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate (1-6) (267 mg, 0.554 mmol), EDC (138 mg, 0.721 mmol), HOBt (97 mg, 0.721 mmol), <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (89 mg, 0.721 mmol), DIPEA (0.367 mL, 2.218 mmol), and DMF (3 mL). The reaction mixture was then capped & heated under microwave irradiation at 100 C. for 5 minutes. The mixture was cooled, acetic acid (0.476 mL, 8.32 mmol) was added and the reaction was then capped & heated under microwave irradiation at 80 C. for 5 minutes. The reaction mixture was permitted to cool to room temperature, suspended in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography 0-10% IPA/DCM. The appropriate fractions were combined and the solvent was removed in vacuo to give tert-butyl{1-[4-(9-phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (1-6d) as an orange solid. MS (M+H)+: observed=570.2, calculated=570.7.

Reference： [1]Patent: US2008/161317,2008,A1 .Location in patent: Page/Page column 60

12
[ 31519-62-7 ]
[ 1071-46-1 ]
[ 1093114-80-7 ]

Yield	Reaction Conditions	Operation in experiment
77%		Ethyl 3-oxo-3-pyrimidin-2-ylpropanoate To a solution of <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (0.99 g, 7.98 mmol) in anhydrous THF (20 ml) was added carbonyl diimidazole (1.55 g, 9.57 mmol) and the suspension was heated at reflux for 2 hours. The mixture was then cooled to room temperature and used without workup or purification. In a separate flask, mono-ethyl malonate (0.94 ml, 7.98 mmol) was suspended in anhydrous THF (20 ml) and cooled to 0 C. Methyl magnesium bromide (5.32 ml, 15.96 mmol, 3.0 M in diethyl ether) was added dropwise. After stirring at 0 C. for 20 mins, the crude imidazolide solution prepared earlier was added slowly. The reaction was then heated at reflux overnight. After cooling to room temperature, the reaction mixture was diluted with water and acidified with concentrated HCl to pH 5. The solution was extracted with EtOAc (*3), dried with MgSO4 and concentrated to a yellow oil (1.19 g, 77%). NMR showed a 2:1 mixture of the keto:enol forms. MS (ES) (M+H)+: 195 for C9H10N2O3; NMR: 1.13-1.29 (t, 3H), 4.05-4.28 (q, 2H), 4.18 (s, 2H), 7.62-7.76 (t, 1H), 8.95-9.06 (d, 2H), 11.79 (s, 4H)

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6060 - 6082
[2]Patent: US2008/312255,2008,A1 .Location in patent: Page/Page column 75

13
[ 31519-62-7 ]
sodium azide [ No CAS ]
copper(II) choride dihydrate [ No CAS ]
[ 1055308-65-0 ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

14
[ 31519-62-7 ]
copper(II) choride dihydrate [ No CAS ]
potassium tetracyanoaurate(III) [ No CAS ]
[ 7664-41-7 ]
K[[μ-Au(CN)2]2[(Cu(NH3)2)2(μ-pyrimidine-2-carboxylato)]][Au(CN)2]2 [ No CAS ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

15
[ 31519-62-7 ]
copper(II) choride dihydrate [ No CAS ]
[ 333-20-0 ]
Cu(μ-pyrimidine-2-carboxylato)(SCN)(H2O)*4H2O [ No CAS ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

16
[ 31519-62-7 ]
copper(II) choride dihydrate [ No CAS ]
[ 1055308-63-8 ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

17
[ 31519-62-7 ]
copper(II) choride dihydrate [ No CAS ]
[ 1934-75-4 ]
Cu2(μ-dicyanato)2(pyrimidine-2-carboxylato)2 [ No CAS ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

18
[ 31519-62-7 ]
copper (II) nitrate tetrahydrate [ No CAS ]
copper(II) pyrimidine-2-carboxylate [ No CAS ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

19
[ 31519-62-7 ]
[ 7789-45-9 ]
[ 1055308-61-6 ]

Reference： [1]Inorganic Chemistry,2008,vol. 47,p. 8143 - 8158

20
[ 31519-62-7 ]
[ 13431-34-0 ]
[ 74-88-4 ]
[ 1144033-63-5 ]

Yield	Reaction Conditions	Operation in experiment
29%		The corresponding aryl-carboxylic acid (n mmol) was taken up in thionyl chloride (n x 1.05 mL) and refluxed for 4h. Excess thionyl chloride was removed under reduced pressure and replaced with pyridine (n x 0.52 mL). While chilled on ice bath 4-ethyl-3- thiosemicarbazide was added portion-wise (1 equivalent, rinsed/scraped in with n x 0.16 mL/mmol dichloromethane). The ice bath was removed and the reaction mixture was stirred at room temperature for 24h. The pyridine was removed under reduced pressure and replaced with aq. NaOH (IN, n x 3.16 mL) and the resulting mixture was stirred at 70-80 0C for 4 hours. After cooling to room temperature, methyl iodide (1.5eq.) in ethanol (n x 0.42 mL) was added dropwise over 20 minutes. The reaction mixture was stirred at room temperature for 16h. The product was extracted with dichloromethane (2x (n x 4.2 mL)). <n="21"/>Removal of the solvent in vacuo and flash chromatography (silica gel, 3% methanol in chloroform) yielded the title compound.

Reference： [1]Patent: WO2009/51556,2009,A1 .Location in patent: Page/Page column 19-20

21
[ 31519-62-7 ]
[ 357925-36-1 ]
C₁₉H₁₆F₂N₄O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1670 - 1674

22
[ 31519-62-7 ]
[ 1172068-36-8 ]
[ 1196508-29-8 ]

Yield	Reaction Conditions	Operation in experiment
38%	With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine; In dichloromethane; at 20℃; for 48h;	[00406] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2CL (10 mL) was treated with pyrimidine-2- carboxylic acid (129 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 48 hour, and then water (10 mL) was added. The reaction was stirred for 1 hour. The solid which separated was filtered and washed with CH9CL (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-2-carboxamide (110 mg, 38% yield). 1H NMR (400 MHz, (CD3^SO) delta 12.21 (br s, IH), 10.47 (s, IH), 9.06 (d,2H), 8.40 (d, IH), 7 87 (d, IH), 7.77 (t, IH); LCMS (APCI+) m/z 335.9, 337.9 (M+H)+, Retention time = 2.70 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 123

23
[ 31519-62-7 ]
[ 1198170-76-1 ]
[ 1198168-42-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 18h;	Example 2. General amide coupling procedure to prepare N-(2-(3- (trifluoromethyl)phenyl)imidazo[l,2-a]pyridin-8-yl)pyrimidine-2-carboxamide (Compound 122) and related analogs:; 2-(3-(Trifluoromethyl)phenyl)imidazo[l)2-a]pyridin-8-amine (14; 50 mg, 0.15 mmol) and <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (15; 18 mg, 0.18 mmol) were taken up in <n="71"/>dimethylformamide (DMF; 2 ml). To this mixture was added 2-(7-Aza- 1 H-benzotriazole- l-yl)-lX3,3-tetramethyluronium hexafluorophosphate (HATU; 118 mg, 0.31 mmol) and N,N-Diisopropylethylamine (DIPEA; 80 mg, 0.62 mmol). The resulting reaction mixture was stirred at room temperature for 18 h. Water and aqueous NaHCO3 were then added. The resulting precipitate was collected by filtration, washed with MeOH and dried to afford the desired product, namely N-(2-(3-(trifluoromethyl)phenyl)imidazo[l,2-a]pyridin- 8-yl)pyrimidine-2-carboxamide (Compound 122) (35 mg, yield: 64%). Analytically pure sample could be obtained by additional purification using silica gel chromatography. MS (ESI) calculated for C19H12F3N5O 383.10; found 384 [M+H]. This general amide coupling procedure is used to prepare a variety of imidazo[l,2- ajpyridine derivatives by substituting the appropriate carboxylic acid components.

Reference： [1]Patent: WO2009/146358,2009,A1 .Location in patent: Page/Page column 107

24
[ 31519-62-7 ]
[ 1223404-88-3 ]
[ 1223404-33-8 ]

Yield	Reaction Conditions	Operation in experiment
9%		Example 67; (R)-N-(5-(2-(2,5-difluorophenyl)pyrrolidin-l-yl)pyrazolo[l,5-alpyrimidin-3- yl)pyrimidine-2-carboxamide; [00483] To a mixture of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-l-yl)pyrazolo[l,5- a]pyrimidin-3 -amine (Preparation B; 25 mg, 0.079 mmol), <strong>[31519-62-7]pyrimidine-2-carboxylic acid</strong> (12 mg, 0.095 mmol), and HATU (36 mg, 0.095 mmol) was added 0.6 mL DMF. A few drops of DMSO were added to obtain a solution. After cooling in an ice bath for 10 minutes, DIEA (0.041 mL, 0.24 mmol) was added to the reaction drop-wise. The reaction was allowed to warm up to ambient temperature and stirred for one hour, then at 80 0C for 16 hours. Reaction did not reach completion before workup. The reaction mixture was diluted with EtOAc (15 mL), washed with water and brine (5 mL each), concentrated, and purified by reverse-phase column chromatography, eluting with 5 to 60% acetonitrile/water to yield the final product as a light yellowish solid (3 mg, 9% yield). MS (apci) m/z = 422.2 (M+H).

Reference： [1]Patent: WO2010/48314,2010,A1 .Location in patent: Page/Page column 85

25
[ 31519-62-7 ]
[ 1243634-24-3 ]
C₂₅H₄₁N₅O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4483 - 4486

26
[ 31519-62-7 ]
[ 1243634-25-4 ]
C₂₅H₄₁N₅O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4483 - 4486

27
[ 31519-62-7 ]
C₁₅H₂₁ClN₂O [ No CAS ]
[ 1261242-58-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7458 - 7461

28
[ 31519-62-7 ]
[ 298201-68-0 ]
[ 1120368-20-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 401 - 410

29
[ 31519-62-7 ]
4-phenyldecahydroquinolin-4-ol [ No CAS ]
C₂₀H₂₃N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 2359 - 2364

30
[ 31519-62-7 ]
bis[2-(2,4-difluorophenyl)pyridinato-N,C₆']iridium(III) chloride dimer [ No CAS ]
[Ir(2-(4',6'-difluoro-phenyl)pyridine^(1-))2(2-carboxypyrimidine)] [ No CAS ]

Reference： [1]Dalton Transactions,2011,vol. 40,p. 5476 - 5482

31
[ 31519-62-7 ]
[iridium(III)(μ-chloro)(2-phenylpyridine)2]2 [ No CAS ]
[Ir(2-phenylpyridine^(1-))2(2-carboxypyrimidine)] [ No CAS ]

Reference： [1]Dalton Transactions,2011,vol. 40,p. 5476 - 5482

32
[ 14080-23-0 ]
[ 31519-62-7 ]

Yield	Reaction Conditions	Operation in experiment
35.4%		Pyrimidine-2-carboxylic acid (11):To a stirred solution of pyrimidine-2-carbonitrile (10) (201 mg, 1.914 mmol) in water (5 mL), KOH (214.3 mg, 3.83 mmol) was added and the reaction was refluxed for 3 h. After consumption of the starting material (by TLC), the reaction was slowly brought to RT, neutralized with 2N HC1 and water was removed from the reaction mixture to give the crude residue which was extracted with EtOAc. The combined organic extracts were filtered through a pad of celite and the filtrate was concentrated under reduced pressure to provide compound 11 (84 mg, 35.4%) which was carried for the next step without any purification.TLC: 80% EtOAc/Hexane (Rf: 0.05)1H NMR (400MHz, CD3OD-d4): delta 8.83 (br s, 2H), 7.47 (t, J = 4.8 Hz, 1H).
0.10 g	With water; sodium hydroxide; at 70℃; for 0.5h;	To the flask was added 0.10g of 2cyanopyrimidine,12% by mass aqueous sodium hydroxide solution 13mL was stirred at 70 30 minutes. Of 1N dilutehydrochloric acid to pH ~ 3 by adding little by little and, by concentration of the resulting organic layer was extracted three times with 10mL of ethyl acetate, to give0.10g of Compound A218

Reference： [1]Dalton Transactions,2011,vol. 40,p. 5476 - 5482
[2]Journal of Organic Chemistry,2015,vol. 80,p. 2676 - 2699
[3]Chemical Communications,2016,vol. 52,p. 8459 - 8462
[4]Patent: WO2013/13238,2013,A2 .Location in patent: Page/Page column 49
[5]Patent: KR2015/128789,2015,A .Location in patent: Paragraph 0818; 0820; 0821
[6]Inorganic Chemistry,2018,vol. 57,p. 6266 - 6282

33
[ 31519-62-7 ]
[ 530-62-1 ]
C₈H₆N₄O [ No CAS ]