Name: 41864-22-6|Di(1H-1,2,4-triazol-1-yl)methanone|95%
Brand: Ambeed
SKU: A105434
Price: 9.0 USD
Availability: InStock
Rating: 92 (27 reviews)

1
[ 41864-22-6 ]
[ 1552-96-1 ]
[ 150020-94-3 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 7192 - 7198

2
[ 41864-22-6 ]
[ 3562-73-0 ]
1-(1-biphenyl-4-yl-ethyl)-1H-[1,2,4]triazole [ No CAS ]
4-(1-biphenyl-4-yl-ethyl)-4H-[1,2,4]triazole [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 1245 - 1252

3
[ 41864-22-6 ]
[ 52449-77-1 ]
[1,2,4]triazole-1-carboxylic acid 3-cyano-naphthalen-2-yl ester [ No CAS ]

Reference： [1]Synthesis,2004,p. 1987 - 1990

4
[ 41864-22-6 ]
[ 932-35-4 ]
[1,2,4]triazole-1-carboxylic acid 2-cyano-pyridin-3-yl ester [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3091 - 3096

5
[ 41864-22-6 ]
[ 613-08-1 ]
[ 865313-74-2 ]

Reference： [1]Monatshefte fur Chemie,2005,vol. 136,p. 397 - 410

6
[ 41864-22-6 ]
[ 58333-75-8 ]
[ 204693-44-7 ]
[(S)-5-((R)-3-(3,5-Dibromo-4-hydroxy-phenyl)-2-[4-(2-methoxy-phenyl)-piperidine-1-carbonyl]-amino}-propionylamino)-6-oxo-6-(4-pyridin-4-yl-piperazin-1-yl)-hexyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5921 - 5931

7
[ 41864-22-6 ]
[ 79098-75-2 ]
[ 204693-44-7 ]
[5-(3-(3,5-dibromo-4-hydroxy-phenyl)-2-[4-(2-oxo-3,4-dihydro-2H-quinazolin-1-yl)-piperidine-1-carbonyl]-amino}-propionylamino)-6-oxo-6-(4-pyridin-4-yl-piperazin-1-yl)-hexyl]-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5921 - 5931

8
[ 41864-22-6 ]
[ 215878-20-9 ]
[ 204693-44-7 ]
[ 204696-88-8 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5921 - 5931

9
[ 41864-22-6 ]
[ 880100-33-4 ]
[ 910377-40-1 ]

Yield	Reaction Conditions	Operation in experiment
59%	In tetrahydrofuran;	c) tert.butyl[3-methyl-3-(6-methyl-2-oxo-2,3-dihydro-benzimidazol-1-yl)-butyl]-carbamate 1.76 g (5.7 mmol) tert.butyl[3-(2-amino-5-methyl-phenylamino)-3-methyl-butyl]-carbamate are dissolved in 35 mL THF, combined with 2.1 g (12.7 mmol) 1,1'-carbonyldi-(1,2,4-triazole) and stirred overnight. The solvent is distilled off and the residue is dissolved in ethyl acetate. The solution is washed successively with potassium hydrogen sulphate solution and sodium chloride solution and dried with sodium sulphate. The residue is chromatographed (silica gel; dichloromethane with 0-16% methanol:ammonia=9:1) and the crude product thus obtained is stirred with diethyl ether. Light yellow solid. Yield: 1.12 g (59%); mass spectroscopy: [M+H]+=334.

Reference： [1]Patent: US2007/203125,2007,A1 .Location in patent: Page/Page column 31-32

10
[ 41864-22-6 ]
[ 83-88-5 ]
N-e-Lys-riboflavin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Riboflavin (Sigma-Aldrich) was dissolved at 37.6 mg/ml in DMSO and heated until in solution. A 2.5 molar excess of Solid l,l'-carbonyl-di(l,2,4-triazole) (150 mg) was added and reacted for 20 minutes. A two-fold weight excess of Lys-Cu-Lys dissolved in DMSO was added plus 300 ul TEA. The reaction was allowed to proceed overnight, and then the reaction was precipitated at pH 4.5. The product was dissolved in EDTA and applied to a Dowex 1x2 resin and the flow-though applied to XAD resin and washed with 0.2M EDTA. The product was eluted with methanol, rotary evaporated and lyophilized

Reference： [1]Patent: WO2007/131286,2007,A1 .Location in patent: Page/Page column 72

11
[ 41864-22-6 ]
methyl-4-amino-3,5-dibromo-D-phenylalanine hydrochloride [ No CAS ]
[ 79098-75-2 ]
C₂₄H₂₇Br₂N₅O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

12
[ 41864-22-6 ]
[ 63024-25-9 ]
[ 2039-67-0 ]
C₂₄H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In tetrahydrofuran

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US6344449, 2002, B1 Location in patent: Page column 166-167

13
[ 41864-22-6 ]
[ 79098-75-2 ]
[ 61039-29-0 ]
C₂₄H₂₆Br₂N₄O₅ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

14
[ 41864-22-6 ]
[ 79098-75-2 ]
[ 131235-51-3 ]
C₂₅H₂₇F₃N₄O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

15
[ 41864-22-6 ]
C₁₁H₁₃Br₂NO₃*ClH [ No CAS ]
[ 79098-75-2 ]
C₂₅H₂₈Br₂N₄O₅ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

16
[ 41864-22-6 ]
C₁₂H₁₁F₆NO₂*ClH [ No CAS ]
[ 79098-75-2 ]
C₂₆H₂₆F₆N₄O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

17
[ 41864-22-6 ]
methyl 2-amino-3-(3-bromophenyl)propanoate hydrochloride [ No CAS ]
[ 79098-75-2 ]
C₂₄H₂₇BrN₄O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

18
[ 41864-22-6 ]
C₁₀H₁₁Br₂NO₂*ClH [ No CAS ]
[ 79098-75-2 ]
C₂₄H₂₆Br₂N₄O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

19
[ 41864-22-6 ]
[ 79098-75-2 ]
2-amino-3-(3-chloro-phenyl)-propionic acid methyl ester; hydrochloride [ No CAS ]
C₂₄H₂₇ClN₄O₄ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

20
[ 41864-22-6 ]
[ 79098-75-2 ]
methyl 2-amino-3-(3-methoxyphenyl)propanoate hydrochloride [ No CAS ]
C₂₅H₃₀N₄O₅ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

21
[ 41864-22-6 ]
C₈H₁₂N₂O₂S*ClH [ No CAS ]
[ 79098-75-2 ]
C₂₂H₂₇N₅O₄S [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

22
[ 41864-22-6 ]
[ 79098-75-2 ]
3-Nitro-phenylalanin-methylester-hydrochlorid [ No CAS ]
C₂₄H₂₇N₅O₆ [ No CAS ]

Reference： [1]Patent: US6344/449,2002,B1 .Location in patent: Page column 166-167

23
[ 41864-22-6 ]
4-(2-oxo-1,2,4,5-tetrahydro-benzo[d][1,3]diazepin-3-yl)piperidine-1-carboxylic acid (R)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-1-(7-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-ylmethyl)-2-oxo-ethylester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%		120 mg (0.17 mmol) (R)-1-(4-amino-3-methyl-5-nitro-benzyl)-2-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate were dissolved in 10 mL THF and combined with 30 mg 10% Pd/C. The mixture was hydrogenated for 2 h in a Parr apparatus at 50 C. and 50 psi hydrogen pressure, the catalyst was filtered off and the filtrate was evaporated down i.vac. The residue was dissolved in 10 mL 1,4-dioxane, combined with 30 mg (0.18 mmol) CDT, refluxed for 2 h and then evaporated to dryness i.vac. The residue was purified by chromatography (Alox, DCM/MeOH 9:1), the fractions containing the product were combined, evaporated down i.vac., dissolved in MeOH, combined with diethyl ether, the precipitate was suction filtered and dried. Yield: 95 mg (82% of theory) ESI-MS: (M+H)+=673 Rf=0.57 (Polygram-Alox, DCM/MeOH 9:1)

Reference： [1]Patent: US2005/256099,2005,A1 .Location in patent: Page/Page column 166-167
[2]Patent: WO2005/103037,2005,A2 .Location in patent: Page/Page column 186

24
[ 41864-22-6 ]
tert-butyl [3-(2-amino-5-methyl-phenyl-amino)-3-methyl-butyl]-carbamate [ No CAS ]
tert-butyl [3-methyl-3-(6-methyl-2-oxo-2,3-dihydro-benzimidazol-1-yl)-butyl]-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	In tetrahydrofuran;	c) tert-butyl[3-methyl-3-(6-methyl-2-oxo-2,3-dihydro-benzimidazol-1-yl)-butyl]-carbamate: 1.76 g (5.7 mmol) tert-butyl[3-(2-amino-5-methyl-phenylamino)-3-methyl-butyl]-carbamate are dissolved in 35 mL THF, combined with 2.1 g (12.7 mmol) 1,1'-carbonyldi-(1,2,4-triazole) and stirred overnight. The solvent is distilled off and the residue is dissolved in ethyl acetate. The solution is washed successively with potassium hydrogen sulphate solution and sodium chloride solution and dried with sodium sulphate. The residue is chromatographed (silica gel; dichloromethane with 0-16% methanol:ammonia=9:1) and the crude product thus obtained is stirred with diethyl ether. Yield: 1.12 g (59%); mass spectroscopy: [M+H]+=334.
59%	In tetrahydrofuran;	1.76 g (5.7 mmol) tert-butyl [3-(2-amino-5-methyl-phenylamino)-3-methyl-butyl]-carbamate are dissolved in 35 mL THF, combined with 2.1 g (12.7 mmol) 1,1'-carbonyldi-(1,2,4-triazole) and stirred overnight. The solvent is distilled off and the residue is dissolved in ethyl acetate. The solution is washed successively with potassium hydrogen sulphate solution and sodium chloride solution and dried with sodium sulphate. The residue is chromatographed (silica gel; dichloromethane with 0-16% methanol:ammonia=9:1) and the crude product thus obtained is stirred with diethyl ether. Light yellow solid. Yield: 1.12 g (59%); mass spectroscopy: [M+H]+=334.

Reference： [1]Patent: US2007/249595,2007,A1 .Location in patent: Page/Page column 7
[2]Patent: US2006/63817,2006,A1 .Location in patent: Page/Page column 8

25
[ 41864-22-6 ]
[ 51077-16-8 ]
[ 36725-28-7 ]
[ 104434-77-7 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; water;	EXAMPLE 54 6-(4-(3-tert.-Butoxycarbonyl-L-thiazolidin-4-yl-carbonyl-amino)phenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone 9.3 g (0.04 mole) of 3-tert.-butoxycarbonyl-L-thiazolidine-4-carboxylic acid and 7.0 g (0.04 mole) of 1,1'-carbonyl-di-1,2,4-triazole are stirred in 15 ml of N-methylpyrrolidinone at 60 C. for 15 minutes. After addition of 7.1 g (0.035 mole) of <strong>[36725-28-7]6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone</strong> the mixture is stirred at room temperature for 6 hours, water is added, the mixture is extracted, the extract is crystallized with methanol and the product is recrystallized from methanol/ethyl acetate. Yield: 6.5 g (39% of theory), melting point: 200 to 201 C. Elemental analysis: C20 H26 N4 O4 S (418.52),

Reference： [1]Patent: US4816454,1989,A

26
[ 41864-22-6 ]
[ 3435-27-6 ]
C₁₁H₁₄N₆O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane; at 65℃; for 72h;	Example 8; 1-(6-^erf-Butylpyrimidi?-4-ylV3-f4-(2-cva?opyricli?-4-yloxyV2-fluoroDhenyl1upsilonrea; To a solution of 6-amino-4-terf-butylpyrimidine (150.0 mg; 0.99 mmol) in anhydrous 1 ,2-dichloroethane (1.9 ml_) was added 1 ,1'-carbonyldi(1 ,2,4-triazole) (195.4 mg, 1.19 mmol, 1.2 eq), and the reaction mixture was stirred at 650C for 3 days. A solution of 4-(4-amino-3-fIuorophenoxy)pyridine-2-carbonitrile (227.4 mg; 0.99 mmol, 1.0 1 ,2-dichloroethane (1.9 mL) was then added, and the reaction mixture was heated at 65C for 5h. The reaction was diluted with EtOAc, and the organic layer was washed with water and brine, dried over sodium sulfate, and evaporated under reduced pressure to give a crude oil. Trituration from DCM afforded the title compound (211 mg, 52%) as a white solid. "1H-NMR (DMSOd6) delta 10.37 (broad s, 1H), 10.08 (broad s, 1 H)1 8.75 (d, J - 1.2 Hz, 1 H), 8.59 (d, J = 5.4 Hz, 1H), 8.25 (t, J = 9.3 Hz, 1H), 7.73 (d, J = 2.7 Hz, 1 H), 7.59 (s, 1H), 7.37 (dd, J = 12.0, 2.7 Hz, 1H), 7.24 (dd, J = 5.4, 2.4 Hz, 1H), 7.08 (ddd, J = 9.0, 2.7, 1.5 Hz, 1 H), 1.26 (s, 9H); LC-MS m/z407 [M+H]+, RT = 3.17 min.

Reference： [1]Patent: WO2007/75650,2007,A2 .Location in patent: Page/Page column 47

27
[ 41864-22-6 ]
[ 68-19-9 ]
bovine insulin [ No CAS ]
AKP₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0179] Ditertbutyl dicarbonate (0.001 g, 5.0 x 10~6mol) was stirred with N- hydroxysuccinimide (0.0012 g, 1.0 x 10"5 mol) in 500 muL dry DMSO with 200 muL TEA for one hour at room temperature. This was then added drop-wise to a rapidly stirring solution of bovine insulin (O.OlOg, 1.74 x 10'6 mol) via syringe over two hours, then stirred at room temperature for an additional hour. The solution was precipitated in 35 mL chilled isopropyl alcohol and collected via centrifugation. The resulting solid was washed in chilled isopropyl alcohol, then ether. The dried sample was then dissolved in 4 mL DMSO with 1 % triethylamine. Cyanocobalamin (0.005g, 3.69 x 10"6 mol) was activated with 1.2 molar equivalents of CDT in 2 mL dry DMSO at room temperature for 30 minutes. The insulin solution was then added to the activated cyanocobalamin and allowed to rotate gently over night at room temperature. The resulting reaction was dialyzed against 5 L of deionized water and then purified by anion exchange chromatography.

Reference： [1]Patent: WO2008/109068,2008,A2 .Location in patent: Page/Page column 50

28
[ 41864-22-6 ]
O,O'-bis(2-aminoethyl)polyethylene glycol [ No CAS ]
[ 68-19-9 ]
[ 305-53-3 ]
bovine insulin [ No CAS ]
AKP₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0180] Ditertbutyl dicarbonate (0.001 g, 5.0 x 10"6mol) was stirred with N- hydroxysuccinimide (0.0012 g, 1.0 x 10"5 mol) in 500 muL dry DMSO with 200 muL TEA for one hour at room temperature. This was then added drop-wise to a rapidly stirring solution of bovine insulin (O.Ol Og, 1.74 x 10"6 mol) via syringe over two hours, then stirred at room temperature for an additional hour. The solution was precipitated in 35 mL chilled isopropyl alcohol and collected via centrifugation. The resulting solid was washed in chilled isopropyl alcohol, then ether. The dried sample was then dissolved in 4 mL DMSO with 0.5 % triethylamine. <n="53"/>\|0181] To attach PEG to the terminal amine of the B strand, O,O'-Bis(2- aminoethyl)polyethylene glycol 2,000 was reacted with sodium iodoacetate in 2 mL 500 itiM phosphate buffer containing 0.15 M NaCI and 5 mM EDTA, pH 8.3. This was stirred under nitrogen atmosphere at room temperature overnight. The PEG-acetate product was then dried in vacuo. It was redissolved in 2 mL dry DMSO and activated with CDT for 30 minutes at room temperature. The activated PEG was then added to the protected insulin and rotated at room temperature overnight. The reaction was then dialyzed with a MWCO of 3,500 against 5 L deionized water. The addition of 1 % TFA served to deprotect the Lys29 amine on the B chain of insulin. After dialyzing the deprotected system against 50 mM HEPES buffer, pH 6.9, the internal pH was adjusted to 6.9 and the previously established DMMA protection was carried out to protect the terminal amine located on the A strand of insulin.[0182] Cyanocobalamin (0.005g, 3.69 x 10"6 mol) was activated with 1.2 molar equivalents of CDT in 2 mL dry DMSO at room temperature for 30 minutes. The insulin- PEG solution was then added to the activated cyanocobalamin and allowed to rotate gently over night at room temperature. The resulting reaction was dialyzed with a MWCO of 7,000 against 5 L of deionized water and then purified by anion exchange chromatography.

Reference： [1]Patent: WO2008/109068,2008,A2 .Location in patent: Page/Page column 50; 51

29
[ 41864-22-6 ]
O,O'-bis(2-aminoethyl)polyethylene glycol [ No CAS ]
[ 68-19-9 ]
bovine insulin, dimethylmaleic anhydride protected [ No CAS ]
[ 305-53-3 ]
AKP₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0177] Cyanocobalamin (0.005g, 3.69 x 10"6 mol) was dissolved in 2 mL dry DMSO and activated with CDT at room temperature for 30 minutes. This was then added to O,O'-Bis(2-aminoethyl)polyethylene glycol 2,000 (0.0147 g, 7.37 x 10"6 mol) and the B12- PEG product was purified by high pressure liquid chromatography using 5 mM Phosphate buffer, pH 7, and acetonitrile. The gradient went from 20 % acetonitrile to 50 % acetonitrile over 20 minutes. B)2-PEG had a Tr at 1 1 minutes and was then verified by MALDI-MS. Bi2-PEG was reacted with 50 mM sodium iodoacetate with the presence of a ten-fold molar excess of sodium iodoacetate. The reaction was run in 2 mL 500 mM phosphate buffer containing 0.15 M NaCI and 5 mM EDTA, pH 8.3. This was stirred under nitrogen atmosphere at room temperature overnight. The B\|2-PEG-acetate product was then dried in vacuo and activated with CDT in 2 mL dry DMSO for 30 minutes at room temperature.[0178] Bovine insulin (0.01 Og, 1.74 x 10"6 mol) was protected with a three-fold molar excess of dimethylmaleic anhydride by the previously established procedure. The <n="52"/>protected insulin solution was then collected by precipitation in 35 mL chilled isopropyl alcohol. The resulting solid was washed in chilled isopropyl alcohol, then ether. The dried sample was then dissolved in 4 mL DMSO with 1 % triethylamine. The insulin solution was then added to the activated B I2-PEG -acetate and allowed to rotate gently over night at room temperature. The resulting reaction was dialyzed against 5 L of deionized water and then purified by anion exchange chromatography.

Reference： [1]Patent: WO2008/109068,2008,A2 .Location in patent: Page/Page column 49; 50

30
[ 41864-22-6 ]
[ 68-19-9 ]
bovine insulin, dimethylmaleic anhydride protected [ No CAS ]
AKP₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0175] Use of coupling agents, such as CDI or CDT for in this application coupling the B)2 to insulin is now the standard in chemistry, and review books exist on this topic, such as, for example Hermanson, G. "Bioconjugate Techniques", AP Press.[0176] Bovine insulin (0.01Og, 1.74 x 10"6 mol) was protected with a three-fold molar excess of dimethylmaleic anhydride by the previously established procedure. The protected insulin solution was then collected by precipitation in 35 mL chilled isopropyl alcohol. The resulting solid was washed in chilled isopropyl alcohol, then ether. The dried sample was then dissolved in 4 mL DMSO with 1 % triethylamine. Cyanocobalamin (0.005g, 3.69 x 10"6 mol) was activated with 1.2 molar equivalents of CDT in 2 mL dry DMSO at room temperature for 30 minutes. The insulin solution was then added to the activated cyanocobalamin and allowed to rotate gently over night at room temperature. The resulting reaction was dialyzed against 5 L of deionized water and then purified by anion exchange chromatography.

Reference： [1]Patent: WO2008/109068,2008,A2 .Location in patent: Page/Page column 49

31
[ 41864-22-6 ]
[ 1115406-58-0 ]
[ 1115084-31-5 ]

Reference： [1]European Journal of Organic Chemistry,2008,p. 6029 - 6033

32
[ 41864-22-6 ]
[ 1115406-56-8 ]
[ 1115084-30-4 ]

Reference： [1]European Journal of Organic Chemistry,2008,p. 6029 - 6033

33
[ 41864-22-6 ]
[ 329974-09-6 ]
[ 1158784-18-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 0.188 g 2.6-diamino-4-bromopyridine in 2 ml acetonitrile was added 0.164 g 1,1-carbonyldi(1,2,4-triazole) and the mixture was stirred at room temperature. After a short period of a clear solution a suspension formed. The mixture was stirred at room temperature for 1 h. To the resulting suspension was added 0.5 ml of a 25% aqueous ammonia solution and the resulting solution was stirred at room temperature for 0.5 h. The mixture was partitioned between water and ethyl acetate. The organic phase was separated and evaporated to dryness. The residue was taken up in methanol whereby crystallisation occurred. The crystals were collected by filtration and dried to constant weight to yield 0.068 g of the title compound as white crystals. MS (ISP) M+H+=231.0; 232.9

Reference： [1]Patent: US2009/143439,2009,A1 .Location in patent: Page/Page column 15

34
[ 41864-22-6 ]
[ 29679-58-1 ]
[ 1213788-19-2 ]

Reference： [1]Advanced Synthesis and Catalysis,2009,vol. 351,p. 2333 - 2341

35
[ 41864-22-6 ]
[ 600725-39-1 ]
[ 79098-75-2 ]
[ 686297-92-7 ]

Reference： [1]Patent: WO2004/37811,2004,A1 .Location in patent: Page/Page column 96

36
[ 41864-22-6 ]
[ 401573-46-4 ]
[ 79098-75-2 ]
[ 686298-40-8 ]

Reference： [1]Patent: WO2004/37811,2004,A1 .Location in patent: Page/Page column 161

37
[ 41864-22-6 ]
[ 669002-20-4 ]
[ 31053-03-9 ]
4-methylphenyl-piperidine-1-carboxylic acid-[2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22.2%		2.12.a 4-methylphenyl-piperidine-1-carboxylic acid-[2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethyl]-amide Prepared according to general working method II described hereinbefore from 4-methylphenyl-piperidine (175 mg, 1.0 mmol) and 2-(4-pyrrolidin-1-ylmethyl-phenyl)-ethylamine (204 mg, 1.0 mmol). Yield: 90.0 mg (22.2% of theory); C26H35N3O (M=405.558); calc.: molar peak (M+H)+: 406 fnd.: molar peak (M+H)+: 406; Rf value: 0.30 (silica gel, ethyl acetate/methanol/NH3 9:1:0.1). General Working Method II (CDT Coupling): [0530] CDT (1 eq.) is added to a solution of the primary amine (1.0 eq.) in DMF (1 mmol/mL) at 0 C. and the mixture is stirred at 0 C. for a further 30 min. The reaction is heated to 25 C. and triethylamine (3 eq.) is added. Then the secondary amine (1.0 eq.) in DMF (0.25 mmol/mL) is added and the reaction solution is heated to 60 to 80 C. for 30 min to 3 h. DMF is removed in vacuo and the residue is taken up with dichloromethane and 5%-Na2CO3 solution or with water and tert-butylmethyl ether. The organic phase is extracted with water and the solvent is removed using the rotary evaporator optionally after drying over magnesium sulphate; further purification is carried out by column chromatography or crystallisation. The reaction may also be carried out in a Chemspeed automatic synthesiser.

Reference： [1]Patent: US2004/242572,2004,A1 .Location in patent: Page/Page column 34; 61

38
[ 41864-22-6 ]
[ 291509-61-0 ]
[ 688020-65-7 ]
[ 688020-67-9 ]

Yield	Reaction Conditions	Operation in experiment
100%		1.8 g (11.0 mmol) CDT were added to a solution of 3.2 g (10.2 mmol) ethyl (R)-2-amino-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-propionate and 1.8 mL (10.3 mmol) ethyldiisopropylamine in 150 mL THF cooled to 0 C. and the reaction mixture was stirred for 45 min at this temperature and after removal of the ice bath stirred for a further 30 min. Then 2.5 g (10.2 mmol) 3-piperidin-4-yl-1,3,4,5-tetrahydro-1,3-benzdiazepin-2-one, suspended in 50 mL THF was added. 40 mL DMF were added to the reaction solution and this was stirred for 2 h at 80 C. The mixture was evaporated down i. vac., combined with 200 mL EtOAc and 200 mL 10% citric acid solution, the organic phase was separated off, extracted with 150 mL NaHCO3 solution and dried over Na2SO4. After the desiccant and solvent had been eliminated the desired product was obtained. Yield: 5.9 g (100% of theory) ESI-MS: (M+H)+=582/584 (Cl)

Reference： [1]Patent: WO2005/100343,2005,A1 .Location in patent: Page/Page column 56; 57
[2]Patent: US2005/282857,2005,A1 .Location in patent: Page/Page column 95

39
[ 41864-22-6 ]
[ 291509-61-0 ]
[ 868383-97-5 ]
[ 868383-98-6 ]

Yield	Reaction Conditions	Operation in experiment
95%		An ice-cooled mixture of 2.09 g (8.1 mmol) ethyl (R)-2-amino-3-(4-amino-3-chloro-5-methyl-phenyl)-propionate and 100 ml DMF was combined with 1.6 g (9.7 mmol) CDT and stirred for 30 minutes while cooling with ice. Then while cooling with ice 2.0 g (8.1 mmol) 3-piperidin-4-yl-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, dissolved in 80 ml DMF, was added dropwise and the mixture was stirred for 12 hours at ambient temperature. The reaction mixture was poured onto 300 ml ice water, the precipitate was suction filtered and dried in the circulating air dryer at 30 C. Yield: 4.1 g (95% of theory) ESI-MS: (M+H)+=528/530 (Cl)

Reference： [1]Patent: WO2005/100343,2005,A1 .Location in patent: Page/Page column 62
[2]Patent: US2005/282857,2005,A1 .Location in patent: Page/Page column 98

40
[ 41864-22-6 ]
[ 329974-09-6 ]
[ 74-89-5 ]
[ 1158784-24-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 0.188 g 2.6-diamino-4-bromopyridine in 2 ml acetonitrile was added 0.164 g 1,1-carbonyldi(1,2,4-triazole) and the mixture was stirred at room temperature. After a short period of a clear solution a suspension formed. The mixture was stirred at room temperature for 1 h. To the resulting suspension was added 0.5 ml of a methylamine solution in THF (ca 3 M) and the resulting solution was stirred at room temperature for 0.5 h. The mixture was partitioned between water and ethyl acetate. The phases were separated and the organic phase evaporated to dryness. The residue was taken up in methanol whereby crystallisation occurred. The crystals were collected by filtration and dried to constant weight to yield 0.196 g of the title compound as white crystals. MS (ISP) M+H+243.3; 245.2

Reference： [1]Patent: US2009/143439,2009,A1 .Location in patent: Page/Page column 15

41
[ 41864-22-6 ]
[ 4897-50-1 ]
[ 337909-88-3 ]
[ 337910-16-4 ]

Yield	Reaction Conditions	Operation in experiment
65%		EXAMPLE A21N-{2-[1.4']bipiperidinyl-1'-ylcarbonylamino}phenylmethyl}-N-(1,1-dimethylethoxycarbonyl)-1-(phenylmethyl)-4-piperidine-amineA mixture of 2.56 g (15.6 mmol) of CDT, 5.14 g (13 mmol) of N-[(2-aminophenyl)methyl]-N-(1,1-dimethylethoxycarbonyl)-1-(phenylmethyl)-4-piperidineamine and 200 ml of tetrahydrofuran was stirred for 0.5 hours while cooling with ice and then for 30 minutes at ambient temperature. 2.4 g (14.3 mmol) of [1,4']piperidinyl were added with stirring and the mixture was refluxed for 4 hours. The reaction mixture was diluted with 200 ml of ethyl acetate and the organic phase was washed twice with 150 ml of aqueous saturated sodium hydrogen carbonate solution and once with 100 ml of saturated aqueous sodium chloride solution. After the organic phase had been dried and the solvent eliminated in vacuo the residue was purified by column chromatography (MN-silica gel 60, Macherey-Nagel, 70-230 mesh ASTM, eluant: dichloromethane/isopropanol=9/1 (v/v)). 5.0 g (65% of theoretical) of a colourless amorphous product were obtained, Rf 0.5 (El D).IR (KBr): 1687.6, 1660.6 cm-1 (CO)

Reference： [1]Patent: US7230001,2007,B1 .Location in patent: Page/Page column 83

42
[ 41864-22-6 ]
[ 473-98-3 ]
28-hydroxy-lup-20(29)-en-3β-yl-1H-triazole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%		A solution of betulin 1 (200 mg, 0.45 mmol) andCDT (443 mg, 2.7 mmol) in anhydrous THF (8 ml) was refluxed for 10 h to obtained compound 19. Silica gel (200 mg) was added and this mixture was stirred at room temperature for 15 h. The solid was filtered off and the filtrate was poured into water (30 ml) and extracted with diethyl ether (3 * 30 ml) . The organic phase was then washed with water (30 ml) , and brine (30 ml) , dried with Na2SO4, filtered, and evaporated to dryness. The crude product was purified by FCC eluting with petroleum ether 40-60C/ethyl acetate (3:2) to yield compound 21 (152 mg, 63 %) : mp (acetone/n- hexane) 221-224C; IR (film) upsilonmaA 3406, 3070, 1764, 1642, 886 cm"1; 1H NMR (CDCl3, 300 MHz) delta 8.79 (s, IH, H-5'}, 8.08 (s, IH, H-31 ) , 4.79 (dd, J = 9.1, 7.5 Hz, IH, H-3alpha) , 4.69 (brs, IH, H-29a) , 4.59 (brs, IH, H-29b) , 3.80 (d, J = 10.8 Hz, IH, H-28a) , 3.34 (d, J= 10.8 Hz, IH, H-28b) , 2.40 (dt, J = 10.5 Hz, J = 5.8 Hz, IH, H-19) , 1.69 (s, 3H, H-30) , 1.04 (s, 3H) , 0.99 (s, 6H) , 0.98 (s, 3H) , 0.90 (s, 3H) ; 13C NMR (CDCl3, 75 MHz) delta 153.4 (C31 ) , 150.4 (C20) , 147.2 (OCO) , 145.3 (C51 ) , 109.7 (C29) , 87.8 (C3) , 60.4 (C28) ; EI- MS m/z (% rel. intensity): 537 (6) M 119 (49) , 107 (46) , 105 (60) , 93 (55) , 91 (100) , 81 (46) , 79 (53) , 77 (51) , 70 (38) .

Reference： [1]Patent: WO2010/134830,2010,A1 .Location in patent: Page/Page column 42

43
[ 41864-22-6 ]
[ 1184303-05-6 ]
[ 1184303-06-7 ]

Yield	Reaction Conditions	Operation in experiment
36%	In tetrahydrofuran; at 50℃;	Q.iv. 6-{(S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-oneA solution of intermediate Q.iii (14.5 g, 37.9 mmol) and CDT (8.60 g, 1.4 eq.) in THF (180 mL) was heated at 50 C. overnight. The mixture was concentrated under reduced pressure and partitioned between EA and water. The aq. layer was extracted once more with EA and the combined org. layers were dried over MgSO4 and concentrated. The residue was purified by CC (DCM/MeOH/NH4OH 1000:50:4) to afford the title intermediate as a colourless solid (5.56 g, 36% yield).MS (ESI, m/z): 409.3 [M+H+].

Reference： [1]Patent: US2010/331318,2010,A1 .Location in patent: Page/Page column 36

44
[ 41864-22-6 ]
[ 1184303-10-3 ]
[ 1184303-11-4 ]

Yield	Reaction Conditions	Operation in experiment
43%	In tetrahydrofuran; at 50℃;	R.ii. 6-{(R)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-oneA solution of intermediate R.i (5.8 g, 15.8 mmol) and CDT (3.07 g, 1.2 eq.) in THF (50 mL) was heated at 50 C. overnight. The mixture was concentrated under reduced pressure and partitioned between EA and water. The aq. layer was extracted once more with EA and the combined org. layers were dried over MgSO4 and concentrated. The residue was triturated with Et2O/EA/MeOH to afford the title intermediate as a beige solid (2.7 g, 43% yield).MS (ESI, m/z): 393.5 [M+H+].

Reference： [1]Patent: US2010/331318,2010,A1 .Location in patent: Page/Page column 37

45
[ 41864-22-6 ]
[ 920-66-1 ]
[ 53786-28-0 ]
[ 1352010-36-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 3 (compound No. 12)2,2,2-Trifluoro-1 -(trifluoromethyl)ethyl 4-(5-chloro-2-oxo-2,3-dihydrobenzimidazol-1 - yl)piperidine-1 -carboxylate0.328 g (2 mmol) of carbonyldi(1 ,2,4-triazole) is added to a solution of 0.6725 g (4 mmol) of 1 ,1 ,1 ,3,3,3-trifluoro-2-propanol and 0.012 g (0.1 mmol) of 4-dimethylaminopyridine in 10 ml of dichloromethane. The mixture is stirred at ambient temperature overnight and then 0.503 g (2 mmol) of 5-chloro-1 -piperidin-4-yl-1 ,3-dihydrobenzimidazol-2-one is added. Stirring is continued at ambient temperature for 3 hours and the dichloromethane is evaporated under vacuum. The residue is taken up in a mixture of 50 ml of ethyl acetate and 20 ml of 1 N aqueous hydrochloric acid. The organic phase is separated by settling and is then washed with 2 times 20 ml of water and then with 20 ml of a saturated aqueous sodium chloride solution. It is dried over sodium sulphate and evaporated under vacuum. The product is purified by chromatography on silica gel, elution being carried out with a 30:70, then 40:60 and 50:50 mixture of ethyl acetate and cyclohexane. Recrystallization is subsequently carried out under hot conditions for a mixture of ethyl acetate and cyclohexane in order to obtain 0.28 g (0.62 mmol) of product in the form of a white crystalline powder.Melting point (C): 231 -233 LC/MS (method B): Rt 9.3 min, m/z 446 (MH+)IR (KBr, cm"1): 1751 , 16971H NMR (CDCIs, delta ppm, 200 MHz): 8.6 (s, 1 H), 7.15-6.95 (m, 3H), 5.85 (sept, 1 H), 4.6- 4.3 (m, 3H), 3.1 (m, 2H), 2.4 (m, 2H), 1 .95 (m, 2H).

Reference： [1]Patent: WO2011/151808,2011,A1 .Location in patent: Page/Page column 25-26

46
[ 41864-22-6 ]
vitamin B₁₂ [ No CAS ]
C₆₆H₈₉CoN₁₇O₁₅P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 50℃; for 1.25h;	0.145 mmol of Cyanocobalamin (196.53 mg) was activated by 0.725 mmol of 1,1?-Carbonyl-di-(1,2,4-triazole) (CDT) for 1 hour in 5 mL of dry DMSO at 50 C. 0.159 mmol (37.738 mg) of 1,1-bisthiazolate-(1,4)-diaminobutane in DMSO was added to the reaction, and allowed to react for 16 hours. The product was then precipitated using ether and acetone. The calculated yield of this reaction was 0.5%. In an attempt to increase reaction yield, this reaction was repeated using 0.045 mmol of cyanocobalamin (60.99 mg) activated by 0.36 mmol of CDT (59.34 mg) at 50 C. in dry DMSO for 1 hour and 15 minutes. The reaction then sat at room temperature for 15 minutes to cool down. 0.050 mmol of 1,1-bisthiazolate-(1,4)-diaminobutane (14 mg) in 1 mL of dry DMSO was added to the reaction mixture and reacted for 16 hours. The yield of this reaction was 1.5%. The B12-bisthiazole reaction may be optimized to increase the yield
	In dimethyl sulfoxide; at 30 - 33℃; for 0.5h;Sonication;	(Take 0.2 mg of vitamin B12 in 5 ml of DMSO(Dimethyl sulfoxide)Put the equivalent of vitamin B12 8Times the amount of CDT.CDT and vitamin B12 in the ultrasonic bath reaction, the ultrasonic power of 70w,The bath temperature is maintained between 30 C and 33 C,Reaction for half an hour,To give the ester imidazoleProduct,Followed by the addition of 4 volumes of ethyl acetate to stop the reaction.The reaction solution was transferred to a centrifuge tube,8000r / min centrifugal 5min,After going to the supernatant,Add 5ml DMSO dissolved centrifugal precipitate,Add 300 mul of DIEA quickly(N, N-diisopropylethylamine) and 600 mul putrescine.Ultrasonic water bath auxiliary reaction,Ultrasonic power of 70w, water bath temperature maintained at between 30 to 33 ,After 2 h of reaction, 4 volumes of ethyl acetate were added to stop the reaction,8000r / min centrifugal 5min, to the supernatant.The precipitate was blown off using a nitrogen blower to obtain a synthetic sample of vitamin B12-OD.

Reference： [1]Dalton Transactions,2011,vol. 40,p. 9665 - 9667
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 8707 - 8711
[3]Angewandte Chemie - International Edition,2015,vol. 54,p. 6196 - 6199
Angew. Chem.,
[4]Patent: US2016/199500,2016,A1 .Location in patent: Page/Page column 16
[5]Patent: CN106581645,2017,A .Location in patent: Paragraph 0105; 0106

47
[ 41864-22-6 ]
2BrH*C₂₂H₂₄ClFN₄O₂ [ No CAS ]
[ 1326217-60-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 20.3333h;	Example 6Preparation of Compound (7)-Step (F) 10 g (content approx. 90%, 15.2 mmol) of compound (5.2) are suspended in 100 mL THF (tetrahydrofuran) and 6.5 mL diisopropylethylamine (38.0 mmol). 1,1'-carbonyldi(1,2,4-triazole) (3.95 g, 25.3 mmol) is added at RT. After 20 hours, further 1,1'-carbonyldi(1,2,4-triazole) (0.13 g, 0.79 mmol) is added. After 20 min, 100 mL water are added dropwise. The reaction mixture is stirred for 4 hours at RT and then cooled to 5 C.The precipitate is suction filtered and washed twice with 10 mL of a 1:1 mixture of water:THF. The product (compound (7)) is dried at 50 C. in the circulating air dryer.Mass spectrum (ESI+): m/z=526-528 [M+H]+ 1H-NMR selected data (DMSO-d6): 9.50 (1H, s), 9.06 (1H, s), 8.51 (1H, s), 8.24 (1H, s), 8.12 (1H, dd, J=7.1 and 2.5 Hz), 7.96 (1H, s), 7.78 (1H, m), 7.44 (1H, t, J=8.98 Hz), 7.25 (1H, s). 4.82 (1H, m), 3.98 (3H, s),

Reference： [1]Patent: US2012/46284,2012,A1 .Location in patent: Page/Page column 10-11

48
[ 41864-22-6 ]
[ 288315-03-7 ]
[ 1360624-56-1 ]
[ 1360622-21-4 ]

Yield	Reaction Conditions	Operation in experiment
		(b) A/-(frans-4-Trifluoromethyl-cyclohex-1-yl)- 2-{2,6-dichloro-3-[(3,3-difluoro-azetidine-1- carbonylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1 H-benzimidazole-5- carboxylic acid amide CDT (45 mg, 90%) is added to an ice-cooled mixture of crude A/-(frans-4-trifluoromethyl- cyclohex-1-yl)- 2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl- 1 H-benzimidazole-5-carboxylic acid amide (140 mg), DIPEA (0.12 mL, 0.68 mmol) and THF (5.0 mL) and it is stirred for 30 min. Then 3,3-difluoroazetidine x HCI (30 mg, 0.22 mmol) is added and the mixture is heated to 60C for 4 d (every day another 30 mg of the azetidine is added). The reaction mixture is concentrated and purified via chromatography (silica gel, DCM->DCM/EtOH 95:5). Yield: 60 mg (38%). Rf(TLC): 0.26 (DCM/EtOH 95:5). MS m/z: 713 [M+H]+ .
		(b) N-(trans-4-Trifluoromethyl-cyclohex-1-yl)-2-{2,6-dichloro-3-[(3,3-difluoro-azetidine-1-carbonylamino)-methyl]-phenylamino}-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide CDT (45 mg, 90%) is added to an ice-cooled mixture of crude N-(trans-4-trifluoromethyl-cyclohex-1-yl)-2-(2,6-dichloro-3-aminomethyl-phenylamino)-6-(2,2-difluoroethoxy)-1-methyl-1H-benzimidazole-5-carboxylic acid amide (140 mg), DIPEA (0.12 mL, 0.68 mmol) and THF (5.0 mL) and it is stirred for 30 min. Then 3,3-difluoroazetidine*HCl (30 mg, 0.22 mmol) is added and the mixture is heated to 60 C. for 4 d (every day another 30 mg of the azetidine is added). The reaction mixture is concentrated and purified via chromatography (silica gel, DCM->DCM/EtOH 95:5). Yield: 60 mg (38%). Rf(TLC): 0.26 (DCM/EtOH 95:5). MS m/z: 713 [M+H]+.

Reference： [1]Patent: WO2012/22793,2012,A1 .Location in patent: Page/Page column 83
[2]Patent: US2012/214786,2012,A1 .Location in patent: Page/Page column 49

49
[ 41864-22-6 ]
[ 1394034-63-9 ]
[ 1394034-64-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	In 1,4-dioxane; at 20 - 50℃; for 6.25h;	Step 7. Synthesis of 5-(5-bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (C3) 1,1'-Carbonylbis(1H-1,2,4-triazole) (90%, 2.69 g, 14.8 mmol) and N-[4-(5-bromo-1-methyl-1H-pyrazol-4-yl)-2-methyl-1H-imidazol-1-yl]imidoformamide (2.69 g, 9.50 mmol) were combined in 1,4-dioxane (63 mL) and the mixture was stirred for 3.5 hours at room temperature, then heated to 50 C. for 1 hour. Additional 1,1'-carbonylbis(1H-1,2,4-triazole) (90%, 1.34 g, 7.35 mmol) was added, and heating was continued for 30 minutes. After another addition of 1,1'-carbonylbis(1H-1,2,4-triazole) (90%, 269 mg, 1.48 mmol), heating at 50 C. was carried out for an additional 75 minutes. The reaction was allowed to cool to room temperature, and was then concentrated to half its original volume; the precipitate was collected and washed with ethyl acetate to afford a white solid. This was dissolved in methanol (50 mL), concentrated to dryness and triturated with water (25 mL). After collection of the solid, it was washed with 2-propanol followed by diethyl ether to provide C3 as a white solid. Yield: 1.95 g, 6.31 mmol, 66%. LCMS m/z 309.4 (M+1). 1H NMR (500 MHz, DMSO-d6) delta 2.53 (s, 3H), 3.87 (s, 3H), 7.87 (s, 1H), 8.17 (s, 1H), 11.69 (br s, 1H).

Reference： [1]Patent: US2012/214791,2012,A1 .Location in patent: Page/Page column 24
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018

50
[ 41864-22-6 ]
[ 1394034-82-2 ]
[ 1394034-79-7 ]

Yield	Reaction Conditions	Operation in experiment
19%	In 1,4-dioxane; at 70℃; for 18h;	This was dissolved in 1,4-dioxane (4 mL) and treated with 1,1'-carbonylbis(1H-1,2,4-triazole) (212 mg, 1.16 mmol); the reaction was heated at 70 C. for 18 hours, then concentrated under reduced pressure. After addition of dichloromethane and methanol to the residue, the mixture was filtered, and the filtrate was applied to a silica gel column and eluted (Gradient: 0% to 100% [90:5:5 ethyl acetate/triethylamine/methanol] in heptane) to afford the product. Yield: 55 mg, 0.19 mmol, 19%. LCMS m/z 295.0 (M+1). 1H NMR (400 MHz, CD3OD) delta 3.95 (s, 3H), 7.73 (s, 1H), 8.10 (s, 1H), 8.34 (s, 1H).

Reference： [1]Patent: US2012/214791,2012,A1 .Location in patent: Page/Page column 32

51
[ 41864-22-6 ]
[ 71623-71-7 ]
[ 1403683-29-3 ]

Yield	Reaction Conditions	Operation in experiment
46%	In tetrahydrofuran; at 70℃; for 2h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

52
[ 41864-22-6 ]
[ 94482-51-6 ]
[ 1403683-32-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	In tetrahydrofuran; at 70℃; for 5h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

53
[ 41864-22-6 ]
[ 73047-75-3 ]
[ 1403683-35-1 ]

Yield	Reaction Conditions	Operation in experiment
43%	In tetrahydrofuran; at 70℃; for 4h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

54
[ 41864-22-6 ]
2-hydroxymethylene-3-oxours-12-en-28-oic acid [ No CAS ]
28-(4H-triazol-4-yl)-3,28-dioxours-12-en-2-(4H-triazol-4-yl)methylene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	In tetrahydrofuran; at 70℃; for 7.5h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

55
[ 41864-22-6 ]
methyl 2-hydroxymethylene-3,11-dioxours-12-en-28-oate [ No CAS ]
methyl 2-(4H-triazol-4-yl)methylene-3,11-dioxours-12-en-28-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	In tetrahydrofuran; at 70℃; for 23.5h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

56
[ 41864-22-6 ]
[ 14087-68-4 ]
methyl 2-(4H-triazol-4-yl)methylene-3-oxours-12-en-28-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	In tetrahydrofuran; at 70℃; for 23h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)],

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

57
[ 41864-22-6 ]
[ 915-79-7 ]
[ 1403683-26-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	In tetrahydrofuran; at 70℃; for 2h;Inert atmosphere;	General procedure: To a stirred solution of 2 (300 mg 0.60 mmol) in THF (4 mL), under N2 atmosphere at 70 C, was added CDT (295.43 mg 1.8 mmol). After 2 h the reaction mixture was diluted with water (60 mL), the aqueous phase was extracted with ethyl acetate (3 * 50 mL). The resulting organic phases were washed with NaCl 10% (3 * 50 mL), dried over Na2SO4, filtered and evaporated to the dryness, to afford a yellow solid. The residue was subjected to flash column chromatography [hexanes-ethyl acetate from (85:15) to (80:20)], to afford 14 (94%). Mp 124.0-128.8 C. IR (film CHCl3): 3139.5, 2950.6, 2924.5, 2872.5, 1732.7, 1511.9, 1456.0, 1348.0, 1275.7, 1246.7, 1183.1 cm-1. 1H NMR (400 MHz CDCl3): delta 8.81 (1H s), 7.98 (1H s), 5.23 (1H s), 4.48 (1H t J = 15.77), 2.04 (3H s), 1.10 (3H s), 0.98 (3H d J = 6.29), 0.92 (6H s), 0.85 (3H s), 0.84 (3H s), 0.66 (3H s). 13C NMR (100 MHz CDCl3): delta174.87, 170.99, 152.20, 145.30, 137.54, 126.09, 80.84, 55.28, 52.96, 51.30, 47.43, 42.14, 39.47, 39.11, 38.54, 38.29, 37.66, 36.82, 34.44, 32.76, 30.45, 28.15, 28.03, 23.56, 23.51 (2C), 23.29, 21.29, 21.06, 18.09, 17.05, 16.74, 16.69, 15.51. EI-MS m/z: 548.86 (1) M+, 452.08 (23), 202.96 (32), 201.92 (100), 201.03 (25), 190.04 (85), 189 (53), 188.05 (26), 145.02 (21), 133.05 (31), 131.93 (97), 119.02 (39), 117.04 (53), 104.98 (28), 91.00 (30), 78.96 (22). Anal. Calcd for C34H51N3O3 C, 74.28; H, 9.35; N, 7.64. Found: C, 74.56; H, 9.21; N, 8.00.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5774 - 5786

58
[ 41864-22-6 ]
[ 147403-65-4 ]
[ 147403-52-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 20℃; for 3h;Product distribution / selectivity;	Example 4Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 (2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1H- benzo[< ]imidazole-7-carboxylate of formula la l ,8-Diazabicyclo[5.4.0.]undec-7-ene (DBU; 0.1 g, 0.65 mmol) was added dropwise to a mixture of methyl 2-methoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- lH- benzo[i ]imidazole-7-carboxylate (of formula Va; 0.22 g, 0.5 mmol), the corresponding solvent (3 ml) and carbonyldiimidazole (0.1 g, 0.6 mmol) in a reaction vial under stirring and the mixture was stirred at the room temperature for 3 hours. Then, the content of the vial was poured into water ( 10 ml) and, after acidification with acetic acid, the separated solids were aspirated and washed with water. The yields and purity of the products are summarized in Table I. Table I - Yield and purity of the product of Example 4* - Also contains 40.4 percent of the starting compound of formula Va; ** - Carbonyl-di- 1 ,2,4- triazole was used instead of carbonyldiimidazole

Reference： [1]Patent: WO2012/139536,2012,A1 .Location in patent: Page/Page column 11-12

59
[ 41864-22-6 ]
[ 932741-19-0 ]
vitamin B-12 [ No CAS ]
C₇₃H₁₀₃CoN₁₅O₁₈P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 1,1'-Carbonyl-di-(1,2,4-triazole); vitamin B-12 In dimethyl sulfoxide for 0.5h; Inert atmosphere; Heating; Stage #2: 2-(2-(2-(prop-2-yn-1-yloxy)ethoxy)ethoxy)ethanamine In dimethyl sulfoxide at 20℃; Inert atmosphere;

Reference： [1]Loska, Rafał; Janiga, Anita; Gryko, Dorota [Journal of Porphyrins and Phthalocyanines, 2013, vol. 17, # 1-2, p. 104 - 117]

60
[ 41864-22-6 ]
2-((1-benzyl-piperidin-4-ylamino)-methyl)-phenyl-ammonium dihydrochloride [ No CAS ]
[ 79098-88-7 ]

Yield	Reaction Conditions	Operation in experiment
50 mg	With diisopropylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 20 - 85℃;	6.01.1 1.03 3 - 1 -Benzyl-piperidin-4-yl)-3 , 4-dihydro- 1 H-quinazo lin-2-one 1 10 diisopropylamine and 22 mg CDT were added to 50 mg 2-((l-benzyl-piperidin-4- ylamino)-methyl)-phenyl-ammonium dichloride in 2.5 mL THF and 1 mL DMF. The reaction was stirred lh at RT and 4 h at 85 C. Then, 55 mu, diisopropylamine and 17 mg CDT were added and the reaction was stirred at 85 C over night.The solvent was removed and the residue was purified by column chromatographie (silica gel, eluent: dichlormethane/ methanole/ ammonia: 9/1/0.1) to give 50 mg of the desired product. Rf: 0.45 (dichlormethane 9: methanol 1 : ammonia 0.1), (M+H)+: 322

Reference： [1]Patent: WO2013/83741,2013,A1 .Location in patent: Page/Page column 65

61
[ 41864-22-6 ]
[ 851983-85-2 ]
[ 1441047-13-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	In dichloromethane; acetonitrile; for 3h;Reflux;	[00170] 3beta-(IotaEta- 1 ,2,4-Triazole- 1-carboxylate)- 17-(lH-benzimidazol- l-yl)-androsta- 5,16-diene (49): A solution of 5 (0.15 g, 0.386 mmol), CDT (0.19 g, 1.16 mmol) in anhydrous acetonitrile (3 mL) and DCM (1.5 mL) was refluxed for 3h. The solvent evaporated, residue treated with water, and extracted with DCM. The crude white product obtained on evaporation of solvent was purified by FCC using 4 percent Ethanol in DCM in presence of traces of TEA (0.06percent). The product was triturated with petroleum ether to give 49 (0.15 g, 80percent> ): mp 205-206 °C; IR (Neat) 2950, 2855, 1776, 1489, 1375, 1289, 978, 750 cm"1; 1H NMR (500 MHz, CDCI3) delta 1.03 (s, 3 H, I8-CH3), 1.12 (s, 3 H, 19-CH3), 4.96 (m, 1 H, 3a-H), 5.52 (m, 1 H, 6-H), 5.99 (s, 1 H, 16-H), 7.30 (m, 2 H, aromatic-Hs), 7.50 (t, 1 H, J = 3.8 Hz, aromatic -H), 7.81 (m, H, aromatic- H), 7.96 (s, 1 H, 2'-H), 8.07 (s, 1 H, 5"-H), and 8.83 (s, 1 H, 3"-H); 13C NMR (500 MHz, CDC13) delta 153.8, 147.3, 145.8, 143,5, 141.8, 139.2, 134.7, 124.3, 123.6, 122.7, 120.4, 111.3, 80.0, 55.9, 50.5, 47.4, 37.9, 37.0, 35.0, 31.3, 30.5, 27.6, 20.8, 19.4, 16.2. HRMS calcd 506.2526 (C29H3302N5.Na+), found 506.2525.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 4880 - 4898
[2]Patent: WO2014/153215,2014,A1 .Location in patent: Paragraph 00170

62
[ 41864-22-6 ]
[ 124-41-4 ]
[ 27298-97-1 ]
[ 1353776-47-2 ]

Yield	Reaction Conditions	Operation in experiment
		17.2 g (105 mmol) CDT are added to a mixture of 20.0 g (100 mmol) (Sj-1 -(4- bromophenyl)-ethylamine and 17.6 mL (125 mmol) TEA in 300 mL dichloromethane at 0C. Stirring is continued for 15 min at 5C. After that time, the solvent is removed in vacuo and taken up in 50 mL methanol. 33.4 mL (180 mmol) sodium methoxide in methanol (30%) are added and stirring is continued for 48 h at rt. After that time, the solvent is removed in vacuo, the residue is taken up in ethyl acetate and washed with sat. KHSO4-solution (2x) and water. The organic layer is dried over magnesium sulphate and the solvent is removed by evaporation. Ci0Hi2BrNO2 (M = 258.1 g/mol), ESI-MS: 258 [M+H]+ Rt (HPLC): 2.60 min (method B)

Reference： [1]Patent: WO2013/92976,2013,A1 .Location in patent: Page/Page column 72

63
[ 41864-22-6 ]
[ 27298-97-1 ]
[ 124-40-3 ]
[ 1353776-48-3 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: 17.2 g (105 mmol) CDT are added to a mixture of 20.0 g (100 mmol) (Sj-1 -(4- bromophenyl)-ethylamine and 17.6 mL (125 mmol) TEA in 300 mL dichloromethane at 0C. Stirring is continued for 15 min at 5C. After that time, the solvent is removed in vacuo and taken up in 50 mL methanol. 33.4 mL (180 mmol) sodium methoxide in methanol (30%) are added and stirring is continued for 48 h at rt. After that time, the solvent is removed in vacuo, the residue is taken up in ethyl acetate and washed with sat. KHSO4-solution (2x) and water. The organic layer is dried over magnesium sulphate and the solvent is removed by evaporation. Ci0Hi2BrNO2 (M = 258.1 g/mol), ESI-MS: 258 [M+H]+ Rt (HPLC): 2.60 min (method B)
		17.2 g (105 mmol) CDT are added to a mixture of 20.0 g (100 mmol) (S)-1 -(4- bromophenyl)-ethylamine and 17.6 ml_ (125 mmol) TEA in 300 ml_ DCM at 0 C. Stirring is continued for 2 h at 5 C. 13.5 g (300 mmol) dimethylamine are added and the mixture is allowed to warm to rt. DCM is added and the organic layer is washed with 1 N KHSO4 solution (2x) and water (1 x). The organic layer is dried over 5 magnesium sulphate and the solvent is removed by evaporation to yield the desired product. CnHi5BrN2O (M = 271 .2 g/mol), ESI-MS: 271/273 [M+H]+ Rt (HPLC): 1 .68 min (method C1 )
		Example II.1 (S)-3-[1-(4-Bromo-phenyl)-ethyl]-1,1-dimethyl-urea 17.2 g (105 mmol) CDT are added to a mixture of 20.0 g (100 mmol) (S)-1-(4-bromophenyl)-ethylamine and 17.6 mL (125 mmol) TEA in 300 mL DCM at 0 C. Stirring is continued for 2 h at 5 C. 13.5 g (300 mmol) dimethylamine are added and the mixture is allowed to warm to rt. DCM is added and the organic layer is washed with 1 N KHSO4 solution (2) and water (1). The organic layer is dried over magnesium sulphate and the solvent is removed by evaporation to yield the desired product. C11H15BrN2O (M=271.2 g/mol), ESI-MS: 271/273 [M+H]+ Rt (HPLC): 1.68 min (method C1)

Reference： [1]Patent: WO2013/92976,2013,A1 .Location in patent: Page/Page column 72
[2]Patent: WO2013/98373,2013,A1 .Location in patent: Page/Page column 71; 72
[3]Patent: US2013/172312,2013,A1 .Location in patent: Paragraph 0369; 0370; 0371; 0372

64
[ 41864-22-6 ]
[ 624-78-2 ]
[ 1444780-57-7 ]
[ 1444779-04-7 ]

Yield	Reaction Conditions	Operation in experiment
		To 36 mg (0.10 mmol) (S)-1 -{4-[4-(4-ethoxy-phenyl)-piperidin-1 -yl]-phenyl}- ethylamine hydrochloride (XII.1 ) in 1 .5 mL 1 ,4-dioxane are added 37 mu (0.25 mmol) DBU and 33 mg (0.20 mmol) CDT. The mixture is stirred for 5 min at rt. Subsequently 7.1 mg (0.12 mmol) ethyl-methyl-amine in 1 .0 mL 1 ,4-dioxane are added and stirring is continued for 12 h at rt. The solvent is removed under reduced pressure, the residue is taken up in DMF and purified by HPLC (Sunfire, narrow gradients, water (+0.1 % TFA) / methanol) to yield the desired product. C27H22N4O4 (M = 409.6 g/mol), ESI-MS: 410 [M+H]+ Rt (HPLC): 1 .36 min (method P)

Reference： [1]Patent: WO2013/92976,2013,A1 .Location in patent: Page/Page column 88; 89

65
[ 41864-22-6 ]
[ 212268-13-8 ]
[ 1364719-75-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	In acetonitrile; at 80℃; for 6h;	Example 13 To a solution of Compound 39 (795 mg, 6.25 mmol) in MeCN (70 ml) was added CDT (1.52 g, 9.38 mmol), and the reaction mixture was stirred at 80 C. for 6 hours. The reaction mixture was allowed to cool to room temperature, and the solvent was removed under reduced pressure, followed by the addition of 50 ml of chloroform. The mixture was stirred for 30 minutes, and a solid was filtered to obtain Compound 40 (738 mg, 77%) as a white solid. [0718] Compound 40; 1H-NMR (DMSO-d6) delta: 7.24 (dd, J=8.62, 2.53 Hz, 1.0H), 7.84 (t, J=2.28 Hz, 1.0H), 11.04 (br s, 1.0H), 11.40 (br s, 1.0H).

Reference： [1]Patent: US2013/184240,2013,A1 .Location in patent: Paragraph 0710; 0717; 0718

66
[ 41864-22-6 ]
[ 1594130-84-3 ]
[ 124-40-3 ]
[ 1594129-25-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In tetrahydrofuran; at 20℃;	To 35.2 mg (0.10 mmol) of amine XXII.3 in 1 mL dioxane are added 32.8 mg (0.20 mmol) CDT and 29.9 muL (0.20 mmol) DBU and the resulting mixture is stirred at r.t. for 5 min. Then 0.06 mL (0.20 mmol) of a dimethylamine solution in THF (c=2 mol/L) are added stirring is continued over night. The mixture is purified by HPLC (MeOH/H2O/TFA). [0570] C25H33N3O3(M=423.6 g/mol) [0571] ESI-MS: 424 [M+H]+ [0572] Rt (HPLC): 1.54 min (method R)
		General procedure: Method B) To 35.2 mg (0.10 mmol) of amine XXII.3 in 1 ml_ dioxane are added 32.8 mg (0.20 mmol) CDT and 29.9 muIota_ (0.20 mmol) DBU and the resulting mixture is stirred at r.t. for 5 min. Then 0.06 ml_ (0.20 mmol) of a dimethylamine solution in THF (c = 2 mol/L) are added stirring is continued over night. The mixture is purified by HPLC (MeOH/H2O/TFA). C25H33N3O3 (M= 423.6 g/mol) ESI-MS: 424 [M+H]+ Rt (HPLC): 1 .54 min (method R)

Reference： [1]Patent: US2014/100211,2014,A1 .Location in patent: Paragraph 0569-0572
[2]Patent: WO2014/56771,2014,A1 .Location in patent: Page/Page column 123

67
[ 41864-22-6 ]
[ 1594129-74-4 ]
[ 124-40-3 ]
[ 1594129-82-4 ]

Yield	Reaction Conditions	Operation in experiment
		To 2.00 g (5.31 mmol) of example IX and 1.86 mL (13.3 mmol) TEA in 40 mL DCM are added 914 mg (5.57 mmol) CDT and the resulting mixture is stirred at r.t. for 15 min. After that 716 mg (15.9 mmol) dimethylamine are added and stirring is continued over night. Finally the solvent is removed in vacuo and the crude product is purified by HPLC (MeOH/H2O/NH3). [0381] C23H29N3O4 (M=411.5 g/mol) [0382] ESI-MS: 412 [M+H]+ [0383] Rt (HPLC): 1.05 min (method C)
	With triethylamine; In dichloromethane; at 20℃;	Example XII (R -Benzyl 3-(4-((S)-1 -(3,3-dimethylureido)ethyl)phenoxy)pyrrolidine-1 -carboxylate To 2.00 g (5.31 mmol) of example IX and 1 .86 mL (13.3 mmol) TEA in 40 mL DCM are added 914 mg (5.57 mmol) CDT and the resulting mixture is stirred at r.t. for 15 min. After that 716 mg (15.9 mmol) dimethylamine are added and stirring is continued over night. Finally the solvent is removed in vacuo and the crude product is purified by HPLC (MeOH/H2O/NH3). C23H29N3O4 (M= 41 1 .5 g/mol) ESI-MS: 412 [M+H]+ Rt (HPLC): 1 .05 min (method C)
		To 2.00 g (5.31 mmol) of example XIV and 1.86 mL (13.3 mmol) TEA in 40 mL DCM are added 0.91 g (5.57 mmol) CDT and the resulting mixture is stirred at r.t. for 15 min. Then 0.72 g (15.9 mmol) dimethylamine are added and stirring is continued over night. The solvent is removed in vacuo and the crude product is purified by HPLC (MeOH/H20/NH3). C23H29N304 (M= 411.5 g/mol) ESI-MS: 412 [M+H]+ Rt (HPLC): 1.05 min (metriod C)

Reference： [1]Patent: US2014/100211,2014,A1 .Location in patent: Paragraph 0380-0383
[2]Patent: WO2014/56771,2014,A1 .Location in patent: Page/Page column 76; 77
[3]Patent: WO2014/114578,2014,A1 .Location in patent: Page/Page column 89

68
[ 41864-22-6 ]
[ 1594130-84-3 ]
[ 75-04-7 ]
[ 1594129-26-6 ]

Yield	Reaction Conditions	Operation in experiment
		The following compounds are prepared analogously to example 3.1 . For the examples 3.2- 3.6 TEA is used as base and DCM as solvent. For example 3.7 CDT is reacted with 3- aminoisoxazole in presence of DBU for 15 min before the amine XXI.3 is added. For the examples 3.8-3.1 1 the appropriate isocyanate is used and the reaction mixture is stirred at r.t. over night. Method B) To 35.2 mg (0.10 mmol) of amine XXII.3 in 1 ml_ dioxane are added 32.8 mg (0.20 mmol) CDT and 29.9 muIota_ (0.20 mmol) DBU and the resulting mixture is stirred at r.t. for 5 min. Then 0.06 ml_ (0.20 mmol) of a dimethylamine solution in THF (c = 2 mol/L) are added stirring is continued over night. The mixture is purified by HPLC (MeOH/H2O/TFA). C25H33N3O3 (M= 423.6 g/mol) ESI-MS: 424 [M+H]+ Rt (HPLC): 1 .54 min (method R)

Reference： [1]Patent: WO2014/56771,2014,A1 .Location in patent: Page/Page column 123

69
[ 41864-22-6 ]
[ 162401-62-9 ]
[ 1601300-21-3 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 2h;	Preparation of ( 3-(cvclopropylmethoxy)-4-(difluoromethoxy)-phen yl)(1H-1, 2, 4-triazol- 1 - vD-methanone (IVb) 15 mL of DMSO were added to 5.0 g of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)- benzoic acid (II) and 3.81 g of CDT (1 .2 eq). The mixture was stirred for 2 h at room temperature. A solution of (3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)(1 H- 1 ,2,4-triazol-1 -yl)-methanone (IVb) in DMSO was thus obtained.

Reference： [1]Patent: WO2014/60464,2014,A1 .Location in patent: Page/Page column 18

70
[ 41864-22-6 ]
[ 1750-42-1 ]
[ 1620690-90-5 ]
[ 1620688-42-7 ]

Yield	Reaction Conditions	Operation in experiment
		To 45.0 mg (0.12 mmol) of amine XXII.1 and 39.0 muIota_ (0.23 mmol) DIPEA in 3 ml_ THF are added 38.8 mg (0.23 mmol) CDT and the resulting mixture is stirred at r.t for 15 min. Then 19.0 mg (0.23 mmol) of 3-aminoisoxazole are added and the resulting mixture is stirred at r.t over night. Afterwards some DMF is added and the mixture is directly purified by HPLC (MeOH/H20/NH4OH).

Reference： [1]Patent: WO2014/114578,2014,A1 .Location in patent: Page/Page column 151

71
[ 41864-22-6 ]
[ 69038-76-2 ]
[ 84712-08-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In tetrahydrofuran; at 20℃;Reflux;	Step 1: Synthesis of Intermediate 1-27.1 4-bromo-l-n-methylbenzene-l,2-diamine (4.42g, 21.98 mmol), N,N'-carbonyl-di-(l ,2,3-triazole (4.178g, 24.18 mmol), and TEA (9.184 mL, 65.95 mmol) in THF (70mL) are stirred at r.t. for 30min, then heated under reflux overnight. The reaction mixture is concentrated, triturated with water, filtered off and dried. The residue is triturated again with DIPE and filtered off. Yield 88%

Reference： [1]Patent: WO2014/140075,2014,A1 .Location in patent: Page/Page column 232

72
[ 41864-22-6 ]
N-[4-(2-fluorophenyl)-2-methyl-1H-imidazol-1-yl]imidoformamide [ No CAS ]
5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	In tetrahydrofuran; at 55℃; for 5h;	Compound C4 (8.16 g, 37.4 mmol) in tetrahydrofuran (187 mL) was heated to 55 C., treated with 1,1'-carbonyldi(1,2,4-triazole) (7.36 g, 44.8 mmol) and stirred at 55 C. for 5 hours. The reaction was then cooled and stirred for an additional 3 days at room temperature. Removal of solvent in vacuo gave a solid, which was stirred with water (200 mL) for 1 hour and filtered to afford a pale brown powder. This was stirred in heptane (?35 mL) and ethyl acetate (?35 mL) for 24 hours and filtered, providing the product as an off-white powder (5.08 g). The aqueous filtrate was extracted once with ethyl acetate; this organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from heptane/ethyl acetate to provide additional product as a white powder. Total yield: 5.33 g, 21.8 mmol, 58%. LCMS m/z 245.0 [M+H]+. 1H NMR (500 MHz, CD3OD) delta 7.73 (s, 1H), 7.62 (ddd, J=7.6, 7.3, 1.7 Hz, 1H), 7.40-7.46 (m, 1H), 7.24 (ddd, J=7.6, 7.6, 1.0 Hz, 1H), 7.18 (br dd, J=10, 8.5 Hz, 1H), 2.63 (s, 3H).

Reference： [1]Patent: US2014/329820,2014,A1 .Location in patent: Paragraph 0144

73
[ 41864-22-6 ]
[ 337915-79-4 ]
[ 84712-08-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In tetrahydrofuran; at 20℃; for 0.5h;Reflux;	4-bromo-1-n-methylbenzene-1,2-diamine (4.42 g, 21.98 mmol), N,N?-carbonyl-di-(1,2,3-triazole (4.178 g, 24.18 mmol), and TEA (9.184 mL, 65.95 mmol) in THF (70 mL) are stirred at r.t. for 30 min, then heated under reflux overnight. The reaction mixture is concentrated, triturated with water, filtered off and dried. The residue is triturated again with DIPE and filtered off. Yield 88%.

Reference： [1]Patent: US2014/275025,2014,A1 .Location in patent: Paragraph 0628; 0629

74
[ 41864-22-6 ]
(S)-1-(4-((R)-1-(6-(cyclopropylmethoxy)-5-fluoropyrimidin-4-yl)pyrrolidin-3-yloxy)phenyl)ethanamine [ No CAS ]
[ 124-40-3 ]
C₂₃H₃₀FN₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To 0.17 mmol of the appropriate 1-phenethylamine and 0.42 mmol TEA in 3 mL DCM are added to 0.19 mmol CDT and stirred for at r.t. 10 min. Then 0.51 mmol of the other amine are added and the resulting mixture is stirred at r.t over night. Afterwards some DMF is added and the mixture is directly purified by HPLC (ACN/H2O/TFA).C22H30F2N6O2 (M=448.5 g/mol)ESI-MS: 449 [M+H]+Rt (HPLC): 0.97 min (method E)

Reference： [1]Patent: US2014/315882,2014,A1 .Location in patent: Paragraph 0493; 0494; 0495; 0496; 0500; 0501

75
[ 41864-22-6 ]
[ 1750-42-1 ]
(S)-1-(4-((R)-1-(6-(cyclopropylmethoxy)-5-fluoropyrimidin-4-yl)pyrrolidin-3-yloxy)phenyl)ethanamine [ No CAS ]
C₂₄H₂₇FN₆O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To 0.34 mmol of the appropriate heteroaniline in 3 mL dioxane are added 0.34 mmol CDT and 0.34 mmol DBU and the resulting mixture is stirred at r.t. for 1 h. Then 0.17 mmol of the appropriate 1-phenethylamine are added and stirring is continued over night. The mixture is purified by HPLC (ACN/H2O/NH3).

Reference： [1]Patent: US2014/315882,2014,A1 .Location in patent: Paragraph 0492; 0497; 0500; 0501

76
[ 41864-22-6 ]
C₁₉H₂₅F₂N₅O*ClH [ No CAS ]
[ 124-40-3 ]
3-((S)-1-(4-((R)-1-(2-((2,2-difluoroethyl)(methyl)amino)pyrimidin-4-yl)pyrrolidin-3-yloxy)phenyl)ethyl)-1,1-dimethylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To 0.17 mmol of the appropriate 1-phenethylamine and 0.42 mmol TEA in 3 mL DCM are added to 0.19 mmol CDT and stirred for at r.t. 10 min. Then 0.51 mmol of the other amine are added and the resulting mixture is stirred at r.t over night. Afterwards some DMF is added and the mixture is directly purified by HPLC (ACN/H2O/TFA).C22H30F2N6O2 (M=448.5 g/mol)ESI-MS: 449 [M+H]+Rt (HPLC): 0.97 min (method E)

Reference： [1]Patent: US2014/315882,2014,A1 .Location in patent: Paragraph 0493; 0494; 0495; 0496

77
[ 41864-22-6 ]
C₂₀H₂₇N₅O₂*ClH [ No CAS ]
[ 75-04-7 ]
C₂₃H₃₂N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To 0.17 mmol of the appropriate 1-phenethylamine and 0.42 mmol TEA in 3 mL DCM are added to 0.19 mmol CDT and stirred for at r.t. 10 min. Then 0.51 mmol of the other amine are added and the resulting mixture is stirred at r.t over night. Afterwards some DMF is added and the mixture is directly purified by HPLC (ACN/H2O/TFA).C22H30F2N6O2 (M=448.5 g/mol)ESI-MS: 449 [M+H]+Rt (HPLC): 0.97 min (method E)

Reference： [1]Patent: US2014/315882,2014,A1 .Location in patent: Paragraph 0493; 0494; 0495; 0496; 0499; 0500; 0501

78
[ 41864-22-6 ]
[ 1446818-43-4 ]
(4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidin-1-yl)(1H-1,2,4-triazol-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran;	Compound 12a (775 mg, 1.58 mmol) was hydrogenated as previously described 27 to yield 560 mg (100%) of bis(benzo[d][1,3]dioxol-5-yl)(piperidin-4-yl)methanol (15). 1H NMR (CDCl3/DMSO-d6, 500 MHz): delta 1.63 (m, 2H), 1.74 (m, 2H), 2.88 (m, 2H), 3.59 (m, 2H), 3.92 (br s, 1H), 5.10 (br s, 1H), 5.91 (s, 4H), 6.72 (d, J = 7.9 Hz, 2H), 6.95 (d, J = 7.9 Hz, 2H), 6.97 (s, 2H). Portion of the resulting alcohol (100 mg, 0.28 mmol) was dissolved in THF (5 mL) and 1,1'-carbonyl-di-(1,2,4-triazole) (CDT) was added as one portion, followed by DIPEA. After stirring for several days, reaction was not completed. Additional portion (40 mg) of CDT was added with DMF (5 ml) and stirred for 6 h after which solution turned clear. Solvents were evaporated. CH2Cl2 was added and solution was washed with water (3 * 50 mL). Crude product was purified by flash chromatography on silica gel, eluting with EtOAc/petroleum ether 1:1 to give 12c as a white foamy product (50 mg, yield 39%). 1H NMR (CDCl3, 500 MHz): delta 1.48-1.57 (m, 2H), 1.67-1.70 (m, 2H), 2.01 (s, 1H), 2.55 (tt, J = 3.3, 11.9 Hz, 1H), 3.03 (br t, J = 11.3 Hz, 2H), 4.60 (br s, 2H), 5.93 (s, 4H), 6.75 (dd, J = 7.6, 1.1 Hz, 2H), 6.92 (dd, J = 7.6, 1.5 Hz), 6.92 (s, 2H), 7.95 (s, 1H), 8.74 (s, 1H). 13C NMR (CDCl3, 120 MHz) delta 151.9, 147.8, 146.5, 146.4, 144.2, 139.5, 118.8, 107.9, 106.7, 101.1, 79.3, 44.4, 38.4, 21.1.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6694 - 6705

79
[ 41864-22-6 ]
C₁₅H₂₀O₄ [ No CAS ]
JVM 2-16 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In dichloromethane; at 20℃; for 0.166667h;	To a stirred solution of MMB (50 mg, 0.18 mmol) in dichloromethane, carbonylditriazole (46.5 mg, 0.28 mmol) was added at ambient temperature. The reaction mixture was stirred at ambient temperature for 10 minutes. Upon completion, water was added and the mixture extracted with dichloromethane, dried over Na2SO4 and concentrated under reduced pressure to afford pure product JVM 2-16 as white solid (yield: 85%). 1H NMR (CDCl3, 400 MHz): delta 8.83 (s, 1H), 8.06 (s, 1H), 6.26 (d, J=3.6 Hz, 1H), 5.92 (t, J=8.4 Hz, 1H), 5.55 (d, J=3.2 Hz, 1H), 5.08 (d, J=11.6 Hz, 1H), 4.90 (d, J=12 Hz, 1H), 3.89 (t, J=9.6 Hz, 1H), 2.91 (m, 2H), 2.56-2.17 (m, 6H), 1.84-1.72 (m, 1H), 1.55 (s, 3H), 1.17 (t, J=12.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz): delta 169.2, 154.0, 147.7, 145.8, 138.6, 134.4, 133.3, 120.6, 80.9, 71.5, 63.3, 59.9, 42.7, 36.5, 25.7, 24.3, 24.1, 18.1 ppm.

Reference： [1]Patent: US2015/133444,2015,A1 .Location in patent: Paragraph 0214-0216

80
[ 41864-22-6 ]
[ 29608-05-7 ]
[ 15996-82-4 ]
1-(4'-chloro-biphenyl-4-ylmethyl)-3-(4-piperidin-1-ylmethyl-phenyl)-urea [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3270 - 3274

81
[ 41864-22-6 ]
5-(7-amino-3-methyl-benzimidazol-5-yl)oxy-4-methyl-pyridine-2-carbonitrile [ No CAS ]
C₁₈H₁₄N₈O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 50℃; for 1h;	General procedure: 2.3.3. Method M: General method of synthesis of urea 1003081 Carbonylditriazol (1.5 eq.) is added to a mixture of Cpd 28 (1.0 eq.) and pyridine (5 eq;) in DCM. The mixture is then stirred at 50C for lh. Without any further treatment the required amine RaNH2 is added to the solution at 50C and allowed to stir for another lh. After completion of the reaction by UPLC, the reaction mixture is cooled to room temperature and diluted with DCM, and ehe mixture is then partitioned in water. The two phases are separated and the organic layer is washed with 0.25 M HC1 solution, sodium bicarbonate solution, dried and concentrated. The residue can be purified by silica chromatography, by preparative HPLC or by precipitation using the appropriate solvent mixture2.3.4. Illustrative example of Method M: synthesis of 1-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1- methyl-benzimidazol-4-yl]-3-isopropyl-urea (Cpd 33)1003091 Carbonylditriazol (1.07 mmol) was added to a mixture of Cpd 28 (0.71 mmol) and pyridine (3.55 mmol) in DCM (3 mL) and the resulting mixture was stirred at 50C. A precipitate formed after 2 mm and the mixture was further stirred for lh. Methyl amine (2M solution in THF) (2.84 mmol) was then added to the solution at 50C and allowed to stir for another lh. After completion of the reaction by UPLC, the reaction mixture was cooled to room temperature and was diluted with DCM and partitioned in water. The two phases were separated and the organic layer was washed with 0.25 M HC1 solution, sodium bicarbonate solution, dried and concentrated. The residue the used without any further purification.

Reference： [1]Patent: WO2015/110378,2015,A1 .Location in patent: Paragraph 00308; 00309

82
[ 41864-22-6 ]
UDP tributylamine salt [ No CAS ]
UDP-triazolide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With diisopropyl-carbodiimide; In N,N-dimethyl acetamide; water; at 20℃; for 1h;	Dimethylacetamide (2.0 ml) was added to an aqueous solution of 0.37 M UDP-tributylamine salt (1.6 ml, 0.6mmol), and the mixture was azeotropically dehydrated four times. The resulting residue was dissolved in dimethylacetamide(2.0 ml), and 1,1?- carbonyldi-(1,2,4-triazole) (0.25 g, 1.5 mmol) was added thereto, then the mixed solution wasstirred at room temperature for 1 hour. Water (0.2 ml) was added to the reaction solution under ice cooling, and further,a 0.5 M aqueous hydrochloric acid solution was added to have pH 7.4. The mixture was concentrated under reducedpressure to prepare a UDP-triazolide solution

Reference： [1]Patent: EP2940030,2015,A1 .Location in patent: Paragraph 0058

83
[ 41864-22-6 ]
(S)-1-[4-(6-cyclopropylmethoxy-4-fluoro-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-phenyl]ethyl amine [ No CAS ]
[ 124-40-3 ]
C₂₅H₃₂FN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To 40 mg (0.10 mmol) (S)-1-[4-(6-cyclopropylmethoxy-4-fluoro-3,4-dihydro-1H- isoquinolin-2-ylmethyl)-phenyl]-ethylamine hydrochloride (example XLVIII. 1) in 1 .0 mL DCM are added 30 iL (0.21 mmol) TEA and 18 mg (0.11 mmol) CDT. The resulting mixture is stirred at r.t. for 1 h. Then 61 iL (0.12 mmol) dimethylamine solution (2.0 M in THF) are added and the mixture is stirred at 3000 for 4 h. After that time the reaction mixture is purified by HPLC.C25H32FN302 (M = 425.5 g/mol)ESI-MS: 426 [M+H]R (HPLC): 0.92 mm (method E)

Reference： [1]Patent: WO2016/41845,2016,A1 .Location in patent: Page/Page column 144; 145

84
[ 41864-22-6 ]
[ 2022-85-7 ]
[ 71-41-0 ]
[ 27821-07-4 ]
[ 154361-50-9 ]

Yield	Reaction Conditions	Operation in experiment
73.5%		Take 0.2m0l 5-fluorocytosine and 68g potassium carbonate, stirring to 300mL dichloromethane, stirring slowlyDropping O.Smol trimethylchlorosilane, heating reflux lh TLC detection reaction is complete, vacuum concentration, in a concentrate A, directly withIn the next step reaction,0.18 mol BF3 · OEt2 was dissolved in 300 mL dichloromethane and 0.2 mol was added with stirring1,2,3-triacetoxy-5-deoxy-D-ribose and concentrate A were stirred at 25 C under nitrogen,Should be 7h. TLC detection reaction is complete, concentrated under reduced pressure, obtained concentrate B, used directly in the next step should.The concentrate B was dissolved in 300 mL of methylene chloride, and 0.24 mL of N, N'-carbonyldi (1,2,4-triazoOxazole) and stir at 25 C. After completion of the reaction with TLC, the reaction solution C was obtained and used in the next stet. 0 .24 ml of n-pentanol was added to the reaction solution C and stirred at 25 C. The reaction was complete by TLC and concentrated under reduced pressure.The concentrate D was obtained and used directly in the next reaction.Concentrate D was dissolved in 200 mL of methanol and a 6.5 mol / L aqueous solution of sodium hydroxide was slowly added dropwise at 0 C with stirring,After the reaction was continued, the pH was adjusted to 6 with concentrated hydrochloric acid, the methanol was removed under reduced pressure, and the mixture was extracted with methyl tert-butyl etherThe organic layer was extracted twice with methyl tert-butyl ether, and the organic layers were combined, washed with saturated brine, washed with water, and dried over anhydrous sulfuric acidSodium dried, filtered, dropping n-heptane, precipitation products, filtration, vacuum drying at 40 C for 6 hours, that was capecitabine pure product (yield73.5 %.

Reference： [1]Patent: CN105646625,2016,A .Location in patent: Paragraph 0036; 0038; 0040; 0042; 0044

85
[ 41864-22-6 ]
C₁₅H₂₀O₄ [ No CAS ]
C₁₈H₂₁N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In dichloromethane; at 20℃; for 1h;	To a stirred solution of MMB (50 mg, 0.18 mmol) in dichloromethane,was added carbonyl-di-(1,2,4-triazole) (46.5 mg,0.28 mmol) at room temperature and the reaction mixture wasstirred for 1 h. After completion of the reaction (monitored byTLC), water (5 mL) was added and the mixture was extracted withdichloromethane (2 5 mL). The organic layer was washed withwater (3 5 mL), dried over anhydrous Na2SO4 and concentratedunder reduced pressure to afford pure product 7 as a white solid(yield 93%).1H NMR (CDCl3, 400 MHz): d 8.83 (s, 1H), 8.06 (s, 1H), 6.26 (d,J = 3.6 Hz, 1H), 5.92 (t, J = 8.4 Hz, 1H), 5.55 (d, J = 3.2 Hz, 1H), 5.08(d, J = 11.6 Hz, 1H), 4.90 (d, J = 12 Hz, 1H), 3.86 (t, J = 9.6 Hz, 1H),2.91-2.83 (m, 2H), 2.56-2.17 (m, 6H), 1.84-1.72 (m, 1H), 1.55 (s,3H), 1.14 (t, J = 12.4 Hz, 1H) ppm. 13C NMR (CDCl3, 100 MHz): d169.2, 154.0, 147.7, 145.8, 138.6, 134.4, 133.3, 120.6, 80.9, 71.5,63.3, 59.9, 42.7, 36.5, 25.7, 24.3, 24.1, 18.1 ppm. MS (ESI), m/z:382.10 (M+Na)+.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 1235 - 1241

86
[ 41864-22-6 ]
[ 4734-09-2 ]
C₁₄H₁₈N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 2-methyltetrahydrofuran at 60℃; for 2h; Inert atmosphere;	6 Example 6 1 -(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)- 1 -( 1 -methylpiperidin-4-yl)urea of formula I To a suspension of l, -carbonyldi(l,2,4-triazole) (1.17 g; 6.14 mmol) in 2- methyltetrahydrofuran (10 ml) 4-isobutoxybenzylamine (VII) (1.0 g; 5.58 mmol) was added by dripping under an inert atmosphere at 60°C during 2 minutes, the mixture was further stirred for 2 h at 60°C. Then, N-(4-fluorobenzyl)-l-methylpiperidine-4-amine (II) (1.36 g; 6.14 mmol) was added to the solution by dripping during 2 minutes and the mixture was further stirred for 5 h at 60°C. The reaction mixture was washed with 3.5% hydrochloric acid (2 x 10 ml) and subsequently with water (1 x 10 ml). The organic fraction was evaporated until dry, the evaporation product was dissolved in isopropyl alcohol (10 ml) and a solution of p-toluenesulfonic hydrate (1.06 g; 5.58 mmol) in isopropyl alcohol (55 ml) was added to the solution obtained this way in a hot state. The mixture was slowly left to crystallize to the lab. t, the separated crystalline fraction was removed by filtration and washed with ethyl methyl ketone. The amount of 2.17 g of the crystalline product was obtained (65%).

Reference： [1]Current Patent Assignee: ADVENT INTERNATIONAL CORPORATION - WO2017/54786, 2017, A1 Location in patent: Page/Page column 7

87
[ 41864-22-6 ]
[ 594-58-1 ]
1-(2-chloroisobutyryl)-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.3%	In tetrahydrofuran; at 50℃; for 2h;	1.64g (10 mmol) of N, N'-carbonylbis (1,2,4-triazole) was mixed with 16.4 ml of tetrahydrofuran, 1.23 g (10 mmol) of 2-chloroisobutyric acid was added, and the reaction was stirred at 50 C for 2 hours, cool, and concentrate under reduced pressure to dryness. 10 ml of methyl tert-butyl ether was added, stirred for 30 minutes, filtered and the cake was dried to obtain 1.55 g of product, yield 89.3%.

Reference： [1]Patent: CN106866558,2017,A .Location in patent: Paragraph 0071; 0072

88
[ 41864-22-6 ]
dicyanocobinamide [ No CAS ]
[ 14044-63-4 ]
C₅₅H₇₇CoN₁₄O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0042] Referring to FIG. 20, another exemplary conjugate 10 were formed using Ex-4 as peptide drug 14 and evaluated for the mitigation of side effects. In this Example, a cobinamide (Cbi) was synthesized and conjugated to Ex-4 as seen in FIG. 20. Cbi-Ex4 was synthesized through Huisgen/Sharpless 'Click' Chemistry. Cu(I) (0.01 mmol) and Tris[(l- benzyl-lH-l,2,3-triazol-4-yl)methyl]amine (0.015 mmol) were dissolved in 0.5 mL (0064) DMF/H20 (4: 1 v/v). Once color change occurred, the peptide exendin-4 and a previously synthesized cobinamide-alkyne conjugate was dissolved and allowed to stir at room temperature overnight.

Reference： [1]Patent: WO2017/181007,2017,A1 .Location in patent: Paragraph 0025; 0042

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	41864-22-6	MDL No. :	MFCD00043399
Formula :	C₅H₄N₆O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YHNUDLCUIKMNSN-UHFFFAOYSA-N
M.W :	164.12	Pubchem ID :	4393961
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	36.24
TPSA :	78.49 Å²

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) :	-7.26 cm/s

Log Po/w (iLOGP) :	0.6
Log Po/w (XLOGP3) :	0.06
Log Po/w (WLOGP) :	-0.61
Log Po/w (MLOGP) :	-0.35
Log Po/w (SILICOS-IT) :	-1.4
Consensus Log Po/w :	-0.34

[ CAS No. 41864-22-6 ] {[proInfo.proName]}

Quality Control of [ 41864-22-6 ]

Related Doc. of [ 41864-22-6 ]

Product Details of [ 41864-22-6 ]

Calculated chemistry of [ 41864-22-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 41864-22-6 ]

Application In Synthesis of [ 41864-22-6 ]

[ 41864-22-6 ] Synthesis Path-Upstream 1~1

[ 41864-22-6 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-1.38
Solubility :	6.84 mg/ml ; 0.0417 mol/l
Class :	Very soluble
Log S (Ali) :	-1.26
Solubility :	8.98 mg/ml ; 0.0547 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.13
Solubility :	121.0 mg/ml ; 0.735 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.16

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

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Code	Phrase
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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.
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P363	Wash contaminated clothing before reuse.
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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
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P401
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Disposal
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P501	Dispose of contents/container to ...
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