[ CAS No. 219511-71-4 ] {[proInfo.proName]}

Name: 219511-71-4|Boc-Guanidine|97%
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Quality Control of [ 219511-71-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 219511-71-4 ]

Product Details of [ 219511-71-4 ]

CAS No. :	219511-71-4	MDL No. :	MFCD07369706
Formula :	C₆H₁₃N₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UMOZLQVSOVNSCA-UHFFFAOYSA-N
M.W :	159.19	Pubchem ID :	11378649
Synonyms :

Calculated chemistry of [ 219511-71-4 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.67
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	41.77
TPSA :	88.2 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) :	-6.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.01
Log Po/w (XLOGP3) :	0.78
Log Po/w (WLOGP) :	0.4
Log Po/w (MLOGP) :	0.23
Log Po/w (SILICOS-IT) :	-0.88
Consensus Log Po/w :	0.31

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.05
Solubility :	14.0 mg/ml ; 0.0882 mol/l
Class :	Very soluble
Log S (Ali) :	-2.21
Solubility :	0.975 mg/ml ; 0.00613 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-0.55
Solubility :	44.5 mg/ml ; 0.279 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.75

Safety of [ 219511-71-4 ]

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

Application In Synthesis of [ 219511-71-4 ]

* 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 [ 219511-71-4 ]
Downstream synthetic route of [ 219511-71-4 ]

[ 219511-71-4 ] Synthesis Path-Upstream 1~9

1
[ 219511-71-4 ]
[ 207857-15-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With trifluoromethylsulfonic anhydride; triethylamine In dichloromethane	Example 7 N'-Di-Boc-N"-Trifluoromethanesulfonyl-Guanidine A solution of N-,N'-di-Boc-guanidine (0.52 g, 2.0 mmol) and triethyl amine (0.29 ml) in anhydrous dichloromethane (10 ml) is cooled to -78° C. under an atmosphere of argon. Triflic anhydride (0.35 ml, 2.1 mmol) is added dropwise at a rate such that reaction temperature does not exceed -65° C. After the addition is completed, the mixture is allowed to warm to room temperature within 4 h. The solution is transferred to a separation funnel, washed with 2M sodium bisulfate and water and dried with anhydrous sodium sulfate. After filtering and removal of the solvent under reduced pressure the crude product is purified by flash chromatography on silica gel (eluent: dichloromethane). N-N'-Di-Boc-N'"-trifluoromethanesulfonyl-guanidine (686 mg, 88percent) is obtained as pale yellow crystals. The product can be further purified by recrystallization from hexanes: mp: 115° C.; ¹ H NMR (360 MHz, DMSO-d₆) δ 11.45 (br s, 2H), 1.45 (s, 18H). FAB-MS m/e (relative intensity) 414 (16, M+Na⁺), 392 (13, M+H⁺), 336 (43), 280 (100), 236 (9); Anal. Calc. for C, 36.83percent; H, 5.15percent;.N, 10.74percent; F, 14.56percent; S, 8.19percent; Found: C, 36.93percent; H, 5.21percent;.N, 10.66percent; F, 14.80percent; S, 8.33percent.

Reference： [1] Patent: US6072075, 2000, A,

2
[ 24424-99-5 ]
[ 50-01-1 ]
[ 219511-71-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: With sodium hydroxide In water at 0℃; for 0.166667 h; Stage #2: at 0 - 27℃; for 15 h;	a) BOC-guanidine BOC-guanidine was synthesised in accordance with Ando et al., Tetrahedron (2010), 66(32), 6224-6237: 22.93 g (0.24 mol) of guanidinium chloride are added to the solution of 19.2 g (0.48 mol) of sodium hydroxide pellets in 50 ml of water at 0° C. The solution is left to stir for 10 min., a solution of 13.1 g (60 mmol) of di-tert-butyl dicarbonate in 150 ml of acetone is then added in one portion at 0° C., and the reaction mixture is then left to stir at room temperature for 15 hours. The acetone is subsequently stripped off in vacuo, and the aqueous mixture is extracted twice with 50 ml of ethyl acetate. The combined organic phases are washed with 50 ml of saturated sodium chloride solution and dried over sodium sulfate. After the solvent has been stripped off, the residue is recrystallised from ethyl acetate/n-heptane, giving 8.7 g (91percent) of BOC-guanidine as white crystals. EI−MS (M+): 159

Reference： [1] European Journal of Organic Chemistry, 2008, # 2, p. 324 - 329
[2] Patent: US2015/361037, 2015, A1, . Location in patent: Paragraph 0232; 0233
[3] Tetrahedron Letters, 2007, vol. 48, # 39, p. 6996 - 6999
[4] Organic and Biomolecular Chemistry, 2012, vol. 10, # 25, p. 4899 - 4906
[5] Chemical Communications, 2008, # 3, p. 344 - 346
[6] Angewandte Chemie, International Edition, 2009, vol. 48, # 36, p. 6722 - 6725[7] Angewandte Chemie, 2009, vol. 121, # 36, p. 6850 - 6853
[8] Chemistry - A European Journal, 2011, vol. 17, # 51, p. 14508 - 14517
[9] Supramolecular Chemistry, 2011, vol. 23, # 6, p. 470 - 479
[10] Patent: WO2009/141386, 2009, A1, . Location in patent: Page/Page column 176

3
[ 24424-99-5 ]
[ 124-46-9 ]
[ 219511-71-4 ]

Reference： [1] Organic Letters, 2004, vol. 6, # 22, p. 3933 - 3936

4
[ 123-91-1 ]
[ 24424-99-5 ]
[ 50-01-1 ]
[ 219511-71-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium hydroxide In water	Example 6 N-,N'-Di-Boc-Guanidine 1,4-Dioxane (50 ml) is added to a solution of guanidine hydrochloride (2.39 g, 25 mmol) and sodium hydroxide (4.0 g, 0.1 mol) in water (25 ml) and the resulting mixture is cooled to 0° C. Di-tert-butyl-pyrocarbonate(12.0 g, 55 mmol) is added in one portion while stirring. The reaction mixture is allowed to warm to room temperature within 2 h. After stirring for 20 h the mixture is concentrated in vacuo to one third of its original volume. The resulting suspension is diluted with water (50 ml) and extracted three times with ethyl acetate (50 ml each). The combined extracts are washed with 10percent citric acid, water and brine and dried with magnesium sulfate. After filtering and removal of the solvent under reduced pressure the crude product is purified by flash chromatography on silica gel (eluent: dichloromethane-methanol 97:3). N-,N'-di-Boc-guanidine (3.84 g, 59percent) is obtained as a colorless powder: mp: 144° C.; ¹ H NMR (360 MHz, DMSO-d₆) δ 10.42 (br s, 1H), 8.47 (br s, 2H), 1.39 (s, 18H); FAB-MS m/e (relative intensity) 260 (50; M+H⁺), 204 (48), 148 (100); Anal. Calc. for: C, 50.95percent; H, 8.16percent;.N, 16.21percent; Found: C, 50.83percent; H, 8.04percent;.N, 16.26percent.

Reference： [1] Patent: US6072075, 2000, A,

5
[ 24424-99-5 ]
[ 219511-71-4 ]

Reference： [1] Patent: WO2014/70978, 2014, A1, . Location in patent: Page/Page column 52

6
[ 24424-99-5 ]
[ 50-01-1 ]
[ 332882-82-3 ]
[ 219511-71-4 ]

Reference： [1] Patent: US2010/4450, 2010, A1, . Location in patent: Page/Page column 16

7
[ 332882-82-3 ]
[ 219511-71-4 ]

Reference： [1] Patent: US2010/4450, 2010, A1, . Location in patent: Page/Page column 16
[2] Patent: WO2006/123020, 2006, A1, . Location in patent: Page/Page column 87-88

8
[ 24424-99-5 ]
[ 50-01-1 ]
[ 332882-82-3 ]
[ 219511-71-4 ]
[ 216584-22-4 ]

Reference： [1] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8432 - 8439
[2] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8432 - 8439

9
[ 24424-99-5 ]
[ 113-00-8 ]
[ 219511-71-4 ]

Reference： [1] Journal of the American Chemical Society, 2014, vol. 136, # 43, p. 15403 - 15413

[ 219511-71-4 ] Synthesis Path-Downstream 1~88

1
[ 66531-21-3 ]
[ 219511-71-4 ]
(cis)-2-amino-1,3a,5,7-tetrahydroimidazo[4,5-b]pyridine-4-carboxylic acid 2,2,2-trichloroethyl ester hydrochloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

2
[ 56475-87-7 ]
[ 219511-71-4 ]
5-[3-(methoxycarbonylamino)propyl]-1H-imidazol-2-ylammonium chloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

3
[ 131667-57-7 ]
[ 219511-71-4 ]
3a,4,5,6,7,7a-hexahydro-1H-imidazo[4,5-b]pyridin-2-ylamine dihydrochloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

4
[ 81097-36-1 ]
[ 219511-71-4 ]
5-[3-(4-methylbenzenesulfonylamino)propyl]-1H-imidazol-2-ylammonium chloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

5
[ 79328-86-2 ]
[ 219511-71-4 ]
(cis)-2-amino-1,3a,5,7-tetrahydroimidazo[4,5-b]pyridine-4-carboxylic acid phenyl ester hydrochloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

6
[ 68471-58-9 ]
[ 219511-71-4 ]
5-(3-aminopropyl)-2-amino-1H-imidazole dihydrochloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

7
[ 68471-58-9 ]
[ 219511-71-4 ]
5-[3-(benzyloxycarbonylamino)propyl]-1H-imidazol-2-ylammonium chloride [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 8208 - 8211

8
[ 790664-98-1 ]
[ 219511-71-4 ]
2,3-dibromo-8H,10H-pyrrolo[1',2':3,4]imidazo[1,2-a]pyridin-10-one [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 2961 - 2964

9
[ 790664-98-1 ]
[ 219511-71-4 ]
4-(1H-pyrrol-2-ylcarbonyl)-3a,4,5,7a-tetrahydro-1H-imidazo[4,5-b]pyridine-2-amine [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 2961 - 2964

10
[ 790664-98-1 ]
[ 219511-71-4 ]
tert-butyl-2-amino-4-(1H-pyrrole-2-carbonyl)-3a,4,5,7a-tetrahydro-1H-imidazo[4,5-b]-pyridine-1-carboxylate [ No CAS ]
tert-butyl-[4-(1H-pyrrole-2-carbonyl)-3a,4,5,7a-tetrahydro-1H-imidazo[4,5-b]pyridin-2-yl]carbamate [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 2961 - 2964

11
[ 790664-98-1 ]
[ 219511-71-4 ]
(E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-1H-pyrrole-2-carboxamide [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 2961 - 2964

12
[ 872369-09-0 ]
[ 219511-71-4 ]
[ 872369-12-5 ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 8635 - 8638

13
[ 900794-20-9 ]
[ 219511-71-4 ]
2-amino-5-(6,7-dibromo-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-<i>a</i>]pyrazin-4-ylmethyl)-imidazole-1-carboxylic acid <i>tert</i>-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 5561 - 5563

14
[ 926912-94-9 ]
[ 219511-71-4 ]
[ 926912-96-1 ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 9186 - 9195

15
[ 6750-85-2 ]
[ 219511-71-4 ]
[ 917112-24-4 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4385 - 4392

16
[ 917112-29-9 ]
[ 219511-71-4 ]
[ 917112-31-3 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4385 - 4392

17
[ 917112-30-2 ]
[ 219511-71-4 ]
[ 917112-32-4 ]

Reference： [1]European Journal of Organic Chemistry,2006,p. 4385 - 4392

18
[ 219511-71-4 ]
[ 1018929-94-6 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure for solution-phase PyBroP coupling (side-chain acid coupling)Boc > cThe appropriate side-chain carboxylic acid (50 - 150 mg, 1 eq) and bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (1.5 eq) were suspended in dichloromethane (5 ml_) and the mixture was stirred at 20 0C for 10 minutes. N,N-Diisopropylethylamine (9 eq) was added to the mixture and the solution stirred for a further 10 minutes. Tert-Butoxycarbonylguanidine (1.5 eq, prepared in accordance with reference 1) was added and the reaction mixture was then stirred for 20 hours at 20 0C. After this time the reaction solvent was removed in vacuo and the residue partitioned between hydrochloric acid (1 M aqueous solution, 20 ml_) and ethyl acetate (20 mL). The phases were separated and the aqueous phase extracted with ethyl acetate (3 x 20 mL). The organic phases were combined and washed with brine (saturated, aqueous solution, 25 mL), dried over magnesium sulfate, filtered and the solvent removed in vacuo to afford the crude residue.

Reference： [1]Patent: WO2008/40979,2008,A1 .Location in patent: Page/Page column 23-24

19
[ 848352-99-8 ]
[ 219511-71-4 ]
[ 878627-28-2 ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 6832 - 6839
[2]Journal of Organic Chemistry,2007,vol. 72,p. 6162 - 6170
[3]Angewandte Chemie - International Edition,2009,vol. 48,p. 6722 - 6725
Angewandte Chemie,2009,vol. 121,p. 6850 - 6853

20
[ 3392-07-2 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[2-(tert-butoxycarbonylamino)acetyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

21
[ 27687-14-5 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[trans-4-(tert-butoxycarbonylaminomethyl)cyclohexanecarbonyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

22
[ 32703-87-0 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[3-(tert-butoxycarbonylamino)propanoyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

23
[ 69038-04-6 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[3-(tert-butoxycarbonylamino)propyl]oxycarbonyl}guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

24
C₁₄H₂₂N₂O₇ [ No CAS ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxycarbonyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

25
[ 57294-38-9 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[4-(tert-butoxycarbonylamino)butanoyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

26
[ 27219-07-4 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[5-(tert-butoxycarbonylamino)pentanoyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

27
[ 6404-29-1 ]
[ 219511-71-4 ]
1-tert-butoxycarbonyl-2-[6-(tert-butoxycarbonylamino)hexanoyl]guanidine [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999

28
[ 24424-99-5 ]
[ 50-01-1 ]
[ 219511-71-4 ]

Yield	Reaction Conditions	Operation in experiment
91%		a) BOC-guanidine BOC-guanidine was synthesised in accordance with Ando et al., Tetrahedron (2010), 66(32), 6224-6237: 22.93 g (0.24 mol) of guanidinium chloride are added to the solution of 19.2 g (0.48 mol) of sodium hydroxide pellets in 50 ml of water at 0 C. The solution is left to stir for 10 min., a solution of 13.1 g (60 mmol) of di-tert-butyl dicarbonate in 150 ml of acetone is then added in one portion at 0 C., and the reaction mixture is then left to stir at room temperature for 15 hours. The acetone is subsequently stripped off in vacuo, and the aqueous mixture is extracted twice with 50 ml of ethyl acetate. The combined organic phases are washed with 50 ml of saturated sodium chloride solution and dried over sodium sulfate. After the solvent has been stripped off, the residue is recrystallised from ethyl acetate/n-heptane, giving 8.7 g (91%) of BOC-guanidine as white crystals. EI-MS (M+): 159
	With sodium hydroxide; In water; acetone; at 0 - 20℃; for 16h;	Guanidine hydrochloride (175 g, 1833 mmol, 4 equiv) was added to a solution of NaOH (147 g, 3666 mmol, 8 equiv) in H2O (360 ml_), portionwise and keeping the internal temperature around O0C. tert-Butoxycarbonyl anhydride (100 g, 458 mmol) in acetone (1.5 L) was then added over 2 h and the reaction mixture was allowed to warm to rt over 14 h. The acetone was removed under vacuum and the resulting aqueous mixture was extracted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated to afford 61.6 g of the title compound as a white solid: ES-MS: 160 [M+H]+.

Reference： [1]European Journal of Organic Chemistry,2008,p. 324 - 329
[2]Patent: US2015/361037,2015,A1 .Location in patent: Paragraph 0232; 0233
[3]Chemistry - A European Journal,2019,vol. 25,p. 785 - 795
[4]Tetrahedron Letters,2007,vol. 48,p. 6996 - 6999
[5]Organic and Biomolecular Chemistry,2012,vol. 10,p. 4899 - 4906
[6]Chemical Communications,2008,p. 344 - 346
[7]Angewandte Chemie - International Edition,2009,vol. 48,p. 6722 - 6725
Angewandte Chemie,2009,vol. 121,p. 6850 - 6853
[8]Chemistry - A European Journal,2011,vol. 17,p. 14508 - 14517
[9]Supramolecular Chemistry,2011,vol. 23,p. 470 - 479
[10]Patent: WO2009/141386,2009,A1 .Location in patent: Page/Page column 176

29
[ 219511-71-4 ]
[ 863201-70-1 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 10486 - 10487

30
[ 219511-71-4 ]
C₁₇H₂₈N₆O₄ [ No CAS ]

Reference： [1]Tetrahedron Letters,2005,vol. 46,p. 1295 - 1298

31
[ 383867-17-2 ]
[ 219511-71-4 ]
[7-(2-tert-butoxycarbonylamino-1H-imidazol-4-yl)-4-methoxy-benzothiazol-2-yl]-carbamic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	In acetonitrile;	EXAMPLE 214 [7-(2-tert-Butoxycarbonylamino-1H-imidazol-4-yl)-4-methoxy-benzothiazol-2-yl]-carbamic acid methyl ester 0.25 g of (7-bromoacetyl-4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester (0.0007 Mol) and 0.33 g of tert-butoxycarbonylguanidine (0.0021 Mol) were heated to reflux in acetonitril (3 ml) for 3 hrs. After evaporation of the solvent the residue was triturated with water (10 ml) and filtered. The filtrate was evaporated and the residue subjected to column chromatography (silicagel, ethyl-acetate/hexanes 1:1) to yield the title compound as a white solid (17%); F.p.: 255-265 C.

Reference： [1]Patent: US2002/45615,2002,A1

32
[ 241800-91-9 ]
[ 219511-71-4 ]
[ 241801-79-6 ]

Yield	Reaction Conditions	Operation in experiment
22.5%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide;	EXAMPLE 33A N-tert-Butoxycarbonyl-N'-[5-isopropyl-1-(6-quinolinyl)-1H-pyrazole-4-carbonyl]guanidine To a solution of 5-isopropyl-1-(6-quinolinyl)-1H-pyrazole-4-carboxylic acid (336.7 mg, 1.2 mmol) in 5 ml dimethylformamide was added N,N-diisopropylethylamine (0.42 ml, 2.39 mmol), benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) (582 mg, 1.32 mmol) and tert-butoxycarbonylguanidine (210 mg, 1.32 mmol). The resulting solution was stirred at room temperature for 2 h, then heated to 60 C. for 2 h. The reaction mixture was then cooled to room temperature and concentrated to dryness in vacuo. The solid residue was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried (sodium sulfate) and concentrated to dryness in vacuo. The solid residue was triturated with methanol (1.5 ml), filtered, washed with diethyl ether and dried to yield the title compound as a white solid (114.3 mg, 22.5% yield). 1H NMR (DMSO-d6) delta1.27 (d, 6H); 1.42 (s, 9H); 3.28 (m, 1H); 7.62 (q, 1H); 7.74 (q, 1H); 8.08-8.15 (m, 4H); 8.47 (d, 1H); 8.98 (d, 1H); 9.21 (bs, 1H); 10.9 (bs, 1H).

Reference： [1]Patent: US6492401,2002,B1

33
[ 123-91-1 ]
[ 24424-99-5 ]
[ 50-01-1 ]
[ 219511-71-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium hydroxide; In water;	Example 6 N-,N'-Di-Boc-Guanidine 1,4-Dioxane (50 ml) is added to a solution of guanidine hydrochloride (2.39 g, 25 mmol) and sodium hydroxide (4.0 g, 0.1 mol) in water (25 ml) and the resulting mixture is cooled to 0 C. Di-tert-butyl-pyrocarbonate(12.0 g, 55 mmol) is added in one portion while stirring. The reaction mixture is allowed to warm to room temperature within 2 h. After stirring for 20 h the mixture is concentrated in vacuo to one third of its original volume. The resulting suspension is diluted with water (50 ml) and extracted three times with ethyl acetate (50 ml each). The combined extracts are washed with 10% citric acid, water and brine and dried with magnesium sulfate. After filtering and removal of the solvent under reduced pressure the crude product is purified by flash chromatography on silica gel (eluent: dichloromethane-methanol 97:3). N-,N'-di-Boc-guanidine (3.84 g, 59%) is obtained as a colorless powder: mp: 144 C.; 1 H NMR (360 MHz, DMSO-d6) delta 10.42 (br s, 1H), 8.47 (br s, 2H), 1.39 (s, 18H); FAB-MS m/e (relative intensity) 260 (50; M+H+), 204 (48), 148 (100); Anal. Calc. for: C, 50.95%; H, 8.16%;.N, 16.21%; Found: C, 50.83%; H, 8.04%;.N, 16.26%.

Reference： [1]Patent: US6072075,2000,A

34
[ 219511-71-4 ]
[ 207857-15-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With trifluoromethylsulfonic anhydride; triethylamine; In dichloromethane;	Example 7 N'-Di-Boc-N"-Trifluoromethanesulfonyl-Guanidine A solution of N-,N'-di-Boc-guanidine (0.52 g, 2.0 mmol) and triethyl amine (0.29 ml) in anhydrous dichloromethane (10 ml) is cooled to -78 C. under an atmosphere of argon. Triflic anhydride (0.35 ml, 2.1 mmol) is added dropwise at a rate such that reaction temperature does not exceed -65 C. After the addition is completed, the mixture is allowed to warm to room temperature within 4 h. The solution is transferred to a separation funnel, washed with 2M sodium bisulfate and water and dried with anhydrous sodium sulfate. After filtering and removal of the solvent under reduced pressure the crude product is purified by flash chromatography on silica gel (eluent: dichloromethane). N-N'-Di-Boc-N'"-trifluoromethanesulfonyl-guanidine (686 mg, 88%) is obtained as pale yellow crystals. The product can be further purified by recrystallization from hexanes: mp: 115 C.; 1 H NMR (360 MHz, DMSO-d6) delta 11.45 (br s, 2H), 1.45 (s, 18H). FAB-MS m/e (relative intensity) 414 (16, M+Na+), 392 (13, M+H+), 336 (43), 280 (100), 236 (9); Anal. Calc. for C, 36.83%; H, 5.15%;.N, 10.74%; F, 14.56%; S, 8.19%; Found: C, 36.93%; H, 5.21%;.N, 10.66%; F, 14.80%; S, 8.33%.

Reference： [1]Patent: US6072075,2000,A

35
[ 332882-82-3 ]
[ 219511-71-4 ]

Yield	Reaction Conditions	Operation in experiment
	In 2-methyltetrahydrofuran; for 1h;Reflux;	Example 8 N-(t-Butyloxycarbonyl)guanidine A 1000 ml 3-neck Morton flask was equipped with an overhead stirrer, a N2 inlet, an addition funnel, and a thermocouple. The flask was charged with guanidine hydrochloride (22.76 g, 235.8 mmol) followed by 3.96M NaOH solution (prepared from 95.0 ml of 5M NaOH and 25 ml of water, 120 ml total). The resultant mixture was stirred to yield a solution and cooled to <2 C. A solution of (Boc)2O (42.53 g, 189.0 mmol) in 1,4-dioxane (103.2 g) was added to the stirred mixture over 50 minutes while maintaining the temperature at <8 C. A solid precipitated from the resultant biphasic mixture during the (Boc)2O/1,4-dioxane addition. The resultant white suspension was stirred at ice bath temperature for about 1.25 h.After addition of water (200.00 g) the resultant mixture was evaporated to yield a solid comprising the crude product together with inorganic salts and a small amount of bis-Boc-guanidine. The solids were suspended in 2-Me-THF (344.00 g), the suspension was stirred and heated to reflux and maintained at reflux for about 1 h. The suspension was then cooled to about 55-60 C. and filtered warm to remove the inorganic salts. Evaporation of the 2-MeTHF yielded a solid. This solid was re-suspended in MTBE (37.00 g) and the resultant suspension was stirred at ambient temperature for 1 h. The suspension was filtered, and the solid was washed with MTBE (18.5 g). The MTBE treatment was repeated again and the resultant product was air dried for several hours at ambient temperature. The product-N-(t-butyloxycarbonyl)-guanidine-was isolated as a solid.1H NMR (300 MHz, DMSO-d6): delta 6.74 (bs, 4H), 1.34 (s, 9H); MS: (Cl)m/z 160 (M++1), 319 (2M++1)
		Step II.; [0254] (R)-3~Benzyloxy-2-(4-methyl-naphthalene-1-sulfonylamino) propionic acid (6.4 mg, 399.47 g/mol, 0.016 mmol, 1.0 eq.) was dissolved in DCM/DMF (1 :1 , 1 ml) before DCC (3.3 mg, 206.33 g/mol, 0.016 mmol, 1.0 eq.) and HOBt (2.4 mg, 153.12 g/mol, 0.016 mmol, 1.0 eq.) were added. 1 ,3- Bis(tert-butoxycarbonyl)guanidine (9.1 mg, 259.3 g/mol, 0.096 mmol, 6.0 eq.) EPO <DP n="89"/>was treated first with HCI, which removed only one boc group,, and then with TEA (20 mul, 101.19 g/mol, 0.73 g/cm3, 0.144 mmol, 9.0 eq.) to liberate the HCI salt, which was added to the reaction mixture above. After stirring for one day at room temperature and then overnight at 30-40 0C, the reaction mixture was evaporated to dryness and the residue was dissolved in DCM. The organic phase was washed with a 5 % aq. NaHCtheta3 solution and brine, dried over Na2SO4 and evaporated. The reaction product was purified by preparative TLC to obtain (f?)-4-methyl-naphthalene-1 -sulfonic acid [1-benzyloxymethyl-2-(1-/V,- Boc-guanidino)-2-oxo-ethyl]-amide.

Reference： [1]Patent: US2010/4450,2010,A1 .Location in patent: Page/Page column 16
[2]Patent: WO2006/123020,2006,A1 .Location in patent: Page/Page column 87-88

36
[ 33707-36-7 ]
[ 219511-71-4 ]
(cis)-2-amino-5,7a-dihydro-3aH-imidazo[4,5-b]pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester [ No CAS ]
(cis)-2-tert-butoxycarbonylamino-1,3a,5,7a-tetrahydroimidazo[4,5-b]pyridine-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In N,N-dimethyl-formamide; acetonitrile; at 0 - 20℃; for 0.25h;Product distribution / selectivity;	A solution of Br2 (0.49 ml, 9.57 mmol, 1 equiv.) in DMF (5 ml) is added over 15 min to a solution of N-methoxycarbonyl-1,2-dihydropyridine 1 (1.33 g, 9.57 mmol, 1 equiv.) and of Boc-guanidine (6.1 g, 38.3 mmol, 4 equiv.) in a mixture of DMF (15 ml) and of CH3CN (5 ml) at ambient temperature and under argon. The reaction being complete from the end of the addition of the bromine, the solvent is evaporated at 50 C. and the crude product (11 g) is chromatographed on silica gel using dichloromethane saturated with ammonia. The regioisomers 2 and 3 are obtained as a mixture, in the form of a hygroscopic yellow solid (1.9 g, 67%). The two products can be easily separated by chromatography on a thick silica layer and analyzed separately: Regioisomer 2: yellow solid; M.p.=75.5 C. (dec.); 1H NMR (300 MHz, CD3OD): delta=1.55 (s, 9H, (CH3)3), 3.63 (m, 4H, 9-Ha), 3.75 (s, 6H, OCH3), 4.19 (dd, J=18 and 2 Hz, 1H, 9-Hb), 4.63 (m, 1H, 6-H), 5.82 (m, J=2 and 11 Hz, 1H, 7-H), 6.07 (broad m, 2H, 2-H and 8-H); 13C NMR (75.5 MHz, CD3OD): delta=28.3 (CH3)3, 39.6 (C-9), 53.5 (C-3'), 55.0 (C-6), 70.0 (C-2), 84.4 (C-8), 122.0 (C-7), 129.0 (C-8), 153.0, 156.0, 158.0 (C-4, CO carbamate); MS(ES): m/z 296.9 [M+H]+, 196.8 [M+H-Boc]+; HRMS, calculated C13H20O4N4 [M+H]+: 297.15628, found: 297.15605. Regioisomer 3: yellow solid; M.p.=117 C. (dec.); 1H NMR (300 MHz, CD3OD): =1.47 (s, 9H, (CH3)3), 3.47 (d, 18 Hz, 1H, 9-Ha), 3.75 (s, 3H, OCH3), 4.12 (broad d, J=8 Hz, 1H, 6-H), 4.31 (broad d, J=18 Hz, 2H, 9-Hb), 5.62 (dd, J=2 and 11 Hz, 1H, 7-H), 5.85 (broad s, 1H, 8-H), 6.46 (broad s, 1H, 2-H); 13C NMR (75.5 MHz, CD3OD): delta=28.4 (CCH3), 39.1 (C-9), 53.6 (OCH3), 55.9 (C-6), 70.2 (C-2), 84.8 C(tBu), 124.3 (C-8), 127.5 (C-7); MS(ES): m/z 296.9 [M+H]+, 196.8 [M+H-Boc]+; HRMS, calculated C13H20O4N4 [M+H]+: 297.15628, found: 297.15769; A solution of Br2 (0.73 ml, 14.3 mmol, 1 equiv.) in DMF (5 ml) is added over 15 min to a solution of N-methoxycarbonyl-1,2-dihydropyridine 1 (2 g, 14.3 mmol, 1 equiv.) and of Boc-guanidine (9.15 g, 57.5 mmol, 4 equiv.) in a mixture of DMF (10 ml) and of CH3CN (5 ml) under cold conditions (0-5 C.) and under argon. The reaction being complete from the end of the addition of bromine, the reaction mixture is poured onto ice-cold water (600 ml). The aqueous phase is subsequently extracted with DCM (3×200 ml). The crude product obtained (3.5 g) is dissolved in the minimum amount of methanol, followed by addition of a 2N hydrochloric acid solution (10 ml). The solution is brought to reflux in [illegible] for 5 min. After cooling, the reaction mixture is washed with ether and then evaporated to dryness to give 2.4 g of the deprotected compound 4 with a yield of 71% over the two stages. 1H NMR (300 MHz, CD3OD): delta=3.69 (broad d, J=19 Hz, 1H, 9-Hb), 3.79 (s, 3H, OCH3), 4.25 (broad dd, J=19 and 4 Hz, 1H, 9-Ha), 4.47 (broad d, J=9 Hz, 1H, 6-H), 5.74 (qd, J=10 Hz, 1H, 7-H), 6.08 (broad dd, J=10 and 4 Hz, 1H, 8-H), 6.39 (d, J=8 Hz, 1H, 2-H); 13C NMR (75.5 MHz, CD3OD): delta=39.7 (C-9), 52.0 (C-6), 54.0 (OCH3), 66.0 (C-2), 123.0 (C-7), 128.0 (C-8), 157.0, 160.0 (CO carbamate, C-4); MS(ES): m/z 196.8 [M+H]+; HRMS, calculated C8H12O2N4 [M+H]+: 197.10385, found: 197.10314.

Reference： [1]Patent: US2007/106077,2007,A1 .Location in patent: Page/Page column 3-5

37
[ 790664-98-1 ]
[ 219511-71-4 ]
[4-(1H-pyrrolyl-2-carbonyl)-3a,4,5,7a-tetrahydro-3H-imidazo[4,5-b]pyridin-2-yl]carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With bromine; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 0.25h;	EXAMPLE 15 [4-(1H-Pyrrolyl-2-carbonyl)-3a,4,5,7a-tetrahydro-3H-imidazo[4,5-b]pyridin-2-yl]carbamic acid tert-butyl ester 21 The dihydropyridine 20 (0.50 g, 2.8 mmol, 1 equiv.) and N-Boc-guanidine (1.36 g, 8.4 mmol, 3 equiv.) are suspended in a mixture of DMF/CH3CN 3/1 (8 ml). Bromine (0.14 ml, 2.8 mmol, 1 equiv.), in solution in DMF (2 ml), is added dropwise to this suspension over a period of 15 min. From the end of the addition, the reaction mixture is concentrated under reduced pressure and then dried using pump vacuum. The residue is purified by chromatography on a column of silica gel eluted with a CH2Cl2 saturated with ammonia/MeOH 99/1 mixture. The coupling product 21 is obtained with a yield of 28% (0.26 g). 1H NMR (300 MHz, CD3OD): 6.97 (m, 1H, H5'), 6.90 (d, J=8.0 Hz, 1H, H2), 6.68 (m, 1H, H3'), 6.24 (dd, J=2.4 and 3.5 Hz, 1H, H4'), 5.86 (dd, J=4.0 and 10 Hz, 1H, H8), 5.70 (bd, J=10.0 Hz, 1H, H7), 4.66 (m, 1H, H9), 4.59 (m, 1H, H6), 4.25 (m, 1H, H9); MS(ES): 354.15 [M+Na+]; 197.0 [M+Na+]; 332.15 [M+H+]; 232.08 [M-Boc]+.

Reference： [1]Patent: US2007/106077,2007,A1 .Location in patent: Page/Page column 10-11

38
[ 790664-98-1 ]
[ 219511-71-4 ]
[4-(4,5-dibromo-1H-pyrrolyl-2-carbonyl)-3a,4,5,7a-tetrahydro-3H-imidazo[4,5-b]pyridin-2-yl]carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With bromine; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 0.25h;	EXAMPLE 17 [4-(4,5-Dibromo-1H-pyrrolyl-2-carbonyl)-3a,4,5,7a-tetrahydro-3H-imidazo[4,5-b]pyridin-2-yl]carbamic acid tert-butyl ester 23 Compound 20 (0.24 g, 1.4 mmol, 1 equiv.) and N-Boc-guanidine (0.65 g, 4.1 mmol, 4 equiv.) are suspended in a DMF/CH3CN 3/1 mixture (8 ml). Bromine (0.21 ml, 4.2 mmol, 3 equiv.), in solution in DMF (2 ml), is added dropwise over a period of 15 min. From the end of the addition, the reaction mixture is concentrated under reduced pressure and dried using pump vacuum. The residue is purified by chromatography on a column of silica gel eluted with a CH2Cl2 saturated with ammonia/MeOH 99/1 mixture. The product 23 is obtained with a yield of 47% (0.31 g). 1H NMR (300 MHz, CD3OD): 6.84 (s, 1H, H3'), 6.67 (d, J=8.5 Hz, 1H, H2), 6.17 (td, J=2.5 and 10.5 Hz, 1H, H8), 5.80 (dd, J=1.6 and 10.5 Hz, 1H, H7), 4.62 (d, 1H, H6), 4.53 and 4.03 (2m, 2H, H9); 13C NMR (75.5 MHz): 27.8 ((CH3)3), 41.7 (C9), 53.1 (C6), 76.1 (CtBu), 84.7 (C2), 95.8 (C4'), 97.2 (C3'), 103.8 (C5'), 114.9 (C8), 124.4 (C2'), 126.5 (C7), 152.2 and 161.8 (C10 and CO carbamate); MS(ES): 490.0 [M+H+], 410.1 [M-HBr]+, 389.9 [M-Boc]+, 332.1 [M-2HBr]+, 310.0 [M-HBr-Boc]+, 232.1 [M-2HBr-Boc]+

Reference： [1]Patent: US2007/106077,2007,A1 .Location in patent: Page/Page column 11-12

39
[ 66531-21-3 ]
[ 219511-71-4 ]
C₁₄H₁₉Cl₃N₄O₄ [ No CAS ]
C₁₄H₁₉Cl₃N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In water; N,N-dimethyl-formamide; acetonitrile; at 0 - 5℃; for 0.25h;	EXAMPLE 8 (cis)-2-Amino-1,3a,5,7a-tetrahydro-imidazo[4,5-b]pyridine-4-carboxylic acid 2,2,2-trichloroethyl ester hydrochloride A solution of Br2 (0.79 ml, 15.5 mmol, 1 equiv.) in DMF (5 ml) is added over a period of 15 min to a solution of N-trichloroethylcarbonyl-1,2-dihydropyridine 11 (4 g, 15.5 mmol, 1 equiv.) and of Boc-guanidine (10 g, 62.0 mmol, 4 equiv.) in DMF (10 ml)/CH3CN (5 ml) under cold conditions (0-5 C.) and under argon. The reaction being complete from the end of the addition of the bromine, the reaction mixture is poured onto ice-cold water (600 ml). The aqueous phase is subsequently extracted with DCM (3*200 ml). The organic phases are combined, then washed with water and evaporated to dryness. The crude product obtained (3.5 g) is dissolved in the minimum amount of methanol and then brought to reflux in 10 ml of a 2N hydrochloric acid solution for 10 minutes. After cooling, the reaction mixture is washed with ether and then evaporated to dryness to give 1.4 g of the deprotected product 14 with a yield of 26% over the two stages. 1H NMR (250 MHz, d6-DMSO): delta=3.74 (broad d, J=17 Hz, 1H, 9-Ha), 4.18 (broad d, J=17 Hz, H, 9-Hb), 4.50 (broad d, J=8 Hz, 1H, 6-H), 4.95 (m, 2H, H-Troc), 5.74 (d, J=9 Hz, 1H, 7-H), 6.07 (m, 1H, 8-H), 6.24 (d, J2-6=8 Hz, 1H, 2-H); 13C NMR (62.5 MHz, CD3OD): delta=40.1 (C-9), 51.8 (C-6), 66.3 (C-2), 76.6 (CH2-Troc), 122.9 (C-8), 127.0 (C-7), 156.0 (C-4), 160.0 (carbamate); MS(ES): m/z 313.0, 315.0, 317.0 [M]+.

Reference： [1]Patent: US2007/106077,2007,A1 .Location in patent: Page/Page column 7

40
[ 79328-86-2 ]
[ 219511-71-4 ]
(cis)-2-Amino-5,7a-dihydro-3aH-imidazo[4,5-b]pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-phenyl ester [ No CAS ]
(cis)-2-tert-Butoxycarbonylamino-1,3a,5,7a-tetrahydro-imidazo[4,5-b]pyridine-4-carboxylic acid phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 0.25h;	A solution of Br2 (0.36 ml, 7 mmol, 1 equiv.) in DMF (5 ml) is added over a period of 15 min to a solution of N-phenyloxycarbonyl-1,2-dihydropyridine 7 (1.42 g, 7 mmol, 1 equiv.) and of Boc-guanidine (4.5 g, 28 mmol, 4 equiv.) in DMF (15 ml)/CH3CN (5 ml) at ambient temperature and under argon. The reaction being complete from the end of the addition of the bromine, the solvent is evaporated under vacuum and the crude product (2 g) chromatographed on silica gel (DCM sat. NH3). The two regioisomers (Rf=0.40, DCM(NH3)) are obtained in the form of a white solid (1.9 g, 6.42 mmol, 20%). The two products 8 and 9 are easily purified by thick layer chromatography. (cis)-2-Amino-5,7a-dihydro-3aH-imidazo[4,5-b]pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-phenyl ester 8 1H NMR (300 MHz, CD3OD): delta=1.56 (s, 9H, (CH3)3), 3.78 (dd, 1H, 9-Ha, J=18 Hz), 4.33 (dd, J=18 Hz, 1H, 9-Hb), 4.73 (m, 1H, 6-H), 5.88 (broad d, 1H, J=10 Hz, 7-H), 6.11 (m, 1H, 8-H), 6.24 (dd, J=8 Hz, 1H, 2-H), 7.26 (m, 5H, H-phenyl); 13C NMR (75.5 MHz, CD3OD): delta 28.7 (C(CH3)3), 40.1 (C-9), 55.6 (C-6), 70.5 (C-2), 84.8 (CtBu), 122.8 (C-8), 127.1 (C-7), 123.3, 130.7 (C-Ph), 153.0 (C-4); MS(EI): m/z 358 [M]+, 257 [M-Boc]+. (cis)-2-tert-Butoxycarbonylamino-1,3a,5,7a-tetrahydro-imidazo[4,5-b]pyridine-4-carboxylic acid phenyl ester 9 1H NMR (300 MHz, CD3OD): delta=1.46 (s, 9H, (CH3)3), 3.57 (dd, J=19 Hz, 1H, 9-Ha), 4.18 (d, J=8 Hz, 1H, 6-H), 4.40 (dd, J=19 Hz, H, 9-Hb), 5.68 (m, 1H, 7-H), 5.87 (m, 1H, 8-H), 6.55 (dd, J=8 Hz, 1H, 2-H), 7.22 (m, 5H, H-phenyl); 13C NMR (75.5 MHz, CD3OD): delta=28.9 ((CH3)3), 40.1 (C-9), 56.5 (C-6), 70.5 (C-2), 85.8 (CtBu), 122.8 (C-Ph), 124.8 (C-8), 127.1 (C-7), 128.3, 130.7 (C-Ph); MS(EI): m/z 358 [M]+, 257 [M-Boc]+.

Reference： [1]Patent: US2007/106077,2007,A1 .Location in patent: Page/Page column 6

41
[ 111-20-6 ]
[ 219511-71-4 ]
[ 955938-55-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6009 - 6012

42
[ 1852-04-6 ]
[ 219511-71-4 ]
[ 955938-56-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6009 - 6012

43
[ 693-23-2 ]
[ 219511-71-4 ]
[ 955938-57-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6009 - 6012

44
[ 505-52-2 ]
[ 219511-71-4 ]
[ 955938-58-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6009 - 6012

45
[ 505-54-4 ]
[ 219511-71-4 ]
[ 955938-60-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6009 - 6012

46
C₁₉H₁₄N₄O₄ [ No CAS ]
[ 219511-71-4 ]
[ 878627-28-2 ]

Reference： [1]European Journal of Organic Chemistry,2008,p. 324 - 329

47
[ 794486-85-4 ]
[ 219511-71-4 ]
[ 1011468-22-6 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 311 - 315

48
[ 2129-30-8 ]
[ 219511-71-4 ]
[ 1011468-24-8 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 311 - 315

49
[ 5469-26-1 ]
[ 219511-71-4 ]
[ 885962-38-9 ]

Reference： [1]Chemical Communications,2008,p. 344 - 346
[2]Chemistry - A European Journal,2019,vol. 25,p. 785 - 795

50
[ 68192-98-3 ]
[ 219511-71-4 ]
[ 1029126-03-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium iodide; In N,N-dimethyl-formamide; at 20℃; for 24h;	2-amino-4-(3-methoxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester (18). 6-bromo-5-oxo-hexanoic acid methyl ester (2.30 g, 10.3 mmol), Boc-guanidine (4.92 g, 30.9 mmol),32 and Nal (3.07 g, 20.6 mmol) were dissolved in DMF (30 mL) and allowed to stir at room temperature. After 24 h the DMF was removed under reduced pressure and the residue was taken up in ethyl acetate (100 mL) and washed with water (3*50 mL) and brine (50 mL) before being dried (Na2SO4), filtered and evaporated to dryness. The resulting oil was purified by flash column chromatography (50-100% EtOAc/Hexanes) to obtain a yellow oil. Trituration of the viscous oil with cold hexanes (20 mL) produced a precipitate, which upon filtration yielded 18 (1.89 g, 65%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) delta 6.53 (s, 1H), 5.6 (br s, 2H), 2.41 (t, 2H, J=7.2 Hz), 2.37 (t, 2H, J=7.2 Hz), 1.93 (quint., 2H, J=7.2 Hz), 1.58 (s, 9H); 13C NMR (75 MHz, CDCl3) delta 174.09, 150.11, 149.61, 138.39, 107.15, 84.81, 51.56, 33.65, 28.18, 27.68, 23.82; HRMS (ESI) calcd for C13H22N3O4 (MH)+284.1604, found 284.1606.
65%	With sodium iodide; In N,N-dimethyl-formamide; at 20℃; for 24h;	2-amino-4-(3-methoxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester (18). 6-bromo-5-oxo-hexanoic acid methyl ester (2.30 g, 10.3 mmol), Boc-guanidine (4.92 g, 30.9 mmol),32 and NaI (3.07 g, 20.6 mmol) were dissolved in DMF (30 mL) and allowed to stir at room temperature. After 24 h the DMF was removed under reduced pressure and the residue was taken up in ethyl acetate (100 mL) and washed with water (3×50 mL) and brine (50 mL) before being dried (Na2SO4), filtered and evaporated to dryness. The resulting oil was purified by flash column chromatography (50-100% EtOAc/Hexanes) to obtain a yellow oil. Trituration of the viscous oil with cold hexanes (20 mL) produced a precipitate, which upon filtration yielded 18 (1.89 g, 65%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) delta 6.53 (s, 1H), 5.6 (br s, 2H), 2.41 (t, 2H, J=7.2 Hz), 2.37 (t, 2H, J=7.2 Hz), 1.93 (quint., 2H, J=7.2 Hz), 1.58 (s, 9H); 13C NMR (75 MHz, CDCl3) delta 174.09, 150.11, 149.61, 138.39, 107.15, 84.81, 51.56, 33.65, 28.18, 27.68, 23.82; HRMS (ESI) calcd for C13H22N3O4 (MH)+ 284.1604, found 284.1606.

Reference： [1]Organic and Biomolecular Chemistry,2008,vol. 6,p. 1356 - 1363
[2]Patent: US2008/181923,2008,A1 .Location in patent: Page/Page column 32
[3]Patent: US2009/143230,2009,A1 .Location in patent: Page/Page column 40

51
[ 1029126-16-6 ]
[ 219511-71-4 ]
[ 1029126-05-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	In N,N-dimethyl-formamide; at 20℃; for 48h;	2-amino-4-(3-benzyloxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester (21). 6-bromo-5-oxo-hexanoic acid benzyl ester (3.42 g, 11.99 mmol) and Boc-guanidine (5.73 g, 35.97 mmol) were dissolved in DMF (35 mL) and allowed to stir at room temperature. After 48 h the DMF was removed under reduced pressure and the residue was taken up in ethyl acetate (100 mL) and washed with water (3*50 mL) and brine (50 mL) before being dried (Na2SO4), filtered and evaporated to dryness. The resulting oil was purified by flash column chromatography (30-100% EtOAc/Hexanes) to obtain the title compound (2.79 g, 66%) as a colorless oil which solidified upon prolonged standing. 1H NMR (400 MHz, CDCl3) delta 7.35 (m, 5H), 6.51 (s, 1H), 5.91 (s, 2H), 5.12 (s, 2H), 2.41 (m, 4H), 1.94 (quint., 2H, J=7.2 Hz), 1.57 (s, 9H); 13C NMR (75 MHz, CDCl3) delta 173.45, 150.31, 149.59, 138.27, 136.36, 128.67, 128.29, 128.27, 107.05, 84.73, 66.23, 33.82, 28.16, 27.62, 23.79; HRMS (ESI) calcd for C19H26N3O4 (MH)+360.1917, found 360.1919.

Reference： [1]Chemical Communications,2011,vol. 47,p. 4896 - 4898
[2]Organic and Biomolecular Chemistry,2008,vol. 6,p. 1356 - 1363
[3]Patent: US2008/181923,2008,A1 .Location in patent: Page/Page column 32

52
[ 501-53-1 ]
[ 219511-71-4 ]
[ 194985-14-3 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 305 - 311

53
C₂₁H₃₁Cl₂N₉O₅ [ No CAS ]
[ 24424-99-5 ]
[ 219511-71-4 ]
C₄₂H₆₅ClN₁₂O₁₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 3578 - 3580

54
C₂₁H₃₁Cl₂N₉O₅ [ No CAS ]
[ 219511-71-4 ]
C₂₁H₃₀ClN₉O₅ [ No CAS ]
C₂₇H₄₁ClN₁₂O₆ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 3578 - 3580

55
C₂₁H₃₁Cl₂N₉O₅ [ No CAS ]
[ 219511-71-4 ]
C₂₇H₄₁ClN₁₂O₆ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 3578 - 3580

56
C₂₁H₃₃Cl₂N₉O₅ [ No CAS ]
[ 24424-99-5 ]
[ 219511-71-4 ]
C₄₂H₆₅ClN₁₂O₁₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 4785 - 4788

57
[ 1467-79-4 ]
[ 219511-71-4 ]
[ 1108717-33-4 ]

Reference： [1]Synthesis,2008,p. 3619 - 3624

58
[ 54322-10-0 ]
[ 219511-71-4 ]
[ 1029126-05-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	In N,N-dimethyl-formamide; at 20℃; for 48h;	2-amino-4-(3-benzyloxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester (21). 6-bromo-5-oxo-hexanoic acid benzyl ester (3.42 g, 11.99 mmol) and Boc-guanidine (5.73 g, 35.97 mmol) were dissolved in DMF (35 mL) and allowed to stir at room temperature. After 48 h the DMF was removed under reduced pressure and the residue was taken up in ethyl acetate (100 mL) and washed with water (3×50 mL) and brine (50 mL) before being dried (Na2SO4), filtered and evaporated to dryness. The resulting oil was purified by flash column chromatography (30-100% EtOAc/Hexanes) to obtain the title compound (2.79 g, 66%) as a colorless oil which solidified upon prolonged standing. 1H NMR (400 MHz, CDCl3) delta 7.35 (m, 5H), 6.51 (s, 1H), 5.91 (s, 2H), 5.12 (s, 2H), 2.41 (m, 4H), 1.94 (quint., 2H, J=7.2 Hz), 1.57 (s, 9H); 13C NMR (75 MHz, CDCl3) delta 173.45, 150.31, 149.59, 138.27, 136.36, 128.67, 128.29, 128.27, 107.05, 84.73, 66.23, 33.82, 28.16, 27.62, 23.79; HRMS (ESI) calcd for C19H26N3O4 (MH)+ 360.1917, found 360.1919.

Reference： [1]Patent: US2009/143230,2009,A1 .Location in patent: Page/Page column 41

59
[ 1110786-48-5 ]
[ 219511-71-4 ]
[ 1110786-19-0 ]

Reference： [1]Chemistry - A European Journal,2008,vol. 14,p. 10745 - 10761
[2]Journal of Organic Chemistry,2009,vol. 74,p. 1755 - 1758

60
[ 1110786-34-9 ]
[ 219511-71-4 ]
[ 1110786-35-0 ]