[ CAS No. 134003-84-2 ]

Name: 134003-84-2|(1R,4R)-tert-Butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate|95%
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SKU: A223324
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Quality Control of [ 134003-84-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 134003-84-2 ]

Product Details of [ 134003-84-2 ]

CAS No. :	134003-84-2	MDL No. :	MFCD01321293
Formula :	C₁₀H₁₈N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UXAWXZDXVOYLII-HTQZYQBOSA-N
M.W :	198.26 g/mol	Pubchem ID :	11860399
Synonyms :

Calculated chemistry of [ 134003-84-2 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.9
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	61.2
TPSA :	41.57 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.46
Log Po/w (XLOGP3) :	0.72
Log Po/w (WLOGP) :	0.21
Log Po/w (MLOGP) :	0.86
Log Po/w (SILICOS-IT) :	0.39
Consensus Log Po/w :	0.93

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.32
Solubility :	9.38 mg/ml ; 0.0473 mol/l
Class :	Very soluble
Log S (Ali) :	-1.17
Solubility :	13.4 mg/ml ; 0.0674 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.09
Solubility :	16.0 mg/ml ; 0.0809 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.65

Safety of [ 134003-84-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 134003-84-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 134003-84-2 ]
Downstream synthetic route of [ 134003-84-2 ]

[ 134003-84-2 ] Synthesis Path-Upstream 1~7

1
[ 134003-83-1 ]
[ 134003-84-2 ]

Yield	Reaction Conditions	Operation in experiment
93.4%	With hydrogen In ethanol for 16 h;	Example 15B tert-butyl (1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 15A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H₂ atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4 percent) of the title compound. ¹H NMR (DMSO-d₆, MHz) δ 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50, 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 (d, J=10.17 Hz, H); MS (DCI/NH₃) m/z 199 (M+H)⁺, 216 (M+NH₄)⁺.
93.4%	With hydrogen In ethanol for 16 h;	The product from Example 15A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H2 atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4percent) of the title compound. 1H NMR (DMSO-d6, MHz) δ 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50, 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 (d, J=10.17 Hz, H); MS (DCIINH3) m/z 199 (M+H)+, 216 (M+NH4)+.
93.4%	With hydrogen In ethanol for 16 h;	Example 25B tert-butyl(1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 25A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H₂ atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4percent) of the title compound. ¹H NMR (DMSO-d₆, MHz) δ 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50. 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 ppm (d, J=10.17 Hz, H); MS (DCl/NH₃) m/z 199 (M+H)⁺, 216 (M+NH₄)⁺.

Reference： [1] Patent: EP1147112, 2003, B1, . Location in patent: Page/Page column 19
[2] Patent: US2003/225268, 2003, A1, . Location in patent: Page 21
[3] Patent: US2005/101602, 2005, A1, . Location in patent: Page/Page column 37
[4] RSC Advances, 2015, vol. 5, # 14, p. 10386 - 10392
[5] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3627 - 3644

2
[ 326596-46-7 ]
[ 134003-84-2 ]

Yield	Reaction Conditions	Operation in experiment
66%	With ammonia In water at 65℃; for 16 h;	Step B: (2R,5R)-2,5-Diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester. A heterogeneous mixture of (4S,2R)-4-methanesulfonyloxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1 g, 2.7 mmol) in ammonium hydroxide (27 wt percent solution in water, 10 mL) was warmed to 65° C. in a sealed tube for 16 h during which time the mixture became homogeneous. The aqueous was extracted with CH₂Cl₂(2.x.) and the combined organics were dried over Na₂SO₄, filtered, and concentrated to provide the title compound as a yellow solid that was used directly in subsequent steps (350 mg, 66percent). MS (ESI): mass calcd. for C₁₀H₁₈N₂O₂, 198.1; m/z found, 199.0 [M+H]⁺. ¹H NMR (400 MHz, CDCl₃): 4.48-4.27 (m, 1H), 3.70 (s, 1H), 3.41-3.30 (m, 1H), 3.22-3.11 (m, 1H), 3.08-2.95 (m, 2H), 1.80-1.65 (m, 2H), 1.48 (s, 9H).

Reference： [1] Patent: US2009/111794, 2009, A1, . Location in patent: Page/Page column 15

3
[ 24424-99-5 ]
[ 134003-84-2 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3627 - 3644

4
[ 116258-17-4 ]
[ 134003-84-2 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3627 - 3644

5
[ 51-35-4 ]
[ 134003-84-2 ]

Reference： [1] RSC Advances, 2015, vol. 5, # 14, p. 10386 - 10392

6
[ 31560-19-7 ]
[ 134003-84-2 ]

Reference： [1] RSC Advances, 2015, vol. 5, # 14, p. 10386 - 10392

7
[ 31560-25-5 ]
[ 134003-84-2 ]

Reference： [1] RSC Advances, 2015, vol. 5, # 14, p. 10386 - 10392

[ 134003-84-2 ] Synthesis Path-Downstream 1~58

1
[ 134003-84-2 ]
[ 50720-12-2 ]
tert-butyl (1R,4R)-5-(6-methoxy-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

2
[ 134003-84-2 ]
[ 59782-89-7 ]
[ 286946-94-9 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 2-chloro-5-iodo-3-methylpyridine, prepared as described in (U.S. Pat. No. 5,733,912) were processed as described in Example 15C to provide the title compound. MS (DCI/NH3) m/z 324 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[3]Patent: US2003/225268,2003,A1 .Location in patent: Page 30

3
[ 134003-84-2 ]
[ 85148-26-1 ]
C₁₆H₂₀F₃N₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

4
[ 97966-01-3 ]
[ 134003-84-2 ]
[ 286946-96-1 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 2,3-dichloro-5-iodopyridine, prepared as described in (U.S. Pat. No. 5,733,912) were processed as described in Example 15C to provide the title compound. MS (DCI/NH3) m/z 344 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Patent: US2003/225268,2003,A1 .Location in patent: Page 31

5
[ 141-30-0 ]
[ 134003-84-2 ]
[ 286946-35-8 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 3,6-dichloropyridazine (purchased from Aldrich Chemical Co.) were processed as described in Example 2A to provide the title compound. 1H NMR (DMSO-d6, 300 MHz) delta 1.48 (m 9H), 2.93 (br, s 2H), 3.18 (d, J=12.17 Hz, 1H), 3.3-3.51 (m, 2H), 3.55 (m, 1H), 4.49 (m, 1H), 4.86 (br, s 1H), 7.12 (m, 1H), 7.51 (d, J=9.49 Hz, 1H); MS (DCI/NH3) m/z 311 (M+H)+.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3636 - 3639
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[3]Patent: US2003/225268,2003,A1 .Location in patent: Page 22

6
[ 53939-30-3 ]
[ 134003-84-2 ]
[ 286946-33-6 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

7
[ 134003-84-2 ]
[ 94191-12-5 ]
C₁₇H₂₁N₃SO₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

8
[ 134003-84-2 ]
[ 94191-17-0 ]
[ 286947-12-4 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

9
[ 134003-84-2 ]
[ 216394-05-7 ]
[ 1001407-42-6 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

10
[ 134003-84-2 ]
[ 5326-23-8 ]
[ 1001403-51-5 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

11
[ 134003-84-2 ]
[ 130722-95-1 ]
[ 286946-75-6 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 5-(benzyloxy)-3-bromo-pyridine, prepared as described in (U.S. Pat. No. 5,733,912) were coupled according to the procedure described in Example 15C to provide the title compound. MS (DCI/NH3) m/z 382 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Patent: US2003/225268,2003,A1 .Location in patent: Page 28

12
[ 134003-83-1 ]
[ 134003-84-2 ]

Yield	Reaction Conditions	Operation in experiment
93.4%	With hydrogen;palladium 10% on activated carbon; In ethanol; under 760.051 Torr; for 16h;	Example 15B tert-butyl (1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 15A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H2 atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4 percent) of the title compound. 1H NMR (DMSO-d6, MHz) delta 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50, 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 (d, J=10.17 Hz, H); MS (DCI/NH3) m/z 199 (M+H)+, 216 (M+NH4)+.
93.4%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 16h;	The product from Example 15A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H2 atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4percent) of the title compound. 1H NMR (DMSO-d6, MHz) delta 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50, 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 (d, J=10.17 Hz, H); MS (DCIINH3) m/z 199 (M+H)+, 216 (M+NH4)+.
93.4%	With hydrogen;palladium 10% on activated carbon; In ethanol; under 760.051 Torr; for 16h;	Example 25B tert-butyl(1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 25A (2 g, 6.9 mmol) in 50 mL of EtOH was treated with 10percent Pd/C (150 mg) under an H2 atmosphere (1 atm) for 16 hours. The mixture was filtered and the solvent was evaporated under reduced pressure to yield 1.28 g (93.4percent) of the title compound. 1H NMR (DMSO-d6, MHz) delta 1.39 (s, 9H), 1.54 (d, J=5.6 Hz, 1H), 1.58 (t, J=9.5 Hz, H), 2.70-2.81 (M, 2H), 3.50 (dd, J=1.02, 10.50. 1H), 3.17 (m, 1H), 3.50 (s, 1H), 4.17 ppm (d, J=10.17 Hz, H); MS (DCl/NH3) m/z 199 (M+H)+, 216 (M+NH4)+.

Reference： [1]Patent: EP1147112,2003,B1 .Location in patent: Page/Page column 19
[2]Patent: US2003/225268,2003,A1 .Location in patent: Page 21
[3]Patent: US2005/101602,2005,A1 .Location in patent: Page/Page column 37
[4]RSC Advances,2015,vol. 5,p. 10386 - 10392
[5]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

13
[ 626-55-1 ]
[ 134003-84-2 ]
[ 286946-50-7 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 3-bromopyridine (available from Aldrich Chemical Co.) were coupled according to the procedure described in Example 15C to provide the title compound. MS (DCI/NH3) m/z 276 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Patent: US2003/225268,2003,A1 .Location in patent: Page 24

14
[ 134003-84-2 ]
[ 286946-78-9 ]
[ 286946-79-0 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 80℃; for 4h;	Example 40D tert-butyl (1R,4R)-5-(6-chloro-5-methoxymethoxy-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 15B (1.0 g, 5.0 mmol) in anhydrous toluene (50 mL) was treated with the product from Example 40C (1.27g, 5.0 mmol), Pd2(dba)3 (0.093 g, 0.1 mmol), BINAP (0.126 g, 0.2 mmol) and sodium tert-butoxide (0.83 g, 8.6 mmol). The reaction mixture was heated at 80 °C for 4 hours. The mixture was allowed to cool to ambient temperature, diluted with ether (100 mL), washed with brine (100 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 (5percent MeOH/CH2Cl2) to provide the title compound (1.0 g, 52percent yield) as a yellow oil. MS (DCI/NH3) m/z 370 (M+H)+.
52%	With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 80℃; for 4h;	The product from Example 15B (1.0 g, 5.0 mmol) in anhydrous toluene (50 mL) was treated with the product from Example 40C (1.27 g, 5.0 mmol), Pd2(dba)3 (0.093 g, 0.1 mmol), BINAP (0.126 g, 0.2 mmol) and sodium tert-butoxide (0.83 g, 8.6 mmol). The reaction mixture was heated at 80° C. for 4 hours. The mixture was allowed to cool to ambient temperature, diluted with ether (100 mL), washed with brine (100 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was purified by chromatography on SiO2 (5percent MeOH/CH2Cl2) to provide the title compound (1.0 g, 52percent yield) as a yellow oil. MS (DCI/NH3) m/z 370 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644
[2]Patent: EP1147112,2003,B1 .Location in patent: Page/Page column 30
[3]Patent: US2003/225268,2003,A1 .Location in patent: Page 28

15
[ 134003-84-2 ]
[ 171197-80-1 ]
[ 286946-62-1 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 2-fluoro-5-iodopyridine were processed as described in Example 30A to provide the title compound. MS (DCIINH3) m/z 294 (M+H)+.

16
[ 134003-84-2 ]
[ 286947-03-3 ]
[ 286947-05-5 ]

Yield	Reaction Conditions	Operation in experiment
74%		The product from Example 15B and the product from Example 51A were processed as described in Example 15C to provide the title compound (74percent yield). MS (DCI/NH3) m/z 340 (M+H)+.

Reference： [1]Patent: US2003/225268,2003,A1 .Location in patent: Page 32
[2]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

17
[ 134003-84-2 ]
[ 13472-85-0 ]
[ 286946-92-7 ]

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18
[ 134003-84-2 ]
[ 35590-37-5 ]
[ 286946-87-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

19
[ 134003-84-2 ]
(1R,4R)-2-(5-methoxy-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

20
[ 134003-84-2 ]
(1R,4R)-2-(6-chloro-5-methyl-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

21
[ 134003-84-2 ]
(1R,4R)-2-(5-trifluoromethyl-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

22
[ 134003-84-2 ]
(1R,4R)-2-(5,6-dichloro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

23
[ 134003-84-2 ]
(1R,4R)-2-(6-chloro-5-methoxy-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

24
[ 134003-84-2 ]
[ 286947-01-1 ]

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25
[ 134003-84-2 ]
(1R,4R)-2-(5-aminocarbonyl-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane bis(trifluoroacetate) [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

26
[ 134003-84-2 ]
(1R,4R)-2-(6-chloro-3-pyridazinyl)-2,5-diazabicyclo[2.2.1]heptane bis(p-toluenesulfonate) [ No CAS ]

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27
[ 134003-84-2 ]
(1R,4R)-2-(3-methyl-(1,2,4)-thiadiazol-5-yl)-2,5-diazabicyclo[2.2.1]heptane [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

28
[ 134003-84-2 ]
(1R,4R)-3-(2,5-diazabicyclo[2.2.1]hept-2-yl)-thieno[3,2-b]pyridine [ No CAS ]

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29
[ 134003-84-2 ]
(1R,4R)-2-(2,5-diazabicyclo[2.2.1]hept-2-yl)-thieno[3,2-b]pyridine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

30
[ 134003-84-2 ]
(1R,4R)-2-(5-bromo-6-chloropyridine-3-sulfonyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

31
[ 134003-84-2 ]
(1R,4R)-2-(6-chloropyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

32
[ 134003-84-2 ]
(1R,4R)-2-(6-chloro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane p-toluenesulfonate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

33
[ 134003-84-2 ]
(1R,4R)-2-(6-fluoro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane [ No CAS ]

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34
[ 134003-84-2 ]
(1R,4R)-2-(3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane [ No CAS ]

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35
[ 134003-84-2 ]
(1R,4R)-2-(6-methoxy-3-pyridinyl)-2,5-diazabicyclo [2.2.1]heptane [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

36
[ 134003-84-2 ]
(1R,4R)-2-(5-cyano-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane [ No CAS ]

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37
[ 134003-84-2 ]
C₁₅H₂₁N₃O₃ [ No CAS ]

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38
[ 134003-84-2 ]
[ 286943-85-9 ]

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39
[ 24424-99-5 ]
[ 134003-84-2 ]

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[ 116258-17-4 ]
[ 134003-84-2 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3627 - 3644

41
[ 134003-84-2 ]
[ 13472-85-0 ]
tert-butyl (1R,4R)-5-(6-methoxy-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 2-methoxy-5-bromopyridine (purchased from Frontier Scientific) were processed as described in Example 15C to provide the title compound. MS (DCI/NH3) m/z 306 (M+H)+.

Reference： [1]Patent: US2003/225268,2003,A1 .Location in patent: Page 30

42
[ 625-92-3 ]
[ 134003-84-2 ]
[ 286946-86-9 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 3,5-dibromopyridine were processed as described in Example 1A to provide the title compound.

Reference： [1]Patent: US2003/225268,2003,A1 .Location in patent: Page 30

43
[ 69045-79-0 ]
[ 134003-84-2 ]
[ 286946-33-6 ]

Yield	Reaction Conditions	Operation in experiment
67%	With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 70℃; for 16h;	Example 15C tert-butyl (1R,4R)-5-(6-chloro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate The product from Example 15B (0.5 g, 2.5 mmole), 2-chloro-5-iodopyridine (0.88 g, 3.35 mmole, available as described in Tetrahedron Lett., 1993, 34, 7493-7496), Pd2(dba)3 (0.13 g, 0.16 mmole), BINAP (0.22 g, 0.34 mmole), and sodium tert-butoxide (0.325 g, 3.57 mmole) in anhydrous toluene (10 mL) were heated to 70 °C for16 hours. The mixture was filtered, concentrated under reduced pressure, and the residue purified by chromatography (silica gel; hexane:EtOAc, 9:1 to 1:1) to provide the title compound (0.522 g, 67percent). 1H NMR (DMSO-d6, 300 MHz) delta 1.33-1.38 (m 9H), 2.50 (br s, 2H), 3.02 (m, 1H), 3.16 (d, J=10.17 Hz, 1H), 3.27 (m, 1H), 3.53 (m, 1H), 4.43 (m, 1H), 4.58 (br, s 1H), 7.11 (dd, J=3.05, 8.81 Hz, 1H), 7.24 (d, J=27.46 Hz, 1H), 7.77 (d, J=3.05Hz, 1H); MS (DCI/NH3) m/z 310 (M+H)+.
67%	With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 70℃; for 16h;	The product from Example 15B (0.5 g, 2.5 mmole), 2-chloro-5-iodopyridine (0.88 g, 3.35 mmole, available as described in Tetrahedron Lett., 1993, 34, 7493-7496), Pd2(dba)3 (0.13 g, 0.16 mmole), BINAP (0.22 g, 0.34 mmole), and sodium tert-butoxide (0.325 g, 3.57 mmole) in anhydrous toluene (10 mL) were heated to 70° C. for 16 hours. The mixture was filtered, concentrated under reduced pressure, and the residue purified by chromatography (silica gel; hexane:EtOAc, 9:1 to 1:1) to provide the title compound (0.522 g, 67percent). 1H NMR (DMSO-d6, 300 MHz) delta 1.33-1.38 (m 9H), 2.50 (br s, 2H), 3.02 (m, 1H), 3.16 (d, J=10.17 Hz, 1H), 3.27 (m, 1H), 3.53 (m, 1H), 4.43 (m, 1H), 4.58 (br, s 1H), 7.11 (dd, J=3.05, 8.81 Hz, 1H), 7.24 (d, J=27.46 Hz, 1H), 7.77 (d, J=3.05 Hz, 1H); MS (DCI/NH3) m/z 310 (M+H)+.

Reference： [1]Patent: EP1147112,2003,B1 .Location in patent: Page/Page column 19
[2]Patent: US2003/225268,2003,A1 .Location in patent: Page 21-22

44
[ 134003-84-2 ]
[ 94191-15-8 ]
[ 286947-12-4 ]

Yield	Reaction Conditions	Operation in experiment
		The product from Example 15B and 2-bromothieno[3,2-b]pyridine, prepared as described in (J. Het. Chem. (1984), 785-789), were processed as described in Example 1A to provide the title compound.

Reference： [1]Patent: US2003/225268,2003,A1 .Location in patent: Page 33

45
[ 134003-84-2 ]
[ 13636-88-9 ]
[ 851527-70-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	In methanol; at 70℃; for 4h;	5-(1-Methylsulfanyl-3-oxo-3-phenyl-propenyl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic Acid tert-butyl Ester 3,3-Bis-methylsulfanyl-1-phenyl-propenone (0.675 g, 3.0 mmol), was prepared according to literature procedure (Galli, f. et al WO 01/92251 A1) and was combined with the product of Example 24 (0.200 g, 1.0 mmol) in 10 mL MeOH. This mixture was warmed to 70° C. for 4 h then was cooled to ambient temperature, concentrated under reduced pressure and purified via column chromatrography (SiO2, 10percent CH3 OH-CH2Cl2 with 1percent NH4OH) to give 0.159 g of the title compound (0.38 mmol, 38percent yield). MS (DCl/NH3) m/z 375 (M+H)+.

Reference： [1]Patent: US2005/101602,2005,A1 .Location in patent: Page/Page column 80

46
[ 134003-84-2 ]
1-(4-chloro-3-methoxyphenyl)ethan-1-one [ No CAS ]
C₂₈H₄₁ClN₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 20℃; for 1h;	A solution of 4-chloro-3-methoxybenzaldehyde (170 mg) and 2,5- Diazabicyclo [2.2. 1] heptane-2-carboxylic acid tert-butyl ester (35 mg) in THF (5 mL) was stirred at room temperature for 1 hour and then sodium triacetoxyborohydride (212 mg) was added in one portion. The mixture was stirred at room temperature for another hour and EtOAc (5 mL) was added followed by the addition of saturated aqueous ammonium chloride (1 mL). The aqueous phase was extracted by EtOAc (3 x l mL) and the combined organic extractants was dried, filtered and concentrated in vacuo. The reaction crude was used as it was.

Reference： [1]Patent: WO2005/84667,2005,A1 .Location in patent: Page/Page column 80

47
[ 134003-84-2 ]
[ 534601-70-2 ]
5-{7-(2-chloro-pyridin-4-yl)-8-(3-(trifluoromethyl)phenyl)-1,2,4-triazolo[4,3-c]pyrimidin-5-yl}-2-(tert-butoxycarbonyl)-(1R)-2,5-diaza-bicyclo[2.2.1]heptane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide;	EXAMPLE 7 Preparation of 5-{7-(2-chloro-4-pyridyl)-8-(3-(trifluoromethyl)phenyl)-1,2,4-triazolo[4,3-c]pyrimidin-5-yl}-2-(tert-butoxycarbonyl)-(1R)-2,5-diaza-bicyclo[2.2.1]heptane A mixture of 5-chloro-7-(2-chloro-4-pyridyl)-8-(3-(trifluoromethyl)-phenyl)-1,2,4-triazolo[4,3-c]pyrimidine (820 mg, 2.0 mmole), potassium carbonate (ca. 1.0 g) and (-)-2-(tert-butoxycarbonyl)-(1R,4R)-2,5-diaza-bicyclo[2.2.1]heptane (436 mg, 2.2 mmole) in 10 ml of DMF was stirred at room temperature for 16 hours. The reaction solution was poured into water (50 mL), and precipitate was filtered and washed with water and dried under vacuum to give product as off white solid; MS m/z (M)+572.3; C27H25ClF3N7O2 requir. 572.

Reference： [1]Patent: US2003/195221,2003,A1

Yield	Reaction Conditions	Operation in experiment
93.2%		(11) 2-(t-butyloxycarbonyl)-(1R,4R)-2,5-diazabicyclo [2.2.1]heptane. Into a solution of (10) (3.65 g, 12.67 mmol) in 200 mL of EtOH was added AcOH (1 mL). The reaction mixture was treated with 10percent palladium-on-carbon (1.10 g) and hydrogenated at 50 psi for 2 h at 23° C. The mixture was then heated to 60° C. and hydrogenation was continued for 2 h. After this time, heating was discontinued; the reaction mixture was allowed to cool to room temperature and hydrogenation was continued for 3 h. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was made alkaline by the addition of 5N NaOH and extracted with CH2 Cl2 (5*100 mL). Combined CH2 Cl2 extracts were dried over K2 CO3, filtered and concentrated under reduced pressure to give the title compound (2.34 g, 93.2percent). The product was used in the next step without further purification.

49
[ 134003-84-2 ]
[ 777-44-6 ]
C₁₇H₂₁F₃N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In dichloromethane; at 20℃;	EXAMPLE 5To a solution of (IS, 4S)-2-tert-butoxycarbonyl-2,5-diazabicyclo[2.2.1]heptane (0.04g, 0.2 mMol) inCH2CI2 (1 mL) were added 3-trifluoromethylbenzene sulfonylchloride (0.05 g), Et3N (0.07 mL) andDMAP (0.00 Ig), and the reaction was stirred at room temperature overnight. The reaction was diluted 15 with EtOAc and washed with water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The crude product obtained was then purified by chromatography on silica-gel usingEtOAc-hexanes (1 :2) to give the titled compound (0.048g).1H-NMR (CDCl3): delta 1.46 (s, 9H), 1.66 (d, 2H), 2.76-3.45 ( complex m, 6H), 3.65 (m, IH), 4.13 (d, IH),4.29 (d, I H), 4.48 (d, IH), 4.70 (s,lH), 7.18-7.65 (m, 4H). .0 Mass Spectra (m/e): 407.3 (M+H).

Reference： [1]Patent: WO2007/84394,2007,A2 .Location in patent: Page/Page column 28

50
[ 134003-84-2 ]
[ 606-83-7 ]
C₂₅H₃₀N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In dichloromethane; at 20℃;	EXAMPLE 1To a solution of (1 S, 4S)-2-tert-butoxycarbonyI-2,5-dazabicyclo[2.2.1]heptane (0^g, 0.2 mMol) in CH2Cl2 (1 mL) were added 3,3-diphenylpropionic acid (0.05 g, 0.22 mMol) and l-Ethyl-l-(3- dimethylaminopropyl)carbodiimide (EDC) (0.06g, 0.31 mMol) at room temperature, and the mixture was stirred overnight. The reaction was diluted with EtOAc (10 mL) and washed with water, saturated aqueous NaHCO3 and water. After drying over anhydrous Na2SOj5 the organic phase was concentrated to give the crude product, which was then purified by radial chromatography using acetone-hexanes ( 1 :2) to give the title compound as white solid (0.076g).1H-NMR (CDCl3): delta 1.46 (s, 9H), 1.66 (d, 2H), 2.89-3.33 ( complex m, 6H), 4.20-4.86 (m, 3H), 7.34-7.15 (m, 10 H). Mass Spectra (m/e): 407.55 (M+H) and 351.49 (M-56+H).

Reference： [1]Patent: WO2007/84394,2007,A2 .Location in patent: Page/Page column 26

51
[ 134003-84-2 ]
[ 1042224-71-4 ]
C₂₂H₂₅N₅O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3656 - 3660

52
[ 326596-46-7 ]
[ 134003-84-2 ]

Yield	Reaction Conditions	Operation in experiment
66%	With ammonia; In water; at 65℃; for 16h;	Step B: (2R,5R)-2,5-Diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester. A heterogeneous mixture of (4S,2R)-4-methanesulfonyloxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1 g, 2.7 mmol) in ammonium hydroxide (27 wt % solution in water, 10 mL) was warmed to 65 C. in a sealed tube for 16 h during which time the mixture became homogeneous. The aqueous was extracted with CH2Cl2 (2×) and the combined organics were dried over Na2SO4, filtered, and concentrated to provide the title compound as a yellow solid that was used directly in subsequent steps (350 mg, 66%). MS (ESI): mass calcd. for C10H18N2O2, 198.1; m/z found, 199.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 4.48-4.27 (m, 1H), 3.70 (s, 1H), 3.41-3.30 (m, 1H), 3.22-3.11 (m, 1H), 3.08-2.95 (m, 2H), 1.80-1.65 (m, 2H), 1.48 (s, 9H).

Reference： [1]Patent: US2009/111794,2009,A1 .Location in patent: Page/Page column 15

53
[ 134003-84-2 ]
[ 698981-68-9 ]
C₂₀H₂₅N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5653 - 5656

54
[ 134003-84-2 ]
[ 1178903-94-0 ]
1,1-dimethylethyl (1S,4S)-5-[(5'-[({6-[([1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃;	Example 140 N-({3'-[(1S,4S)-2,5-Diazabicyclo[2.2.1]hept-2-ylmethyl]-6-methyl-3-biphenylyl}methyl)-N'-[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide A mixture of N-[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(3'-formyl-6-methyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (610 mg, 0.925 mmol), 1,1-dimethylethyl (1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (183 mg, 0.925 mmol), sodium triacetoxyborohydride (392 mg, 1.849 mmol) and acetic acid (0.064 mL, 1.109 mmol) in DCM (10 mL) was stirred at room temperature overnight. The reaction mixture was quenched with saturated NaHCO3 and extracted with DCM twice. The combined organic layers were concentrated under vacuum to give a crude residue. It was purified with Companion, eluding with 0 to 100percent ethyl acetate in hexane to get rid of impurities and then 10percent methanol in DCM to elute the product. The product fractions were combined and concentrated under vacuum to give 1,1-dimethylethyl (1S,4S)-5-[(5'-[({6-[([1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2'-methyl-3-biphenylyl)methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate as a solid. It was re-dissolved in 25percent TFA in DCM (2 mL) and stirred at room temperature for 2 h. Solvent was evaporated under a stream of nitrogen and then the residue was purified with a Gilson HPLC (with 0.1percent TFA in the solvents), eluding with 10 to 70percent CH3CN in water at a flow rate of 20 mL/min. The product fractions were combined and converted to the free base with 1 N NaOH, and the basified solution was extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and then concentrated under vacuum to give N-({3'-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl]-6-methyl-3-biphenylyl}methyl)-N'-[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide as a solid (431 mg, 62.8percent). LC-MS m/z 743 (M+H)+, 1.18 min (ret time).

Reference： [1]Patent: US2009/203657,2009,A1 .Location in patent: Page/Page column 98

55
[ 134003-84-2 ]
[ 1190927-36-6 ]
C₂₄H₂₈N₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With potassium carbonate; In acetonitrile; at 80℃; for 16h;	To a solution of 2-[4-([1,3]thiazolo[4,5-b]pyridin-2-yloxy)phenyl]ethyl methanesulfonate (500 mg, 1.42 mmol, 1 equiv.) and K2CO3 (196 mg, 1.42 mmol, 1 equiv.) in CH3CN (14 mL) was added <strong>[134003-84-2](1R,4R)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester</strong> (340 mg, 1.7 mmol, 1.2 equiv.). The mixture was stirred at 80° C. for 16 h, concentrated, diluted in CH2Cl2 (25 mL), and washed with satd. aq. NaHCO3 (225 mL). The organic layer was dried, filtered, and concentrated. Purification using column chromatography (10percent MeOH/CH2Cl2) afforded an oil (202 mg, 31percent), which was re-dissolved in CH2Cl2. To this solution was added HCl (4 M in dioxane, 1.3 mL, 10 equiv.). The reaction mixture was stirred at rt for 16 h and concentrated to afford the amine hydrochloride salt as a pink solid (100percent). To a solution of this amine hydrochloride salt (164 mg, 0.42 mmol, 1 equiv.) and Et3N (0.23 mL, 1.68 mmol, 4 equiv.) in CH2Cl2 (2.3 mL) was added acetic anhydride (0.14 mL, 0.63 mmol, 1.5 equiv.). The reaction mixture was stirred at rt for 2 h, diluted with CH2Cl2 (15 mL) and washed with satd. aq. NaHCO3 (120 mL). The organic layer was dried, filtered, and concentrated. Purification using column chromatography (30percent MeOH/CH2Cl2) afforded the product as a light pink oil (37 mg, 22percent). 1H NMR (500 MHz, CDCl3): 8.58-8.56 (m, 1H), 8.03 (ddd, J=7.9, 2.3, 1.7, 1H), 7.36-7.28 (m, 4H), 7.21 (ddd, J=7.9, 4.9, 1.3, 1H), 4.77 (s, 0.5H), 4.24 (s, 0.5H), 3.68 (dd, J=11.4, 1.5, 0.5H), 3.61 (s, 1H), 3.57 (dd, J=9.5, 1.1, 0.5H), 3.33 (dd, J=9.4, 2.2, 0.5H), 3.27 (dd, J=11.4, 1.9, 0.5H), 3.11 (dd, J=9.5, 2.2, 0.5H), 2.96 (dd, J=9.6, 2.2, 0.5H), 2.89-2.70 (m, 4.5H), 2.56 (dd, J=9.5, 1.2, 0.5H), 2.03 (s, 3H), 1.96 (d, J=10.1, 0.5H), 1.89 (d, J=9.9, 0.5H), 1.80 (d, J=9.7, 0.5H), 1.69 (d, J=9.9, 0.5H). MS (ESI): mass calcd. for C21H22N4O2S, 394.15; m/z found, 395.1 [M+H]+.

Reference： [1]Patent: US2009/258854,2009,A1 .Location in patent: Page/Page column 52

56
[ 872-85-5 ]
[ 134003-84-2 ]
tert-butyl 5-(pyridin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃; for 15h;	Amine F-26: 2-(Pyridin-4-ylmethyl)-2,5-diazabicyclo[2.2.1]heptane dihydrochloride(i): Tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (5 g, 25.214 mmol) and pyridine-4-carbaldehyde (2.97 g, 27.74 mmol) were placed in dichloromethane (650 ml); sodium triacetoxyborohydride (10.6 g, 50.43 mmol) and glacial acetic acid (0.14 ml, 2.521 mmol) were added, and the reaction mixture was stirred for 15 hours at room temperature. Hydrolysis was then carried out with saturated sodium hydrogen carbonate solution, the phases were separated, and the aqueous phase was extracted 2x with diethyl ether. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel; dichloromethane/methanol).Yield: 5.8 g, 79percent.

Reference： [1]Patent: US2010/173889,2010,A1 .Location in patent: Page/Page column 59

57
[ 134003-84-2 ]
[ 39856-50-3 ]
[ 1331847-50-7 ]

Yield	Reaction Conditions	Operation in experiment
57%	In N,N-dimethyl-formamide; at 100℃;	Step 1 :Preparation of 5-(6-Nitro-pyridin-3-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester.2-Bromo-5-Nitropyridine (4.75 g, 23.4 mmol, 1.0 eq) and (R,R)-2,5-Diaza- bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (5.04 g, 25.4 mmol, 1.1 eq) were combined in DMF (60mL) and heated to 100C. The reaction was cooled and diluted with Ethyl Acetate, washed with water several times followed by brine, the organic layer dried (Na2S04), filtered, and the organic concentrated. Crude was purified using chromatography eluting with MeOH/DCM mixtures giving the desired product (4.3g, 57%). MS m/z 278.4 (M-C4H9).

Reference： [1]Patent: WO2011/101409,2011,A1 .Location in patent: Page/Page column 222-223

58
[ 134003-84-2 ]
[ 1331847-51-8 ]

Reference： [1]Patent: WO2011/101409,2011,A1

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P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 134003-84-2 ]

Quality Control of [ 134003-84-2 ]

Related Doc. of [ 134003-84-2 ]

Product Details of [ 134003-84-2 ]

Calculated chemistry of [ 134003-84-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 134003-84-2 ]

Application In Synthesis of [ 134003-84-2 ]

[ 134003-84-2 ] Synthesis Path-Upstream 1~7

[ 134003-84-2 ] Synthesis Path-Downstream 1~58

Related Functional Groups of [ 134003-84-2 ]

Amides

Related Parent Nucleus of [ 134003-84-2 ]

Aliphatic Heterocycles

Other Aliphatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 134003-84-2 ]

Related Parent Nucleus of
[ 134003-84-2 ]