[ CAS No. 674792-04-2 ] {[proInfo.proName]}

Name: 674792-04-2|(R)-1-Boc-2-Isopropylpiperazine|98%
Brand: Ambeed
SKU: A247383
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Quality Control of [ 674792-04-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 674792-04-2 ]

SDS Specification

Alternatived Products of [ 674792-04-2 ]

Product Details of [ 674792-04-2 ]

CAS No. :	674792-04-2	MDL No. :	MFCD07772101
Formula :	C₁₂H₂₄N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NZTWGWFHWJARJX-JTQLQIEISA-N
M.W :	228.33	Pubchem ID :	24820392
Synonyms :

Calculated chemistry of [ 674792-04-2 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.92
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	72.92
TPSA :	41.57 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.38 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.95
Log Po/w (XLOGP3) :	1.85
Log Po/w (WLOGP) :	1.09
Log Po/w (MLOGP) :	1.44
Log Po/w (SILICOS-IT) :	1.19
Consensus Log Po/w :	1.7

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.16
Solubility :	1.59 mg/ml ; 0.00696 mol/l
Class :	Soluble
Log S (Ali) :	-2.34
Solubility :	1.03 mg/ml ; 0.00453 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.88
Solubility :	3.03 mg/ml ; 0.0133 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.85

Safety of [ 674792-04-2 ]

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

Application In Synthesis of [ 674792-04-2 ]

* 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 [ 674792-04-2 ]
Downstream synthetic route of [ 674792-04-2 ]

[ 674792-04-2 ] Synthesis Path-Upstream 1~4

1
[ 674791-98-1 ]
[ 674792-04-2 ]

Reference： [1] Patent: WO2004/24720, 2004, A1, . Location in patent: Page 82

2
[ 674791-88-9 ]
[ 674792-04-2 ]

Reference： [1] Patent: WO2004/24720, 2004, A1,

3
[ 674791-86-7 ]
[ 674792-04-2 ]

Reference： [1] Patent: WO2004/24720, 2004, A1,

4
[ 24424-99-5 ]
[ 674791-94-7 ]
[ 674792-04-2 ]

Reference： [1] Patent: WO2004/24720, 2004, A1,

[ 674792-04-2 ] Synthesis Path-Downstream 1~29

2
[ 674791-98-1 ]
[ 674792-04-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃;	Compound 38 (0.40 g, 1.25 mmol) was dissolved in 6.3 mL of MeOH and 10% Pd/C (0.04 g) was added, and then stirred at room temperature under H2 overnight. This mixture was filtered through Celite using [CH2C12] and concentrated to give compound 41 as an oil.

Reference： [1]Patent: WO2004/24720,2004,A1 .Location in patent: Page 82

3
[ 674792-04-2 ]
[ 914636-38-7 ]
(R)-tert-butyl 4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In toluene; tert-butyl alcohol; at 110℃; for 20h;Sealed tube; Inert atmosphere;	[00132] A 50-mL RBF, equipped with a stir bar, was charged with (R)-tert-butyl 2- isopropylpiperazine- 1-carboxylate (250 mg, 1.1 mmol), 4-bromo- 1-fluoro-2- (methylsulfonyl)benzene (277 mg, 1.1 mmol), Pd2(dba)3 (66 mg, 0.066 mmol), X-phos (157 mg, 0.33 mmol) and Cs2CO3 (892 mg, 2.74 mmol). The flask was sealed with a rubber septum and flushed with N2 for 10 mm. Dry toluene (5 mL) and dry t-BuOH (1 mL) were introduced by syringe and the mixture was heated at 110 C for 20 h. The mixture was diluted with EtOAc (90 mL), washed with water (10 mL) and brine (10 mL), and dried over Na2SO4. Removal of the solid left a yellow solid (730 mg) which was purified by chromatography on a 40-g silica cartridge, eluted with a 0 - 100% EtOAc in hexanes gradient, to afford (R)-tert-butyl 4-(4-fluoro-3-(methylsulfonyl)phenyl)-2- isopropylpiperazine-1-carboxylate (420 mg, 95%). ?H NMR (CDC13) 0.88 (d, 3H), 1.00 (d, 3H), 1.44 (s, 9H), 2.22-2.34 (m, 1H), 2.68-2.71 (m, 2H), 3.02-3. 14 (m, 1H), 3.18 (s, 3H),3.36-3.44 (m, 1H), 3.54-3.62 (m, 1H), 3.70-3.90 (m, 1H), 4.00-4.15 (m, 1H), 7.05-7.18 (m, 2H), 7.36-7.39 (m, 1H). ?9F NMR (CDC13) -122.5. LC-MS Method 4 tR = 1.01 mm, mlz =423, 401, 345.

Reference： [1]Patent: WO2016/22521,2016,A1 .Location in patent: Paragraph 00132
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271

4
[ 674792-04-2 ]
[ 36282-26-5 ]
[ 20277-69-4 ]
(R)-tert-butyl 4-(4-cyano-3-(methylsulfonyl)phenyl)-2-isopropylpiperazine-1-carboxylate [ No CAS ]
(R)-tert-butyl 4-(3-bromo-4-cyanophenyl)-2-isopropylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%; 62%		[00134] A stirred solution of <strong>[674792-04-2](R)-tert-butyl 2-isopropylpiperazine-1-carboxylate</strong> (360 mg, 1.58 mmol), 2-bromo-4-fluorobenzonitrile (316 mg, 1.58 mmol), i-Pr2NEt (0.6 mL, 3.3 mmol) and DMSO (4 mL) was heated at 120 C for 2 h. The mixture was cooled to rt and used directly in the next step.[00135] Step 2[00136] NaSO2Me (1.61 g, 15.8 mmol) and proline (55 mg, 0.47 mmol) were added to the mixture. The mixture was sparged with N2 for 10 mm and CuT (54 mg, 0.28 mmol) was added. The mixture was heated at 110 C under N2 for 16 h. The mixture was cooled, diluted with EtOAc (100 mL), washed with water (2 x 10 mL) and brine (10 mL), and dried over Na2504. Removal of the solvent left an orange oil (677 mg). Chromatography on a 40- g silica cartridge eluted with a 0-100% EtOAc in hexanes gradient afforded (R)-tert-butyl 4- (3-bromo-4-cyanophenyl)-2-isopropylpiperazine- 1 -carboxylate (403 mg, 62%) and the title compound (75 mg, 11%). LC-MS Method 4 tR = 0.96 mm, mlz = 408, 352, 308.

Reference： [1]Patent: WO2016/22521,2016,A1 .Location in patent: Paragraph 00134; 00135; 00136

5
2-bromo-4-fluoro-1-(trifluoromethyl)benzene [ No CAS ]
[ 674792-04-2 ]
[ 20277-69-4 ]
tert-butyl (R)-2-isopropyl-4-(3-(methylsulfonyl)-4-(trifluoromethyl)phenyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[00134] A stirred solution of <strong>[674792-04-2](R)-tert-butyl 2-isopropylpiperazine-1-carboxylate</strong> (360 mg, 1.58 mmol), 2-bromo-4-fluorobenzonitrile (316 mg, 1.58 mmol), i-Pr2NEt (0.6 mL, 3.3 mmol) and DMSO (4 mL) was heated at 120 C for 2 h. The mixture was cooled to rt and used directly in the next step.[00135] Step 2[00136] NaSO2Me (1.61 g, 15.8 mmol) and proline (55 mg, 0.47 mmol) were added to the mixture. The mixture was sparged with N2 for 10 mm and CuT (54 mg, 0.28 mmol) was added. The mixture was heated at 110 C under N2 for 16 h. The mixture was cooled, diluted with EtOAc (100 mL), washed with water (2 x 10 mL) and brine (10 mL), and dried over Na2504. Removal of the solvent left an orange oil (677 mg). Chromatography on a 40- g silica cartridge eluted with a 0-100% EtOAc in hexanes gradient afforded (R)-tert-butyl 4- (3-bromo-4-cyanophenyl)-2-isopropylpiperazine- 1 -carboxylate (403 mg, 62%) and the title compound (75 mg, 11%).[00137] Cpd No 3-2, tert-butyl (R)-2-isopropyl-4- (3- (methylsulfonyl)-4- (trifluoromethyl)phenyl)piperazine- 1 -carboxylate, is prepared following similar procedures using 2-bromo-4-fluoro-1-(trifluoromethyl)benzene in Step 1. LC-MS mlz = 473, 395, 351..

Reference： [1]Patent: WO2016/22521,2016,A1 .Location in patent: Paragraph 00134; 00135; 00136; 00137

6
[ 674792-04-2 ]
[ 773134-43-3 ]
tert-butyl (R)-2-isopropyl-4-(4-(methoxycarbonyl)-3-(methylsulfonyl)phenyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In toluene; at 100℃; for 2h;Inert atmosphere; Sealed tube;	[00196] To a mixture of amine 7 (740 mg, 3.0 mmol), bromide 8 (1.05 g, 3.6 mmol), Xphos (160, 0.33 mmol) and Cesium carbonate (2.93 g, 9.0 mmol) in toluene (7 mL) was added Pd2(dba)3 (140 mg, 0.15 mmol). The mixture was purged with nitrogen and the tube was sealed. It was heated in an oil bath at 100C for 10 h. After cooling to rt, the reaction mixture was filtered and concentrated. The residue was purified by silica gel chromatography (EtOAc/hexanes = 40/60) to afford the coupling product 9 (1.17 g, 86% yield). LC-MS tR = 1.66 mm in 2 mm chromatography, MS (ESI) m/z 463 [M + 231+.

Reference： [1]Patent: WO2016/22521,2016,A1 .Location in patent: Paragraph 00196
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271
[3]European Journal of Medicinal Chemistry,2019,vol. 178,p. 458 - 467

7
[ 674792-04-2 ]
(R)-(2-(4-(4-(hydroxymethyl)-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidin-5-yl)methanol [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271
[3]European Journal of Medicinal Chemistry,2019,vol. 178,p. 458 - 467

8
[ 674792-04-2 ]
(R)-5-chloro-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1

9
[ 674792-04-2 ]
(R)-5-bromo-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1

10
[ 674792-04-2 ]
(R)-5-cyclopropyl-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1

11
[ 674792-04-2 ]
methyl (R)-4-(3-isopropylpiperazin-1-yl)-2-(methylsulfonyl)benzoate [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271
[3]European Journal of Medicinal Chemistry,2019,vol. 178,p. 458 - 467

12
[ 674792-04-2 ]
ethyl (R)-2-(2-isopropyl-4-(4-(methoxycarbonyl)-3-(methylsulfonyl)phenyl)piperazin-1-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271

13
[ 674792-04-2 ]
(R)-1-(4-fluoro-3-(methylsulfonyl)phenyl)-3-isopropylpiperazine hydrochloride [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1

14
[ 674792-04-2 ]
(R)-2-(4-(4-fluoro-3-(methylsulfonyl)phenyl)-2-isopropylpiperazin-1-yl)-4-(trifluoromethyl)pyrimidine trifluoroacetic acid salt [ No CAS ]

Reference： [1]Patent: WO2016/22521,2016,A1

15
[ 674792-04-2 ]
[ 373384-18-0 ]
(R)-tert-butyl 2-isopropyl-4-(3-(methylsulfonyl)phenyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With oxygen; copper diacetate; In 1,2-dichloro-ethane; at 70℃; under 760.051 Torr; for 18.0h;Molecular sieve;	[00130] A mixture of (R)-tert-butyl 2-isopropylpiperazine- 1-carboxylate (377 mg, 1.65 mmol), <strong>[373384-18-0](3-(methylsulfonyl)phenyl)boronic acid</strong> (660 mg, 3.30 mmol), Cu(OAc)2.H20 (33 mg, 0.17 mmol), powdered 4 A sieves (930 mg) and dry 1,2-dichloroethane (8 mL) was heated at 70 C under 02 (1 atm, balloon) for 18 h. The mixture was diluted with EtOAc (75 mL) and filtered through Celite. The filtrate was concentrated to leave a brown oil (1.34 g). Chromatography on a 40-g silica cartridge, eluted with a 0-100% EtOAc in hexanes gradient afforded an oil (604 mg). Prep HPLC afforded the title compound (329 mg, 52%) as an oil. LC-MS Method 4 tR = 0.97 mm, mlz = 383, 368, 327, 283. 1H NMR (CDC13) 0.86 (d, 3H), 1.02 (d, 3H), 1.44 (s, 9H), 2. 17-2.30 (m, 1H), 2.75-2.90 (m, 2H), 3.01 (s, 3H), 3.02-3.15 (m, 1H), 3.48-3.57 (m, 1H), 3.68-3.74 (m, 1H), 3.95-4.10 (m, 1H), 7.05-7. 12 (m, 1H), 7.29-7.45 (m, 3H).

Reference： [1]Patent: WO2016/22521,2016,A1 .Location in patent: Paragraph 00130
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 3264 - 3271

16
[ 674792-04-2 ]
(R)-3-isopropyl-1-(3-(methylsulfonyl)phenyl)piperazine hydrochloride [ No CAS ]