[ CAS No. 1021298-67-8 ] {[proInfo.proName]}

Name: 1021298-67-8|1-(Cyclopropylcarbonyl)piperazine hydrochloride|97%
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Quality Control of [ 1021298-67-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1021298-67-8 ]

CAS No. :	1021298-67-8	MDL No. :	MFCD03428576
Formula :	C₈H₁₅ClN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WIHDAPMHNYYTOA-UHFFFAOYSA-N
M.W :	190.67	Pubchem ID :	20847955
Synonyms :

Calculated chemistry of [ 1021298-67-8 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.88
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	57.03
TPSA :	32.34 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.23 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.33
Log Po/w (WLOGP) :	-0.19
Log Po/w (MLOGP) :	0.6
Log Po/w (SILICOS-IT) :	0.91
Consensus Log Po/w :	0.33

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.1
Solubility :	15.2 mg/ml ; 0.0798 mol/l
Class :	Very soluble
Log S (Ali) :	-0.57
Solubility :	51.0 mg/ml ; 0.267 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.91
Solubility :	23.5 mg/ml ; 0.123 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.35

Safety of [ 1021298-67-8 ]

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 [ 1021298-67-8 ]

* 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 [ 1021298-67-8 ]
Downstream synthetic route of [ 1021298-67-8 ]

[ 1021298-67-8 ] Synthesis Path-Upstream 1~2

1
[ 414910-15-9 ]
[ 1021298-67-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride In methanol at 0 - 20℃;	To a stirred mixture of compound tert-butyl 4-(cyclopropanecarbonyl)piperazine-1-carboxylate (3.7 g, 14.5 mmol) in methanol (15 mL) was added hydrochloride/methanol (15 mL, 3M)) at 0° C. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was concentrated to give cyclopropyl(piperazin-1-yl)methanone hydrochloride (2.74 g, yield 100percent) as an off-white solid. ¹H-NMR (400 MHz, DMSO-d6) δ (ppm): 0.71-0.76 (m, 4H), 1.96-2.03 (m, 1H), 3.04-3.16 (m, 4H), 3.69-4.08 (m, 4H), 9.58 (s, 2H); LC-MS (ESI) m/z: 155(M+1)⁺
100%	With hydrogenchloride In methanol at 0 - 20℃;	Example 17BCyclopropyl(piperazin- 1 -yl)methanone hydrochloride[00524] To a stirred mixture of compound ter/-butyl 4-(cyclopropanecarbonyl)piperazine- 1 -carboxylate (3.7 g, 14.5 mmol) in methanol (15 mL) was added hydrochloride/methanol (15 mL, 3M)) at 0 °C. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was concentrated to give cyclopropyl(piperazin- 1 -yl)methanone hydrochloride (2.74 g, yield 100percent) as an off- white solid. ^-NMR (400 MHz, DMSO-i/6) δ (ppm): 0.71-0.76 (m, 4H), 1.96-2.03 (m, 1H), 3.04-3.16 (m, 4H), 3.69-4.08 (m, 4H), 9.58 (s, 2H); LC-MS (ESI) m/z: 155(M+1)⁺.

Reference： [1] Patent: US2010/35883, 2010, A1, . Location in patent: Page/Page column 56
[2] Patent: WO2011/130661, 2011, A1, . Location in patent: Page/Page column 102-103

2
[ 110-85-0 ]
[ 4023-34-1 ]
[ 1021298-67-8 ]

Reference： [1] Patent: WO2008/47082, 2008, A2, . Location in patent: Page/Page column 25

[ 1021298-67-8 ] Synthesis Path-Downstream 1~5

1
[ 763114-26-7 ]
[ 1021298-67-8 ]
[ 763113-22-0 ]

Yield	Reaction Conditions	Operation in experiment
94.5%	Stage #1: 2-fluoro-5-((4-oxo-3,4-dihydrophthalazine-1-yl)methyl)benzoic acid With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In tetrahydrofuran at 25℃; for 1h; Stage #2: cyclopropyl(piperazin-1-yl)methanone hydrochloride With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20 - 25℃; for 5.5h;	5 A method for preparing olaparib, comprising the steps of: adjusting a temperature to 25 °C, 2-fluoro-5-[(4-oxo-3,4-dihydronaphthyridin-1-yl)- yl] benzoic acid in tetrahydrofuran was added, in batches 1-ethyl - (3-dimethylaminopropyl) carbodiimide hydrochloride, stirred for 1h resulting solution was incubated as A; 1-cyclopropyl Formylpiperazine hydrochloride, N,N-diisopropylethylamine was added to tetrahydrofuran, stirred at room temperature for 30 min to obtain solution B; solution A was added dropwise to solution B, the temperaturewasadjustedto 25 °C, the reaction was kept for 5 h, and the temperature was lowered. To the temperature of 20 °C, and then quenched with water, control the temperature below 25 °C, concentrate to remove tetrahydrofuran, add the recrystallization solvent ethyl acetate and activated carbon, warmed to reflux, filtered hot, the filtrate was recrystallized, followed by water,Washed with ethyl acetate and dried to obtain olaparib;
92.2%	With triethylamine In dichloromethane at -10 - 20℃; for 4h;	2 Example 2: A preparation method of olaparib includes the following steps: Combine 2-fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid (10g, 33.53mmol) and 1-cyclopropylformylpiperazine hydrochloride (5.17g, 33.53mmol) was added to 120g of dichloromethane, triethylamine (10.18g, 100.6mmol) was added, Cool down, add ethyl chloroformate (4.37g, 40.23mmol) dropwise at -10°C for about 1h, keep the reaction for 2h, then remove the freezing, warm to room temperature and react for 1h. After the completion of the reaction, 100g of water was added dropwise to the reaction solution for liquid separation, the organic phase was washed twice with 100ml×2 water, and concentrated under reduced pressure to obtain a solid. The solid was added to absolute ethanol, stirred and refluxed to dissolve, added 0.5g of activated carbon, stirred for 20 minutes, and then added water dropwise. After the solid was precipitated, the temperature was kept and stirred for 1 hour, cooled to 0°C, filtered, and dried to obtain 13.4g of olaparib, with a yield. 92.2%, purity 99.73% (HPLC area normalization method).
91.5%	With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 10℃; for 10h;	1-2 Example 1 Add 1000ml DMF to the reaction flask, cool down to 0-10°C , 2-fluoro-5-((3,4-dihydro-4-oxo-1-phthalazinyl)methyl)benzoic acid(100.0 g),1-Cyclopropylformylpiperazine hydrochloride (73.5g), EDCI (115g) and HOBt (52.1g), N,N-diisopropylethylamine (77.8g), in the range of 0 to 10°C reaction for 10 hours, Slowly add purified water to the system, continue stirring for 2 hours, filter, and rinse the filter cake with purified water;Drying in vacuum at 65±5° C. obtained 44.5 g of new crystal form Q1 of olaparib with a yield of 91.5%.

85.2%	With O-(6-chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 5h;	1.4 Step 4:The 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (213.0g, 0.71mol),cyclopropyl(piperazin-1-yl)methanone Hydrochloride(135.8g, 0.71mol),DIEA (109.9g, 0.85mol) was placed in acetonitrile (1000ml), HCTU (351.6g, 0.85mol) was added at room temperature,The reaction was incubated for 5 hours, and the reaction was monitored by TLC. After the reaction was completed, the acetonitrile was removed under reduced pressure, and 500 ml of water was added to quench the reaction.Then ethyl acetate (800 ml) was added, and the organic layer was dried, filtered, and concentrated to obtain an off-white solid.The off-white solid obtained above was placed in DMF (750ml), the temperature was raised to 80°C, and the solid was dissolved.After hot filtration, the temperature was lowered to room temperature, and a solid was precipitated. The mixture was stirred at room temperature for 2 hours, filtered, and the filter cake was dried to obtain 262.3 g of a white solid with a yield of 85.2%.
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 5 - 20℃;	3.b (b) Compound A; 2-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid (D)(0.95g, 3.19 mmol) was suspended with stirring under nitrogen in acetonitrile (4 ml). 2-(1 H-benzotriazol-1-yl)-1 ,1 ,3,3- tetramethyluronium hexafluorophosphate (HBTU) (1.45g, 3.83 mmol) was added followed by 1-cyclopropylcarbonylpiperazine HCI salt (l')(0.73g, 3.83 mmol). Diisopropylethylamine (1.39ml, 7.98 mmol) was added over 3 minutes and the reaction mixture was stirred for overnight at room temperature. The reaction mixture was cooled to 50C and maintained at this temperature for 1 hour, before being filtered. The filter cake was washed with cold (30C) acetonitrile (2 ml) before being dried in vacuo at up to 400C to give the title compound as a pale yellow solid (0.93g).
18.92 g	With triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 8h;	3.4 Synthesis of Olaparib A solution of 14.91 g of 2-fluoro-5 - ((4-oxo-3,4-dihydrophthalazin-1-yl) methyl) benzoic acid was added 11.44 g of 1-cyclopropyl formylpiperazine hydrochloride, G DCC, 150 ml of methylene chloride. After stirring for about 15 minutes, 12.66 g of triethylamine was added. After 8 h at 20 ° C, the reaction solution was added to 100 ml of methylene chloride and dissolved with saturated NaHCO3Washed with 10 ml of saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The concentrate was recrystallized from 30 ml of methanol, filtered and dried to give a white color Solid 18.92g, HPLC purity greater than 99.5%.
159.2 g	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 3h;	1-3; 5; 7-9 (3) 1900 ml of acetonitrile, 133.69 g of compound IIc, 247.14 g of DIEA and 290.08 g of HBTU were sequentially added to the 5L reaction flask, 190.00 g of compound V was added in batches, the temperature was controlled at 25°C, and the reaction was carried out for 3 hours. Suction filtration, rinse with acetonitrile, add the filter cake into 1900ml of water, stir at 25°C for 2 hours, suction filter, and blow dry the filter cake at 60°C for 20 hours to obtain olaparib solid 190g, purity 99.40%, impurity D content 0.17 %.
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 3h;	2.3; 4.3; 5.3; 6.3 (3) 1900ml of acetonitrile, 133.69g of compound IIc, 247.14g of DIEA and 290.08g of HBTU were sequentially added to the 5L reaction flask,190.00 g of compound V was added in batches, the temperature was controlled at 25°C, and the reaction was carried out for 3 hours.Suction filtration, rinse with acetonitrile, add the filter cake to 1900ml of water, stir at 25°C for 2 hours, suction filter, and blow dry the filter cake at 60°C for 20h,190 g of olaparib solid was obtained, with a purity of 99.40% and an impurity D content of 0.17%.

Reference： [1]Current Patent Assignee: HEFEI CHUANGXIN MEDICAL TECH - CN109535082, 2019, A Location in patent: Paragraph 0058; 0064; 0070; 0076; 0083; 0084; 0085; 0093
[2]Current Patent Assignee: JARI PHARMACEUTICAL - CN112047890, 2020, A Location in patent: Paragraph 0038-0041
[3]Current Patent Assignee: ZILUO PHARMACEUTICAL CO LTD - CN114249695, 2022, A Location in patent: Paragraph 0020; 0063-0066
[4]Current Patent Assignee: BEIJING MESOCHEM TECH - CN113234024, 2021, A Location in patent: Paragraph 0020; 0026
[5]Current Patent Assignee: ASTRAZENECA PLC - WO2008/47082, 2008, A2 Location in patent: Page/Page column 25-26
[6]Current Patent Assignee: GUANGZHOU RENHENG PHARMACEUTICAL TECH - CN106905243, 2017, A Location in patent: Paragraph 0066; 0067
[7]Current Patent Assignee: JILIN SIHUAN PHARMA; JILIN HUIKANG PHARMACEUTICAL; BEIJING SIHUAN PHARM - CN114075159, 2022, A Location in patent: Paragraph 0059; 0107-0116; 0137-0158
[8]Current Patent Assignee: JILIN HUIKANG PHARMACEUTICAL; JILIN SIHUAN PHARMA; BEIJING SIHUAN PHARM - CN114075143, 2022, A Location in patent: Paragraph 0153; 0158-0159; 0164-0165; 0169-0170; 0174

2
[ 414910-15-9 ]
[ 1021298-67-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride; In methanol; at 0 - 20℃;	To a stirred mixture of compound <strong>[414910-15-9]tert-butyl 4-(cyclopropanecarbonyl)piperazine-1-carboxylate</strong> (3.7 g, 14.5 mmol) in methanol (15 mL) was added hydrochloride/methanol (15 mL, 3M)) at 0 C. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was concentrated to give cyclopropyl(piperazin-1-yl)methanone hydrochloride (2.74 g, yield 100%) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6) delta (ppm): 0.71-0.76 (m, 4H), 1.96-2.03 (m, 1H), 3.04-3.16 (m, 4H), 3.69-4.08 (m, 4H), 9.58 (s, 2H); LC-MS (ESI) m/z: 155(M+1)+
100%	With hydrogenchloride; In methanol; at 0 - 20℃;	Example 17BCyclopropyl(piperazin- 1 -yl)methanone hydrochloride[00524] To a stirred mixture of compound ter/-butyl 4-(cyclopropanecarbonyl)piperazine- 1 -carboxylate (3.7 g, 14.5 mmol) in methanol (15 mL) was added hydrochloride/methanol (15 mL, 3M)) at 0 C. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was concentrated to give cyclopropyl(piperazin- 1 -yl)methanone hydrochloride (2.74 g, yield 100%) as an off- white solid. ^-NMR (400 MHz, DMSO-i/6) delta (ppm): 0.71-0.76 (m, 4H), 1.96-2.03 (m, 1H), 3.04-3.16 (m, 4H), 3.69-4.08 (m, 4H), 9.58 (s, 2H); LC-MS (ESI) m/z: 155(M+1)+.

Reference： [1]Patent: US2010/35883,2010,A1 .Location in patent: Page/Page column 56
[2]Patent: WO2011/130661,2011,A1 .Location in patent: Page/Page column 102-103

3
[ 1021298-67-8 ]
[ 619-21-6 ]
[ 1207453-37-9 ]

Yield	Reaction Conditions	Operation in experiment
94%		To a stirred mixture of 3-formylbenzoic acid (450 mg, 3 mmol) in anhydrous dichloromethane (20 mL) was added triethylamine (758 mg, 7.5 mmol), 1-hydroxybenzotriazole (466 mg, 3.45 mmol), followed by 1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (629 mg, 3.45 mmol). After the addition, the mixture was stirred at room temperature for 40 mins. Then the mixture was cooled to 0° C. and cyclopropyl(piperazin-1-yl)methanone hydrochloride (629 mg, 3.3 mmol) was added in portion-wise. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was diluted with dichloromethane (50 mL), washed with saturated citric acid (100 mL.x.2), followed by saturated sodium bicarbonate (100 mL.x.2), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give 3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde (810 mg, yield 94percent) as a light yellow oil. 1H-NMR (400 MHz, CDCl3) delta (ppm): 0.79-0.85 (m, 2H), 1.00-1.04 (m, 2H), 1.73-1.76 (m, 1H), 3.47-3.77 (m, 8H), 7.62-7.66 (t, J=7.6 Hz, 1H), 7.70-7.72 (d, J=7.6 Hz, 1H), 7.95-7.98 (m, 2H), 10.1 (s, 1H); LC-MS (ESI) m/z: 287 (M+1)+
94%		Example 28A3-(4-(Cyclopropanecarbonyl)piperazine- 1 -carbonyl) benzaldehyde[00555] To a stirred mixture of 3-formylbenzoic acid (450 mg, 3 mmol) in anhydrous dichloromethane (20 mL) was added triethylamine (758 mg, 7.5 mmol), 1 -hydroxybenzotriazole (466 mg, 3.45 mmol), followed by l-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (629 mg, 3.45 mmol). After the addition, the mixture was stirred at room temperature for 40 mins. Then the mixture was cooled to 0 °C and cyclopropyl(piperazin- 1 -yl)methanone hydrochloride (629 mg, 3.3 mmol) was added in portion- wise. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was diluted with dichloromethane (50 mL), washed with saturated citric acid (100 mL2), followed by saturated sodium bicarbonate (100 mL2), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give 3-(4-(cyclopropanecarbonyl)piperazine-l -carbonyl) benzaldehyde (810 mg, yield 94percent ) as a light yellow oil. H-NMR (400 MHz, CDC13) delta (ppm): 0.79-0.85 (m, 2H), 1.00-1.04 (m, 2H), 1.73- 1.76 (m, 1H), 3.47-3.77 (m, 8H), 7.62-7.66 (t, J= 7.6 Hz, 1H), 7.70-7.72 (d, J= 7.6 Hz, 1H), 7.95- 7.98 (m, 2H), 10.1 (s, 1H); LC-MS (ESI) m/z: 287 (M+l)+.

Reference： [1]Patent: US2010/35883,2010,A1 .Location in patent: Page/Page column 61-62
[2]Patent: WO2011/130661,2011,A1 .Location in patent: Page/Page column 114

4
[ 1021298-67-8 ]
[ 619-66-9 ]
[ 1207453-21-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4-Carboxybenzaldehyde With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 0.666667h; Stage #2: cyclopropyl (piperazin-1-yl)methanone hydrochloride In dichloromethane at 0 - 20℃;	17C To a stirred mixture of 4-formylbenzoic acid (900 mg, 6 mmol) in anhydrous dichloromethane (30 mL) was added triethylamine (1.52 mg, 15 mmol), 1-hydroxybenzotriazole (891 mg, 6.6 mmol), followed by 1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (1.254 g, 6.6 mmol). After the addition, the mixture was stirred at room temperature for 40 mins. Then the mixture was cooled to 0° C. and cyclopropyl(piperazin-1-yl)methanone hydrochloride (1.259 g, 6.6 mmol) was added in portion-wise. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was diluted with dichloromethane (50 mL), washed with saturated citric acid (100 mL×2), followed by saturated sodium bicarbonate (100 mL×2), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give 4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde (810 mg, yield 80%) as a light yellow oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 0.79-0.85 (m, 2H), 1.00-1.04 (m, 2H), 1.72-1.80 (m, 1H), 3.41-3.81 (m, 8H), 7.58-7.60 (d, J=8.0 Hz, 1H), 7.95-7.97 (d, J=8.0 Hz, 1H), 10.07 (s, 1H); LC-MS (ESI) m/z: 287 (M+1)+
80%	Stage #1: 4-Carboxybenzaldehyde With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 0.666667h; Stage #2: cyclopropyl (piperazin-1-yl)methanone hydrochloride In dichloromethane at 0 - 20℃;	17C Example 17C4-( 4-(Cyclopropanecarbonyl)piperazine- 1 -carbonyl)benzaldehyde[00525] To a stirred mixture of 4-formylbenzoic acid (900 mg, 6 mmol) in anhydrous dichloromethane (30 mL) was added triethylamine (1.52 mg, 15 mmol), 1 -hydroxybenzotriazole (891 mg, 6.6 mmol), followed by l-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride (1.254 g, 6.6 mmol). After the addition, the mixture was stirred at room temperature for 40 mins. Then the mixture was cooled to 0 °C and cyclopropyl(piperazin- 1 -yl)methanone hydrochloride (1.259 g, 6.6 mmol) was added in portion- wise. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was diluted with dichloromethane (50 mL), washed with saturated citric acid (100 mL2), followed by saturated sodium bicarbonate (100 mL2), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give 4-( 4-(cyclopropanecarbonyl)piperazine- l- carbonyl)benzaldehyde (810 mg, yield 80% ) as a light yellow oil. ^-NMR (400 MHz, CDC13) δ (ppm): 0.79-0.85 (m, 2H), 1.00-1.04 (m, 2H), 1.72- 1.80 (m, 1H), 3.41-3.81 (m, 8H), 7.58-7.60 (d, J= 8.0 Hz, 1H), 7.95-7.97 (d, J= 8.0 Hz, 1H), 10.07 (s, 1H); LC-MS (ESI) m/z: 287 (M+l)+.

Reference： [1]Current Patent Assignee: PFIZER INC - US2010/35883, 2010, A1 Location in patent: Page/Page column 56
[2]Current Patent Assignee: BIOMARIN PHARMACEUTICAL INC - WO2011/130661, 2011, A1 Location in patent: Page/Page column 103

5
[ 1021298-67-8 ]
[ 1801984-48-4 ]
[ 1802088-50-1 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: cyclopropyl (piperazin-1-yl)methanone hydrochloride; 7-isopentyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purine-8-carbaldehyde With triethylamine In dichloromethane at 20℃; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 4h;	6.4 STEP 4: 8-((4-(cyclopropanecarbonyl)piperazin-l-yl)methyl)-7-isopentyl-l,3-dimethyl-lH-purine- 2.6(3H.7H)-dione (Cpd. 59) STEP 4: 8-((4-(cyclopropanecarbonyl)piperazin-l-yl)methyl)-7-isopentyl-l,3-dimethyl-lH-purine- 2.6(3H.7H)-dione (Cpd. 59) To a mixture of 7-isopentyl-l,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-lH-purine-8- carbaldehyde (195 mg, 0.7 mmol) and cyclopropyl(piperazin-l-yl)methanone, HC1 (267 mg, 1.400 mmol) was added CH2C12 (Volume: 6 mL) and then Et3N (0.293 mL, 2.100 mmol) at rt. The mixture was stirred for 3-5 min and sodium triacetoxyborohydride (297 mg, 1.400 mmol) was added. The mixture was stirred at rt for 4 h and was poured into CH2Cl2/Na2C03(aq) (5 mL/5 mL). The aqueous layer was extracted with CH2C12 (5 mL x 2). The combined organic layer was dried (Na2S04) and filtered. After removal of solvent, the crude product was purified by silica gel chromatography using 0-5% MeOH/EtOAc as the eluent to give 8-((4-(cyclopropanecarbonyl)piperazin-l-yl)methyl)-7- isopentyl-l,3-dimethyl-lH-purine-2,6(3H,7H)-dione (251 mg, 0.603 mmol, 86 % yield). H NMR (400 MHz, DMSO-d6) δ 4.30 (dd, / = 9.7, 5.6 Hz, 2H), 3.70 (s, 2H), 3.63 (s, 2H), 3.43 (s, 2H), 3.39 (s, 3H), 3.21 (s, 3H), 2.41 (m, 4H), 1.93 (m, 1H), 1.68 (m, 3H), 0.94 (d, / = 5.9 Hz, 6H), 0.68 (tt, / = 7.9, 2.9 Hz, 4H); LC-MS (Method 1): fR = 2.82 min, mJz (M+H)+ = 417.

Reference： [1]Current Patent Assignee: UNIVERSITY OF COLORADO (SYSTEM); GOVERNMENT OF THE UNITED STATES - WO2016/86008, 2016, A1 Location in patent: Paragraph 0246

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[ 763114-26-7 ]

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[ 61260-15-9 ]

Dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate

[ 763114-25-6 ]

2-Fluoro-5-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)benzonitrile

[ 218301-22-5 ]

2-Fluoro-5-formylbenzonitrile

[ 1021298-68-9 ]

2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzonitrile

Related Functional Groups of
[ 1021298-67-8 ]

Amides

[ 59878-57-8 ]

1-(Cyclopropylcarbonyl)piperazine

Similarity: 0.97

[ 1956325-48-6 ]

(3-Aminoazetidin-1-yl)(cyclopropyl)methanone hydrochloride

Similarity: 0.92

[ 926237-53-8 ]

Cyclopropyl(1,4-diazepan-1-yl)methanone

Similarity: 0.92

[ 1018826-44-2 ]

(4-Methylpiperazin-1-yl)(piperidin-4-yl)methanone hydrochloride

Similarity: 0.89

[ 81486-91-1 ]

Cyclohexyl(piperazin-1-yl)methanone hydrochloride

Similarity: 0.89

Related Parent Nucleus of
[ 1021298-67-8 ]

Aliphatic Heterocycles

[ 1956325-48-6 ]

(3-Aminoazetidin-1-yl)(cyclopropyl)methanone hydrochloride

Similarity: 0.92

[ 1019852-03-9 ]

(4-Methylpiperazin-1-yl)piperidin-4-yl-methanone dihydrochloride

Similarity: 0.89

[ 1286207-68-8 ]

(R)-(3-Aminopyrrolidin-1-yl)(cyclopropyl)methanone hydrochloride

Similarity: 0.87

[ 27561-62-2 ]

Cyclohexyl(piperazin-1-yl)methanone

Similarity: 0.87

[ 909409-91-2 ]

(R)-2,2-Dimethyl-1-(3-methylpiperazin-1-yl)propan-1-one

Similarity: 0.81

Piperazines

[ 59878-57-8 ]

1-(Cyclopropylcarbonyl)piperazine

Similarity: 0.97

[ 1019852-03-9 ]

(4-Methylpiperazin-1-yl)piperidin-4-yl-methanone dihydrochloride

Similarity: 0.89

[ 1018826-44-2 ]

(4-Methylpiperazin-1-yl)(piperidin-4-yl)methanone hydrochloride

Similarity: 0.89

[ 81486-91-1 ]

Cyclohexyl(piperazin-1-yl)methanone hydrochloride

Similarity: 0.89

[ 1181458-07-0 ]

3-Methyl-1-(piperazin-1-yl)butan-1-one hydrochloride

Similarity: 0.89

Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
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

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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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. 1021298-67-8 ] {[proInfo.proName]}

Quality Control of [ 1021298-67-8 ]

Related Doc. of [ 1021298-67-8 ]

Product Details of [ 1021298-67-8 ]

Calculated chemistry of [ 1021298-67-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1021298-67-8 ]

Application In Synthesis of [ 1021298-67-8 ]

[ 1021298-67-8 ] Synthesis Path-Upstream 1~2

[ 1021298-67-8 ] Synthesis Path-Downstream 1~5

Pharmaceutical Intermediates of [ 1021298-67-8 ]

Olaparib Related Intermediates

Related Functional Groups of [ 1021298-67-8 ]

Amides

Related Parent Nucleus of [ 1021298-67-8 ]

Aliphatic Heterocycles

Piperazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Pharmaceutical Intermediates of
[ 1021298-67-8 ]

Related Functional Groups of
[ 1021298-67-8 ]

Related Parent Nucleus of
[ 1021298-67-8 ]