[ CAS No. 111628-39-8 ]

Name: 111628-39-8|2-(Piperazin-1-yl)benzo[d]oxazole|98%
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Product Details of [ 111628-39-8 ]

CAS No. :	111628-39-8	MDL No. :	MFCD04035522
Formula :	C₁₁H₁₃N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HLKHIJZYKGDCJM-UHFFFAOYSA-N
M.W :	203.24	Pubchem ID :	647818
Synonyms :

Safety of [ 111628-39-8 ]

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

Application In Synthesis of [ 111628-39-8 ]

* 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.

Downstream synthetic route of [ 111628-39-8 ]

[ 111628-39-8 ] Synthesis Path-Downstream 1~65

1
[ 110-85-0 ]
[ 615-18-9 ]
[ 111628-39-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; In dichloromethane; water; at 0℃; for 0.5h;	5.6g (65 mmol) Piperazine (water free) and 3.27g (0.325 mol) triethylamine was dissolved in 50 ml of dry CH2Cl2 and the solution cooled to 0C in an ice/salt bath. 2-Chlorobenzoxazole (4d) dissolved in 20 ml of dry CH2Cl2 was added dropwise to the solution under stirring keeping the solution at 0C. After the addition, the mixture was stirred for a further 30 min at 0C and then quenched with 200 ml of ice-water. After separation of the organic phase, the water phase was extracted with ethyl acetate (2 x 100 ml), the combined organic phases was washed with sat. NaCl solution, dried over anhyd. Na2SO4, filtered and evaporated to dryness. Compound 8d was isolated as a white solid over column chromatography using silica gel with CH2Cl2/MeOH (5:1) as eluent. Yield 4.96 g (75%). 1HNMR (δ ppm): 3.48-3.53 (m, 4H, PZI); 3.17 (s, 1H, NH); 2.75-2.80 (m, 4H, PZI); 6.99 (dt, J=1.6Hz, J=8Hz, 1H, BZO-H5); 7.18 (dt, J=1.2Hz, J=7.6Hz, 1H, BZO-H6); 7.27 (dd, J=1.4Hz, J=7.6Hz, 1H, BZO-H7); 7.37 (dd, J=0.6Hz, J=7.8Hz, 1H, BZO-H4).
75%	With triethylamine; In dichloromethane; at 0℃;	5.6g (65 mM) Piperazine (water free) and3.27g (0.325 mol) triethylamine was dissolved in 50 ml of dry CH2Cl2 and the solution cooledto 0C in an ice/salt bath. 2-Chlorobenzoxazole (1c) dissolved in 20 mL of dry CH2Cl2 wasadded dropwise to the solution under stirring keeping the solution at 0C. After the addition,the mixture was stirred for a further 30 min at 0C and then quenched with 200 mL of icewater.After separation of the organic phase, the water phase was extracted with ethyl acetate(2 x 100 mL), the combined organic phases was washed with sat. NaCl solution, dried overanhyd. Na2SO4, filtered and evaporated to dryness. Compound 8d was isolated as a white solidover column chromatography using silica gel with CH2Cl2/MeOH (5:1) as eluent. Yield 4.96 g(75%). 1H NMR (200 MHz, d6-DMSO, d): 3.48-3.53 (m, 4H, 4x Pip-H); 3.17 (s, 1H, NH);2.75-2.80 (m, 4H, 4x Pip-H); 6.99 (dt, J = 1.6Hz, J = 8Hz, 1H, BZO-H5); 7.18 (dt, J = 1.2Hz,J = 7.6Hz, 1H, BZO-H6); 7.27 (dd, J = 1.4Hz, J = 7.6Hz, 1H, BZO-H7); 7.37 (dd, J = 0.6Hz,J = 7.8Hz, 1H, BZO-H4).
72%	In N,N-dimethyl-formamide; at 90℃; for 3h;Inert atmosphere;	A solution of piperazine (0.7 g, 8.2 mmol, 2.5 eq.) and 2-chlorobenzoxazole (0.5 g, 3.27 mmol) in dry DMF (10 mL) was stirred at 90 C for 3 hours under inert conditions. After the mixture was allowed to cool down, water (10mL) was added and the mixture was acidified to pH 2 with concentrated HCI prior to be washed with DCM (2X20 mL). The aqueous phase was adjusted to pH 12 with NaOH 4N and extracted with DCM (3X25 mL). The organic phase was washed with water (4X10 mL), dried over MgS04 and concentrated under reduced pressure to afford 2-piperazin-1 -yl-1 ,3-benzoxazole (0.48 g, 72%). ESI-MS m/z: 204 ([M+H]+ , 100%); RT= 0.9 min(Method 3).

55%	With triethylamine; In dichloromethane; at 0℃; for 0.5h;	Step l 0.90 g (10.4 mmol) of piperazine was dissolved in 50 ml of dichloromethane in a dried round flask provided with nitrogen gas, 0.80 g (5.2 mmol) of 2-chlorobenzooxazole and 0.9 ml (52.1 mmol) of triethylamine were added thereto at 0C , and the mixture was incubated at 0C for 30 mins. After adding water thereto, the reaction mixture was extracted with ethyl acetate, and the formed organic layer was dried over anhydrous magnesium sulfate and concentrated under a reduced pressure. The resulting residue was subjected to silica gel column chromatography (dichloromethane:methanol=9:l) to obtain 0.58 g of 2-(piperazin-l-yl)benzooxazole (yield: 55%).
	With triethylamine; In dichloromethane; water;	INVENTIVE EXAMPLE 14 2-(1-Piperazinyl)benzoxazole Anhydrous piperazine (5.6 g) was dissolved in methylene chloride (100 ml) to which was subsequently added triethylamine (4.5 ml). With cooling in an ice bath, to this was added dropwise 2-chlorobenzoxazole (3.7 ml) in small portions, followed by 45 minutes of stirring. The reaction solution was mixed with water, extracted with methylene chloride and then washed with saturated sodium bicarbonate aqueous solution and saturated brine in that order. The organic layer was dried with magnesium sulfate and the solvent was evaporated under a reduced pressure. Thereafter, the thus obtained mixture was purified by a silica gel column chromatography (methanol) to obtain the title compound 2-(1-piperazinyl)benzoxazole (4.751 g) in the form of yellow crystalline powder.
	With potassium carbonate;potassium iodide; In methanol; chloroform; acetonitrile;	Reference example 16 Synthesis of 1-(2-benzoxazolyl)piperazine STR79 In 200 ml of acetonitrile were dissolved 33.6 g (0.39 mole) of piperazine and 10.0 g (0.065 mole) of 2-chlorobenzoxazole, and 9.0 g (0.065 mole) of potassium carbonate and a catalytic amount of potassium iodide were added thereto. The mixture was refluxed by heating for 11 hours under stirring. The mixture was cooled to room temperature and then filtered. The filtrate was concentrated under reduced pressure, and the residue was applied to silica gel column chromatography (the eluent used was a mixture of chloroform: methanol = 9: 1) to obtain 7.54 g of 1-(2-benzoxazolyl)piperazine as white crystals. MS spectrum (CI): m/e 204 (M+ +1)
	In dichloromethane; water;	EXAMPLE 10 8-(Benzoxazol-2-yl)-8-aza-5-azoniaspiro[4,5]decane iodide A 3.07 g portion of 2-chlorobenzoxazole was dissolved in 10 ml of dichloromethane. Under cooling with ice, to this was added dropwise 3.45 g of anhydrous piperazine which has been dissolved in 30 ml of dichloromethane, followed by 1 hour of reaction. The reaction solution was concentrated under a reduced pressure, and the resulting residue was purified by a silica gel column chromatography (dichloromethane:methanol=20:1), followed by concentration of the elude under a reduced pressure. Thereafter, the resulting residue was dissolved in 30 ml of water, neutralized with 1N hydrochloric acid, extracted with dichloromethane, washed with water, dehydrated with Na2 SO4 and then concentrated under a reduced pressure to obtain 1.77 g of 2-(1-piperazinyl)benzoxazole.
	In ethanol;	Preparation 4 1-(Benzoxazol-2-yl)piperazine STR22 To a stirred solution of piperazine (8 g, 93 mmole) in ethanol (30 ml) was added 2-chlorobenzoxazole (3 g, 19.5 mmole) dropwise. The resulting reaction was exothermic. The mixture was then stirred for 18 hours at room temperature, quenched by the addition of methylene chloride (50 ml) and the resulting precipitate removed by filtration. The filtrate was concentrated under reduced pressure then purified by flash column chromatography on silica gel eluding with methylene chloride: methanol: 0.88 ammonia solution (90:10:1) to yield the title compound, m.p. 70-72 (1.8 g, 46%), which was used directly.
	With potassium carbonate;potassium iodide; In methanol; chloroform; acetonitrile;	(Reference example 16) Synthesis of 1-(2-benzoxazolyl)piperazine 33.6 g (0.39 mol) of piperazine and 10.0 g (0.065 mol) of 2-chlorobenzoxazole were dissolved in 200 ml of acetonitrile, and 9.0 g (0.065 mol) of potassium carbonate and a catalytic amount of potassium iodide were added thereto, followed by heating under reflux with stirring for 11 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography (eluding solution: mixture of chloroform:methanol = 9:1) to obtain 7.54 g of 1-(2-benzoxazolyl)piperazine as white crystals. MS spectrum (CI): m/e 204 (M++1)
	With triethylamine; In toluene; at 40℃; for 5h;	To a solution of piperazine (2.24 g, 26 mmol, 1 equiv.) in toluene was added 2-chlorobenzoxazole (1.0 g, 6.51 mmol, 1 equiv.), followed by Et3N (3.62 mL, 4 equiv.). The resulting mixture was stirred at 40 C. for 5 hours. The solvent was removed under reduced pressure, and the residue was dissolved in EtOAc. The solution was washed with H2O (*4), brine and dried over Na2SO4. The solvent was evaporated under reduced pressure to afford 0.87 g of intermediate IV-A-17.
	In chloroform; at 20℃; for 16h;	Step i) To a stirred solution of piperazine (560.9 mg, 6.50 mmol) in CHCl3 (16 ml_) was added 2-chlorobenzoxazole (500 mg, 3.25 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16 hr. CHCl3 was removed and the resulting white solid was dissolved in water. After stirring in water for 30 min, the aqueous layer was extracted with CH2CI2. The combined organic layer was dried over MgSO4, filtered, and concentrated. The white solid (20, 439 mg, 67 %) was used for the next step without purification.

Reference： [1]Organic Process Research and Development,2016,vol. 20,p. 982 - 988
[2]Organic Letters,2016,vol. 18,p. 5272 - 5275
[3]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5397 - 5400
[4]PLoS ONE,2015,vol. 10
[5]Chemical and Pharmaceutical Bulletin,1998,vol. 46,p. 445 - 451
[6]Journal of Medicinal Chemistry,1998,vol. 41,p. 3015 - 3021
[7]Journal of Medicinal Chemistry,2005,vol. 48,p. 7075 - 7079
[8]Patent: WO2014/122303,2014,A1 .Location in patent: Page/Page column 33
[9]Patent: WO2008/153325,2008,A1 .Location in patent: Page/Page column 24
[10]Patent: US6037342,2000,A
[11]Patent: US5519016,1996,A
[12]Patent: US5631257,1997,A
[13]Patent: US4885294,1989,A
[14]Patent: EP878194,1998,A1
[15]European Journal of Medicinal Chemistry,2009,vol. 44,p. 5071 - 5079
[16]Patent: US2005/234046,2005,A1 .Location in patent: Page/Page column 50
[17]Patent: WO2010/147947,2010,A2 .Location in patent: Page/Page column 188-189
[18]Medicinal Chemistry Research,2013,vol. 22,p. 4980 - 4991

2
[ 137-43-9 ]
[ 111628-39-8 ]
2-(4-cyclopentyl-1-piperazinyl)benzoxazole [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1998,vol. 46,p. 445 - 451

3
[ 543-59-9 ]
[ 111628-39-8 ]
2-(4-n-pentyl-1-piperazinyl)benzoxazole [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1998,vol. 46,p. 445 - 451

4
[ 111628-39-8 ]
[ 501083-62-1 ]
6-(4-benzooxazol-2-yl-piperazin-1-yl)-1-(2-hydroxy-phenyl)-hexan-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 646 - 649

5
[ 111628-39-8 ]
[ 173061-57-9 ]
[ 1026651-20-6 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5567 - 5578

6
[ 111628-39-8 ]
[ 824958-33-0 ]
6-(4-benzooxazol-2-yl-piperazin-1-yl)-hexanoic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 6616 - 6624

7
[ 111628-39-8 ]
6-amino-7-(4-benzooxazol-2-yl-piperazin-1-yl)-1-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5567 - 5578

8
[ 111628-39-8 ]
[ 1027904-29-5 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5567 - 5578

9
[ 295790-40-8 ]
[ 111628-39-8 ]
[ 295790-28-2 ]

Reference： [1]Patent: US6660751,2003,B1 .Location in patent: Page column 13

Yield	Reaction Conditions	Operation in experiment
72%	With trifluoroacetic acid; In dichloromethane; at 22℃; for 4h;	General procedure: GP4-2: N-Boc protected amine in DCM (5 volume) was added by TFA (2.5 volume). The mixture was stirred at rt for four hours and monitored by TLC. After consumption of starting material, volatile solvent was removed under reduced pressure and the residue was neutralized by saturated Na2CO3 solution to obtain the slurry, which was extracted by 10% methanol in DCM (3 times). The organic layers were collected, dried and concentrated to give the desired free amine, for direct use for next step.; 2-(piperazin-1-yl)benzothiazole The title compound was prepared according to GP4-2 as light yellow solid. (7.6 g, 97% yield) LC-MS (ESI): [M+1]+=219.9, tR=3.07 min. 1NMR (400 MHz, d6-DMSO) δ 7.75 (d, J=7.7 Hz, 1H), 7.45 (d, J=7.9 Hz, 1H), 7.29-7.25 (m, 1H), 7.08-7.04 (m, 1H), 2.83 (s, 4H). 13C NMR (101 MHz, DMSO) δ 168.39, 152.48, 130.14, 125.88, 121.05, 121.02, 118.45, 49.43, 44.89.
		Example 1.3 Starting from 0.2 g (IV-1) (cf. 1.2) and 0.287 g 2-piperazin-1-yl-benzoxazole 0.31 g Example 1.3 are prepared analogously to Example 1.1 (cf. 1.3). The reaction mixture is mixed with water and the product is suction filtered. Analytical HPLC-MS (method A): RT=1.23 min.

11
[ 111628-39-8 ]
[ 182438-98-8 ]
[ 348133-26-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran;	b. 9-[4-(4-(benzoxazol-2-yl)-piperazin-1-yl)-butyl]-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide A solution of 0.3 g (0.7 mmol) of <strong>[182438-98-8]9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide</strong>, 0.2 g (0.98 mmol) of 2-(piperazin-1-yl)-benzoxazole and 1 ml of triethylamine in 10 ml of tetrahydrofuran is refluxed for 48 hours. The reaction mixture is then poured onto water, extracted twice with dichloromethane and the combined organic phases are dried over sodium sulphate. The product is purified by column chromatography on silica gel (eluant: cyclohexane/ethyl acetate=1:1). Yield: 0.15 g (27.2% of theory), Melting point: 128 C.

Reference： [1]Patent: US2003/166637,2003,A1

12
[ 628-21-7 ]
[ 111628-39-8 ]
[ 159731-48-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dichloromethane; N,N-dimethyl-formamide;	A 245 mg portion of potassium carbonate was added to 300 mg of 2-(1-piperazinyl)benzoxazole which had been dissolved in 5 ml of DMF, and the reaction was carried out for 30 minutes. Under cooling with ice, 0.23 ml of 1,4-diiodobutane was added to the resulting solution, and the reaction was carried out for 1 hour at the same temperature and then for 2 hours at room temperature. The reaction solution was concentrated under a reduced pressure, and the resulting residue was dissolved in 300 ml of dichloromethane and extracted three times with 100 ml of water. Thereafter, the aqueous layers were combined and lyophilized. By purifying the residue by Diaion HP-20 (Mitsubishi Chemicals), 175 mg of the title compound was obtained. NMR (CD3 OD) δ: 7.39 (1H, d), 7.36 (1H, d), 7.23 (1H, t), 7.12 (1H, t), 4.06 (4H, brs), 3.75 (4H, t), 3.70 (4H, t), 2.28 (4H, brs)

Reference： [1]Patent: US5631257,1997,A

13
[ 15448-58-5 ]
[ 111628-39-8 ]
2-[4-(2-Benzoxazolyl)-1-piperazinyl]-3-hydroxy-1,4-naphthalenedione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; dichloromethane;	EXAMPLE 64 2-[4-(2-Benzoxazolyl)-1-piperazinyl]-3-hydroxy-1,4-naphthalenedione A mixture of 3.48 g of 2,3-epoxy-2,3-dihydro-1,4-naphthoquinone, 2.03 g of 2-(1-piperazinyl)benzoxazole and 200 ml of absolute ethanol was stirred for 18 hours and then filtered. The filtrate was concentrated to dryness and the residue flash chromatographed, eluding with dichloromethane, then 1% methanol in dichloromethane. The desired fraction was evaporated, then recrystallized twice from dichloromethane/ethanol, giving 533 mg of the desired product, mp 190 C. (dec.).

Reference： [1]Patent: US4686220,1987,A

14
[ 111628-39-8 ]
1-methylamino-6,7-difluoro-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid [ No CAS ]
6-fluoro-8-difluoromethoxy-1,4-dihydro-4-oxo-1-methylamino-7-[4-(2-benzoxazolyl)piperazin-1-yl]quinoline-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		(Preparation example 156) Synthesis of 1-methylamino-6-fluoro-8-difluoromethoxy-1,4-dihydro-4-oxo-7-[4-(2-benzoxazolyl)piperazin-1-yl]quinoline-3-carboxylic acid Reaction of 1-methylamino-6,7-difluoro-8-difluoromethoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid with 1-(2-benzoxazolyl)piperazine and purification of the reaction mixture were carried out in a similar manner to that described in Preparation example 1 to afford the title compound.

Reference： [1]Patent: EP878194,1998,A1

15
[ 35231-44-8 ]
[ 111628-39-8 ]
[ 1072879-88-9 ]

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2008,vol. 63,p. 83 - 89

16
BF₂*C₁₁H₈ClNO₃ [ No CAS ]
[ 111628-39-8 ]
[ 1056878-97-7 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5454 - 5458

17
[ 1056879-05-0 ]
[ 111628-39-8 ]
[ 1056879-08-3 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5454 - 5458

18
[ 75001-52-4 ]
[ 111628-39-8 ]
[ 1056879-18-5 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5454 - 5458

19
C₂₃H₃₂O₇S [ No CAS ]
[ 111628-39-8 ]
C₃₃H₄₁N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In N,N-dimethyl-formamide; at 20 - 70℃;	To a stirred solution of mesylate 109 (200 mg, 0.44 mmol) in DMF (4.4 mL) was added 2-piperazin-1 -ylbenzoxazole (128,4 mg, 0.63 mmol) and triethylamine (0.198 mL, 1.42 mmol) at room temperature. The reaction mixture was heated to 70 C overnight and then cooled down to room temperature, The reaction mixture was poured into NaHCO3 (aq) solution and extracted with dichloromethane (50 mL x 2). The combined organic layer was washed with H2O and brine solution, dried over MgSO4, filtered and concentrated by. The crude product was purified by flash chromatography (10 % MeOH/ CH2CI2) to give 122 mg of the titie compound. MH+ 561

Reference： [1]Patent: WO2009/85879,2009,A2 .Location in patent: Page/Page column 171

20
[ 869488-91-5 ]
[ 111628-39-8 ]
C₂₅H₃₃F₂N₅O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1991 - 1995

21
[ 1203701-93-2 ]
[ 111628-39-8 ]
[ 1203799-94-3 ]

Reference： [1]European Journal of Medicinal Chemistry,2009,vol. 44,p. 5071 - 5079

22
[ 111628-39-8 ]
[ 234107-57-4 ]
C₂₇H₂₅N₅O₆ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 3354 - 3365

23
1-(((2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)-methyl)-1H-1,2,4-triazole [ No CAS ]
[ 111628-39-8 ]
[ 1092847-72-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With lithium perchlorate; In acetonitrile; for 24h;Heating / reflux;	Step 20.60 g (2.4 mmol) of an oxirane compound was dissolved in acetonitrile in a dried round flask provided with nitrogen gas, 0.50 g (2.4 mmol) of the compound obtained in Step 1 and 0.39 g (3.7 mmol) of lithium perchlorate were added thereto, and the mixture was refluxed with stirring for 24 hrs. After adding distilled water and ethyl acetate thereto, the aqueous layer was further extracted with an organic solvent(more than 3 times), and the formed organic layer was washed with a saturated NaCl solution, dried over anhydrous magnesium sulfate and filtered. The resulting solution was distilled under a reduced pressure, and the residue was subjected to silica gel column chromatography (dichloromethane:methanol=49:l) to obtain 0.54 g of the title compound (yield: 50%).

Reference： [1]Patent: WO2008/153325,2008,A1 .Location in patent: Page/Page column 24-25

24
[ 111628-39-8 ]
[ 540475-57-8 ]
[ 1258527-71-7 ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine; In N,N-dimethyl-formamide; at 20 - 80℃; for 16h;	Step 2) To as stirred solution of 7 (200 mg, 0.358 mmol) in DMF (3.60 ml_) was added piperazine 20 (182 mg, 0.511 mmol) and Et3N (160. 7 μL, 1.15 mmol) at room temperature. The reaction mixture was heated to 70-80 C for 16 hr. After cooling down to room temperature, the reaction mixture was poured into sat. NaHCO3 (aq) solution and extracted with EtOAc. The organic layer was washed with H2O and brine, dried over MgSO4, filtered and concentrated. The resulting crude product was purified by flash column chromatography on silica gel eluting with 10 % MeOH in CH2CI2 to afford the desired product, 6-1 (98 mg, 41 %).

Reference： [1]Patent: WO2010/147947,2010,A2 .Location in patent: Page/Page column 189-190

25
[ 56675-37-7 ]
[ 111628-39-8 ]
(S)-2-amino-1-(4-(benzo[d]oxazol-2-yl)piperazin-1-yl)-3-(thiophen-2-yl)propan-1-one hydrochloride [ No CAS ]

Reference： [1]Patent: US2011/152287,2011,A1

26
[ 56675-37-7 ]
[ 111628-39-8 ]
[ 1312762-81-4 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 18h;Cooling with ice;	STEP A: 2-Piperidino-1,3-benzoxazole (203.6 mgs, 1.00 mmol), N-hydroxybenzotriazole hydrate (138.2 mg, 1.02 mmol) and Boc-β-(2-thienyl)-L-alanine (272.6 mgs, 1.00 mmol) in dichloromethane (10 mL) was cooled in an ice bath, then treated with triethylamine (0.30 mL, 2.15 mmol) and 1-[3-dimethylaminopropyl]-3-ethyl carbodiimide hydrochloride (199.5 mg, 1.04 mmol). The resulting mixture was stirred overnight at room temperature. After 18 h, the resulting mixture was diluted with chloroform and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated to a residue. The residue was purified by flash column chromatography, eluting with 3% methanol in chloroform to yield (S)-tert-butyl 1-(4-(benzo[d]oxazol-2-yl)piperazin-1-yl)-1-oxo-3-(thiophen-2-yl)propan-2-ylcarbamate as a colorless glass. 1HNMR (DMSO-d6) δ 8.31 (s, 1H), 7.36 (d, J=7.83 Hz, 1H), 7.33-7.29 (m, 2H), 7.19-7.14 (m, 1H), 7.06-7.01 (m, 1H), 6.94-6.92 (m, 2H), 4.66-4.53 (m, 1H), 3.80-3.54 (m, 8H), 3.25-0.00 (m, 2H), 1.36 (s, 9H); MS (MH+)=457.

Reference： [1]Patent: US2011/152287,2011,A1 .Location in patent: Page/Page column 19

27
[ 405279-59-6 ]
[ 111628-39-8 ]
[ 1222786-24-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1044 - 1048

28
[ 59762-06-0 ]
[ 111628-39-8 ]
[ 1318753-88-6 ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 1249 - 1257

29
[ 401564-36-1 ]
[ 111628-39-8 ]
[ 401566-37-8 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of 7a (450 mg, 1.50 mmol), 1-(4-chloroisoquinolin-1-yl)piperazine (446 mg, 1.80 mmol) and acetic acid (0.090 mL, 1.6 mmol) in 1,2-dichloroethane (8 mL) was added sodium triacetoxyborohydride (636 mg, 3.00 mmol) and the mixture was stirred at room temperature for 3 h. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution and extracted with chloroform. The extract was washed with brine, dried and concentrated under reduced pressure. The residue purified by silica gel chromatography with chloroform/methanol (50:1, v/v) to give 3-{(2S,4S)-1-tert-butoxycarbonyl-4-[4-(4-chloroisoquinolin-1-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine (596 mg, 75%) as a white powder.The above compound (592 mg, 1.11 mmol) was dissolved in 1.1 mol/L hydrogen chloride in methanol (10 mL), and the mixture was stirred at room temperature for 5 days. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized with ethanol to give the title compound (318 mg, 52%) as a pale-yellow powder.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5033 - 5041

30
[ 157160-99-1 ]
[ 111628-39-8 ]
C₂₂H₂₄N₄O₅ [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2013,vol. 61,p. 486 - 488

31
[ 15084-51-2 ]
[ 111628-39-8 ]
[ 695221-93-3 ]