[ CAS No. 84807-09-0 ] {[proInfo.proName]}

Name: 84807-09-0|4-(Piperazin-1-yl)-1H-indole|97%
Brand: Ambeed
SKU: A111681
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Quality Control of [ 84807-09-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 84807-09-0 ]

Product Details of [ 84807-09-0 ]

CAS No. :	84807-09-0	MDL No. :	MFCD00831776
Formula :	C₁₂H₁₅N₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YZKSXUIOKWQABW-UHFFFAOYSA-N
M.W :	201.27	Pubchem ID :	594590
Synonyms :

Calculated chemistry of [ 84807-09-0 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.33
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	2.0
Molar Refractivity :	69.66
TPSA :	31.06 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.45 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.76
Log Po/w (XLOGP3) :	1.52
Log Po/w (WLOGP) :	0.82
Log Po/w (MLOGP) :	1.22
Log Po/w (SILICOS-IT) :	2.21
Consensus Log Po/w :	1.51

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.42
Solubility :	0.759 mg/ml ; 0.00377 mol/l
Class :	Soluble
Log S (Ali) :	-1.78
Solubility :	3.33 mg/ml ; 0.0166 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.79
Solubility :	0.033 mg/ml ; 0.000164 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.79

Safety of [ 84807-09-0 ]

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 [ 84807-09-0 ]

* 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 [ 84807-09-0 ]
Downstream synthetic route of [ 84807-09-0 ]

[ 84807-09-0 ] Synthesis Path-Upstream 1~4

1
[ 5192-23-4 ]
[ 821-48-7 ]
[ 84807-09-0 ]

Yield	Reaction Conditions	Operation in experiment
90.8%	With potassium carbonate In isopropyl alcohol at 90℃; for 48 h;	4-aminoindole (2g, 15.2mmol), bis(2-chloroethyl)amine hydrochloride (3.2g, 18.2mmol) and potassium carbonate (4.2g, 30.4mmol) was added to isopropanol (30 mL) after the reaction solution was reacted at 90 °C for 48 hours, and thereto was added dichloromethane (50mL) and methanol (50mL). The reaction mixture was filtered and the filtrate under reduced pressure to spin dry, the residue was purified by silica gel column chromatography (dichloromethane/methanol (v/v)= 10/1) by to give the title compound as a brown solid (2.78g, 90.8percent).

Reference： [1] Patent: CN105367472, 2016, A, . Location in patent: Paragraph 0179; 0180; 0181; 0182
[2] Patent: US2008/318941, 2008, A1, . Location in patent: Page/Page column 19-20

2
[ 5192-23-4 ]
[ 84807-09-0 ]

Yield	Reaction Conditions	Operation in experiment
90.8%	With potassium carbonate In isopropyl alcohol at 90℃; for 48 h;	[00190] To 30 mL of i-propanol were added 4-aminoindole (2 g, 15.2 mmol), bis(2-chloroethyl)amine hydrochloride (3.2 g, 18.2 mmol) and potassium carbonate (4.2 g, 30.4 mmol). The mixture was stirred at 90 °C for 48 hours. To the reaction mixture were added dichlormethane (50 mL) and methanol (50 mL), and the mixture was filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography eluted with DCMIMeOH (v/v = 10/1) to give the title compound as a brown solid (2.78 g, 90.8percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 202.1 [M+H] and ‘H NMR (600 MHz, DMSO-d6) (ppm): 11.17 (s, 1H), 7.29-7.25 (m, 1H), 7.09 (d, J= 8.1 Hz, 1H), 6.98 (t, J= 7.8 Hz, 1H), 6.49 (d, J= 7.5 Hz, 1H), 6.46 (s, 1H), 3.32-3.28 (m, 8H).

Reference： [1] Patent: WO2016/4882, 2016, A1, . Location in patent: Paragraph 00190

3
[ 252978-89-5 ]
[ 84807-09-0 ]

Yield	Reaction Conditions	Operation in experiment
81%	at 150℃; for 2 h; Microwave irradiation	EXAMPLE 5; In general, it was found that HFIP is a more reactive solvent than TFE for N-BOC deprotection reactions. Thus, the use of HFIP over TFE on the same substrate under similar conditions consistently reduced reaction times (see Examples 2 and 3 above). On the basis of the reactivity differences between TFE and HFIP, 4-N-BOC-4-(4-BOC-piperazin-1-yl)-indole was sequentially deprotected. As set forth in the Scheme below, TFE (microwave heating for 2 h at 150° C.) was used to selectively remove the indole BOC moiety in good yields (80percent). Further treatment of the partially-deprotected compound with HFIP (microwave heating for 2 h at 150° C.) efficiently completed the cleavage of the remaining N-BOC group on the piperazine ring (yield=81percent). On the other hand, if selectivity is not required both BOC groups can be removed simultaneously using HFIP as a solvent. 4-(1H-Indol-4-yl)-piperazine-1-carboxylic acid t-butyl ester: mp=139-140° C.; ¹H NMR (CDCl₃), δ 8.27 (broad s, 1H), 7.25-7.07 (m, 3H), 6.60-6.54 (m, 2H), 3.67 (t, 4H), 3.19 (t, 4H), 1.50 (s, 9H); ¹³C NMR (CDCl₃), δ 154.94, 145.53, 136.97, 122.87, 122.66, 121.36, 106.87, 106.18, 100.94, 76.60, 51.31, 43.69, 28.47; MS ESI m/z (percent) 302 (M+H⁺, 100percent); HRMS ESI m/z (M+H⁺) 302.18616. Calcd. 302.18630. 4-piperazin-1-yl-1H-indole: mp=198-199° C. (dec.); ¹H NMR (CDCl₃), δ 8.37 (broad s, 1H), 7.19-7.03 (m, 3H), 6.67-6.51 (m, 2H), 3.24-3.18 (m, 4H), 3.19-3.05 (m, 4H), 2.01 (broad s, 1H); ¹³C NMR (DMSO-d₆), δ 145.99, 136.96, 123.25, 121.57, 120.78, 105.75, 105.30, 99.93, 52.28, 45.98; MS ESI m/z (percent) 202 (M+H⁺, 100percent); HRMS ESI m/z (M+H⁺) 202.13351. Calc 202.13387.
81%	at 150℃; for 2 h; Microwave irradiation	Example 5; In general, it was found that HFIP is a more reactive solvent than TFE for N-BOC deprotection reactions. Thus, the use of HFIP over TFE on the same substrate under similar conditions consistently reduced reaction times (see Examples 2 and 3 above). On the basis of the reactivity differences between TFE and HFIP, 4-N-BOC-4-(4-BOC-piperazin-1-yl)-indole was sequentially deprotected. As set forth in the Scheme below, TFE (microwave heating for 2 h at 150°C) was used to selectively remove the indole BOC moiety in good yields (80percent). Further treatment of the partially-deprotected compound with HFIP (microwave heating for 2 h at 150°C) efficiently completed the cleavage of the remaining N-BOC group on the piperazine ring (yield = 81 percent). On the other hand, if selectivity is not required both BOC groups can be removed simultaneously using HFIP as a solvent. [Show Image] 4-(1H-Indol-4-yl)-piperazine-1-carboxylic acid t-butyl ester: mp = 139 - 140°C; ¹H NMR (CDCl₃), 8.27 (broad s, 1H), 7.25-7.07 (m, 3H), 6.60-6.54 (m, 2H), 3.67 (t, 4H), 3.19 (t, 4H), 1.50 (s, 9H); ¹³C NMR (CDCl₃), 154.94, 145.53, 136.97, 122.87, 122.66, 121.36, 106.87, 106.18, 100.94, 76.60, 51.31, 43.69, 28.47; MS ESI m/z (percent) 302 (M+H+,100percent); HRMS ESI m/z (M+H+) 302.18616. Calcd. 302.18630. 4-Piperazin-1-yl-1H-indole: mp = 198 - 199°C (dec.); ¹H NMR (CDCl₃), 8.37 (broad s, 1H), 7.19-7.03 (m, 3H), 6.67 - 6.51 (m, 2H), 3.24-3.18 (m, 4H), 3.19-3.05 (m, 4H), 2.01 (broad s, 1H); ¹³C NMR (DMSO-d6), 145.99, 136.96, 123.25, 121.57, 120.78, 105.75, 105.30, 99.93, 52.28, 45.98; MS ESI m/z (percent) 202 (M+H+,100percent); HRMS ESI m/z (M+H+) 202.13351. Calc 202.13387.

Reference： [1] Synthetic Communications, 2008, vol. 38, # 21, p. 3840 - 3853
[2] Patent: US2009/203910, 2009, A1, . Location in patent: Page/Page column 5-6
[3] Patent: EP2070899, 2009, A1, . Location in patent: Page/Page column 9

4
[ 5192-23-4 ]
[ 84807-09-0 ]

Reference： [1] Patent: US5627177, 1997, A,

[ 84807-09-0 ] Synthesis Path-Downstream 1~88

1
[ 84807-09-0 ]
1-benzo[<i>b</i>]thiophen-3-yl-3-[4-(1<i>H</i>-indol-4-yl)-piperazin-1-yl]-propan-1-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4128 - 4139

2
[ 84807-09-0 ]
1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(indol-4-yl)piperazin-1-yl]propan-1-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4128 - 4139

3
[ 209745-29-9 ]
[ 84807-09-0 ]
4-[4-[2-(Indan-2-yl)ethyl]piperazin-1-yl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With potassium carbonate; In 1-methyl-pyrrolidin-2-one; 4-methyl-2-pentanone; for 3.0h;Heating / reflux;	A mixture of <strong>[84807-09-0]4-(piperazin-1-yl)-1H-indole</strong> (1.5 g), 2-(2-iodoethyl)indane (2.0 g), K2CO3, methyl isobutyl ketone (150 ml), and N-methylpyrrolidone (10 ml) was boiled under reflux for 3 h. The mixture was allowed to cool to room temperature, filtered, and concentrated in vacuo. The residue was purified on silica gel eluted with ethyl acetate-heptane (1:2) to give a crystalline compound, which was recrystallized (ethyl acetate) to give the title compound (1.2 g, 47percent). Mp146-147° C. 1H NMR (CDCl3) delta1.70-1.85 (m, 2H), 2.40-2.70 (m, 5H), 2.75 (broad s, 4H), 3.00-3.15 (m, 2H), 3.30 (broad s, 4H), 6.55 (s, 1H), 6.60 (d, 1H), 7.00-7.30 (m, 7H), 8.20 (broad s, 1H). MS m/z (percent): 346 (MH+, 34percent), 159 (88percent), 145 (100percent).

Reference： [1]Patent: US6352988,2002,B2 .Location in patent: Page column 35

4
[ 18505-77-6 ]
[ 84807-09-0 ]
[ 220383-03-9 ]

Yield	Reaction Conditions	Operation in experiment
40%	With triethylamine; In DMF (N,N-dimethyl-formamide); for 2.5h;Heating / reflux; Nitrogen atmosphere;	A mixture containing 0.49 g of N-(2-chloroethyl)-2-nitroaniline, prepared according to the procedure described by Ramage G.R. et al. in J. Chem. Soc. 4406-4409 (1952), 0.55 g of <strong>[84807-09-0]1-(4-indolyl)-piperazine</strong> (prepared according to WO 95/33743), 1 ml of triethylamine and 3 ml of dimethylformamide was heated at reflux while stirring under nitrogen for 2.5 h. After cooling at room temperature, the mixture was poured into water and extracted with dichloromethane. The organic phase was dried on anhydrous sodium sulphate and evaporated to dryness. The residue was purified via flash chromatography (ethyl acetate : petroleum ether 3:7) giving 0.35 g (40percent) of 1-[N-(2-nitrophenyl)-2-aminoethyl]-4-(4-indolyl)-piperazine.1H-NMR (CDCl3, delta): 8.60-8.45 (br, 1H, aniline NH), 8.18 (dd, 1H, aniline H3), 8.20-8.10 (br, 1H, indole NH), 7.43 (td, 1H, aniline H5), 7.20-7.05 (m, 3H, indole H3,6,7), 6.85 (dd, 1H, aniline H4), 6.70-6.57 (m, 2H, aniline H6 and indole H5), 6.50 (t, 1H, indolylic H2), 3.45 (q, 2H, NHCH2CH2), 3.35-3.25 (m, 4H, piperazine protons), 3.85-2.70 (m, 6H, NHCH2CH2 and piperazine protons). The title compound was prepared following the procedure described in Example 2, second step, except that 1-[N-(2-nitrophenyl)-2-aminoethyl]-4-(4-indolyl)-piperazine, prepared as described above, was used in place of 1-[N-(2-trifluoromethoxyphenyl)-2-aminoethyl]-4-(2-methoxyphenyl)-piperazine, the mixture being heated for 5 h at reflux. The crude was purified via flash chromatography (ethyl acetate : petroleum ether 7:3, then only ethyl acetate was used and at the end only dichloromethane). Yield: 32percent1H-NMR (CDCl3, delta): 8.37-8.20 (br, 1H, NH), 8.05 (dd, 1H, nitrophenyl ring H3), 7.65-7.45 (m, 3H, nitrophenyl ring H4,5,6), 7.20-7.00 (m, 3H, indole H3,6,7), 6.55 (dd, 1H, indole H5), 6.50 (t, 1H, indole H2), 4.15-3.95 (m, 1H, C(O)NC(H)HCH2), 3.70-3.55 (m, 1H, C(O)NC(H)HCH2), 3.25-2.95 (m, 4H, piperazine protons), 2.75-2.45 (m, 7H, C(O)NCH2CH2, CHC(O), piperazine protons), 2.10-0.80 (m, 10H, cyclohexyl protons).
	With triethylamine; In N,N-dimethyl-formamide;	EXAMPLE 12 1-[N-(2-nitrophenyl)-2-aminoethyl]-4-(4-indolyl)piperazine A mixture containing 0.49 g of N-(2-chloroethyl)-2-nitroaniline, prepared according to the procedure described by Ramage G. R. et al. in J. Chem. Soc. 4406-4409 (1952), 0.55 g of 1-(4-indolyl)piperazine (prepared according to WO 95/33743), 1 mL of triethylamine and 3 mL of DMF was heated at reflux while stirring under nitrogen for 2.5 h. After cooling at room temperature, the mixture was poured into H2O, extracted with CH2Cl2, and the organic phase dried on anhydrous Na2SO4 and evaporated to dryness. The residue was purified via flash chromatography (EtOAc-petrolium ether 3:7) giving 0.35 g (40percent) of the title compound. 1H-NMR (CDCl3, delta): 8.60-8.45 (br, 1H, aniline NH), 8.18 (dd, 1H, aniline H3), 8.20-8.10 (br, 1H, indole NH), 7.43 (td, 1H, aniline H5), 7.20-7.05 (m, 3H, indole H3,6,7), 6.85 (dd, 1H, aniline H4), 6.70-6.57 (m, 2H, aniline H6 and indole H5), 6.50 (t, 1H, indole H2), 3.45 (q, 2H, NHCH2CH2), 3.35-3.25 (m, 4H, piperazine protons), 3.85-2.70 (m, 6H, NHCH2 and piperazine protons).
	With triethylamine; In N,N-dimethyl-formamide;	EXAMPLE 12 1-[N-(2-nitrophenyl)-2-aminoethyl]-4-(4-indolyl)piperazine A mixture containing 0.49 g of N-(2-chloroethyl)-2-nitroaniline, prepared according to the procedure described by Ramage G. R. et al. in J. Chem. Soc. 4406-4409 (1952), 0.55 g of 1-(4-indolyl)piperazine (prepared according to WO 95/33743), 1 mL of triethylamine and 3 mL of DMF was heated at reflux while stirring under nitrogen for 2.5 h. After cooling at room temperature, the mixture was poured into H2 O, extracted with CH2 Cl2, and the organic phase dried on anhydrous Na2 SO4 and evaporated to dryness. The residue was purified via flash chromatography (EtOAc-petrolium ether 3:7) giving 0.35 g (40percent) of the title compound. 1 H-NMR (CDCl3, delta): 8.60-8.45 (br, 1H, aniline NH), 8.18 (dd, 1H, aniline H3), 8.20-8.10 (br, 1H, indole NH), 7.43 (td, 1H, aniline H5), 7.20-7.05 (m, 3H, indole H3,6,7), 6.85 (dd, 1H, aniline H4), 6.70-6.57 (m, 2H, aniline H6 and indole H5), 6.50 (t, 1H, indole H2), 3.45 (q, 2H, NHCH2 CH2), 3.35-3.25 (m, 4H, piperazine protons), 3.85-2.70 (m, 6H, NHCH2 CH2 and piperazine protons).

Reference： [1]Patent: EP1000047,2003,B1 .Location in patent: Page 10-11
[2]Patent: US6399614,2002,B1
[3]Patent: US6071920,2000,A

5
[ 3874-54-2 ]
[ 84807-09-0 ]
4-[4-(indol-4-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;potassium iodide; In acetonitrile;	Analogously to Example 4, using [TABLE-US-00003] 4 g (0.02 mol) of <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> 10, 4 g (0.02 mol) of 4-chloro-1-(4-fluorophenyl)butan-1-one 2, 2.8 g (0.02 mol) of potassium carbonate, 40 mg of potassium iodide and 75 ml of acetonitrile, the compound 11 was obtained. [0075] For the formation of the acid addition salt, 800 mg of base were dissolved in 10 ml of ethanol with warming and acidified with ethanol/HCl. The hydrochloride which crystallized after cooling was filtered off with suction and washed with ethanol and ether (m.p. 233-234°, [M+H]+: 366).

Reference： [1]Patent: US2004/14972,2004,A1 .Location in patent: Page 8-9

6
[ 127561-33-5 ]
[ 84807-09-0 ]
3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]
3-[trans-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%; 21%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(1H-indol-3-yl)-cyclohexanone (0.53 g,2.5 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.5g, 2.5 mmol), sodium triacetoxyborohydride (0.78 g, 3.5 mmol) and acetic acid (0.14 ml, 2.5 mmol) in 1,2-dichloroethane (11 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 60 ml), and washed with brine (3 x 60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.52 g (53percent) of product as a white solid: mp 85-87°C. The HCl salt was prepared in ethyl acetate: mp 198-200°C.; The trans compound was isolated at the same time as the cis isomer in 21percent yield (0.21 g) as a white solid: mp 105-107°C. The HCl salt was prepared in ethyl acetate: mp 305°C (decomposed).

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 50-51

7
[ 282547-09-5 ]
[ 84807-09-0 ]
4-fluoro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]
4-fluoro-3-[trans-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%; 17%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(4-fluoro-1H-indol-3-yl)-cyclohexanone (0.88 g, 3.8 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.7 g, 3.5 mmol), sodium triacetoxyborohydride (1.1 g, 5.2 mmol) and acetic acid (0.4 ml, 7 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 60 ml), and washed with brine (3 x 60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (5-7percent methanol-ethyl acetate) afforded 1.14 g (79percent) of product as a white foam. The HCl salt was prepared in ethanol: mp 283-285°C.; The trans compound was isolated at the same time as the cis isomer in 17percent yield (0.24 g) as a white solid: mp 206-208°C. The HCl salt was prepared in ethanol: mp 297-299°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 51

8
[ 282547-11-9 ]
[ 84807-09-0 ]
5-chloro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]
5-chloro-3-[trans-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%; 24%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-chloro-1H-indol-3-yl)-cyclohexanone (0.78 g, 3.1 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.6 g, 3 mmol), sodium triacetoxyborohydride (0.95 g, 4.5 mmol) and acetic acid (0.34 ml, 6 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 60 ml) and washed with brine (3 x 60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (5percent methanol-ethyl acetate) afforded 0.84 g (65percent) of product as a white foam. The HCl salt was prepared in ethanol: mp 283-285°C.; The trans compound was isolated at the same time as the cis isomer in 24percent yield (0.32 g) as a white foam. The HCl salt was prepared in ethanol: mp 314-315.5°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 53

9
[ 185383-65-7 ]
[ 84807-09-0 ]
5-methoxy-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]
5-methoxy-3-[trans-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%; 20%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-methoxy-1H-indol-3-yl)-cyclohexanone (1.2 g, 5 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1 g, 5 mmol), sodium triacetoxyborohydride (1.47 g, 6.2 mmol) and acetic acid (0.28 ml, 4 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 60 ml) and washed with brine (3 x 60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (2.5percent methanol-ethyl acetate) afforded 1.18 g (55percent) of product as a white solid: mp 105-108°C. The HCl salt was prepared in ethyl acetate: mp 283-285°C.; The trans compound was isolated at the same time as the cis isomer in 20percent yield (0.43 g) as a white foam. The HCl salt was prepared in ethyl acetate: mp 194-196°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 53

10
[ 282547-20-0 ]
[ 84807-09-0 ]
3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-methyl-1H-indole-5-carbonitrile [ No CAS ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-methyl-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%; 33%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-cyano-1-methyl-3-indolyl)-cyclohexanone (0.75 g, 3 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.6 g, 3 mmol), sodium triacetoxyborohydride (0.95 g, 4.5 mmol) and acetic acid (0.34 ml, 6 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 60 ml) and washed with brine (3 x 60 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.73 g (56percent) of product as a white solid: mp 274-275°C. The HCl salt was prepared in ethyl acetate: mp 285.5-288°C.; The trans compound was isolated at the same time as the cis isomer in 33percent yield (0.42 g) as a white solid: mp 239-240°C. The HCl salt was prepared in ethyl acetate: mp 286-288°C

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 56

11
4-(5-cyano-1-ethyl-1H-indol-3-yl)-cyclohexanone [ No CAS ]
[ 84807-09-0 ]
1-ethyl-3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile [ No CAS ]
1-ethyl-3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%; 19%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-cyano-1-ethyl-indol-3-yl)-cyclohexanone (1.5 g, 5.6 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.19 g, 5.9 mmol), sodium triacetoxyborohydride (1.73 g, 8.2 mmol) and acetic acid (0.9 ml, 15 mmol) in 1,2-dichloroethane (30 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (3 x 80 ml), and washed with brine (3 x 80 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (2.5percent methanol-ethyl acetate) afforded 0.98 g (39percent) of product as a white solid: mp 226°C (dec.). The HCl salt was prepared in ethyl acetate: mp 245°C.; The trans compound was isolated at the same time as the cis isomer in 19percent yield (0.48 g) as a light brown solid: mp decomposed at 110°C. The HCl salt was prepared in ethyl acetate: mp 250°C (decomposed).

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 56-57

12
[ 282547-22-2 ]
[ 84807-09-0 ]
3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-propyl-1H-indole-5-carbonitrile [ No CAS ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-propyl-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%; 14%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-cyano-1-n-propyl-indol-3-yl)-cyclohexanone (1.68 g, 6 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.27 g, 6.3 mmol), sodium triacetoxyborohydride (1.84 g, 8.9 mmol) and acetic acid (0.94 ml, 16 mmol) in 1,2-dichloroethane (80 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (20 ml), extracted with methylene chloride (3 x 100 ml) and washed with brine (3 x 100 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.42 g(15percent) of product as a white powder. The HCl salt was prepared in ethanol: mp 200-206°C.; The trans compound was isolated at the same time as the cis isomer in 14percent yield (0.39 g) as a white foam. The HCl salt was prepared in ethanol: mp decomposed >245°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 57

13
[ 282547-23-3 ]
[ 84807-09-0 ]
3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-iso-propyl-1H-indole-5-carbonitrile [ No CAS ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-iso-propyl-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%; 12%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-cyano-1-n-propyl-indol-3-yl)-cyclahexanone (1.68 g, 6 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.27 g, 6.3 mmol), sodium triacetoxyborohydride (1.84 g, 8.9 mmol) and acetic acid (0.94 ml, 16 mmol) in 1,2-dichloroethane (80 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (20 ml), extracted with methylene chloride (3 x 100 ml), and washed with brine (3 x 100 ml). The organic layer was dried over anhydrous sodium sulfate, and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.49 g (18 percent) of product as a white powder. The HCl salt was prepared in ethanol: mp 285-286°C.; The trans compound was isolated at the same time as the cis isomer in 12percent yield (0.34 g) as a white foam. The HCl salt was prepared in ethanol: mp decomposed > 245°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 57-58

14
4-(2-methyl-1H-indol-3-yl)-cyclohexanone [ No CAS ]
[ 84807-09-0 ]
3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-2-methyl-1H-indole [ No CAS ]
3-[trans-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-2-methyl-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40.7%; 25.7%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(1H-indol-3-yl)-cyclohexanone (1.44 g, 6.33 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.27 g, 6.33 mmol), sodium triacetoxyborohydride (1.88 g, 8.86 mmol) and acetic acid (0.76 mg, 12.6 mmol) in 1,2-dichloroethane (100 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (80 ml), extracted with methylene chloride (3 x 300 ml), and washed with brine (150 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed under vacuum to afford an off-white solid. Trituration of the solid with warm methylene chloride (80 ml) followed by filtration afforded 0.88 g of white solid. The mother liquor was concentrated and chromatographed (2percent methanol-methylene chloride) to afford another 0.18 g (total yield 40.7percent) of product as a white solid: mp 279-280°C. The HCl salt was prepared in ethanol: mp 200-203°C.; The trans compound was isolated at the same time as the cis isomer in 25.7percent yield (0.67 g) as a white foam. The HCl salt was prepared in ethanol: mp >310°C.

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 53

15
4-(5-cyano-1-iso-propyl-1H-indol-3-yl)-cyclohexanone [ No CAS ]
[ 84807-09-0 ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-iso-propyl-1H-indole-5-carbonitrile [ No CAS ]
1-benzyl-3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%; 37%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃;	A solution of 4-(5-cyano-1-benzyl-indol-3-yl)-cyclohexanone (2.97 g, 9 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.94 g, 9.6 mmol), sodium triacetoxyborohydride (2.7 g, 13 mmol) and acetic acid (1 ml, 24 mmol) in 1,2-dichloroethane (50 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (20 ml), extracted with methylene chloride (3 x 100 ml) and washed with brine (3 x 100 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (25-50percent ethyl acetate-hexanes) afforded 1.71 g (37percent) of product as a white powder. The HCl salt was prepared in ethanol: mp dec. > 245°C.; The trans compound was isolated at the same time as the cis isomer in 15percent yield (0.68 g) as a white foam. The HCl salt was prepared in ethanol: mp> 240°C (dec.).

Reference： [1]Patent: EP1147083,2004,B1 .Location in patent: Page 58

Yield	Reaction Conditions	Operation in experiment
		The solid was dissolved in chlorobenzene (150 mL) and bis(2-chloroethyl)amine hydrochloride (9 g) was added followed by reflux for 90 hours. Filtration gave a crystalline product (9.2 g) which was heated in a mixture of conc. aq. ammonia (50 mL) and ethyl acetate (200 mL) for 15 min. Separation of the organic phase, drying and evaporation gave the titel compound as a crystalline material (5.6 g).
		The grey powder was dissolved in water (1 L), made basic with sodium hydroxide solution then extracted with dichloromethane/methanol (3 L of CH2 Cl2:MeOH 10:1). After the organic layer was washed with water, it was dried (MgSO4) and evaporated under reduced pressure to leave a grey solid. The solid was triturated with isopropanol/ethylacetate and filtered to give 40 g of a pale grey solid.

17
[ 220422-01-5 ]
[ 84807-09-0 ]
1-(4-1H-indolyl)-4-[3,3-bis-(pyridin-2-yl)-propyl]-piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃; for 24.0h;	A mixture of 1.15 g of 3,3-bis-(2-pyridyl)-propionaldehyde, 1.2 g of <strong>[84807-09-0]1-(4-indolyl)-piperazine</strong> (prepared as described in EP 0138280), 1.24 ml of acetic acid, 1.71 g of sodium triacetoxyborohydride and 85 ml of 1,2-dichloroethane was stirred at room temperature for 24 hours. Afterwards, it was diluted with water and alkalinised with sodium carbonate. The organic layer was dried on anhydrous sodium sulphate and evaporated to dryness to give 1.53 g of crude. This was purified by flash chromatography (ethyl acetate : 2.2N methanolic ammonia, gradient from 9.4:0.6 to 9.2:0.8) giving 0.28 g (13percent) of the title product as an oil. 1H-NMR (CDCl3, delta) : 8.55 (dd, 2H, pyridine H6); 8.25 (bs, 1H, NH), 7.52 (ddd, 2H, pyridine H4 ); 7.38 (dd, 2H, pyridine H3); 7.02-7.17 (m, 5H, pyridine H5, indole H2, 6, 7); 6.50-6.60 (m, 2H, indole H3, 5); 4.40 (t, 1H, CH); 3.15-3.30 (m, 4H, piperazine protons); 2.60 - 2.75 (m, 4H, piperazine protons); 2.35 - 2.60 (m, 4H, CCH2CH2N).
13%	With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; at 20℃; for 24.0h;	A mixture of 1.15 g of Compound 16B, 1.2 g of 1-(4-indolyl)piperazine (prepared as described in EP 138,280), 1.24 mL of acetic acid, 1.71 g of sodium triacetoxyborohydride and 85 mL of 1,2-dichloroethane was stirred at room temperature for 24 h. Afterwards it was diluted with water and alkalinized with sodium carbonate. The organic layer was dried on sodium sulphate and evaporated to dryness affording 1.53 g of crude, which was purified by flash chromatography (ethyl acetate-2.2 N methanolic ammonia, gradient from 9.4:0.6 to 9.2:0.8) affording 0.28 g (13percent) of the title product as an oil.

Reference： [1]Patent: EP1000046,2003,B1 .Location in patent: Page/Page column 15
[2]Patent: US6894052,2005,B1 .Location in patent: Page/Page column 22

18
2-(7-methoxy-3,4-dimethyl-2-oxo-2H-chromen-6-yloxy)ethyl methanesulfonate [ No CAS ]
[ 84807-09-0 ]
6-{2-[4-(1H-indol-4-yl)piperazin-1-yl]ethoxy}-7-methoxy-3,4-dimethylchromen-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In acetonitrile; for 25.0h;Heating / reflux;	0.66 g of 4-piperazin-1-yl-1H-indol and 0.84 g of sodium hydrogencarbonate are added to a solution of 1 g of ethyl 2-(7-methoxy-3,4-dimethyl-2-oxo-2H-chromen-6-yloxy)methanesul fonate in 30 ml of acetonitrile, and the mixture is refluxed for 25 hours. After the mixture has been cooled to room temperature, it is poured onto ice and subjected to conventional work-up, giving 6-{2-[4-(1H-indol-4-yl)piperazin-1-yl]ethoxy}-7-methoxy-3,4-dimethylchromen-2-one; m.p. 201-202° C

Reference： [1]Patent: US2004/14768,2004,A1 .Location in patent: Page 5

19
[ 4377-41-7 ]
[ 84807-09-0 ]
[ 511230-03-8 ]

Yield	Reaction Conditions	Operation in experiment
2.87 g (70%)	With N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide;	d) 1-(4-Indolyl)-4-(quinoline-2-ylmethyl)piperazine (Compound 1C) A mixture of 2-chloromethylquinoline (2.56 g), DIPEA (4.16 ml) and 1-(4-indolyl)piperazine (2.65 g) in DMF (4 ml) was heated at 120-130° C. for 3-4 hours. After cooling to room temperature, the mixture was diluted with water (50-60 ml); the liquids were decanted and extracted with diethyl ether (3*40 ml), washed with water, dried on sodium sulphate and filtered; the solid residue was dissolved in dichloromethane, washed with water, dried on sodium sulphate and filtered. The combined organic layers were evaporated to dryness at reduced pressure. The crude was purified by flash chromatography eluding with ethyl acetate-petroleum ether 75:25 to give 2.87 g (70percent) of the desired compound as a solid. 1H-NMR (delta): 2.65-2.96 (m, 4H), 3.28-3.42 (m, 4H), 3.99 (s, 2H), 6.51-6.66 (m, 2H), 6.98-7.18 (m, 3H), 7.48-7.61 (m, 1H), 7.61-7.89 (m, 3H), 8.07-8.28 (m, 3H)

Reference： [1]Patent: US2003/162777,2003,A1

20
1,2,3,4-tetrahydroquinoline-2-carboxilic acid [ No CAS ]
[ 2942-58-7 ]
[ 84807-09-0 ]
[ 511230-04-9 ]

Yield	Reaction Conditions	Operation in experiment
0.7 g (58%)	With triethanolamine; In dichloromethane; N,N-dimethyl-formamide;	g) 1-(4-Indolyl)-4-(1,2,3,4-tetrahydroquinoline-2-ylcarbonyl)piperazine (Compound 1D) TEA (0.48 ml) and diethyl cyanophosphonate (0.53 ml) were added to a stirred solution of 1,2,3,4-tetrahydroquinoline-2-carboxilic acid (0.594 g) and 1-(4-indolyl)piperazine (0.675 g) in DMF (24 ml) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. It was diluted with H2O (300 ml) and the white precipitate which formed was filtered and dried on sodium sulphate by dissolving in CH2Cl2, and the solution was evaporated to dryness in vacuo. The residue was purified by flash chromatography eluding with petroleum ether-EtOAc 1:1 to give 0.7 g (58percent) of the title compound. 1H-NMR (delta): 1.60-1.90 (m, 1H), 2.10-2.25 (m, 1H), 2.70-3.00 (m, 2H), 3.20-3.35 (m, 4H), 3.65-4.10 (m, 4H), 4.40 (dd, 1H), 4.50 (s, 1H), 6.51-6.75 (m, 4H), 6.95-7.30 (m, 5H), 8.25 (s, 1H)

Reference： [1]Patent: US2003/162777,2003,A1

21
2-chloromethyl-1,2,3,4-tetrahydroquinoline [ No CAS ]
[ 84807-09-0 ]
[ 511230-02-7 ]

Yield	Reaction Conditions	Operation in experiment
0.08 g (32%)	In water; N,N-dimethyl-formamide;	b) 1-(4-Indolyl)-4-(1,2,3,4-tetrahydroquinoline-2-ylmethyl)piperazine (Compound 1B) 0.13 g of Compound 1A and 0.20 g of 1-(4-indolyl)piperazine (WO 99/67237) in 1.5 ml of DMF was stirred at 100° C. under nitrogen atmosphere for 2 hours. The cooled mixture was poured into 20 ml of water and extracted with ethyl acetate (3*5 ml). The organic layer was dried on anhydrous sodium sulphate and evaporated to dryness. The residue was purified by flash chromatography (petroleum ether-ethyl acetate 7:3) to give 0.08 g (32percent) of the title compound. 1H-NMR (delta): 1.45-1.75 (m, 1H), 1.85-2.00 (m, 1H), 2.45-3.10 (m, 8H), 3.20-3.60 (m, 6H), 6.50-6.70 (m, 4H), 6.90-7.05 (m, 2H), 7.05-7.20 (m, 3H), 8.25 (bs, 1H)

Reference： [1]Patent: US2003/162777,2003,A1

22
[ 7252-83-7 ]
[ 865-47-4 ]
[ 84807-09-0 ]
[ 108-95-2 ]
[ 349671-61-0 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; sodium tris(acetoxy)borohydride; In 1,4-dioxane; hydrogenchloride; methanol; water; ethyl acetate; 1,2-dichloro-ethane; N,N-dimethyl-formamide; tert-butyl alcohol;	Example 5 5aa, 4-{4-[2-(2,6-Dimethyl-phenoxy)-ethyl]-piperazin-1-yl}-1H-indole. To a solution of phenol (1.6 mmol) in DMF (1.6 mL) was added a solution of potassium-tert.-butoxide (1.6 mL, 1.6 mmol, 1.0M in tert.-butanol). The mixture was stirred for 5 min at room temperature. An aliquot of the resulting solution (850 muL) was added to a solution of 2-bromo-1,1-dimethoxyethane (59 mg, 0.35 mmol) in DMF (0.70 mL). The reaction mixture was warmed to 80° C. and stirred for 16 h. After cooling to room temperature, ethyl acetate (6 mL) was added. The organic phase was washed with water (24 mL) and dried over sodium sulphate. After evaporation of the volatiles in vacuo, the resulting oil was dissolved in a mixture of dioxane and 3M HCl (4 mL, dioxane: 3M HCl 8:1) and heated to 80° C. for 1 h. After cooling to room temperature, ethyl acetate (6 mL) was added. The organic phase was washed with water (24 mL) and dried over sodium sulphate. After evaporation of the volatiles in vacuo, the resulting oil was dissolved in 1,2-dichloroethane (1.80 mL). An aliquot of the resulting solution (600 muL) was added to a solution of 1-[1H-indol-4-yl]piperazine (4.5 mg, 22.4 mumol) in DMF (60 muL), followed by sodium triacetoxyborohydride (30 mg, 0.14, mmol). After shaking the mixture at room temperature for 2 h, a mixture of methanol/water (600 muL, methanol:water 9:1) was added, and the resulting solution was loaded on a pre-conditioned ion exchange column. The column was washed with acetonitrile (2.5 mL) and methanol (2.5 mL), followed by elution of the product with 4 N solution of ammonia in methanol (4.5 mL). After removal of solvents in vacuo, the the title compound was obtained as a colourless oil (5.7 mg, 16.9 mumol, 75percent). LC/MS (m/z) 350 (MH+), Rt=2,32 (method B), purity 89,5percent.

Reference： [1]Patent: US2003/50307,2003,A1

23
etheral hydrogen chloride [ No CAS ]
[ 50912-59-9 ]
[ 84807-09-0 ]
[ 349671-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; potassium carbonate; In N-methyl-acetamide; ethanol; ethyl acetate; 4-methyl-2-pentanone;	A mixture of <strong>[84807-09-0](1H-indole-4-yl)piperazine</strong> (0.77 g), potassium carbonate (1.6 g), potassium iodide (cat.) and 3-(2-chlorophenoxy)-1-propylbromide (1.0 g) in methyl isobutylketone/dimethylformamide (1/1, 100 mL) was heated to 120° C. When TLC indicated the reaction to be completed (24 h), the mixture was cooled, filtered and evaporated. The crude material was dissolved in ethyl acetate and washed using standard procedure, followed by drying, filtration and evaporation. The crude material was purified using silicagel flash chromatography (heptane: ethylacetate: triethylamine/55:43:2). The collected pure oil was dissolved in ethanol followed by addition of etheral hydrogen chloride. Filtration gave the title compound as pure crystalline material (0.3 g). Mp. 189-99° C. 1H NMR (DMSO-d6): 2.30 (m, 2H); 3.20-3.45 (m, 6H); 3.60-3.75 (m, 4H); 4.20 (t, 2H); 6.45 (m, 1H); 6.55 (d, 1H); 6.95-7.05 (m, 2H); 7.10-7.20 (m, 2H); 7.25-7.35 (m, 2H); 7.45 (d, 1H); 11.05 (b, 1H); 11.20 (s, 1H). MS: m/z: 370 (MH+), 199, 117. Anal. Calcd for C21H24ClN3O: C, 54.72; H, 6.14; N, 9.12. Found C, 55.20; H, 6.48; N, 8.45.

Reference： [1]Patent: US2003/50307,2003,A1

24
[ 79-04-9 ]
2-chloro-4-fluorobenzenethiol [ No CAS ]
[ 84807-09-0 ]
[ 349671-91-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; triethylamine; In tetrahydrofuran;	Example 3 3a, 4-{4-[2-(2-Chloro-4-fluoro-phenylsulanyl)-ethyl]-piperazin-1-yl}-1H-indole, 1.25 Oxalate A solution of chloroacetyl chloride (1.86 g) in dry tetrahydrofuran (5 mL) was added dropwise over 10 min to a mixture of <strong>[84807-09-0](1H-indole-4-yl)piperazine</strong> (2.50 g) and triethylamine (3.8 g) in dry tetrahydrofuran at room temperature. The reaction was quenched with water after 40 min and washed using standard procedure (ethyl acetate). Drying and evaporation gave 3.5 g of the chloroacetylated derivative. This crude product was directly used in the subsequent step. 2-chloro-4-fluorothiophenol (1.1 g) was dissolved in tetrahydrofuran (40 mL) and potassium tert-butoxide (0.84 g) was added followed by stirring for 10 min. This mixture was treated dropwise with a solution of the chloroacetylated derivative (1.70 g), prepared above, in tetrahydrofuran (20 mL). The reaction was allowed to proceed at room temperature for 1 h and then 20 min at reflux, whereafter is was cooled and evaporated. The crude mixture was washed using standard procedure (ethyl acetate) and evaporated to give, after purification by silicagel flash chromatography (heptane: 30-50percent ethylacetate), the pure alkylated product (2.00 g), 1-[2-chloro-4-fluorophenylthiomethylcarbonyl]-4-[1H-indol-4-yl]piperazine.

Reference： [1]Patent: US2003/50307,2003,A1

25
[ 349671-89-2 ]
[ 84807-09-0 ]
[ 349671-28-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; oxalic acid; potassium carbonate; In N-methyl-acetamide; ethanol; ethyl acetate; 4-methyl-2-pentanone;	A mixture of <strong>[84807-09-0](1H-indole-4-yl)piperazine</strong> (1.1 g), potassium carbonate (2.3 g), potassium iodide (cat.) and 3-(2-chlorophenylthio)-1-propylbromide (1.5 g) in methyl isobutylketone/dimethylformamide (1/1, 100 mL) was heated to 120° C. When TLC indicated the reaction to be completed (24 h), the mixture was cooled, filtered and evaporated. The crude material was dissolved in ethyl acetate and washed using standard procedure, followed by drying, filtration and evaporation. The crude materials were purified using silicagel flash chromatography (heptane: ethylacetate: ethanol: triethylamine/85:5:25:5). The collected pure oil was dissolved in ethanol (150 mL) followed by addition of oxalic acid. Filtration gave the title compound as pure crystalline material (1.2 g). Mp. 182-83° C. 1H NMR (DMSO-d6): 1.95 (q, 2H); 2.75-3.00 (m, 6H); 3.10 (t, 2H); 3.15-3.25 (m, 4H); 6.40 (m, 1H); 6.45 (d, 1H); 6.95-7.05 (m, 2H); 7.15-7.25 (m, 2H); 7.35 (t, 1H); 7.40-7.50 (m, 2H); 11.05 (s, 1H). MS: m/z: 386 (MH+), 285, 157. Anal. Calcd for C21H24ClN3S: C, 59.58; H, 5.68; N, 9.27. Found C, 59.28; H, 6.01; N, 9.33.

Reference： [1]Patent: US2003/50307,2003,A1

26
[ 24424-99-5 ]
[ 84807-09-0 ]
[ 762-75-4 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In chloroform; N,N-dimethyl-formamide;	Step (a) BOC Protection of the Piperazine N4 Nitrogen 4-Piperazinoindole (1 eq), DMAP (0.1 eq) and Et3N (4 eq) were dissolved in DMF. (BOC)2O (1.1 eq) was added and the reaction mixture was stirred at room temperature (12 h). DMF was evaporated and the residue was purified by chromatography on silica gel using a mixture of chloroform, methanol and ammonia as eluent. HPLC: 100percent purity. MS m/z 302.2 (M+H).

Reference： [1]Patent: US2002/68732,2002,A1

27
[ 84807-09-0 ]
1-(phenylsulfonyl)-4-(1-piperazinyl)-1H-indole hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		Briefly, BVT.5182C was prepared according the general procedure depicted in Scheme 1, below, starting from commercially available 4-piperazinoindole (compound 1) that undergoes steps (a) to (c) to afford 1-(phenylsulfonyl)-<strong>[84807-09-0]4-(1-piperazinyl)-1H-indole</strong>, hydrochloride (yield 80percent). HPLC purity >95percent; 1H NMR (DMSO-d6) delta9.64 (br s, 2 H), 8.00-7.85 (m, 3 H), 7.79 (d, J=3.77 Hz, 1 H), 7.70-7.65 (m, 1 H), 7.63-7.60 (m, 3 H), 7.27-7.22 (m, 1 H), 6.95 (d, J=3.76 Hz, 1 H), 6.81-6.77 (m, 1 H), 3.30-3.20 (m, 4 H); 13C NMR (DMSO-d6) delta144.79, 137.02, 135.22, 134.62, 129.82, 126.85, 125.63, 125.54, 123.49, 111.15, 107.87, 107.76, 47.81, 42.86; MS (posES-FIA) m/z 342 (M+H).

Reference： [1]Patent: US2002/68732,2002,A1

28
[ 107-04-0 ]
[ 84807-09-0 ]
[ 433214-36-9 ]

Yield	Reaction Conditions	Operation in experiment
0.57 g (36%)	With N-ethyl-N,N-diisopropylamine; In water;	Preparation of 1-(2-chloroethyl)-4-(4-indolyl)piperazine (Compound 76B) 8.3 mL of 1-bromo-2-chloroethane, 1.2 g of 1-(4-indolyl)piperazine and 1.2 mL of DIPEA was stirred at 60° C. for 3 h under nitrogen atmosphere. To the solution, cooled at r.t., was added 30 mL of H2O. The mixture was then extracted with CH2Cl2-MeOH 7:3 (3*15 mL). The organic layer, dried on an. Na2SO4, was evaporated to dryness. The crude was purified by flash chromatography (CH2Cl2-MeOH 98:2) to give 0.57 g (36percent) of the title compound. 1H-NMR (CDCl3, delta): 11.05 (s, 1H, NH), 6.90-7.35 (m, 3H, H2, H6, H7), 6.45 (d, 1H, H5), 6.35 (t, 1H, H3), 3.70 (t, 2H, CH2CH2Cl), 3.00-3.15 (m, 4H, piperazine protons), 2.55-2.80 (m, 6H, CH2CH2Cl, piperazine protons).

Reference： [1]Patent: US6399614,2002,B1

29
[ 24424-99-5 ]
[ 84807-09-0 ]
[ 252978-89-5 ]

Yield	Reaction Conditions	Operation in experiment
8%	With triethylamine; In tetrahydrofuran; isopropyl alcohol; at 0 - 20℃;	Synthesis of tert-butyl <strong>[84807-09-0]4-(1H-indol-4-yl)-piperazine</strong>-1-carboxylate Into a 1000 mL round-bottom flask, was placed a solution of 4-piperazin-1-yl-1H-indole (8 g, 39.60 mmol, 1.00 equiv) in i-PrOH (600 mL). To the mixture was added Et3N (3 mL). This was followed by the addition of a solution of (Boc)2O (12.1 g, 55.50 mmol, 1.00 equiv) in THF (200 mL), which was added dropwise with stirring, while cooling to a temperature of 0° C. The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at room temperature. The reaction progress was monitored by LC-MS. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The residue was dissolved in 2000 mL of EtOAc. The resulting mixture was washed 3 times with 500 mL of brine. The mixture was dried over Na2SO4. The residue was purified by eluding through a column with a 1:50 MeOH/DCM solvent system. The collected fractions were combined and concentrated by evaporation under vacuum using a rotary evaporator. The resulting mixture was washed with hexane. This results in 1 g (8percent) of <strong>[84807-09-0]4-(1H-indol-4-yl)-piperazine</strong>-1-carboxylic acid tert-butyl ester as a brown solid.
	With sodium hydroxide; In 1,4-dioxane; water;	EXAMPLE 1 Preparation of 1-(Phenylsulfonyl)-4-piperazin-1-yl-1H-indole Hydrochloride A mixture of 1H-indol-4-ylpiperazine (4.0 g, 20 mmol), di-t-butyl dicarbonate (4.8 g, 22 mmol) and NaOH (0.8 g, 20 mmol) in 40percent dioxane is stirred at room temperature for 10 hours and treated with water. The reaction mixture is extracted with ethyl acetate. The extracts are combined, dried over Na2SO4 and concentrated in vacuo to give t-butyl 4-(1H-indol-4-yl)piperazine-1-carboxylate as a colorless solid, mp 137° C., identified by mass spectral and elemental analyses.

Reference： [1]Patent: US2008/318941,2008,A1 .Location in patent: Page/Page column 19-20
[2]Patent: US2002/115670,2002,A1

30
[ 84807-09-0 ]
[ 252979-03-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran;	A part of this product (2.5 g) was dissolved in dry tetrahydrofuran (25 mL) and added dropwise to a solution of 1-(1H-indol-4-yl)piperazine (1.4 g) and triethylamine (15 mL) in tetrahydrofuran (100 mL). After stirring for 16 hours the reaction mixture was concentrated in vacuo. The remaining oil was purified by flash chromatography (eluent: ethyl acetate/methanol/triethylamine 85:10:5) giving 1-(2-(6-chloro-1H-indol-3-yl)-1,2-dioxoethyl)-4-(1H-indol-4-yl)piperazine (1.6 g) as a crystalline material.

Reference： [1]Patent: US6391882,2002,B1

31
3-(3-bromo-1-propyl)-6-fluoro-1,2-benzisoxazole [ No CAS ]
[ 84807-09-0 ]
[ 252978-31-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; potassium carbonate; In 4-methyl-2-pentanone;	Example 4 4a, 1-(3-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-propyl)-4-(1H-indol-4-yl)piperazine, fumarate. A solution of 3-(3-bromo-1-propyl)-6-fluoro-1,2-benzisoxazole (1.1 g), 1-(1H-indol-4-yl)piperazine (1.0 g), potassium carbonate (1.9 g), and potassium iodide (50 mg) in 4-methyl-2-pentanone (100 mL) was refluxed for 16 hours. Filtration and removal of solvent in vacuo gave an oil which was purified by flash chromatography (eluent: heptane/ethyl acetate/triethylamine 75:20:5) giving an oil (1.0 g) which was crystallized as the title fumarate from acetone by addition of fumaric acid.

Reference： [1]Patent: US6391882,2002,B1

32
(R)-2-(toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one [ No CAS ]
[ 110-17-8 ]
[ 84807-09-0 ]
2-[4-(1H-Indol-4-yl)-piperazin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1.4-dioxino[2.3-e]indol-8-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; chloroform; dimethyl sulfoxide; ethyl acetate;	EXAMPLE 6 2-[4-(1H-Indol-4-yl)-piperazin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1.4-dioxino[2.3-e]indol-8-one (R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (1.0 g, 2.7 mmole) and <strong>[84807-09-0]4-(1H-indol-4-yl)-piperazine</strong> (2.0 g, 10 mmole) were combined in 30 ml of dry DMSO and heated to 80° C. for 4 hours under an argon atmosphere. After cooling to room temperature, the mixture was diluted with 400 ml of 1:1 ethyl acetate/hexane and washed with 400 ml of saturated sodium bicarbonate solution, with two 250 ml portions of water and with saturated brine. The mixture was dried over sodium sulfate, filtered and concentrated in vacuum to yield an oil, which was column chromatographed on silica gel using 0.5percent methanol/CHCl3 as eluant. The free base of the title compound (0.80 g) thus obtained was crystallized from methanol with the addition of one equivalent of fumaric acid to give 077 g of the (S) enantiomer of the title compound as a white solid fumarate, m.p. 237°-238° C.
	In methanol; chloroform; dimethyl sulfoxide; ethyl acetate;	EXAMPLE 6 2-[4-(1H-Indol-4-yl)-piperazin-1-ylmethyl]-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one (1.0 g, 2.7 mmole) and <strong>[84807-09-0]4-(1H-indol-4-yl)-piperazine</strong> (2.0 g, 10 mmole) were combined in 30 ml of dry DMSO and heated to 80 °C for 4 hours under an argon atmosphere. After cooling to room temperature, the mixture was diluted with 400 ml of 1:1 ethyl acetate/hexane and washed with 400 ml of saturated sodium bicarbonate solution, with two 250 ml portions of water and with saturated brine. The mixture was dried over sodium sulfate, filtered and concentrated in vacuum to yield an oil, which was column chromatographed on silica gel using 0.5percent methanol/CHCl3 as eluant. The free base of the title compound (0.80 g) thus obtained was crystallized from methanol with the addition of one equivalent of fumaric acid to give 077 g of the (S) enantiomer of the title compound as a white solid fumarate, m.p. 237-238 °C.

Reference： [1]Patent: US5869490,1999,A
[2]Patent: EP932609,2003,B1

33
[ 127561-33-5 ]
[ 84807-09-0 ]
3-[cis-4-[4-(1H-Indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 1A 3-[cis-4-[4-(1H-Indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole A solution of 4-(1H-indol-3-yl)-cyclohexanone (0.53 g,2.5 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.5 g, 2.5 mmol), sodium triacetoxyborohydride (0.78 g, 3.5 mmol) and acetic acid (0.14 ml, 2.5 mmol) in 1,2-dichloroethane (11 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (360 ml), and washed with brine (360 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.52 g (53percent) of product as a white solid: mp 85-87° C. The HCl salt was prepared in ethyl acetate: mp 198-200° C. Elemental analysis for C26H30N4.HCl; Calc'd: C, 68.25; H, 7.38; N, 12.25; Found: C, 68.12; H, 7.16; N, 11.93.

Reference： [1]Patent: US6313126,2001,B1

34
[ 127561-33-5 ]
[ 84807-09-0 ]
3-[cis-4-[4-(1H-Indol-4-yl)-1-piperazinyl]cyclohexyl]-2-methyl-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; 1,2-dichloro-ethane;	EXAMPLE 9a 3-[cis-4-[4-(1H-Indol-4-yl)-1-piperazinyl]cyclohexyl]-2-methyl-1H-indole A solution of 4-(1H-indol-3-yl)-cyclohexanone (1.44 g, 6.33 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.27 g, 6.33 mmol), sodium triacetoxyborohydride (1.88 g, 8.86 mmol) and acetic acid (0.76 mg, 12.6 mmol) in 1,2-dichloroethane (100 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (80 ml), extracted with methylene chloride (3*300 ml), and washed with brine (150 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed under vacuum to afford an off-white solid. Trituration of the solid with warm methylene chloride (80 ml) followed by filtration afforded 0.88 g of white solid. The mother liquor was concentrated and chromatographed (2percent methanol-methylene chloride) to afford another 0.18 g (total yield 40.7percent) of product as a white solid: mp 279-280° C. The HCl salt was prepared in ethanol: mp 200-203° C. Elemental analysis for C271H32N4.2HCl; Calc'd: C, 64.99; H, 7.17; N, 11.23; Found: C, 65.05; H, 7.07; N, 11.23.

Reference： [1]Patent: US6313126,2001,B1

35
[ 282547-09-5 ]
[ 84807-09-0 ]
4-Fluoro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 2a 4-Fluoro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole A solution of 4-(4-fluoro-1H-indol-3-yl)-cyclohexanone (0.88 g, 3.8 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.7 g, 3.5 mmol), sodium triacetoxyborohydride (1.1 g, 5.2 mmol) and acetic acid (0.4 ml, 7 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (360 ml), and washed with brine (360 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (5-7percent methanol-ethyl acetate) afforded 1.14 g (79percent) of product as a white foam. The HCl salt was prepared in ethanol: mp 283-285° C. Elemental analysis for C26H29FN4.HCl.0.25H2O; Calc'd: C, 68.26; H, 6.72; N, 12.25; Found: C, 68.16; H, 6.74; N, 12.04.

Reference： [1]Patent: US6313126,2001,B1

36
[ 282547-11-9 ]
[ 84807-09-0 ]
5-Chloro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 6a 5-Chloro-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl] -1 H-indole A solution of 4-(5-chloro-1H-indol-3-yl)-cyclohexanone (0.78 g, 3.1 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.6 g, 3 mmol), sodium triacetoxyborohydride (0.95 g, 4.5 mmol) and acetic acid (0.34 ml, 6 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (360 ml) and washed with brine (360 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (5percent methanol-ethyl acetate) afforded 0.84 g (65percent) of product as a white foam. The HCl salt was prepared in ethanol: mp 283-285° C. Elemental analysis for C26H29ClN4.HCl.0.25H2O; Calc'd: C, 65.46; H, 6.69; N, 11.45; Found: C, 65.14; H, 6.73; N, 11.33.

Reference： [1]Patent: US6313126,2001,B1

37
[ 185383-65-7 ]
[ 84807-09-0 ]
5-Methoxy-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 8a 5-Methoxy-3-[cis-4-[4-(1H-indol-4-yl)-1-piperazinyl]cyclohexyl]-1H-indole A solution of 4-(5-methoxy-1H-indol-3-yl)-cyclohexanone (1.2 g, 5 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1 g, 5 mmol), sodium triacetoxyborohydride (1.47 g, 6.2 mmol) and acetic acid (0.28 ml, 4 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (360 ml) and washed with brine (360 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (2.5percent methanol-ethyl acetate) afforded 1.18 g (55percent) of product as a white solid: mp 105-108° C. The HCl salt was prepared in ethyl acetate: mp 283-285° C. Elemental analysis for C27H32N4O.HCl.1.5H2O; Calc'd: C, 68.55; H, 7.03; N, 11.85; Found: C, 68.86; H, 7.29; N, 11.76.

Reference： [1]Patent: US6313126,2001,B1

38
[ 282547-20-0 ]
[ 84807-09-0 ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-methyl-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 12a 3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-methyl-1H-indole-5-carbonitrile A solution of 4-(5-cyano-1-methyl-3-indolyl)-cyclohexanone (0.75 g, 3 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (0.6 g, 3 mmol), sodium triacetoxyborohydride (0.95 g, 4.5 mmol) and acetic acid (0.34 ml, 6 mmol) in 1,2-dichloroethane (20 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (10 ml), extracted with methylene chloride (360 ml) and washed with brine (360 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.73 g (56percent) of product as a white solid: mp 274-275° C. The HCl salt was prepared in ethyl acetate: mp 285.5-288° C. Elemental analysis for C28H31N5.2HCl.H2O; Calc'd: C, 68.35; H, 6.97; N, 14.23; Found: C, 68.51; H, 6.65; N, 14.06.

Reference： [1]Patent: US6313126,2001,B1

39
[ 282547-22-2 ]
[ 84807-09-0 ]
3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-propyl-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 14a 3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1-propyl-1H-indole-5-carbonitrile A solution of 4-(5-cyano-1-n-propyl-indol-3-yl)-cyclohexanone (1.68 g, 6 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.27 g, 6.3 mmol), sodium triacetoxyborohydride (1.84 g, 8.9 mmol) and acetic acid (0.94 ml, 16 mmol) in 1,2-dichloroethane (80 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (20 ml), extracted with methylene chloride (3100 ml) and washed with brine (3100 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (10percent methanol-ethyl acetate) afforded 0.42 g(15percent) of product as a white powder. The HCl salt was prepared in ethanol: mp 200-206° C. Elemental analysis for C30H35N5.2HCl.0.75H2O; Calc'd: C, 65.27; H, 7.03; N, 12.69; Found: C, 65.18; H, 6.97; N, 12.68.

Reference： [1]Patent: US6313126,2001,B1

40
[ 282547-23-3 ]
[ 84807-09-0 ]
1-Benzyl-3-{(1,4-trans)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane;	EXAMPLE 16a 1-Benzyl-3-{(1,4-cis)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-cyclohexyl}-1H-indole-5-carbonitrile A solution of 4-(5-cyano-1-benzyl-indol-3-yl)-cyclohexanone (2.97 g, 9 mmol), <strong>[84807-09-0]1-(indol-4-yl)piperazine</strong> (1.94 g, 9.6 mmol), sodium triacetoxyborohydride (2.7 g, 13 mmol) and acetic acid (1 ml, 24 mmol) in 1,2-dichloroethane (50 ml) was allowed to stir at room temperature overnight. The reaction was quenched with 1N sodium hydroxide (20 ml), extracted with methylene chloride (3100 ml) and washed with brine (3100 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. Chromatography (25-50percent ethyl acetate-hexanes) afforded 1.71 g (37percent) of product as a white powder. The HCl salt was prepared in ethanol: mp dec.>245° C. Elemental analysis for C34H35N5.HCl.0.5H2O; Calc'd: C, 68.56; H, 6.43; N, 11.76; Found: C, 68.93; H, 6.55; N, 11.52.

Reference： [1]Patent: US6313126,2001,B1

41
[ 125228-75-3 ]
[ 84807-09-0 ]
1-[4-(1H-indol-4-yl)-piperazin-1-yl]-3-(4-nitro-phenoxy)-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 4 1-[4-(1H-Indol-4-yl)-piperazin-1-yl]-3-(4-nitro-phenoxy)-propan-2-ol A methanolic solution (65 ml) of 1,2-epoxy-3-(4-nitrophenoxy)-propane (0.59 g, 3.0 mmole) and 1-(indol-4yl)-piperazine (0.6 g, 3.0 mmole) was refluxed for 1 hr under an atmosphere of nitrogen. The mixture was concentrated in vacuo to afford the product as a yellow solid (1.1 g, 93percent). Treatment with a 4M etheral HCl solution gave the required product, which was recrystallized from ethanol to afford the title compound as a light yellow solid. m.p. 248° C. Elemental Analysis for: C21H24N4O4. 1.0HCl Calculated: C, 58.26; H, 5.82; N, 12.94 Found: C, 57.92; H, 5.76; N, 12.66

Reference： [1]Patent: US6310066,2001,B1

42
[ 18123-82-5 ]
[ 84807-09-0 ]
1-(4-Fluoro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 6 1-(4-Fluoro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol A methanolic solution (50 ml) of 1-(4-fluorophenoxy)-2,3-epoxypropane (0.50 g, 3.0 mmole) and 1-(indol-4yl)-piperazine (0.6 g, 3.0 mmole) was refluxed for 1 hr under an atmosphere of nitrogen. The mixture was concentrated in vacuo, and the product purified by silica gel chromatography (EtOAc) to afford a white solid (1.1 g, 99percent). Treatment with a 0.25M ethanolic fumaric acid solution gave the required salt, which was recrystallized from ethanol to afford the title compound as a white solid. m.p. 234-235° C. Elemental Analysis for: C21H24FN3O2. 0.5C4H4O4 Calculated: C, 64.62; H, 6.13; N, 9.83 Found: C, 64.38; H, 6.01; N, 9.67

Reference： [1]Patent: US6310066,2001,B1

43
(+/-)-4-chlorophenyl-2,3-epoxypropyl ether [ No CAS ]
[ 84807-09-0 ]
1-(4-Chloro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 2 1-(4-Chloro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol A methanolic solution (75 ml) of 4-chlorophenyl-2,3-epoxypropyl ether (0.55 g, 3.0 mmole) and 1-(indol-4yl)-piperazine (0.6 g, 3.0 mmole) was refluxed for 1 hr under an atmosphere of nitrogen. The mixture was concentrated in vacuo, and the product purified by silica gel chromatography (EtOAc:Hexane 90:10) to afford a white solid (1.25 g, 100percent). Treatment with a 0.25M ethanolic fumaric acid solution gave the required product, which was recrystallized from ethanol to afford the title compound as a white solid. m.p. 224-2250C. Elemental Analysis for: C21H24ClN302. 0.5C4H4O4 Calculated: C, 62.23; H, 5.9; N, 9.47 Found: C, 61.98; H, 5.79; N, 9.21

Reference： [1]Patent: US6310066,2001,B1

44
4-methoxyphenyl-2,3-epoxypropyl ether [ No CAS ]
[ 84807-09-0 ]
1-[4-(1H-indol-4-yl)-piperazin-1-yl]-3-(4-methoxy-phenoxy)-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3 1-[4-(1H-Indol-4-yl)-piperazin-1-yl]-3-(4-methoxy-phenoxy)-propan-2-ol A methanolic solution (75 ml) of 4-methoxyphenyl-2,3-epoxypropyl ether (0.54 g, 3.0 mmole) and <strong>[84807-09-0]1-(indol-4-yl)-piperazine</strong> (0.6 g, 3.0 mmole) was refluxed for 1 hr under an atmosphere of nitrogen. The mixture was concentrated in vacuo, and the product purified by silica gel chromatography (CH2Cl2:MeOH 90:10) to afford a white solid (1.1 g, 96percent). Treatment with a 0.25M ethanolic fumaric acid solution gave the required product, which was recrystallized from ethanol to afford the title compound as a white solid. m.p. 226-227° C. Elemental Analysis for: C22H27N3O03. 0.5C4H4O4 Calculated: C, 65.59; H, 6.65; N, 9.56 Found: C, 65.36; H, 6.48; N, 9.36

Reference： [1]Patent: US6310066,2001,B1

45
[ 35308-87-3 ]
[ 84807-09-0 ]
1-(1H-Indol-4yloxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	EXAMPLE 1 1-(1H-Indol-4yloxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol A methanolic solution (20 ml) of 1-(indole4-oxy)-2,3-epoxypropane (0.38 g, 2.0 mmole) was added dropwise under a nitrogen atmosphere to a stirred solution of <strong>[84807-09-0]1-(indol-4-yl)-piperazine</strong> (0.4 g, 2.0 mmole) in methanol (75 ml). The mixture was heated to reflux for 2 hrs, concentrated in vacuo, and the product purified by column chromatography over silica gel (CH2Cl2:MeOH 95:5) to afford an oil (0.7 g, 90percent yield). Treatment with a 0.25M ethanolic fumaric acid solution gave the required product, which was recrystallized from ethanol to afford the title compound as a white solid. m.p. 147-150° C. Elemental Analysis for: C23H26N402. 1.0C4H4O4 Calculated: C, 64.02; H, 5.97; N, 11.06 Found: C, 64.59; H, 6.36; N, 11.81

Reference： [1]Patent: US6310066,2001,B1

46
[ 2212-04-6 ]
[ 84807-09-0 ]
1-(2-Chloro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 5 1-(2-Chloro-phenoxy)-3-[4-(1H-indol-4-yl)piperazin-1-yl]-propan-2-ol A methanolic solution (75 ml) of 1-(2-chlorophenoxy)-2,3-epoxypropane (0.55 g, 3.0 mmole) and <strong>[84807-09-0]1-(indol-4-yl)-piperazine</strong> (0.6 g, 3.0 mmole) was refluxed for 1 hr under an atmosphere of nitrogen. The mixture was concentrated in vacuo, and the product purified by silica gel chromatography (CH2Cl2:MeOH 90:10) to afford a white solid (1.09 g, 94percent). Treatment with a 0.25M ethanolic fumaric acid solution gave the required product, which was recrystallized from ethanol to afford the title compound as a white solid. m.p. 207° C. Elemental Analysis for: C21H24ClN302. 0.5C4H4O4 Calculated: C, 62.23; H, 5.9; N, 9.47 Found: C, 62.13; H, 5.72; N, 9.34

Reference： [1]Patent: US6310066,2001,B1

47
[ 196308-76-6 ]
[ 497-19-8 ]
[ 107-06-2 ]
[ 84807-09-0 ]
N-{2-[4-(4-indolyl)-1-piperazinyl]-ethyl}-N-(pyridin-2-yl)-cyclohexanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium tris(acetoxy)borohydride; acetic acid; In diethyl ether; dichloromethane; water;	Step c: N-[2-[4-(4-Indolyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide HCL 1.25 H2 O A mixture of 0.94 g of N-formylmethyl-N-(2-pyridyl)cyclohexanecarboxamide, 0.69 g of 1-(4-indolyl)piperazine, 1.21 g of sodium triacetoxyborohydride, 0.44 ml of acetic acid and 30 ml of 1,2-dichloroethane was stirred at room temperature for 3 h. Afterwards, it was diluted with 20 ml of water and alkalinized to pH=10 with 20percent Na2 CO3. The aqueous layer was extracted twice with 1,2-dichloroethane and the combined organic layers were dried (sodium sulfate) and evaporated to dryness in vacuo affording a crude which was purified by flash chromatography (methylene chloride-methanol 98:2 to 95:5) affording 0.96 g of the title compound as a base. This was dissolved in 40 ml of methylene chloride and to the solution was added 3.8 N hydrogen chloride in diethyl ether. The precipitated title compound was filtered, yielding 0.66 g. M.p. 181-7° C.

Reference： [1]Patent: US5990114,1999,A

48
[ 5221-37-4 ]
[ 84807-09-0 ]
2-[4-(4-indolyl)-1-piperazinyl]-N-(pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In water; N,N-dimethyl-formamide;	Step a) 2-[4-(4-Indolyl)-1-piperazinyl]-N-(2-pyridyl)acetamide A mixture of 1.4 g of 1-(4-indolyl)piperazine, 1.26 g of 2-chloro-N-(2-pyridyl)acetamide (prepared as described in Beilstein E III/IV, 22, 3881), 1.3 ml of diisopropylethylamine, and 14 ml of N,N-dimethylformamide was stirred at 60° C. under nitrogen stream for 4 h. Afterwards, the mixture was diluted with 200 ml of water and extracted with ethyl acetate (4*50 ml). The organic layers were washed with water, dried (sodium sulfate) and evaporated to dryness in vacuo affording 2.37 g of the title compound as a crude base, which was crystallized from MeOH affording 1.6 g melting at 198-201° C.

Reference： [1]Patent: US5990114,1999,A

49
[ 178974-28-2 ]
[ 84807-09-0 ]
[ 178974-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide;	EXAMPLE 5 1-(8-Aza-bicyclo[3.2.1]oct-8-yl)-4-[4-(1H-indol-4-yl)-piperazin- 1-yl]-2-phenyl-butan-1-one The title compound was prepared from <strong>[84807-09-0]4-(1H-indol-4-yl)-piperazine</strong> (1.0 g, 4.97 mmole), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (1.6 g, 4.97 mmole), diisopropylethylamine (0.65 g, 4.97 mmole) and potassium iodide (0.83 g, 4.97 mmole) in dimethylformamide (8 mL) in the manner described in example 2 to yield 0.6 g of product as the hydrochloride 0.75 hydrate, m.p. 150°-170° C. Elemental Analysis For: C29 H36 N4 O. HCl. 0.75H2 O Calcd: C, 68.76; H, 7.66; N, 11.06. Found: C, 68.59; H, 7.74; N, 11.00.

Reference： [1]Patent: US5610154,1997,A

50
1-(3-azabicyclo[3.2.2]non-3-yl)-4-chloro-2-phenyl-butan-1-one [ No CAS ]
[ 84807-09-0 ]
[ 178974-53-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; hexane; ethyl acetate;	EXAMPLE 14 1-(3-Aza-bicyclo[3.2.2]non-3-yl)-4-[4-(1H-indol-4-yl)-piperazin-1-yl]-2-phenylbutan-1-one A mixture of 4-piperazinoindole (1.03 g, 5.1 mmole) 1-(3-azabicyclo[3.2.2]non-3-yl)-4-chloro-2-phenyl-butan-1-one (1.44 g, 4.7 mmole) and diisopropylethylamine (0.66 g, 0.89 mL, 5.1 mmole) in anhydrous dimethylformamide (50 mL) were stirred and heated at 80° C. for 1 h. The dimethylformamide was removed under reduced pressure and the brown residue dissolved dilute hydrochloric acid, washed with ether, basified with potassium carbonate solution and the oil extracted into dichloromethane, dried (MgSO4) and evaporated under reduced pressure to give a brown oil. The oil was purified by chromatography on alumina (30percent ethylacetate in hexane) to yield 1.3 g of oil. Solution of the oil in ethylacetate and addition of an ethereal solution of hydrogen chloride precipitated of the title compound, as the hydrochloride salt 1.25 g, mp 175°-179.5° C.

Reference： [1]Patent: US5610154,1997,A

51
[ 164340-66-3 ]
[ 84807-09-0 ]
[ 174854-84-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In dichloromethane; acetonitrile;	(e) (R)-1-(4-indolyl)-4-[2-methyl-2-(2-pyridylamino)ethyl]piperazine A solution of (R)-4-methyl-3-pyridin-2-yl-[1,2,3]-oxathiazolidine-2,2-dioxide (4.04 g 0.019 moles) and 4-piperazinoindole (3.80 g 0.019 moles) in acetonitrile (200 ml) was heated to 60° C. for 0.5 h then evaporated in vacuo. The residue was taken up into dilute HCl (100 ml), warmed to 60° C. for 0.5 h, cooled, washed with ethyl acetate (2100 ml), made basic with potassium carbonate, extracted into dichioromethane (3100 ml), dried (MgSO4) then evaporated in vacuo to give a brown glass. This was purified on a silica column eluding with 10percent propan-2-ol in dichloromethane to give (R)-1-(4-indolyl)-4-[2-methyl-2-(2-pyridinylamino)ethyl]piperazine (4.3 g) as a clear glass.

Reference： [1]Patent: US5723464,1998,A

52
[ 5192-23-4 ]
bis-chloroethylamine hydrochloride [ No CAS ]
[ 84807-09-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium carbonate; In butan-1-ol;	EXAMPLE 9 1-Azepan-1-yl-4-[4-(1H-indol-4-yl)piperazin-1-yl]-2-phenylbutan-1-one A suspension of 4-aminoindole (2.30 g, 0.017 moles), bischloroethylamine hydrochloride (3.49 g, 0.02 moles) and potassium carbonate (5.41 g, 0.02 moles) in butanol (50 ml) was heated at reflux under argon for 7 h. Further bischloroethylamine hydrochloride (0.70 g, 0.04 moles) and potassium carbonate (1.1 g 0.04 moles) was added, then the suspension was heated at reflux for 18 h. The solvent was evaporated in vacuo to give a brown gummy residue which was taken up into dilute hydrochloric acid (200 ml), washed with ethyl acetate (2100 ml), made basic with potassium carbonate, extracted into dichloromethane (350 ml), dried (MgSO4) then evaporated in vacuo to give a white solid which was triturated with ethyl acetate and dried to give 4-(1-piperazinyl)indole (0.78 g, 0.0038 moles) as white crystals.

Reference： [1]Patent: US5627177,1997,A

53
N-butoxycarbonylpiperidine-4-carboxylic acid [ No CAS ]
[ 84807-09-0 ]
[4-(1H-Indol-4-yl)-piperazin-1-yl]-piperidin-4-yl-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With NMM; benzotriazol-1-ol; In 4M-HCl dioxan; diethyl ether; water; N,N-dimethyl-formamide;	Example 11 [4-(1H-Indol-4-yl)-piperazin-1-yl]-piperidin-4-yl-methanone 4-(Indol-4-yl)piperazine (1.75 g, 8.7 mmol) was added to a mixture of DAEC (1.67 g, 1 equivalent), HOBT (1.3 equivalents, 1.53 g,) and N-butoxycarbonylisonipecotic acid (2 g, 8.7 mmol) in DMF (15 mL), and the resulting solution was treated with NMM (1.5 equivalents, 1.5 mL) and stirred at 0° C. for 16 hours. Water (100 mL) was added, the product extracted into ethyl acetate (3*50 mL) and the combined organics were washed with 1N-HCl (20 mL), saturated NaHCO3 (25 mL) and dried over anhydrous sodium sulfate. Filtration and concentration in vacuum afforded the product as a white solid (3.07 g, 85percent yield). A sample of the carbamate (1.5 g, 3.63 mmol) was dissolved in 4M-HCl dioxan (20 mL) and the solution stirred at ambient temperature for 4 hours. The mixture was concentrated in vacuum, diethyl ether (50 mL) added and the precipitated product collected by filtration and washed with ether (50 mL) to afford a tan colored solid (1.2 g, 98percent yield)

Reference： [1]Patent: US6255302,2001,B1

54
[ 209745-29-9 ]
[ 108-10-1 ]
[ 84807-09-0 ]
4-[4-[2-(Indan-2-yl)ethyl]piperazin-1-yl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With 1-methyl-pyrrolidin-2-one;	EXAMPLE 25 4-[4-[2-(Indan-2-yl)ethyl]piperazin-1-yl]-1H-indole, 25a. A mixture of <strong>[84807-09-0]4-(piperazin-1-yl)-1H-indole</strong> (1.5 g), 2-(2-iodoethyl)indane (2.0 g), K2C(3, methyl isobutyl ketone (150 ml), and N-methylpyrrolidone (10 ml) was boiled under reflux for 3 h. The mixture was allowed to cool to room temperature, filtered, and concentrated in vacuo. The residue was purified on silica gel eluted with ethyl acetate-heptane (1:2) to give a crystalline compound, which was recrystallized (ethyl acetate) to give the title compound (1.2 g, 47percent). Mp 146-147° C. 1H NMR (CDCl3) delta 1.70-1.85 (m, 2H), 2.40-2.70 (m, 5H), 2.75 (broad s, 4H), 3.00-3.15 (m, 2H), 3.30 (broad s, 4H), 6.55 (s, 1H), 6.60 (d, 1H), 7.00-7.30 (m, 711), 8.20 (broad s, 1H). MS m/z (percent): 346 (MH+, 34percent), 159 (88percent), 145 (100percent).

Reference： [1]Patent: US6262087,2001,B1

55
[ 917251-75-3 ]
[ 84807-09-0 ]
[ 917251-49-1 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 0.270 g of 1-quinolin-8-yl-piperidin-4-one (Example A, Step 6, above) and 0.240 g of 4-piperazino-indole (commercially available) in 15 mL CH2Cl2 was added 0.327 g of sodium triacetoxyborohydride and 0.2 mL acetic acid. The reaction was stirred at room temperature overnight. It was quenched with 1N NaOH, and the product was extracted with CH2Cl2. The organic phase was washed with water, dried over magnesium sulfate and evaporated. The product crystallized to give 0.200 g of the desired product. Mp: 256° C.; MS (ES) m/z (relative intensity): 412 (M++-H, 100).

Reference： [1]Patent: US2007/27160,2007,A1 .Location in patent: Page/Page column 47

56
[ 917251-80-0 ]
[ 84807-09-0 ]
[ 917251-54-8 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 1-(6-chloro-quinolin-8-yl)-piperidin-4-one (Step 1, 0.13 g) and of 4-piperazino-indole (commercially available, 0.100 g) in 15 mL CH2Cl2 in 10 mL of dichloroethane, was added 0.137 g of sodium triacetoxyborohydride and 0.1 mL acetic acid. The reaction was stirred at room temperature overnight. It was quenched with 1N NaOH, and the product was extracted with CH2Cl2. The organic phase was washed with water and dried over magnesium sulfate. The product was filtered through 100 ml of silica gel using 100percent Ethyl acetate, to give 0.070 g of the desired product. Mp: 224° C.; MS (ES) m/z (relative intensity): 447 (M++-H, 100).

Reference： [1]Patent: US2007/27160,2007,A1 .Location in patent: Page/Page column 51

57
[ 196308-76-6 ]
[ 107-06-2 ]
[ 84807-09-0 ]
[ 174854-81-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium tris(acetoxy)borohydride; sodium carbonate; acetic acid; In diethyl ether; dichloromethane; water;	Step c N-{2-[4-(4-Indolyl)-1-piperazinyl]-ethyl}-N-(2-pyridyl)-cyclohexanecarboxamide HCl. 1.25H2O A mixture of 0.94 g of N-formylmethyl-N-(2-pyridyl)-cyclohexanecarboxamide, 0.69 g of <strong>[84807-09-0]1-(4-indolyl)-piperazine</strong>, 1.21 g of sodium triacetoxyborohydride, 0.44 ml of acetic acid and 30 ml of 1,2-dichloroethane was stirred at room temperature for 3 hours. The mixture was then diluted with 20 ml of water and adjusted to pH 10 by addition of a 20percent solution of sodium carbonate. The aqueous layer was extracted twice with 1,2-dichloroethane and the combined organic layers were dried over anhydrous sodium sulphate. Evaporation to dryness in vacuo gave a crude product which was purified by flash chromatography, eluding with dichloromethane:methanol 98:2 to 95:5, to give 0.96 g of the base of the title compound. This was dissolved in 40 ml of dichloromethane and 3.8N hydrogen chloride in diethyl ether was added. The title compound precipitated and was filtered off. Yield 0.66 g. M.p. 181-187°C.

Reference： [1]Patent: EP906100,2004,B1

58
[ 282547-13-1 ]
[ 84807-09-0 ]
[ 282544-03-0 ]
[ 282544-01-8 ]