Name: 130-85-8|4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)|97%
Brand: Ambeed
SKU: A215829
Price: 5.0 USD
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1
[ 121-44-8 ]
[ 130-85-8 ]
C₄₆H₂₄B₂O₁₂^(2-)*2C₆H₁₅N*2H⁽¹⁺⁾ [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2000,vol. 161,p. 143 - 156

2
[ 130-85-8 ]
[ 217327-72-5 ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076

3
[ 130-85-8 ]
(S)-2-({4-[3-((S)-1-Carboxy-2-methyl-propylcarbamoyl)-2-hydroxy-naphthalen-1-ylmethyl]-3-hydroxy-naphthalene-2-carbonyl}-amino)-3-methyl-butyric acid [ No CAS ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076
[2]Chemical Communications,1998,p. 2075 - 2076

4
[ 130-85-8 ]
[ 217327-74-7 ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076

5
[ 130-85-8 ]
(E)-(S)-4-({4-[3-((E)-(S)-3-Carboxy-1-isopropyl-allylcarbamoyl)-2-hydroxy-naphthalen-1-ylmethyl]-3-hydroxy-naphthalene-2-carbonyl}-amino)-5-methyl-hex-2-enoic acid [ No CAS ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076

6
[ 130-85-8 ]
(S)-2-{(S)-2-[(4-{3-[(S)-1-((S)-1-Carboxy-2-methyl-propylcarbamoyl)-2-methyl-propylcarbamoyl]-2-hydroxy-naphthalen-1-ylmethyl}-3-hydroxy-naphthalene-2-carbonyl)-amino]-3-methyl-butyrylamino}-3-methyl-butyric acid [ No CAS ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076

7
[ 130-85-8 ]
[ 217327-73-6 ]

Reference： [1]Chemical Communications,1998,p. 2075 - 2076

8
[ 130-85-8 ]
[ 153495-52-4 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

9
[ 130-85-8 ]
[ 177267-85-5 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

10
[ 130-85-8 ]
[ 153495-50-2 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

11
[ 130-85-8 ]
homocalixnaphthalene [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

12
[ 130-85-8 ]
[ 177267-86-6 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

13
[ 130-85-8 ]
[ 177267-84-4 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869
[2]Journal of Organic Chemistry,1996,vol. 61,p. 3865 - 3869

14
[ 76144-81-5 ]
[ 130-85-8 ]
meldonium hydrogen pamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetone; toluene;	EXAMPLE 10 Meldonium pamoate (1 : 1 ; X H20). MELDONIUM (5. 46 G, 30 MMOL) AND PAMOIC acid (5.82 g, 15 MMOL) are mixed with water and acetone (15 + 15 ml), the formed suspension is evaporated, 30-40 ml toluene is added to the residual viscous mass, it is grated, and evaporation is repeated. If the residue is insufficiently dry, treatment with toluene is repeated. Mp. 128-133C (DECOMP.). H NMR spectrum (DMSO-d6), 8, ppm: 2.41 (2H, t, CH2COO-) ; 3.14 (2H, t, CH2N) ; 3.25 (9H, s, ME3N+) ; 4.75 (2H, s, - CH2- (PAM.)) ; 7.12 (2H, t, Harem) ; 7.26 (2H, td, HAROM) ; 7.77 (2H, d, HAROM) ; 8. 18 (2H, d, HAROM) ; 8. 35 (2H, s, Harom). Found, percent : C 62,90 ; H 5, 83 ; N 4,98. Calculated, percent: C 63,07 ; H 5, 84; N 5,07. Initially HA0 content in the sample was 1.71percent ; after 24 hours maintenance at 100percent humidity sample mass increased by 9percent due to absorbed water.

Reference： [1]Patent: WO2005/12233,2005,A1 .Location in patent: Page/Page column 6

15
[ 152459-95-5 ]
[ 130-85-8 ]
[ 862366-33-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; water;Heating / reflux;	Example 10; 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl] amino] phenyl]-benzamide, pamoate; A mixture of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl] amino] phenyl]-benzamide (4.94 g, 10 mmol) and 4, 4'-methylenebis [3-hydroxy-2- naphthoic acid (Fluka, Buchs, Switzerland ; 3.88 g, 10 mmol) in ethanol (50 mL) is heated. Water (25 mL) is then added. Upon cooling, the product crystallises and is filtered-off and dried to afford 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2- pyrimidinyl] amino] phenyl]-benzamide, pamoate as a pale-yellow solid, having the following analytical properties: Analysis found: C, 69.12 ; H, 5.62 ; N, 10.88percent ; H20, 2.50percent. Calculated for C52H47N707-1. 26 H20 : C, 69.04 ; H, 5.52 ; N, 10.84percent ; H20, 2. 51percent.

Reference： [1]Patent: WO2005/75454,2005,A2 .Location in patent: Page/Page column 7

16
cetrorelix acetate [ No CAS ]
[ 130-85-8 ]
cetrorelix embonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;pH 7 - 7.5;Product distribution / selectivity;	In an equimolar ratio of peptide (calculated as free base) to embonic acid, an aqueous solution of embonic acid containing alkali in excess is combined with the acetate cetrorelix acetate solution, embonic acid precipitating as yellow crystals. On addition of dilute sodium hydroxide solution up to pH 7 - 7.5, the embonic acid dissolves and precipitates with the decapeptide as aqueous cetrorelix embonate salt of the molar composition peptide : embonic acid 2:1 (Mol/Mol). The precipitate is filtered off, washed with H2O and dried.
	In ethanol; water;Product distribution / selectivity;	The alkaline embonate solution is added to the aqueous ethanolic solution of the peptide acetate in the molar ratio peptide : embonic acid 2:1. The white precipitate is filtered off and dried. The dried precipitate is moistened with 50percent ethanol, dried in a vacuum drying cabinet and sieved. The white product contains the 2:1 peptide embonate salt (Mol/Mol). Example 5 The alkaline embonate solution is added to the aqueous ethanolic solution of the peptide acetate in the molar ratio peptide : embonic acid 1:1.6. The yellow precipitate is filtered off and dried. The dried precipitate is moistened with 50percent ethanol, dried in a vacuum drying cabinet at 35°C and sieved. The yellow product contains the 2:1 peptide embonate salt (Mol/Mol) in addition to the excess of embonic acid.
	In ISOPROPYLAMIDE; water;Product distribution / selectivity;	Cetrorelix acetate and embonic acid are dissolved in equimolar proportions in dimethylacetamide and the solution is dropped into water. The white precipitate of the cetrorelix embonate peptide : embonic acid 2:1 (Mol/Mol) is filtered off and dried. Example 3 Cetrorelix and embonic acid are dissolved in a molar ratio of 1:1.6 in a mixture of dimethyl acetamide and optionally water and the solution dropped into water. The yellow precipitate is filtered off and dried. The precipitate obtained is pasted with 70percent ethanol, dried at 35°C and sieved through a sieve of mesh size 80 to 125 um.

Reference： [1]Patent: EP732934,2005,B1 .Location in patent: Page/Page column 4
[2]Patent: EP732934,2005,B1 .Location in patent: Page/Page column 5
[3]Patent: EP732934,2005,B1 .Location in patent: Page/Page column 4

17
[ 132539-06-1 ]
[ 130-85-8 ]
relprevv [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;Molecular sieve;	Preparation 1; Preparation of 2-methyl-4-(4-methyl- 1 -piperazinvD- 10H-thieno\|"2.3 - b]ri,5~\|benzodiazepine pamoate (olanzapine pamoate. See for example Preparation 3 in U.S. Patent No. 6.169.084 BlVOlanzapine (3.12 g, 0.01 mole) is dissolved in tetrahydrofuran (50 mL) with heating. <strong>[130-85-8]Pamoic acid</strong> (3.88 g, 0.01 mole) is dissolved in tetrahydrofuran (100 mL) with heating. The two solutions are mixed and filtered through a pad of Celite.(R). while it is still warm. The yellow solution is transferred to a Buchi flask and evaporated under reduced pressure (bath temperature 5O0C). After about 50 mL of solvent are removed ethanol (50 mL) is introduced and evaporation continued. A further 50 mL of ethanol is introduced after a further 50 mL of solvent is collected. Evaporation is continued until crystallization commences. The crystals are collected by filtration and dried under high vacuum at 12O0C. m.p. 203-2050C.
	In N,N-dimethyl-formamide; at 20℃; for 0.333333h;Product distribution / selectivity;	Example 1 : Preparation of amorphous form of olanzapine pamoate[00098] <strong>[130-85-8]Pamoic acid</strong> (2.5 g, 6.4 mmol) and olanzapine (2 g, 6.4 mmol) were dissolved in dimethylformamide (DMF) (10 mL) by stirring at room temperature for 20 min. The resulting orange solution was added dropwise via dropping funnel to a 250 mL round flask containing isopropyl alcohol (IP A) (extra-dry, 100 mL) at 5°C. The obtained yellow slurry was stirred at 5°C for 3 h. The yellow-orange solid was collected by suction filtration and was washed with IPA (extra-dry (>99.9percent), 50 mL). The product was dried in a vacuum oven at 60°C. The resulting powder was analyzed by XRPD to give a pattern of olanzapine pamoate amorphous form, as shown in Figure 1.

Reference： [1]Patent: WO2006/73886,2006,A1 .Location in patent: Page/Page column 6
[2]Patent: WO2011/91142,2011,A2 .Location in patent: Page/Page column 14

18
[ 132539-06-1 ]
[ 130-85-8 ]
olanzapine pamoate monohydrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		Preparation of olanzapine pamoate monohydrate by Ammonia and HCI<strong>[130-85-8]Pamoic acid</strong> (6.2 g, 16 mmol) was mixed with water (100 ml) and aqueous ammonia (7.5g, 32mmol) to get a clear solution. Olanzapine (5.0 g, 16 mmol) was mixed with water (100ml) and aqueous hydrochloric acid (3.65 g, 32mmol) to get a clear solution. The prepared disodium pamoate solution was added into the prepared olanzapine solution at room temperature of 25- 30°C and the reaction mixture was stirred for 30 minutes at the same temperature. The resultant yellow solid was filtered, washed with water (15 ml) and dried in a vacuum oven at 40-45°C. percent Yield: 97percent
		Preparation 2; Preparation of 2-methyl-4-(4-methyl-l-piperazinylV10H-thieno[2.3- biri.5~\|benzodiazepine pamoate (olanzapine pamoate monohydrate, See for example Preparation 6 in U.S. Patent No. 6.169.084 BlV Into a suitable beaker equipped with a magnetic stirrer is added methyl sulfoxide(22 ml), pamoic acid (2.49 g, 6.41 mmol), and olanzapine (2.0 g, 6.40 mmol). The slurry is stirred at 20-250C to dissolve (about 20 minutes). The solution is added over 20 minutes to a 250 mL three-necked flask equipped with a mechanical stirrer and containing water (96 ml) at 4O0C. After the addition is complete, the slurry is stirred about 20 minutes at 400C, cooled to 20-25°C over about 30 minutes, filtered, and washed with water (25 ml). The product is dried in vacuo at 500C to provide the title compound (4.55g).

Reference： [1]Patent: WO2014/125500,2014,A1 .Location in patent: Page/Page column 8
[2]Patent: WO2006/73886,2006,A1 .Location in patent: Page/Page column 6

19
[ 130-85-8 ]
[ 6640-22-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;	a) preparation of sodium embonate 3.88 g of embonic acid are suspended in water. While stirring, the suspension was dissolved by adding 20 ml 1N NaOH, after which the volume of the solution was adjusted to 100 ml (0.1 molar),

Reference： [1]Patent: EP626170,1994,A2

20
[ 13520-78-0 ]
[ 130-85-8 ]
2(WOCl₃)⁽¹⁺⁾*((C₁₀H₅(COO)(OH))2CH₂)^(2-)*2O(C₂H₅)2 = (WOCl₃)2((C₁₀H₅(COO)(OH))2CH₂)*2O(C₂H₅)2 [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 7916 - 7917

21
[ 553-26-4 ]
[ 64-17-5 ]
[ 5743-04-4 ]
[ 1310-73-2 ]
[ 130-85-8 ]
([Cd5(μ3-acetate)2(μ2-acetate)2(μ3-OH)2(pamoate)2(4,4'-bipyridyl)2]*ethanol)n [ No CAS ]

Reference： [1]Inorganic Chemistry Communications,2007,vol. 10,p. 269 - 272

22
[ 59803-98-4 ]
[ 130-85-8 ]
[ 1084892-10-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	In ethanol; dimethyl sulfoxide; at 20 - 65℃;Product distribution / selectivity;	EXAMPLE 11; Preparation of Other Lots of Complexes Comprising Brimonidine and Selected CounterionsSeveral lots of complexes, in quantities of 1-4 grams, comprising brimonidine and selected counterions were prepared.EXAMPLE 11-1Complex Comprising Brimonidine and Pamoic AcidIn a two-liter, three-neck round bottom flask equipped with overhead stirrer, heating mantle, condenser, temperature probe, and N2 inlet, 2.0 g of brimonidine (lot BRMB-001 L08) was dissolved in ethanol (800 mL) at 65° C. <strong>[130-85-8]Pamoic acid</strong> (1.05 eq, 7.5 mL, 0.5M in DMSO) was then added. The resulting solution was stirred for 10 minutes and then cooled at 20° C./h to ambient temperature. At 50° C., precipitation of solids was observed. The mixture stirred overnight at ambient temperature and was then filtered. The solids were then dried under vacuum at ambient temperature for 72 h affording 2.872 g (86percent yield) of yellow solids (lot No. PDH-P-36(1)). XRD spectra of this material and another sample (lot JMS-A-23(1)) previously prepared are shown in FIG. 6. The spectra are consistent, indicating that the material was reproduced. A proton NMR spectrum of lot No. PDH-P-36(1) is shown in FIG. 9.
	In 1-methyl-pyrrolidin-2-one; water; at 70℃;Product distribution / selectivity;	EXAMPLE 9; Preparation of Brimonidine Pamoate ComplexBrimonidine and pamoic acid, at a molar ratio of 1:1, were mixed and dispersed in N-methylpyrrolidone ("NMP"). The solution of brimonidine and pamoic acid in NMP was heated while stirring to dissolve brimonidine (the final temperature, typically less than 70° C., was chosen so as not to lose significant amount of solvent). Water, as an anti-solvent, was added until the solution began to become cloudy, indicating that the complex started to precipitate. The precipitation was allow to proceed; for example, for several hours or overnight. The precipitated was filtered under vacuum, and dry solid comprising the brimonidine pamoate complex was recovered. Other solvents, known to people skilled in the art, may be used for a compound that provides the counterion to the alpha2-adrenergic agonist, as appropriate. Solubilities of brimonidine free base, brimonidine pamoate, and brimonidine tartrate in water were measured, after 11 days on a twist shaker, to be 215.1 mug/ml, 20.7 mug/ml, and 41588 mug/ml, respectively. FIGS. 1, 2, and 3 show NMR spectra of brimonidine free base, pamoic acid, and brimonidine pamoate complex, respectively. FIG. 4 shows XRD spectra of pamoic acid (bottom curve), brimonidine free base (middle curve), and simple solid mixture of brimonidine and pamoic acid (top curve). FIG. 5 shows XRD spectra of pamoic acid (bottom curve), brimonidine free base (top curve), and complex of brimonidine and pamoic acid (middle curve).
	at 60 - 70℃;Product distribution / selectivity;	EXAMPLE 10; Preparation of Various Complexes Comprising Brimonidine and Selected CounterionsIn this experiment, various complexes comprising Brimonidine and counterions of one of the following acids were prepared: pamoic acid, capric acid, sebacic acid, hippuric acid, naproxen, 1-hydroxy-2-naphthoic acid, palmitic acid, and stearic acid. Variations of the procedure described in the following disclosure may be made within the skill of a person of ordinary skill in the art without departing from the scope of the present invention. Brimonidine free base in a preselected solvent was heated to about 60-70° C. The organic acid in another portion of the solvent was added into the heated mixture or was included in the original mixture before heating. The heating of the combined mixture was continued for an additional period, which was not critical. In certain embodiments, an antisolvent was added to the combined mixture, preferably at a lower temperature, to effect a precipitation of the complex of brimonidine and the counterion. It may be advantageous to remove a portion of the solvent and antisolvent to assist the precipitation. In certain other embodiments, the heated combined mixture was cooled down to a lower temperature, such as room temperature (or below) to effect the precipitation of the complex of brimonidine and the counterion. The precipitate was then filtered and dried to yield the final complex. The solubility of various complexes in water at the resulting pH is shown in Table 9.

Reference： [1]Patent: US2008/293728,2008,A1 .Location in patent: Page/Page column 9
[2]Patent: US2008/293728,2008,A1 .Location in patent: Page/Page column 8-9
[3]Patent: US2008/293728,2008,A1 .Location in patent: Page/Page column 9

23
[ 64-17-5 ]
[ 7732-18-5 ]
[ 5743-04-4 ]
[ 5144-89-8 ]
[ 130-85-8 ]
[Cd(pamoic acid)(1,10-phenanthroline)]n*0.5EtOH*0.5H₂O [ No CAS ]

Reference： [1]Journal of Molecular Structure,2008,vol. 891,p. 364 - 369

24
[ 366-18-7 ]
[ 5970-45-6 ]
[ 130-85-8 ]
[ 1095905-74-0 ]

Reference： [1]Journal of Molecular Structure,2008,vol. 891,p. 364 - 369

25
[ 5970-45-6 ]
[ 5144-89-8 ]
[ 130-85-8 ]
[ 1095905-78-4 ]

Reference： [1]Journal of Molecular Structure,2008,vol. 891,p. 364 - 369

26
[ 366-18-7 ]
cadmium(II) nitrate tetrhydrate [ No CAS ]
[ 130-85-8 ]
[Cd(pamoic acid)(2,2'-bipyridine)2]n [ No CAS ]

Reference： [1]Journal of Molecular Structure,2008,vol. 891,p. 364 - 369

27
[ 1132073-57-4 ]
[ 130-85-8 ]
N-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-3-(7,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-methyl-3-oxopropan-1-amine hemipamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3c N-[(7S)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-3-(7,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-methyl-3-oxopropan-1-amine hemipamoate The expected product is obtained by converting N-[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl }-3(7,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-methyl-3-oxopropan-1-amine, obtained by returning the hydrochloride obtained in Example 3a to the base, to a salt using pamoic acid.

Reference： [1]Patent: US2009/69296,2009,A1 .Location in patent: Page/Page column 13

28
[ 7732-18-5 ]
[ 7646-85-7 ]
4′-(3-pyridyl)-2,2′:6′,2′′-terpyridine [ No CAS ]
[ 130-85-8 ]
[Zn(pamotate^(2-))(4'-(3-pyridyl)-2,2':6',2''-terpuridine)]n*2nH₂O [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2009,vol. 362,p. 3475 - 3483

29
[ 66-71-7 ]
[ 5743-04-4 ]
[ 130-85-8 ]
[ 1221273-08-0 ]

Reference： [1]Zeitschrift fur Anorganische und Allgemeine Chemie,2009,vol. 635,p. 1664 - 1668

30
[ 553-26-4 ]
[ 16986-94-0 ]
[ 7732-18-5 ]
[ 68-12-2 ]
[ 130-85-8 ]
4,4'-bipyridinium [bis(4,4'-methylenebis(3-oxidonaphthalene-2-carboxylato)(μ-O)(DMF)2dititanate(IV)]*4DMF monohydrate [ No CAS ]

Reference： [1]Polyhedron,2009,vol. 28,p. 3507 - 3514

31
[ 16986-94-0 ]
[ 68-12-2 ]
[ 130-85-8 ]
[bis(4-((2-carboxy-3-oxidonaphthalen-4-yl)methyl)-3-oxidonaphthalene-2-carboxylato)dititanium(IV)(μ-O)(DMF)2]*6DMF [ No CAS ]

Reference： [1]Polyhedron,2009,vol. 28,p. 3507 - 3514

32
[ 59803-98-4 ]
[ 130-85-8 ]
brimonidine hemipamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; dimethyl sulfoxide; at 65℃; for 0.5h;	Brimonidine Pamoate Polymorph Form AIn a 5 L 3-neck round bottom flask equipped with overhead stirrer, heating mantle, condenser, temperature probe, and N2 inlet, 4.8 g of brimonidine (lot 1-080085) was dissolved in ethanol (2000 mL) at 65° C. <strong>[130-85-8]Pamoic acid</strong> (1.05 eq, 19.0 mL, 0.5M in DMSO (dimethyl sulfoxide)) was then added. The resulting solution was stirred for 30 minutes at 65° C. and then cooled at 20° C./hour to ambient temperature. At the onset of the cooling profile, precipitation of solids was observed. The mixture stirred overnight at ambient temperature and was then filtered. The resulting solids were dried under vacuum at ambient temperature for 4 days before being analyzed by XRPD to confirm the solid form, designated as Form A. FIG. 1 shows an XRPD spectrum of brimonidine pamoate polymorph Form A (lot SUC-I-130(1)).In one aspect, polymorph Form A is characterized by an XRPD spectrum comprising major peaks at 2psi angles of 13.5, 20.6, 21.1, and 24.4°+/-0.2°.In another aspect, polymorph Form A is characterized by an XRPD spectrum comprising peaks at 2psi angles of 7.6, 12.2, 12.7, 13.5, 20.6, 21.1, 24.4, 26.5, and 27.7°+/-0.2°.1H NMR analysis of this material showed approximately 3.7 wt percent residual ethanol and a 0.5:1 pamoate to brimonidine ratio confirming the formation of a hemi-pamoate salt of brimonidine. FIG. 2 shows an NMR spectrum for brimonidine pamoate polymorph Form A (lot SUC-I-130(1).Thermal analysis of Form A showed a single DSC endotherm at 221° C. (see FIG. 3) attributed to the melting of the salt and 3.5percent TGA weight loss through 190° C. (see FIG. 4) attributed to the removal of ethanol.FIG. 5 shows a Raman spectroscopy spectrum of Form A (lot SUC-I-130(1), to be compared to Raman spectra of other polymorphs.In one aspect, polymorph Form A is characterized by a Raman spectroscopy spectrum comprising major peaks at 1340.8, 1352.4, 1365.8, 1402.0, and 1460.3 cm-1.In another aspect, polymorph Form A is characterized by a Raman spectroscopy spectrum comprising peaks at 135.4, 169.3, 189.2, 233.0, 326.9, 547.9, 693.3, 719.4, 838.3, 938.3, 1031.1, 1197.6, 1252.4, 1270.2, 1340.8, 1352.4, 1365.8, 1402.0, 1460.3, 1549.0, 1556.0, and 1571.0 cm-1.Moisture sorption analysis of Form A showed this hemi-pamoate polymorph to be slightly hygroscopic, adsorbing 2.2 percent by weight ("wt percent") water at 60 percent relative humidity ("percent RH") and 2.5 wt percent water at 90percent RH. Upon desorption, no hysteresis or indication of hydrate formation was observed. XRPD analysis of the solids following moisture sorption analysis afforded a diffraction pattern which was consistent with the Form A starting material, indicating no polymorphic form conversion had occurred during the experiment.

Reference： [1]Patent: US2010/125077,2010,A1 .Location in patent: Page/Page column 3

33
[ 553-26-4 ]
cobalt(II) nitrate hexahydrate [ No CAS ]
[ 130-85-8 ]
[ 1238846-20-2 ]

Reference： [1]Polyhedron,2010,vol. 29,p. 2075 - 2080

34
[ 110-86-1 ]
manganese (II) sulfate monohydrate [ No CAS ]
[ 130-85-8 ]
[Mn₂((pamoic acid)(-2H))2(pyridine)6(water)2]n*2n(pyridine) [ No CAS ]

Reference： [1]Polyhedron,2010,vol. 29,p. 2075 - 2080

35
[ 553-26-4 ]
nickel(II) nitrate hexahydrate [ No CAS ]
[ 75-05-8 ]
[ 130-85-8 ]
[Ni((pamoic acid)(-2H))(4,4'-bipyridine)(water)2]n*2n(acetonitrile) [ No CAS ]

Reference： [1]Polyhedron,2010,vol. 29,p. 2075 - 2080

36
[ 110-86-1 ]
cadmium(II) nitrate tetrhydrate [ No CAS ]
[ 130-85-8 ]
[ 1238846-24-6 ]

Reference： [1]Polyhedron,2010,vol. 29,p. 2075 - 2080

37
[ 644-97-3 ]
[ 130-85-8 ]
[ 914377-83-6 ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2011,vol. 186,p. 742 - 753

38
[ 208989-24-6 ]
[ 15532-75-9 ]
[ 130-85-8 ]
1-(3-trifluoromethylphenyl)-4-[2-(4-methyl-3-pentylphenyl)-5-ethyl]piperazine hemipamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1Compound 1: 1-[2-(4-methyl-3-pentylphenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine and its hemipamoate1.98 g (0.00777 mol) of the compound of preparation 1, 1.5 g (0.0065 mol) of (3-trifluoromethylphenyl)-1-piperazine, 1.35 g (0.00975 mol) of potassium carbonate and 40 ml of n-butanol are placed in a round-bottom flask. The mixture is refluxed for 6 hours. The n-butanol is evaporated off, the residue is taken up in ethyl acetate and washed with water, the organic phase is dried and the solvent is evaporated off. The residue is purified by column chromatography on silica gel eluting with a 95/5 hexane/ethyl acetate mixture.A solution of 300 mg of the free base obtained in THF is mixed with a solution of 180 mg of pamoic acid in 8/2 THF/water.The reaction mixture is concentrated under vacuum, 6 ml of ethanol are added and a solid is obtained, which is then filtered off. The solid is crystallized by heating with ethanol and the off-white hemipamoate is obtained: 450 mg, m.p.=156-157. A further crystallization in ethanol affords an m.p. of 157-158.Melting point=157-158° C.;M+H+ (method A)=RT 10.9 min m/z 419 (MH+)1H NMR: delta (ppm, DMSO-d6): 0.88 (m; 3H); 1.27-1.39 (m; 4H); 1.45-1.59 (m; 2H); 2.23 (s; 3H); 2.50-2.58 (m; 2H*); 2.75-2.89 (m; 2H); 2.89-3.50 (m; 10H); 4.74 (s; 1H); 6.97 (dd; Ja=7.7 Hz; Jb=1.4 Hz; 1H); 7.02 (d; J=1.4 Hz; 1H); 7.07 (d; J=7.7 Hz; 1H); 7.08-7.15 (m; 2H); 7.16-7.32 (m; 3H); 7.45 (dd-->t; J=8 Hz; 1H); 7.74 (d; J=8 Hz; 1H); 8.17 (d; J=8 Hz; 1H); 8.30 (s; 1H).

Reference： [1]Patent: US2011/144120,2011,A1 .Location in patent: Page/Page column 5-6

39
[ 999-97-3 ]
[ 130-85-8 ]
C₃₅H₄₈O₆Si₄ [ No CAS ]

Reference： [1]Russian Journal of General Chemistry,2010,vol. 80,p. 536 - 537

40
[ 130-85-8 ]
[ 914377-83-6 ]

Reference： [1]Russian Journal of General Chemistry,2010,vol. 80,p. 536 - 537

41
[ 130-85-8 ]
[ 1233816-08-4 ]

Reference： [1]Russian Journal of General Chemistry,2010,vol. 80,p. 536 - 537

42
[ 56613-80-0 ]
[ 130-85-8 ]
[ 1313514-66-7 ]

Reference： [1]Revue Roumaine de Chimie,2010,vol. 55,p. 455 - 458

43
[ 121-44-8 ]
[ 130-85-8 ]
bis(triethylammonium) pamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In water; for 1h;pH ~ 8.5 - 9;	To a one liter round-bottom flask equipped with a magnetic stir bar was charged 20.0 g (51.2 mmol) pamoic acid (0.5percent moisture) and 640 mL water. To this suspension was added 11.2 g (110.1 mmol) triethylamine over a period of about 30 seconds which produced a solution with a pH about 8.5-9. The solution was stirred for approximately 1 hour and filtered to remove any particulates. The clear filtrate was concentrated under reduced pressure at 85° C. and dried (under vacuum overnight to provide 29.82 g (99percent) of a tan to light brown solid (1.46percent moisture) which was characterized by DSC (FIG. 94), FTIR (FIG. 95) PXRD (FIG. 96), and 1H NMR (FIG. 97). The results were consistent with the assigned structure and the PXRD diffractogram indicated the material was amorphous.

Reference： [1]Patent: US2012/28960,2012,A1 .Location in patent: Page/Page column 28

44
[ 121-44-8 ]
[ 19262-68-1 ]
[ 130-85-8 ]
[ 1357157-24-4 ]

Yield	Reaction Conditions	Operation in experiment
67%	In water; for 3h;	To a 100 mL round-bottom flask equipped with a magnetic stir bar and addition funnel was charged 722.1 mg (1.85 mmol) pamoic acid, 20 mL water and 423.0 mg (4.18 mmol) triethylamine. A solution of 0.5 g (1.85 mmol) d-methylphenidate hydrochloride in 20 mL water was added to the above solution over 3 hours with formation of a gum.The water was carefully decanted and the residual gum dried under vacuum to provide 0.9 g (67percent) of a tan solid (3.47percent water) which was characterized by DSC, FTIR (FIG. 51), PXRD (FIG. 52), 1H NMR (FIG. 53), and HPLC. The PXRD diffractogram indicated the isolated drug substance was amorphous. The relative ratio of d-methylphenidate to pamoate was determined to be 1.0/1 by HPLC analysis and further corroborated by the relative ratio of triethylammonium ion to pamoate moiety as 1/1 as determined by 1H NMR. The DSC is provided in FIG. 50 wherein illustrated is an endothermic phase change of at least 12 J/g at a temperature above 240° C.

Reference： [1]Patent: US2012/28960,2012,A1 .Location in patent: Page/Page column 26

45
imipramine hydrochloride [ No CAS ]
[ 121-44-8 ]
[ 130-85-8 ]
[ 1357157-28-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	In water; for 3h;	To a 100 mL round-bottom flask equipped with a magnetic stir bar and addition funnel was charged 1.23 g (3.16 mmol) pamoic acid, 40 mL water and 769.0 mg (7.6 mmol) triethylamine. A solution of 1.0 g (3.16 mmol) imipramine hydrochloride in 20 mL water was added to the above solution over 3 hours with gum formation. The water was carefully decanted and the gum dried under vacuum to provide 2.1 g (86percent) of a tan solid (2.24percent water). The relative ratio of imipramine to pamoate was determined to be 1.1/1 by HPLC (and corroborated by 1H NMR). The relative ratio of triethylammonium ion to pamoate was 1/1 by 1H NMR.

Reference： [1]Patent: US2012/28960,2012,A1 .Location in patent: Page/Page column 26

46
[ 130-85-8 ]
[ 10075-24-8 ]

Reference： [1]Patent: US2012/28960,2012,A1

47
[ 113-45-1 ]
[ 130-85-8 ]
di(racemic-methylphenidate) pamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere;	To a 100 mL one neck round bottom flask equipped with a magnetic stir bar, thermowell and nitrogen inlet was charged 2.20 g (9.43 mmol) racemic-methylphenidate. As solvent, 17 mL dimethylformamide (DMF) was then added which produced a clear colorless solution. <strong>[130-85-8]Pamoic acid</strong> (1.83 g; 4.71 mmol; 0.36percent moisture) was subsequently added over thirty seconds which produced a clear yellow solution. The solution was stirred under nitrogen for 3 hours at ambient temperature followed by filtration through a medium fritted glass filter to remove any particulates. The filtrate was transferred to a 250 mL one-neck round bottom flask and 54 g isopropanol was added over one minute. The solution was concentrated under reduced pressure at 100° C. to yield 4.2 g of a residue which was subsequently triturated in 24 g isopropanol and the yellow solids collected by filtration (medium fritted glass filter). The product was dried overnight under vacuum at ambient temperature to provide 3.7 g (92percent) of a yellow solid (0.36percent water) which was analyzed by DSC, FTIR (FIG. 5), and PXRD (FIG. 6). An HPLC analysis indicated a 1.8/1 ratio of methylphenidate/pamoate which was corroborated by NMR. The PXRD analysis indicated the drug substance salt was crystalline. The DSC is provided in FIG. 4 wherein an endotherm of at least 75 J/gram is illustrated above 200° C.

Reference： [1]Patent: US2012/28960,2012,A1 .Location in patent: Page/Page column 23

48
imipramine hydrochloride [ No CAS ]
[ 130-85-8 ]
[ 10075-24-8 ]

Reference： [1]Patent: US2012/28960,2012,A1

49
[ 1254036-66-2 ]
[ 130-85-8 ]
N-[5-[4-(5-[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide hemi pamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; water; at 20℃;	Hemi Pamoate saltTetrahydrofuran (1 ml) was added to pamoic acid (0.0759g) to give a suspension. This suspension was added to A/-[5-[4-(5-[(2f?,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1 ,3- oxazol-2-yl)-1 /-/-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide (0.2g). Further tetrahydrofuran (7ml) and water (12ml) were added before the solution was reduced in volume by ca. 10percent under a nitrogen flow. The resultant suspension was sonicated and stirred at ambient conditions overnight. The suspension was filtered, washed with water and dried under vacuum at 50°C to give the hemi pamoate (0.092g) containing 5percentw/w water.NMR: Consistent with hemi pamoate formation1 H NMR (400MHz, DMSO d6) d = 13.51 (br s, 1 H), 9.40 (s, 1 H), 8.60 (s, 1 H), 8.42 (m, 2H), 8.13 (d, J = 8.8Hz, 1 H), 7.99 (d, J = 2.2Hz, 1 H), 7.95 (s, 1 H), 7.90 (s, 1 H), 7.85 (d, J = 8.0Hz, 1 H), 7.42 (s, 1 H), 7.33 (t, J = 7.3Hz, 1 H), 7.18 (t, J = 7.1 Hz, 1 H), 4.78 (s, 1 H), 4.00 (s, 3H), 3.92 (br s, 2H), 3.63 (m, 2H), 3.11 (s, 3H), 2.95 (d, J = 1 1.0Hz, 2H), 1.97 (m, 2H), 1.07 (d, J = 6.4Hz, 6H)
0.092 g	In tetrahydrofuran; water; at 20℃;Inert atmosphere; Sonication;	Tetrahydrofuran (1 ml) was added to pamoic acid (0.0759 g) to give a suspension. This suspension was added to N-[5-[4-(5-[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide (0.2 g). Further tetrahydrofuran (7 ml) and water (12 ml) were added before the solution was reduced in volume by ca. 10percent under a nitrogen flow. The resultant suspension was sonicated and stirred at ambient conditions overnight. The suspension was filtered, washed with water and dried under vacuum at 50° C. to give the hemi pamoate (0.092 g) containing 5percent w/w water. NMR: Consistent with hemi pamoate formation 1H NMR (400 MHz, DMSO d6) d=13.51 (br s, 1H), 9.40 (s, 1H), 8.60 (s, 1H), 8.42 (m, 2H), 8.13 (d, J=8.8 Hz, 1H), 7.99 (d, J=2.2 Hz, 1H), 7.95 (s, 1H), 7.90 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.42 (s, 1H), 7.33 (t, J=7.3 Hz, 1H), 7.18 (t, J=7.1 Hz, 1H), 4.78 (s, 1H), 4.00 (s, 3H), 3.92 (br s, 2H), 3.63 (m, 2H), 3.11 (s, 3H), 2.95 (d, J=11.0 Hz, 2H), 1.97 (m, 2H), 1.07 (d, J=6.4 Hz, 6H)

Reference： [1]Patent: WO2012/32067,2012,A1 .Location in patent: Page/Page column 70
[2]Patent: US9326987,2016,B2 .Location in patent: Page/Page column 242

50
[ 175591-23-8 ]
[ 130-85-8 ]
[ 1356394-22-3 ]

Yield	Reaction Conditions	Operation in experiment
95.16%	In isopropyl alcohol; for 24h;Product distribution / selectivity;	b1-4-3:110 g (0.496 mol) of tapentadol were dissolved in 3 L of 2-propanol. To this solution, 193.0 g (0.496 mol) of embonic acid were added as a solid to the resulting solution in portions. Then, 1 L of 2-propanol was added. After addition, the resulting suspension was stirred for 24 hours. The crystallized yellow precipitate was then slowly filtered off and dried at 60°C under reduced pressure (6 mbar) (yield: 298.14 g, 98.36percent). 1H-NMR analysis showed a 1 :0.9- stochiometry of tapentadol and embonic acid. To remove the excessive free tapentadol base, the solid was suspended in 1.7 L of ethyl acetate and stirred. After 3 hours, the crystallized yellow precipitate was then slowly filtered off and dried at 60°C under reduced pressure (3 mbar) (yield: 288.43 g, 95.16percent; melting point (DSC): T0= 217.3 °C, Tp = 220.1 , °C; 57.2 J/g. Weight loss (TGA, range 31 to 171 °C): less then 0.1 percent. 1H-NMR analysis showed a 1 :1- stochiometry of tapentadol and embonic acid. According to XRPD analysis polymorph A was obtained. b1-4-4:

Reference： [1]Patent: WO2012/10316,2012,A1 .Location in patent: Page/Page column 37

51
[ 175591-23-8 ]
[ 130-85-8 ]
tapentadol hemiembonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.3%	In ethanol; for 1h;	b1-4-2:877.32 mg of embonic acid (0.00226 mol) were suspended in 50 mL of ethanol. To this mixture, 1 g (0.0045 mol) of tapentadol in 5 mL of ethanol was added. After addition, the resulting suspension was stirred for 1 hour. The crystallized white precipitate was then slowly filtered off and dried at 40°C under reduced pressure (6 mbar) for 3 days (yield: 1.564 g, 83.3percent, melting point (DSC): T0= 222.6 °C, Tp = 226.5, °C, 96.7 J/g). 1H-NMR analysis showed a 2:1 -stochiometry of tapentadol and embonic acid (hemi-embonate)

Reference： [1]Patent: WO2012/10316,2012,A1 .Location in patent: Page/Page column 37

52
[ 109-06-8 ]
[ 130-85-8 ]
2-picolinium pamoate [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

53
[ 108-89-4 ]
[ 130-85-8 ]
4-picolinium pamoate 2:1 [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

54
[ 591-22-0 ]
[ 130-85-8 ]
[ 863988-16-3 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236
[2]CrystEngComm,2013,vol. 15,p. 2450 - 2455

55
[ 583-61-9 ]
[ 130-85-8 ]
2,3-lutidinium pamoate [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

56
[ 583-61-9 ]
[ 130-85-8 ]
2,3-lutidinium pamoate 2:1 [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

57
[ 583-58-4 ]
[ 130-85-8 ]
[ 863988-14-1 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

58
[ 583-58-4 ]
[ 130-85-8 ]
3,4-lutidinium pamoate 1:2 [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

59
[ 108-99-6 ]
[ 130-85-8 ]
3-picolinium pamoate 2:1 [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

60
[ 108-47-4 ]
[ 130-85-8 ]
[ 863988-09-4 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

61
[ 589-93-5 ]
[ 130-85-8 ]
[ 1365425-72-4 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

62
[ 589-93-5 ]
[ 130-85-8 ]
2,4-lutidinium pamoate 1:2 [ No CAS ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

63
[ 68-12-2 ]
[ 130-85-8 ]
[ 1365425-67-7 ]

Reference： [1]CrystEngComm,2011,vol. 13,p. 2227 - 2236

64
[ 280-57-9 ]
[ 130-85-8 ]
C₆H₁₂N₂*C₂₃H₁₆O₆*2H₂O [ No CAS ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 11507 - 11509

65
[ 280-57-9 ]
[ 130-85-8 ]
2C₆H₁₂N₂*C₂₃H₁₆O₆*3H₂O [ No CAS ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 11507 - 11509

66
[ 106266-06-2 ]
[ 130-85-8 ]
[ 160390-88-5 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; N,N-dimethyl-formamide; at 25 - 30℃; for 5h;	700 ml of dimethyl formamide and 16.6 gm of pamoic acid were charged in the flask. The reaction mixture was stirred for 10 minutes at 25-30°C to obtain clear solution. 35 gm Risperidone solution in 1050 ml ethanol was added to the reaction mixture at 25-30°C. The reaction mixture was stirred further for 5 hours at 25-30°C. The solid was filtered off, washed with 70 ml ethyl alcohol and dried under vacuum at 50-55°C for 12 hours.Dry weight: 42.10 gmDSC: 188°C1 H NMR in accord with structure (400 MHz, DMSO-d6+D20) 8(ppm): 8.22 (2H) s; 8.14-8.16 (2H) d; 8.00-8.03 (2H) d of d; 7.67-7.69 (4H) m; 7.29-7.33 (2H) d of t; 7.14- 7.18 (2H) t; 7.05-7.09 (2H) t; 4.77 (2H) s; 3.81 (4H) t; 3.54 (2H) m; 3.16 3.74 (12 H) m; 2.89-2.91 (4H) m; 2.75-2.78 (4H) t; 2.10-2.15 2.36-2.42 (8H) m; 2.28 (6H) s; 1.75- 1. (8H) m.Elemental analysis (wt percent) calculated for C69H70F2N8O10: C, 68.53; H, 5.83; N, 9.27. Found: C, 68.37; H, 6.00; N, 9.65.The structural characteristics were also confirmed by BRUKER' s SMART APEX Single crystal X-ray CCD Diffractometer.

Reference： [1]Patent: WO2012/147035,2012,A1 .Location in patent: Page/Page column 17

67
[ 120014-06-4 ]
[ 130-85-8 ]
1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hemipamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3 g	In water; N,N-dimethyl-formamide; isopropyl alcohol; at 80 - 85℃; for 1h;	A mixture of isopropyl alcohol (40 ml), dimethyl formamide (20 ml) and water (40 ml) in round bottom flask was added with donepezi l base (5 gm.) and pamoic acid (2.56 gm.) with stirring at 25°C-30°C. The reaction mixture was heated at 80°C to 85°C and stirred for about 1 hour at same temperature. The resulting reaction mass was then cooled to 25°C-30°C followed by stirring for about 2 hour. The obtained solid was fi ltered under vacuum, washed with isopropyl alcohol ( 10 ml) and dried under vacuum at 50-55°C for 20 hours. Dry weight: 3.0 gm 1 H NMR in accord with structure (400 MHz, DMSO-d6+D20) 8(ppm): 8.26 (2H) s; 8. 1 1 -8.13 (2H) d; 7.72-7.74 (2H) d; 7.50 ( 10H) s; 7.02-7.18 (8H) m; 4.69 (2H) s; 4.23 (4H) s; 3.80-3.86 & 3.85 ( 12H) d; 4.61 (2H) m; 2.60, 3.1 1 -3.15. 3.62 (8H) m; 2.91 -2.94 (4H) m; 1 .81- 1 .97 (4H) m; 1.26-1.38, 1 .70 ( 10 H) m.
	In water; dimethyl sulfoxide; at 20℃; for 5h;	Example 2: Making donepezil pamoate at a 2: 1 molar ratio of donepezil to pamoic acid from DMSO/water system (Semi-pamoate salt of donepezil)1554 mg of donepezil free base and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 5 hours at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-50°C to yield donepezil pamoate at a 2: 1 molar ratio of donepezil to pamoic acid. A typical example of an x-ray diffraction pattern for an Example 2 salt is shown in FIG. 3 and the interplanar spacing and typical relative intensities are set forth in Table 2. The key peaks are bolded and underlined in Table 2.
	In dimethyl sulfoxide; at 20℃; for 5h;	1554 mg of donepezil freebase and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 5 hrs at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-50°C to yield donepezil pamoate at a 2: 1 molar ratio of donepezil to pamoic acid. A typical example of an x-ray diffraction pattern for an Example 2 salt is shown in Figure 3 and the interplanar spacing and typical relative intensities are set forth in Table 2.

3 g	In water; N,N-dimethyl-formamide; isopropyl alcohol; at 25 - 85℃; for 3h;	Example-2 Preparation of Donepezil Hemipamoate A mixture of isopropyl alcohol (40 ml), dimethyl formamide (20 ml) and water (40 ml) in round bottom flask was added with donepezil base (5 gm.) and pamoic acid (2.56 gm.) with stirring at 25° C.-30° C. The reaction mixture was heated at 80° C. to 85° C. and stirred for about 1 hour at same temperature. The resulting reaction mass was then cooled to 25° C.-30° C. followed by stirring for about 2 hour. The obtained solid was filtered under vacuum, washed with isopropyl alcohol (10 ml) and dried under vacuum at 50-55° C. for 20 hours. Dry weight: 3.0 gm 1H NMR in accord with structure (400 MHz, DMSO-d6+D2O) delta(ppm): 8.26 (2H) s; 8.11-8.13 (2H) d; 7.72-7.74 (2H) d; 7.50 (10H) s; 7.02-7.18 (8H) m; 4.69 (2H) s; 4.23 (4H) s; 3.80-3.86 & 3.85 (12H) d; 4.61 (2H) m; 2.60, 3.11-3.15, 3.62 (8H) m; 2.91-2.94 (4H) m; 1.81-1.97 (4H) m; 1.26-1.38, 1.70 (10H) m.
	In dimethyl sulfoxide; at 20℃; for 5h;	1554 mg of donepezil free base and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 5 hours at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-50° C. to yield donepezil pamoate at a 2:1 molar ratio of donepezil to pamoic acid. A typical example of an x-ray diffraction pattern for an Example 2 salt is shown in FIG. 3 and the interplanar spacing and typical relative intensities are set forth in Table 2. The key peaks are bolded and underlined in Table 2.

Reference： [1]Patent: WO2013/5094,2013,A1 .Location in patent: Page/Page column 25; 26
[2]Patent: WO2013/79007,2013,A1 .Location in patent: Page/Page column 15
[3]Patent: WO2013/78608,2013,A1 .Location in patent: Paragraph 0056
[4]Patent: US2014/243278,2014,A1 .Location in patent: Paragraph 0178; 0179; 0180
[5]Patent: US2014/315952,2014,A1 .Location in patent: Paragraph 0067

68
[ 120014-06-4 ]
[ 130-85-8 ]
[ 1417425-02-5 ]

Yield	Reaction Conditions	Operation in experiment
6 g	In methanol; water; N,N-dimethyl-formamide; at 70 - 75℃; for 1h;	A mixture of methanol (60 ml), dimethyl formamide (50 ml) and water (60 ml) in round bottom flask was added with donepezil base (5 gm.) and pamoic acid (5.12 gm.) with stirring at 25°C-30°C. The reaction mixture was heated at 70°C to 75°C and stirred for about 1 hour at same temperature. The resulting reaction mass was then cooled to 25°C- 30°C followed by stirring for about 2 hour. The obtained solid was filtered under vacuum, washed with water (25 ml) and dried under vacuum at 50-55°C for 20 hours. Dry weight: 6.0 gm DSC: 245.2°C 1 H N R in accord with structure (400 MHz, DMSO-d6) 5(ppm): 8.35 (2H) s; 8.16-8.18 (2H) d of d; 7.77-7.79 (2H) d; 7.47-7.52 (5H) m; 7.25-7.28 (2H) t; 7.1 1 -7.14 (2H) t; 7.05 (2H) s; 4.75 (2H) s; 4.30 (2H) s; 3.78 & 3.85 (6H) s; 3.37 ( 1 H) bs; 3.16-3.23, 2.61 & 2.65 (4H) m; 2.89-2.92 (2H) m; 1.83- 1.98 (2H) m; 1 .29- 1 .42 & 1 .70 (5H) m.
	In water; dimethyl sulfoxide; at 20℃; for 7h;	Example 1 : Making donepezil pamoate at a 1 : 1 molar ratio of donepezil to pamoic acid from DMSO/water (Mono-pamoate salt of donepezil)796 mg of donepezil free base and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 7 hours at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-60 °C to yield donepezil pamoate at a 1 : 1 molar ratio of donepezil to pamoic acid.X-ray powder diffraction ("XRPD") patterns of above solids were obtained using a Bruker D8 Advance x-ray powder diffractometer with copper Ka radiation at a wavelength of 1.5406A. Instrumental conditions included a step size of 0.02°/step, a scan rate of 0.2 seconds/step, a 2-theta range of 3 to 40 degrees, a voltage of 40 kV, a current of 40 mA, and a Lynxeye detector. Samples were packed into recessed sample holders for analysis. A typical example of an x-ray diffraction pattern for an Example 1 salt is shown in FIG. 2. Table 1 sets forth the x-ray diffraction data wherein d(A) represents the interplanar spacing and 1percent represents the typical relative intensities. The key peaks are bolded and underlined in Table 1.
	In dimethyl sulfoxide; at 20℃; for 7h;	796 mg of donepezil free base and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 7 hrs at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-60 °C to yield donepezil pamoate at a 1 : 1 molar ratio of donepezil to pamoic acid. [0055] X-ray powder diffraction ("XRPD") patterns of above solids were obtained using a Bruker D8 Advance x-ray powder diffractometer with copper Koc radiation at a wavelength of 1.5406A. Instrumental conditions included a step size of 0.027step, a scan rate of 0.2 seconds/step, a 2-theta range of 3 to 40 degrees, a voltage of 40 kV, a current of 40 mA, and a Lynxeye detector. Samples were packed into recessed sample holders for analysis. A typical example of an x-ray diffraction pattern for an Example 1 salt is shown in Figure 2. Table 1 sets forth the x-ray diffraction data wherein d(A) represents the interplanar spacing and 1percent represents the typical relative intensities.

6 g	In methanol; water; N,N-dimethyl-formamide; at 25 - 75℃; for 3h;	Example-1 Preparation of Crystalline Form T1 of Donepezil Monopamoate A mixture of methanol (60 ml), dimethyl formamide (50 ml) and water (60 ml) in round bottom flask was added with donepezil base (5 gm.) and pamoic acid (5.12 gm.) with stirring at 25° C.-30° C. The reaction mixture was heated at 70° C. to 75° C. and stirred for about 1 hour at same temperature. The resulting reaction mass was then cooled to 25° C.-30° C. followed by stirring for about 2 hour. The obtained solid was filtered under vacuum, washed with water (25 ml) and dried under vacuum at 50-55° C. for 20 hours. Dry weight: 6.0 gm DSC: 245.2° C. 1H NMR in accord with structure (400 MHz, DMSO-d6) delta(ppm): 8.35 (2H) s; 8.16-8.18 (2H) d of d; 7.77-7.79 (2H) d; 7.47-7.52 (5H) m; 7.25-7.28 (2H) t; 7.11-7.14 (2H) t; 7.05 (2H) s; 4.75 (2H) s; 4.30 (2H) s; 3.78 & 3.85 (6H) s; 3.37 (1H) bs; 3.16-3.23, 2.61 & 2.65 (4H) m; 2.89-2.92 (2H) m; 1.83-1.98 (2H) m; 1.29-1.42 & 1.70 (5H) m.
	In dimethyl sulfoxide; at 20℃; for 7h;	796 mg of donepezil free base and 776 mg of pamoic acid were dissolved in 6 ml of DMSO and stirred for 7 hours at room temperature. 30 ml of water were added to precipitate the solids. The solids were filtered and dried at 40-60° C. to yield donepezil pamoate at a 1:1 molar ratio of donepezil to pamoic acid.

Reference： [1]Patent: WO2013/5094,2013,A1 .Location in patent: Page/Page column 25
[2]Patent: WO2013/79007,2013,A1 .Location in patent: Page/Page column 14
[3]Patent: WO2013/78608,2013,A1 .Location in patent: Paragraph 0054; 0055
[4]Patent: US2014/243278,2014,A1 .Location in patent: Paragraph 0174; 0175; 0176; 0177
[5]Patent: US2014/315952,2014,A1 .Location in patent: Paragraph 0065

69
[ 913611-97-9 ]
[ 130-85-8 ]
7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-1H-quinolin-2-one hemipamoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.5 g	In N,N-dimethyl-formamide; acetonitrile; at 20 - 60℃;	1/2 pamoate:A suspension of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin- 1-yl) -butoxy] -lH-quinolin-2-one (1 g) in dimethylformamide (10 ml) and acetonitrile (10 ml) was warmed to give a solution, and pamoic acid (0.49 g) was added. The mixture was warmed to 60°C, dissolved, and the mixture was stood at room temperature. Water was added, the suspended substances were collected by filtration, and dried to give 7- [ 4- ( 4-benzo [b] thiophen-4-yl- piperazin-l-yl) -butoxy] -lH-quinolin-2-one 1/2 pamoate (1.5 g) .[0900][0901]7- [4- (4-benzo [b] thiophen-4-yl-piperazin-l-yl) -butoxy] -1H- quinolin-2-one 1/2 pamoate: yellow amorphous1H-NMR (D SO-de) delta ppm : 1.78-1.92 (4H, m) , 3.4-3.8 (10H, br) , 4.05-4.12 (2H, m) , 4.71 (1H, s) , 6.31 (1H, d, J=9.5Hz), 6.78- 6.84 (2H, m) , 6.96 (1H, d, J=7.6Hz), 7.04 (1H, t, J=7.4Hz), 7.13-7.19 (1H, m), 7.31 (1H, t, J=7.8Hz), 7.49 (1H, d,J=5.5Hz), 7.56 (1H, d, J=8.7Hz), 7.69 (2H, d, J=8.0Hz), 7.76 (1H, d, J=5.5Hz), 7.81 (1H, d, J=9.5Hz), 8.18 (1H, d, J=8.6Hz) 8.25 (1H, s), 11.63 (1H, brs) .
1.5 g	In N,N-dimethyl-formamide; acetonitrile; at 60℃;	7- [4- (4-benzo [b] thiophene-4-yl-piperazin-l-yl) -butoxy]-1 H-quinolin-2-one (1 g) in dimethylformamide(10 ml) and acetonitrile (10 ml) was warmed to prepare a solution, and pamoic acid (0.49 g) was added. It was heated to 60 ° C.,After dissolution, it was allowed to stand at room temperature. Water was added, the suspended matter was collected by filtration,After drying,7- [4- (4-benzo [b] thiophen-4-yl-Piperazin-l-yl) -butoxy]-1 H-quinolin-2-one 1/2 pamoate(1.5 g).

Reference： [1]Patent: WO2013/35892,2013,A1 .Location in patent: Paragraph 0899-0901
[2]Patent: JP2018/203793,2018,A .Location in patent: Paragraph 0973; 0974

70
[ 109-99-9 ]
[ 109-06-8 ]
[ 130-85-8 ]
[ 1365425-51-9 ]