Name: 341031-54-7|(Z)-N-(2-(Diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysuccinate|98%
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[ 97-67-6 ]
[ 557795-19-4 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	In methanol; ethanol at 20℃; for 2h; Darkness;	b b) Under dark conditions: 140 g, 0.351 mol B6 (MW: 398.47) were added to 2.8 L of a mixed solution of methanol and ethanol(1: 1 by volume), 56.5 g of 0.421 mol L-malic acid (MW: 134.09) was added under stirring at room temperature,The reaction was stirred for 2h, concentrated under reduced pressure to remove the reaction solution of methanol and ethanol; then added to the remaining concentration of acetonitrile, warmingTo reflux, stirring 1h; then cooled to room temperature, stirred for 1.5h, a solid precipitated, filtered and the filter cake was dried to obtain a yellow solidBody: Sunitinib L-malate (182 g, molar yield: 100%, HPLC purity 99.92%, unblended content less than 0.1%See the HPLC chromatogram shown in Figure 2).
93.6%	In ethanol for 2 - 4h; Reflux; Industry scale;	14 Example 14: Preparation of (2S)-2-hydroxy butanedioic acid compound with N- [2- (diethylamino)ethyl]-5-[(Z)-(5-fluoro-l,2-dihydro-2-oxo-3/.r-indol-3-ylidine) methyl]- 2,4-dimethyl-lHr-pyrrole-3-carboxamide (1:1) - Sunitinib Malate-I(a):Into a 250 mL four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, and a reflux condenser were charged N- [2- (diethylamino)ethyl]-5-[(Z)-(5-fluoro-l,2-dihydro-2-oxo-3/f-indol-3-ylidine) methyl]- 2,4-dimethyl-lH-pyrrole-3-carboxamide (Sunitinib) (I) (2.0 g; 0.005 mole), L(-)-malic acid (0.67 g; 0.005 mole) and ethanol (35 mL). The solution was then heated to reflux and maintained for 2-4 hours. The bright yellow precipitate was then cooled to 30-35° C and maintained for 1 hour, the product filtered and washed with ethanoj. The product was dried at 80-85° C. Dry Weight: 2.5 g Yield: 93.6% ΗPLC Purity: > 99.7%
93.6%	In ethanol for 2 - 4h; Reflux;	14 Into a 250 mL four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, and a reflux condenser were charged N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (Sunitinib) (I) (2.0 g; 0.005 mole), L(-)-malic acid (0.67 g; 0.005 mole) and ethanol (35 mL). The solution was then heated to reflux and maintained for 2-4 hours. The bright yellow precipitate was then cooled to 30-35oC. and maintained for 1 hour, the product filtered and washed with ethanol. The product was dried at 80-85oC. Dry Weight: 2.5 g Yield: 93.6% HPLC Purity: >99.7%

90.9%	In acetone at 20℃; for 1h; Reflux;	4 N-[2-(Diemylarnino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-l,2-dihydro-3H-indol-3-ylidene)methyl]- 2,4-dimethyl-lH~pyrrole-3-carboxamide (sunitinib) (leq) was dissolved in acetone (30vol) at reflux temperature. L-Malic acid (leq) was slowly added at a rate of O.OSeq per minute to the solution whilst stirring. The formation of a slurry was observed. The slurry was refluxed for about 15 minutes and then gradually cooled to room temperature (about 20-350C). The slurry was stirred at room temperature for about 15-30 minutes and then filtered using a Buchner funnel under vacuum. The filtered solid obtained was washed with acetone and then dried on a rotavapour at 4O0C under reduced pressure until a constant weight was achieved to obtain the L-malic acid salt of N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fiuoro-2- oxo-1 ,2-dihydro-3H-indol-3-ylidene)methyl] -2,4-ditnethyl-l H-pyrrole-3-carboxamide (sunitinib) anhydrous crystal form I as a yellow solid. Molar yield = 90.90%. HPLC purity = 99.07%.
90.9%	In acetone at 20 - 35℃; Reflux;	4 N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (sunitinib) (1 eq) was dissolved in acetone (30 vol) at reflux temperature. L-Malic acid (1 eq) was slowly added at a rate of 0.05 eq per minute to the solution whilst stirring. The formation of a slurry was observed. The slurry was refluxed for about 15 minutes and then gradually cooled to room temperature (about 20-35° C.). The slurry was stirred at room temperature for about 15-30 minutes and then filtered using a Buchner funnel under vacuum. The filtered solid obtained was washed with acetone and then dried on a rotavapour at 40° C. under reduced pressure until a constant weight was achieved to obtain the L-malic acid salt of N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (sunitinib) anhydrous crystal form I as a yellow solid.Molar yield=90.90%.HPLC purity=99.07%.
90%	In methanol at 25℃; for 8h; Inert atmosphere;	1; 15.4 Under N2, crude sunitinib (98.5 g, 0.247 mol, 1 .0 eq. 99.2% by HPLC) and MeOH (31 13 g, 3940 mL, 40 P w.r.t. crude sunitinib) were charged into a flask with a mechanical stirrer and a thermometer at ambient temperature. The heterogeneous mixture was stirred for 30 min at ambient temperature and L-malic acid (34.8 g, 0.259 mol, 1.05 eq.) was added at about 25°C. The mixture turned clear after 5 to 30 min and was vacuum filtered. The filtrate was stirred for 8 h at about 25°C. The mixture was vacuum filtered at ambient temperature, washed with MeOH (156 g, 197 mL, 2 P w.r.t. crude sunitinib) and dried in vacuo (relative vacuum NLT 0.095 MPa) at about 40°C for 15 to 18 h to give 1 18.0 g of crude sunitinib malate with 99.5% purity by HPLC analysis and 0.40% by LOD in 90% yield, m.p. 195.0 to 1 96.0 °C. Under N2, DMSO (506 g, 460 mL, 4 P w.r.t. crude sunitinib malate) was charged into a flask with a mechanical stirrer and a thermometer at ambient temperature and heated to about 45°C for 5 to 10 min. Crude Sunitinib malate (1 15 g, 0.216 mol, 1.0 eq.) was charged and DMSO (64 g, 58 mL, 4 P w.r.t. crude sunitinib malate) was used to assist the transformation and after 5 to 10 min the mixture almost turn clear and was vacuum filtered. MIBK (1 104 g, 1380 mL, 12 P w.r.t. crude sunitinib malate) was charged into the flask, and the solution was allowed to cool about 20°C and was stirred for a further 30 h at about 20°C. The mixture was vacuum filtered and washed with MIBK (368 g, 460 mL, 4 P w.r.t crude sunitinib malate) and dried in vacuo (relative vacuum NLT 0.095 MPa) at about 40°C for 30 to 40 h to give 98.1 g of pure sunitinib malate as a yellow powder with 99.8% purity by HPLC analysis and 0.27% by LOD in 85.3% yield. No individual impurities were present at greater than 0.10% by HPLC analysis. NMR (300 MHz, DMSO-d6) δ: 0.98 (t, 6H, J=7.2 Hz, CH3), 2.31-2.38 (dd, l H, J=5.8 Hz, 15.75 Hz, CH2), 2.43, 2.45 (s. 6H, CH3), 2.56-2.62 (m, 1 H, CH2), 3.03-3.12 (m, 6H, 3*CH2), 3.51-3.55 (t, 3H, CH2), 3.95-3.99 (dd, 1 Η, CH).
90%	In methanol at 25 - 30℃;	3 Example 3 Preparation of Sunitinib L-Malate Example 3 Preparation of Sunitinib L-Malate [0115] Sunitinib (10 g) was suspended in methanol (1540 mL) under stirring and L-malic acid (3.36 g) was added to it at a temperature 25-30° C. The reaction mass was stirred to get a clear solution. It was filtered and methanol was distilled off under vacuum below 40° C. Acetonitrile (50 mL) was charged and the solvent was distilled off. It was cooled to 25-30° C. 380 mL of acetonitrile was added to the mass and it was mentained at 45-50° C. under stirring for a period of 15 minutes. The reaction mass was cooled to 30-35° C. The solid obtained was filtered and washed with acetonitrile (10 mL). The resultant compound was suck dried and dried under vacuum over a period of 4-5 hrs at 50° C. to obtain sunitinib L-malate. (12.0 g; yield 90%) [0116] Purity by HPLC: 98.5%; L-malic acid content: 24-26% (w/w); [0117] DSC: onset 195° C. and endset 198.77° C.; TGA: No loss observed till 200° C.; [0118] Moisture content: 0.79% [0119] IR (cm-1): 3328, 3233, 3073, 2984, 2885, 1673, 1635, 1574, 1529, 1496, 1477, 1439, 1322, 1278, 1256, 1196,807, 791 [0120] The XRPD is set forth in FIG. 01.
88%	In methanol at 40℃; for 1h; Large scale;	1 Specific Example 1: Preparation of a compound of formula I In a 20 L reactor, 4 L of acetonitrile and 1.8 kg of Compound II (10.8 mol) were added in that order.1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride 2.5 kg (12.9 mol),1.75 kg (12.9 mol) of 1-hydroxybenzotriazole, stirred well, and reacted at 35 ° C for 2 hours.At the end of the reaction, 1.9 kg (16.2 mol) of N,N diethylethylenediamine was added, and the reaction was carried out at 35 ° C for 2 hours. The reaction was completed, and 1.6-kg (10.8 mol) of 5-fluoroindol-2-one and 3 kg of triethylamine were added. ,The temperature was raised to 60 ° C for 2 hours, the reaction was completed, and the temperature was lowered to below 40 ° C.4L of methanol and 5kg (37.7mol) of L-malic acid were added, and the mixture was heated to 60 ° C for 1 hour.The reaction was completed, and it was cooled to room temperature, and filtered to give an orange-yellow solid, 5.1 kg.That is, compound I sunitinib malate, the yield was 88%, and the HPLC purity was 99.8%.
85.3%	Stage #1: sunitinib In methanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: (S)-Malic acid In methanol at 25℃;	1 Example 1 Two-Pot Synthesis of Sunitinib Base Synthesis of Sunitinib Malate Under N2, crude sunitinib (98.5 g, 0.247 mol, 1.0 eq. 99.2% by HPLC) and MeOH (3113 g, 3940 mL, 40 P w.r.t. crude sunitinib) were charged into a flask with a mechanical stirrer and a thermometer at ambient temperature. The heterogeneous mixture was stirred for 30 min at ambient temperature and L-malic acid (34.8 g, 0.259 mol, 1.05 eq.) was added at about 25° C. The mixture turned clear after 5 to 30 min and was vacuum filtered. The filtrate was stirred for 8 h at about 25° C. The mixture was vacuum filtered at ambient temperature, washed with MeOH (156 g, 197 mL, 2 P w.r.t. crude sunitinib) and dried in vacuo (relative vacuum NLT 0.095 MPa) at about 40° C. for 15 to 18 h to give 118.0 g of crude sunitinib malate with 99.5% purity by HPLC analysis and 0.40% by LOD in 90% yield. m.p. 195.0 to 196.0° C. Under N2, DMSO (506 g, 460 mL, 4 P w.r.t. crude sunitinib malate) was charged into a flask with a mechanical stirrer and a thermometer at ambient temperature and heated to about 45° C. for 5 to 10 min.
	In methanol at 20℃; for 0.5h;	1 Sunitinib base (13 g) was suspended in 2 L of methanol at ambient temperature and L-malic acid (4.7 g) was added. The mixture was stirred for 30 minutes and then concentrated under vacuum to dryness. Acetonitrile (500 mL) was added and the mixture was stirred at 70 0C for 1 hour. After cooling to ambient temperature the solid was collected by filtration and dried under vacuum at 40 0C for 48 hours.[0093] Analytical data: XRD: Form I, as shown in Figure 1; IR as shown in Figure 2.
	In methanol	19 Example 19: Conversion of Sunitinib to Sunitinib Malate (according to Example1, Preparation A of U.S. publication No. 2003/0069298)Preparation of the Anhydrous Crystal Form I of the L-Malic Acid Salt of N-[2- (Diethylamino) ethyl]-5-[(5fluoro-l, 2-dihydro-2-oxo-3H-indol- 3-ylidene) methyl]-2, 4-dimethyl-lH-pyrrole-3-carboxamide.Preparation A:N-[2-(Diethylamino)ethyl]-5-[(5-fluoro-l,2-dihydro-2- -oxo-3H-indol-3- ylidene)methyl]-2,4-dimethyl-lH-pyrrole-3-carboxamide (130 mg, 0.326 mMol) was added to 20 mL methanol, and the mixture was stirred. L-malic acid (47.2 mg, 0.352 mMol) was added, resulting in rapid dissolution of all the solids. The methanol was removed under reduced pressure to produce a poorly crystalline orange solid. Acetonitrile (5 mL) was added, and the slurry was stirred and heated for about 10 minutes. Stirring was continued while the slurry was allowed to cool to room temperature. The crystals were filtered and dried, resulting in 149 mg of solids (86% yield).
	In water at -90 - 80℃; Freeze drying;	2 Example 2The mixture of sunitinib free base (5.0 gm), L-malic acid (1.8 gm) and water (75 ml) was heated to 80 deg C to obtain a clear solution, stirred for 30 minutes at 80 deg C and slowly cooled to room temperature. The solution was subjected to freez drying at about -90 deg C for 7 hours to obtain 6.5 gm of sunitinib malate crystalline form III.
	In propan-1-ol at 60 - 65℃; for 2h;	1 Sunitinib base (2 g) was added to n-propanol (50 ml) and stirred for 30 minutes. L-Malic acid (0.7 g) was added to the mixture and stirred at 60°C to 65°C for 2 hours. The mixture was further stirred at about 20°C to 25°C for 18 hours, filtered under vacuum at 100 mBar to 150 mBar and dried under vacuum at 800 mBar to 900 mBar at 55°C to 60°C to obtain the title compound.Yield: 2.6 gMoisture content: 0.25%
	In water at 80℃; for 0.5h;	2 Example 2 The mixture of sunitinib free base (5.0 gm), L-malic acid (1.8 gm) and water (75 ml) was heated to 80 deg C. to obtain a clear solution, stirred for 30 minutes at 80 deg C. and slowly cooled to room temperature. The solution was subjected to freeze drying at about -90 deg C. for 7 hours to obtain 6.5 gm of sunitinib malate crystalline form Ill.
	In methanol for 0.166667h;	5 Preparation of sunitynib L-malate (1) N-[2-(diethylamine)ethyl]-5-formyl-2,4-dimethyl-lH-pyrrole-3-carboxyamide (2) (50 g, 0.188 mol) of 99.86 % purity, containing 0.06 % (HPLC) of (4), and 5-fluoro-l ,3- dihydroindol-2-one (3) (28.46 g, 0,188 mol) were dissolved in ethanol (650 mL). After addition of pyrrolidine (807 μ), the mixture was stirred and refluxed, in 1.40 h precipitation of the product was observed. After 3 h the mixture was cooled down to room temperature, than the solid was filtered off and washed with ethanol (2 x 150 mL). The wet paste was transferred into the flask, suspended in ethanol (500 mL) and refluxed for 15 min. After cooling down the solution to room temperature, the solid was filtered off, washed with ethanol (2 x 100 mL) and air dried. After transfer of the wet solid into the flask, methanol (625 mL) and L-malic acid (27.12 g, 0.202 mol) were added, the resulting mixture was stirred for 10 min. The solvents were removed under reduced pressure, to the residue acetonitrile (625 mL) was added. The solution was stirred for 10 min., than the product was filtered off, washed with methylene dichloride (3 x 200 mL) and air dried to furnish 87.7 g of sunitynib L- malate (1) with 87% yield. Purity according to HPLC: 99.61%, contents of desethyl sunitynib L-malate (6) - 013% and other single impurities < 0.02%. NMR (600 MHz, DMSOd6): δ 1.14 (6H,2 x CH3, Ν-6 ιΛ J= 7.1 Hz), 2.45(s,3H,C4- CH3,pyrro,e), 2.47 (s,3H,C2-CH3,pyrroie), 2.96(4H, 2 x CH2, N-ethyi, q, J = 7.2 Hz), 2.98(2H,CH2-NEt2, t, J = 6.4 Hz), 3.48(2H, CH2-NHamide, dt, J = 6.1, 6.0 Hz), 6.85(lH,C7-Hindoi,dd, J = 8.4, 4.5 Hz), 6.93(1H, C6-Hindoi, ddd, J = 9.3, 8.5, 2.3 Hz), 7.69 (1H, NHamide,t, J =5.4 Hz), 7.73(s,lH,CHvinyl), 7.77(1H, C4-Hindol, dd, J = 9.9, 2.2 Hz), 10.92 (s,lH,NHindoi), 13.73(s,lH,pyrroie), and L-malic acid: 2.36(lH,dd, J = 15.6, 5.3Hz i 2.55(lH,dd, J = 15.6, 8.2 Hz), 4.01(1H,CH-OH, dd, J = 8.1, 5.4 Hz), ~10.2(lH,OH,bs), ~10.2(lH,COOH,bs), -10.2 (lH,COOH,bs); ,3C NMR: δ 169.56(Cl=Oindoi), 165.18(C=Oamide), 158.22(C5-Findoi,d, J - 232.8 Hz), 136.82(C2pyrroie), 134.56(C8i„doi), 130.58(C4), 130.19(C4pyrro,e), 127.09(C3indol,d, J = 9.9 Hz), 125.83(C5 indol), 124.81(Cvinyl), 119.95(C3pyrrole), 114.92(C2indol,d, J = 2.8 Hz), 112.46(C6indoi,d, J = 24.2 Hz), 110.04(C7indoi, d, J = 8.1 Hz), 105.97(C4indol,d, J = 2.9 Hz), 50.59(CH2-NEt2), 46.71(CH2,Nethyi), 35.19(CH2-NHamide), 13.41(C2-CH3), 10.63(C4-CH3), 9.78(CH3,Nethyi) and L-malic acid: 176.04, 172.10 (2 x COOH), 66.41(C-OH), 40.89(CH2).

Reference： [1]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN106588888, 2017, A Location in patent: Paragraph 0048; 0050
[2]Current Patent Assignee: NATCO PHARMA LIMITED - WO2009/157011, 2009, A1 Location in patent: Page/Page column 39
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[6]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1 Location in patent: Page/Page column 15; 22; 25-26
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[8]Current Patent Assignee: NANJING TIANYUEXING BIO TECH - CN109503555, 2019, A Location in patent: Paragraph 0042; 0043
[9]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1 Location in patent: Paragraph 0060; 0061
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Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; N,N-dimethyl-formamide at 23 - 80℃;	9 Example 9 (Form I) (see Table 2); DMF (3vol) and sunitinib malate (leq) were charged to a two-neck round-bottom flask equipped with a thermopocket and a reflux condenser and stirred at 23-27°C for 10 minutes. A slurry was observed. The reaction mixture was heated to about 800C and then maintained at this temperature for about 5-10 minutes. A clear solution was observed. Anti-solvent* (a-z) (5-10vol) was added and the reaction mixture was stirred at about 800C for a further 15-20 minutes. The reaction mixture was allowed to cool to 23-27°C gradually over a period of 45-60 minutes and stirred at this temperature for 30 minutes. A solid was observed. The solid was filtered on a Buchner funnel under vacuum and dried on a rotavapour at 400C under high vacuum to obtain a yellow solid, which was characterized as sunitinib malate form I. Yield = 75-99%. * The anti-solvent was selected from one or more of the following: a. Water, b. Methanol, c. Ethanol, d. 1-Propanol, e. 1-Butanol, f. 1-Pentanol, g. iso-Propanol, h. iso-Butanol, i. t-Butanol, j. Ethoxy Ethanol, k. Acetonitrile, 1. Acetone, m. Methyl Ethyl Ketone, n. Methyl iso-Butyl Ketone, o. Diethyl Ketone, p. Ethyl Acetate, q. iso-Propyl Acetate, r. iso-Butyl Acetate, s. n-Pentyl Acetate, t. DCM, u. 1,4-Dioxane, v. THF, w. t-Butyl Methyl Ether, x. Diethyl Ether, y. Toluene, z. Xylene.
	In 2-ethoxy-ethanol Heating;	8 Sunitinib malate (100 mg) was dissolved with heating in the solvent indicated in the table below. After cooling to ambient temperature the mixture was stirred for 24 hours and then concentrated under vacuum at 40 0C.Table 1[0117] Analytical data of Example 7: XRD: Form VI, as shown in Figure 9 (i.e., mixture of sunitinib malate known Form I and at least one unknown crystalline form). Sunitinib L-malate crystalline Form VI has the XRD shown in Figure 9 and the IR shown in Figure 10. [0118] Analytical data of Examples 8 and 9: XRD: Form I, as shown in Figure 1; Sunitinib L-malate crystalline Form I has the XRD shown in Figure 1 and the IR shown in Figure 2.
	In ISOPROPYLAMIDE Heating;	9 Sunitinib malate (100 mg) was dissolved with heating in the solvent indicated in the table below. After cooling to ambient temperature the mixture was stirred for 24 hours and then concentrated under vacuum at 40 0C.Table 1[0117] Analytical data of Example 7: XRD: Form VI, as shown in Figure 9 (i.e., mixture of sunitinib malate known Form I and at least one unknown crystalline form). Sunitinib L-malate crystalline Form VI has the XRD shown in Figure 9 and the IR shown in Figure 10. [0118] Analytical data of Examples 8 and 9: XRD: Form I, as shown in Figure 1; Sunitinib L-malate crystalline Form I has the XRD shown in Figure 1 and the IR shown in Figure 2.

	In water at -90 - 80℃; Freeze drying;	1 Example 1Sunitinib malate (5.0 gm) was added to water (75 ml), and the mixture was heated to 80 deg C to obtain a clear solution, stirred for 30 minutes at 80 deg C. The solution was slowly cooled to room temperature. The solution was subjected to freez drying at about -90 deg C for 8 hours to obtain 4.7 gm of sunitinib malate crystalline form III.
	In water; butan-1-ol at 25 - 65℃;	2 2-( ,N-Diemylamino)ethyl ammonium dimalate (4.3g, 1.5 mol equivalent), N-[2- (diemylammo)emyl]-5-formyl-2,4-dimemyl-lH-pyrrole-3-carboxamide (2g, 1 mol equivalent) and 5-fiuoro-2-oxindole (1.13g, 1 mol equivalent) were added to 20ml of acetonitrile : methanol (3:2) at 25-30°C to obtain a clear solution. After 3 hours stirring at 25-30°C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 55-60°C for 3-4 hours.Yield = 3.2g (80%)Chemical Purity (HPLC) > 98%This solid was further purified by dissolving in butanol : water (4:1, 20 volumes) at 60- 65°C, cooling to 25-30°C, and filtering and drying the precipitated sunitinib malate.Yield = 80%Chemical Purity (HPLC) > 99.7%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit) The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1. Sunitinib malate polymorphic form I was obtained before and after recrystallisation.
	In water; dimethyl sulfoxide; 4-methyl-2-pentanone at 20 - 55℃; for 30.417h;	20 A mixture of DMSO (22.5 mL, 4.50 P, water content by Karl Fischer analysis 303 ppm) and water (0.1 mL, 0.02 P, 0.6 eq.) was pre-heated to 55°C and Sunitinib malate (5.0 g, 99.48% purity by HPLC analysis, 1.0 eq.) was charged into the solvent and stirred for 25 min at 55°C. Then a mixture of MIBK (60 mL, 12 P, water content by Karl Fischer analysis 76 ppm) and water (0.1 mL, 0.02 P, 0.6 eq.) was charge at 55°C. The mixture was cooled to 20 °C and further stirred for about 30 h. The mixture was filtered and the cake was washed with MIBK (20 mL, 4.0 P, water content by Karl Fischer analysis 76 ppm), then was dried under vacuum at 40°C overnight to give a sunitinib new malate salt form (3.70 g, 74.0% yield) as an orange to red powder with about 99.58% purity by HPLC analysis, m.p. 213 °C -216 °C.

3
[ 56341-41-4 ]
[ 97-67-6 ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	With pyrrolidine; In ethanol; at 78℃; for 3h;	N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-lH-pyrrole-3-carboxamide (1.0 g), 5-Fluoro-l,3-dihydro-2H-indol-2-one (0.57 g), pyrrolidine (0.013 g) and L-malic acid (0.37 g) were added to absolute ethanol (15 ml) and the reaction mixture was stirred at 78C (internal temperature) for 3 hours. The reaction mixture was cooled to 20C to 25C, filtered under vacuum, washed with absolute ethanol (10 ml) and dried under vacuum at 50C for 10 hours to 12 hours to obtain the title compound. Percentage yield: 80%Purity: 99.37%.
80%	With pyrrolidine; In ethanol; at 78℃; for 3h;	Preparation of L-Malic Acid Salt of Sunitinib N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide (1.0 g), 5-Fluoro-1,3-dihydro-2H-indol-2-one (0.57 g), pyrrolidine (0.013 g) and L-malic acid (0.37 g) were added to absolute ethanol (15 ml) and the reaction mixture was stirred at 78 C. (internal temperature) for 3 hours. The reaction mixture was cooled to 20 C. to 25 C., filtered under vacuum, washed with absolute ethanol (10 ml) and dried under vacuum at 50 C. for 10 hours to 12 hours to obtain the title compound. Percentage yield: 80% Purity: 99.37%.
71.2%		Example 3; Preparation of the Malic Acid Salt of SunitinibMalic Acid Salt of Compound of Formula (I)In accordance with an embodiment of the invention, this example describes the preparation of the malic acid salt of sunitinib via (i) preparation of the malic acid salt of compound II without isolation, and (ii) reaction of the non-isolated malic acid salt of compound II with compound III.2.50 g of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl) amide and 25 mL of n-butanol were heated to 48 C. to completely dissolve the solid. A previously prepared solution of 1.50 g L-(-)-malic acid and 7.5 mL of n-butanol was then added dropwise to the reaction mixture while maintaining the reaction temperature. Once addition was complete stirring was continued for 15 minutes. A previously prepared solution of 1.43 g of 5-fluoro-1,3-dihydroindol-2-one and 20 mL n-butanol was then added dropwise while maintaining the temperature of the reaction mixture. After the addition was complete 40 muL of pyrrolidine were added and the mixture was heated to 94 C. After 20 minutes at 94 C. an orange solid started to crystallize. The reaction was monitored by TLC and after 2.5 h at 94 C. the mixture was cooled to 0-5 C. and stirred for 1 h. The orange suspension was then filtered, the collected solid was washed with 2×8 mL of n-butanol and then dried at 60 C. for 4 h under vacuum to give 3.92 g (78.1% yield) of a light orange solid.3.16 g of the dry solid obtained previously and 15.8 mL of distilled water were heated to dissolution. At 77 C. a clear red solution was obtained. The solution was filtered to remove insolubles, and the filter was washed with 4.25 mL of water. The filtrate was heated to 75 C. and 23.7 mL of 2-propanol were added dropwise, while maintaining the temperature of the mixture. Once the addition was complete, the mixture was cooled to room temperature and stirred for 1 h. Crystallization was observed at 26 C. The light orange suspension was then cooled to 0-5 C., stirred for 1 h and filtered. The collected solid was washed with 2×6.4 mL of 2-propanol, and then dried at 60 C. for 4 h under vacuum to give 2.88 g (91.1% yield) of a light orange solid, which was the malic acid salt of sunitinib. Overall yield: 71.2%.Analytical data: IR (KBr): Essentially identical to the IR spectrum shown in FIG. 2; Potentiometric assay: 100.07%; HPLC: 99.56% (% area); Melting point: 188.3-189.1 C. Crystalline Form I.

71%		Into a 500 mL four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, and a reflux condenser were charged 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)-amide (VII) (10.0 g; 0.03 mole), 5-fluoro-2-oxindole (5.46 g; 0.03 mole) and ethanol (70 mL). The reaction mixture was then heated to refluxed for 8-10 hours. The progress of the reaction was monitored by TLC. After completion of reaction, L(-)-malic acid (3.9 g; 0.029 mole) was charged and further maintained at reflux temperature for 4-6 hours. After maintenance, the reaction mixture was cooled to room temperature and filtered the solids. The wet solids were then triturated in acetone (60 mL) at reflux temperature for 1 hour and cooled to room temperature. The product was isolated by filtration and dried at 80-85oC. Dry Weight: 14.3 g Yield: 71.0% HPLC Purity: >99.5%
		Example 25: Preparation of (2S)-2-hydroxy butanedioic acid compound with N-[2- (diethylamino)ethyl]-5-[(Z)-(5-fluoro-l,2-dihydro-2-oxo-3fT-indol-3-yIidine) methyl]- 2,4-dimethyl-l/-pyrrole-3-carboxamide (1:1) - Sunitinib Malate-I(a):Into a 500 mL four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, a nitrogen bubbler, and a reflux condenser were charged 5- formyl-2,4-dimethyl-lH-pyrrole-3-carboxylic acid (V) (10.0 g; 0.06 mole), 1 -Hydroxy benzotriazole (12.0 g), dicyclohexylcarbodimide (17.2 g) and tetrahydrofuran (150 mL). To this stirred solution, a solution of triethyl amine (16.8 mL) in 65 mL tetrahydrofuran followed by N,N-diethylaminoethyl amine (10 mL; 0.07 mole) in 65 mL tetrahydrofuran were added through addition funnel and stirred for 20 hours. The progress of the reaction was monitored by TLC. After completion of reaction, the urea derivative was filtered off and the filtrate was re-charged into a fresh 500 mL round-bottomed flask equipped with a mechanical stirrer, thermometer pocket, a nitrogen bubbler, and a reflux condenser. To this stirred solution L(-)-malic acid (8.9 g; 0.06 mole) was charged and further maintained for 4-6 hours. To the resulting solution, 5-fluoro-2-oxindole (8.99 g; 0.06 mole) was charged and continued at reflux temperature for 4-6 hours. The yellow crystalline precipitate was filtered off and wet cake was washed with tetrahydrofuran (50 mL). The product was again triturated in tetrahydrofuran (70 mL) at reflux temperature for 1 hour and filtered. The product was dried at 80-85 C. Dry Weight: 21.5 g Yield: 67.0% HPLC Purity: > 99.5%

Reference： [1]Patent: WO2011/107919,2011,A1 .Location in patent: Page/Page column 4
[2]Patent: US2013/123511,2013,A1 .Location in patent: Paragraph 0014; 0015; 0016
[3]Patent: US2009/318525,2009,A1 .Location in patent: Page/Page column 4
[4]Patent: US2011/92717,2011,A1 .Location in patent: Page/Page column 19-20
[5]Patent: WO2009/157011,2009,A1 .Location in patent: Page/Page column 44

4
[ 56341-41-4 ]
[ 1200435-83-1 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
75.1%	With pyrrolidine; In butan-1-ol; at 20℃;Reflux;	Example 2; Preparation of the Malic Acid Salt of SunitinibMalic Acid Salt of Compound of Formula (I)This example describes the preparation of the malic acid salt of sunitinib via reaction of the malic acid salt of compound II with compound III in accordance with an embodiment of the invention.4.52 g of the malic acid salt of 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl) amide obtained in Example 1, 1.70 g of 5-fluoro-1,3-dihydroindol-2-one and 60 mL of n-butanol were stirred at room temperature. 46.5 muL of pyrrolidine were then added and the suspension was heated to reflux. Complete dissolution of the materials was observed at 79 C. Once at reflux, an orange solid started to crystallize. The reaction was monitored by TLC and after 2.25 h at reflux it was complete. The suspension was then cooled to 0-5 C., stirred for 1 h and filtered. The collected solid was washed with 2×9 mL of n-butanol and then dried at 60 C. for 4 h under vacuum to give 5.26 g (87.7% yield) of a light orange solid.4.12 g of the dry solid obtained above and 20.6 mL of distilled water were heated to dissolution. At 78 C. a clear red solution was obtained. The solution was filtered to remove insolubles, and the filter was washed with 3 mL of water. The filtrate was heated to 75 C. and 30.9 mL 2-propanol were added dropwise, while maintaining the temperature of the mixture. Once the addition was complete, the mixture was cooled to room temperature and stirred for 1 h. Crystallization was observed at 35 C. The light orange suspension was then cooled to 0-5 C., stirred for 1 h and filtered. The collected solid was washed with 2×8.5 mL of 2-propanol, and then dried at 60 C. for 4 h under vacuum to give 3.72 g (90.3% yield) of a light orange solid, which was the malic acid salt of sunitinib. Overall yield: 75.1%.Analytical data: IR (KBr): Characteristic peaks at (cm-1): 3410, 3327, 3231, 2980, 2883, 2696, 2484, 1836, 1672, 1634, 1574, 1529, 1475, 1439, 1421, 1402, 1385, 1361, 1319, 1292, 1277, 1256, 1229, 1196, 1177, 1159, 1146, 1103, 1095, 1026, 960, 922, 908, 891, 862, 806, 791, 770, 737, 710, 692, 663, 654, 606, 586, 447. See FIG. 2; Potentiometric assay: 99.82%; HPLC: 99.78% (% area); Melting point: 188.9-189.9 C. Crystalline Form I.

Reference： [1]Patent: US2009/318525,2009,A1 .Location in patent: Page/Page column 3-4

5
[ 341031-54-7 ]
(Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-yliden)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide L-malate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol Reflux;	2 Sunitinib malate (100 mg) was dissolved in ethanol (20 mL) at reflux. After cooling to ambient temperature the solid was collected by filtration and dried under vacuum at ambient temperature.[0097] Analytical data: XRD: Form III, as shown in Figure 3; IR as shown in Figure 4.Sunitinib L-malate crystalline Form III has the XRD shown in Figure 3 and the IR shown inFigure 4.

Reference： [1]Current Patent Assignee: MEDICHEM, S.A. - WO2010/10454, 2010, A2 Location in patent: Page/Page column 10

6
[ 253870-02-9 ]
[ 56341-41-4 ]
[ 97-67-6 ]
[ 100-36-7 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
67%		Into a 500 mL four necked round-bottomed flask equipped with a mechanical stirrer, a thermometer pocket, a nitrogen bubbler, and a reflux condenser were charged 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (V) (10.0 g; 0.06 mole), 1-Hydroxy benzotriazole (12.0 g), dicyclohexylcarbodiimide (17.2 g) and tetrahydrofuran (150 mL). To this stirred solution, a solution of triethyl amine (16.8 mL) in 65 mL tetrahydrofuran followed by N,N-diethylaminoethyl amine (10 mL; 0.07 mole) in 65 mL tetrahydrofuran were added through addition funnel and stirred for 20 hours. The progress of the reaction was monitored by TLC. After completion of reaction, the urea derivative was filtered off and the filtrate was re-charged into a fresh 500 mL round-bottomed flask equipped with a mechanical stirrer, thermometer pocket, a nitrogen bubbler, and a reflux condenser. To this stirred solution L(-)-malic acid (8.9 g; 0.06 mole) was charged and further maintained for 4-6 hours. To the resulting solution, 5-fluoro-2-oxindole (8.99 g; 0.06 mole) was charged and continued at reflux temperature for 4-6 hours. The yellow crystalline precipitate was filtered off and wet cake was washed with tetrahydrofuran (50 mL). The product was again triturated in tetrahydrofuran (70 mL) at reflux temperature for 1 hour and filtered. The product was dried at 80-85oC.Dry Weight: 21.5 g Yield: 67.0% HPLC Purity: >99.5%

Reference： [1]Patent: US2011/92717,2011,A1 .Location in patent: Page/Page column 20

7
[ 56341-41-4 ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Reference： [1]Patent: US2011/92717,2011,A1
[2]Patent: US2013/190512,2013,A1

8
[ 2199-59-9 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 2.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 2.2: 16 h / 25 - 30 °C 3.1: pyrrolidine / methanol / 5 - 7 h / Reflux 4.1: ethanol / 2 - 4 h / Reflux
	Multi-step reaction with 2 steps 1.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 2.1: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 20 h 2.2: 4 - 6 h / Reflux 2.3: 4 - 6 h / Reflux
	Multi-step reaction with 3 steps 1.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 2.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 2.2: 16 h / 25 - 30 °C 3.1: ethanol / 8 - 10 °C / Reflux 3.2: 4 - 6 h / Reflux

Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[2]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[3]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1

9
[ 86770-31-2 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: hydrogenchloride / isopropyl alcohol / 25 - 50 °C 2.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 2.2: 25 - 30 °C / pH 12 - 13 3.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 4.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 4.2: 16 h / 25 - 30 °C 5.1: pyrrolidine / methanol / 5 - 7 h / Reflux 6.1: ethanol / 2 - 4 h / Reflux
	Multi-step reaction with 4 steps 1.1: hydrogenchloride / isopropyl alcohol / 25 - 50 °C 2.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 2.2: 25 - 30 °C / pH 12 - 13 3.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 4.1: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 20 h 4.2: 4 - 6 h / Reflux 4.3: 4 - 6 h / Reflux
	Multi-step reaction with 5 steps 1.1: hydrogenchloride / isopropyl alcohol / 25 - 50 °C 2.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 2.2: 25 - 30 °C / pH 12 - 13 3.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 4.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 4.2: 16 h / 25 - 30 °C 5.1: ethanol / 8 - 10 °C / Reflux 5.2: 4 - 6 h / Reflux

Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[2]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[3]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1

10
[ 253870-02-9 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 1.2: 16 h / 25 - 30 °C 2.1: pyrrolidine / methanol / 5 - 7 h / Reflux 3.1: ethanol / 2 - 4 h / Reflux
	Multi-step reaction with 2 steps 1.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 1.2: 16 h / 25 - 30 °C 2.1: ethanol / 8 - 10 °C / Reflux 2.2: 4 - 6 h / Reflux
	Multi-step reaction with 4 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / ammonium sulfate / 5 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h 2.2: 25 °C 3.1: N,N-dimethyl-formamide / 25 °C 4.1: methanol / 8 h / 25 °C / Inert atmosphere

	Multi-step reaction with 4 steps 1.1: ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane / 5 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 25 °C 2.2: 1 h / 40 °C 3.1: acetonitrile; N,N-dimethyl-formamide / 1 h / 25 °C 4.1: methanol / 0.5 h / 20 °C / Inert atmosphere 4.2: 25 °C
	Multi-step reaction with 3 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / acetonitrile / 2 h / 35 °C / Large scale 1.2: 2 h / 35 °C / Large scale 2.1: triethylamine / 2 h / 60 °C / Large scale 3.1: methanol / 1 h / 40 °C / Large scale

Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[2]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[3]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1
[4]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1
[5]Current Patent Assignee: NANJING TIANYUEXING BIO TECH - CN109503555, 2019, A

11
[ 443-69-6 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrazine / 5.5 h / 100 - 130 °C 2: pyrrolidine / methanol / 5 - 7 h / Reflux 3: ethanol / 2 - 4 h / Reflux
	Multi-step reaction with 2 steps 1.1: hydrazine / 5.5 h / 100 - 130 °C 2.1: ethanol / 8 - 10 °C / Reflux 2.2: 4 - 6 h / Reflux
	Multi-step reaction with 2 steps 1.1: hydrazine / 5.5 h / 100 - 130 °C 2.1: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 20 h 2.2: 4 - 6 h / Reflux 2.3: 4 - 6 h / Reflux

Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[2]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[3]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1

12
[ 2199-51-1 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 1.2: 25 - 30 °C / pH 12 - 13 2.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 3.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 3.2: 16 h / 25 - 30 °C 4.1: pyrrolidine / methanol / 5 - 7 h / Reflux 5.1: ethanol / 2 - 4 h / Reflux
	Multi-step reaction with 3 steps 1.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 1.2: 25 - 30 °C / pH 12 - 13 2.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 3.1: triethylamine; dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 20 h 3.2: 4 - 6 h / Reflux 3.3: 4 - 6 h / Reflux
	Multi-step reaction with 4 steps 1.1: trichlorophosphate / 2 - 3 h / 0 - 50 °C 1.2: 25 - 30 °C / pH 12 - 13 2.1: potassium hydroxide; water / methanol / 4 - 6 h / 60 - 70 °C 3.1: dicyclohexyl-carbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 3.2: 16 h / 25 - 30 °C 4.1: ethanol / 8 - 10 °C / Reflux 4.2: 4 - 6 h / Reflux

Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[2]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1
[3]Current Patent Assignee: NATCO PHARMA LIMITED - US2011/92717, 2011, A1

Yield	Reaction Conditions	Operation in experiment
	In methanol at 20 - 22℃;	2 Crystalline Form V of L-malic acid salt of sunitinib (2 g) was stirred in methanol (12 ml) at 20°C to 22°C for 5 hours to 6 hours. The mixture was filtered under vacuum at 20°C to 25 °C and dried under vacuum at 60°C for 12 hours to 15 hours to obtain the title compound.

14
[ 56341-41-4 ]
[ 2689-91-0 ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	Into 20ml of acetonitrile : methanol (3:2), diammonium malate (1.9g, 1.5 mol equivalent), N-[2-(diemylamino)ethyl]-5-formyl-2,4-dimethyl-lH-pyrrole-3-carboxam^ (2g, 1 mol equivalent) and 5-fluoro-2-oxindole (1.13g, 1 mol equivalent) were added at 25-30C to obtain a clear solution. After 3 hours stirring at 25-30C, an orange solid progressively precipitated out of the solution. The orange solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 60-65C for 3-4 hours.Yield = 3g (75%)Chemical Purity (HPLC) > 98.51%This solid was further purified by dissolving in butanol : water (4:1, 20 volumes) at 60- 65C, cooling to 25-30C, and filtering and drying the precipitated sunitinib malate.Yield = 50%Chemical Purity (HPLC) > 99.49%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit)The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1. Sumtinib malate polymorphic form I was obtained before and after recrystallisation.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 25

15
[ 56341-41-4 ]
di-(diisopropyl ammonium) L-malate [ No CAS ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
72.5%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	Into 20ml of acetonitrile : methanol (3:2), di-diisopropyl ammonium malate (1.9g, 1.5 mol equivalent), N-[2-(<diethylamino)emyl]-5-formyl-2,4-dimemyl-lH-pyrrole-3-carboxami (2g, 1 mol equivalent) and 5-fluoro-2-oxindole (1.13g, 1 mol equivalent) were added at 25- 30C to obtain a clear solution. After stirring for 3 hours at 25-30C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried in a vacuum oven at 60-65C for 3-4 hours.Yield = 2.9g (72.5%)Chemical Purity (HPLC) > 97.84%This solid was further purified by dissolving in butanol : water (4:1, 20 volumes) at 60- 65C, cooling to 25-30C, and filtering and drying the precipitated sunitinib malate.Yield = 70%Chemical Purity (HPLC) > 98.77%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit)The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1. Sunitinib malate polymorphic form I was obtained before and after recrystallisation.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 26

16
[ 56341-41-4 ]
dipyrrolidine L-malate [ No CAS ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
32%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	Into 20ml of acetonitrile : methanol (3:2), dipyrrolidine malate (3.1g, 1.5 mol equivalent), N-[2-(diethylamino)ediyl]-5-foimyl-2,4-dimemyl-lH-pyrrole-3-carboxamide (2g, 1 mol equivalent) and 5-fiuoro-2-oxindole (l-13g, 1 mol equivalent) were added at 25-30C to obtain a clear solution. After 3 hours stirring at 25-30C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 60-65C for 3-4 hours.Yield = 1.3g (32%)Chemical Purity (HPLC) > 97.87%Polymorphic Purity (XRPD) > 95%The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 26-27

17
[ 56341-41-4 ]
di-(n-propyl ammonium) L-malate [ No CAS ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	Into 20ml of acetonitrile : methanol (3:2), di-n-propyl ammonium malate (2.85g, 1.5 mol equivalent), N-[2-(diemylammo)emyl]-5-formyl-2,4-dimemyl-lH-pyrrole-3-carboxami (2g, 1 mol equivalent) and 5-fluoro-2-oxindole (1.13g, 1 mol equivalent) were added at 25- 30C to obtain a clear solution. After 3 hours stirring at 25-30C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 60-65C for 3-4 hours.Yield = 3g (75%)Chemical Purity (HPLC) > 98.39%Polymorphic Purity (XRPD) > 95%The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 27

18
[ 56341-41-4 ]
2-(N,N-diethylamino)ethyl ammonium di(L-malate) [ No CAS ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	2-( ,N-Diemylamino)ethyl ammonium dimalate (4.3g, 1.5 mol equivalent), N-[2- (diemylammo)emyl]-5-formyl-2,4-dimemyl-lH-pyrrole-3-carboxamide (2g, 1 mol equivalent) and 5-fiuoro-2-oxindole (1.13g, 1 mol equivalent) were added to 20ml of acetonitrile : methanol (3:2) at 25-30C to obtain a clear solution. After 3 hours stirring at 25-30C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 55-60C for 3-4 hours.Yield = 3.2g (80%)Chemical Purity (HPLC) > 98%This solid was further purified by dissolving in butanol : water (4:1, 20 volumes) at 60- 65C, cooling to 25-30C, and filtering and drying the precipitated sunitinib malate.Yield = 80%Chemical Purity (HPLC) > 99.7%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit) The structure of sunitinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1. Sunitinib malate polymorphic form I was obtained before and after recrystallisation.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 23

19
[ 56341-41-4 ]
[ 1332307-07-9 ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	In methanol; acetonitrile; at 25 - 30℃; for 3h;	Into 20ml of acetonitrile : methanol (3:2), 2-(N,N-cHethylamino)ethyl ammonium malate (2.83g, 1.5 mol equivalent), N-[2-(diemylamino)emyl]-5-formyl-2,4-dimemyl-lH-pyrrole-3- carboxamide (2g, 1 mol equivalent) and 5-fiuoro-2-oxindole (1.13g, 1 mol equivalent) were added at 25-30C to obtain a clear solution within 15 minutes. After 3 hours stirring at 25- 30C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (10ml) and dried under vacuum at 55-60C for 3-4 hours.Yield = 2.9g (72%)Chemical Purity (HPLC) > 98.77%This solid was further purified by dissolving in butanol : water (4:1, 20 volumes) at 60- 65C, cooling to 25-30C, and filtering and drying the precipitated sunitinib malate.Yield = 80%Chemical Purity (HPLC) > 99.76%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit)The structure of sumtinib malate was confirmed by NMR and HPLC retention time with standard sample. XRPD analysis indicated polymorphic form I as shown in Figure 1. Sunitinib malate polymorphic form I was obtained before and after recrystallisation.

Reference： [1]Patent: WO2011/104555,2011,A2 .Location in patent: Page/Page column 24

20
[ 100-36-7 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol / 1 h / 25 - 30 °C 2: acetonitrile; methanol / 3 h / 25 - 30 °C
	Multi-step reaction with 2 steps 1: methanol / 1 h / 25 - 30 °C 2: acetonitrile; methanol / 3 h / 25 - 30 °C
	Multi-step reaction with 2 steps 1.1: p-toluenesulfonyl chloride / N,N-dimethyl-formamide / 0.25 h / 15 - 19 °C 1.2: 15 - 19 °C 1.3: 0.67 h / 13 - 16 °C 2.1: methanol / 25 - 30 °C

	Multi-step reaction with 6 steps 1.1: dichloromethane / 0.5 h / 0 - 20 °C 2.1: zinc / methanol; acetic acid / 65 - 70 °C 3.1: sulfuric acid / water; methanol / 3.5 h / 60 - 65 °C 4.1: oxalyl dichloride / dichloromethane / 2.5 h / 0 - 10 °C / Inert atmosphere 4.2: 30 °C 5.1: potassium hydroxide / N,N-dimethyl-formamide / 3.5 h / 20 °C / Darkness; Inert atmosphere 6.1: methanol; ethanol / 2 h / 20 °C / Darkness
	Multi-step reaction with 3 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / acetonitrile / 2 h / 35 °C / Large scale 1.2: 2 h / 35 °C / Large scale 2.1: triethylamine / 2 h / 60 °C / Large scale 3.1: methanol / 1 h / 40 °C / Large scale

Reference： [1]Current Patent Assignee: VIATRIS INC - WO2011/104555, 2011, A2
[2]Current Patent Assignee: VIATRIS INC - WO2011/128699, 2011, A2
[3]Current Patent Assignee: LAURUS LABS LIMITED - US2015/25252, 2015, A1
[4]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN106588888, 2017, A
[5]Current Patent Assignee: NANJING TIANYUEXING BIO TECH - CN109503555, 2019, A

21
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydrogensulfite / ethanol; water / 10 - 20 °C 2: acetonitrile; methanol / 3 h / 25 - 30 °C
	Multi-step reaction with 2 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / ammonium sulfate / 5 h / Reflux 1.2: 29.3 h / Reflux 2.1: methanol / 8 h / 25 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: VIATRIS INC - WO2011/128699, 2011, A2
[2]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1

22
[ 1332307-07-9 ]
[ 1032268-12-4 ]
[ 1338703-87-9 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
67%	In methanol; acetonitrile at 25 - 30℃; for 3h;	3 Example 3: Preparation of sunitinib L-malate (IV) using the sodium salt of pyrrole derivative (I) The sodium salt of pyrrole derivative (I) (lOg, 0.028mol), 5-fluoro-2-oxindole (II) (4.3g, 0.028mol) and 2-(N,N-diemylamino)ethyl ammonium L-malate (10.5g, 0.042mol, 1.5 equivalent) were added to acetonitrile : methanol (60ml:40ml, 6vol:4vol) at 25-30°C. A clear solution was obtained within 5 minutes. After stirring for 3 hours at 25-30°C, a yellow solid progressively precipitated out of the solution. The yellow solid was isolated by filtration, washed with methanol (50ml, 5vol) and dried under vacuum at 55-60°C for 3-4 hours. Yield = lOg (67%)Chemical Purity (HPLC) > 99%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit) IR (KBr, cm 1): 3326 (broad, N-H str.), 3231 (broad, O-H str.), 3063, 2927, 1671 (>C=0 str.), 1654, 1636, 1577, 1475, etc.¾-NMR (DMSO-d6): 1.12 (t, 6H, J=7.14Hz, 2 x -CH2-CH3), 2.36 (m, 2H, -CH2-COOH), 2.44 (s, 3H, -CH3), 2.46 (s, 3H, -CH3), 2.55 (m, IH, -CHOH-COOH), 2.92 (m, 6H, 3 x -CH2-), 4.02 (m, 2H, -CH2-), 6.86 (m, IH, vinyl proton), 6.94 (t, IH, J=10.22Hz, aromatic ortho position), 7.64 (bs, IH, -CONH-, D20 exchangeable), 7.73 (s, IH, aromatic ortho position), 7.78 (d, IH, J=9.42Hz, aromatic meta position), 10.92 (s, IH, -CONH-, D20 exchangeable), 13.73 (s, IH, pyrrole -NH-, D20 exchangeable).13C-NMR (DMSO-d6): 9.69 (2C, 2 x -CH2-CH3, DEPT), 10.68 (1C, -CH3, DEPT), 13.46 (1C, -CH3, DEPT), 35.01 (1C, -CH2-, DEPT), 40.89 (1C, -CH2-, DEPT), 46.81 (2C, 2 x -CH2-, DEPT), 50.57 (1C, -CH2-, DEPT), 66.40 (1C, vinyl carbon, DEPT), 106.06 (1C, d, aromatic ortho position, DEPT), 110.08 (1C, d, aromatic ortho position, DEPT), 112.60 (1C, d, aromatic meta position, DEPT), 115.04 (1C, -CHOH-COOH), 124.91 (1C, d, aromatic =CF-, DEPT), 119.90-136.96 (5C, 4 x Ar-C + =C indole ring), 159.86 (1C, -CONH-), 169.52 (1C, -CONH-), 172.21 (1C, -COOH), 176.06 (1C, -COOH).Mass (m/z): (M+l) 399 (100%), [(M+2) +1] 401 (14%).This solid was further purified by dissolving in n-butanol : water (4:1, 20vol) at 50-60°C and cooling to 25-30°C.Recrystallisation Yield = 80%Chemical Purity (HPLC) > 99.5%Polymorphic Purity (XRPD) > 99% (other polymorphic forms below detection limit) The structure of sunitinib L-malate (IV) was confirmed by NMR and HPLC retention time with standard sample. XRPD and DSC analysis indicated polymorphic form I as shown in Figures 1 and 2. Sunitinib L-malate (IV) polymorphic form I was obtained before and after recrystallisation.

Reference： [1]Current Patent Assignee: VIATRIS INC - WO2011/128699, 2011, A2 Location in patent: Page/Page column 31-33

23
[ 97-67-6 ]
[ 557795-19-4 ]
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide L-malate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In methanol; at 25 - 30℃;	<strong>[557795-19-4]Sunitinib</strong> (10 g) was suspended in methanol (1540 mL) under stirring and L-malic acid (3.36 g) was added to it at a temperature 25-30C. The reaction mass was stirred to get a clear solution. It was filtered and methanol was distilled off under vacuum below 40C. Acetonitrile (50mL) was charged and the solvent was distilled off. It was cooled to 25-30 C. 380mL of acetonitrile was added to the mass and it was mentained at 45- 50C under stirring for a period of 15 minutes. The reaction mass was cooled to 30- 35C. The solid obtained was filtered and washed with acetonitrile (10 ml_). The resultant compound was suck dried and dried under vacuum over a period of 4-5 hrs at 50C to obtain <strong>[557795-19-4]sunitinib</strong> L-malate. (12.0 g; yield 90%) Purity by HPLC: 98.5 %; L-malic acid content: 24-26 % (w/w); DSC: onset 195C and endset 198.77 C; TGA: No loss observed till 200C; Moisture content: 0.79 % IR (cm"1): 3328, 3233, 3073, 2984, 2885, 1673, 1635, 1574, 1529, 1496, 1477, 1439, 1322, 1278, 1256, 1196,807, 791 The XRPD is set forth in Figure. 01.
	In 4-methyl-2-pentanone; at 20℃; for 3h;Product distribution / selectivity;	<strong>[557795-19-4]Sunitinib</strong> (1.3 g) was taken in methyl isobutylketone (39 ml) and L- alic acid (0.472 g) was added to the above mixture. Reaction mixture was stirred for 3 hours at room temperature. The product thus obtained was filtered and dried to give 1.3 g of title compound having purity 99.6 % by HPLC.
	at 75℃;	Example 8:Preparation of amorphous <strong>[557795-19-4]sunitinib</strong> malate solid dispersion with copovidone5-Formyl-2,4-dimethyl- I H-pyrrole-3-carboxylic acid(2-diethylamino-ethy1)- amide (100 gm) was dissolved in ethanol (1500 ml) and then added 5-fluoro-1,3-dihydro- indol-2-one (54 gm) and pyrrolidine (1.57 ml). The contents were then heated to reflux and stirred for 3 hours. The reaction mass was then cooled to room temperature, stirred for 1 hour and filtered. To the wet solid thus obtained was added ethanol (1200 ml) andthen heated to 50C. The solution was stirred for 1 hour at 50C and then cooled to room temperature. The contents were stirred for 1 hour at room temperature and then addedwater (2300 ml). To the reaction mass was added L-malic acid (41 gm) and copovidone(230 gm) and then heated to 75C. The solution was then cooled to room temperature andfiltered. The resulting filtrate was subjected to freeze drying at room temperature for 40hours to obtain 378 gm of amorphous <strong>[557795-19-4]sunitinib</strong> malate solid dispersion with copovidone.

Reference： [1]Patent: WO2013/140232,2013,A1 .Location in patent: Page/Page column 16; 17
[2]Patent: WO2012/59941,2012,A1 .Location in patent: Page/Page column 19
[3]Patent: WO2013/160916,2013,A1 .Location in patent: Page/Page column 8; 9

24
[ 56341-41-4 ]
[ 341031-54-7 ]

Reference： [1]Patent: WO2012/58780,2012,A1
[2]Patent: WO2012/58780,2012,A1
[3]Patent: WO2012/58780,2012,A1
[4]Patent: WO2012/58780,2012,A1
[5]Patent: WO2012/58780,2012,A1
[6]Patent: US2013/190512,2013,A1
[7]Patent: US2013/190512,2013,A1
[8]Patent: US2013/190512,2013,A1
[9]Patent: US2013/190512,2013,A1
[10]Patent: US2013/190512,2013,A1
[11]Patent: US2013/190512,2013,A1

25
[ 97-67-6 ]
[ 1374685-40-1 ]
[ 356068-86-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 5-fluoro-1-(trimethylsilyl)-2-(trimethylsilyloxy)-1H-indole; N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide In acetonitrile for 13h; Reflux; Stage #2: (S)-Malic acid In methanol; acetonitrile at 20℃; for 22h;	11 13 (3.0 g), MeCN (35 mL) and TMSOTf (0.38 mL, 0.2 eq.) were charged into a flask with a mechanical stirrer and a thermometer at ambient temperature. The heterogeneous mixture was heated to reflux, 20 (prepared as in example 5; 1.0 eq.) in MeCN (35 mL) was dropped at reflux over 1 h, and the reaction mixture was further stirred at reflux over period of 12 h. The mixture was cooled down to r.t., malic acid (3.03 g, 2.0 eq.) in MeOH (23 mL) was added into above reaction mixture. The reaction mixture turned clear. After 2 h, some solid appeared; after 22 h, filtered, washed with MeOH (10 ml). Filter cake was dried in vacuo to give 4.2 g of crude sunitinib malate with 97.3% purity by HPLC analysis in 70.0% yield
	Stage #1: 5-fluoro-1-(trimethylsilyl)-2-(trimethylsilyloxy)-1H-indole; N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide With trimethylsilyl trifluoromethanesulfonate In acetonitrile for 13h; Reflux; Stage #2: (S)-Malic acid In methanol for 24h;	11 Example 11 Direct Isolation of Sunitinib Malate From Coupling Reaction 13 (3.0 g), MeCN (35 mL) and TMSOTf (0.38 mL, 0.2 eq.) were charged into a flask with a mechanical stirrer and a thermometer at ambient temperature. The heterogeneous mixture was heated to reflux, 20 (prepared as in example 5; 1.0 eq.) in MeCN (35 mL) was dropped at reflux over 1 h, and the reaction mixture was further stirred at reflux over period of 12 h. The mixture was cooled down to r.t., malic acid (3.03 g, 2.0 eq.) in MeOH (23 mL) was added into above reaction mixture. The reaction mixture turned clear. After 2 h, some solid appeared; after 22 h, filtered, washed with MeOH (10 ml). Filter cake was dried in vacuo to give 4.2 g of crude sunitinib malate with 97.3% purity by HPLC analysis in 70.0% yield.
	Stage #1: 5-fluoro-1-(trimethylsilyl)-2-(trimethylsilyloxy)-1H-indole; N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide With trimethylsilyl trifluoromethanesulfonate In acetonitrile for 9.5h; Reflux; Stage #2: (S)-Malic acid In methanol for 24h;	12 Example 12 Direct Isolation of Sunitinib as a MsOH, Tartaric Acid, Frifluoroacetic Acid, CSA, AcOH, BzOH, HCl, or HBr Salt From the Coupling Reaction 13 (5.3 g), MeCN (60 mL) and TMSOTf (1.01 mL, 0.3 eq.) were charged into a flask with a mechanical stirrer and a thermometer at ambient temperature. The heterogeneous mixture was heated to reflux, 20 (prepared as in example 5; 1.0 eq.) in MeCN (60 mL) was dropped at reflux over 1.5 h, and the reaction mixture was further stirred at reflux over period of 8 h. The mixture was divided up and treated as follows: A 40 mL sample from a similar reaction as above was concentrated under vacuum and MeOH (70 mL) and malic acid (1.59 g, 2 eq.) were added at r.t. The reaction mixture turned clear soon. After 24 h the mixture was concentrated, and n-BuOH (30 mL) was added, and after 16 h the mixture was filtered. The filter cake was washed with MeOH and dried in vacuo to give 2.29 g of crude sunitinib malate with 98.9% purity by HPLC analysis in 71.8% yield.

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1 Location in patent: Page/Page column 30
[2]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1 Location in patent: Paragraph 0072
[3]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1 Location in patent: Paragraph 0073; 0081

26
[ 356068-93-4 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h 1.2: 25 °C 2.1: N,N-dimethyl-formamide / 25 °C 3.1: methanol / 8 h / 25 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 25 °C 1.2: 1 h / 40 °C 2.1: acetonitrile; N,N-dimethyl-formamide / 1 h / 25 °C 3.1: methanol / 0.5 h / 20 °C / Inert atmosphere 3.2: 25 °C
	Multi-step reaction with 2 steps 1.1: p-toluenesulfonyl chloride / N,N-dimethyl-formamide / 0.25 h / 15 - 19 °C 1.2: 15 - 19 °C 1.3: 0.67 h / 13 - 16 °C 2.1: methanol / 25 - 30 °C

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1
[2]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1
[3]Current Patent Assignee: LAURUS LABS LIMITED - US2015/25252, 2015, A1

27
[ 452105-55-4 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 25 °C 2: methanol / 8 h / 25 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: acetonitrile; N,N-dimethyl-formamide / 1 h / 25 °C 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 25 °C

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1
[2]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1

28
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidine)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, hydrochloride [ No CAS ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / water / 90 °C / pH 8 - 9 2: methanol / 8 h / 25 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1

29
sunitinib mesylate [ No CAS ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / water / 80 °C / pH 8 - 9 2: methanol / 8 h / 25 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1

30
[ 1374685-40-1 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: trimethylsilyl trifluoromethanesulfonate / N,N-dimethyl-formamide; acetonitrile / Reflux 2: methanol / 8 h / 25 °C / Inert atmosphere
	Multi-step reaction with 4 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / trifluorormethanesulfonic acid / acetonitrile / 48 h / 20 - 65 °C 2.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.17 h 2.2: 25 °C 3.1: N,N-dimethyl-formamide / 25 °C 4.1: methanol / 8 h / 25 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1.1: trimethylsilyl trifluoromethanesulfonate / acetonitrile; N,N-dimethyl-formamide / Reflux 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 25 °C

	Multi-step reaction with 3 steps 1.1: trimethylsilyl trifluoromethanesulfonate / acetonitrile / 9.5 h / Reflux 1.2: 15 h 2.1: water / 80 °C 3.1: methanol / 0.5 h / 20 °C / Inert atmosphere 3.2: 25 °C
	Multi-step reaction with 3 steps 1.1: trimethylsilyl trifluoromethanesulfonate / acetonitrile / 9.5 h / Reflux 1.2: 20 h 2.1: water / 90 °C 3.1: methanol / 0.5 h / 20 °C / Inert atmosphere 3.2: 25 °C
	Multi-step reaction with 4 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / acetonitrile / 0.25 h 2.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 25 °C 2.2: 1 h / 40 °C 3.1: acetonitrile; N,N-dimethyl-formamide / 1 h / 25 °C 4.1: methanol / 0.5 h / 20 °C / Inert atmosphere 4.2: 25 °C

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1
[2]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - WO2012/58780, 2012, A1
[3]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1
[4]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1
[5]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1
[6]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1

31
[ 1327155-72-5 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: water / 90 °C 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 25 °C

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1

32
[ 1275588-72-1 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: water / 80 °C 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 25 °C

Reference： [1]Current Patent Assignee: SCINOPHARM TAIWAN, LTD. - US2013/190512, 2013, A1

33
[ 341031-54-7 ]
[ 557795-19-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In chloroform; water

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

34
[ 341031-54-7 ]
(S,Z)-3-((tert-butoxycarbonyl)amino)-4-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-5-fluoro-2-oxoindolin-1-yl)-4-oxobutyl isobutyrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 120 h / 20 °C

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

35
[ 341031-54-7 ]
C₃₁H₄₂FN₅O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 120 h / 20 °C 3: porcine liver esterase / aq. phosphate buffer / 36.6 °C / pH 7.4 / Enzymatic reaction
	Multi-step reaction with 3 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 120 h / 20 °C 3: porcine liver esterase / aq. phosphate buffer / 36.6 °C / pH 7.4 / Enzymatic reaction

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]
[2]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

36
[ 341031-54-7 ]
(S,Z)-tert-butyl 12-(((1-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-5-fluoro-2-oxoindolin-1-yl)-4-(isobutyryloxy)-1-oxobutan-2-yl)carbamoyl)oxy)dodecanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 48 h / 20 °C

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

37
[ 341031-54-7 ]
(S,Z)-pentafluorophenyl 12-(((1-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-5-fluoro-2-oxoindolin-1-yl)-4-(isobutyryloxy)-1-oxobutan-2-yl)carbamoyl)oxy)dodecanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 48 h / 20 °C 3: trifluoroacetic acid / chloroform / 3 h / 20 °C 4: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 22 h / 0 - 20 °C

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

38
[ 341031-54-7 ]
C₄₃H₆₂FN₅O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / chloroform; water 2: N,N-dimethyl-formamide / 48 h / 20 °C 3: trifluoroacetic acid / chloroform / 3 h / 20 °C

Reference： [1]Takahashi, Yuki; Shoji, Sunao; Morishige, Takuya; Katsumata, Aya; Tsurifune, Fumihiro; Tsutsumi, Mitsuhiro; Honda, Yoshiharu; Hasuda, Tomoyo; Hitotsuyanagi, Yukio; Terachi, Toshiro; Uchida, Toyoaki; Takeya, Koichi [Heterocycles, 2014, vol. 89, # 8, p. 1860 - 1876]

39
[ 590424-05-8 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: oxalyl dichloride / dichloromethane / 2.5 h / 0 - 10 °C / Inert atmosphere 1.2: 30 °C 2.1: potassium hydroxide / N,N-dimethyl-formamide / 3.5 h / 20 °C / Darkness; Inert atmosphere 3.1: methanol; ethanol / 2 h / 20 °C / Darkness

Reference： [1]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN106588888, 2017, A

40
[ 590424-04-7 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sulfuric acid / water; methanol / 3.5 h / 60 - 65 °C 2.1: oxalyl dichloride / dichloromethane / 2.5 h / 0 - 10 °C / Inert atmosphere 2.2: 30 °C 3.1: potassium hydroxide / N,N-dimethyl-formamide / 3.5 h / 20 °C / Darkness; Inert atmosphere 4.1: methanol; ethanol / 2 h / 20 °C / Darkness

Reference： [1]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN106588888, 2017, A

41
[ 590424-03-6 ]
[ 341031-54-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: zinc / methanol; acetic acid / 65 - 70 °C 2.1: sulfuric acid / water; methanol / 3.5 h / 60 - 65 °C 3.1: oxalyl dichloride / dichloromethane / 2.5 h / 0 - 10 °C / Inert atmosphere 3.2: 30 °C 4.1: potassium hydroxide / N,N-dimethyl-formamide / 3.5 h / 20 °C / Darkness; Inert atmosphere 5.1: methanol; ethanol / 2 h / 20 °C / Darkness

Reference： [1]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN106588888, 2017, A

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	341031-54-7	MDL No. :	MFCD08282795
Formula :	C₂₆H₃₃FN₄O₇	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LBWFXVZLPYTWQI-IPOVEDGCSA-N
M.W :	532.56	Pubchem ID :	6456015
Synonyms :	SU 11248 Malate;Sunitinib (malate);SU11248	Chemical Name :	(Z)-N-(2-(Diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysuccinate

Num. heavy atoms :	38
Num. arom. heavy atoms :	11
Fraction Csp3 :	0.38
Num. rotatable bonds :	11
Num. H-bond acceptors :	9.0
Num. H-bond donors :	6.0
Molar Refractivity :	142.35
TPSA :	172.06 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-10.24 cm/s

[ CAS No. 341031-54-7 ] {[proInfo.proName]}

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[ 341031-54-7 ] Synthesis Path-Downstream 1~41

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Log Po/w (iLOGP) :	3.4
Log Po/w (XLOGP3) :	-0.98
Log Po/w (WLOGP) :	1.98
Log Po/w (MLOGP) :	0.47
Log Po/w (SILICOS-IT) :	4.77
Consensus Log Po/w :	1.93

Lipinski :	3.0
Ghose :	None
Veber :	2.0
Egan :	1.0
Muegge :	2.0
Bioavailability Score :	0.11

Log S (ESOL) :	-2.01
Solubility :	5.17 mg/ml ; 0.00971 mol/l
Class :	Soluble
Log S (Ali) :	-2.15
Solubility :	3.79 mg/ml ; 0.00712 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-7.35
Solubility :	0.0000236 mg/ml ; 0.0000000443 mol/l
Class :	Poorly soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	4.64

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P201-P202-P260-P264-P270-P280-P308+P313-P405-P501	UN#:	2811
Hazard Statements:	H360-H372	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 341031-54-7 ] {[proInfo.proName]}

Quality Control of [ 341031-54-7 ]

Related Doc. of [ 341031-54-7 ]

Product Details of [ 341031-54-7 ]

Calculated chemistry of [ 341031-54-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 341031-54-7 ]

Application In Synthesis of [ 341031-54-7 ]

[ 341031-54-7 ] Synthesis Path-Downstream 1~41

Similar Product of [ 341031-54-7 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Similar Product of
[ 341031-54-7 ]