Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:17][CH:18]2[CH2:25][CH:21]3[CH2:22][NH:23][CH2:24][CH:20]3[CH2:19]2)=[N:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)=[N:6][CH:7]=1.CCN(CC)CC.[C:33](OC(=O)C)(=[O:35])[CH3:34]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:17][CH:18]2[CH2:25][CH:21]3[CH2:22][N:23]([C:33](=[O:35])[CH3:34])[CH2:24][CH:20]3[CH2:19]2)=[N:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:15][CH2:16]3)[NH:11][N:10]=2)=[N:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: Clc1cnc(Nc2cc(C3CC3)[nH]n2)nc1NC1CC2CNCC2C1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N1CC2CC(Nc3nc(Nc4cc(C5CC5)[nH]n4)ncc3Cl)CC2C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 45.7 %

Procedure:
To a solution of 5-chloro-N2-(5-cyclopropyl-1H-pyrazol-3-yl)-N4-(octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine (153.3 mg, 0.43 mmol) in DCM (10 mL) were added Et3N (82.3 mg, 0.81 mmol) and acetyl acetate (62.5 mg, 0.61 mmol). The reaction mixture was stirred at rt for 15 min, then quenched with H2O (30 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/50) to give the title compound as a beige solid (79.0 mg, 46.1%).
Reaction SMILES: [OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[CH3:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]3[O:25][CH:24]([CH:26]4[CH2:31][CH2:30][N:29]([C:32]#N)[CH2:28][CH2:27]4)[CH2:23][C:22]=3[CH:34]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH:4]([C:3]1[N:7]=[C:32]([N:29]2[CH2:28][CH2:27][CH:26]([CH:24]3[CH2:23][C:22]4[CH:34]=[C:18]([C:15]5[CH:16]=[CH:17][C:12]([S:9]([CH3:8])(=[O:11])=[O:10])=[CH:13][CH:14]=5)[CH:19]=[CH:20][C:21]=4[O:25]3)[CH2:31][CH2:30]2)[O:1][N:2]=1)([CH3:6])[CH3:5]
Reactant: CS(=O)(=O)c1ccc(-c2ccc3c(c2)CC(C2CCN(C#N)CC2)O3)cc1
Reactant: CC(C)C(=N)NO
Agent: [Cl-]
Agent: [Zn+2]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)c1noc(N2CCC(C3Cc4cc(-c5ccc(S(C)(=O)=O)cc5)ccc4O3)CC2)n1
Temperature: 50 °C
Reaction time: 4 h

Procedure:
A 0.5 M solution of zinc chloride in tetrahydrofuran (0.78 mL) is diluted with tetrahydrofuran (5 mL) and added dropwise at room temperature to a mixture of N-hydroxy-isobutyramidine (40 mg) and 4-[5-(4-methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carbonitrile (100 mg) in ethyl acetate (5 mL). The reaction mixture is stirred at 50° C. for 4 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 2 h in a mixture of ethanol (5 mL) and glacial acetic acid (2.5 mL). The solvents are evaporated and the residue is mixed with dichloromethane and 10% aqueous K2CO3 solution. The organic phase is washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is triturated with diethyl ether to give the title compound. LC (method 2): tR=1.12 min; Mass spectrum (ESI+): m/z=468 [M+H]+.
Reaction SMILES: [CH2:1]([CH:4]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:5][OH:6])[CH2:2][CH3:3].[OH:12][C:13]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=O>O>[O:6]([CH2:5][CH:4]([CH2:1][CH2:2][CH3:3])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[C:13]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:12]
Reactant: CCCCCC(CO)CCC
Reactant: CCCCCCCCCC(=O)O
Solvent: O
Product: CCCCCCCCCC(=O)OCC(CCC)CCCCC
Yield: 84.1 %

Procedure:
1108.0 g 2-propylheptanol (7 mol) and 1205.9 g capric acid (7 mol) were heated for 6 h to 220° C. on a water separator together with 0.27 g Fascat® 2001 (Sn oxalate: 0.1% by weight, based on the composition as a whole). After the separation of water had stopped, the crude product was distilled in an oil pump vacuum through a 250 mm Vigreux column (T=141-152° C.). 1840.1 g of a colorless oil were obtained: OHV=<0.08, AV=<0.18.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][CH2:8][CH2:9][CH2:10][C:11]1[N:15]([C:16]2[C:17]([CH3:25])=[C:18]([CH:22]=[CH:23][CH:24]=2)[C:19]([NH2:21])=O)[C:14]([C:26]2[CH:27]=[N:28][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:30][CH:31]=2)=[N:13][N:12]=1>>[CH3:6][O:7][CH2:8][CH2:9][CH2:10][C:11]1[N:15]([C:16]2[C:17]([CH3:25])=[C:18]([CH:22]=[CH:23][CH:24]=2)[C:19]#[N:21])[C:14]([C:26]2[CH:27]=[N:28][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:30][CH:31]=2)=[N:13][N:12]=1
Reactant: COCCCc1nnc(-c2ccc(-c3ccccc3)nc2)n1-c1cccc(C(N)=O)c1C
Solvent: O=P(Cl)(Cl)Cl
Product: COCCCc1nnc(-c2ccc(-c3ccccc3)nc2)n1-c1cccc(C#N)c1C
Temperature: 25 °C
Yield: 52.3 %

Procedure:
Phosphorus oxychloride (8 ml) was added to 3-[3-(3-methoxypropyl)-5-(6-phenylpyridin-3-yl)-1,2,4-triazol-4-yl]-2-methylbenzamide (770 mg) prepared in the Example 4, and refluxed under heating for 3 hours. After the reaction solution was cooled to ambient temperature, the solution was concentrated under reduced pressure. Chloroform was added to the resulting residue, which was then washed with saturated aqueous sodium hydrogen carbonate solution. Subsequently, the organic layer was dried over anhydrous magnesium sulfate. After the solvent was evaporated under reduced pressure, the resulting solid was recrystallized from ethyl acetate, to afford the entitled compound as white crystal (386 mg, 52%). The physico-chemical values are as follows.
Reaction SMILES: C(OC([NH:8][CH:9]1[C:35](=[O:36])[N:11]2[C:12]([C:19]([O:21][CH:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])=[C:13](/[CH:16]=[CH:17]/[Cl:18])[CH2:14][S:15][C@H:10]12)=O)(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl-].[Na+].C(=O)(O)[O-].[Na+]>C(#N)C>[NH2:8][CH:9]1[C:35](=[O:36])[N:11]2[C:12]([C:19]([O:21][CH:22]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])=[C:13](/[CH:16]=[CH:17]/[Cl:18])[CH2:14][S:15][C@H:10]12
Reactant: CC(C)(C)OC(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(/C=C/Cl)CS[C@H]12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: O
Solvent: CC#N
Product: NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(/C=C/Cl)CS[C@H]12
Temperature: 35 °C
Reaction time: 0.83 h
Yield: 61.7 %

Procedure:
To a solution of benzhydryl 7-t-butoxycarbonylamino-3-[(E)-2-chlorovinyl]-3-cephem-4-carboxylate (5.0 g) in acetonitrile (50 ml) was added p-toluenesulfonic acid monohydrate (3.23 g). After stirring at 35° C. for 50 minutes, the mixture was poured into a saturated aqueous solution of sodium chloride, adjusted to pH 7.5 with 5% aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue as triturated with n-hexane to give benzhydryl 7-amino-3-[(E)-2-chlorovinyl]-3-cephem-4-carboxylate (2.50 g)
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22](Cl)[CH:21]=3)[C:12]2=[O:27])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N:28]1([CH2:33][C:34]2[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=2)[CH2:32][CH2:31][CH2:30][CH2:29]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:38][C:37]4[CH:36]=[CH:35][C:34]([CH2:33][N:28]5[CH2:32][CH2:31][CH2:30][CH2:29]5)=[CH:40][CH:39]=4)[CH:21]=3)[C:12]2=[O:27])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Nc1ccc(CN2CCCC2)cc1
Reactant: CC(C)(C)c1ccc(N2C(=O)N(Cc3ccnc(Cl)c3)C(C)(C)C2=O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC1(C)c2ccc(P(c3ccccc3)c3ccccc3)cc2Oc2cc(P(c3ccccc3)c3ccccc3)ccc21
Solvent: C1COCCO1
Product: CC(C)(C)c1ccc(N2C(=O)N(Cc3ccnc(Nc4ccc(CN5CCCC5)cc4)c3)C(C)(C)C2=O)cc1
Temperature: 90 °C
Yield: 5.7 %

Procedure:
To a solution of 1.15 g of 3-(4-tert-butylphenyl)-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) of Example 7 in 50 mL of dioxane are successively added, under argon, 520 mg of 4-(pyrrolidin-1-ylmethyl)aniline obtained in stage c) below, 3.4 g of caesium carbonate, 207 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) [xantphos] and 67 mg of palladium diacetate. The reaction mixture is heated at 90° C. for 6 hours, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (90/10 by volume) to give 88 mg of 3-(4-tert-butylphenyl)-5,5-dimethyl-1-[(2-{[4-(pyrrolidin-1-ylmethyl)phenyl]amino}pyridin-4-yl)methyl]imidazolidine-2,4-dione, the characteristics of which are as follows:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C=O.P(Cl)(Cl)([Cl:30])=O>O>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:30])=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=[N+]([O-])c1cnc2cc(OCc3ccccc3)ccc2c1O
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1cnc2cc(OCc3ccccc3)ccc2c1Cl
Temperature: 100 °C

Procedure:
A 2-liter round bottom flask was charged with 7-(benzyloxy)-3-nitroquinolin-4-ol (100.0 g, 0.3 mol) and N,N-dimethylformamide (DMF) (650 mL). Phosphorous oxychloride (62.1 g, 37.7 mL, 1.2 equivalents (eq)) was slowly added dropwise. The resulting mixture was heated at 100° C. for 10 minutes, and then allowed to cool to 39° C. The reaction mixture was poured over ice (3 L). A brown precipitate formed. The mixture was diluted with water (1 L) and stirred to break up the precipitate. The precipitate was collected by vacuum filtration. The filter cake was washed with water (2 L) and air-dried on vacuum filter for 1 hour. The solid was dissolved in dichloromethane and placed in a separatory funnel. The water was removed, and the dichloromethane solution was dried over magnesium sulfate. The solution was then filtered through filter agent to provide a solution of 7-(benzyloxy)-4-chloro-3-nitroquinoline in dichloromethane (approximately 1700 mL).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]=[C:5]([OH:33])[C:6]1[C:7](=[C:11](Cl)[C:12]([S:24][C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)=[C:13]([S:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:14]=1Cl)[C:8]([OH:10])=[O:9].[CH2:34]([SH:44])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[OH:1][CH2:2][CH2:3][N:4]=[C:5]([OH:33])[C:6]1[C:7](=[C:11]([S:44][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[C:12]([S:24][C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)=[C:13]([S:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:14]=1[S:44][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[C:8]([OH:10])=[O:9]
Reactant: CCCCCCCCCCS
Reactant: Cc1ccc(Sc2c(Cl)c(C(=O)O)c(C(O)=NCCO)c(Cl)c2Sc2ccc(C)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCSc1c(Sc2ccc(C)cc2)c(Sc2ccc(C)cc2)c(SCCCCCCCCCC)c(C(O)=NCCO)c1C(=O)O

Procedure:
2 g (3.95 millimols) of 4,5-bis-(p-tolylthio)-3,6-dichlorophthalic acid N-2-hydroxyethylimide, 1,51 g (8.69 millimols) of n-decane-1-thiol, 2.29 g (16.58 millimols) of potassium carbonate and 20 ml of N,N-dimethylformamide are stirred at 25° C. for 1 hour. After concentration, the residue is taken up in methylene chloride/dilute HCl solution. The extracts are dried over sodium sulfate and evaporated. After precipitation from n-hexane, 300 mg (10% of theory) of the title compound (waxy substance) are obtained.
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]([C:6]1[CH:31]=[CH:30][CH:29]=[CH:28][C:7]=1[CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:5].[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH:38]=O)=[CH:36][CH:35]=1.C1CN2C(=NCCC2)C1>C(#N)C>[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH:38]=[CH:8][C:7]2[CH:28]=[CH:29][CH:30]=[CH:31][C:6]=2[C:4]([O:3][CH3:2])=[O:5])=[CH:36][CH:35]=1
Reactant: COC(=O)c1ccccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COc1ccc(C=O)cc1
Agent: C1CN=C2CCCN2C1
Agent: [Br-]
Solvent: CC#N
Product: COC(=O)c1ccccc1C=Cc1ccc(OC)cc1

Procedure:
In 50 ml of acetonitrile were dissolved 4.91 g (10 mmol) of 2-methoxycarbonylbenzyltriphenylphosphonium bromide and 1.77 g (13 mmol) of 4-methoxybenzaldehyde, and 2.48 g (20 mmol) of 1,5-diazabicyclo[4.3.0]-5-nonene was added to the solution and the mixture was refluxed for 5 hours.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:4][C:5]([N:18]2[CH:22]=[N:21][N:20]=[N:19]2)=[C:6]([C:13](OCC)=[O:14])[C:7]=1[C:8](OCC)=[O:9].O.[NH2:30][NH2:31]>C(O)C>[NH2:1][C:2]1[C:7]2[C:8](=[O:9])[NH:31][NH:30][C:13](=[O:14])[C:6]=2[C:5]([N:18]2[CH:22]=[N:21][N:20]=[N:19]2)=[N:4][C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CCOC(=O)c1c(-n2cnnn2)nc(-c2ccccc2)c(N)c1C(=O)OCC
Reactant: NN
Solvent: CCO
Solvent: O
Product: Nc1c(-c2ccccc2)nc(-n2cnnn2)c2c(=O)[nH][nH]c(=O)c12

Procedure:
In 2 ml of ethanol was dissolved 0.172 g of 3-amino-4,5-diethoxycarbonyl-2-phenyl-6-(tetrazol-1-yl)pyridine, whereto 1 ml of hydrazine monohydrate was added. The mixture was reacted at 90° C. for 2 hours. After 15 ml of ethanol was added, the mixture was cooled. The precipitate was collected by filtration and washed with ethanol. The thus-obtained precipitate was dissolved in 20 ml of hot water, and 0.7 ml of acetic acid was added. The mixture was cooled, and the resulting precipitate was collected by filtration, washed and dried, to give 0.11 g of the title compound as yellow crystals.
Reaction SMILES: [N+:1]([C:4]1[CH:26]=[CH:25][C:7]2[C:8](=[O:24])[N:9]([C@@H:11]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:10][C:6]=2[CH:5]=1)([O-])=O>C(O)(=O)C.[Fe]>[NH2:1][C:4]1[CH:26]=[CH:25][C:7]2[C:8](=[O:24])[N:9]([C@@H:11]([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[S:10][C:6]=2[CH:5]=1
Reactant: CCOC(=O)CC[C@@H](C(=O)OCC)n1sc2cc([N+](=O)[O-])ccc2c1=O
Agent: [Fe]
Solvent: CC(=O)O
Product: CCOC(=O)CC[C@@H](C(=O)OCC)n1sc2cc(N)ccc2c1=O
Temperature: 55 °C
Reaction time: 1 h
Yield: 93.6 %

Procedure:
A solution of diethyl (S)-2-(2,3-dihydro-6-nitro-3-oxo-1,2-benzisothiazol-2-yl)glutarate (4.0 g, 10 mmol) and suspended iron (1.0 g, 18 mmol) in acetic acid (100 ml) was stirred under nitrogen for 1 hour at 55° C. Additional iron (3×0.25 g, 13 mmol) was added at intervals of 1, 1.25, and 1.75 hours. The reaction mixture was stirred 30 minutes after the last addition, filtered, concentrated in vacuo, and the residue absorbed onto silica gel (20 g) from a methylene chloride solution. Purification by chromatography on silica gel (150 g) eluting with ethyl acetate:hexane (1:1→2:1) gave diethyl (S)-2-(6-amino-2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl)glutarate (3.3 g) as an oil. 1H NMR (DMSO-d6, 300 MHz) δ: 1.15 (t, J=7 Hz, 3H, ester CH3), 1.17 (t, J=7 Hz, 3H, ester CH3 ), 1.95-2.38 (m, 4H, glu CH2CH2), 4.02 (q, J=7 Hz, 2H, ester CH2), 4.13 (q, J=7 Hz, 2H, ester CH2), 5.08-5.15 (m, 1H, glu CH), 6.09 (br s, 2H, NH2), 6.62 (dd, J=9,2 Hz, 1H, Ar), 6.84 (d, J=2 Hz, 1H, Ar), 7.50 (d, J=9 Hz, 1H, Ar). Mass spectrum (CI-CH4): 353 (M+1, 100%). Anal. Calculated for C16H20N2O5S: C, 54.53; H, 5.72; N, 7.95; S, 9.10. Found: C, 54.34; H, 5.73; N, 7.87; S, 9.00.
Reaction SMILES: [C:1]1([C:7]2([CH2:12][OH:13])[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>ClCCl>[C:1]1([C:7]2([CH2:12][O:13][S:22]([CH3:21])(=[O:24])=[O:23])[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCC1(c2ccccc2)CCCC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCC1(c2ccccc2)CCCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.9 %

Procedure:
To a stirred solution of 1-phenyl-cyclopentyl)-methanol (23-01) (9.1 gm, 51.70 mmol) in dichloromethane (100 mL) was added triethyl amine (14.4 mL, 104.96 mmol) followed by methanesulfonyl chloride (5.09 ml, 62.045 mmol) at cooling condition, it was stirred at room temperature for 16 h. After completion of the reaction, the mixture was diluted with dichloromethane, washed with water, sodium bicarbonate solution and brine. The separated organic part was dried over sodium sulfate and evaporated under reduced pressure to get methanesulfonic acid 1-phenyl-cyclopentylmethyl ester (24-01) (13 g) as a crude product.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[C:14]([O:16][CH3:17])[CH:15]=2)[NH:12][C:11](=[O:18])[C:10]23OCC[O:19]2)=[C:5]([CH3:23])[O:4][N:3]=1.C(O)(=O)C.Cl>CCOC(C)=O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[C:14]([O:16][CH3:17])[CH:15]=2)[NH:12][C:11](=[O:18])[C:10]3=[O:19])=[C:5]([CH3:23])[O:4][N:3]=1
Reactant: COc1cc(-c2c(C)noc2C)cc2c1NC(=O)C21OCCO1
Agent: Cl
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: COc1cc(-c2c(C)noc2C)cc2c1NC(=O)C2=O
Reaction time: 1.5 h

Procedure:
A solution of compound 5′-(3,5-dimethylisoxazol-4-yl)-7′-methoxyspiro[[1,3]dioxolane-2,3′-indolin]-2′-one (57 mg, 0.18 mmol), acetic acid (1 mL), and hydrogen chloride solution (4 mL) was heated to 90° C. After 1.5 h, the mixture was cooled, EtOAc (20 mL) was added, washed with brine (15 mL×3), dried over Na2SO4, concentrated in vacuo to give the expected compound 5-(3,5-dimethylisoxazol-4-yl)-7-methoxyindoline-2,3-dione as a dark red solid (50 mg, crude, 102%). This material was used in the next step without further purification. MS (ESI) m/e [M+1]+ 273.
Reaction SMILES: F[C:2]1[CH:3]=[CH:4][C:5]([N+:14]([O-:16])=[O:15])=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:7]=1.[CH3:17][NH2:18]>CO>[CH3:17][NH:18][C:2]1[CH:3]=[CH:4][C:5]([N+:14]([O-:16])=[O:15])=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:7]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1N1CCCCC1
Reactant: CN
Solvent: CO
Product: CNc1ccc([N+](=O)[O-])c(N2CCCCC2)c1
Yield: 100 %

Procedure:
A solution of 1-(5-fluoro-2-nitro-phenyl)-piperidine (200 mg, 0.89 mmol, as prepared in Example 5, step (a)) in 4 mL of 2M methylamine in MeOH was heated in a sealed tube for 12 h at 80° C. solvent under vacuum afforded methyl-(4-nitro-3-piperidin-1-yl-phenyl)-amine (209 mg, 100%). Mass spectrum (ESI, m/z): Calcd. for C12H17N3O2, 236.1 (M+H), found 236.1.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[NH:7][CH2:6][C:5]=12.[CH:15]1[C:27]2[CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]=2[CH:18]=[CH:17][C:16]=1[C:28](Cl)=[O:29].C1C2CC3C(=CC=CC=3)C=2C=CC=1C(O)=O.S(Cl)(Cl)=O.CN(C)C1C=CC=CC=1>O1CCOCC1.O>[CH:15]1[C:27]2[CH2:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]=2[CH:18]=[CH:17][C:16]=1[C:28]([N:7]1[C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[CH2:10][N:4]2[CH:3]=[CH:2][CH:1]=[C:5]2[CH2:6]1)=[O:29]
Reactant: O=C(Cl)c1ccc2c(c1)Cc1ccccc1-2
Reactant: c1ccc2c(c1)Cn1cccc1CN2
Agent: O=C(O)c1ccc2c(c1)Cc1ccccc1-2
Solvent: O=S(Cl)Cl
Solvent: C1COCCO1
Solvent: CN(C)c1ccccc1
Product: O=C(c1ccc2c(c1)Cc1ccccc1-2)N1Cc2cccn2Cc2ccccc21
Reaction time: 2 h
Yield: 95.4 %

Procedure:
A solution containing 1.84 g (0.01 mol) of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine, 2.28 g (0.01 mol) of 9H-fluorene-2-carbonyl chloride (generated via the reaction of 9H-fluorene-2-carboxylic acid and thionyl chloride) and 1.21 g (0.01 mol) of N,N-dimethylaniline in 125 mL of 1,4-dioxane was allowed to stand at room temperature for two hours. The reaction mixture was poured into 1 L of water, the precipitate was collected, washed with water and dried to provide the title compound (3.59 g). The material was recrystallized from acetone, m.p. 202-204° C.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:15]=[C:16]([S:20](Cl)(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=3)[N:9]=2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[CH:3]=1.[NH:34]1[CH2:39][CH2:38][S:37](=[O:41])(=[O:40])[CH2:36][CH2:35]1.CCN(CC)CC>C1COCC1.CCOC(C)=O>[O:40]=[S:37]1(=[O:41])[CH2:38][CH2:39][N:34]([S:20]([C:16]2[CH:15]=[C:14]([C:10]3[N:9]=[C:8]([C:6]4[CH:5]=[C:4]([C:24]5[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:26][CH:25]=5)[CH:3]=[C:2]([CH3:1])[N:7]=4)[CH:13]=[CH:12][CH:11]=3)[CH:19]=[CH:18][CH:17]=2)(=[O:22])=[O:21])[CH2:35][CH2:36]1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(=O)(=O)Cl)c3)n2)n1
Reactant: O=S1(=O)CCNCC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(=O)(=O)N4CCS(=O)(=O)CC4)c3)n2)n1
Yield: 47.2 %

Procedure:
The title compound was prepared from 3-[6′-methyl-4′-(4-trifluoromethyl-phenyl)-[2,2′]bipyridinyl-6-yl]-benzenesulfonyl chloride (example I.2) (0.300 g, 0.613 mmol) by treatment with commercially available thiomorpholine-1,1-dioxide (0.166 g, 1.226 mmol) and Et3N (0.260 mL, 1.84 mmol) in THF (5 mL) at 23° C. for 16 h. Diluted with EtOAc, washed with 5% citric acid, sat. NaHCO3-sol. and brine, dried organic layer over Na2SO4. Removal of the solvent in vacuum left a crude product, which was purified by silica gel column chromatography with EtOAc followed by trituration with diethyl ether/heptane to give the title compound (0.170 g, 47%) as a white solid. MS (ISP) 588.1 [(M+H)+]; mp 230° C. (dec.).
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:12]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([OH:60])=O)(=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].C(N(CC)CC)C.[OH:68][CH2:69][C@@H:70]([C@@H:72]([C@@H:74]([CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[OH:75])[OH:73])[NH2:71]>C(Cl)Cl>[C:12]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][C:58]([NH:71][C@H:70]([C@@H:72]([C@@H:74]([CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[OH:75])[OH:73])[CH2:69][OH:68])=[O:60])(=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO
Reactant: CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)[C@H](O)CCCCCCCCCCCCCC
Temperature: 30 °C
Reaction time: 2.42 h
Yield: 75.1 %

Procedure:
p-Toluenesulphonic acid (13.55 g; 71.1 mmoles) was added to a refluxing solution of 27-stearoyloxyheptacosanoic acid (53.45 g; about 77.1 mmoles) and triethylamine (100 ml) in methylene chloride (2 l; free of alcohol) under nitrogen. After refluxing for 1 hour phytosphingosine (18.6 g; purity 94%; 55 mmoles) was added and refluxing was continued for 145 minutes. After cooling the reaction mixture to 30° C. the precipitate was filtered off and washed with methylene chloride (1 l). This solid was dissolved in hot, ethanol-free ##STR10## chloroform and filtered off while warm. The filtrate was allowed to cool. The precipitate formed was filtered off, washed with chloroform (250 ml) and acetone (2×200 ml) and dried in vacuo affording 41 g of the title product.