Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[CH2:14][NH2:15]>>[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[CH2:14][NH:15][CH:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1
Reactant: CN1CCC(=O)CC1
Reactant: NCc1cccs1
Product: CN1CCC(NCc2cccs2)CC1

Procedure:
1-Methyl-4-piperidone (0.5 g, 4.4 mmol, 1.0 eq.), 2-thienylmethylamine (0.52 g, 1.0 eq.).
Reaction SMILES: Cl.[O:2]([NH2:4])[CH3:3].C([O-])(=O)C.[Na+].[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[Cl:19])[CH:14]=O.C([BH3-])#N.[Na+].[OH-].[Na+]>O.C1COCC1.C(OCC)C.C(O)(=O)C>[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[Cl:19])[CH2:14][NH:4][O:2][CH3:3]
Reactant: CON
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [BH3-]C#N
Solvent: O
Solvent: CCOCC
Solvent: CC(=O)O
Product: CONCc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To methoxylamine hydrochloride (20 g, 0.24 mol) in water (200 mL) and THF (74 mL) was added sodium acetate (16.3 g, 0.2 mol) followed by 3,4-dichlorobenzaldehyde (25 g, 0.14 mol). The mixture was stirred at room temp for 6 h and diluted with diethyl ether. The aqueous phase was extracted with ethyl acetate, dried (sodium sulfate) and concentrated to give a colorless oil. The oil was dissolved in glacial acetic acid (200 mL) and cooled to 0° C. Sodium cyanoborohydride (18.8 g, 0.26 mol) was added over 30 min. The mixture was stirred at room temp for 4 days, cooled to 0° C. and made basic with 10 N NaOH. The mixture was extracted with EtOAc (3×'s) and the combined organic extracts were washed with water and brine and concentrated to give an oil that solidifies upon standing. This residue was stirred in diethyl ether and the resulting title compound was filtered as a white solid (9.61 g, 33% yield). 1HNMR (300 MHz, DMSO) δ: 10.12 (1H, bs), 7.74 (1H, s), 7.67 (1H, d, J=8.42 Hz), 7.44 (1H, d, J=8.05 Hz), 4.21 (2H, s), 3.59 (3H, s).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]2[N:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:18]([O:20]CC)=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>C(O)C>[C:1]1([CH2:7][CH2:8][C:9]2[N:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:18]([OH:20])=[O:19])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1nc2ccccn2c1CCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1nc2ccccn2c1CCc1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 128.9 %

Procedure:
Ethyl 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylate (883 mg) was dissolved in ethanol (50 ml), 2N aqueous sodium hydroxide solution (3 ml) was added, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, neutralized with 1N hydrochloric acid, subjected to DIAION HP-20 (manufactured by Mitsubishi Chemical), and washed with water. The fraction eluted with acetone was concentrated under reduced pressure to give 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (1.03 g). The obtained 3-(2-phenylethyl)imidazo[1,2-a]pyridine-2-carboxylic acid (341 mg), tert-butyl(3S, 5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (370 mg) and N,N-diisopropylethylamine (862 μl) were dissolved in acetonitrile (20 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (561 mg) was added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated, and the residue was diluted with aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (9:1) was concentrated under reduced pressure to give the object product (522 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:40]=[CH:39][C:7]([C:8]([O:10][C@H:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C@@H:12]2[NH:20][C:21]2[C:26]([CH2:27][CH3:28])=[N:25][C:24]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[Cl:36])=[C:23]([CH2:37][CH3:38])[N:22]=2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(C1C(N[C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=NC(CC)=CN=1)C>>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][C@@H:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C@H:12]2[NH:20][C:21]2[C:26]([CH2:27][CH3:28])=[N:25][C:24]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[Cl:36])=[C:23]([CH2:37][CH3:38])[N:22]=2)=[O:9])=[CH:39][CH:40]=1)([O-:3])=[O:2]
Reactant: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@H]1c2ccccc2C[C@@H]1OC(=O)c1ccc([N+](=O)[O-])cc1
Agent: CCc1cnc(CC)c(N[C@@H]2c3ccccc3C[C@@H]2O)n1
Product: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@H]1OC(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
Following the procedure for the preparation of (1S,2S)-1-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-yl 4-nitrobenzoate but substituting (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol and making non-critical variations provided the title compound as a yellow solid. IR (diffuse reflectance) 1725, 1568, 1550, 1527, 1498, 1467, 1392, 1372, 1349, 1320, 1273, 1119, 1103, 1014, 719 cm−1; OAMS supporting ions at: ESI+ 577.1; MS (CI) m/z 577 (MH+); HRMS (FAB) calcd for C30H26CL2N4O4+H1 577.1409, found 577.1393; [α]25D=−118 (c 0.62, methylene chloride).
Reaction SMILES: [NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].C[Si](N[Si](C)(C)C)(C)C.C(O[C@@H:22]1[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:54])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C@@H:33]([O:34][C:35](=[O:42])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@H:23]1[O:24][C:25](=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=O)C>C(#N)C>[C:25]([O:24][C@@H:23]1[C@H:33]([O:34][C:35](=[O:42])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@@H:43]([CH2:45][O:46][C:47](=[O:54])[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[O:44][C@H:22]1[N:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=c1cc[nH]c(=O)[nH]1
Reactant: CC(=O)O[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Solvent: CC#N
Product: O=C(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Yield: 58 %

Procedure:
0.56 g. (5 mmol) of uracil was agitated in 70 ml. of absolute acetonitrile with 1.86 g. (3.5 mmol) of HMDS and 2.55 g. (15.5 mmol) of TCS, as well as 1.69 g. (12 mmol) of NaClO4.H2O for 30 minutes at 24° C. The reaction mixture was then combined with 2.52 g. (5 mmol) of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose and refluxed for 20 hours. The mixture was worked up as described in Example 1, yielding 58% of crystalline uridine tribenzoate.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:4]([CH2:13][NH2:14])=[N:5][CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)CC)C.[C:22]1([CH3:33])[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][CH2:29][C:30](Cl)=[O:31]>O1CCCC1>[Cl:2][C:3]1[C:4]([CH2:13][NH:14][C:30](=[O:31])[CH2:29][CH2:28][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[CH3:33])=[N:5][CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1
Reactant: Cc1ccccc1CCC(=O)Cl
Reactant: NCc1ncc(C(F)(F)F)cc1Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccccc1CCC(=O)NCc1ncc(C(F)(F)F)cc1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of (3-chloro-5-trifluoromethyl-2-pyridyl)methylamine hydrochloride (1 mmol, 0.247 g) in tetrahydrofuran (5 ml) was added triethylamine (2 mmol, 0.202 g) at room temperature and the mixture was stirred at room temperature for 1 hour. The mixture was filtered and the filtrate added to a solution of 3-(2-tolyl)propionyl chloride (1.1 mmol, 0.2 g) in tetrahydrofuran (5 ml) at room temperature. After 4 hours stirring at room temperature the solvent was evaporated and the residue washed with water. The solid was filtered and washed with diethyl ether/light petroleum (1:20) to give the title product, m.p. 152-3° C.
Reaction SMILES: [CH2:1]([C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH:7]=[CH2:8])[CH:2]([CH3:4])[CH3:3]>[Pd]>[CH2:1]([C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7][CH3:8])[CH:2]([CH3:4])[CH3:3]
Reactant: C=Cc1ccccc1CC(C)C
Agent: [Pd]
Product: CCc1ccccc1CC(C)C
Yield: 99.8 %

Procedure:
In a 1-liter autoclave equipped with a stirrer were placed 35.8 g of a 10% palladium black catalyst and all of the above-mentioned crude o-isobutylstyrene, and hydrogenation was carried out at a reaction temperature of 50° C. under a hydrogen pressure of 20 kg/cm2. After hydrogen had not been absorbed any more, the used catalyst was removed from the reaction mixture by filtration, followed by distillation, thereby obtaining 642 g of o-isobutylethylbenzene having 99.8% purity.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([CH3:18])[C:12]([C:19]([O:21]C)=[O:20])=[CH:11]3)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>O1CCCC1CCO>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([CH3:18])[C:12]([C:19]([OH:21])=[O:20])=[CH:11]3)=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc2cc(-c3ccc(C)cc3)ccc2nc1C
Agent: Cl
Agent: OCCC1CCCO1
Agent: [Na+]
Product: Cc1ccc(-c2ccc3nc(C)c(C(=O)O)cc3c2)cc1
Reaction time: 48 h
Yield: 68.8 %

Procedure:
To a solution of methyl 6-(4-methylphenyl)-2-methylquinoline-3-carboxylate (0.99 g) in tetrahydrofuranethanol (5-5 ml) was added 2N sodium hydroxide (2 ml) at room temperature, and the mixture was stirred for 2 days. To the reaction mixture was added 1N hydrochloric acid (4 ml), and the mixture was concentrated under reduced pressure to precipitate crystals, which were collected by filtration and washed with ethanol and diethylether to give 6-(4-methylphenyl)-2-methylquinoline-3-carboxylic acid (648 mg) as colorless crystals.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:28]([O:29]C(=O)C)[C@H:27]([O:33]C(=O)C)[C@@H:26]([CH2:37][O:38]C(=O)C)[O:25][C@H:6]1[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([O:23]C)=[O:22])=[CH:17][CH:16]=1)(=O)C.[OH-].[Na+]>CO>[O:7]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17][CH:16]=1)[C@@H:6]1[O:25][C@H:26]([CH2:37][OH:38])[C@@H:27]([OH:33])[C@H:28]([OH:29])[C@H:5]1[OH:4]
Reactant: COC(=O)c1ccc(Cc2ccccc2O[C@@H]2O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]2OC(C)=O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1ccc(Cc2ccccc2O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 111.5 %

Procedure:
To a solution of 2-[4-(methoxycarbonyl)benzyl]phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (0.050 g) in methanol (1 mL) was added 2 mol/L aqueous sodium hydroxide solution (0.26 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was purified by column chromatography on benzenesulfonylpropyl silica gel (eluent: methanol) to give 2-(4-carboxybenzyl)phenyl β-D-gluco-pyranoside (0.038 g).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](O)=[O:24])=[CH:18][CH:17]=1)#[N:2].C(OC([N:33]([CH2:37][C:38]1[CH:39]=[C:40]([CH:42]=[C:43]([CH3:45])[CH:44]=1)[NH2:41])[CH:34]1[CH2:36][CH2:35]1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[CH:34]1([NH:33][CH2:37][C:38]2[CH:39]=[C:40]([NH:41][C:23](=[O:24])[CH2:22][C:19]3[CH:18]=[CH:17][C:16]([O:15][C:6]4[C:5]5[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([C:1]#[N:2])[CH:4]=5)[N:9]=[CH:8][CH:7]=4)=[CH:21][CH:20]=3)[CH:42]=[C:43]([CH3:45])[CH:44]=2)[CH2:36][CH2:35]1
Reactant: COc1cc2nccc(Oc3ccc(CC(=O)O)cc3)c2cc1C#N
Reactant: Cc1cc(N)cc(CN(C(=O)OC(C)(C)C)C2CC2)c1
Solvent: O=C(O)C(F)(F)F
Product: COc1cc2nccc(Oc3ccc(CC(=O)Nc4cc(C)cc(CNC5CC5)c4)cc3)c2cc1C#N
Yield: 48 %

Procedure:
Using an analogous procedures to those described in Example 15, 2-[4-(6-cyano-7-methoxyquinolin-4-yloxy)phenyl]acetic acid was reacted with 3-(N-tert-butoxycarbonyl-N-cyclopropylaminomethyl)-5-methylaniline and the product was reacted with trifluoroacetic acid. The resultant product was purified by column chromatography on silica using a solvent gradient from 100:0 to 9:1 mixtures of ethyl acetate and methanol as eluent. There was thus obtained the title compound in 48% yield. A portion of the material so obtained was dissolved in methylene chloride and a solution of maleic acid (1 equivalent) in ethanol was added. The resultant solution was evaporated to provide a maleate salt of the title compound which gave the following characterising data:—1H NMR: (DMSOd6) 0.73 (m, 4H), 2.3 (s, 3H), 2.64 (m, 1H), 3.72 (s, 2H), 4.07 (s, 3H), 4.11 (s, 2H), 6.01 (s, 2H), 6.52 (m, 1H), 7.0 (s, 1H), 7.3 (d, 2H), 7.35 (s, 1H), 7.5 (d, 2H), 7.62 (s, 1H), 7.66 (s, 1H), 8.76 (m, 2H), 10.26 (s, 1H); Mass Spectrum: M+H+ 493.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1O[C:10](=O)[C:9]([C:13]#[N:14])=[C:8]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:7]=1.[H-].[Na+].[CH2:23]1[CH2:27]O[CH2:25][CH2:24]1>>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:4]2[C:3]3[C:24](=[CH:23][CH:27]=[CH:6][CH:2]=3)[CH2:25][C:10]=2[C:9]([C:13]#[N:14])=[C:8]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:7]=1
Reactant: C1CCOC1
Reactant: N#Cc1c(N2CCCCC2)cc(-c2ccco2)oc1=O
Agent: [H-]
Agent: [Na+]
Product: N#Cc1c(N2CCCCC2)cc(-c2ccco2)c2c1Cc1ccccc1-2

Procedure:
A mixture of 6-(furan-2-yl)-2-oxo-4-(piperidin-1-yl)-2H-pyran-3-carbonitrile (270 mg), indanone-2 (132 mg) and NaH (28 mg) in THF was stirred for <5 min. After completion, the reaction solvent was evaporated under vacuum to dryness and crude solid was quenched with ice water and subsequently neutralized with dil. HCl, finally purified by column chromatography using ethylacetate-hexane as eluent White solid; mp 160-162° C.; ESIMS 341 (M++1); IR (KBr) 2218 cm−1 (CN).
Reaction SMILES: CN(C)C=O.CS([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:18])[F:17])(=O)=O.[S:20]1[C:24]([C:25](O)=[O:26])=[CH:23][C:22]2[CH:28]=[CH:29][CH:30]=[CH:31][C:21]1=2.C(=O)([O-])O.[Na+]>O>[S:20]1[C:24]([C:25]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:17])[F:18])=[O:26])=[CH:23][C:22]2[CH:28]=[CH:29][CH:30]=[CH:31][C:21]1=2
Reactant: O=C(O)c1cc2ccccc2s1
Reactant: CC(CCCCOS(C)(=O)=O)=C(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(CCCCOC(=O)c1cc2ccccc2s1)=C(F)F
Temperature: 100 °C
Reaction time: 3 h
Yield: 80.6 %

Procedure:
To 40 ml of N,N-dimethylformamide were dissolved 5.00 g (22 mmol) of 6,6-difluoro-5-methyl-5-hexenyl methanesulfonate and 4.30 g (24 mmol) of benzo[b]thiophene-2-carboxylicacid, followed by the addition of 6.00 g (71 mmol) of sodium hydrogencarbonate and stirring at 100° C. for 3 hours. The reaction liquid was then poured in water and extracted with diethyl ether. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentration under reduced pressure. The residue was purified with silica gel column chromatography (diisopropyl ether:hexane=1:7) to obtain 5.50 g (yield: 81%) of 6,6-difluoro-5-methyl-5-hexenyl benzo[b]thiophene-2-carboxylate.
Reaction SMILES: O=C1[N:6]([C:7]2[CH:18]=[CH:17][C:10]([CH2:11][NH:12][C:13](=[O:16])[CH2:14][CH3:15])=[C:9]([C:19]([F:22])([F:21])[F:20])[CH:8]=2)[CH2:5][C:4]([C:27]2[CH:32]=[C:31]([Cl:33])[C:30]([Cl:34])=[C:29]([Cl:35])[CH:28]=2)([C:23]([F:26])([F:25])[F:24])[O:3]1.O.[OH-].[K+]>O1CCOCC1>[F:25][C:23]([F:24])([F:26])[C:4]([OH:3])([C:27]1[CH:28]=[C:29]([Cl:35])[C:30]([Cl:34])=[C:31]([Cl:33])[CH:32]=1)[CH2:5][NH:6][C:7]1[CH:18]=[CH:17][C:10]([CH2:11][NH:12][C:13](=[O:16])[CH2:14][CH3:15])=[C:9]([C:19]([F:20])([F:21])[F:22])[CH:8]=1
Reactant: CCC(=O)NCc1ccc(N2CC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)OC2=O)cc1C(F)(F)F
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCC(=O)NCc1ccc(NCC(O)(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)cc1C(F)(F)F
Temperature: 70 °C
Reaction time: 1 h
Yield: 97.3 %

Procedure:
N-{4-[2-oxo-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-1,3-oxazolidin-3-yl]-2-(trifluoro-methyl)benzyl}propane amide (542 mg) was added to a solution of 1,4-dioxane (10 mL), water (10 mL) and potassium hydroxide (108 mg), and stirred at 70° C. for 1 hour. After the reaction, 1,4-dioxane was distilled off under reduced pressure, and conc. hydrochloric acid (70 mg) was added and stirred under ice cooling. The resultant was extracted with ethyl acetate, washed with water and saturated brine, and the organic layer is dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residues were purified by silica-gel column chromatography to give N-[4-{[3,3,3-trifluoro-2-hydroxy-2-(3,4,5-trichlorophenyl)propyl]amino}-2-(trifluoromethyl)benzyl]propane amide (503 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([CH2:13][C:14](OCC)=[O:15])[N:12]=2)=[CH:4][CH:3]=1.[NH3:25]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([CH2:13][C:14]([NH2:25])=[O:15])[N:12]=2)=[CH:4][CH:3]=1
Reactant: N
Reactant: CCOC(=O)Cc1nc(-c2ccc(Cl)cc2)sc1-c1ccccc1
Solvent: CO
Product: NC(=O)Cc1nc(-c2ccc(Cl)cc2)sc1-c1ccccc1
Reaction time: 72 h

Procedure:
Ethyl 2-(4-chlorophenyl)-5-phenylthiazol-4-ylacetate (4.5 g) was dissolved in methanol (50 ml), and ammonia was saturated in the solution at 0° C. and the resulting mixture was allowed to stand at room temperature for 3 days. After removing the solvent, methanol was added to the residue. The resulting precipitate was collected and dried to obtain 2-(4-chloro-phenyl)-5-phenylthiazol-4-yl acetamide (4.2 g).
Reaction SMILES: [N:1]([CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6])=[N+:2]=[N-:3].[Li+].CC([N-]C(C)C)C.[CH:21]1([CH2:26][CH2:27][C:28](Cl)=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22]1.O>C1COCC1>[CH:21]1([CH2:26][CH2:27][C:28]([O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:4][N:1]=[N+:2]=[N-:3])=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: [N-]=[N+]=NCC(=O)c1ccccc1
Reactant: O=C(Cl)CCC1CCCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: [N-]=[N+]=NC=C(OC(=O)CCC1CCCC1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 67.1 %

Procedure:
To a stirred solution of α-azidoacetophenone (3.37 g, 20.9 mmol) in dry THF (50 mL) was added a solution of LDA (2.0 M in cyclohexane, 12.5 mL, 25 mmol) at -78° C. under nitrogen dropwise. After the reaction mixture was stirred for 1 h, a solution of 3-cyclopentylpropionyl chloride (5.04 g, 31.35 mmole, 1.5 eq.) was added to the dark red mixture, and after 10 min, the mixture was slowly warmed to room temperature. Stirring was continued for 1 h and the resultant yellow mixture was poured into water and extracted with ethyl acetate (3×50 mL). The combined organics were washed with water and brine, dried over magnesium sulfate, and filtered. Evaporation of solvent followed by column chromatography on silca gel (eluent: 2:1 ethyl acetate:hexanes) gave 4.0 g (71.5%) of the title compound: 1H NMR (400 MHz, CDCl3) ε 7.32-7.26 (m, 5H), 6.53 (s, 1H), 2.58 (t, 2H, J=7.5 Hz), 1.89-1.70 (m, 5H), 1,65-1.40 (m, 4H), 1.2 (m, 2H).
Reaction SMILES: [OH-].[Na+].CO.[CH3:5][O:6][C:7]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[C:13]([O:20][CH3:21])=[C:12]2[C:8]=1[CH2:9][CH:10]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=1)[CH2:11]2.Cl>O>[CH3:21][O:20][C:13]1[C:14]([O:18][CH3:19])=[C:15]([O:16][CH3:17])[C:7]([O:6][CH3:5])=[C:8]2[C:12]=1[CH2:11][CH:10]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=1)[CH2:9]2
Reactant: COC(=O)c1ccc(OCCCCC2Cc3c(c(OC)c(OC)c(OC)c3OC)C2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCOc1ccc(C(=O)O)cc1)C2
Yield: 95.9 %

Procedure:
An aqueous sodium hydroxide solution (3 N, 1.04 ml, 3.12 mmols) was added to a methanol (10 ml) solution of methyl 4-[4-(4,5,6,7-tetramethoxyindan-2-yl)butoxy]benzoate (920 mg, 2.07 mmols), and heated under reflux for 6 hours. Water was added to the reaction mixture, which was made acidic by adding 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and then dried. The solvent was evaporated out in vacuo, and the resulting crude product was purified by recrystallization (from hexane-ethyl acetate) to obtain the entitled compound (855 mg) as crystals.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:13][CH:12]=3)[S:10][C:3]=12.Cl.[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][N:33]=1.CC(C)([O-])C.[K+]>CS(C)=O>[NH2:31][C:32]1[N:33]=[CH:34][C:35]([O:38][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([C:11]4[N:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:13][CH:12]=4)[S:10][C:3]=23)=[CH:36][CH:37]=1
Reactant: Nc1ccc(O)cn1
Reactant: COCCN(Cc1ccc(-c2cc3nccc(Cl)c3s2)nc1)C(=O)OC(C)(C)C
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CS(C)=O
Product: COCCN(Cc1ccc(-c2cc3nccc(Oc4ccc(N)nc4)c3s2)nc1)C(=O)OC(C)(C)C
Temperature: 95 °C
Yield: 54.3 %

Procedure:
A stirred suspension of 22 (1.0 g, 2.3 mmol), 2-amino-5-hydroxypyridine hydrochloride (405 mg, 2.77 mmol) and potassium tert-butoxide (817 mg, 6.91 mmol) in DMSO (20 mL) under nitrogen was heated to 95° C. for 1 hr then cooled to RT. The reaction mixture was then partitioned between water and AcOEt. The organic layer was successively washed with water, 0.1 N NaOH, a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of ammonium chloride and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified twice by Biotage (SNAP 50 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV and Silia Flash 80 g; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 27 (634 mg, 1.249 mmol, 54% yield) as pale yellow sticky oil. MS (m/z): 508.6 (M+H).
Reaction SMILES: [SH:1][CH2:2][CH2:3][OH:4].Cl.Cl[CH2:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1>[O-]CC.[Na+]>[N:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][S:1][CH2:2][CH2:3][OH:4])[CH:9]=1
Reactant: ClCc1cccnc1
Reactant: OCCS
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Product: OCCSCc1cccnc1
Yield: 76.8 %

Procedure:
A stirred solution of sodium ethoxide (4.6 g of sodium in 100 ml ethanol) was treated with 2-mercaptoethanol (7.8 g, 0.1 mol) followed by 3-chloromethylpyridine hydrochloride (16.4 g, 0.1 mol). The mixture was then refluxed under argon for 3.5 hours, filtered and evaporated in vacuo and the residue purified by flash chromatography on silica, eluting with 3% methanol in ethyl acetate, to give 2-(3-pyridylmethylthio)ethanol (13 g), as a yellow oil;