Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:34])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[O:21][C:20]4[CH:28]=[CH:29][CH:30]=[C:31]([CH:32]=O)[C:19]=4[CH2:18]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH2:35][C:36]([NH2:38])=[O:37].C[Si](Cl)(C)C.[BH4-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:34])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:27]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[O:21][C:20]4[CH:28]=[CH:29][CH:30]=[C:31]([CH2:32][NH:35][C:36]([NH2:38])=[O:37])[C:19]=4[CH2:18]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: O=Cc1cccc2c1CC(=CCCN1CCC(O)(c3ccc(Cl)cc3)CC1)c1cccnc1O2
Reactant: NC(N)=O
Agent: C[Si](C)(C)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Product: NC(=O)NCc1cccc2c1CC(=CCCN1CCC(O)(c3ccc(Cl)cc3)CC1)c1cccnc1O2
Reaction time: 2 h
Yield: 28.6 %

Procedure:
To a solution of the product of example 314 (800 mg) in acetic acid (20 ml) were added urea (2 g) and trimethylsilyl chloride (0.24 ml) at room temperature, and the mixture stirred for 2 hours. Sodium borohydride was added to the reaction mixture at room temperature, and the mixture was stirred for 1 hour. The solvent was distilled off under reduced pressure, and, chloroform, 2-propanol and water were added. The organic layer was extracted, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography eluting with chloroform-methanol-ammonium hydroxide (100:10:1) to give the titled compound (250 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH:11]1(/[CH:17]=[C:18](\B2OC(C)(C)C(C)(C)O2)/[CH2:19][OH:20])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[F-].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:11]1(/[CH:17]=[C:18](\[C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)/[CH2:19][OH:20])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: CC1(C)OB(/C(=C\C2CCCCC2)CO)OC1(C)C
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Agent: c1ccc([PH](c2ccccc2)(c2ccccc2)[Pd-4]([PH](c2ccccc2)(c2ccccc2)c2ccccc2)([PH](c2ccccc2)(c2ccccc2)c2ccccc2)[PH](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(/C(=C\C2CCCCC2)CO)cc1
Temperature: 25 °C
Yield: 68.2 %

Procedure:
Add tetrakis(triphenylphosphino)palladium(0) (0.60 g, 0.52 mmol) to a solution of 1-bromo-4-nitro-benzene (0.76 g, 3.76 mmol) and (E)-3-cyclohexyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-prop-2-en-1-ol (1.13 g, 4.24 mmol) in dioxane (20 mL). Add cesium fluoride (1.75 g, 12 mmol) and stir the reaction mixture for 12 h at 80° C. Allow the reaction mixture to cool to r.t. Dilute the reaction mixture with ethyl acetate and wash with water. Separate the layers. Dry the organic phase over sodium sulfate, filter and concentrate. Purify the residue via silica gel chromatography, eluting with a gradient from 95:5 to 7:3 hexanes:ethyl acetate to obtain the title compound (0.67 g). 1H-NMR (CDCl3) δ=1.05-1.72 (m, 10 H), 1.89-2.04 (m, 1H), 4.28-4.36 (m, 2H), 5.61-5.69 (m, 1H), 7.34-7.43 (m, 2H), 8.18-8.26 (m, 2H).
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19](=[S:21])[NH:18][C:17]3=[O:22])=[CH:12][CH:13]=2)[CH:8]=[N:7]1.I[CH2:34][CH3:35]>>[F:32][C:2]([F:31])([F:1])[C:3]1[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19]([S:21][CH2:34][CH3:35])=[N:18][C:17]3=[O:22])=[CH:12][CH:13]=2)[CH:8]=[N:7]1
Reactant: CCI
Reactant: O=C1NC(=S)SC1=Cc1ccc2c(cnn2Cc2ccc(C(F)(F)F)cc2C(F)(F)F)c1
Product: CCSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(C(F)(F)F)cc3C(F)(F)F)c2)S1

Procedure:
5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-thioxo-thiazolidin-4-one and iodoethane following General Procedure C.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([CH3:20])[C:14]3=[C:13](Br)[N:12]=2)[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[CH3:22][O:23][C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[C:27]([C:34]([NH:36][C:37]1[CH:42]=[CH:41][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][C:38]=1[O:52][CH3:53])=[O:35])[N:28]2[CH3:33]>>[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([CH3:20])[C:14]3=[C:13]([C:40]3[CH:41]=[CH:42][C:37]([NH:36][C:34]([C:27]4[N:28]([CH3:33])[C:29]5[C:25]([CH:26]=4)=[C:24]([O:23][CH3:22])[CH:32]=[CH:31][CH:30]=5)=[O:35])=[C:38]([O:52][CH3:53])[CH:39]=3)[N:12]=2)[CH2:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@H](c2nc(Br)c3c(C)nccn32)CC1
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1NC(=O)c1cc2c(OC)cccc2n1C
Product: COc1cc(-c2nc([C@H]3CC[C@H](OC(C)=O)CC3)n3ccnc(C)c23)ccc1NC(=O)c1cc2c(OC)cccc2n1C

Procedure:
Using the procedure described in example 1 step 1f (trans)-4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)cyclohexyl acetate (0.568 mmol, 200 mg) and 4-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide (0.568 mmol, 248 mg) gave after purification using column chromatography (silica gel; gradient heptanes/ethyl acetate 1/1 to ethyl acetate) the title compound (245 mg).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=1)(=O)=O.[CH3:22][C:23]1([OH:29])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(Cl)Cl.CO>[I:21][C:18]1[CH:17]=[CH:16][C:15]([O:14][CH2:13][CH2:12][N:26]2[CH2:27][CH2:28][C:23]([CH3:22])([OH:29])[CH2:24][CH2:25]2)=[CH:20][CH:19]=1
Reactant: CC1(O)CCNCC1
Reactant: CS(=O)(=O)OCCOc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: CC1(O)CCN(CCOc2ccc(I)cc2)CC1

Procedure:
The product was obtained analogously to Example 1.1g (3 hours at 70° C., potassium carbonate as base) from 4.79 g (14.0 mmol) of 2-(4-iodophenoxy)ethyl methanesulfonate and 1.94 g (16.8 mmol) of 4-methylpiperidin-4-ol. Yield: 3.40 g (67% of theoretical); C14H20INO2 (M=361.219); calc.: molpeak (M+H)+: 362; found: molpeak (M+H)+: 362; Rf value: 0.20 (silica gel, DCM/MeOH 9:1).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)[OH:10])=[CH:4][N:3]=1>ClCCl.CO.O=[Mn]=O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)=[O:10])=[CH:4][N:3]=1
Reactant: CSc1nccc(C(O)c2cnc(Cl)nc2Cl)n1
Agent: O=[Mn]=O
Solvent: ClCCl
Solvent: CO
Product: CSc1nccc(C(=O)c2cnc(Cl)nc2Cl)n1
Temperature: 25 °C

Procedure:
To a stirred solution of (2,4-dichloro-pyrimidin-5-yl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanol (13.6 g, 45 mmol) in dichloromethane (160 mL) and methanol (40 mL) was added MnO2 (55 g, 632 mmol), The mixture was heated at reflux for 16 hours. After cooling to room temperature, the precipitate was removed off by filtration. The filtrate was concentrated and the residue was purified by column chromatography (silica, 20 g, 200-300 mesh, eluting with methanol:dichloromethane, 1:200) to afford (2,4-dichloro-pyrimidin-5-yl)-(2-methylsulfanyl-pyrimidin-4-yl)-methanone. (Yield 9.52 g, 71%).
Reaction SMILES: [N+:1]([CH2:4][CH:5]1[C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9][CH2:8][C:7](=O)[CH2:6]1)([O-:3])=[O:2].[CH2:24]([OH:27])[CH2:25][OH:26].Cl[Si](C)(C)C>C(Cl)Cl>[N+:1]([CH2:4][CH:5]1[C:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9][CH2:8][CH2:7][C:6]21[O:27][CH2:24][CH2:25][O:26]2)([O-:3])=[O:2]
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)C(C[N+](=O)[O-])C1
Reactant: OCCO
Agent: C[Si](C)(C)Cl
Solvent: ClCCl
Product: O=[N+]([O-])CC1C2(CCCC1(c1ccccc1)c1ccccc1)OCCO2
Yield: 80.3 %

Procedure:
A solution of 3-nitromethyl-4,4-diphenylcyclohexanone (69 g), ethylene glycol (30.48 g) and chlorotrimethylsilane (106.8 g) in anhydrous methylene chloride (1 liter) is brought to reflux for 2 hours, then cooled to +25° C., washed with saturated aqueous sodium hydrogen carbonate solution (600 cc) and then with saturated aqueous sodium chloride solution (300 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel with a slight excess pressure of nitrogen (0.04-0.063 mm, diameter 6.5 cm, height 45 cm), eluting with a mixture of cyclohexane and ethyl acetate (90:10 by volume) and collecting 500-cc fractions. Fractions 1 to 3 are combined and concentrated to dryness under reduced pressure (2.7 kPa). (RS)-6-Nitromethyl-7,7-diphenyl-1,4-dioxaspiro[4.5]decane (63.3 g) is obtained in the form of white crystals, m.p. 148° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[NH:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.N>[Cu].O>[N:10]1([C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[CH:5]=[O:6])[CH:14]=[CH:13][N:12]=[CH:11]1
Reactant: O=Cc1cccc(Br)c1
Reactant: c1c[nH]cn1
Agent: [Cu]
Agent: N
Solvent: O
Product: O=Cc1cccc(-n2ccnc2)c1
Yield: 53.6 %

Procedure:
A mixture comprising 9.25 g of 3-bromobenzaldehyde, 20.4 g of imidazole, 0.31 g of copper powder and 50 ml of water was heated under reflux in a nitrogen atmosphere for 3 days, followed by the addition of aqueous ammonia. The obtained mixture was extracted with chloroform. The extract was purified by silica gel column chromatography (solvent: methylene chloride/methanol) to obtain 4.61 g of the title compound as a pale yellow crystal (yield: 54%).
Reaction SMILES: [CH2:1]([N:19]([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][CH3:55])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:56]([I:74])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH3:73]>CC#N>[I-:74].[CH2:38]([N+:19]([CH2:73][CH2:72][CH2:71][CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][CH2:64][CH2:63][CH2:62][CH2:61][CH2:60][CH2:59][CH2:58][CH2:57][CH3:56])([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[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][CH3:55]
Reactant: CCCCCCCCCCCCCCCCCCI
Reactant: CCCCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCCC
Solvent: CC#N
Product: CCCCCCCCCCCCCCCCCC[N+](CCCCCCCCCCCCCCCCCC)(CCCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCCC
Product: [I-]
Reaction time: 120 h

Procedure:
Tetraoctadecylammonium iodide is prepared according to the following process. 70 mg (0.090 mmol) trioctadecylamine, 0.10 g (0.26 mmol) octadecyl iodide (recrystallized from 95% material, Fluka), and 3 ml CH3CN (HPLC grade, Fisher) are placed into a 10 ml roundbottomed flask. The mixture is refluxed under a dry nitrogen atmosphere with stirring for 5 days. 55 mg (53%) white solid, mp 104°-105° C., is recovered after the solvent is evaporated, and recrystallized twice in ethanol/Et2O. IR(KBr) 2918, 2855 (C-H stretching, vvs), 1471, 1386(C-H bending, w) cm-1. 1HNMR(CDCl3) δ 3.48-3.16(CH2, m, 8H), 1.78-0.81 (heptadecyl groups, m, 148H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH2:9][C:10](=[O:16])[NH:11]2.[CH3:17][C:18]1[C:22]([C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[O:24])=[C:21]([CH3:32])[NH:20][C:19]=1[CH:33]=O.N1CCCCC1>C(O)C>[CH3:17][C:18]1[C:22]([C:23]([N:25]2[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]2)=[O:24])=[C:21]([CH3:32])[NH:20][C:19]=1[CH:33]=[C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[CH:15][C:7]=2[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[NH:11][C:10]1=[O:16]
Reactant: O=C1Cc2c(cccc2-c2ccccn2)N1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)N1CCN(C)CC1
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1[nH]c(C=C2C(=O)Nc3cccc(-c4ccccn4)c32)c(C)c1C(=O)N1CCN(C)CC1
Temperature: 70 °C

Procedure:
A mixture of 4-pyridin-2-yl-1,3-dihydroindol-2-one (31.5 mg, 0.15 mmol), 3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (37.4 mg, 0.15 mmol) and piperidine (0.1 mL) in ethanol (1 mL) was heated in a sealed tube at 70° C. for 6 hours. The reaction was concentrated and the residue was re-crystallized from ethyl acetate and hexane to give the title compound.
Reaction SMILES: [CH2:1]([N+:5]([CH2:14][CH2:15][CH2:16][CH3:17])([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[NH2:18][C:19]1([O:28][CH3:29])[CH2:22][N:21]([S:23]([O-:26])(=[O:25])=[O:24])[C:20]1=[O:27].N1C=CC=CC=1.[N:36]([CH:39]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:40](Cl)=[O:41])=[N+:37]=[N-:38].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C>[CH2:14]([N+:5]([CH2:1][CH2:2][CH2:3][CH3:4])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:10][CH2:11][CH2:12][CH3:13])[CH2:15][CH2:16][CH3:17].[N:36]([CH:39]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:40]([NH:18][C:19]1([O:28][CH3:29])[CH2:22][N:21]([S:23]([O-:26])(=[O:24])=[O:25])[C:20]1=[O:27])=[O:41])=[N+:37]=[N-:38]
Reactant: COC1(N)CN(S(=O)(=O)[O-])C1=O
Reactant: [N-]=[N+]=NC(C(=O)Cl)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: c1ccncc1
Product: COC1(NC(=O)C(N=[N+]=[N-])c2ccccc2)CN(S(=O)(=O)[O-])C1=O
Temperature: -20 °C
Reaction time: 0.33 h

Procedure:
3-Amino-3-methoxy-2-oxo-1-azetidinesulfonic acid tetrabutylammonium salt (202 mgs; see Example 74A) is dissolved in 20 ml of dry acetonitrile. To the well stirred solution at -20° C. under dry nitrogen are added dry pyridine (167 μl) and α-azidophenylacetyl chloride (96 μl). After 20 minutes, 0.5M pH 5.5 monobasic potassium phosphate buffer (12 ml) is added and the acetonitrile removed in vacuo. The aqueous residue is extracted three times with methylene chloride. The extract is dried over anhydrous sodium sulfate and evaporated in vacuo to give 281 mg of crude product as a gum. This is purified by chromatography through a column of silica gel (30 g) using methylene chloride and mixtures of methylene chloride-methanol up to 6% methanol, and yielding 231 mg of the title compound.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=O.[CH2:9]([NH:11][CH2:12][CH3:13])[CH3:10]>ClCCl>[CH2:9]([N:11]([CH2:12][CH3:13])[C:6]([C:2]1[NH:1][CH:5]=[CH:4][CH:3]=1)=[O:8])[CH3:10]
Reactant: CCNCC
Reactant: O=C(O)c1ccc[nH]1
Solvent: ClCCl
Product: CCN(CC)C(=O)c1ccc[nH]1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 70.2 %

Procedure:
Pyrrole-2-carboxylic acid (10.0 g, 90 mmol) was dissolved. in 250 mL of dichloromethane. DCC (N,N-dicyclohexylcarbodiimide) (20.4 g, 99 mmol), DMAP (4-dimethyl-aminopyridine) (2.2 g, 18 mmol) and diethylamine (10.2 mL, 99 mmol) were added subsequently at 0° C. under an Argon atmosphere. The reaction mixture was stirred at 0° C. for 30 mins then stirred at root temperature for 8 hours. The solution was diluted with dichloromethane and the solid was filtered off. The filtrates were washed by diluted hydrochloric acid, followed by saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane=1/2) to obtain N,N-diethyl-1H-pyrrole-2-carboxamide as a white solid (10.5 g, 70% yield). mp 78.6-79.9° C.; 1H NMR (300 MHz, CDCl3): δ 10.1 (br, 1H), 6.94-6.88 (m, 1H), 6.57-6.51 (m, 1H), 6.26-6.21 (m, 1H), 3.95-3.86 (m, 4H), 1.31-1.24 (m, 6H); 13C NMR (75.5 Hz, CDCl3): δ 161.9, 120.7, 111.3, 110.1, 109.5, 41.9, 13.4; IR (CH2Cl2) 3442, 2981, 2937, 1716, 1600 cm−1; LRMS (EI) m/z (%) 166 (M+; 100); HRMS (EI): calcd for C9H14N2O: 166.1106, Found: 116.1106.
Reaction SMILES: [Br:1][C:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:4][C:3]=1[C:15]([O:17][CH2:18][S:19][CH3:20])=[O:16].ClC1C=C(C=CC=1)C(OO)=[O:26]>C(Cl)(Cl)Cl>[Br:1][C:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:4][C:3]=1[C:15]([O:17][CH2:18][S:19]([CH3:20])=[O:26])=[O:16]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCOC(=O)c1oc(-c2ccccc2)cc(=O)c1Br
Solvent: ClC(Cl)Cl
Product: CS(=O)COC(=O)c1oc(-c2ccccc2)cc(=O)c1Br

Procedure:
A solution of methylthiomethyl 3-bromo-4-oxo-6-phenyl-4H-pyran-2-carboxylate (0.36 g) and m-chloroperoxybenzoic acid (0.22 g, 80% pure) in chloroform (5 ml) was stirred for 4 hours at room temperature, filtered, washed with sodium bicarbonate solution, and evaporated. The residue was recrystallised from ethyl acetate-petroleum ether 60°-80° C. to give the title product (mp 159° C.).
Reaction SMILES: [CH:1]1([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[C:7]([O:9]C)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1COCC1.[OH-].[Li+].Cl>O.CO>[CH:1]1([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][CH:12]=2)[C:7]([OH:9])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(=O)C(c1ccc(C(F)(F)F)cc1)C1CCCC1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)C(c1ccc(C(F)(F)F)cc1)C1CCCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 96.3 %

Procedure:
4.98 g (17.4 mmol) of methyl cyclopentyl[4-(trifluoromethyl)phenyl]acetate were initially charged in a mixture of in each case 24.9 ml of THF, methanol and water, and 1.04 g (43.49 mmol) of lithium hydroxide were added at 0° C. The reaction mixture was warmed to RT and stirred at this temperature for 4 h. The mixture was then diluted with water and acidified slightly with 1 N hydrochloric acid. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave 4.56 g of the target compound as a crude product (yield 96.3% of theory).
Reaction SMILES: C1(C2C=CC(C([O:13][C@@H:14]3[CH2:21][C@H:20]4[C@H:16]([CH2:17][C:18](=[O:22])[O:19]4)[C@H:15]3/[CH:23]=[CH:24]/[C@@H:25]([O:33][CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][O:35]3)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=O)=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CO>[OH:13][C@@H:14]1[CH2:21][C@H:20]2[C@H:16]([CH2:17][C:18](=[O:22])[O:19]2)[C@H:15]1/[CH:23]=[CH:24]/[C@@H:25]([O:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][O:35]1)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCC[C@@H](/C=C/[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1OC(=O)c1ccc(-c2ccccc2)cc1)OC1CCCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CCCCCCC[C@@H](/C=C/[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1O)OC1CCCCO1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
The tetrahydropyranyl ether (5) (5.03 9) was dissolved into a dry methanol (300 ml), into which potassium carbonate (1.49 g ) was added, and stirred at room temperature for 6 hours. A crude compound obtained by a usual work-up was column-chromatographed to give the title compound (6). Yield: 3.25 g
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[CH2:5]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][CH2:21][CH:22]([CH2:27][CH3:28])[CH2:23][CH2:24][CH2:25][CH3:26])[CH:6]1[O:8][CH2:7]1>C(O)C>[OH:2][CH2:1][CH2:3][NH:4][CH2:7][CH:6]([OH:8])[CH2:5][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][CH2:21][CH:22]([CH2:27][CH3:28])[CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: CCCCC(CC)COCCCCCCCCCCOCC1CO1
Reactant: NCCO
Solvent: CCO
Product: CCCCC(CC)COCCCCCCCCCCOCC(O)CNCCO
Temperature: 80 °C
Yield: 68.4 %

Procedure:
A 200-ml two-necked flask equipped with a stirrer, reflux tube and dropping funnel was charged with 32.7 g (0.54 mol) of ethanolamine and 10.1 g of ethanol. While heating and stirring the mixture at 80° C., 1.76 g (5.14 mmol) of 10-(2-ethylhexyloxy)decyl glycidyl ether were added dropwise over 2 hours. After the resultant mixture was heated and stirred further for 18 hours, it was concentrated under reduced pressure, and the resultant residue was purified by column chromatography on silica gel, thereby obtaining 1.42 g (yield: 68%) of the title compound (Ia-14).
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C)C=CC=CC=1.[C@@H:17]12[O:25][CH2:24][C@@H:22]([O:23]1)[CH:21]=[CH:20][C@@H:18]2[OH:19]>C(N(CC)CC)C>[C:1]1([NH:7][C:8]([O:19][C@H:18]2[CH:20]=[CH:21][C@H:22]3[CH2:24][O:25][C@@H:17]2[O:23]3)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O[C@H]1C=C[C@H]2CO[C@@H]1O2
Reactant: O=C=Nc1ccccc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(Nc1ccccc1)O[C@H]1C=C[C@H]2CO[C@@H]1O2
Yield: 86.4 %

Procedure:
0.56 g of phenyl isocyanate was added at room temperature to 30 ml of a dry toluene solution containing 0.3 g of 1,6-anhydro-3,4-dideoxy-β-D-threo-hex-3-enopyranose under an inert atmosphere of nitrogen gas. Further, 0.1 ml of triethylamine was added thereto, and the reaction mixture was refluxed under heating for two hours. Completion of the reaction was confirmed by thin layer chromatography, and then the solvent was immediately distilled off under reduced pressure to obtain a syrup crude product. This crude product was purified by silica gel chromatography (ethyl acetate: hexane=1:3) to obtain 0.5 g of the desired product (Compound No. 23). The NMR analytical data of this product are as follows.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=O)[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:5]2O.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[O:29])=[CH:24][CH:23]=1.[Cl:36]C1C=C(C(C2C=NC=CC=2)=O)C=CC=1>>[Cl:36][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:28]([C:25]3[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=3)([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[OH:29])[CH:3]=2)[N:8]=[CH:7][C:6]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=c1[nH]c2ccc(Br)cc2c(O)c1-c1ccccc1
Reactant: COc1ccc(C(=O)c2cccnc2)cc1
Reactant: O=C(c1cccnc1)c1cccc(Cl)c1
Product: COc1ccc(C(O)(c2cccnc2)c2ccc3ncc(-c4ccccc4)c(Cl)c3c2)cc1

Procedure:
The title compound was prepared using 6-bromo-4-chloro-3-phenylquinoline (Intermediate 3, step c) and (4-methoxyphenyl)(pyridin-3-yl)methanone in place of 6-bromo-2,4-dichloro-3-phenylquinoline and (3-chlorophenyl)(pyridin-3-yl)methanone, respectively, according to the procedure described in Example 25. 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 8.60-8.68 (m, 1H), 8.51-8.57 (m, 1H), 8.38 (d, J=1.96 Hz, 1H), 8.08 (d, J=8.80 Hz, 1H), 7.67-7.78 (m, 2H), 7.44-7.57 (m, 5H), 7.25-7.32 (m, 1H), 7.20 (d, J=8.80 Hz, 2H), 6.88 (d, J=8.80 Hz, 2H), 3.81 (s, 3H); MS m/e 452.9 [M+H]+.