Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[S:41][C:40]([N:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]2=[O:48])=[N:39][CH:38]=1>>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[S:41][C:40]([N:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]4=[O:48])=[N:39][CH:38]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Reactant: O=c1ccccn1-c1ncc(Br)s1
Product: C[C@@H](c1ccc(-c2cnc(-n3ccccc3=O)s2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O

Procedure:
The title compound was prepared from (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-1,3-oxazinan-2-one and 1-(5-bromothiazol-2-yl)pyridin-2(1H)-one following a procedure analogous to that described in Example 31. LC (method 5): tR=1.72 min; Mass spectrum (ESI+): m/z=472, 530 [M+H]+; 1H NMR (CDCl3) δ 1.12 (s, 3H), 1.18 (s, 3H), 1.56 (d, 3H), 2.19 (s, 2H), 2.25 (m, 1H), 2.39 (m, 1H), 2.60 (m, 1H), 2.86 (m, 1H), 5.69 (q, 1H), 6.45 (t, 1H), 6.80 (d, 1H), 6.99 (d, 2H), 7.25-7.40 (7H), 7.46 (m, 1H), 7.77 (s, 1H), 8.81 (d, 1H).
Reaction SMILES: [CH2:1]([OH:7])[C:2]1[O:6][CH2:5][CH2:4][CH:3]=1.[H-].[Na+].[CH2:10](Br)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].O>CN(C)C=O>[CH2:25]([O:7][CH2:1][C:2]1[O:6][CH2:5][CH2:4][CH:3]=1)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH3:10]
Reactant: OCC1=CCCO1
Reactant: CCCCCCCCCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCOCC1=CCCO1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.7 %

Procedure:
A solution of 4.09 g of 4,5-dihydrofurfuryl alcohol (prepared as described in Preparation 12) in 10 ml of dimethylformamide was added dropwise to 2.62 g of a 55% w/w suspension of sodium hydride in mineral oil, itself suspended in 40 ml of dimethylformamide, whilst maintaining the temperature of the mixture at from 5° to 12° C. by ice-cooling. The mixture was then stirred at room temperature for 30 minutes, 18.32 g of hexadecyl bromide were added to the solution, and the whole was stirred at room temperature for 15 hours. The reaction mixture was then poured into 200 ml of water, and extracted twice with diethyl ether. The extract was washed with water, dried and condensed by evaporation under reduced pressure. The oily residue, 17 g, was subjected to column chromatography through 400 g of Grade II-III alumina (a product of Woelm Pharma, West Germany). The fraction eluted with a 1:20 by volume mixture of diethyl ether and hexane gave 9.512 g of the title compound as a solid, melting at 30.5°-31.5° C. (cold hexane).
Reaction SMILES: Cl.Cl.[OH:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.CS(C)=O.C(N(CC)CC)C.[CH:21]1([N:24]2[C:33]3[C:28](=[CH:29][C:30]([F:36])=[C:31](F)[C:32]=3[F:34])[C:27](=[O:37])[C:26]([C:38]#[N:39])=[CH:25]2)[CH2:23][CH2:22]1>O>[C:38]([C:26]1[C:27](=[O:37])[C:28]2[C:33](=[C:32]([F:34])[C:31]([N:7]3[CH2:8][CH2:9][N:4]([OH:3])[CH2:5][CH2:6]3)=[C:30]([F:36])[CH:29]=2)[N:24]([CH:21]2[CH2:22][CH2:23]2)[CH:25]=1)#[N:39]
Reactant: ON1CCNCC1
Reactant: N#Cc1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1cn(C2CC2)c2c(F)c(N3CCN(O)CC3)c(F)cc2c1=O
Temperature: 100 °C
Yield: 82.1 %

Procedure:
1-Hydroxypiperazine dihydrochloride (2.45 g) (which is prepared in Preparation 1), dimethylsulfoxide (20 ml) and triethylamine (5.05 g) are added to 1-cyclopropyl-3-cyano-1,4-dihydro-4-oxo-6,7,8-trifluoroquinoline (2.64 g), which is prepared in Preparation 3, and the mixture is stirred with heating at 100° C. for 4 hours. After cooling to room temperature, water (300 ml) is added to the reaction mixture, and the resulting precipitate is filtered and washed with water to afford 3-cyano-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(4-hydroxypiperazin-1-yl)-4-oxoquinoline (2.84 g) as pale yellow powder. The powder is recrystallized from dimethylsulfoxide to yield light brown needles, m.p. about 214° C. (decomposition).
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=3)[N:10]=2)[CH:5]=[CH:6][N:7]=1.[NH2:22][CH2:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:22][CH2:23][C:24]1[CH:29]=[C:28]([C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH:11][C:12]4[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=4)[N:10]=3)[CH:5]=[CH:6][N:7]=2)[CH:27]=[CH:26][CH:25]=1
Reactant: COc1cc(Nc2nc3c(Cl)nccn3n2)cc(OC)c1
Reactant: NCc1cccc(B(O)O)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1cc(Nc2nc3c(-c4cccc(CN)c4)nccn3n2)cc(OC)c1
Temperature: 120 °C

Procedure:
To a solution of (8-chloro-[1,2,4]triazolo[1,5-a]pyrazine-2-yl]-(3,5-dimethoxy-phenyl)-amine (0.2 g, 0.65 mmol, 1 eq) in a mixture of dimethoxy ethane (3 ml) and water (1 ml), 3-aminomethylphenyl boronic acid (0.28 g, 1.31 mmol, 2 eq), sodium carbonate (0.14 g, 1.31 mmol, 2 eq)) and dichlorobis(triphenyl-phospine)palladium (II) (0.023 g, 0.03 mmol, 5%) are taken in a microwave vial and heated at 120° C. for 2 hours. The reaction mixture is concentrated and the residue is taken in dichloromethane (10 ml×1), washed with brine solution (10 ml×1), the organic layer is dried over anhydrous MgSO4 and concentrated. The crude product obtained is purified by silica gel column using (230-400) mesh to get the titled product as yellow solid.
Reaction SMILES: [SH:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].S([O:20][CH2:21][C:22]1([CH:28]=O)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)(C)(=O)=O.CCOCC(OCC)COCC.Cl>COCCOCCOC>[C:4]([C:3]1[CH:12]=[CH:13][CH:14]=[CH:15][C:2]=1[S:1][CH2:28][C:22]1([CH:21]=[O:20])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)(=[O:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(c1ccccc1)c1ccccc1S
Reactant: CS(=O)(=O)OCC1(C=O)CCCCC1
Agent: CCOCC(COCC)OCC
Agent: Cl
Solvent: COCCOCCOC
Product: O=CC1(CSc2ccccc2C(=O)c2ccccc2)CCCCC1
Reaction time: 24 h
Yield: 18.1 %

Procedure:
A mixture of 69 g (0.303 mole) of 2-mercaptobenzophenone, 82 g (0.303 mole) of mesylate 55, 32 g of triethyline, and 150 ml of diglyme was stirred and held at relux for 24 h. The mixture was cooled, poured into dil. HCl and extracted with methylene chloride. The organic layer was washed with 10% NaOH, water, brine, and dried over sodium sulfate and concentrated under vacuum to remove excess diglyme. This was purified by silica gel flush column (5% EtOAc-Hexane) and gave 18.6 g (75.9%) of yellow oil. Proton NMR and mass spectra were consistent with the product.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:8]=2)[CH:3]=[CH:2]1.[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1/[CH:28]=[CH:29]/[N+:30]([O-:32])=[O:31]>ClCCl>[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH:28]([C:3]1[C:4]2[C:9](=[CH:8][C:7]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:6][CH:5]=2)[NH:1][CH:2]=1)[CH2:29][N+:30]([O-:32])=[O:31]
Reactant: O=[N+]([O-])/C=C/c1ccccc1F
Reactant: O=C(Nc1ccc2cc[nH]c2c1)OCc1ccccc1
Solvent: ClCCl
Product: O=C(Nc1ccc2c(C(C[N+](=O)[O-])c3ccccc3F)c[nH]c2c1)OCc1ccccc1
Temperature: 105 °C
Yield: 80.7 %

Procedure:
Benzyl 1H-indol-6-ylcarbamate (0.981 g, 3.68 mmol) and (E)-1-fluoro-2-(2-nitrovinyl)benzene (0.770 g, 4.60 mmol) were suspended and well mixed in dichloromethane (15 mL). The suspension was concentrated under vacuum to dryness. The solid mixture was then heated at 105° C. under nitrogen for 7 hr. The mixture was subjected to ISCO (120 g silica gel, solid loading, 20-45% ethyl acetate) to afford the desired product (1.287 g, 2.97 mmol, 81% yield) as a white solid.
Reaction SMILES: C(#N)C1C=CC=C(C#N)C=1.[OH-:11].[Na+].[C:13](#[N:22])[C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1>C(O)C>[C:18]([C:17]1[CH:20]=[CH:21][C:14]([C:13]([NH2:22])=[O:11])=[CH:15][CH:16]=1)#[N:19]
Reactant: N#Cc1ccc(C#N)cc1
Reactant: [OH-]
Agent: N#Cc1cccc(C#N)c1
Agent: [Na+]
Solvent: CCO
Product: N#Cc1ccc(C(N)=O)cc1
Temperature: 78 °C
Yield: 69 %

Procedure:
Isophthalonitrile (128 g) and ethanol (1700 g) were placed in a four-neck flask, and the mixture was heated to 78° C. with stirring. To the mixture, a 20% aqueous solution (10 g) of sodium hydroxide was added over three hours by use of a tube pump. Liquid chromatographic analysis revealed that the reaction mixture contained 100.7 g of p-cyanobenzamide (yield 69%) and 38.4 g of terephthalonitrile (conversion 70%). The reaction mixture was cooled to 25° C., neutralized with concentrated sulfuric acid, and heated under reduced pressure so as to concentrate the mixture and to remove ethanol (1275 g). After normal pressure was restored, the mixture was cooled to 25° C., and water (720 g) was added thereto. Subsequently, an aqueous solution (887.5 g) of sodium hypochlorite (effective chlorine 12%) was added to the reaction mixture over six hours while a 50% aqueous solution of sulfuric acid was added so as to maintain the pH of the mixture at 5-6. Liquid chromatographic analysis revealed that the reaction mixture contained 100.0 g of crude p-cyanobenzoic acid (yield 68%) and terephthalonitrile (38 g). Subsequently, the residual solvent (1090 g) was removed from the reaction mixture through distillation under reduced pressure. To the resultant mixture, a 48% aqueous solution of sodium hydroxide was added to thereby adjust the pH to 8, and precipitated terephthalonitrile (36 g) was recovered through filtration. To the filtrate, concentrated sulfuric acid was added so as to adjust the pH to 3.0 and precipitate p-cyanobenzoic acid from its salt. The precipitate was dissolved by adding ethanol (309 g) with heat, and the solution was cooled for crystallization, to thereby obtain 90.6 g of m-cyanobenzoic acid having a purity of 99% (yield 61%).
Reaction SMILES: C([C:5]1[C:6]([CH2:23][C:24]([CH2:39][C:40]2[CH:45]=[CH:44][C:43](C(P(OC(C)(C)C)(OC(C)(C)C)=O)(F)F)=[C:42]([Br:61])[CH:41]=2)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:7](C(C)(C)C)[C:8]([Br:18])=[C:9]([C:11]([P:14](=[O:17])([O-:16])[O-:15])([F:13])[F:12])[CH:10]=1)(C)(C)C>CC(O)=O.O>[Br:61][C:42]1[CH:41]=[C:40]([CH2:39][C:24]([CH2:23][C:6]2[CH:5]=[CH:10][C:9]([C:11]([F:13])([F:12])[P:14]([OH:16])([OH:15])=[O:17])=[C:8]([Br:18])[CH:7]=2)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:45]=[CH:44][C:43]=1[O:16][P:14]([CH:11]([F:13])[F:12])(=[O:15])[OH:17]
Reactant: CC(C)(C)OP(=O)(OC(C)(C)C)C(F)(F)c1ccc(CC(Cc2c(C(C)(C)C)cc(C(F)(F)P(=O)([O-])[O-])c(Br)c2C(C)(C)C)(C(=O)c2ccccc2)c2ccccc2)cc1Br
Solvent: CC(=O)O
Solvent: O
Product: O=C(c1ccccc1)C(Cc1ccc(OP(=O)(O)C(F)F)c(Br)c1)(Cc1ccc(C(F)(F)P(=O)(O)O)c(Br)c1)c1ccccc1
Yield: 227.7 %

Procedure:
The product of Step 8 (96 mg, 0.094 mmol) was stirred overnight in HOAc (3 mL) and H2O (0.3 mL). The solvent was removed under vacuum and the residue was co-evaporated with toluene/acetone (3×) to give a tan coloured foam (85 mg).
Reaction SMILES: [F:1][C:2]1[C:3]([N+:12]([O-])=O)=[C:4]([CH2:8][C:9](O)=[O:10])[CH:5]=[CH:6][CH:7]=1>C(O)(=O)C.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[NH:12][C:9](=[O:10])[CH2:8]2
Reactant: O=C(O)Cc1cccc(F)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: CC(=O)O
Product: O=C1Cc2cccc(F)c2N1
Yield: 82.7 %

Procedure:
(3-fluoro-2-nitro-phenyl)-acetic acid (9.6 g, 48 mmol) was dissolved in acetic acid (100 mL) and hydrogenated over 10% palladium on carbon (1.3 g), at 50 psi for 24 hours. The catalyst was removed by filtration through the Celite® reagent and the solvent was evaporated. The mixture was then dissolved in ethanol (100 mL), para-toluenesulfonic acid (50 mg) was added and the mixture heated under reflux for 1 hour. The mixture was cooled, poured into water, extracted with ethyl acetate, dried (MgSO4), and evaporated. The solid was triturated with hexane/ethyl acetate (95/5) to give 7-fluoro-1,3-dihydro-indol-2-one (6 g, 83%). HRMS: calc'd for C8H6FNO, 151.0433; found (ESI, [M+H]+), 152.0515
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[C:9]([CH2:21][NH:22][CH3:23])=[C:10]([CH:14]2[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]2)[CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][NH2:25]>>[C:1]([O:5][C:6]([C:8]1[C:9]([CH2:21][NH:22][CH3:23])=[C:10]([C@H:14]2[CH2:19][CH2:18][C@H:17]([NH:25][CH3:24])[CH2:16][CH2:15]2)[CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN
Reactant: CNCc1c(C(=O)OC(C)(C)C)cccc1C1CCC(=O)CC1
Product: CNCc1c(C(=O)OC(C)(C)C)cccc1[C@H]1CC[C@H](NC)CC1

Procedure:
from 4-(3-tert.butoxycarbonyl-methylaminomethylphenyl)-cyclohexanone and methylamine. Colourless oil.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[S:16][C:17]3[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([N:33]=[C:34]=[S:35])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[C:25]([NH:33][C:34]([NH:24][C:22]1[CH:21]=[CH:20][C:18]2[N:19]=[C:15]([NH:14][CH:11]3[CH2:12][CH2:13][N:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:9][CH2:10]3)[S:16][C:17]=2[CH:23]=1)=[S:35])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Nc1ccc2nc(NC3CCN(Cc4ccccc4)CC3)sc2c1
Reactant: O=C(N=C=S)c1ccccc1
Solvent: C1CCOC1
Product: O=C(NC(=S)Nc1ccc2nc(NC3CCN(Cc4ccccc4)CC3)sc2c1)c1ccccc1
Yield: 100 %

Procedure:
N2-(1-Benzyl-piperidin-4-yl)-benzothiazole-2,6-diamine (Example 27b, 39 mg, 0.12 mmol) was stirred with benzoylisothiocyanate (17 μl, 1.1 eq.) in dry THF at room temperature under argon for 24 hours. The solvent was evaporated to give a yellow oil. The oil was purified by chromatography on silica gel (30% ethyl acetate/hexanes) to give a yellow oil (60.7 mg, 100%).
Reaction SMILES: Br[CH2:2][CH:3]=[C:4]([CH2:12][CH3:13])[CH2:5][CH2:6][CH:7]=[C:8]([CH3:11])[CH2:9][CH3:10].[OH:14][C:15]1[CH:24]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1>>[CH2:12]([C:4]([CH2:5][CH2:6][CH:7]=[C:8]([CH3:11])[CH2:9][CH3:10])=[CH:3][CH2:2][O:14][C:15]1[CH:24]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1)[CH3:13]
Reactant: CCC(C)=CCCC(=CCBr)CC
Reactant: Oc1ccc2c(c1)OCCC2
Product: CCC(C)=CCCC(=CCOc1ccc2c(c1)OCCC2)CC

Procedure:
Following the procedure of Example 1, 1-bromo-3-ethyl-7-methyl-2,6-nonadiene and 7-hydroxy-chromane are reacted to form 7-(3-ethyl-7-methyl-2,6-nonadienyloxy)-chromane of boiling point 140°-141°C/0.001 mmHg.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][O:11][C:12](=[O:14])[CH3:13])[O:8][C@@H:7]([N:15]2[CH:22]=[C:21]([F:23])[C:19](=[O:20])[NH:18][C:16]2=[O:17])[CH2:6]1)(=[O:3])[CH3:2].C(N(CC)CC)C.[C:31](Br)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCOCC1>[C:31]([N:18]1[C:19](=[O:20])[C:21]([F:23])=[CH:22][N:15]([C@@H:7]2[O:8][C@H:9]([CH2:10][O:11][C:12](=[O:14])[CH3:13])[C@@H:5]([O:4][C:1](=[O:3])[CH3:2])[CH2:6]2)[C:16]1=[O:17])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: O=C(Br)c1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cc(F)c(=O)[nH]c2=O)C[C@@H]1OC(C)=O
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(F)c(=O)n(C(=O)c3ccccc3)c2=O)C[C@@H]1OC(C)=O
Reaction time: 0.25 h
Yield: 60.8 %

Procedure:
500 mg of 2'-deoxy-3',5'-di-O-acetyl-5-fluorouridine and 0.76 ml of triethylamine were dissolved in 10 ml of dry dioxane, and the resulting mixture was cooled with ice. To the mixture was added 850 mg of benzoyl bromide, and the resulting mixture was allowed to stand at room temperature for 15 minutes and then at 70° C. for 30 minutes. The same procedure as in Example 8 gave 400 mg (yield: 60.5%) of 3-benzoyl-2'-deoxy-3',5'-di-O-acetyl-5-fluorouridine. The absorption spectra of the present product were identical with those of the compound obtained in Example 8.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:16])([CH3:15])[C:9](N(OC)C)=[O:10])=[CH:4][C:3]=1[O:17][CH3:18].[Li][CH3:20]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:15])([CH3:16])[C:9](=[O:10])[CH3:20])=[CH:4][C:3]=1[O:17][CH3:18]
Reactant: [Li]C
Reactant: COc1cc(C(C)(C)C(=O)N(C)OC)ccc1F
Solvent: C1CCOC1
Product: COc1cc(C(C)(C)C(C)=O)ccc1F
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 2-(4-fluoro-3-methoxyphenyl)-N-methoxy-N,2-dimethylpropanamide (123 g, 0.48 mol) in THF (1 L)-78° C. was added 3M ethereal solution of MeLi (210 mL, 0.627 mol). The resulting solution was warmed to ambient temperature and stirred 16 h. The reaction mixture was quenched with 3N HCl (400 mL) and extracted with EtOAc (600 mL×2). The combined extracts were washed with satd NaHCO3 (1.0 L) and brine (1.0 L), then dried over MgSO4 and concentrated at reduced pressure to give 3-(4-fluoro-3-methoxyphenyl)-3-methylbutan-2-one as yellow color oil (92.5 g, 91%). 1H NMR (400 MHz, CDCl3): δ 7.05 (m, 1H), 6.83-6.78 (m, 2H), 3.88 (s, 3H), 1.95 (s, 3H), 1.47 (s, 6H).
Reaction SMILES: [C:1]1([C:7]([C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)([C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]3[CH:24]=[CH:23][C:22]([CH2:25][N:26]4[N:30]5[N:31]=[C:32]([CH3:34])[N:33]=[C:29]5[C:28](CC5C=CC(C6C=CC=CC=6C6N(C(C7C=CC=CC=7)(C7C=CC=CC=7)C7C=CC=CC=7)N=NN=6)=CC=5)=[C:27]4[CH2:72][CH3:73])=[CH:21][CH:20]=3)=[N:11][N:10]=[N:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:86]([C:88]1[CH:95]=[C:94]2[N:90]([N:91]=[C:92]([CH3:133])[N:93]2CC2C=CC(C3C=CC=CC=3C3N(C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)N=NN=3)=CC=2)[N:89]=1)[CH3:87].C(C1C(CC2C=CC(C3C=CC=CC=3C3N(C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)N=NN=3)=CC=2)=C2N(N=C(C)N2)N=1)C.C(C1N(CC2C=CC(C3C=CC=CC=3C3N(C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)N=NN=3)=CC=2)N2C(C=1)=NC(C)=N2)C>>[CH2:72]([C:27]1[N:26]([CH2:25][C:22]2[CH:21]=[CH:20][C:19]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[N:8]([C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)([C:80]4[CH:81]=[CH:82][CH:83]=[CH:84][CH:85]=4)[C:74]4[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=4)[N:9]=[N:10][N:11]=3)=[CH:24][CH:23]=2)[N:30]2[C:29]([CH:28]=1)=[N:33][C:32]([CH3:34])=[N:31]2)[CH3:73].[CH2:86]([C:88]1[CH:95]=[C:94]2[N:90]([N:91]=[C:92]([CH3:133])[NH:93]2)[N:89]=1)[CH3:87]
Reactant: CCc1cc2n(Cc3ccc(-c4ccccc4-c4nnnn4C(c4ccccc4)(c4ccccc4)c4ccccc4)cc3)c(C)nn2n1
Reactant: CCc1c(Cc2ccc(-c3ccccc3-c3nnnn3C(c3ccccc3)(c3ccccc3)c3ccccc3)cc2)c2nc(C)nn2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCc1cc2nc(C)nn2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCc1nn2nc(C)[nH]c2c1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: CCc1cc2[nH]c(C)nn2n1

Procedure:
In the same manner as described in Example 38, 0.40 g of 5,7-bis[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-6-ethyl-2-methyl-5H-pyrazolo[1,5-b][1,2,4]triazole (compound 49a), 2.96 g of 6-ethyl-2-methyl-1-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole (compound 49b), 0.29 g of 6-ethyl-2-methyl-7-[[2' -(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-pyrazolo[1,5-b][1,2,4]triazole (compound 49c) and 1.75 g of 6-ethyl-2-methyl-5-[[2'-(N-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole (compound 49d) were obtained from 1.84 g of 6-ethyl-2-methyl-1H-pyrazolo[1,5-b][1,2,4]triazole.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9](O)=[O:10])[CH2:5][CH2:4]1.C([Mg]Br)C(C)C.CCOCC.Cl>>[F:1][C:2]([F:12])([F:13])[C@H:3]1[CH2:4][CH2:5][C@H:6]([CH:9]=[O:10])[CH2:7][CH2:8]1
Reactant: O=C(O)[C@H]1CC[C@H](C(F)(F)F)CC1
Agent: CC(C)C[Mg]Br
Agent: Cl
Solvent: CCOCC
Product: O=C[C@H]1CC[C@H](C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.05 mol of trans-4-trifluoromethylcyclohexanecarboxylic acid (prepared as in Example 1) is added dropwise to 100 ml of a solution of isobutylmagnesium bromide in ether (1 mol/1) and 0.3 mmol of dichlorobis[π-cyclopentadienyl]titanium at 0° C., and the mixture is stirred at room temperature for 4 hours. 30 ml of a 4 normal hydrochloric acid are added, and customary workup gives the product as a colourless oil.
Reaction SMILES: Br[C:2]1[C:3]2[CH:12]=[CH:11][N:10]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH2:23]([O:25][C:26]([C:28]1[CH:29]=[CH:30][C:31]([F:37])=[C:32](B(O)O)[CH:33]=1)=[O:27])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([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)=CC=1>[F:37][C:31]1[CH:30]=[CH:29][C:28]([C:26]([O:25][CH2:23][CH3:24])=[O:27])=[CH:33][C:32]=1[C:2]1[C:3]2[CH:12]=[CH:11][N:10]([S:13]([C:16]3[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: CCOC(=O)c1ccc(F)c(B(O)O)c1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(Br)cn(C)c(=O)c32)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)c1ccc(F)c(-c2cn(C)c(=O)c3c2ccn3S(=O)(=O)c2ccc(C)cc2)c1
Temperature: 90 °C
Yield: 87.2 %

Procedure:
A mixture of Example 1e (1.33 g, 3.5 mmol), 5-(ethoxycarbonyl)-2-fluorophenylboronic acid (1.04 g, 4.9 mmol), Pd(PPh3)4 (0.20 g, 5 mol %), and sodium carbonate (0.742 g, 7.0 mmol) in toluene (12 mL), ethanol (3 mL) and water (3 mL) was degassed and stirred under a nitrogen atmosphere. The reaction mixture was heated at 90° C. for 24 hours. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate twice. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 20-50% ethyl acetate in hexanes) to afford 1.43 g (87%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:4]([CH:5]=O)[C:3]=1[OH:10].[Br:11][C:12]1[CH:25]=[CH:24][C:15]([NH:16][S:17]([CH2:20][C:21](O)=[O:22])(=[O:19])=[O:18])=[CH:14][CH:13]=1>C(O)(=O)C>[Br:11][C:12]1[CH:13]=[CH:14][C:15]([NH:16][S:17]([C:20]2[C:21](=[O:22])[O:10][C:3]3[C:4]([CH:5]=2)=[CH:7][CH:8]=[CH:9][C:2]=3[Br:1])(=[O:19])=[O:18])=[CH:24][CH:25]=1
Reactant: O=C(O)CS(=O)(=O)Nc1ccc(Br)cc1
Reactant: O=Cc1cccc(Br)c1O
Solvent: CC(=O)O
Product: O=c1oc2c(Br)cccc2cc1S(=O)(=O)Nc1ccc(Br)cc1

Procedure:
A solution of 3-bromosalicylaldehyde (1 mmol) and 4-bromoanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 206-208° C.
Reaction SMILES: C(O[C:4](=O)[CH2:5][C:6](=O)[C:7]1C=CC=C[C:8]=1N=NC1C=CC(Cl)=CC=1)C.Cl[C:25]1[CH:30]=[CH:29][C:28]([N:31]2[N:35]=[C:34]([CH:36]=[O:37])[C:33]([CH3:38])=[N:32]2)=[CH:27][CH:26]=1.C(OC(=O)C(N=NC1C=CC(Cl)=CC=1)C(C)=O)C>>[CH:36]([C:34]1[C:33]([C:38]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:32][N:31]([C:28]2[CH:29]=[CH:30][CH:25]=[CH:26][CH:27]=2)[N:35]=1)=[O:37]
Reactant: Cc1nn(-c2ccc(Cl)cc2)nc1C=O
Reactant: CCOC(=O)CC(=O)c1ccccc1N=Nc1ccc(Cl)cc1
Agent: CCOC(=O)C(N=Nc1ccc(Cl)cc1)C(C)=O
Product: O=Cc1nn(-c2ccccc2)nc1-c1ccccc1

Procedure:
In a similar manner, 2-(4'-chlorophenyl)-4-formyl-5-phenyl-1,2,3-triazole of melting point 137° - 138° C. is obtained using 2-(4'-chlorophenylazo)-benzoylacetic acid ethyl ester and 2-(4'chlorophenyl)-4-formyl-5-methyl-1,2,3-triazole of melting point 110° - 111° C. is obtained using 2-(4'-chlorophenylazo)-acetoacetic acid ethyl ester.