Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[N+:30]([O-])([N+]([O-])=O)=[O:31]>O1CCCC1.C(Cl)Cl>[Cl:1][CH2:2][CH2:3][N:4]([N:30]=[O:31])[C:5]([N:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6]
Reactant: O=[N+]([O-])[N+](=O)[O-]
Reactant: CCCCCN(C(=O)NCCCl)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCCCCN(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Yield: 71.3 %

Procedure:
3.5 g of 1-(2-chloroethyl)-3-n-pentyl-3-D-galactopyranosylurea are dissolved in a mixture of 80 ml of tetrahydrofuran and 80 ml of methylene chloride, and 15 g of sodium carbonate anhydrate are added thereto. 5 g of nitrogen tetroxide gas are introduced into the mixture for 10 minutes under ice-cooling. The mixture is treated in the same manner as described in Example 2. 2.7 g of 1-(2-chloroethyl)-1-nitroso-3-n-pentyl-3-D-galactopyranosylurea are thereby obtained as yellow caramel.
Reaction SMILES: [CH2:1]([N:10]1[C:14](=[O:15])[CH:13]=[CH:12][C:11]1=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[SH:17][CH2:18][CH2:19][NH2:20].C(N(CC)CC)C>C(#N)C>[NH2:20][CH2:19][CH2:18][S:17][CH:13]1[CH2:12][C:11](=[O:16])[N:10]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[C:14]1=[O:15]
Reactant: CCCCCCCCCN1C(=O)C=CC1=O
Reactant: NCCS
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCCCCCCCN1C(=O)CC(SCCN)C1=O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of N-nonyl maleimide (0.01 M) prepared as described in Example 12 above, mercapto ethylamine (0.01 M) and triethylamine (0.001 M) in acetonitrile (50 ml) was stirred for 24 hours at room temperature. Acetonitrile was evaporated in vacuo and the residue obtained was triturated with ethyl acetate (25 ml). The resultant suspension was filtered and the solid washed with ethyl acetate. The solid was then dried and characterised as the desired product, N-nonyl,3-mercapto ethylamino maleimide.
Reaction SMILES: [NH2:1][NH2:2].[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:21])OC2C=CC=CC=2)=[CH:8][CH:7]=1)([O-:5])=[O:4]>O1CCOCC1>[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([NH:1][NH2:2])=[O:21])=[CH:8][CH:7]=1)([O-:5])=[O:4]
Reactant: O=C(Nc1ccc([N+](=O)[O-])cc1)Oc1ccccc1
Reactant: NN
Solvent: C1COCCO1
Product: NNC(=O)Nc1ccc([N+](=O)[O-])cc1

Procedure:
Hydrazine (1.18 mol) was added dropwise over a 1 hour period to a solution of intermediate (1) in 1,4-dioxane (1000 ml) and the mixture was stirred and refluxed overnight. The mixture was cooled and filtered off, yielding N-(4-nitro-phenyl)hydrazinecarboxamide (intermediate 2).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][NH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)(O)[O-].[Na+].[Cl:15][CH2:16][C:17](Cl)=[O:18].O>C1(C)C=CC=CC=1>[Cl:15][CH2:16][C:17]([NH:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:18]
Reactant: O=C(Cl)CCl
Reactant: NCCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(CCl)NCCc1ccccc1
Temperature: 2.5 °C
Reaction time: 3 h

Procedure:
β-phenylethylamine (0.68 kg) was taken in dry toluene (4.42 L) and sodium bicarbonate (0.612 kg) was added at 30° C. and cooled to 0-5° C. Chloroacetyl chloride was slowly added under nitrogen blanket at 0-10° C., stirred and maintained for 2 hr. After completion of the reaction, water was added slowly and reaction mass was allowed to attain 33±2° C. and the layers were separated. To the aqueous layer toluene was added, stirred and two layers were separated. To the organic layer dil HCl solution (0.653 L DM water+0.272 L con HCl) was added, stirred and two layers were separated. To the organic layer again sodium bicarbonate solution (0.653 L DM water+0.068 kg sodium bicarbonate) was added, stirred and two layers were separated. Water was added to the organic layer, stirred and two layers were separated. From the organic layer toluene was distilled out, methanol was added, heated to 58° C., stirred. To the reaction mass water was added, temperature was maintained at 58° C., stirred for 1-1.5 hr, cool to 30±2° C. for 3 hrs under stirring. Stirring was continued for 3 hrs at 0-5° C. The reaction mass was filtered, washed with water and dried.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:13]2[C:21]3[C:16](=[C:17]([CH:22]=[O:23])[CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14]2)[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:35][CH3:36]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:13]2[C:21]3[C:16](=[C:17]([CH:22]=[O:23])[CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14]2)([CH2:35][CH3:36])[C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=1
Reactant: COC(=O)C(c1ccc(Cl)cc1)n1ccc2c(C=O)cccc21
Reactant: CCI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCC(C(=O)OC)(c1ccc(Cl)cc1)n1ccc2c(C=O)cccc21
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of methyl 2-(4-chlorophenyl)-2-(4-formyl-1H-indol-1-yl)acetate (2.34 g, 7.17 mmol) in THF (60 mL) and HMPA (15 mL) was added LiHMDS (1 M in THF, 11.0 mL, 11 mmol) dropwise at 0° C. The mixture was stirred at 0° C. for 30 min before adding iodoethane (1.23 g, 7.88 mmol). After stirring for another 30 min at 0° C., the mixture was diluted with EtOAc (120 mL) and then quenched with water (20 mL). The organic layer was separated and washed with brine (20 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was purified via column chromatography (0-15% EtOAc/hexanes) to provide the title compound.
Reaction SMILES: O[CH2:2][CH2:3][N:4]([C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([O:13][CH3:14])=[O:12])[CH2:5]CO.O=P(Cl)(Cl)[Cl:20].[CH:23]([Cl:26])(Cl)Cl>>[Cl:20][CH2:2][CH2:3][N:4]([C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([O:13][CH3:14])=[O:12])[CH2:5][CH2:23][Cl:26]
Reactant: ClC(Cl)Cl
Reactant: O=P(Cl)(Cl)Cl
Reactant: COC(=O)c1cccc(N(CCO)CCO)c1
Product: COC(=O)c1cccc(N(CCCl)CCCl)c1
Reaction time: 2.7 h

Procedure:
A solution of 120a (6.9 g, 29 mmol) in chloroform (50 mL) was added over 2 h to POCl3 (9.9 g) with heating under reflux. After 2.7 h additional reflux, the mixture was cooled in an ice bath, and filtered to remove a white precipitate. The filtrate was neutralized by extraction with saturated aqueous NaHCO3 and chloroform. The organic phase was dried (Na2SO4), filtered, and evaporated to an oil (5.4 g). IR(neat): cm-1 1720. 1H NMR(300 MHz, CDCl3): 7.42-6.87 (m, 4H), 3.90(s, 3H), 3.77 (t,4H, J=7 Hz), 3.64 (t, 4H, J=7 Hz). HR-MS: Calc'd. 276.0558, Found 276.0553.
Reaction SMILES: [C:1]([C:3]1[C:8]2[S:9][CH:10]=[CH:11][C:7]=2[C:6]([NH:12][C@H:13]([C@@H:17]([OH:19])[CH3:18])[C:14]([OH:16])=O)=[CH:5][CH:4]=1)#[N:2].[C:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)#[N:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC>C1COCC1>[C:20]([C:22]1[CH:23]=[CH:24][C:25]([C:26]([NH:28][NH:29][C:14](=[O:16])[C@H:13]([NH:12][C:6]2[C:7]3[CH:11]=[CH:10][S:9][C:8]=3[C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[C@@H:17]([OH:19])[CH3:18])=[O:27])=[CH:30][CH:31]=1)#[N:21]
Reactant: N#Cc1ccc(C(=O)NN)cc1
Reactant: C[C@H](O)[C@@H](Nc1ccc(C#N)c2sccc12)C(=O)O
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: C1CCOC1
Product: C[C@H](O)[C@@H](Nc1ccc(C#N)c2sccc12)C(=O)NNC(=O)c1ccc(C#N)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 67.8 %

Procedure:
To a mixture of (2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid (0.66 g, 2.39 mmol), 4-cyanobenzhydrazide (390 mg, 2.42 mmol), HOBt (327 mg, 2.42 mmol) in THF (40 mL) was added EDC (696 mg, 3.63 mmol) and Et3N (0.56 mL, 4.02 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min., then at room temperature overnight. The reaction was quenched by adding water and extracted with EtOAc (400 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. Removal of the solvent and purification of the residue gave the title compound 4-cyano-N′-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide (0.68 g, 68%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.09 (d, J=8.6 Hz, 2H), 7.93 (d, J=8.6 Hz, 2H), 7.81 (d, J=5.7 Hz, 1H), 7.73 (d, J=5.7 Hz, 1H), 7.67 (d, J=8.2 Hz, 1H), 6.68 (d, J=8.2 Hz, 1H), 6.21 (d, J=7.2 Hz, 1H), 4.42 (m, 1H), 4.25 (dd, J=3.9, 7.2 Hz, 1H), 1.39 (d, J=6.4 Hz, 3H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([I:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].CCN(C(C)C)C(C)C.[CH3:24][CH:25]([SH:27])[CH3:26]>>[CH:25]([S:27][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([I:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14])([CH3:26])[CH3:24]
Reactant: N#Cc1cnc2ccc(I)cc2c1Cl
Reactant: CC(C)S
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)Sc1c(C#N)cnc2ccc(I)cc12

Procedure:
Similar procedure as described in example 39a was used, starting from 4-chloro-6-iodo-quinoline-3-carbonitrile (example 14c), DIEA and 2-propanethiol to give 4-isopropylsulfanyl-6-iodo-quinoline-3-carbonitrile. LC-MS m/e 355 (MH+).
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[Br:7][C:8]1[CH:16]=[CH:15]C(C(O)=O)=[CH:10][C:9]=1[F:17].CN(C=O)C>C(Cl)Cl>[Br:7][C:8]1[CH:16]=[CH:15][C:1]([C:2]([Cl:4])=[O:3])=[CH:10][C:9]=1[F:17]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1ccc(Br)c(F)c1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(Br)c(F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Oxalyl dichloride (6.1 g, 48 mmol) was added to a solution of 4-bromo-3-fluoro-benzoic acid (7 g, 32 mmol) in DCM (80 mL) at 0° C. followed by DMF (0.2 mL) and the reaction mixture was stirred at RT for 2 h and then concentrated under vacuum to provide crude 4-bromo-3-fluoro-benzoyl chloride.
Reaction SMILES: C[O:2][CH:3]=[C:4]1[CH2:9][CH2:8][CH:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1.O1CCCC1>O>[C:14]([C:13]1[CH:16]=[CH:17][C:10]([CH:7]2[CH2:8][CH2:9][CH:4]([CH:3]=[O:2])[CH2:5][CH2:6]2)=[CH:11][CH:12]=1)#[N:15]
Reactant: COC=C1CCC(c2ccc(C#N)cc2)CC1
Solvent: C1CCOC1
Solvent: O
Product: N#Cc1ccc(C2CCC(C=O)CC2)cc1
Yield: 99 %

Procedure:
A mixture of 4.2 g of p-[4-(methoxymethylene)cyclohexyl]benzonitrile and 100 ml of tetrahydrofuran/2N hydrochloric acid (vol. 4:1) was heated to reflux for 30 minutes in a round flask. The mixture was subsequently poured into 100 ml of water and extracted three times with 100 ml of diethyl ether each time. The organic phases were washed once with 100 ml of water, dried over magnesium sulphate and concentrated. There were obtained 3.9 g (100%) of 4-(p-cyanophenyl)cyclohexanecarboxaldehyde as a colourless oil which was used in the next step without further purification: trans/cis ratio about 3:1, Rf-value (ethyl acetate/petroleum ether, vol. 3:7) 0.41. By recrystallization from hexane there could be obtained pure trans-4-(p-cyanophenyl)cyclohexanecarboxaldehyde; m.p. 57.1° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][C:5]([Br:8])=[CH:6][CH:7]=1.O=S(Cl)Cl.[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH2:23]>C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:3]([C:9]([NH:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[F:16])=[O:11])=[N:4][C:5]([Br:8])=[CH:6][CH:7]=1
Reactant: Nc1ccccc1F
Reactant: Nc1ccc(Br)nc1C(=O)O
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Product: Nc1ccc(Br)nc1C(=O)Nc1ccccc1F
Temperature: 130 °C
Reaction time: 2 h
Yield: 44.8 %

Procedure:
A mixture of 3-amino-6-bromopicolinic acid (250 mg, 1.152 mmol) and SOCl2 (5 mL) in toluene (10 mL) was stirred at 130° C. for 2 h, then evaporated and dissolved in tetrahydrofuran (20 mL). 2-fluoro-phenylamine (256 mg, 2.3 mmol) was added dropwise maintaining the temperature at 5° C. The reaction mixture was heated to 90° C. for 15 h. The mixture was cooled to room temperature and quenched with saturated aqueous K2CO3 (10 mL) and extracted with ethyl acetate (10 mL*3), the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified with column chromatograph (PE:EtOAc=3:1) to give 3-amino-6-bromo-N-(2-fluorophenyl)picolinamide (160 mg, yield: 45%). MS (M+H)+: 311/313.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([NH:13][CH:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[CH2:15][O:16][CH2:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[O:12])=[CH:8][CH:9]=2)[NH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:43][C:44]([F:47])([F:46])[F:45])(=O)=O.O>CS(C)=O>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([NH:13][CH:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[CH2:15][O:16][CH2:17][CH:18]3[CH2:23][CH2:22][N:21]([CH2:43][C:44]([F:47])([F:46])[F:45])[CH2:20][CH2:19]3)=[O:12])=[CH:8][CH:9]=2)[NH:4][CH:3]=1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: O=C(NC(COCC1CCNCC1)c1ccccc1Cl)c1ccc2c(Cl)c[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: O=C(NC(COCC1CCN(CC(F)(F)F)CC1)c1ccccc1Cl)c1ccc2c(Cl)c[nH]c2c1
Yield: 29.6 %

Procedure:
To a solution of 3-chloro-N-[1-(2-chlorophenyl)-2-(piperidin-4-ylmethoxy)ethyl]-1H-indole-6-carboxamide (700 mg, 1.6 mmol) in 5 mL of DMSO was added potassium carbonate (1.0 g, 7.9 mmol) and 2,2,2-trifluoroethyl trifluoromethane-sulfonate (364 mg, 1.6 mmol). The reaction was allowed to stir at room temperature overnight after which time water was added and the resulting precipitate was isolated by filtration. Purification of the filtrate (SiO2: 30% EtOAc in hexane) provided 250 mg (30%) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][N:5]=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:14](O)=O>>[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:14]2[NH:8][C:7]3[C:2](=[N:3][CH:4]=[N:5][CH:6]=3)[N:1]=2)[CH:17]=[CH:18][C:19]=1[NH:20][S:21]([CH3:24])(=[O:23])=[O:22]
Reactant: COc1cc(C(=O)O)ccc1NS(C)(=O)=O
Reactant: Nc1cncnc1N
Product: COc1cc(-c2nc3ncncc3[nH]2)ccc1NS(C)(=O)=O

Procedure:
Prepared analogously to Example 14 from 4,5-diaminopyrimidine and 3-methoxy-4-methanesulfonylamino-benzoic acid.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[P:20](Cl)([Cl:22])[Cl:21]>>[C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:8][CH2:9][CH:10]([O:13][P:20]([Cl:22])[Cl:21])[CH2:11][CH2:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: ClP(Cl)Cl
Reactant: OC1CCC(c2ccccc2)(c2ccccc2)CC1
Product: ClP(Cl)OC1CCC(c2ccccc2)(c2ccccc2)CC1

Procedure:
A process for preparing (4,4-diphenylcyclohexyl)phosphooxymethyl diethylene triaminepenta-acetic acid comprising the steps of: (a) phosphorylating 1.0 equivalents of 4,4-diphenylcyclohexanol with about one equivalent of phosphorous trichloride to obtain 4,4-diphenylcyclohexyloxy dichlorophosphine having the formula: ##STR20## (b) coupling the 4,4-diphenylcyclohexyloxy-dichlorophosphine formed in step (a) with from about 5 to about 6 equivalents of imidazole to obtain 4,4-diphenycyclohexyloxy-diimidazolylphosphine having the formula: ##STR21## where imido refers to imidazolyl (c) coupling of the 4,4-diphenylcyclohexyloxy- diimidazolylphosphine formed in step (b) with from about 0.75 to about 1.0 equivalents of hydroxymethyl-DTPA penta tert-butyl ester to obtain 4,4-diphenylcyclohexyloxy (hydroxymethyl-DTPA -oxy, penta tert-butyl ester) imidazolyl-phosphine having the formula: ##STR22## where imido refers to imidazolyl (d) hydrolysis and oxidation of the 4,4-diphenylcyclohexyloxy (hydroxymethyl-DTPA oxy, penta tert butyl ester) imidazolylphosphine formed in step (c) with dilute HCl and from about 0.5 to about 2.0 equivalents to sodium periodate to form (4,4-diphenylcyclohexyl)phosphonooxymethyl diethylene triamine, penta t-butyl ester having the formula: ##STR23##
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:8]1(OC)[C:9](=[CH:11][CH:12]=[CH:13][CH:14]=1)[OH:10].[CH3:17][C:18]([CH3:20])=O.C(C1C=CC=CC=1C=C)=C.C(S)C>>[CH3:17][C:18]([C:13]1[CH:12]=[CH:11][C:9]([OH:10])=[CH:8][CH:14]=1)([C:4]1[CH:3]=[CH:2][C:1]([OH:7])=[CH:6][CH:5]=1)[CH3:20]
Reactant: Oc1ccccc1
Reactant: COc1ccccc1O
Reactant: CC(C)=O
Agent: C=Cc1ccccc1C=C
Solvent: CCS
Product: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Yield: 12.9 %

Procedure:
A molten solution of phenol (1848 g, 19.65 mol), guaiacol (812 g, 6.55 mol), and acetone (120 g, 2.14 mol) at 50 C was fed downflow to a jacketed reactor containing 35 g of attached promoter IER catalyst (a monodispersed strongly acidic ion exchange resin with 2% divinylbenzene crosslinking, modified with ethylmercaptan promoter, 2.2 meg strong acid/g, 1.4 meg SH/g) with weighted hourly space velocity=1.0 while the reactor was held at 70 C. The reactor effluent was cooled to 40 C and filtered to remove the BPA-phenol adduct. The filtrate was then stripped to 170 C/20 ml torr and the residue crystallized from isopropyl alcohol. The filtrate from the isopropyl alcohol was stripped to dryness on a rotovap and the residue purified by column chromatography (eluting with 85% cyclohexane/15% ethyl acetate on silica gel) to give 63 g of a BPA:monomethoxyBPA:dimethoxyBPA mixture that was 18% BPA, 63% monomethoxyBPA, and 18% dimethoxyBPA by UPLC peak area.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][O:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:22])[CH3:21])=[CH:16][CH:15]=1>>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH:21][C:20]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH2:12][O:11][CH3:10])=[CH:15][CH:16]=2)=[O:22])=[CH:4][CH:3]=1
Reactant: COCOc1ccc(C(C)=O)cc1
Reactant: O=Cc1ccc(Cl)cc1
Product: COCOc1ccc(C(=O)C=Cc2ccc(Cl)cc2)cc1

Procedure:
By a procedure similar to that of example 1.59.1, starting from 4-chlorobenzaldehyde and p-methoxymethoxyacetophenone, 3-(4-chlorophenyl)-1-(4-methoxymethoxy-phenyl)prop-2-en-1-one was obtained as yellowish solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[CH:16]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][CH2:26][F:27].O>CN(C)C=O.C(Cl)(Cl)Cl>[F:27][CH2:26][CH2:25][CH2:24][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[CH:16]=2)=[CH:6][CH:7]=1
Reactant: Oc1ccc(-c2cn3ccccc3n2)cc1
Reactant: FCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: FCCCOc1ccc(-c2cn3ccccc3n2)cc1
Temperature: 25 °C
Reaction time: 20.5 h
Yield: 51.9 %

Procedure:
398 mg (corresponding to 1.89 mmol) of 2-(4′-hydroxyphenyl)imidazo[1,2-a]pyridine was dissolved in 15 mL of N,N-dimethylformamide, and 788 mg (corresponding to 5.7 mmol) of potassium carbonate was added thereto. 260 μL (corresponding to 2.8 mmol) of 1-bromo-3-fluoropropane was added to the resulting mixture, and the mixture was stirred for 20.5 hours at room temperature. After the completion of the reaction, the reaction solution was poured into water and extracted three times with chloroform. The combined chloroform layer was washed with water and a saturated sodium chloride solution, and then dried over anhydrous sodium sulfate, filtered and concentrated. The resulting crude product was purified by recycle preparative HPLC (HPLC apparatus: LC-908 (under trade name; manufactured by Japan Analytical Industry Co., Ltd.); column: two of JAIGEL 2H (under trade name; manufactured by Japan Analytical Industry Co., Ltd.) connected together; mobile phase: chloroform), to obtain 264 mg (corresponding to 0.98 mmol) of 2-[4′-(3″-fluoropropoxy)phenyl]imidazo[1,2-a]pyridine (hereinafter referred to as Compound 3) (FIG. 4, Step 3).
Reaction SMILES: Br[CH2:2][C:3]1[NH:8][C:7]([C:9]2[N:10]=[CH:11][S:12][CH:13]=2)=[N:6][CH:5]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[C:4]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23].Cl.[NH:28]1[CH2:33][CH2:32][O:31][CH:30]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH2:29]1>>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH:5]1[N:6]=[C:7]([C:9]2[N:10]=[CH:11][S:12][CH:13]=2)[NH:8][C:3]([CH2:2][N:28]2[CH2:33][CH2:32][O:31][CH:30]([CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH2:29]2)=[C:4]1[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: O=C(O)CCC1CNCCO1
Reactant: CCOC(=O)C1=C(CBr)NC(c2cscn2)=NC1c1ccc(Cl)cc1Cl
Agent: Cl
Product: CCOC(=O)C1=C(CN2CCOC(CCC(=O)O)C2)NC(c2cscn2)=NC1c1ccc(Cl)cc1Cl
Yield: 44.9 %

Procedure:
Ethyl 6-(bromomethyl)-4-(2,4-dichlorophenyl)-2-(thiazol-4-yl)-1,4-dihydropyrimidine-5-carboxylate (0.73 g, 1.53 mmol) was reacted with 3-(morpholin-2-yl)propanoic acid hydrochloride (0.3 g, 1.53 mmol) according to the procedure as described in Example 28 to give the title compound as a yellow solid (0.38 g, 45%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1.O.[C:27](OCC)(=[O:29])C.Cl>C[O-].[Na+].CN(C)C=O>[CH3:27][O:29][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1
Reactant: CCOC(C)=O
Reactant: O=C(O)c1ccc(-c2ccc(OCCCCCCCCBr)cc2)cc1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCCCCCCCOc1ccc(-c2ccc(C(=O)O)cc2)cc1

Procedure:
A solution of 4-[4-(8-Bromooctyloxy)phenyl]benzoic acid (1 g) in a mixture of sodium methylate (28% solution in metanol) (10 ml) and N,N-dimethylformamide (5 ml) was refluxed for 5 hours. The reaction mixture was added to a mixture of water and ethyl acetate and adjusted to pH 2.0 with conc. HCl. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give 4-[4-(8-Methoxyoctyloxy)phenyl]benzoic acid (0.77 g).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:11][C:10](=[O:12])[C:9]([CH2:13][CH:14]([CH3:16])[CH3:15])=[N+:8]([O-:17])[C:7]=1[OH:18])=[O:5])[CH3:2].[CH2:19](OCC)C.[N+](=C)=[N-].C(O)(=O)C>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[NH:11][C:10](=[O:12])[C:9]([CH2:13][CH:14]([CH3:15])[CH3:16])=[N+:8]([O-:17])[C:7]=1[O:18][CH3:19])=[O:5])[CH3:2]
Reactant: CCOCC
Reactant: CCOC(=O)c1[nH]c(=O)c(CC(C)C)[n+]([O-])c1O
Agent: C=[N+]=[N-]
Solvent: ClC(Cl)Cl
Solvent: CC(=O)O
Product: CCOC(=O)c1[nH]c(=O)c(CC(C)C)[n+]([O-])c1OC
Reaction time: 0.5 h

Procedure:
To a suspension of 5.45 g of 6-ethoxycarbonyl-5-hydroxy-3-isobutyl-1,2-dihydropyrazin-2-one 4-oxide in chloroform was added dropwise gradually about equivalent quantity of diethyl ether solution of diazomethane at -15° C. 30 Minutes after the addition, 0.5 ml of acetic acid was added to the reaction mixture, and this mixture was allowed to stand for 30 minutes. Then the whole mixture was washed with water, and the solvent was removed by distillation, to the thus obtained residue was added 30 ml of chloroform and dissolved by heating, then 200 ml of diisopropyl ether was added gradually thereto so as to form crystals. The precipitated crystals were collected by filtration, and said operation were repeated twice to obtain 3.10 g of 6-ethoxycarbonyl-3-isobutyl-5-methoxy-l,2-dihydropyrazin-2-one 4-oxide.