Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([F:11])[C:4]=1[NH2:5])#[CH:2]>C(O)C.O.O.[Au](Cl)(Cl)Cl.[Na]>[F:10][C:8]1[CH:9]=[C:3]2[C:4](=[C:6]([F:11])[CH:7]=1)[NH:5][CH:2]=[CH:1]2
Reactant: C#Cc1cc(F)cc(F)c1N
Agent: Cl[Au](Cl)Cl
Agent: [Na]
Solvent: CCO
Solvent: O
Product: Fc1cc(F)c2[nH]ccc2c1
Reaction time: 3 h
Yield: 68.7 %

Procedure:
The impure 2-ethynyl-4,6-difluoroaniline (4.2 g, 19 mmol) from the previous example was dissolved in ethanol (75 mL), treated with sodium gold(III) chloride dihydrate (310 mg, 0.77 mmol) and stirred for 3 h under an atmosphere of nitrogen. The mixture was concentrated, taken up in ethyl acetate, washed with water, washed with sat. NaCl, dried over sodium sulfate (Na2SO4) and evaporated. Purification by flash chromatography (SiO2, 100-200 mesh; eluting with 0-15% EtOAc in hexanes containing 2% acetic acid) provided of the title product (2.0 g, ca 85% purity): 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.26 (dd, J=4.8, 2.0 Hz, 1H), 7.09 (dd, J=9.1, 2.2 Hz, 1H), 6.74 (ddd, J=11.2, 9.3, 2.0 Hz, 1H), 6.55 (td, J=3.3, 2.2 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ −122.11, −131.96. EIMS m/z 153.
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1>>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:2]2[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:19][CH:18]=1
Reactant: Nc1nnc(Br)c(-c2ccccc2)n1
Reactant: COc1ccc(O)cc1
Product: COc1ccc(Oc2nnc(N)nc2-c2ccccc2)cc1
Yield: 12.8 %

Procedure:
6-(4-Methoxyphenoxy)-5-phenyl-1,2,4-triazin-3-amine (45 mg, 13%) was prepared from 6-bromo-5-phenyl-1,2,4-triazin-3-amine (0.30 g, 1.19 mmol) and 4-methoxyphenol (0.30 g, 2.39 mmol) according to the general procedure of Example 3.
Reaction SMILES: Cl.[F:2][C:3]1[C:4]([O:13][CH3:14])=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[NH2:12])[CH:6]=[CH:7][CH:8]=1.[CH:15]([CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CO.C(Cl)Cl>[F:2][C:3]1[C:4]([O:13][CH3:14])=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[NH:12][CH2:15][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][CH2:18]2)[CH:6]=[CH:7][CH:8]=1
Reactant: CC(C)(C)OC(=O)N1CCC(C=O)CC1
Reactant: COc1c(F)cccc1[C@@H]1C[C@H]1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Solvent: CO
Product: COc1c(F)cccc1[C@@H]1C[C@H]1NCC1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 0.05 h
Yield: 23.9 %

Procedure:
To a solution of trans-2-(3-fluoro-2-methoxyphenyl)cyclopropanamine hydrochloride (Biochemistry 2010, 49(30), 6494) (500 mg, 2.76 mmol) in a mixture of 1,2-dichloroethane (20 mL) and MeOH (5 mL) was added tert-butyl 4-formylpiperidine-1-carboxylate (588 mg, 2.76 mmol) and stirred for 3 min then Na(OAc)3BH (1.75 g, 8.28 mmol) was added and stirred for 10 min at RT. The reaction mixture was diluted with DCM (100 mL) and washed with water (2×50 mL), and brine (20 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated. The crude was purified by column chromatography using silica gel, eluting with 2% MeOH in DCM to afford tert-butyl 4-(((trans)-2-(3-fluoro-2-methoxyphenyl)cyclopropylamino)methyl)piperidine-1-carboxylate (250 mg, 25% yield) as yellow liquid. LCMS (ES) m/e 379.45 (M+H)+. To a solution of tert-butyl 4-(((trans)-2-(3-fluoro-2-methoxyphenyl)cyclopropylamino)methyl)piperidine-1-carboxylate (200 mg, 0.529 mmol) in 1,4-dioxane (5 mL) was added 4N HCl in 1,4-dioxane (30 mL) and stirred for 8 h at RT. The reaction mixture was concentrated and the residue was triturated with diethyl ether (50 mL), EtOAc (20 mL) and dried under high vacuum to afford (trans)-2-(3-fluoro-2-methoxyphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine hydrochloride (130 mg, 88%) as off white solid. LCMS (ES) m/e 279.45 (M+H)+, 95.34%, (DMSO-d6) δ ppm 9.53 (bs, 2H), 8.88 (bs, 1H), 8.69 (bs, 1H), 7.15 (t, J=8.4 Hz, 1H), 7.09-7.07 (m, 1H), 6.78 (d, J=8.0 Hz, 1H), 3.90 (s, 3H), 3.29 (d, 2H), 3.0 (bs, 3H), 2.79-2.89 (m, 3H), 2.05 (bs, 1H), 1.96 (d, J=13.6 Hz, 2H), 1.63 (m, 1H), 1.38-1.47 (m, 2H), 1.24-1.29 (m, 1H).
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[S:8][C:9]2[C:10]([CH2:15][S:16][CH2:17][CH2:18][NH:19]C(OC(C)(C)C)=O)=[N:11][CH:12]=[CH:13][CH:14]=2)C=CC=CC=1.C([SiH](CC)CC)C.[F:46][C:47]([F:52])([F:51])[C:48]([OH:50])=[O:49]>ClCCl>[F:46][C:47]([F:52])([F:51])[C:48]([OH:50])=[O:49].[SH:8][C:9]1[C:10]([CH2:15][S:16][CH2:17][CH2:18][NH2:19])=[N:11][CH:12]=[CH:13][CH:14]=1
Reactant: CC(C)(C)OC(=O)NCCSCc1ncccc1SC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCCSCc1ncccc1S
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Into a 1 L round bottom flask equipped with a mechanical stirrer, thermometer and nitrogen purge was charged 3-triphenylmethylthio-2-(t-butoxycarbonylaminoethylthiomethyl)pyridine (40.0 g, 0.074 mol, 1 eq) followed by dichloromethane (200 mL). The light yellow solution was cooled to 0° C. and triethylsilane (60 mL) was added followed by dropwise addition of trifluoroacetic acid (200 mL) over approximately five minutes. The cold bath was removed and the solution was allowed to warm to room temperature (over 30 minutes) and was then allowed to stir at 20° C. for 30 minutes. The solvent was removed by rotary evaporation to give 27.75 g of the title compound as an orange waxy solid. 1H NMR (D2O) δ 2.88 (t, 2H); 3.28 (t, 3H); 4.18 (s, 2H); 7.45 (dd, 1H); 8.22 (d, 1H); 8.55 (d, 1H).
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:28])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)C.[BH4-].[Na+]>O1CCCC1>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([CH2:5][CH2:4][OH:3])[N:7]=2)=[O:28])[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CCOC(=O)Cc1csc(NC(=O)C(CC2CCCC2)c2ccc(Cl)c(Cl)c2)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(Nc1nc(CCO)cs1)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 58.8 %

Procedure:
A solution of {2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (prepared as in Example 1(B)(c), 129 mg, 0.28 mmol) in tetrahydrofuran (1.4 mL) at 25° C. was slowly treated with sodium borohydride (22.5 mg, 0.59 mmol). The resulting reaction mixture was stirred at 25° C. for 10 h. After 10 h at 25° C., a substantial amount of starting material still remained. An additional amount of sodium borohydride (21.4 mg, 0.57 mmol) was added to the reaction mixture, and the reaction mixture was heated under reflux for 14 h. The reaction mixture was allowed to cool to 25° C. and then slowly quenched by the dropwise addition of water. The resulting reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The resulting residue was diluted with ethyl acetate (100 mL) and washed with a saturated aqueous sodium chloride solution (1×50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 then 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-[4-(2-hydroxyethyl)-thiazol-2-yl]-propionamide (68.1 mg, 58%) as a white foam: mp 85-86° C.; FAB-HRMS m/e calcd for C19H22Cl2N2O2S (M+H)+ 413.0858, found 413.0838.
Reaction SMILES: [OH:1][CH2:2][C@:3]([C:6]1[CH:25]=[CH:24][C:9]([C:10]([NH:12][C:13]2[N:18]=[CH:17][C:16]3[CH:19]=[CH:20][N:21]([CH2:22][CH3:23])[C:15]=3[CH:14]=2)=[O:11])=[CH:8][CH:7]=1)([OH:5])[CH3:4].[Cl:26]N1C(=O)CCC1=O>CN(C=O)C>[Cl:26][C:19]1[C:16]2[CH:17]=[N:18][C:13]([NH:12][C:10](=[O:11])[C:9]3[CH:24]=[CH:25][C:6]([C@@:3]([OH:5])([CH3:4])[CH2:2][OH:1])=[CH:7][CH:8]=3)=[CH:14][C:15]=2[N:21]([CH2:22][CH3:23])[CH:20]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCn1ccc2cnc(NC(=O)c3ccc([C@](C)(O)CO)cc3)cc21
Solvent: CN(C)C=O
Product: CCn1cc(Cl)c2cnc(NC(=O)c3ccc([C@](C)(O)CO)cc3)cc21
Temperature: 60 °C
Yield: 23 %

Procedure:
In a 50 mL pear flask was added (S)-4-(1,2-dihydroxypropan-2-yl)-N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (92 mg, 0.27 mmol) in DMF (2 ml) to give a solution. At room temperature 1-chloropyrrolidine-2,5-dione (36 mg, 0.27 mmol) was added, and the mixture was heated to 60° C. for 4 hours, at which point the reaction seemed to have stalled. An additional 0.2 equivalence of 1-chloropyrrolidine-2,5-dione was added, and the mixture was heated to 60° C. for another hour. The mixture was then cooled, and partitioned between brine and EtOAc. The aqueous layer was further extracted with EtOAc, and the organic layers were combined, washed with brine, dried, filtered and concentrated in vacuo. The residue was then triturated with hot EtOAc, and the resulting precipitate was collected on a fritted-glass funnel. The collected solid was then recrystallized from EtOH to give the product (S)-N-(3-chloro-1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (23 mg, 0.062 mmol, 22% yield) as a pink solid. 1H NMR (DMSO-d6) δ 10.68 (s, 1 H), 8.60 (s, 1 H), 8.37 (s, 1 H), 8.02 (s, 2 H), 7.69 (s, 1 H), 7.59 (s, 2 H), 5.05 (s, 1 H), 4.76 (t, J=5.8 Hz, 1 H), 4.19 (q, J=7.1 Hz, 2 H), 3.40-3.50 (m, 2 H), 1.34-1.45 (m, 6 H); m.p. 223.0-223.9° C.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:17]([C:20]2[CH:24]=[C:23]([CH3:25])[NH:22][N:21]=2)=[CH:16][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([OH:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:5].[CH3:26][O:27][C:28](=[O:31])[CH2:29]Br>CN(C)C=O>[CH3:26][O:27][C:28](=[O:31])[CH2:29][N:22]1[C:23]([CH3:25])=[CH:24][C:20]([C:17]2[CH:18]=[CH:19][C:2]([Cl:1])=[C:3]([C:4](=[O:5])[NH:6][CH2:7][C:8]3([OH:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]3)[CH:16]=2)=[N:21]1
Reactant: Cc1cc(-c2ccc(Cl)c(C(=O)NCC3(O)CCCCCC3)c2)n[nH]1
Reactant: COC(=O)CBr
Solvent: CN(C)C=O
Product: COC(=O)Cn1nc(-c2ccc(Cl)c(C(=O)NCC3(O)CCCCCC3)c2)cc1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 80.7 %

Procedure:
A mixture of 2-chloro-N-(1-hydroxy-cycloheptylmethyl)-5-(5-methyl-1H-pyrazol-3-yl)-benzamide (1.08 g, 3 mmol), 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,2,3-diazaphosphorine on polystyrene (2.0 g, 4.6 mmol) and bromo-acetic acid methyl ester (0.69 g, 4.5 mmol) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 2 h. The mixture was filtered and washed with dichloromethane. The filtrate was concentrated in vacuo. The residue was triturated with ethyl acetate to afford the title compound (1.05 g). (3-{4-Chloro-3-[(1-hydroxy-cycloheptylmethyl)-carbamoyl]-phenyl}-5-methyl-pyrazol-1-yl)-acetic acid.
Reaction SMILES: C1(N[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:8]=2)CCCC1.[O:23]1[C:27]2[CH:28]=[CH:29][C:30]([NH2:32])=[CH:31][C:26]=2[O:25][CH2:24]1>>[O:23]1[C:27]2[CH:28]=[CH:29][C:30]([NH:32][C:7]3[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:8]=3)=[CH:31][C:26]=2[O:25][CH2:24]1
Reactant: Cc1nc(NCc2ccccn2)nc(NC2CCCC2)c1C
Reactant: Nc1ccc2c(c1)OCO2
Product: Cc1nc(NCc2ccccn2)nc(Nc2ccc3c(c2)OCO3)c1C

Procedure:
The titled compound was synthesized according to the procedure described for preparation of N4-cyclopentyl-5,6-dimethyl-N2-(pyridin-2-ylmethyl)pyrimidine-2,4-diamine (Example 29) using 1,3-benzodioxol-5-amine instead of cyclopentanamine. The crude material was purified by column chromatography eluting with mixture of chloroform/ethanol/20% water solution of ammonia (200:10:1), and then the final product was washed with diethyl ether to afford the titled compound as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 2.04 (s, 3H), 2.32 (s, 3H), 4.69 (d, J=4.2 Hz, 2H), 5.76 (bs, 1H), 5.95 (s, 2H), 6.22 (s, 1H), 6.67-7.75 (m, 2H), 7.14 (t, J=6.4 Hz, 1H), 7.21 (s, 1H), 7.32 (d, J=7.8 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 8.56 (d, J=3.6 Hz, 1H); MS (ESI) m/z 350.7 (M+1)+.
Reaction SMILES: [C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[CH:17]N(C)C)[CH:15]=O)=[CH:10][CH:9]=1>[Na]>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:17]=[C:3]([C:1]#[N:2])[C:4](=[O:5])[NH:6][CH:15]=2)=[CH:10][CH:9]=1
Reactant: CN(C)C=C(C=O)c1ccc(Cl)cc1
Reactant: N#CCC(N)=O
Agent: [Na]
Product: N#Cc1cc(-c2ccc(Cl)cc2)c[nH]c1=O

Procedure:
Sodium (7 grams in 300 ml methanol) was stirred while a methanolic solution of 2-cyanoacetamide (16 grams) and 2-(4-chlorophenyl)-3-(dimethylamino)acrolein (37 grams) was added. The mixture was refluxed for 1 hour and the resulting precipitate was filtered, washed with ethanol, dissolved in hot water, and then acidified. The resulting precipitate was filtered, washed with water, and identified as the desired product, m.p. 278°-280° C.
Reaction SMILES: [CH:1]1([CH:6]([CH2:12][CH:13]=[CH2:14])[C:7](OCC)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[F-].[Na+]>O1CCCC1.O.C(OCC)(=O)C>[CH:1]1([CH:6]([CH2:12][CH:13]=[CH2:14])[CH2:7][OH:8])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C=CCC(C(=O)OCC)C1CCCC1
Agent: [Al+3]
Agent: [F-]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: C=CCC(CO)C1CCCC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A tetrahydrofuran (15 mL) solution of ethyl 2-cyclopentylpent-4-enoate (6.10 g, 31.6 mmol) was added dropwise over 20 minutes to a tetrahydrofuran (40 mL) solution of lithium aluminum hydride (1.21 g, 31.9 mmol) cooled to 0° C., and the mixture was then stirred at 0° C. for 1 hour and then stirred at room temperature for 2 hours. The mixture was cooled again to 0° C. Ethyl acetate (14.0 mL), water (11.3 mL), tetrahydrofuran (21.0 mL), and sodium fluoride (13.4 g) were added thereto, and the mixture was stirred for 1 hour. The mixture was filtered through Celite to remove insoluble matter. Then, the solution was concentrated, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a colorless oil substance (3.50 g, 56%).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([C:15]([O:17][CH3:18])=[O:16])[CH2:3]1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.C(N(CC)CC)C>ClCCl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH:4]([C:15]([O:17][CH3:18])=[O:16])[CH2:3]1
Reactant: COC(=O)C1CC(O)CCN1C(=O)OC(C)(C)C
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C1CC(OC2CCCCO2)CCN1C(=O)OC(C)(C)C
Reaction time: 3 h
Yield: 97.1 %

Procedure:
To a stirred solution of the alcohol from step D (3.8 g, 15.0 mmol) in anhydrous dichloromethane (50 mL) was added dihydropyran (7.5 mL, 88.6 mmol) followed by p-toluenesulfonic acid monohydrate (71 mg, 0.4 mmol). After 3 h, triethylamine (0.42 mL, 3.0 mmol) was added and the reaction mixture was concentrated in vacuo. Ethyl acetate (100 mL) was added and the resulting solution was washed with brine (3×50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue purified by column chromatography (SiO2, 9:1 to 7:3, hexanes/ethyl acetate) to afford 1-tert-butyl 2-methyl 4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1,2-dicarboxylate (5.0 g, 96%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 5.00-4.62 (m, 2H), 4.15-4.02 (m, 1H), 3.71 (t, J=7.2 Hz, 3H), 3.50-3.47 (m, 1H), 2.49 (br s, 1H), 1.95-1.70 (m, 4H), 1.60-1.42 (m, 13H), 1.27-1.24 (m, 4H).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[CH:6]=[CH:7][C:8]=1Cl.[CH:15]([NH2:18])([CH3:17])[CH3:16]>CS(C)=O>[CH:15]([NH:18][C:8]1[CH:7]=[CH:6][C:5]([N+:10]([O-:12])=[O:11])=[CH:4][C:3]=1[C:2]([F:14])([F:13])[F:1])([CH3:17])[CH3:16]
Reactant: CC(C)N
Reactant: O=[N+]([O-])c1ccc(Cl)c(C(F)(F)F)c1
Solvent: CS(C)=O
Product: CC(C)Nc1ccc([N+](=O)[O-])cc1C(F)(F)F
Temperature: 0 °C
Yield: 100.2 %

Procedure:
To a solution of 45 g of 3-(trifluoromethyl)-4-chloronitrobenzene in 150 ml of DMSO was added 13 g of isopropylamine. The mixture was heated at 80°-90° C. for two hours, poured over ice water, acidified and filtered. The filter cake was dried to yield 49.6 g of product; m.p. 35°-36° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.[Li]CCCC.[CH:14]1([CH:20]=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>C1COCC1.CCOC(C)=O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([CH:20]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[OH:21])=[CH:3][CH:4]=1
Reactant: Brc1ccc(Br)cc1
Reactant: O=CC1CCCCC1
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OC(c1ccc(Br)cc1)C1CCCCC1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1,4-dibromobenzene (42.4 mmol, 10 g) in THF (100 mL) at −78° C. was added dropwise n-BuLi (42.4 mmol, 2 M in hexane). The mixture was stirred at −78° C. for 0.5 h., cyclohexanecarboxaldehyde (42.4 mmol, 4.8 g) was added. The mixture was stirred at −78° C. for 0.5 h and then warmed to r.t. The reaction mixture was diluted with EtOAc, washed with NaHCO3 and brine. The organic extract was dried (anhyd. MgSO4) and concentrated under reduced pressure to give an oil. Chromatography gave the title compound.
Reaction SMILES: [CH:1]1([CH2:5][O:6][C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH:9]=[C:10]([C:16]([OH:18])=O)[NH:11]3)[CH2:4][CH2:3][CH2:2]1.Cl.Cl.Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][C@@H:30]([N:32]2[CH2:37][CH2:36][C@H:35]([OH:38])[C@@H:34]([CH3:39])[CH2:33]2)[CH3:31])[CH2:25][CH2:24]1>>[OH:38][C@H:35]1[CH2:36][CH2:37][N:32]([C@@H:30]([CH3:31])[CH2:29][N:26]2[CH2:25][CH2:24][CH:23]([NH:22][C:16]([C:10]3[NH:11][C:12]4[C:8]([CH:9]=3)=[C:7]([O:6][CH2:5][CH:1]3[CH2:2][CH2:3][CH2:4]3)[CH:15]=[CH:14][CH:13]=4)=[O:18])[CH2:28][CH2:27]2)[CH2:33][C@@H:34]1[CH3:39]
Reactant: C[C@H]1CN([C@@H](C)CN2CCC(N)CC2)CC[C@@H]1O
Reactant: O=C(O)c1cc2c(OCC3CCC3)cccc2[nH]1
Agent: Cl
Product: C[C@H]1CN([C@@H](C)CN2CCC(NC(=O)c3cc4c(OCC5CCC5)cccc4[nH]3)CC2)CC[C@@H]1O

Procedure:
This compound is synthesized analogously to example 1 from 4-cyclobutylmethoxy-1H-indole-2-carboxylic acid, 82 (see example 22) and amine 56.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:19]3[O:20][CH:21]=[CH:22][CH:23]=3)=[C:11]([CH2:13][C:14]([O:16]CC)=[O:15])[N:12]=2)=[CH:4][CH:3]=1.CO.[OH-].[Na+]>O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]([C:19]3[O:20][CH:21]=[CH:22][CH:23]=3)=[C:11]([CH2:13][C:14]([OH:16])=[O:15])[N:12]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)Cc1nc(-c2ccc(C)cc2)oc1-c1ccco1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1ccc(-c2nc(CC(=O)O)c(-c3ccco3)o2)cc1
Yield: 55 %

Procedure:
4.0 g of ethyl 2-[2-(4-methylphenyl)-5-(2-furyl)-4-oxazolyl]acetate, 60 ml of methanol, 10 ml of water and 1.5 g of sodium hydroxide are treated in the same manner as described in Example 16. 2.0 g of 2-[2-(4-methylphenyl)-5-(2-furyl)-4-oxazolyl]acetic acid are thereby obtained. Yield: 55.6%
Reaction SMILES: [C:1]([C:3]1[CH:30]=[CH:29][C:6]2[NH:7][C:8]([CH:10]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH2:11][CH2:12][C:13]([O:15]C)=[O:14])=[N:9][C:5]=2[CH:4]=1)#[N:2].[OH-].[Na+]>CO>[C:1]([C:3]1[CH:30]=[CH:29][C:6]2[NH:7][C:8]([CH:10]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[N:9][C:5]=2[CH:4]=1)#[N:2]
Reactant: COC(=O)CCC(c1nc2cc(C#N)ccc2[nH]1)c1c(OC)cc(C)c2[nH]ccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1cc(C)c2[nH]ccc2c1C(CCC(=O)O)c1nc2cc(C#N)ccc2[nH]1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
(±)-Methyl 4-(5-cyano-1H-benzo[d]imidazol-2-yl)-4-(5-methoxy-7-methyl-1H-indol-4-yl)butanoate (Example 146-B) (40 mg, 0.099 mmol) was dissolved in MeOH (1 mL) and then added 1 N NaOH (248 μl, 0.248 mmol). The reaction was stirred at room temperature for 3 h, concentrated and then directly purified via RP-HPLC (HC-B) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) d ppm 10.92 (br. s., 1H) 7.61-8.32 (m, 1H) 7.47-7.51 (m, 2H) 7.13 (d, J=5.56 Hz, 1H) 6.79 (s, 1H) 5.99 (br. s., 1H) 4.90 (dd, J=8.59, 5.81 Hz, 1H) 3.74 (s, 3H) 2.72-2.82 (m, 1H) 2.45 (s, 3H) 2.20-2.32 (m, 2H) 2.06-2.18 (m, 1H). HRMS calcd. for C22H20N4O3 (M+H)+ 389.1605. found 389.1604.
Reaction SMILES: [CH:1]([O:3][CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:2].C(OCCCCCCCCC=CCCCC)(=O)C.C(OCCCCCCCCC=C)=O.C(OC=CCCCCCCCCCCCC)(=O)C.C([O-])([O-])=O.[K+].[K+]>C(O)=O.C(OCC)C.O.CO>[CH:1]([O:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:2]
Reactant: CCCCCCCCCCCCC=COC=O
Agent: C=CCCCCCCCCOC=O
Agent: CCCCC=CCCCCCCCCOC(C)=O
Agent: CCCCCCCCCCCCC=COC(C)=O
Solvent: O
Solvent: CO
Solvent: O=CO
Product: CCCCC=CCCCCCCCCOC=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Three fields of cotton in a late fruiting stage were used to evaluate the effectiveness of tetradecenyl formate in controlling Heliothis species. In this case, the 9-tetradecenyl formate was prepared from 9-tetradecenyl acetate rather than directly from 9-decenyl formate. In a typical process 21.1 g (0.08 mol) of tetradecenyl acetate, 22.2 g (0.16 mol) K2CO3, 200 mL methanol, and 2 mL water were added to a 500 mL one neck round bottom flask. The mixture was stirred for two hours at room temperature. Then 200 mL of diethyl ether was added, and the mixture was filtered. The ether layer was washed with water, then saturated NaCl solution, then dried over MgSO4. The dried solution was filtered and concentrated on a rotary evaporator. The product consisting of 9-tetradecenyl alcohol was then reacted with formic acid in benzene at gentle reflux (~80° C.) for 24 hours. Then additional formic acid was added and the gentle reflux continued for another 24 hours. The 9 -tetradecenyl formate was recovered by extraction.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH:15]=[CH:14][N:13]=[N:12]2)=[N:9][CH:10]=1)=O.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][N:18]=1>C(#N)C>[I:23][C:20]1[CH:21]=[CH:22][C:17]2[N:18]([CH:2]=[C:3]([C:5]3[CH:6]=[CH:7][C:8]([N:11]4[CH:15]=[CH:14][N:13]=[N:12]4)=[N:9][CH:10]=3)[N:16]=2)[CH:19]=1
Reactant: O=C(CBr)c1ccc(-n2ccnn2)nc1
Reactant: Nc1ccc(I)cn1
Solvent: CC#N
Product: Ic1ccc2nc(-c3ccc(-n4ccnn4)nc3)cn2c1
Temperature: 100 °C
Yield: 45.4 %

Procedure:
66.4 mg (corresponding to 0.249 mmol) of 5-(2-bromoacetyl)-2-(1H-1,2,3-triazole-1-yl)pyridine and 54.8 mg (corresponding to 0.249 mmol) of 2-amino-5-iodopyridine were dissolved in 2.0 mL of acetonitrile. The resulting solution was heated under reflux for 1.5 hours in an oil bath at 100° C. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 2 mL of water and 2 mL of methanol. Then, about 1 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 44.0 mg (corresponding to 0.113 mmol) of 6-iodo-2-[2-(1H-1,2,3-triazole-1-yl)pyridine-5-yl]imidazo[1,2-a]pyridine (FIG. 1, step 3).