Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][CH:5]=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].O.C(=O)([O-])[O-].[Na+].[Na+].[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:25]1([C:2]2[N:3]=[N:4][CH:5]=[C:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:7]=2[C:8]([O:10][CH3:11])=[O:9])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)c1c(-c2ccccc2)cnnc1Cl
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1c(-c2ccccc2)cnnc1-c1ccccc1
Temperature: 100 °C
Yield: 86.1 %

Procedure:
A solution of methyl 3-chloro-5-phenylpyridazine-4-carboxylate (300 mg, 1.20 mmol) in 1,4-dioxane (15 mL), distilled water (5 mL), sodium carbonate (256 mg, 2.41 mmol) and phenyl boronic acid (1.91 g, 1.57 mmol) were added and the reaction mixture was degassed for 10 min, followed by addition of tetrakis(triphenylphosphine) palladium (139 mg, 0.12 mmol) and refluxed at 100° C. for 12 h under argon atmosphere. After the completion of starting materials, the reaction mixture was cooled to rt and filtered through a celite pad to remove the solid impurities. The filtrate was diluted with ethyl acetate (40 mL), washed with aq NaHCO3 (5 mL×1), brine solution (5 mL×1) and dried over anhydrous Na2SO4. The organic extracts were evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (100-200 mesh silica gel, 5% EtOAc in hexane) to furnish methyl 3,5-diphenylpyridazine-4-carboxylate (300 mg, 82%) as a white solid.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.[C-:13]#[N:14].[Na+]>C(O)C>[N:9]1[C:10]2[C:5](=[CH:4][C:3]([CH2:2][C:13]#[N:14])=[CH:12][CH:11]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: [C-]#N
Reactant: BrCc1ccc2ncccc2c1
Agent: [Na+]
Solvent: CCO
Product: N#CCc1ccc2ncccc2c1
Temperature: 50 °C
Yield: 18.3 %

Procedure:
To a solution of crude 6-bromomethylquinoline (1.8 g) in 95% ethanol (30 mL) was added NaCN (2.0 g, 40.8 mmol) at room temperature. The mixture was heated at 50° C. for 3 hours and then concentrated under vacuum. Water (50 mL) and ethyl acetate (50 mL) were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4 and concentrated under vacuum. The combined crude product was purified by column (Petroleum Ether/EtOAc 5:1) to give 2-(quinolin-6-yl)acetonitrile (0.25 g, 8% over two steps). 1H NMR (300 MHz, CDCl3) δ 8.95 (dd, J=1.5, 4.2 Hz, 1 H), 8.12-8.19 (m, 2 H), 7.85 (s, 1 H), 7.62 (dd, J=2.1, 8.7 Hz, 1 H), 7.46 (q, J=4.2 Hz, 1 H), 3.96 (s, 2 H). MS (ESI) m/e (M+H)+ 169.0.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=O.[Cl:8][C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1.[BH4-].[Na+].O>CO>[Cl:8][C:9]1[CH:15]=[CH:14][C:12]([NH:13][CH2:6][C:2]2[NH:3][CH:4]=[CH:5][N:1]=2)=[CH:11][CH:10]=1
Reactant: O=Cc1ncc[nH]1
Reactant: Nc1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Clc1ccc(NCc2ncc[nH]2)cc1
Temperature: 25 °C
Yield: 53.9 %

Procedure:
The solution of 2-imidazolecarboxaldehyde (570 mg, 5.9 mmol) and 4-chloroaniline (756 mg, 5.9 mmol) in methanol (5 ml) was stirred at 60° C. for 4 hours, and allowed to cool to room temperature. To the reaction was added NaBH4 (337 mg, 8.9 mmol), and the mixture was additionally stirred for an hour. Water (20 mL) was added to the reaction, which was extracted with ethyl acetate (50 mL). Organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% methanol in chloroform) to give the title compound (660 mg, 53%).
Reaction SMILES: C([O:4][CH2:5][C:6]1[O:7][C:8]2[C:14]([O:15][CH3:16])=[C:13]([O:17][CH3:18])[CH:12]=[C:11]([CH2:19][C:20]3[C:21]([NH2:27])=[N:22][C:23]([NH2:26])=[N:24][CH:25]=3)[C:9]=2[CH:10]=1)C=C.C([O-])=O.[NH4+]>C(#N)C>[NH2:26][C:23]1[N:22]=[C:21]([NH2:27])[C:20]([CH2:19][C:11]2[C:9]3[CH:10]=[C:6]([CH2:5][OH:4])[O:7][C:8]=3[C:14]([O:15][CH3:16])=[C:13]([O:17][CH3:18])[CH:12]=2)=[CH:25][N:24]=1
Reactant: C=CCOCc1cc2c(Cc3cnc(N)nc3N)cc(OC)c(OC)c2o1
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CC#N
Product: COc1cc(Cc2cnc(N)nc2N)c2cc(CO)oc2c1OC
Yield: 91.7 %

Procedure:
Under argon, to a solution of 5-(2-allyloxymethyl-6,7-dimethoxy-benzofuran-4-ylmethyl)-pyrimidine-2,4-diamine (610 mg, 1.64 mmol) in ACN was added Pd(PPh3)4 complex (571 mg, 0.424 mmol) and ammonium formate (519 mg, 8.23 mmol). The reaction mixture was stirred at reflux for 2 h. Then the reaction was quenched with 1N HCl, the impurities were extracted with ethyl acetate and the solution neutralised with Na2CO3 to pH=7 and saturated with NaOAc. The compound was extracted with ACN dried over MgSO4 and the solvent evaporated to give [4-(2,4-diamino-pyrimidin-5-ylmethyl)-6,7-dimethoxy-benzofuran-2-yl]-methanol (497 mg, 84%) as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH:12]=[C:13]([OH:15])[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:30]=1[C:38]([F:41])([F:40])[F:39]>>[CH3:1][O:2][C:3](=[O:26])[CH:4]([C:9]1[CH:10]=[C:11]([C:16]2[CH:17]=[CH:18][C:19]([C:22]([F:23])([F:25])[F:24])=[CH:20][CH:21]=2)[CH:12]=[C:13]([O:15][C:32]2[CH:33]=[CH:34][C:29]([O:28][CH3:27])=[C:30]([C:38]([F:39])([F:41])[F:40])[CH:31]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7]
Reactant: COc1ccc(B(O)O)cc1C(F)(F)F
Reactant: COC(=O)C(CC(C)C)c1cc(O)cc(-c2ccc(C(F)(F)F)cc2)c1
Product: COC(=O)C(CC(C)C)c1cc(Oc2ccc(OC)c(C(F)(F)F)c2)cc(-c2ccc(C(F)(F)F)cc2)c1
Yield: 25 %

Procedure:
The title compound was prepared in 25% yield from 2-(5-hydroxy-4′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid methyl ester and 4-methoxy-3-trifluoromethylphenylboronic acid under the conditions described in Example 15, step (g).
Reaction SMILES: [CH3:1][O:2][N:3]([CH3:19])[C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:6]=1[N+:15]([O-])=O>[Pd]>[NH2:15][C:6]1[CH:7]=[C:8]([C:11]([F:12])([F:13])[F:14])[CH:9]=[CH:10][C:5]=1[C:4]([N:3]([O:2][CH3:1])[CH3:19])=[O:18]
Reactant: CON(C)C(=O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Agent: [Pd]
Product: CON(C)C(=O)c1ccc(C(F)(F)F)cc1N

Procedure:
N-Methoxy-N-methyl-2-nitro-4-trifluoromethyl-benzamide (2.54 g, 9.12 mmol) was reacted with Pd/C (441 mg) under hydrogen atmosphere as described above to yield title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[SH:15][C:16]1[S:17][C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:15][C:16]2[S:17][C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Sc1nc2ccccc2s1
Product: CC(C)(C)OC(=O)N1CCC(Sc2nc3ccccc3s2)CC1

Procedure:
By a similar manner to Reference Example 35, 1-tert-butoxycarbonyl-4-hydroxypiperidine (1.01 g, 5.0 mmol) was reacted with 2-mercaptobenzothiazole (1.00 g, 6.0 mmol) to give the titled compound as a colorless oily substance (1.54 g, 88%).
Reaction SMILES: Cl.F[C:3]1[CH:4]=[C:5]([NH:11]N)[C:6](OC)=[CH:7][CH:8]=1.[C:13](O)(=O)[CH2:14]CC(C)=O>C(O)(=O)C>[NH:11]1[C:5]2[C:6](=[CH:7][CH:8]=[CH:3][CH:4]=2)[CH:14]=[CH:13]1
Reactant: CC(=O)CCC(=O)O
Reactant: COc1ccc(F)cc1NN
Agent: Cl
Solvent: CC(=O)O
Product: c1ccc2[nH]ccc2c1

Procedure:
Condensation of hydrazine hydrochloride (2) with levulinic acid (3) in acetic acid results in the formation of two regioisomeric indole derivatives 4 and 5 in a 1:7 ratio. The major regioisomer 5 can be isolated in pure form by crystallization of the reaction mixture. Alternatively, the indole mixture can be esterified with an alcohol such as 2-trimethylsilylethanol to afford the corresponding esters that can then be separated by a number of means, for example by chromatography.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[CH:11][NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.C(O)C>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:9]3[N:10]=[CH:11][NH:12][C:13]=3[C:14]3[C:19](=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:7]=2[CH:8]=1
Reactant: COc1ccc(-c2nc[nH]c2-c2ccc(OC)cc2)cc1
Solvent: CCO
Product: COc1ccc2c(c1)c1cc(OC)ccc1c1[nH]cnc21

Procedure:
A solution of 4,5-bis(4-methoxyphenyl)imidazole in absolute ethanol[3.5 gms (0.0125 mole) in 800 ml absolute ethanol, 140 mg iodine as catalyst] was photolysed using a 450 watt Havovia lamp, and a Vycor filter for four hours.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH:12]=[C:13]2[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15][CH2:14]2)=[C:4](Cl)[N:3]=1.C(N(CC)CC)C>[Pd].C(OCC)(=O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH:13]2[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[O:15][CH2:14]2)=[CH:4][N:3]=1
Reactant: CC1(C)OCC(=CCn2cnc3c(Cl)nc(N)nc32)CO1
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC1(C)OCC(CCn2cnc3cnc(N)nc32)CO1
Reaction time: 18 h
Yield: 74.5 %

Procedure:
A mixture of 5-[2-(2-amino-6-chloropurin-9-yl)]ethylidene-2,2-dimethyl-1,3-dioxane (0.45 g), 5% palladium on carbon (0.225 g) and triethylamine (0.22 ml) in ethyl acetate (22.5 ml) was hydrogenated at 50° C. for 18 hours at 50 p.s.i. The catalyst was removed by filtration and the filter washed with ethyl acetate. The combined filtrate and wash were concentrated under reduced pressure to give a gum which was purified by silica gel chromatography (eluted with dichloromethane/methanol 99:1 increasing to 97:3) to give the title compound (300 mg, 74% yield).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15](O)=[O:16])[N:10]=[N:9]2)=[CH:5][CH:4]=1.C(C1C=CC(CN2C=C(C=CC(O)=O)N=N2)=CC=1)#N>>[C:2]([C:3]1[CH:19]=[CH:18][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([CH:13]=[CH:14][CH:15]=[O:16])[N:10]=[N:9]2)=[CH:5][CH:4]=1)#[N:1]
Reactant: NCc1ccc(Cn2cc(CCC(=O)O)nn2)cc1
Agent: N#Cc1ccc(Cn2cc(C=CC(=O)O)nn2)cc1
Product: N#Cc1ccc(Cn2cc(C=CC=O)nn2)cc1
Yield: 41 %

Procedure:
3-[1-(4-aminomethylbenzyl)-1,2,3-triazol-4-yl]-propionic acid (m.p. 207°-210° C.; prepared by catalytic hydrogenation of 3-[1-(4-cyanobenzyl)-1,2,3-triazol-4-yl]-acrylic acid (m.p. 168°-170° C.) which is obtained by oxidation of the corresponding 3-[1-(4-cyanobenzyl)-1,2,3-triazol-4-yl]-acrolein (m.p. 152°-155° C.)):
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([SH:9])[CH:6]=[CH:7][CH:8]=1.F[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[CH3:1][S:2][C:3]1[CH:4]=[C:5]([S:9][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: CSc1cccc(S)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CSc1cccc(Sc2ccc(C=O)cc2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 33 %

Procedure:
A solution of 3-(methylthio)benzenethiol (19.9 g, 127.3 mmol), prepared as indicated in Rumpf, P., Bull. soc. chim. (1940), 7, pp. 632-4, in acetonitrile (60 mL) was treated with 4-fluorobenzaldehyde (13.4 mL, 127 mmol) followed by potassium carbonate (19.4 g, 140 mmol). After stirring at ambient temperature for 18 hours the suspension was diluted with water (200 mL) and extracted with ethyl acetate (3-fold 300 mL). The combined organic extracts were washed with brine (2-fold 100 mL) and dried (magnesium sulphate) and the solvent removed in vacuo to give a colourless oil. The crude oil was purified by flash column chromatography on silica gel eluting with heptane:ethyl acetate (1:0 changing to 9:1, by volume) to give the title compound as a colourless oil, 33% yield, 10.8 g.
Reaction SMILES: [CH3:1][Si:2]([CH3:31])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][CH:13]([CH2:16][C:17]1[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:19]=[CH:20][N:21]=1)[CH2:14][NH2:15].[CH:32]([C:34]1[CH:42]=[CH:41][C:37]([C:38](O)=[O:39])=[CH:36][CH:35]=1)=[O:33].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=C1>O.CN(C)C=O>[CH:32]([C:34]1[CH:42]=[CH:41][C:37]([C:38]([NH:15][CH2:14][CH:13]([CH2:16][C:17]2[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:27])[CH3:29])[CH:19]=[CH:20][N:21]=2)[CH2:12][C:8]2[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:1])([CH3:30])[CH3:31])[CH:11]=[CH:10][N:9]=2)=[O:39])=[CH:36][CH:35]=1)=[O:33]
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: C[Si](C)(C)CCOCn1ccnc1CC(CN)Cc1nccn1COCC[Si](C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: On1cnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: C[Si](C)(C)CCOCn1ccnc1CC(CNC(=O)c1ccc(C=O)cc1)Cc1nccn1COCC[Si](C)(C)C
Temperature: 25 °C
Reaction time: 17 h
Yield: 132.4 %

Procedure:
To a dimethylformamide (2 mL) solution of the compound (300 mg) produced in Example 29 and 4-formylbenzoic acid (116 mg), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (hereafter abbreviated to EDC) (274 mg) and 1-hydroxybenzimidazole (104 mg) were added in this order. The reaction solution was stirred at room temperature for 17 hour. To the reaction solution, water (10 mL) was added. The aqueous layer was extracted twice with dichloromethane (20 mL). The combined organic layer was washed with saturated sodium chloride solution (20 mL) and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (ethyl acetate:methanol: 28% aqueous ammonia=1:0:0→100:10:1) to obtain the title compound (510 mg).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.CN(C)[CH:8]=[O:9].[CH3:11][CH:12]1[CH2:21][CH2:20][CH:19]([CH3:22])[C:18]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]1=2.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CCCCCC>[CH3:11][CH:12]1[CH2:21][CH2:20][CH:19]([CH3:22])[C:18]2[NH:17][CH:16]([CH:8]=[O:9])[CH:15]=[CH:14][C:13]1=2
Reactant: CN(C)C=O
Reactant: CC1CCC(C)c2ncccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: O=P(Cl)(Cl)Cl
Product: CC1CCC(C)C2=C1C=CC(C=O)N2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 59.6 %

Procedure:
Phosphorus oxychloride (18.6 g, 0.12 mol) was added dropwise to 29.2 g (0.4 mol) of N,N-dimethylformamide under ice cooling. After stirring at room temperature for 30 minutes, the reaction mixture was cooled over ice bath, followed by the dropwise addition of 17.0 g (0.1 mol) of 5,8-dimethyl-5,6,7,8-tetrahydroquinoline. After stirring at room temperature for one hour, the reaction mixture was poured into ice water and neutralized with an aqueous solution of sodium bicarbonate, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue so obtained was subjected to chromatography on a silica gel column (developing solvent: 10% ethyl acetate/n-hexane), whereby 11.4 g of the title compound were obtained in the form of a reddish brown oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:28]([F:31])([F:30])[F:29])[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:24][CH:23]([C:25](O)=[O:26])[CH2:22]4)=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].C(Cl)(=O)C(Cl)=O.[CH3:38][NH2:39]>C(Cl)Cl>[CH3:38][NH:39][C:25]([CH:23]1[CH2:24][N:21]([C:18]2[CH:17]=[CH:16][C:15]([C:12]3[CH2:11][C:10]([C:4]4[CH:3]=[C:2]([Cl:1])[C:7]([Cl:8])=[C:6]([Cl:9])[CH:5]=4)([C:28]([F:29])([F:30])[F:31])[O:14][N:13]=3)=[CH:20][CH:19]=2)[CH2:22]1)=[O:26]
Reactant: O=C(O)C1CN(c2ccc(C3=NOC(c4cc(Cl)c(Cl)c(Cl)c4)(C(F)(F)F)C3)cc2)C1
Reactant: CN
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CNC(=O)C1CN(c2ccc(C3=NOC(c4cc(Cl)c(Cl)c(Cl)c4)(C(F)(F)F)C3)cc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 54 %

Procedure:
To a stirred solution of 1-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-azetidine-3-carboxylic acid (Preparation 12, 0.1 g, 0.203 mmol) in DCM (4 mL) was added oxalyl chloride (0.030 g, 0.0.243 mmol) at 0° C. and stirred for 1 hour under nitrogen atmosphere at room temperature. After 1 hour, saturated solution of methyl amine (4 mL) was added. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to get crude. Crude was purified by column chromatography on silica gel (100-200 mesh). Compound was eluted using 0.7% methanol in DCM to afford pale yellow solid (0.055 g, 54%). 1H-NMR (400 MHz, CDCl3) δ: 2.86-2.90 (d, 3H, J=4.84 Hz), 3.36-3.39 (m, 1H), 3.61 (d, 1H, J=17 Hz), 4.01-4.09 (m, 5H), 5.62-5.63 (m, 1H), 6.40-6.42 (m, 2H), 7.46-7.50 (m, 2H), 7.63 (s, 2H); LC-MS (m/z): [M−H] 503.80. HPLC purity: 96.77%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2.[CH3:13][NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][N:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2
Reactant: CNc1ccccc1
Reactant: O=C1CCCc2cc(Br)ccc21
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CN(c1ccccc1)c1ccc2c(c1)CCCC2=O
Temperature: 100 °C
Reaction time: 8 h
Yield: 68 %

Procedure:
To a solution of 6-bromo-1,2,3,4-tetrahydronaphthalen-1-one (2.0 g, 8.9 mmol) in toluene (20 mL) was added N-methylaniline (960 mg, 8.9 mmol), Cs2CO3 (4.4 g, 13.4 mmol), BINAP (310 mg, 0.5 mmol) and Pd(OAc)2 (110 mg, 0.5 mmol). The mixture was stirred overnight at 100° C. under nitrogen. The mixture was filtered and concentrated, and the residue was purified by silica gel chromatography (30%-80% EtOAc/Hex) to give 1.52 g (68%) of the title compound as a light brown oil. [M+H] calc'd for C17H17NO, 252. found 252.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][C:17]([CH3:20])([CH3:19])[N:16]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:15]([CH3:31])([CH3:30])[CH2:14]2)[N:5]=[C:4]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]2[CH2:42][C:41]([CH3:44])([CH3:43])[N:40]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[C:39]([CH3:55])([CH3:54])[CH2:38]2)[N:3]=1.[NH2:56][NH2:57]>>[CH2:22]([O:21][N:16]1[C:17]([CH3:19])([CH3:20])[CH2:18][CH:13]([CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]2[N:5]=[C:4]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]3[CH2:42][C:41]([CH3:43])([CH3:44])[N:40]([O:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[C:39]([CH3:55])([CH3:54])[CH2:38]3)[N:3]=[C:2]([NH:56][NH2:57])[N:7]=2)[CH2:14][C:15]1([CH3:31])[CH3:30])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: NN
Reactant: CCCCCCCCON1C(C)(C)CC(CCCCNc2nc(Cl)nc(NCCCCC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)n2)CC1(C)C
Product: CCCCCCCCON1C(C)(C)CC(CCCCNc2nc(NN)nc(NCCCCC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)n2)CC1(C)C

Procedure:
The title compound is prepared from the reaction of 2-chloro-4,6-bis[N-(1-octyloxy-2,2,6,6-tetramethylpiperidin-4-yl)butylamino]-1,3,5-triazine and hydrazine.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3].C(=O)([O-])[O-].[Na+].[Na+].[F:16][CH2:17][C:18]([C:22]1[CH:23]=[C:24]([NH2:34])[N:25]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[N:26]=1)([CH2:20][F:21])[CH3:19].O>C1COCC1>[Cl:7][C:6]([Cl:9])([Cl:8])[CH2:5][O:4][C:2](=[O:3])[NH:34][C:24]1[N:25]([C:27]2[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[N:26]=[C:22]([C:18]([CH2:17][F:16])([CH3:19])[CH2:20][F:21])[CH:23]=1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Reactant: Cc1ccc(-n2nc(C(C)(CF)CF)cc2N)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(-n2nc(C(C)(CF)CF)cc2NC(=O)OCC(Cl)(Cl)Cl)cc1
Reaction time: 24 h

Procedure:
Add 2,2,2-trichloroethyl chloroformate (8.1 mmol, 1.1 mL) and aqueous sodium carbonate solution (4.8 mL) over a solution of 5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-ylamine (7.3 mmol, 1.9 g) in 37 mL of THF. Stir for 24 hours. Pour the solution over water and extract in ethyl acetate. Combine organic layers and wash with saturated aq. sodium chloride. Dry over sodium sulfate, filter, and concentrate under reduced pressure to give [5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester. LCMS ES+ (m/z) 440 [M+H].
Reaction SMILES: [CH3:1][N:2]([CH3:18])[C:3]1[NH:4][N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[C:7](=[O:9])[N:8]=1.[C:19](=O)=O.CC(C)=O.C([Li])CCC.CI>O1CCCC1.CCCCCC.CO>[CH3:19][N:4]1[C:3]([N:2]([CH3:18])[CH3:1])=[N:8][C:7](=[O:9])[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[N:5]1
Reactant: COc1ccccc1-c1n[nH]c(N(C)C)nc1=O
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: CI
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: COc1ccccc1-c1nn(C)c(N(C)C)nc1=O
Temperature: 25 °C
Reaction time: 10 h
Yield: 90 %

Procedure:
3-Dimethylamino-6-(o-methoxyphenyl)-5-oxo-2,5-dihydro-1,2,4-triazine (0.5 g) was dissolved in tetrahydrofuran (40 ml), and the mixture was cooled to -30° C. with dry ice/acetone. A solution of n-butyl lithium in n-hexane (15%, 1.2 ml) was dropwise added to the mixture, which was then warmed to room temperature. To the resultant mixture, methyl iodide (0.42 g) was dropwise added and, upon completion of the addition, the resulting mixture was stirred at room temperature for 10 hours to complete the reaction. Then, methanol (10 ml) was added thereto, and the resultant mixture was evaporated to dryness under reduced pressure to give a crude product. Recrystallization of the crude product from ethanol gave 0.47 g of 2-methyl-3-dimethylamino-6-(o-methoxyphenyl)-5-oxo-2,5-dihydro-1,2,4-triazine in 90% yield. M.P., 202° C.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]1[CH:7]=[CH:6][NH:5][N:4]=1.[O-][Cl:11].[Na+]>C(O)(=O)C>[Cl:11][C:7]1[C:3]([C:2]([F:9])([F:8])[F:1])=[N:4][NH:5][CH:6]=1
Reactant: FC(F)(F)c1cc[nH]n1
Reactant: [O-]Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: FC(F)(F)c1n[nH]cc1Cl

Procedure:
Following protocol K, 3-trifluoromethylpyrazole was treated with glacial acetic acid and NaOCl, yielding title compound.
Reaction SMILES: [CH3:1][C@H:2]1[C@@H:27]([OH:28])[C:26]([CH3:29])=[CH:25][CH2:24][CH2:23][C:18]2=[CH:19][C:20]([OH:22])=[CH:21][C:16](=[C:17]2[OH:30])[NH:15][C:13](=[O:14])[CH2:12][C@@H:11]([O:31][CH3:32])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=[CH:5][CH2:4][C@@H:3]1[O:33]C([C@H](NC(C1CCCCC1)=O)C)=O.[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:1][C@@H:2]1[C@H:27]([OH:28])[C:26]([CH3:29])=[CH:25][CH2:24][CH2:23][C:18]2[C:17](=[O:30])[C:16](=[CH:21][C:20]([CH:19]=2)=[O:22])[NH:15][C:13](=[O:14])[CH2:12][C@@H:11]([O:31][CH3:32])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=[CH:5][CH2:4][C@H:3]1[OH:33]
Reactant: CO[C@H]1C=CC=CC=CC[C@H](OC(=O)[C@@H](C)NC(=O)C2CCCCC2)[C@@H](C)[C@@H](O)C(C)=CCCc2cc(O)cc(c2O)NC(=O)C1
Agent: CO[C@H]1/C=C/C=C/C=C/C[C@@H](O)[C@H](C)[C@H](O)/C(C)=C/CCC2=CC(=O)C=C(NC(=O)C1)C2=O
Agent: CO[C@H]1/C=C/C=C/C=C/C[C@H](OC(=O)[C@@H](C)NC(=O)C2CCCCC2)[C@@H](C)[C@@H](O)/C(C)=C/CCc2cc(O)cc(c2O)NC(=O)C1
Agent: [BH4-]
Solvent: CO
Solvent: ClCCl
Product: CO[C@H]1C=CC=CC=CC[C@@H](O)[C@H](C)[C@H](O)C(C)=CCCC2=CC(=O)C=C(NC(=O)C1)C2=O

Procedure:
Mycotrienin II (1.00 g, 1.56 mmol) was reduced with NaBH4 as described by the literature method to afford 1.04 g of a crude material. The crude material was immediately oxidized with FeCl3 as described by the literature method to afford 600 mg of Mycotrienol I as a yellow solid after chromatography (25:1 CH2Cl2/methanol, Rf=0.44) in 87% combined yield.