Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH:6]=[CH:7][CH2:8]2.ClC1C=CC=C(C(OO)=[O:21])C=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH:6]1[O:21][CH:7]1[CH2:8]2
Reactant: COc1cccc2c1CC=CC2
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1cccc2c1CC1OC1C2
Temperature: 25 °C
Reaction time: 15 h

Procedure:
3.00 g (0.019M) of 1,4-dihydro-5-methoxynaphthalene are dissolved in 52 ml of methylene chloride, and cooled with an ice bath to 0°. 3.07 g (0.018M) of m-chloro-perbenzoic acid are subsequently added to this solution over the course of one minute. The ice bath is removed, and the reaction mixture is stirred for 15 hours at room temperature. The suspension is then added to a mixture of 20 ml of 10% sodium hydroxide and 40 g of ice. The organic phase is separated, and the aqueous phase is extracted twice, each time with 20 ml of methylene chloride. The combined organic phases are washed with water and sodium chloride solution, dried and concentrated by evaporation. 1a,2,7,7a-tetrahydro-3-methoxynaphth[2,3-b]oxirane is obtained (melting point 49.5°-50.5°, after purification by column chromatography, silica gel 0.063-0.200 mm, methylene chloride and recrystallisation from hexane).
Reaction SMILES: C([O:4][CH:5]1[CH2:11][NH:10][CH2:9][CH2:8][NH:7][CH2:6]1)(=O)C.[CH2:12]([N:19]1[C:27]2[C:26](=[O:28])[N:25]([CH3:29])[C:24](=[O:30])[N:23]([CH3:31])[C:22]=2[N:21]=[C:20]1Cl)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>CC(O)C>[CH2:12]([N:19]1[C:27]2[C:26](=[O:28])[N:25]([CH3:29])[C:24](=[O:30])[N:23]([CH3:31])[C:22]=2[N:21]=[C:20]1[N:7]1[CH2:6][CH:5]([OH:4])[CH2:11][NH:10][CH2:9][CH2:8]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cn1c(=O)c2c(nc(Cl)n2Cc2ccccc2)n(C)c1=O
Reactant: CC(=O)OC1CNCCNC1
Solvent: CCN(CC)CC
Solvent: CC(C)O
Product: Cn1c(=O)c2c(nc(N3CCNCC(O)C3)n2Cc2ccccc2)n(C)c1=O
Yield: 97 %

Procedure:
[1,4]Diazepan-6-ol acetate (2B) (116 mg, 0.49 mmol) and 7-benzyl-8-chloro-1,3-dimethyl-3,7-dihydropurine-2,6-dione (100 mg, 0.33 mmol) were dissolved in 2-propanol (20 ml) and triethylamine (0.68 ml, 4.9 mmol) and the mixture was subjected to micro waves (150° C., 6 bar, 300 W, 8 hours). The solvents were evaporated and the remaining was redissolved in dichloromethane (20 ml) and water (20 ml). The aqueous layer was acidified with potassium hydrogen sulfate until pH=2. The aqueous layer was separated and aqueous sodium hydroxide was added until pH=12. The aqueous layer was extracted with 3×50 ml of dichloromethane, and the combined organic material were added excess trifluoroacetic acid, and evaporated, to afford 123 mg of the title compound as a brown oil in 75% yield.
Reaction SMILES: [CH3:1][Mg]Br.[Br:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:9]([CH:15]=[O:16])=[N:10]2.O>C1COCC1>[Br:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:9]([CH:15]([OH:16])[CH3:1])=[N:10]2
Reactant: CC(C)(C)Nc1nc2c(Br)cccc2nc1C=O
Reactant: C[Mg]Br
Solvent: C1CCOC1
Solvent: O
Product: CC(O)c1nc2cccc(Br)c2nc1NC(C)(C)C
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 92.2 %

Procedure:
Methylmagnesium bromide (Aldrich) (3.0M in Et2O; 2.23 mL, 6.70 mmol) was added to a solution of 5-bromo-3-(tert-butylamino)quinoxaline-2-carbaldehyde (306a) (983.0 mg, 3.19 mmol) in THF (15.0 mL) at 0° C., and the resulting solution was stirred at 0° C. for 5 min. Water (5 mL) was added, and the resulting mixture was partitioned between saturated aq. NaHCO3 (80 mL) and EtOAc (120 mL). The organic layer was separated and sequentially washed with brine (60 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes) furnished 1-(5-bromo-3-(tert-butylamino)quinoxalin-2-yl)ethanol (952 mg, 2.94 mmol, 92% yield) as a light-yellow solid (following trituration with hexanes). 1H NMR (400 MHz, CDCl3) δ ppm 7.83 (1H, dd, J=7.6, 1.4 Hz), 7.75 (1H, dd, J=8.2, 1.4 Hz), 7.19 (1H, t, J=7.9 Hz), 5.74 (1H, br. s.), 5.01 (1H, q, J=6.7 Hz), 3.55 (1H, br. s.), 1.63 (9H, s), 1.59 (3H, d, J=6.7 Hz). m/z (EST, +ve) 324.1/326.1 (M+H)+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11](O)[CH3:12].[CH:14]1([NH:17][S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[N+:27]([O-:29])=[O:28])(=[O:20])=[O:19])[CH2:16][CH2:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH:14]1([N:17]([CH:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[CH3:12])[S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[N+:27]([O-:29])=[O:28])(=[O:20])=[O:19])[CH2:16][CH2:15]1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)NC1CC1
Reactant: CC(O)c1ccc2ccccc2c1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(c1ccc2ccccc2c1)N(C1CC1)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 63 %

Procedure:
To a solution of 1-(2-naphthyl)ethanol (344 mg), N-cyclopropyl-2-nitrobenzenesulfonamide (581 mg) and triphenylphosphine (787 mg) in tetrahydrofuran (10 mL) was added dropwise diisopropyl azodicarboxylate (590 μL) under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=4/1→1/1), and then triturated with diethyl ether-n-hexane (1:1) to give N-cyclopropyl-N-[1-(2-naphthyl)ethyl]-2-nitrobenzenesulfonamide j[REx(1-1)] (499 mg) as a colorless powder.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH:21]=O)=[CH:13]1.[OH-].[Na+].O>CO>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](/[CH:21]=[C:6]2/[C:7](=[O:11])[C:8]3[C:4]([CH2:5]/2)=[CH:3][C:2]([OH:1])=[CH:10][CH:9]=3)=[CH:13]1
Reactant: O=C1CCc2cc(O)ccc21
Reactant: O=Cc1c[nH]c2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C1/C(=C/c2c[nH]c3ccccc23)Cc2cc(O)ccc21
Temperature: 50 °C
Reaction time: 2 h
Yield: 81.7 %

Procedure:
A solution of 5-hydroxy-2,3-dihydro-1H-inden-1-one (0.30 g, 2.0 mmol) and 1H-indole-3-carboxaldehyde (0.32 g, 2.2 mmol) in methanol (10 mL) was added with 50% sodium hydroxide (0.34 mL), and the mixture was stirred at 50° C. for 2 hours. The reaction mixture was cooled to room temperature, and then added with water, and the precipitated solid was collected by filtration, and washed with methanol to obtain (E)-2-[(1H-indol-3-yl)methylene]-5-hydroxy-2,3-dihydro-1H-inden-1-one (0.45 g, 83%).
Reaction SMILES: [F:1][C:2]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:3]=1[O:4][C:5]1[N:6]=[C:7]([O:27][CH2:28][CH2:29][CH3:30])[C:8]2[N:13]=[C:12]([C:14]3[CH:24]=[C:23]([CH3:25])[C:17]([O:18][CH2:19][C:20](O)=[O:21])=[C:16]([CH3:26])[CH:15]=3)[O:11][C:9]=2[N:10]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH:67]1[CH2:78][CH2:77][CH2:76][C@H:68]1[C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70].Cl>CN(C)C=O.O>[F:1][C:2]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:3]=1[O:4][C:5]1[N:6]=[C:7]([O:27][CH2:28][CH2:29][CH3:30])[C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[C:16]([CH3:26])[C:17]([O:18][CH2:19][C:20]([N:67]4[CH2:78][CH2:77][CH2:76][C@H:68]4[C:69]([O:71][C:72]([CH3:74])([CH3:75])[CH3:73])=[O:70])=[O:21])=[C:23]([CH3:25])[CH:24]=3)[O:11][C:9]=2[N:10]=1
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN1
Reactant: CCCOc1nc(Oc2cc(F)ccc2F)nc2oc(-c3cc(C)c(OCC(=O)O)c(C)c3)nc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: CCCOc1nc(Oc2cc(F)ccc2F)nc2oc(-c3cc(C)c(OCC(=O)N4CCC[C@H]4C(=O)OC(C)(C)C)c(C)c3)nc12
Reaction time: 16 h

Procedure:
60 mg of {4-[5-(2,5-difluorophenoxy)-7-propoxyoxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy}acetic acid were dissolved in 1 ml of N,N-dimethylformamide, and 35 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 7 mg of 1-hydroxy-7-azabenzotriazole and 139 μl of N,N-diisopropylethylamine were added, and 5 min later 17 mg of tert-butyl L-prolinate were added. After 16 h at room temperature, 10 ml of water were added, after which the mixture was adjusted to pH 3 by addition of 2 M aqueous hydrochloric acid and extracted twice with ethyl acetate. The combined organic layers were washed with saturated sodium bicarbonate solution and sodium chloride solution, dried and concentrated under reduced pressure. This gave 61 mg of the title compound.
Reaction SMILES: [O:1]=C1CC(C)(C)CC(C)=C1.[O:11]=[O+:12][O-].[CH3:14][C:15]([CH3:24])([CH2:20][C:21](=[O:23])C)[CH2:16][C:17]([OH:19])=[O:18]>>[CH3:24][C:15]([CH3:14])([CH2:16][C:17]([OH:19])=[O:18])[CH2:20][C:21]([OH:23])=[O:1].[OH:11][OH:12]
Reactant: CC1=CC(=O)CC(C)(C)C1
Reactant: CC(=O)CC(C)(C)CC(=O)O
Reactant: O=[O+][O-]
Product: CC(C)(CC(=O)O)CC(=O)O
Product: OO

Procedure:
The process of the invention converts isophorone into an ozone-addition product, which is then converted into 3,3-dimethyl-5-oxo-hexanoic acid. From the latter, 3,3-dimethylglutaric acid is produced by means of hydrogen peroxide treatment.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1[CH:7]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:10][CH:11]=1.C1(C(F)(F)F)C=CC=CC=1>C(Cl)Cl>[N+:1]([C:7]1[C:6]([CH3:5])=[CH:11][CH:10]=[CH:9][C:8]=1[C:12]([F:13])([F:15])[F:14])([O-:4])=[O:2]
Reactant: Cc1cccc(C(F)(F)F)c1
Reactant: O=[N+]([O-])O
Solvent: FC(F)(F)c1ccccc1
Solvent: ClCCl
Product: Cc1cccc(C(F)(F)F)c1[N+](=O)[O-]
Temperature: -18 °C
Reaction time: 0.25 h

Procedure:
The nitration vessel is charged with 250 gms (3.97 moles) of 98% HNO3 and cooled to about -18° C. Then 100 gms (0.62 moles) of 3-methyl benzotrifluoride is added dropwise with stirring and the temperature is maintained within the range of about -16° C. to about -22° C. The addition of the benzotrifluoride takes about 2 hours and 15 minutes. After it has been added, stirring is continued for about another 15 minutes. The reaction mixture is poured into ice water and methylene chloride is added to phase separate the nitration products. The organic layer is washed with sodium carbonate solution. The solvent is then stripped on a rotary evaporator. Yield is 127.5 gms of oil comprising 43% 2-nitro isomer; 31% 4-nitro isomer, 24% 6-nitro isomer and about 1% of the 5-nitro isomer as determined by glc and 19F NMR.
Reaction SMILES: [Cl:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1.C(N(CC)CC)C.O>C(Cl)Cl>[Br:14][C:11]1[CH:12]=[CH:13][C:8]([NH:7][C:3](=[O:4])[CH:2]([Cl:1])[CH3:6])=[N:9][CH:10]=1
Reactant: CC(Cl)C(=O)Cl
Reactant: Nc1ccc(Br)cn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CC(Cl)C(=O)Nc1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
2.14 mL (22.0 mmol) 2-chloropropionic acid chloride in 5 mL DCM is added dropwise to a solution of 3.46 g (20.0 mmol) 2-amino-5-bromopyridine and 6.12 mL (44.0 mmol) triethylamine in 80 mL DCM at 0° C. The ice bath is removed and the reaction solution is stirred for a further 1.5 h at RT. Another 0.40 mL (4.12 mmol) 2-chloropropionic acid chloride is added and the solution is stirred for a further hour at RT. The reaction mixture is combined with 80 mL water, washed once with 80 mL saturated NaCl solution and dried over MgSO4. The solvent is eliminated i.vac. and the residue is triturated with a little EtOAc, suction filtered and dried.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH:7]([C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([N:16]3[CH2:21][CH2:20][CH:19]([CH3:22])[CH2:18][CH2:17]3)[CH:10]=2)[CH2:6][N:5]([CH2:23][CH3:24])[S:4]1(=[O:26])=[O:25])[CH3:2].[K+].[CH3:28][C:29]1[N:33](COCC[Si](C)(C)C)[C:32]([C:42]([O-])=[O:43])=[N:31][CH:30]=1>>[CH2:23]([N:5]1[CH2:6][CH:7]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:42]([C:32]3[NH:31][CH:30]=[C:29]([CH3:28])[N:33]=3)=[O:43])=[C:11]([N:16]3[CH2:17][CH2:18][CH:19]([CH3:22])[CH2:20][CH2:21]3)[CH:10]=2)[CH2:8][N:3]([CH2:1][CH3:2])[S:4]1(=[O:26])=[O:25])[CH3:24]
Reactant: Cc1cnc(C(=O)[O-])n1COCC[Si](C)(C)C
Reactant: CCN1CC(c2ccc(N)c(N3CCC(C)CC3)c2)CN(CC)S1(=O)=O
Agent: [K+]
Product: CCN1CC(c2ccc(NC(=O)c3nc(C)c[nH]3)c(N3CCC(C)CC3)c2)CN(CC)S1(=O)=O

Procedure:
The title compound is prepared from 4-(2,6-diethyl-1,1-dioxo-1λ6-[1,2,6]thiadiazinan-4-yl)-2-(4-methyl-piperidin-1-yl)-phenylamine (as prepared in the previous step) and 5-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid potassium salt (as prepared above in this example, step (c)) following the procedure of Example 11, steps (d)-(e).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH:12]2[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([F:40])([F:39])[F:38])[CH:28]=2)=[CH:23][CH:22]=1.C(OCC)C>CN(C)C=O>[F:34][C:33]([F:35])([F:36])[C:31]1[CH:32]=[C:27]([CH:28]=[C:29]([C:37]([F:40])([F:38])[F:39])[CH:30]=1)[C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:12]2([S:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)(=[O:10])=[O:11])[S:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])=[CH:22][CH:23]=1
Reactant: COc1ccc(S(=O)(=O)C2SC(=O)NC2=O)cc1
Reactant: FC(F)(F)c1cc(-c2ccc(CBr)cc2)cc(C(F)(F)F)c1
Solvent: CCOCC
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)C2(Cc3ccc(-c4cc(C(F)(F)F)cc(C(F)(F)F)c4)cc3)SC(=O)NC2=O)cc1

Procedure:
Prepared analogously to Example 9 from from 5-(4-methoxybenzenesulfonyl)thiazolidine-2,4-dione and 4′-bromomethyl-3,5-bis(trifluoromethyl)biphenyl in N,N-dimethylformamide. Trituration with diethyl ether provided a white solid. 1H NMR: δ 8.43 (br s, 1H), 7.91-7.99 (m, 4H), 7.85 (s, 1H), 7.53 (dd, J=6.5, 1.8 Hz, 2H), 7.33 (d, J=8.3 Hz, 2H), 7.07 (dm, J=9.0 Hz, 2H), 4.00 (A of AB, J=13.7 Hz, 1H), 3.93 (s, 3H), 3.42 (B of AB), J=13.7 Hz, 1H). MS (m/e): 588.5 (M−H)−. Anal: Calc for C25H17F6NO5S2.C3H7NO: 50.75% C, 3.65% H, 4.23% N; Found: 50.70% C, 3.60% H, 4.01% N. MP: 122-125° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][N:19]=3)=[O:17])=[CH:11][CH:10]=2)[CH:5]=[C:4]([CH3:27])[N:3]=1>[Pd].CO.C1COCC1>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6]3[CH:5]=[C:4]([CH3:27])[N:3]=[C:2]([NH2:1])[N:7]=3)=[CH:14][CH:13]=2)=[O:17])=[N:19][CH:20]=1
Reactant: Cc1cc(Nc2ccc(NC(=O)c3ccc([N+](=O)[O-])cn3)cc2)nc(N)n1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(Nc2ccc(NC(=O)c3ccc(N)cn3)cc2)nc(N)n1
Reaction time: 5 h
Yield: 135.3 %

Procedure:
To a suspension of 20 (523 mg, 1.43 mmol) was suspended in 1:1 MeOH/THF (100 ml) was added 10% Pd/C (100 mg) and hydrogenated at 55 Hg mm. for 5 h. The reaction mixture was filtered and evaporated to dryness and recrystallized from DCM/Pet.ether to give 21 (649 mg, 96%); mp (DCM/Pet.ether)>290° C.; 1H NMR [(CD3)2SO] δ 10.05 (s, 1H, NH), 8.85 (s, 1H, NH), 8.25 (d, J=2.5 Hz, 1H, H-6), 7.82 (d, J=8.6 Hz, 1H, H-3), 7.73 (d, J=9.0 Hz, 2H, H-2′, 6′), 7.60 (d, J=9.0 Hz, 2H, H-3′, 5′), 7.03 (dd, J=8.5, 2.7 Hz, 1H, H-4), 6.04 (brs, 2H, NH2), 6.03 (brs, 2H, NH2), 5.85 (s, 1H, H-5″), 2.08 (s, 3H, CH3); Anal. calc. for C17H17N7).0.25H2O C, 60.1; H, 5.2; N, 28.9; found, C, 60.0; H, 5.2; N, 28.7%.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])[CH3:3].[O-]CC.[Na+].Cl[C@@H:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[S:27][CH2:28][C:29]([OH:31])=[O:30].Cl>C(O)C.O>[CH3:4][C:2]([C:5]1[CH:10]=[C:9]([S:11][C@@H:22]2[CH2:26][CH2:25][CH2:24][C@H:23]2[S:27][CH2:28][C:29]([OH:31])=[O:30])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:1])[CH3:3]
Reactant: O=C(O)CS[C@@H]1CCC[C@H]1Cl
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(C)(C)c1cc(S[C@@H]2CCC[C@H]2SCC(=O)O)cc(C(C)(C)C)c1O
Reaction time: 1.5 h

Procedure:
2.6-bis(1.1-Dimethylethyl)-4-mercaptophenol (0.73 g, 0.0031 mole) was added to freshly prepared sodium ethoxide [sodium (0.16 g, 0,007 mole)] in ethanol (10 ml). Once dissolved, the product of Example 4 (0.50 g, 0.0026 mole) was added and the reaction mixture was stirred for 90 minutes and poured into water (50 ml) containing 1N hydrochloric acid (25 ml). The mixture was extracted three times with 20 ml of diethyl ether, and the combined extracts were washed with water (20 ml), dried over anhydrous magnesium sulfate, filtered and concentrated to an oil with a rotary evaporator. The product was purified by silica gel chromatography. The structure was supported by NMR and elemental analysis.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=O.[C:11]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])#[N:12].O>C(O)C.N1CCCCC1>[C:11]([C:13](=[CH:5][C:4]1[CH:7]=[CH:8][C:9]([OH:10])=[C:2]([OH:1])[CH:3]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])#[N:12]
Reactant: CCOC(=O)CC#N
Reactant: O=Cc1ccc(O)c(O)c1
Solvent: C1CCNCC1
Solvent: O
Solvent: CCO
Product: CCOC(=O)C(C#N)=Cc1ccc(O)c(O)c1
Reaction time: 20 h
Yield: 68.3 %

Procedure:
To a solution of 3,4-dihydroxybenzaldehyde (2.0 g, 14.5 mmol) in ethanol (10 ml) were added ethyl cyanoacetate (1.6 g, 14.5 mmol) and piperidine (3 drops) and the resulting reaction was allowed to proceed for 20 hours at room temperature. Water was then added to the reaction mixture, and the precipitated crystalline was filtered off and recrystallized from ethanol-water to yield the titled compound (2.3 g, 9.9 mmol). Alternatively, the reaction may be conducted in a benzene solution under refluxing conditions. Compound Nos. 2 to 6 were provided in a similar manner.
Reaction SMILES: [CH2:1]=[O:2].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:10]OCC(O)C>>[O:2]1[C:1]2[CH:10]=[CH:5][CH:6]=[CH:7][C:8]=2[CH:9]=[CH:4][NH:3]1
Reactant: Nc1ccccc1
Reactant: COCC(C)O
Reactant: C=O
Product: C1=Cc2ccccc2ON1
Temperature: 105 °C
Reaction time: 2 h

Procedure:
The steps include: in a 2 L four-necked glass reactor equipped with a heating mantle, a temperature controller, an electric mixer and a condenser, 200 g of phenolic novolac resin (D) having high proportion of tetra-functional resin monomer and 124.5 g of paraformaldehyde are dissolved thoroughly in the presence of 816 g of a solvent propylene glycol monomethyl ether at 85° C., 169 g of aniline is dropped in the course of 3 hours into the reactor at constant speed by a quantitative pump to proceed the reaction at 85° C. After finishing the dropping addition of aniline, the temperature is kept at 85° C. for aging for 2 hours, then the temperature is raised to 105° C. After water and part of the solvent are removed, a benzoxazine resin solution with 56 wt % solid is obtained. According to gel permeation chromatography (GPC) analysis, the proportion of the tetra-functional resin monomer in this benzoxazine resin is up to 60 area percent (Area %) or more.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=[C:9]2[CH:18]=O)=[CH:4][CH:3]=1.[F:20][C:21]1[C:27]([F:28])=[CH:26][CH:25]=[C:24]([F:29])[C:22]=1[NH2:23].[B][B][B][B][B][B][B][B][B][B]>C(O)(=O)C.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=[C:9]2[CH2:18][NH:23][C:22]2[C:24]([F:29])=[CH:25][CH:26]=[C:27]([F:28])[C:21]=2[F:20])=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1cnc(C=O)n1-c1ccc(F)cc1
Reactant: Nc1c(F)ccc(F)c1F
Agent: [B][B][B][B][B][B][B][B][B][B]
Solvent: CC(=O)O
Solvent: CO
Product: CCOC(=O)c1cnc(CNc2c(F)ccc(F)c2F)n1-c1ccc(F)cc1

Procedure:
A solution of ethyl 1-(4-fluorophenyl)-2-formyl-1H-imidazole-5-carboxylate (16) (150 mg, 0.57 mmol), 2,3,6-trifluoroaniline (60.4 μL, 0.57 mmol), decaborane (14 mg, 0.11), acetic acid (2 drops), and methanol (6 mL) was stirred at room temperature overnight. The reaction was concentrated and the residue was purified by flash column chromatography on silica gel (0-30% EtOAc in hexanes) to yield ethyl 1-(4-fluorophenyl)-2-(((2,3,6-trifluorophenyl)amino)methyl)-1H-imidazole-5-carboxylate (23).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C:7]([NH:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:12])[CH2:6]2)[CH3:2].[C:22]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[CH2:30][C:29]([NH:35][C:36](=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:34])[CH2:28]2)(=[O:24])[CH3:23]>>[C:22]([C:11]1[CH:10]=[C:9]2[C:5](=[CH:4][C:3]=1[CH2:1][CH3:2])[CH2:6][C:7]([NH:13][C:14](=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([CH3:12])[CH2:8]2)(=[O:24])[CH3:23].[CH2:22]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[CH2:30][C:29]([NH:35][C:36](=[O:43])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)([CH3:34])[CH2:28]2)[CH3:23]
Reactant: CC(=O)c1ccc2c(c1)CC(C)(NC(=O)c1ccccc1)C2
Agent: CCc1ccc2c(c1)CC(C)(NC(=O)c1ccccc1)C2
Product: CCc1cc2c(cc1C(C)=O)CC(C)(NC(=O)c1ccccc1)C2

Procedure:
N-(5-Acetyl-6-ethyl-2-methyl-indan-2-yl)-benzamide is prepared from N-(5-ethyl-2-methyl-indan-2-yl)-benzamide (2.6 g) following the procedure used to prepare N-(5-acetyl-2-methyl-indan-2-yl)-benzamide. The product is purified by chromatography (silica, hexane/ethyl acetate, 4:1) to give the title compound. ES+ MS m/e 322 (MH+)
Reaction SMILES: O.NN.[CH3:4][N:5]1[C:9]([CH3:10])=[CH:8][N:7]([N:11]=CC2C=NC=CC=2)[C:6]1=[O:19]>CO>[NH2:11][N:7]1[CH:8]=[C:9]([CH3:10])[N:5]([CH3:4])[C:6]1=[O:19]
Reactant: Cc1cn(N=Cc2cccnc2)c(=O)n1C
Agent: NN
Solvent: CO
Solvent: O
Product: Cc1cn(N)c(=O)n1C

Procedure:
2 g of hydrazine hydrate are added to a solution of 2 g of 3,4-dimethyl-1-(pyridin-3-ylmethyleneamino)-2,3-dihydroimidazol-2-one in 12 ml of methanol and the suspension is boiled under reflux for 6 hours, then concentrated by evaporation and chromatographed on silica gel. 1 g of pyridine-3-carbaldehyde hydrazone and 0.7 g of the title compound having a melting point of 115°-119° are thus obtained.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11].[C:15](O)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1.CCN=C=NCCCN(C)C>CC#N.CCOC(C)=O>[C:15]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1
Reactant: O=C(O)c1cccnc1
Reactant: CC(C)(C)OC(=O)NCCOCCN
Agent: CCN=C=NCCCN(C)C
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NCCOCCNC(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 43.9 %

Procedure:
tert-Butyl 2-(2-aminoethoxy)ethylcarbamate (420, 2.06 mmol) was then taken up in CH3CN (20 mL) along with nicotinic acid (253 mg, 2.06 mmol) and EDCI (434 mg, 2.3 mmol). The resulting reaction mixture was stirred at room temperature for 18 h. It was then diluted with EtOAc (20 mL), washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (9:1 CH2Cl2/MeOH) to afford tert-butyl 2-(2-(nicotinamido)ethoxy)ethylcarbamate (280 mg, 44%). MS calculated for C15H23N3O4: 309.17. Found: [M+H]+ 310.