Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]12([CH2:11][CH2:12][O:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][CH2:23][C@@H:24]([C:26]4[CH:27]=[CH:28][C:29]([O:35]CC5C=CC=CC=5)=[C:30]([NH:32][CH:33]=[O:34])[CH:31]=4)[OH:25])=[CH:16][CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2>CO.O1CCCC1.[Pd]>[C:1]12([CH2:11][CH2:12][O:13][C:14]3[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][NH:22][CH2:23][C@@H:24]([C:26]4[CH:27]=[CH:28][C:29]([OH:35])=[C:30]([NH:32][CH:33]=[O:34])[CH:31]=4)[OH:25])=[CH:18][CH:19]=3)[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2
Reactant: O=CNc1cc([C@@H](O)CNCCc2ccc(OCCC34CC5CC(CC(C5)C3)C4)cc2)ccc1OCc1ccccc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: O=CNc1cc([C@@H](O)CNCCc2ccc(OCCC34CC5CC(CC(C5)C3)C4)cc2)ccc1O
Reaction time: 72 h
Yield: 38.1 %

Procedure:
To a solution of Intermediate 26 (0.32 g, 0.56 mmol) in a mixture of methanol (5 mL) and tetrahydrofuran (5 mL) was added palladium on charcoal (10%, 0.03 g). The reaction mixture was hydrogenated at 40 psi for 3 days. The catalyst was filtered through Celite® and the solvent removed under reduced pressure. The crude was purified by chromatography eluting with chloroform/methanol (6:1) to give the title compound as a solid (0.102 g, 37%)
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]3[N:29]=[CH:28][C:27]([NH:30][C:31](=[O:43])[C:32]4[CH:37]=[C:36]([NH:38][C:39](=[O:41])[CH3:40])[CH:35]=[CH:34][C:33]=4[Cl:42])=[CH:26][N:25]=3)=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:39]([NH:38][C:36]1[CH:35]=[CH:34][C:33]([Cl:42])=[C:32]([CH:37]=1)[C:31]([NH:30][C:27]1[CH:26]=[N:25][C:24]([NH:23][C:20]2[CH:19]=[CH:18][C:17]([S:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)(=[O:15])=[O:16])=[CH:22][CH:21]=2)=[N:29][CH:28]=1)=[O:43])(=[O:41])[CH3:40]
Reactant: CC(=O)Nc1ccc(Cl)c(C(=O)Nc2cnc(Nc3ccc(S(=O)(=O)C4CCN(C(=O)OC(C)(C)C)CC4)cc3)nc2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(=O)Nc1ccc(Cl)c(C(=O)Nc2cnc(Nc3ccc(S(=O)(=O)C4CCNCC4)cc3)nc2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 23.6 %

Procedure:
To a solution of intermediate 58 (Example 112) (0.25 g, 0.40 mmol) in DCM (8 mL) was added TFA (30% in DCM, 6 mL) and the mixture stirred at room temperature for 2 h. The reaction mixture was concentrated and the residue purified by HPLC to afford the title compound (TFA salt; 50 mg, 23%) as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17](C3N(C4C=CC=CC=4)C4C=CC=CC=4N=3)=[CH:16][CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1.[C:35]1([N:41]2C3C=CC(B(O)O)=CC=3[C:47]3[C:42]2=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.BrC1C=CC=CC=1C1C=CC=CC=1Br.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.C1COCC1.O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:15]=[CH:16][C:17]2[N:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:35]3[C:36]([C:18]=2[CH:19]=1)=[CH:37][CH:38]=[CH:39][CH:40]=3
Reactant: Brc1ccccc1-c1ccccc1-c1ccc(-c2nc3ccccc3n2-c2ccccc2)cc1
Reactant: OB(O)c1ccc2c(c1)c1ccccc1n2-c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Brc1ccccc1-c1ccccc1Br
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: O
Product: Brc1ccccc1-c1ccccc1-c1ccc2c(c1)c1ccccc1n2-c1ccccc1
Yield: 56 %

Procedure:
Following the procedure for Compound 3, (9-phenyl-9H-carbazol-3-yl)boronic acid (1.84 g, 6.41 mmol), 2,2′-dibromo-1,1′-biphenyl (4.00 g, 12.8 mmol), tetrakis(triphenylphosphine)palladium(0) (0.296 g, 0.257 mmol), Na2CO3 (2.54 g, 24.0 mmol), H2O (24 mL) and THF (40 mL) yielded Compound 9 (1.69 g, 56%) as a colorless solid after flash chromatography (SiO2, 19:1-hexanes: CH2Cl2): confirmed by LCMS (APCI): calculated for C30H20NBr (M+): 474; Found: 474.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[NH:20])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Br[CH2:27][C:28](=[O:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C(O)(C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:17])=[O:18])=[CH:12][CH:11]=3)[CH2:27][C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])([OH:34])[N:20]=2)=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)c1ccc(NC(=N)c2ccc(Cl)cc2)cc1
Reactant: CCOC(=O)C(=O)CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Product: CCOC(=O)C1(O)CN(c2ccc(S(C)(=O)=O)cc2)C(c2ccc(Cl)cc2)=N1

Procedure:
A mixture of 4-chloro-N-[4-(methylsulfonyl)phenyl]benzenecarboximidamide (Example 1, step 1) (1.00 g, 3.34 mmol), sodium bicarbonate (544 mg, 6.47 mmol), and ethyl bromopyruvate (1.40 g, 7.19 mmol) in 50 ml of isopropanol was stirred at reflux for 7 hours. After cooling, the mixture was evaporated. The residue was partitioned between dichloromethane and water, and the aqueous layer further extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. Chromatography of the residue over silica gel using mixtures of ethyl acetate and toluene as eluents gave the title compound as a pale yellow solid: mp (DSC) 162° C. Anal. Calc'd. for C19H19ClN2O5S (MW 422.89): C, 53.96; H,.4.53; N, 6.62. Found: C, 53.99; H, 4.49; N, 6.42.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[CH:7]=[O:8].C1C(=O)N([Br:16])C(=O)C1>C1COCC1>[Br:16][C:6]1[C:2]([CH3:1])=[C:3]([CH:7]=[O:8])[NH:4][CH:5]=1
Reactant: Cc1cc[nH]c1C=O
Reactant: O=C1CCC(=O)N1Br
Solvent: C1CCOC1
Product: Cc1c(Br)c[nH]c1C=O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Following a general procedure,50 a stirred solution of 3-methyl-pyrrole-2-carboxaldehyde (2, 5.63 g, 51.6 mmol) in THF (52 mL) was cooled to 0° C. NBS (9.19 g, 51.6 mmol; reagent grade, unrecrystallized) was added all at once. The reaction mixture was stirred for 15 min at 0° C. under argon before the solvent was removed on a rotary evaporator. The resulting solid was dried under high vacuum for 2 h. Water (100 mL, room temperature) was added to the flask and the suspension was filtered (Büchner funnel). The filter cake was washed with an additional 100 mL of water. The solid filtered material was recrystallized from water/ethanol as follows. The solid filtered material was transferred to a 250 mL round bottom flask equipped with a reflux condenser. Water/ethanol (150 mL, 5:1) were added and the mixture was refluxed in a hot water bath until all solid material had dissolved. Upon allowing the solution to cool to room temperature the product crystallized. The mixture was cooled to 4° C. for 2 h to promote more crystallization. The mixture was vacuum-filtered and the resulting off-white crystals were dried under high vacuum for 24 h (7.78 g, 80%): mp 140-143° C.; 1H NMR δ 2.32 (s, 3H), 7.08 (d, J=3.3 Hz, 1H), 9.60 (s, 1H), 9.95 (brs, 1H); 13C NMR δ 9.8, 101.7, 126.0, 129.3, 131.7, 177.9; ESI-MS obsd 187.9708, calcd 187.9706 [(M+H)+, M=C6H6BrNO].
Reaction SMILES: [H-].[Na+].[CH2:3]([N:10]([CH2:14][C:15]1[C:16](Cl)=[N:17][CH:18]=[CH:19][CH:20]=1)[CH2:11][CH2:12][OH:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O>C1COCC1>[CH2:3]([N:10]1[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[N:17][C:16]=2[O:13][CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCCN(Cc1ccccc1)Cc1cccnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: c1ccc(CN2CCOc3ncccc3C2)cc1
Temperature: 90 °C
Reaction time: 1 h
Yield: 75.3 %

Procedure:
Under a nitrogen atmosphere, to a suspension of sodium hydride (60% in oil, 1.99 g) in THF (30 ml) was added a solution of the compound (6.90 g) obtained in step 2 in THF (20 mL) at 0° C., and the mixture was stirred at 90° C. for 1 hr. The reaction mixture was cooled to 10° C., and poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution and brine, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient; 10→66% ethyl acetate/hexane) to give the title compound (4.51 g, 75%) as a pale-yellow oil.
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:14][N:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[N:16]1.[OH2:24].[OH2:25].O.O.O.O.C1(=O)OOOOC(=O)C2=CC=CC=C12.[Mg]>CN(C)C=O.CCOC(C)=O>[CH3:1][S:2]([CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[CH2:14][N:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[N:16]1)(=[O:25])=[O:24]
Reactant: O
Reactant: CSCCn1c(Cn2nnc3ccccc32)nc2ccccc21
Agent: O=c1ooooc(=O)c2ccccc12
Agent: [Mg]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CS(=O)(=O)CCn1c(Cn2nnc3ccccc32)nc2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 41 %

Procedure:
1-[1-(2-Methylthio-ethyl)-1H-benzimidazol-2-ylmethyl]-1H-benzotriazole (100 mg, 0.309 mmol) was dissolved in anhydrous N,N-dimethylformamide (5 mL). Magnesium monoperoxy phthalate hexahydrate (611 mg, 1.24 mmol) was added and the reaction mixture was stirred at room temperature overnight under N2. The solvent was stripped under reduced pressure. The yellow oily residue was taken up in EtOAc (100 mL) and washed with water (2×50 mL) dried over magnesium sulfate, filtered and evaporated. Column chromatography on silica gel (EtOAc) gave 45 mg (41%) of the title compound as an oil.
Reaction SMILES: [CH:1]1([CH2:4][C:5]([O:18][C:19]2[CH:41]=[CH:40][C:22]3[C:23]4[N:27]([CH2:28][CH2:29][O:30][C:21]=3[CH:20]=2)[CH:26]=[C:25]([C:31]2[N:32]([CH:37]([CH3:39])[CH3:38])[N:33]=[C:34]([CH3:36])[N:35]=2)[N:24]=4)([CH2:12]OS(C)(=O)=O)[CH2:6]OS(C)(=O)=O)[CH2:3][CH2:2]1>C(N)(C)C>[CH:1]1([CH2:4][C:5]2([O:18][C:19]3[CH:41]=[CH:40][C:22]4[C:23]5[N:27]([CH:26]=[C:25]([C:31]6[N:32]([CH:37]([CH3:39])[CH3:38])[N:33]=[C:34]([CH3:36])[N:35]=6)[N:24]=5)[CH2:28][CH2:29][O:30][C:21]=4[CH:20]=3)[CH2:12][N:24]([CH:25]([CH3:31])[CH3:26])[CH2:6]2)[CH2:2][CH2:3]1
Reactant: Cc1nc(-c2cn3c(n2)-c2ccc(OC(COS(C)(=O)=O)(COS(C)(=O)=O)CC4CC4)cc2OCC3)n(C(C)C)n1
Solvent: CC(C)N
Product: Cc1nc(-c2cn3c(n2)-c2ccc(OC4(CC5CC5)CN(C(C)C)C4)cc2OCC3)n(C(C)C)n1
Temperature: 25 °C

Procedure:
A solution of methanesulfonic acid 2-cyclopropylmethyl-2-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-3-methanesulfonyloxypropyl ester (87 mg, 0.1427 mmol) in isopropylamine (1.2 mL) was heated at 150° C. for 28 h using microwave irradiation. After cooling to RT, the crude reaction mixture was evaporated and then purified by column chromatography (C18, gradient 25-55% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording 283 as a colourless foam (43.1 mg, 63%). LCMS (Method K): RT 3.15 min [M+H]+ 477.2. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=9.0 Hz), 7.67 (1H, s), 6.57 (1H, dd, J=9.0, 2.6 Hz), 6.36 (1H, d, J=2.5 Hz), 5.87 (1H, septet, J=6.7 Hz), 4.48 (4H, s), 3.72-3.69 (2H, m), 3.38-3.35 (2H, m), 2.49 (1H, septet, J=6.3 Hz), 2.35 (3H, s), 2.04 (2H, d, J=6.6 Hz), 1.52 (6H, d, J=6.6 Hz), 0.99 (6H, d, J=6.3 Hz), 0.80-0.70 (1H, m), 0.45-0.41 (2H, m), 0.03-0.00 (2H, m)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[C:5]([N+:10]([O-:12])=[O:11])[CH:4]=1.[Br:13]Br.C(=O)(O)[O-].[Na+]>ClCCl>[Br:13][C:8]1[CH:9]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]([N+:10]([O-:12])=[O:11])[C:6]=1[NH2:7]
Reactant: BrBr
Reactant: COc1ccc(N)c([N+](=O)[O-])c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1cc(Br)c(N)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-methoxy-2-nitroaniline (35 g) in dichloromethane (350 mL) was subsequently added dropwise bromine (12.9 mL) at −20° C. After stirring for 30 minutes at the same temperature, this was poured into ice water, adjusted to pH 7 to 8 with saturated sodium bicarbonate aqueous solution and then extracted with dichloromethane. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate). After concentration of the desired fraction, the resulting residue was crystallized from hexane and ethyl acetate and then collected by filtration to obtain the title compound as reddish orange crystals (29.6 g).
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([NH2:9])=[O:8])#[N:2].Cl[CH2:14][C:15](=O)[CH3:16]>>[CH3:16][C:15]1[N:9]=[C:7]([C:6]2[CH:5]=[C:4]([CH2:3][C:1]#[N:2])[CH:12]=[CH:11][CH:10]=2)[O:8][CH:14]=1
Reactant: CC(=O)CCl
Reactant: N#CCc1cccc(C(N)=O)c1
Product: Cc1coc(-c2cccc(CC#N)c2)n1

Procedure:
A solution of 3-(cyanomethyl)benzamide (200 mg, 1.25 mmol) in 1-chloropropan-2-one (2 mL) was microwave irradiated at 120 for 20 min in a sealed tube. The mixture was concentrated to give crude product (110 mg), which was directly used to the next reaction without purification. LCMS MH+ 199.
Reaction SMILES: [O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C:30](OCC)=[O:31])=[CH:26][CH:25]=1.[BH4-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC>[OH:31][CH2:30][CH2:29][O:28][C:27]1[CH:26]=[CH:25][C:24]([CH2:23][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:22]4[C:13](=[CH:14][C:15]5[O:20][CH2:19][CH2:18][O:17][C:16]=5[CH:21]=4)[O:12][CH2:11]3)[C:2]2=[O:1])=[CH:36][CH:35]=1
Reactant: CCOC(=O)COc1ccc(CN2C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc32)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH4-]
Agent: [Li+]
Solvent: COCCOC
Product: O=C1N(Cc2ccc(OCCO)cc2)c2ccccc2C12COc1cc3c(cc12)OCCO3
Temperature: 25 °C
Reaction time: 2 h
Yield: 61.2 %

Procedure:
To a solution of ethyl {4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]phenoxy}acetate (0.22 g, 0.44 mmol) in anhydrous 1,2-dimethoxyethane (5 mL) was added at 0° C. lithium borohydride (2.0 M solution in tetrahydrofuran, 0.44 mL, 0.88 mmol) dropwise. The mixture was stirred at ambient temperature for 2 h, cooled to 0° C., and 7% w/v aqueous citric acid (15 mL) was added dropwise. The mixture was extracted with chloroform (3×60 mL). The combined organic layers was washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 50% ethyl acetate in hexanes to afford 1′-[4-(2-hydroxyethoxy)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.12 g, 63%) as a colorless solid: mp 196-197° C.; 1H NMR (300 MHz, CDCl3) δ 7.31-7.24 (m, 2H), 7.23-7.12 (m, 2H), 7.05-6.97 (m, 1H), 6.92-6.86 (m, 2H), 6.83-6.78 (m, 1H), 6.51 (s, 1H), 6.22 (s, 1H), 4.89 (ABq, J=79.6, 15.4 Hz, 2H), 4.79 (ABq, J=83.8, 8.9 Hz, 2H), 4.22-4.08 (m, 4H), 4.08-3.91 (m, 4H), 1.94 (s, 1H); 13C NMR (300 MHz, CDCl3) δ 177.5, 158.2, 155.2, 144.6, 142.0, 138.2, 132.3, 128.8, 128.7, 128.2, 123.8, 123.3, 121.0, 114.9, 111.5, 109.3, 99.4, 80.1, 69.1, 64.5, 63.9, 61.4, 58.0, 43.6; MS (ES+) m/z 446.0 (M+1).
Reaction SMILES: [CH2:1]([C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:42])=[C:8]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[N+:39]([O-])=O)[C:9](=[O:31])[N:10]2[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3[NH:30][N:29]=[N:28][N:27]=3)=[CH:16][CH:15]=2)=[CH:5][CH:4]=1)[CH3:2]>C(O)C>[NH2:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH2:32][C:8]1[C:9](=[O:31])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3[NH:30][N:29]=[N:28][N:27]=3)=[CH:16][CH:15]=2)[C:11]2[C:6]([C:7]=1[CH3:42])=[CH:5][CH:4]=[C:3]([CH2:1][CH3:2])[CH:12]=2
Reactant: CCc1ccc2c(C)c(Cc3ccccc3[N+](=O)[O-])c(=O)n(Cc3ccc(-c4ccccc4-c4nnn[nH]4)cc3)c2c1
Solvent: CCO
Product: CCc1ccc2c(C)c(Cc3ccccc3N)c(=O)n(Cc3ccc(-c4ccccc4-c4nnn[nH]4)cc3)c2c1

Procedure:
A solution of 1 g of 7-ethyl-1,2-dihydro-4-methyl-3-o-nitrobenzyl-2-oxo-1-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]quinoline in 25 ml of ethanol is hydrogenated on 0.3 g of 5% Pd-on-charcoal at 20° and normal pressure until the calculated amount of H2 has been taken up. The catalyst is filtered off, the filtrate is evaporated and the 3-o-aminobenzyl-7-ethyl-1,2-dihydro-4-methyl-2-oxo-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl-methyl]quinoline obtained is purified by chromatography.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:5]([C:7]1[O:11][N:10]=[C:9]([CH2:12][S:13][CH3:14])[N:8]=1)[CH3:6].I([O-])(=O)(=O)=[O:25].[Na+]>C(O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:5]([C:7]1[O:11][N:10]=[C:9]([CH2:12][S:13]([CH3:14])=[O:25])[N:8]=1)[CH3:6]
Reactant: CSCc1noc(C(C)c2ccc(-c3ccccc3)c(F)c2)n1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC(c1ccc(-c2ccccc2)c(F)c1)c1nc(CS(C)=O)no1
Yield: 100.4 %

Procedure:
To a solution of 0.95 g of 5-(3-fluoro-4-phenyl-α-methylbenzyl)-3-methylthiomethyl-1,2,4-oxadiazole in 150 ml of ethanol was added a solution of 1.36 g of sodium metaperiodate in 50 ml of water. After stirring with reflux for 9 hours, the reaction mixture was cooled, diluted with water and extracted with chloroform. The extracts were washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue was chromatographed over silica gel using chloroform to yield 1.0 g of 5-(3-fluoro-4-phenyl-α-methylbenzyl)-3-methylsulfinylmethyl- 1,2,4-oxadiazole. It was recrystallized from ethyl acetate-diisopropyl ether to give colorless needles, m.p. 71°-72° C. (decomp.).
Reaction SMILES: Br[C:2]1[O:6][C:5]([C:7]([OH:9])=[O:8])=[CH:4][CH:3]=1.[CH2:10]([OH:24])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].CC(C)([O-])C.[K+].CC(N(C)C)=O>O1CCCC1.C(O)(C)(C)C>[CH2:10]([O:24][C:2]1[O:6][C:5]([C:7]([OH:9])=[O:8])=[CH:4][CH:3]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCCCCCCCCO
Reactant: O=C(O)c1ccc(Br)o1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: C1CCOC1
Solvent: CC(C)(C)O
Product: CCCCCCCCCCCCCCOc1ccc(C(=O)O)o1

Procedure:
A mixture of 125.0 g (0.652 mole) of 5-bromo-2-furoic acid, 210.0 g (0.978 mole) of 1-tetradecanol 183.0 g (1.630 mole) of potassium tert- butoxide and 2500 ml of dimethyl acetamide is heated with stirring. The tertbutanol formed in the reaction is allowed to distill off, then the mixture is heated to reflux with stirring for 48 hours. To the cooled mixture is added 6 liters of icewater, and the mixture is acidified with malonic acid. The resulting precipitate is collected, dried and recrystallized twice from methanol to give 82.0 g (29%) of 5-(tetradecyloxy)-2-furoic acid, M.P. 112°-115° C (dec.) The 82.0 g (0.253 mole) of 5-(tetradecyloxy)-2-furoic acid, 41.0 g (0.253 mole) of N,N'-carbonyldiimidazole and tetrahydrofuran are combined and stirred at room temperature, during which time carbon dioxide gas is evolved, then cooled to give N-[5-(tetradecyloxy)-2-furoyl]imidazole. The N-substituted imidazole, 50.0 g (0.134 mole) in tetrahydrofuran, is cooled in an ice bath. An equivalent amount of methyl magnesium bromide (50 ml of a 3 Molar solution in ether) is slowly added over 2 hours to the stirred mixture. The reaction is stirred for an additional 3 hours then excess (500 ml.) of 2N HCl is added and the product extracted into ether. The ether layer is separated, washed with water, dried over sodium sulfate, filtered, and evaporated to dryness affording 5-(tetradecyloxy)-2-furyl methyl ketone.
Reaction SMILES: [F:1][C:2]1[C:20]([F:21])=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:3]=1[O:4][C:5]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.C(N(CC)CC)C.[Cl:32][CH2:33][C:34](Cl)=[O:35]>ClCCl.C(OCC)(=O)C>[Cl:32][CH2:33][C:34]([N:8]1[CH2:7][CH2:6][C:5]([O:4][C:3]2[C:17]([F:24])=[C:18]([F:23])[C:19]([F:22])=[C:20]([F:21])[C:2]=2[F:1])([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:10][CH2:9]1)=[O:35]
Reactant: O=C(Cl)CCl
Reactant: Fc1c(F)c(F)c(OC2(c3ccccc3)CCNCC2)c(F)c1F
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: O=C(CCl)N1CCC(Oc2c(F)c(F)c(F)c(F)c2F)(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A chilled solution of 4.0 g of 4-(2,3,4,5,6-pentafluorophenoxy)-4-phenylpiperidine and 2.4 ml of triethylamine in 50 ml of dichloromethane was treated with a solution of 1.4 ml of chloroacetyl chloride in 10 ml of dichloromethane and then stirred at ambient temperature for four hours. The mixture was diluted with 100 ml of ethyl acetate, dried over anhydrous magnesium sulfate, filtered and evaporated to yield 5.0 g of 1-(2-chloroacetyl)-4-(2,3,4,5,6-pentafluorophenoxy)-4-phenylpiperidine as an oil.
Reaction SMILES: [NH2:1][C:2]1[C:7](=[N:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:6]=[C:5]([CH3:16])[C:4](=[O:17])[C:3]=1[Cl:18].S(S([O-])=O)([O-])=O.[Na+].[Na+]>CO.[OH-].[Na+]>[NH2:1][C:2]1[C:3]([Cl:18])=[C:4]([OH:17])[C:5]([CH3:16])=[CH:6][C:7]=1[NH:8][C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1
Reactant: CC1=CC(=Nc2ccc(O)cc2)C(N)=C(Cl)C1=O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1cc(Nc2ccc(O)cc2)c(N)c(Cl)c1O

Procedure:
10 mg (0.04 mol) of 3-amino-2-chloro-4-[(4-hydroxyphenyl)imino]-6-methylcyclohexa-2,5-dien-1-one are added to a solution comprising 16 mg of sodium hydrosulphite in 500 μl of methanol and 5 μl of an aqueous sodium hydroxide solution. The reaction medium is stirred and then the solution is treated according to the usual procedure and characterized. 3-Amino-2-chloro-4-[(4-hydroxyphenyl)amino]-6-methylphenol (2a) is obtained.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][C:10]12[CH2:17][CH2:16][C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[CH:19]=3)([CH2:14][CH2:15]1)[O:12][CH2:11]2)(=O)=O.[C-:31]#[N:32].[Na+]>CN(C=O)C.CCOC(C)=O>[O:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[O:24][C:20]1[CH:19]=[C:18]([C:13]23[CH2:14][CH2:15][C:10]([CH2:9][CH2:8][CH2:7][CH2:6][C:31]#[N:32])([CH2:17][CH2:16]2)[CH2:11][O:12]3)[CH:23]=[CH:22][CH:21]=1
Reactant: CS(=O)(=O)OCCCCC12CCC(c3cccc(OC4CCCCO4)c3)(CC1)OC2
Reactant: [C-]#N
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#CCCCCC12CCC(c3cccc(OC4CCCCO4)c3)(CC1)OC2
Temperature: 60 °C
Reaction time: 18 h
Yield: 91.1 %

Procedure:
A mixture of 4-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo [2.2.2]octan-4-yl)butyl methanesulfonate (133 mg, 0.303 mmol) and NaCN (60 mg, 1.224 mmol) in DMF (2 mL) was stirred at 60° C. for 18 h. The reaction was cooled to rt and diluted with EtOAc (6 mL). The organic phase was washed with water (5×5 mL), dried (MgSO4), and concentrated in vacuo to afford the title compound (102 mg, 91% yield) as a light yellow oil. LCMS, [M+H]+=370.5. 1H NMR (500 MHz, CDCl3) δ 7.23 (t, J=8.0 Hz, 1H), 7.13-7.10 (m, 1H), 7.01 (ddd, J=7.8, 1.6, 1.0 Hz, 1H), 6.94 (ddd, J=8.2, 2.5, 0.9 Hz, 1H), 5.45 (t, J=3.2 Hz, 1H), 3.98-3.89 (m, 1H), 3.83 (s, 2H), 3.66-3.57 (m, 1H), 2.38 (t, J=7.1 Hz, 2H), 2.10-1.96 (m, 5H), 1.90-1.81 (m, 2H), 1.75-1.55 (m, 10H), 1.49-1.37 (m, 2H), 1.22-1.14 (m, 2H).