Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[NH:7][C:8]([N:12]3[CH:16]=[C:15]([C:17]([O:19]CC)=[O:18])[CH:14]=[N:13]3)=[N:9]2)=[CH:4][C:3]=1[CH:23]([CH3:25])[CH3:24].[CH3:26][NH:27][CH3:28]>>[CH3:26][N:27]([CH3:28])[C:6]1[C:5]2[C:10](=[CH:11][C:2]([F:1])=[C:3]([CH:23]([CH3:25])[CH3:24])[CH:4]=2)[N:9]=[C:8]([N:12]2[CH:16]=[C:15]([C:17]([OH:19])=[O:18])[CH:14]=[N:13]2)[N:7]=1
Reactant: CNC
Reactant: CCOC(=O)c1cnn(-c2nc3cc(F)c(C(C)C)cc3c(=O)[nH]2)c1
Product: CC(C)c1cc2c(N(C)C)nc(-n3cc(C(=O)O)cn3)nc2cc1F

Procedure:
The above compound may be made analogous to Example 1 using ethyl 1-(7-fluoro-6-isopropyl-4-oxo-3,4-dihydroquinazolin-2-yl)-1H-pyrazole-4-carboxylate in step D and dimethylamine in step E. MS (ESI): predicted mass calcd. for C17H18FN5O2, 343.1
Reaction SMILES: ClC(OC(Cl)C)=O.C([N:15]1[CH2:20][C@H:19]([CH3:21])[O:18][C@@H:17]([CH3:22])[CH2:16]1)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C.C([O-])([O-])=O.[K+].[K+].F[C:39]1[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][C:40]=1[CH:41]=[O:42]>C(Cl)Cl>[CH3:22][C@@H:17]1[O:18][C@@H:19]([CH3:21])[CH2:20][N:15]([C:39]2[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][C:40]=2[CH:41]=[O:42])[CH2:16]1
Reactant: O=Cc1cc([N+](=O)[O-])ccc1F
Reactant: C[C@H]1CN(Cc2ccccc2)C[C@H](C)O1
Agent: CC(Cl)OC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C[C@H]1CN(c2ccc([N+](=O)[O-])cc2C=O)C[C@H](C)O1
Temperature: 25 °C

Procedure:
1-Chloroethyl chloroformate (292 μL, 2.68 mmol, Aldrich) is added to a solution of (2S,6S)-4-benzyl-2,6-dimethylmorpholine (in CH2Cl2 (6 mL) with stirring in an ice bath. The solution is allowed to warm to room temperature and stirred for 2.5 hours. The solvent is removed by rotary evaporation and the residue is dissolved in methanol (6 mL). This solution is heated to reflux for 2.5 hours and the methanol is removed by rotary evaporation. The residue is dissolved in CH3CN (5 mL) and treated with N,N-diisopropylethylamine (244 μL, 1.4 mmol, Aldrich). K2CO3 (190 mg, 1.37 mmol, Mallinkrodt) and 2-fluoro-5-nitrobenzaldehyde (230 mg, 1.36 mmol, Oakwood) are added and the mixture is heated at 60° C. for 21 hours. The mixture is filtered and the solvent is removed by rotary evaporation. The residue is dissolved in CH2Cl2 (100 mL) and washed sequentially with water (75 mL) and brine (75 mL). The organic layer is purified on a Biotage Flash 25M+ using a 40% EtOAc in heptane as eluent. The product containing fractions are pooled and the solvent is removed by rotary evaporation. The product is dried under vacuum yielding a yellow syrup.
Reaction SMILES: C(O)(=O)C.CN.C([O:9][C:10](=O)[CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=[C:13]1[CH:23]=O)C.[C:26]([BH3-])#[N:27].[Na+]>O1CCCC1>[CH3:26][N:27]1[C:10](=[O:9])[CH2:11][N:12]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:14]=[C:13]2[CH2:23]1
Reactant: CCOC(=O)Cn1cc(-c2ccccc2)cc1C=O
Reactant: [BH3-]C#N
Agent: CN
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CN1Cc2cc(-c3ccccc3)cn2CC1=O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 30 %

Procedure:
Acetic acid was added to a solution of methylamine (0.45 mL, 5.30 mmol, 40% in water) in tetrahydrofuran (8 mL) to adjust the pH to 6. A solution of (2-formyl-4-phenyl-pyrrol-1-yl)-acetic acid ethyl ester (680 mg, 2.65 mmol) in tetrahydrofuran (4 mL) was added and the reaction mixture stirred at ambient temperature for 45 min. Sodium cyanoborohydride (0.33 g, 5.30 mmol) was added and the reaction mixture heated at 75 C for 18 h. Concentration in vacuo yielded a residue which was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the crude product. Purification by column chromatography over silica gel (100-200 mesh) using 30% ethyl acetate in petroleum ether afforded 2-methyl-7-phenyl-1,2-dihydropyrrolo[1,2-a]pyrazin-3-one (180 mg, 30%) as a solid.
Reaction SMILES: CO.C([O:10][C:11]1[CH:30]=[CH:29][C:14]([CH:15]([OH:28])[CH2:16][N:17](CC2C=CC=CC=2)[CH:18]([CH3:20])[CH3:19])=[CH:13][C:12]=1[NH:31][C:32](=[O:42])[CH2:33][O:34]CC1C=CC=CC=1)C1C=CC=CC=1.[ClH:43]>C(O)C.[C].[Pd]>[ClH:43].[OH:10][C:11]1[CH:30]=[CH:29][C:14]([CH:15]([OH:28])[CH2:16][NH:17][CH:18]([CH3:20])[CH3:19])=[CH:13][C:12]=1[NH:31][C:32](=[O:42])[CH2:33][OH:34]
Reactant: CC(C)N(Cc1ccccc1)CC(O)c1ccc(OCc2ccccc2)c(NC(=O)COCc2ccccc2)c1
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: CCO
Product: CC(C)NCC(O)c1ccc(O)c(NC(=O)CO)c1

Procedure:
In 100 ml. of methanol there was dissolved 2.3 g. of 4-benzyloxy-3-benzyloxyacetylamino-α-(N-benzyl-N-isopropylaminomethyl)benzyl alcohol and after adding to the solution 4.3 ml. of 1N hydrogen chloride in ethanol solution and then 0.3 g. of 10% palladium carbon, the catalytic reduction was conducted at normal temperature and pressure. When 300 ml. of hydrogen was absorbed, the reaction was stopped. Thereafter, the catalyst was filtered off and then the solvent was distilled off under reduced pressure to provide a white crystalline material. By crystallizing the crystals from methanol-n-hexane, 600 mg. of 4-hydroxy-3-hydroxyacetylamino-α-(isopropylaminomethyl)benzyl alcohol hydrochloride melting at 188°-190° C was obtained.
Reaction SMILES: Cl.[C:2]1([C:8]2[CH:9]=[C:10]3[C:14](=[C:15]([C:17]([NH2:19])=[O:18])[CH:16]=2)[NH:13][N:12]=[C:11]3[CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:33](Cl)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:2]1([C:8]2[CH:9]=[C:10]3[C:14](=[C:15]([C:17]([NH2:19])=[O:18])[CH:16]=2)[NH:13][N:12]=[C:11]3[CH:20]2[CH2:25][CH2:24][N:23]([C:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:40])[CH2:22][CH2:21]2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: NC(=O)c1cc(-c2ccccc2)cc2c(C3CCNCC3)n[nH]c12
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: NC(=O)c1cc(-c2ccccc2)cc2c(C3CCN(C(=O)c4ccccc4)CC3)n[nH]c12
Reaction time: 8 h
Yield: 49.9 %

Procedure:
A mixture of 5-phenyl-3-(4-piperidinyl)-1H-indazole-7-carboxamide hydrochloride (0.051 g, 0.17 mmols), triethylamine (0.1 mL, 0.71 mmols), DMAP (0.0021 g, 0.017 mmols), and benzoylchloride (0.020 mL, 0.17 mmols) in DMF (3 mL) was kept at ambient temperature overnight. The mixture was concentrated in vacuo and the resulting residue purified via preparative HPLC, eluting with 10% B to 80% B, where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid) to give 0.036 g of a white solid. LC/MS-M+H 425
Reaction SMILES: C([O:8][C:9]1[C:10]2[N:11]([C:15]([C:19]([NH:21][C@H:22]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[O:20])=[C:16]([CH3:18])[N:17]=2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1>C(O)C.[C].[Pd]>[Si:25]([O:24][CH2:23][C@H:22]([NH:21][C:19]([C:15]1[N:11]2[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[C:10]2=[N:17][C:16]=1[CH3:18])=[O:20])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]
Reactant: Cc1nc2c(OCc3ccccc3)cccn2c1C(=O)N[C@@H](CO[Si](C)(C)C(C)(C)C)c1ccccc1
Agent: [Pd]
Solvent: CCO
Product: Cc1nc2c(O)cccn2c1C(=O)N[C@@H](CO[Si](C)(C)C(C)(C)C)c1ccccc1
Reaction time: 3 h
Yield: 81.6 %

Procedure:
To a solution of 5.2 g of 8-(benzyloxy)-N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide in 70 ml of ethanol was added 1.0 g of 10% palladium-carbon (wet), followed by stirring for 3 hours under a hydrogen atmosphere. The reaction mixture was filtered over Celite, the solvent was then evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. To the obtained purified product were added hexane and diisopropyl ether, followed by stirring, and the resulting solid was collected by filtration and dried to obtain 3.5 g of N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxamide.
Reaction SMILES: BrCC(=O)C[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Br:18]CCCCCC(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-].C1C=CC=CC=1.C([SiH](CC)CC)C>ClCCl>[Br:18][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(CBr)CCCCCCCc1ccccc1
Reactant: O=C(Cl)CCCCCBr
Agent: CC[SiH](CC)CC
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: c1ccccc1
Product: BrCCCCCCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 33 %

Procedure:
1-Bromo-9-phenylnonan-2-one--A solution of 6-bromohexanoyl chloride (49.7 g, 0.233mol) in dry dichloromethane (40 ml) was added dropwise over 5 minutes to a suspension of aluminium chloride (31.0 g, 0.233 mol) in dry dichloromethane (100 ml), keeping the temperature between 20° C.-23° C. The mixture was stirred for 30 minutes at room temperature to give a yellow solution. Benzene (18.2 g, 0.233 mol) in dry dichloromethane (30 ml) was added and stirred for 20 hours at room temperature. Triethylsilane (59.9 g, 0.515 mol) was added over 10 minutes, maintaining the temperature between 25° C.-35° C. The solution was stirred for 60 minutes at room temperature. This was then poured onto ice/water (200g). A partial separation was achieved and the organic layer was washed with brine and water several times until the pH of the solution was neutral. The organic solution was dried (MgSO4) and evaporated under reduced pressure to a yellow oil. This was distilled under reduced pressure at 90° C.-110° C./0.5 mbar to give colourless oils. The relevant fractions were combined and purified by flash chromatography on silica gel using hexane to give 6-bromo-1-phenylhexane as a colourless oil (18.33 g, 33%).
Reaction SMILES: [F:1][C:2]1[C:3](I)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:14][CH:15]=[CH:16][C:17]=1[O:18][CH3:19].C([O-])([O-])=O.[Na+].[Na+].[OH:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[C:3]([C:31]2[CH:32]=[CH:33][C:28]([OH:27])=[CH:29][CH:30]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:14][CH:15]=[CH:16][C:17]=1[O:18][CH3:19]
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2ccc(F)c(I)c21
Reactant: OB(O)c1ccc(O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: COc1cc[nH]c1/C=C1\C(=O)Nc2ccc(F)c(-c3ccc(O)cc3)c21

Procedure:
A solution of (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (100 mg, 0.26 mmol) (Starting Material 13), 2M aqueous Na2CO3 solution (0.26 mL), (Ph3P)2PdCl2 (21.2 mg, 0.026 mmol) and 4-hydroxyphenylboronic acid (53.9 mg, 0.39 mmol) in 1,2-dimethoxyethane (10 mL) was heated at 104° C. for 4 days. The reaction mixture was filtered and concentrated. The crude material was purified by reverse phase HPLC to give (Z)-1,3-Dihydro-5-fluoro-4-(4-hydroxyphenyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 41 mg, 45%).
Reaction SMILES: CS(O[CH2:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[N:14][CH:13]=[C:12]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[CH:20]=1)[CH:11]=2)(=O)=O.FC1C=C(C=CC=1F)COC1C=C2C(C=C(CO)C=N2)=[N:35][CH:34]=1.CS(Cl)(=O)=O>C(Cl)Cl>[F:26][C:21]1[CH:20]=[C:19]([CH2:18][O:17][C:12]2[CH:11]=[C:10]3[C:15]([CH:16]=[C:7]([CH2:6][C:34]#[N:35])[CH:8]=[N:9]3)=[N:14][CH:13]=2)[CH:24]=[CH:23][C:22]=1[F:25]
Reactant: CS(=O)(=O)OCc1cnc2cc(OCc3ccc(F)c(F)c3)cnc2c1
Reactant: OCc1cnc2cc(OCc3ccc(F)c(F)c3)cnc2c1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Product: N#CCc1cnc2cc(OCc3ccc(F)c(F)c3)cnc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methyl methanesulfonate. To a solution of (7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanol (Example 73, 90 mg, 0.3 mmol) in DCM (4 mL) was added methanesulfonyl chloride (0.05 mL, 0.61 mmol) followed by TEA (0.06 mL, 0.43 mmol). The reaction mixture was stirred at RT for 1 h and quenched with saturated NaHCO3 solution. The mixture was extracted with DCM (2×) and the combined organic layers were dried, filtered and concentrated under reduced pressure. Purification (FCC, SiO2, 0-80%, EtOAc/hexanes) afforded the title compound as a white solid (73 mg, 64%). [M+H]=381.1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[C:5]2=[N:6][CH:7]=1.C([Li])CCC.CCCCCC.[CH2:29]([S:31]SCC)[CH3:30]>O1CCCC1>[C:14]([Si:11]([CH3:13])([CH3:12])[N:8]1[C:5]2=[N:6][CH:7]=[C:2]([S:31][CH2:29][CH3:30])[CH:3]=[C:4]2[CH2:10][CH2:9]1)([CH3:17])([CH3:16])[CH3:15]
Reactant: CCSSCC
Reactant: CC(C)(C)[Si](C)(C)N1CCc2cc(Br)cnc21
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCSc1cnc2c(c1)CCN2[Si](C)(C)C(C)(C)C
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 71.1 %

Procedure:
To a solution 5-bromo-1-(tert-butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 7, 3.3 g, 10.5 mmol) in anhydrous tetrahydrofuran (50 mL) at −78° C. was added a solution of n-butyllithium in n-hexane (1.6M, 10 mL, 16 mmol) dropwise. After stirring for 20 min at −78° C., ethyl disulfide (1.96 g, 16 mmol) was added. The resulting mixture was stirred for 1 h, quenched with a saturated ammonium chloride solution (20 mL), extracted with ethyl acetate (2×100 mL), dried over anhydrous sodium sulfate, concentrated in vacuo. The residue was purified by flash column chromatography (Qingdao silica gel, 300 mesh, 10% dichloromethane/hexanes) to afford 1-(tert-butyl-dimethyl-silanyl)-5-ethylsulfanyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (2.2 g, 71%): LC/MS m/e calcd for C15H26N2SSi [M+H]+ 295.54.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[CH2:8][CH:7]([NH:13][CH:14]([CH2:18][CH2:19][CH3:20])[C:15]([OH:17])=O)[CH2:6][CH2:5]2.[CH3:21][C:22]([N:31]1[CH:35]=[C:34]([NH2:36])[N:33]=[CH:32]1)([CH3:30])[CH2:23][N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH3:30][C:22]([N:31]1[CH:35]=[C:34]([NH:36][C:15](=[O:17])[CH:14]([NH:13][CH:7]2[CH2:6][CH2:5][C:4]3[C:9](=[C:10]([F:12])[CH:11]=[C:2]([F:1])[CH:3]=3)[CH2:8]2)[CH2:18][CH2:19][CH3:20])[N:33]=[CH:32]1)([CH3:21])[CH2:23][N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CC(C)(CN1CCCCC1)n1cnc(N)c1
Reactant: CCCC(NC1CCc2cc(F)cc(F)c2C1)C(=O)O
Product: CCCC(NC1CCc2cc(F)cc(F)c2C1)C(=O)Nc1cn(C(C)(C)CN2CCCCC2)cn1

Procedure:
Following the procedure for Example 86, 2-(6,8-Difluoro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-pentanoic acid (diastereomer 2) was reacted with 1-(1,1-Dimethyl-2-piperidin-1-yl-ethyl)-1H-imidazol-4-ylamine to afford the title compound: C13 NMR (100 MHz, CDCl3) 14.1, 19.5, 24.1, 25.8, 25.9, 26.7, 28.2, 28.9, 29.8, 36.6, 38.8, 52.8, 56.8, 59.1, 60.9, 69.1, 100.8, 101.0, 101.3, 104.6, 110.7, 110.8, 118.2, 131.3, 137.2, 139.9, 172.3; MS m/z 488.3 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH2:12])=[C:4]([NH:8][CH:9]2[CH2:11][CH2:10]2)[N:5]=[N:6][CH:7]=1.[CH2:13](OC(OCC)OCC)C>>[Cl:1][C:2]1[C:3]2[N:12]=[CH:13][N:8]([CH:9]3[CH2:10][CH2:11]3)[C:4]=2[N:5]=[N:6][CH:7]=1
Reactant: Nc1c(Cl)cnnc1NC1CC1
Reactant: CCOC(OCC)OCC
Product: Clc1cnnc2c1ncn2C1CC1
Yield: 48 %

Procedure:
A mixture of 5-chloro-N-3-cyclopropylpyridazine-3,4-diamine (Preparation 90, 10.0 g, 54 mmol) and triethylorthoformate (120 mL) were heated to reflux for 3 hours. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel column chromatography eluting with CH2Cl2:MeOH 98:2 to afford the title compound as a brown solid in 48% yield, 5 g.
Reaction SMILES: ClC1C=C(C(OO)=[O:9])C=CC=1.[CH2:12]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:18][CH:17]=1)[CH2:13][CH:14]=[CH2:15].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[C:19]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=[CH:21][C:16]([CH2:12][CH2:13][CH:14]2[CH2:15][O:9]2)=[CH:17][CH:18]=1
Reactant: C=CCCc1ccc(-c2ccccc2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: c1ccc(-c2ccc(CCC3CO3)cc2)cc1
Yield: 70.87 %

Procedure:
To a stirred mixture of 88 parts of 3-chlorobenzeneperoxoic acid and 650 parts of dichloromethane are added dropwise 60 parts of 4-(3-butenyl)-1,1'-biphenyl. Upon completion, stirring is continued over week-end at room temperature. Then there are added dropwise 50 parts of a potassium carbonate solution. The organic phase is separated, washed with a sodium bisulfite solution and with water, dried, filtered and evaporated, yielding 63.5 parts (70.87%) of [2-([1,1'-biphenyl]-4-yl)ethyl]oxirane as an oily residue.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N+:12]([O-:14])=[O:13])=[C:7](OC)[CH:6]=[CH:5]2.C[N:18](C)C=O.N.O>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N+:12]([O-:14])=[O:13])=[C:7]([NH2:18])[CH:6]=[CH:5]2
Reactant: CN(C)C=O
Reactant: COc1ccc2cc(Br)ccc2c1[N+](=O)[O-]
Agent: N
Solvent: CO
Solvent: O
Product: Nc1ccc2cc(Br)ccc2c1[N+](=O)[O-]
Temperature: 130 °C
Reaction time: 48 h
Yield: 95 %

Procedure:
6-bromo-2-methoxy-1-nitronaphthalene (12.6 g, 44.7 mmol), dimethylformamide (25.6 mL) and 7N NH3 solution in MeOH (128 mL, purchased from Sigma Aldrich) were combined in a Parr bomb. The bomb was heated in a lab oven at 130° C. After 48 hours, the reactor was removed from the oven and cooled to room temperature. The contents of the bomb were transferred to a glass round bottom flask. The bomb was thoroughly rinsed with dichloromethane and methanol, and the rinsings added to the flask. The contents of the flask were thoroughly concentrated on a rotary evaporator, leaving a brown solid. Water (200 mL) was added to the flask and the resulting suspension was agitated with a stir bar for 30 minutes. The resulting light brown powder was isolated by filtration, rinsing a few times with water. The filter cake was air dried over night to yield 6-bromo-1-nitronaphthalen-2-amine (11.6 g, >95% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1[OH:15].[CH3:16][C:17]([CH3:22])=[CH:18][CH:19](O)[CH3:20].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]=[CH:11][CH:12]=[CH:13][N:14]=2)=[CH:4][C:3]=1[O:15][CH:19]([CH:18]=[C:17]([CH3:22])[CH3:16])[CH3:20]
Reactant: Oc1cc(Nc2ncccn2)ccc1Cl
Reactant: CC(C)=CC(C)O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)=CC(C)Oc1cc(Nc2ncccn2)ccc1Cl
Reaction time: 1 h
Yield: 17 %

Procedure:
To a flask was added 2-chloro-5-(pyrimidin-2-ylamino)phenol (50 mg, 0.23 mmol), 4-methylpent-3-en-2-ol (23 mg, 0.23 mmol), Ph3P (59 mg, 0.23 mmol) and THF (0.08 mL). The reaction vessel was lowered into a sonication bath and sonicated for several minutes giving a clear and highly viscous solution. While sonication, DEAD (0.044 mL, 0.23 mmol) was added. After 1 h, the reaction mixture was concentrated in vacuo and the crude product was purified by flash chromatography on silica gel (hexane:EtOAc 7/3) to give the product in 17% yield (12 mg).
Reaction SMILES: [OH:1][CH2:2][C@H:3]([C:5]1([OH:10])[CH2:9][CH2:8][CH2:7][CH2:6]1)[CH3:4].N1C=CC=CC=1.[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>ClCCl.S([O-])([O-])(=O)=O.[Cu+2]>[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23]([O:1][CH2:2][C@H:3]([C:5]2([OH:10])[CH2:9][CH2:8][CH2:7][CH2:6]2)[CH3:4])(=[O:25])=[O:24])=[CH:19][CH:18]=1
Reactant: C[C@H](CO)C1(O)CCCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@@H](C)C2(O)CCCC2)cc1
Reaction time: 48 h
Yield: 169.5 %

Procedure:
A mixture of 3a (1.79 g, 12.4 mmol) , pyridine (5 mL), and p-toluenesulfonyl chloride (4.26 g, 22.3 mmol) in dichloromethane (40 mL) was stirred below 10° C. for 2 days. The reaction mixture was poured into copper (II) sulfate solution and extracted with diethyl ether. The combined organic layers were washed with copper (II) sulfate solution, water, sodium bicarbonate solution and brine, and dried over sodium sulfate. Filtration and concentration gave 6.27 g of an oily material, which was purified by column chromatography (silica gel 60 g, ethyl acetate in n-hexane, 5-33%) to give 3.74 g (quantitative) of 4a as a colorless oil.
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.[CH2:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1.CCCCCC>[CH2:12]([O: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)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C1CCc2cc(O)ccc21
Reactant: OCc1ccccc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=C1CCc2cc(OCc3ccccc3)ccc21
Reaction time: 24 h
Yield: 77.5 %

Procedure:
A solution of 5-hydroxyindan-1-one (1.00 q, 6.17 mmol), benzyl alcohol (800 mg, 7.40 mmol) and tributylphosphine (1.70 g, 8.40 mmol) in tetrahydrofuran (80 mL) was stirred at room temperature, 1,1′-(azodicarbonyl)dipiperidine (2.12 g, 8.40 mmol) was added, and the mixture was stirred for 24 hr. Hexane was added to the reaction mixture, the precipitated insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-40% ethyl acetate/hexane) to give the title compound (1.14 g, yield 78%) as pale-yellow crystals.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:26][C:27]1[CH:31]=[CH:30][S:29][CH:28]=1>C(C(C)=O)C>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:26][C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]
Reactant: ClCc1ccsc1
Reactant: COC(=O)CCC(=O)c1ccc(O)cc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: COC(=O)CCC(=O)c1ccc(OCc2ccsc2)cc1O
Yield: 74.1 %

Procedure:
A stirred solution of 4-(2,4-dihydroxyphenyl)-4-oxobutyric acid, methyl ester 6.76 g) in methyl ethyl ketone (150 mL) is treated with potassium carbonate (4.17 g), potassium iodide (5 g) tetrabutyl ammonium chloride (1 g) and 3-chloromethylthiophene (4 g), and refluxed for 24 hours. The reaction mixture is filtered, the filtrate is evaporated. The residue is dissolved in ethyl acetate, washed with water, dried, and evaporated. The residue is recrystallised from ethyl acetate/cyclohexane to give 4-(2-hydroxy-4-(thiophen-3-ylmethoxy)phenyl]-4-oxo-butyric acid, methyl ester (7.16 g), a pale cream solid, mp. 100-102° C.
Reaction SMILES: [H-].[Na+].CN(C=O)C.[OH:8][C:9]1[C:10]([CH3:15])=[N:11][CH:12]=[CH:13][CH:14]=1.[Cl:16][C:17]1[CH:22]=[C:21]([N+]([O-])=O)[CH:20]=[CH:19][N:18]=1>O>[Cl:16][C:17]1[CH:22]=[C:21]([O:8][C:9]2[C:10]([CH3:15])=[N:11][CH:12]=[CH:13][CH:14]=2)[CH:20]=[CH:19][N:18]=1
Reactant: Cc1ncccc1O
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ncccc1Oc1ccnc(Cl)c1
Reaction time: 1 h
Yield: 90 %

Procedure:
Sodium hydride (1.07 g, 42.3 mmol) was added to DMF (25 mL). 3-Hydroxy-2-methylpyridine (4.40 g, 40.3 mmol) was slowly added to the mixture and the reaction was stirred for 1 hour. 2-Chloro-4-nitropyridine (6.71 g, 42.3 mmol) was added and the reaction was stirred overnight at ambient temperature. Water was added and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to give the title compound (8.0 g, 90% yield) as a yellow oil, which solidified upon standing at ambient temperature.