Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]([OH:15])=[O:14])=[CH:4]1.[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1.O>CS(C)=O>[F:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][O:14][C:13](=[O:15])[CH2:12][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[N:3]([CH2:21][C:20]3[CH:23]=[CH:24][C:17]([F:16])=[CH:18][CH:19]=3)[CH:4]=2)=[CH:19][CH:18]=1
Reactant: O=C(O)Cc1c[nH]c2ccccc12
Reactant: Fc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=C(Cc1cn(Cc2ccc(F)cc2)c2ccccc12)OCc1ccc(F)cc1

Procedure:
100 ml dimethylsulfoxide (DMSO) are added to a three-necked flask under an N2 atmosphere, 2.1 g sodium hydride (mineral oil suspension) are added with vigorous stirring and treated dropwise with a solution of 5 g (17.8 mmol) indole-3-acetic acid in 50 ml DMSO. 2.58 g (35.6 mMol) 4-fluorobenzyl chloride are added with further stirring. After 12 hours at 25° C. the reaction mixture is added to 300 ml water and extracted with ether. The organic phase is dried and the solvent is removed under reduced pressure. The residue is purified by column chromatography on silica gel.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH3:11][C@@H:12]1[CH2:17][NH:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:11][C@@H:12]1[CH2:17][N:16]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19]
Reactant: C[C@@H]1CNCCN1C(=O)OC(C)(C)C
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: C[C@@H]1CN(c2ccc([N+](=O)[O-])nc2)CCN1C(=O)OC(C)(C)C
Temperature: 65 °C
Yield: 49.4 %

Procedure:
A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with methylsulfinylmethane (50 mL), 5-bromo-2-nitropyridine (2.2 g, 11 mmol), (R)-tert-butyl 2-methylpiperazine-1-carboxylate (2.2 g, 11 mmol), and potassium carbonate (3.08 g, 22 mmol). See FIG. 8. The system was subjected to three cycles of vacuum/nitrogen flush and heated at 65° C. for 15 h. It was then cooled to room temperature, and partitioned between ethyl acetate (100 mL) and water (20 mL). The aqueous layer was separated and extracted with ethyl acetate (50 mL×2). The combined organic layer was washed with brine (50 mL) and dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column chromatography eluting with 2:1 (UV) petroleum/ethyl acetate to afford 108a as a yellow solid (1.75 g, 50%). LCMS: [M+H]+ 323
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH:23]=O)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.Cl.[NH2:27][CH2:28][C:29]([NH2:31])=[O:30]>>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][C:14]=2[CH2:23][NH:27][CH2:28][C:29](=[O:30])[NH2:31])[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1
Reactant: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2C=O)c1
Reactant: NCC(N)=O
Agent: Cl
Product: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CNCC(N)=O)c1

Procedure:
Prepared according to the procedure described in Example 4, Step 1, using the following starting materials: (2′-formyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester and glycinamide hydrochloride.
Reaction SMILES: [CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[N:29]=[CH:28][C:27]([CH:30]=O)=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(O)(=O)C>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:25]=[CH:26][C:27]([CH2:30][N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:28][N:29]=3)[CH2:20][CH2:19]2)=[N:10][N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1COCCN1
Reactant: O=Cc1ccc(N2CCN(c3nnc(Cc4ccccc4)c4ccccc34)CC2)nc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: c1ccc(Cc2nnc(N3CCN(c4ccc(CN5CCOCC5)cn4)CC3)c3ccccc23)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.7 %

Procedure:
To a solution of 6-[4-(4-benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridine-3-carbaldehyde (40 mg, 0.1 mmol) in 5 mL DCM is added a drop of acetic acid, NaBH(OAc)3 (41.4 mg, 0.2 mmol) and morpholine (7.5 mL, 0.12 mmol). The reaction mixture is stirred for 30 min at rt. Aqueous NaHCO3 solution is added and the reaction mixture is stirred for an additional 30 min. The layers are separated and the aqueous layer is extracted with DCM. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography on silica gel (EtOAc/heptane 10%-70%) to yield the title compound (37.8 mg, 80%).
Reaction SMILES: [C:1]1([C@@H:7]2[CH2:10][C@H:9]([NH2:11])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+](N1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[N:17]=[CH:16]1)([O-])=O>>[N+:20]([C:18]1[N:17]=[CH:16][N:11]([C@H:9]2[CH2:8][C@@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:10]2)[CH:19]=1)([O-:22])=[O:21]
Reactant: O=[N+]([O-])c1cn([N+](=O)[O-])cn1
Reactant: N[C@H]1C[C@@H](c2ccccc2)C1
Product: O=[N+]([O-])c1cn([C@H]2C[C@@H](c3ccccc3)C2)cn1
Yield: 46 %

Procedure:
This reaction was carried out using the procedure for Preparation 1 with cis-3-phenylcyclobutylamine (J. Med. Pharm. Chem. 1960, 2, 687–691; ACIEE 1981, 20, 879–880) and 1,4-dinitroimidazole to afford 46 mg (46% yield) of 4-nitro-1-(cis-3-phenyl-cyclobutyl)-1H-imidazole; 1H NMR (300 MHz, CDCl3) δ 7.9 (s, 1H), 7.55 (s, 1H), 7.4–7.2 (m, 5H), 4.73 (m, 1H), 3.48 (m, 1H), 3.12 (m, 2H), 2.54 (m, 2H); MS (AP/CI): 244 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[C:10]([C:16]([O:18][CH3:19])=[O:17])#[C:11][C:12]([O:14][CH3:15])=[O:13]>CO>[O:8]=[C:5]1[NH:4][C:3](=[O:9])[C:2]([NH:1]/[C:11](=[CH:10]/[C:16]([O:18][CH3:19])=[O:17])/[C:12]([O:14][CH3:15])=[O:13])=[CH:7][NH:6]1
Reactant: COC(=O)C#CC(=O)OC
Reactant: Nc1c[nH]c(=O)[nH]c1=O
Solvent: CO
Product: COC(=O)/C=C(/Nc1c[nH]c(=O)[nH]c1=O)C(=O)OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 73.9 %

Procedure:
To a suspension of 5-aminouracil (275 g, 2.16 mol) in dry methanol (5.5 L) was added dropwise dimethyl acetylene dicarboxylate (344 g, 2.42 mol) at room temperature. After the end of the addition, the mixture was stirred at room temperature for 24 hours. The precipitate was filtered off, washed with MeOH (500 mL) and dried under vacuum to afford the title compound (430 g, 74%) as a yellow solid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:13]2[CH:17]=[C:16]([CH3:18])[NH:15][N:14]=2)[N:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[C:4]([NH:12][C:13]3[CH:17]=[C:16]([CH3:18])[NH:15][N:14]=3)[N:3]=2)=[CH:22][CH:21]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: Cc1cc(Nc2cc3ccccc3c(Cl)n2)n[nH]1
Product: Cc1cc(Nc2cc3ccccc3c(-c3ccc(F)cc3)n2)n[nH]1

Procedure:
Similar procedure as described in example 131 was used, starting from (1-chloro-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine and 4-fluoro-phenylboronic acid to give [1-(4-fluoro-phenyl)-isoquinolin-3-yl]-(5-methyl-1H-pyrazol-3-yl)-amine. LC-MS m/e 319(MH+). 1H NMR(CDCl3): δ 2.26(s, 3H), δ 5.89(s, 1H), δ 7.25(m, 3H), δ 7.32(br, 1H), δ 7.55(m, 1H), δ 7.65(s,1H), δ 7.70(m, 4H), δ 7.87(d,1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:12]C(=O)[N:10]([CH:14]([CH3:24])[CH2:15][C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([OH:23])[CH:17]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Br[C:26](Br)([C:30](=[O:32])[CH3:31])[C:27](=[O:29])[CH3:28].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:12])[CH2:9][NH:10][CH:14]([CH3:24])[CH2:15][C:16]2[CH:21]=[CH:20][C:19]3[O:22][C:26]([C:30](=[O:32])[CH3:31])([C:27](=[O:29])[CH3:28])[O:23][C:18]=3[CH:17]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(Cc1ccc(O)c(O)c1)N1CC(c2cccc(Cl)c2)OC1=O
Reactant: CC(=O)C(Br)(Br)C(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(=O)C1(C(C)=O)Oc2ccc(CC(C)NCC(O)c3cccc(Cl)c3)cc2O1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
One equivalent of 5-(3-chlorophenyl)-3-(2-(3,4-dihydroxyphenyl)-1-methylethyl)-2-oxazolidinone, prepared by the procedure of U.S. Pat. No. 5,061,727, Example 1, is combined with 1.1 equivalents of 3,3-dibromo-2,4-pentanedione and 2.2 equivalents of powdered potassium carbonate in acetonitrile. The reaction mixture is stirred at room temperature for 48 hours, evaporated in vacuo and partitioned between methylene chloride and water. The organic layer is dried, filtered and evaporated in vacuo to give 5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)amino)propyl)-2,2-diacetyl-1,3-benzodioxole.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1S(C)(=O)=O.[Cl:15][C:16]1[CH:17]=[C:18]2[N:24]([CH2:25][CH3:26])[C:23](=[O:27])[N:22]([C:28]3[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=3)[C:19]2=[N:20][CH:21]=1.[H-].[Na+]>CN(C=O)C.CO>[Cl:15][C:16]1[CH:17]=[C:18]2[N:24]([CH2:25][CH3:26])[C:23](=[O:27])[N:22]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:3]4[N:2]([CH3:1])[C:6]5=[N:7][CH:8]=[CH:9][CH:10]=[C:5]5[N:4]=4)=[CH:30][CH:29]=3)[C:19]2=[N:20][CH:21]=1
Reactant: CCn1c(=O)n(-c2ccc(O)cc2)c2ncc(Cl)cc21
Reactant: Cn1c(S(C)(=O)=O)nc2cccnc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: CCn1c(=O)n(-c2ccc(Oc3nc4cccnc4n3C)cc2)c2ncc(Cl)cc21
Temperature: 180 °C
Yield: 22.3 %

Procedure:
3-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (90 mg) was added to a solution of 6-chloro-1-ethyl-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (127 mg) and NaH (18.74 mg) in DMF (2 mL) at room temperature. The mixture was heated at 180° C. for 30 min under microwave irradiation. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane) to give 6-chloro-1-ethyl-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (40 mg) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:27])[CH2:18][O:19]CC2C=CC=CC=2)=[CH:12][CH:11]=1>CO.[Pd]>[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][OH:19])=[CH:14][CH:15]=1
Reactant: COC(=O)CCCCCOc1ccc(NC(=O)COCc2ccccc2)cc1
Agent: [Pd]
Solvent: CO
Product: COC(=O)CCCCCOc1ccc(NC(=O)CO)cc1
Reaction time: 5 h
Yield: 65.1 %

Procedure:
6-[4-(2-Benzyloxyacetylamino)-phenoxy]-hexanoic acid methyl ester 53 (1 grams, 2.6 mmol) was dissolved in methanol (10 ml) in a pressure vessel. Palladium on carbon (5%, 250 mg) was added and the mixture stirred under a hydrogen atmosphere (2 kg) for 5 hrs. Catalyst was removed by filtration and methanol distilled off. Crude 54 was recrystallised in chloroform:hexane (1:6) to get pure 54 (0.5 g, 65.3%) as a white powder with an m.p. between 91.5-94° C. IH NMR (CDCl3) δ 1.45 (m, 2H, CH2), 1.62 (m, 4H, CH2x2), 2.36 (t, 2H, CH2), 3.02 (t, 2H, CH2), 3.02 (t, 1H, OH), 3.68 (s, 3H, Ester), 3.92 (t, 2H, CH2), 4.22 (d, 2H, CH2), 6.84 (d, 2H, Ar), 7.46 (d, 2H, Ar), 8.24 (bs, 1H, NH).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]3[C:16]([C:17]([C:27]#[N:28])=[C:18]4[S:22][C:21]5[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=5[C:19]=24)=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:5]=[C:6]([Br:9])[C:7]=1[OH:8].O[C@H:30]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:31]([O:33]C)=[O:32].BrBr>>[Br:9][C:6]1[CH:5]=[C:4]([C:10]2[C:19]3[C:20]4[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=4[S:22][C:18]=3[C:17]([C:27]#[N:28])=[C:16]3[C:11]=2[CH:12]=[CH:13][CH:14]=[CH:15]3)[CH:3]=[C:2]([Br:1])[C:7]=1[O:8][C@@H:30]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:31]([OH:33])=[O:32]
Reactant: N#Cc1c2ccccc2c(-c2cc(Br)c(O)c(Br)c2)c2c1sc1ccccc12
Reactant: COC(=O)[C@H](O)Cc1ccccc1
Agent: BrBr
Product: N#Cc1c2ccccc2c(-c2cc(Br)c(O[C@@H](Cc3ccccc3)C(=O)O)c(Br)c2)c2c1sc1ccccc12

Procedure:
Prepared from 11-(3, 5-dibromo-4-hydroxy-phenyl)-benzo[b]naphtho[2,3-d ]thiophene-6-carbonitrile (Example 58) and (R)-2-hydroxy-3-phenylpropionic acid, methyl ester (Example 97). White solid: mp 176-178° C.: NMR (CDCl3); δ8.36 (ddd, J =8,1,1 Hz, 1 H), 7.85 (d, J=8 Hz, 1 H), 7.77 (ddd, J=8, 8, 2 Hz, 1 H), 7.58 (d, J=2 Hz, 1 H), 7.61-7.54 (m, 2 H), 7.56 (d, J=2 Hz, 1 H), 7.47 (ddd, J=8, 8, 1 Hz, 1 H), 7.41 (ddd, J=8, 1, 1, 2 H ), 7.36-7.26 (m, 3 H), 7.20 (ddd, J=8, 8, 1, 1 H), 6.75 (ddd, J =8, 1, 1 Hz, 1 H), 5.46 (t, J=7 Hz, 1 H), 3.59 (d, J=7 Hz, 2 H); MS (-FAB): [M-H]-, 2 bromine isotope pattern, 654 (2%), 656 (4%) 658 (2%); Anal. Calc. for C32H19Br2NO3S: C, 58.47, H, 2.91, N, 2.13 Found: C, 58.23, H, 2.69, N, 2.03.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][CH2:5][CH2:6][N:7]1[C:15]2[C:14]([NH:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][N:18]=3)=[N:13][C:12](Cl)=[N:11][C:10]=2[C:9]([CH2:24][NH:25][CH2:26][C:27]([F:30])([F:29])[F:28])=[N:8]1.[NH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>CS(C)=O>[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42].[F:1][C:2]([F:32])([F:31])[CH2:3][O:4][CH2:5][CH2:6][N:7]1[C:15]2[C:14]([NH:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][N:18]=3)=[N:13][C:12]([N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[N:11][C:10]=2[C:9]([CH2:24][NH:25][CH2:26][C:27]([F:30])([F:29])[F:28])=[N:8]1
Reactant: C1CNCCN1
Reactant: FC(F)(F)CNCc1nn(CCOCC(F)(F)F)c2c(Nc3ccncn3)nc(Cl)nc12
Solvent: CS(C)=O
Solvent: O=C(O)C(F)(F)F
Product: FC(F)(F)CNCc1nn(CCOCC(F)(F)F)c2c(Nc3ccncn3)nc(N3CCNCC3)nc12
Temperature: 120 °C

Procedure:
1-(2-(2,2,2-trifluoroethoxy)ethyl)-3-((2,2,2-trifluoroethylamino)methyl)-5-chloro-N-(pyrimidin-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine (213 mg, 0.41 mmol) prepared in Step 1 and piperazine (152 mg, 1.8 mmol) were mixed in dimethyl sulfoxide (3.0 ml) in a reaction vial. The reaction mixture was heated at 120° C. for 10 hours. The reaction was cooled to room temperature and brought to acidic condition by adding trifluoroacetic acid. The crude reaction mixture was purified by reverse phase HPLC (5-95% acetonitrile in water with 0.05% trifluoroacetic acid) and lyophilized to give the title compound as a dark yellow solid (70 mg).
Reaction SMILES: [C:1]([C:3]1[N:7]2[CH:8]=[C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[CH:10]=[C:11]([C:12]([F:15])([F:14])[F:13])[C:6]2=[N:5][CH:4]=1)#[CH:2].Br[C:27]1[CH:32]=[CH:31][C:30]([S:33]([NH2:36])(=[O:35])=[O:34])=[CH:29][CH:28]=1>>[F:15][C:12]([F:14])([F:13])[C:11]1[C:6]2[N:7]([C:3]([C:1]#[C:2][C:27]3[CH:32]=[CH:31][C:30]([S:33]([NH2:36])(=[O:35])=[O:34])=[CH:29][CH:28]=3)=[CH:4][N:5]=2)[CH:8]=[C:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH:10]=1
Reactant: NS(=O)(=O)c1ccc(Br)cc1
Reactant: C#Cc1cnc2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)cn12
Product: NS(=O)(=O)c1ccc(C#Cc2cnc3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)cn23)cc1

Procedure:
The title compound was prepared from 3-ethynyl-8-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine (example C.18) (354 mg, 1.0 mmol) and 4-bromobenzenesulfonamide (230 mg, 1.0 mmol) according to general procedure II. Obtained as an off-white (120 mg, 23%). MS (ISP) 511.3 [(M+H)+]; mp 278-280° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:9]=O)[CH:6]=[CH:5][C:4]=1[OH:11].[C:12]([O:15]C(=O)C)(=[O:14])[CH3:13]>>[C:12]([OH:15])(=[O:14])/[CH:13]=[CH:9]/[C:7]1[CH:6]=[CH:5][C:4]([OH:11])=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1cc(C=O)ccc1O
Product: COc1cc(/C=C/C(=O)O)ccc1O

Procedure:
Vaniline is reacted according to Perkin's reaction with acetic anhydride to form ferulic acid which is then decarbonized by heating to prepare 3-methoxy-4-hydroxystyrene. This compound is then acetylated with acetic anhydride, polymerized and then hydrolyzed to obtain 3-methoxy-4-hydroxystyrene polymer. ##STR4## wherein n stands for a positive number corresponding to the number of monomeric units in the polymer.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH:4]1[O:21][C:8]2([CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH2:7][N:6]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:5]1.[ClH:28]>ClCCl>[ClH:28].[CH3:1][O:2][CH2:3][CH:4]1[CH2:5][N:6]([C:22]2[N:23]=[CH:24][CH:25]=[CH:26][N:27]=2)[CH2:7][C:8]2([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[O:21]1
Reactant: COCC1CN(c2ncccn2)CC2(CCN(C(=O)OC(C)(C)C)CC2)O1
Agent: Cl
Solvent: ClCCl
Product: COCC1CN(c2ncccn2)CC2(CCNCC2)O1
Reaction time: 2 h

Procedure:
Tert-butyl 10-(methoxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.18 g, 3.12 mmol) was dissolved in dichloromethane (2 mL) and treated with a solution of HCl (1.6 mL of 4 M in dioxane, 6.2 mmol). The mixture was allowed to stir for 2 h. The reaction mixture was evaporated to dryness to provide 2-(methoxymethyl)-4-(pyrimidin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride. ESI-MS m/z calc. 278.2. found 279.2 M+1)+; Retention time: 0.68 min (3 min run). 1H NMR (400 MHz, MeOD) δ 8.59 (d, J=5.2 Hz, 2H), 6.99 (t, J=5.2 Hz, 1H), 4.52 (ddd, J=44.3, 13.4, 1.7 Hz, 2H), 4.12-3.97 (m, 1H), 3.56 (ddd, J=26.1, 10.3, 4.9 Hz, 2H), 3.42 (s, 3H), 3.34 (dd, J=10.9, 5.0 Hz, 2H), 3.27-3.19 (m, 2H), 3.13 (dd, J=13.2, 11.1 Hz, 2H), 2.42 (d, J=15.2 Hz, 1H), 1.94 (dd, J=10.7, 4.3 Hz, 2H), 1.74 (ddd, J=15.3, 12.8, 4.4 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:11]=[CH:10][C:9](=[O:12])[NH:8][C:7]=2[N:13]=1.I[CH2:15][CH2:16][C@H:17]1[CH2:21][O:20][C:19]([CH3:23])([CH3:22])[O:18]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[CH3:22][C:19]1([CH3:23])[O:18][C@@H:17]([CH2:16][CH2:15][N:8]2[C:9](=[O:12])[CH:10]=[N:11][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[N:13][C:7]2=3)[CH2:21][O:20]1
Reactant: CC1(C)OC[C@H](CCI)O1
Reactant: COc1ccc2ncc(=O)[nH]c2n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2ncc(=O)n(CC[C@H]3COC(C)(C)O3)c2n1
Temperature: 50 °C
Reaction time: 11 h
Yield: 90.2 %

Procedure:
In N,N-dimethylformamide (400 ml) were dissolved 6-methoxypyrido[2,3-b]pyrazin-3(4H)-one (14.53 g, 82.00 mmol) and (4S)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (23.10 g, 90.20 mmol). Cesium carbonate (34.7 g, 1.06.6 mmol) was added to the solution and the mixture was stirred at 50° C. for 11 hours. After cooling in the air, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 22.58 g (90%) of the title compound in the form of a yellow orange oily product.
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].[N:8]1(C(OC(C)(C)C)=O)[CH2:13][CH2:12][CH:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1>CCO>[N:8]1([CH2:3][CH2:2][C:1]([O:5][CH2:6][CH3:7])=[O:4])[CH2:13][CH2:12][CH:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCC(C2CCNCC2)CC1
Reactant: C=CC(=O)OCC
Solvent: CCO
Product: CCOC(=O)CCN1CCC(C2CCNCC2)CC1
Reaction time: 8 h

Procedure:
4.4 mL (40.6 mmol) ethyl acrylate were added to a solution of 10.0 g (37.3 mmol) tert. butyl [4,4′]bipiperidinyl-1-carboxylate in 100 mL EtOH and the reaction mixture was refluxed for 2 h. To complete the reaction a further 1 mL (9.2 mmol) ethyl acrylate were added, the mixture was refluxed for 1 h and left overnight at RT. The solvent was eliminated i. vac. and the crude product was further reacted without any purification.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:7][C@@H:6]([OH:8])[C@H:5]([CH3:9])[O:4][C@H:3]1[O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].[N:25]([CH2:28][C@@H:29]([CH3:33])[C:30](O)=[O:31])=[N+:26]=[N-:27].CCN=C=NCCCN(C)C.Cl.C(O)(C)C>ClCCl.CN(C)C1C=CN=CC=1>[N:25]([CH2:28][C@@H:29]([CH3:33])[C:30]([O:8][C@H:6]1[C@H:5]([CH3:9])[O:4][C@@H:3]([O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@H:2]([OH:1])[CH2:7]1)=[O:31])=[N+:26]=[N-:27]
Reactant: C[C@H](CCC(=O)OCc1ccccc1)O[C@@H]1O[C@@H](C)[C@H](O)C[C@H]1O
Reactant: C[C@H](CN=[N+]=[N-])C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CC(C)O
Product: C[C@H](CCC(=O)OCc1ccccc1)O[C@@H]1O[C@@H](C)[C@H](OC(=O)[C@H](C)CN=[N+]=[N-])C[C@H]1O
Temperature: 25 °C
Reaction time: 12 h
Yield: 17 %

Procedure:
To prepare 8, a solution of 38 (22.6 mg, 66.8 μmol) and 3-azido-(2R)-methylpropanoic acid (Rej et al., J. Org. Chem. 61:6289-95 (1996), which is hereby incorporated by reference in its entirety) (37, 8.6 mg, 66.8 μmol) in 2 mL dichloromethane was treated with 4-dimethylaminopyridine (16.3 mg, 133.6 μmol) and EDC hydrochloride (25.7 mg, 133.6 μmol). After stirring at room temperature for 12 hours the reaction was quenched by addition of 5% aqueous acetic acid (100 μl), dried over Na2SO4, and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-10% isopropanol in dichloromethane afforded (R)-benzyl 4-(((2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate (8) (5.2 mg, 11.6 μmol, 17%) as a colorless oil. 1H NMR (400 MHz, chloroform-d): δ (ppm) 7.40-7.31 (m, 5H), 5.15 (d, J=13.6 Hz, 1H), 5.11 (d, J=13.6 Hz, 1H), 4.86 (ddd, J=10.9 Hz, 9.4 Hz, 4.6 Hz, 1H), 4.73-4.70 (m, 1H), 3.90-3.76 (m, 3H), 3.52 (dd, J=12.2 Hz, 7.5 Hz, 1H), 3.38 (dd, J=12.2 Hz, 5.6 Hz, 1H), 2.71-2.60 (m, 1H), 2.57-2.42 (m, 2H), 2.13-2.05 (m, 2H), 1.93-1.83 (m, 3H), 1.20 (d, J=7.0 Hz, 3H), 1.17 (d, J=6.3 Hz, 3H), 1.16 (d, J=6.2 Hz, 3H). See FIG. 105.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[N:3]=[CH:2]1.C(N(CC)CC)C.[C:18](Cl)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(Cl)(Cl)Cl>[C:18]([N:1]1[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[N:3]=[CH:2]1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)c1c[nH]cn1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A suspension of ethyl imidazole-4-carboxylate (1.4 g), triethylamine (1.2 g) and chloroform (20 ml) was stirred at room temperature while trityl chloride (3.06 g) was added, and the mixture was stirred at room temperature for 1 h. The resulting solution was washed with water, dried and evaporated to dryness under reduced pressure, and the residue was crystallised from a mixture of ethyl acetate and cyclohexane, to give ethyl 1-tritylimidazole-4-carboxylate, mp 163°-164°.