Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH3:6][C:7]1[CH:8]=[CH:9][C:10]2[O:14][CH:13]=[CH:12][C:11]=2[CH:15]=1.[CH3:16][Sn:17](Cl)([CH3:19])[CH3:18]>C1COCC1>[CH3:16][Sn:17]([CH3:19])([CH3:18])[C:13]1[O:14][C:10]2[CH:9]=[CH:8][C:7]([CH3:6])=[CH:15][C:11]=2[CH:12]=1
Reactant: Cc1ccc2occc2c1
Reactant: C[Sn](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1ccc2oc([Sn](C)(C)C)cc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 102.4 %

Procedure:
n-Butyl lithium (1.57M in hexane, 75 ml) was added dropwise to a stirred solution of 5-methylbenzofuran (14 g) in dry THF (150 ml) at -70° under nitrogen over 45 min. The solution was then allowed to warm to -55° before a solution of trimethyltin chloride (23 g) in THF (70 ml) was added dropwise. The solution temperature rose to -32°. The cooling bath was removed and the solution was stirred at room temperature for 2 h. The solution was diluted with ethyl acetate (250 ml) and washed with water (200 ml). The organic layer was dried and concentrated in vacuo to afford a yellow liquid (32 g). Kugelrohr distillation of this liquid gave the title compound (23.3 g) as a colourless liquid, b.p. 115° at 7 mbar.
Reaction SMILES: FC1C=C(O)C=CC=1C1N=C2NN=C(C)C2=C(CN2CCNCC2C2C=CC=CC=2)C=1.C([O:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:47]=[C:48]([C:62](O)=O)[C:49]3[C:54]([CH3:55])=[N:53][N:52](C4CCCCO4)[C:50]=3[N:51]=2)=[C:42]([F:65])[CH:41]=1)C1C=CC=CC=1.[CH3:66][C:67]1([CH3:75])[O:72][CH2:71][C:70]([CH3:74])([CH3:73])[NH:69][CH2:68]1>>[F:65][C:42]1[CH:41]=[C:40]([OH:39])[CH:45]=[CH:44][C:43]=1[C:46]1[N:51]=[C:50]2[NH:52][N:53]=[C:54]([CH3:55])[C:49]2=[C:48]([CH2:62][N:69]2[C:70]([CH3:74])([CH3:73])[CH2:71][O:72][C:67]([CH3:75])([CH3:66])[CH2:68]2)[CH:47]=1
Reactant: CC1(C)COC(C)(C)CN1
Reactant: Cc1nn(C2CCCCO2)c2nc(-c3ccc(OCc4ccccc4)cc3F)cc(C(=O)O)c12
Agent: Cc1n[nH]c2nc(-c3ccc(O)cc3F)cc(CN3CCNCC3c3ccccc3)c12
Product: Cc1n[nH]c2nc(-c3ccc(O)cc3F)cc(CN3CC(C)(C)OCC3(C)C)c12

Procedure:
The title compound was prepared in analogy to Example 1 steps (d) to (g) starting from 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid and 2,2,5,5-tetramethyl-morpholine, however, in the last step only the THP-protecting group on the pyrazole ring was removed.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12](=O)[CH3:13])=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2].[OH:15][CH:16]([C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([CH2:26][OH:27])[CH:20]=1)[CH2:17][NH2:18]>C(O)C.[Pd].C(OCC)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]([NH:18][CH2:17][CH:16]([OH:15])[C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([CH2:26][OH:27])[CH:20]=2)[CH3:13])=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2]
Reactant: COC(=O)c1ccc(CC(C)=O)cc1
Reactant: NCC(O)c1ccc(O)c(CO)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COC(=O)c1ccc(CC(C)NCC(O)c2ccc(O)c(CO)c2)cc1
Reaction time: 18 h
Yield: 43 %

Procedure:
A solution of 1-(4-carbomethoxyphenyl)propan-2-one (70 g) and 2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethanamine (66.7 g) in ethanol (1750 cm3) was stirred under reflux for 4 hours. The solution was cooled and added to a suspension of 10% palladium on charcoal, (Johnson Matthey type 87 L), (20 g) in ethanol (50 cm3) and the resulting mixture hydrogenated at 90 psi and 50°-55° for 18 hours. The mixture was filtered through a Claraid bed, the residue washed with ethanol (about 500 cm3) and the filtrate evaporated under reduced pressure to yield a viscous gum. The gum was dissolved in hot ethyl acetate (100 cm3) and decanted from a small amount of residual brown oil. On standing a white solid crystallised which was filtered off, washed with diethyl ether (about 100 cm3) and dried to give the title compound 56.3 g (43%), mp 139°-141°. (13C NMR indicated this to be a 7:3 mixture of diastereoisomers). On standing two further crops of the title compound crystallised from the filtrate giving a total yield of 84.7 g (64.7%).
Reaction SMILES: [C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:6]=[CH:5][C:4]([CH:7]([CH2:10][CH2:11][N:12]([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:8]#[N:9])=[CH:3][CH:2]=1.C1(C)C=CC=CC=1.[NH2-].[Na+].Cl[CH2:35][CH2:36][N:37]([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39]>O>[C:1]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:6]=[CH:5][C:4]([C:7]([CH2:35][CH2:36][N:37]([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])([CH2:10][CH2:11][N:12]([CH:13]([CH3:14])[CH3:15])[CH:16]([CH3:18])[CH3:17])[C:8]#[N:9])=[CH:3][CH:2]=1
Reactant: CC(C)N(CCC(C#N)c1ccc(-c2ccccc2)cc1)C(C)C
Reactant: CC(C)N(CCCl)C(C)C
Agent: [NH2-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)N(CCC(C#N)(CCN(C(C)C)C(C)C)c1ccc(-c2ccccc2)cc1)C(C)C
Temperature: 100 °C

Procedure:
To a solution of 16 parts of α-(4-biphenylyl)-α-[2-(diisopropylamino)ethyl]acetonitrile in 150 parts by volume of toluene is added 2.7 parts of sodium amide and the solution is heated over a period of 15 minutes at about 100° C. Then 13 parts of 2-chloro-N,N-diisopropylethylamine in 40 parts by volume of toluene is added slowly over a period of 20 minutes. This mixture is heated at 100°-105° C. for about 90 minutes and then cooled to room temperature when 150 parts by volume of water is added. The organic layer is separated, dried over calcium sulfate, filtered and the solvent evaporated to afford α-(4-biphenylyl)-α,α-bis[2-(diisopropylamino)ethyl]acetonitrile, as a low melting solid. This compound is identical with the compound of Example 2, Method A.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.O.[NH2:13][NH2:14]>N1C=CC=CC=1>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([NH:13][NH2:14])=[CH:3][CH:4]=1
Reactant: NN
Reactant: FC(F)(F)c1ccc(Cl)cc1
Solvent: c1ccncc1
Solvent: O
Product: NNc1ccc(C(F)(F)F)cc1
Temperature: 180 °C
Yield: 20 %

Procedure:
A mixture of 4-chlorobenzotrifluoride (1.08 g), hydrazine hydrate (1.8 g, 6 molar equivalents) and pyridine (5 ml) was heated in an autoclave (purged with argon) for 6 hours at 180° C. The mixture was cooled, the excess hydrazine decanted and the organic phase evaporated in vacuo. The residue was crystallised from petroleum ether to give the title compound in 20% yield. It was shown that 20% of the starting material had been consumed, thus indicating that the reaction had occurred with high selectivity.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:19]4[CH:27]=[C:26](Cl)[N:25]=[CH:24][C:20]=4[N:21]=[CH:22][N:23]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]1[O:35][C:36]([CH:39]2[O:43][CH2:42][CH2:41][O:40]2)=[CH:37][CH:38]=1)CCC>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:19]4[CH:27]=[C:26]([C:34]5[O:35][C:36]([CH:39]6[O:43][CH2:42][CH2:41][O:40]6)=[CH:37][CH:38]=5)[N:25]=[CH:24][C:20]=4[N:21]=[CH:22][N:23]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C2OCCO2)o1
Reactant: Clc1cc2c(Nc3ccc4c(cnn4Cc4ccccc4)c3)ncnc2cn1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: c1ccc(Cn2ncc3cc(Nc4ncnc5cnc(-c6ccc(C7OCCO7)o6)cc45)ccc32)cc1

Procedure:
(1-Benzyl-1H-indazol-5-yl)-(6-chloropyrido[3,4-d]pyrimidin-4-yl)-amine (4.28 g), 2-(tributylstannyl)-5-(1,3-dioxolan-2-yl)-furan (J. Chem Soc., Chem. Commun., (1988), p 560) (10 g) and 1,4-bis(diphenylphosphino)butane palladium (II) chloride (1 g) were heated at reflux in dioxane (150 ml) for 24 hr (Procedure B). The solvent was removed in vacuo and the residue chromatographed on silica. Subsequent trituration gave the title compound as a yellow solid; [2H6]-DMSO 10.46 (1H, s), 9.17 (1H, s), 8.74 (1H, s), 8.52 (1H, s), 8.23 (1H, s), 8.18 (1H, s), 7.80-7.68 (2H, m), 7.41-7.22 (5H, m), 7.17 (1H, d), 6.80 (1H, d), 6.06 (1H, s), 5.71 (2H, s), 4.20-3.96 (4H, m).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[C:15]([C:17]3[S:18][C:19]4[C:25]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[CH:24][CH:23]=[C:22]([O:32][CH3:33])[C:20]=4[N:21]=3)[NH:16][C:10]=2[CH2:9]1)=O)(C)(C)C.[ClH:34]>CO>[ClH:34].[CH3:33][O:32][C:22]1[C:20]2[N:21]=[C:17]([C:15]3[NH:14][C:11]4[CH2:12][CH2:13][NH:8][CH2:9][C:10]=4[N:16]=3)[S:18][C:19]=2[C:25]([N:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)=[CH:24][CH:23]=1
Reactant: COc1ccc(N2CCOCC2)c2sc(-c3nc4c([nH]3)CN(C(=O)OC(C)(C)C)CC4)nc12
Agent: Cl
Solvent: CO
Product: COc1ccc(N2CCOCC2)c2sc(-c3nc4c([nH]3)CCNC4)nc12
Temperature: 25 °C
Reaction time: 48 h
Yield: 81 %

Procedure:
0.08 g 2-(4-Methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-3,4,6,7-tetrahydro-imidazo[4,5-c]pyridine-5-carboxylic acid tert-butyl ester was dissolved in 13 ml of a 7.7 molar solution of hydrogen chloride in methanol. After stirring at room temperature for 2 days the solvent was distilled off, toluene was added and distilled off and the residue was suspended in ethanol and filtered to yield 0.056 g (81%) 2-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride as yellow solid; M.p.: 268–271° C.; MS (ISP): m/e=372 (M+H+).
Reaction SMILES: [C:1]1([CH:7]2[N:12]([C:13]([N:15]3[CH2:24][CH2:23][C:22]4[CH:21]=[N:20][C:19]([NH:25][CH:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[N:18][C:17]=4[CH2:16]3)=[O:14])[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:1]1([CH:7]2[CH2:8][NH:9][CH2:10][CH2:11][N:12]2[C:13]([N:15]2[CH2:24][CH2:23][C:22]3[CH:21]=[N:20][C:19]([NH:25][CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[N:18][C:17]=3[CH2:16]2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)N2CCc3cnc(NC4CCOCC4)nc3C2)C(c2ccccc2)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(N1CCc2cnc(NC3CCOCC3)nc2C1)N1CCNCC1c1ccccc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
tert-Butyl 3-phenyl-4-(2-(tetrahydro-2H-pyran-4-ylamino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carbonyl)piperazine-1-carboxylate (0.0446 g, 0.0853 mmol) was dissolved in 3:1 DCM/TFA at 0° C. and then stirred for 45 minutes at room temperature. The solution was concentrated, 0.1 mL of 7N NH3/MeOH was added and the solution was concentrated. DCM was added and the solids were removed by filtration. The mother liquor was concentrated to provide (2-phenylpiperazin-1-yl)(2-(tetrahydro-2H-pyran-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)methanone:MS m/z (APCI-pos) M+1=423.4.
Reaction SMILES: Br[C:2]1[N:3]([CH3:10])[C:4]([N+:7]([O-:9])=[O:8])=[CH:5][N:6]=1.Cl.[Cl:12][C:13]1[C:17]([Cl:18])=[C:16]([CH3:19])[NH:15][C:14]=1[C:20]([NH:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)=[O:21].CCOC(C)=O>CN1CCCC1=O>[Cl:12][C:13]1[C:17]([Cl:18])=[C:16]([CH3:19])[NH:15][C:14]=1[C:20]([NH:22][CH:23]1[CH2:28][CH2:27][N:26]([C:2]2[N:3]([CH3:10])[C:4]([N+:7]([O-:9])=[O:8])=[CH:5][N:6]=2)[CH2:25][CH2:24]1)=[O:21]
Reactant: Cc1[nH]c(C(=O)NC2CCNCC2)c(Cl)c1Cl
Reactant: Cn1c([N+](=O)[O-])cnc1Br
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Cc1[nH]c(C(=O)NC2CCN(c3ncc([N+](=O)[O-])n3C)CC2)c(Cl)c1Cl

Procedure:
TEA (0.26 ml, 1.86 mmol) was added to a mixture of 2-bromo-1-methyl-5-nitro-1H-imidazole (G. B. Barlin, J. Chem. Soc. B, 1967, 641; 126 mg, 0.61 mmol,) and 3,4-dichloro-5-methyl-N-piperidin-4-yl-1H-pyrrole-2-carboxamide hydrochloride (Intermediate 1), 191 mg, 0.61 mmol) in 1-methyl-2-pyrrolidinone (1.5 ml). Using a Smith Microwave Synthesizer, the mixture was subjected to single-mode microwave at 150° C. for 30 min. EtOAc was added and the solution was washed with water (2×). The organic phase was separated, dried over MgSO4, and concentrated under vacuum. The crude material was purified by chromatography on silica gel using 50% EtOAc/hexanes to give 158 mg of the title product.
Reaction SMILES: CON(C)[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[CH:13][CH:12]=[CH:11]2)=[O:5].[CH3:17][Mg]I.C(OCC)C>C1COCC1.C(=O)=O>[N:14]1[C:15]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[C:4](=[O:5])[CH3:17])[CH:11]=[CH:12][CH:13]=1
Reactant: CON(C)C(=O)c1cccc2cccnc12
Reactant: C[Mg]I
Agent: O=C=O
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(=O)c1cccc2cccnc12
Temperature: -78 °C
Reaction time: 8 h
Yield: 83 %

Procedure:
Quinoline-8-carboxylic acid methoxy-methyl-amide (2.16 g, 10 mmol) was dissolved in anhydrous THF (40 mL) and cooled to −78° C. The 3 M methyl magnesium iodide solution in diethyl ether (4.0 mL, 12 mmol, Aldrich) was slowly added to the reaction solution in dry ice bath. The reaction mixture was allowed to stir under nitrogen at room temperature for overnight then the reaction was cooled at ice bath and quenched with saturated aqueous ammonium chloride (40 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (30 mL×2). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated via vacuo to give crude title compound as light yellow solid in 83% yield (1.42 g, 8.3 mmol).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([CH2:20][C:21]([OH:23])=O)[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:12])=[O:11].[CH2:24]([NH:31][CH2:32][CH2:33][OH:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:24]([N:31]([CH2:32][CH2:33][OH:34])[C:21](=[O:23])[CH2:20][N:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:11])=[O:12])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: COc1ccccc1N(CC(=O)O)S(=O)(=O)c1ccccc1C
Reactant: OCCNCc1ccccc1
Product: COc1ccccc1N(CC(=O)N(CCO)Cc1ccccc1)S(=O)(=O)c1ccccc1C

Procedure:
prepared by reaction of [(2-methoxy-phenyl)-(toluene-2-sulfonyl)-amino]-acetic acid with 2-benzylamino-ethanol
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[SH:11].[Hg](C#N)C#N.[C:17]([O:20][C@@H:21]1[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:25]([O:31][C:32](=[O:34])[CH3:33])[CH2:24][S:23][C@@H:22]1Br)(=[O:19])[CH3:18]>>[C:17]([O:20][C@@H:21]1[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:25]([O:31][C:32](=[O:34])[CH3:33])[CH2:24][S:23][C@H:22]1[S:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)(=[O:19])[CH3:18]
Reactant: Sc1ccc2ccccc2c1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@@H](Br)SC[C@H]1OC(C)=O
Agent: N#C[Hg]C#N
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](Sc2ccc3ccccc3c2)SC[C@H]1OC(C)=O
Yield: 39.8 %

Procedure:
If the procedure described in Preparation I is followed starting from 6.8 g (42.4.10-3 mol) of naphthalene-2-thiol, 10.8 g (42.4.10-3 mol) of mercuric cyanide, Hg(CN)2, and 12 g (33.2.10-3 mol) of 2,3,4-tri-O-acetyl-5-thio-α-D-xylopyranosyl bromide, 5.84 g (yield: 40%) of the expected product are obtained.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C([O:19][C:20]1[C:21](=[O:36])[O:22][CH:23]([CH2:33][CH2:34]O)[C:24]=1[O:25]CC1C=CC=CC=1)C1C=CC=CC=1>>[OH:19][C:20]1[C:21](=[O:36])[O:22][CH:23]([CH2:33][CH2:34][O:1][C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[C:24]=1[OH:25]
Reactant: O=C1OC(CCO)C(OCc2ccccc2)=C1OCc1ccccc1
Reactant: Oc1ccc2ccccc2n1
Product: O=C1OC(CCOc2ccc3ccccc3n2)C(O)=C1O
Yield: 17.4 %

Procedure:
Mitsunoble coupling of 0.17 g (1.2 mmol) of 2-hydroxyquinoline with 0.34 g (1.0 mmol) of 3,4-dibenzyloxy-5-(2-hydroxyethyl)-2(5H)-furanone and subsequent benzyl group deprotection by hydrogenation were performed in a similar manner as described in the synthesis of 3,4-dihydroxy-5-[2-(4-phenoxy)phenoxyethyl]-2(5H)-furanone to provide 50 mg (17% yield) of 3,4-dihydroxy-5-[2-(quinoline-2-oxy)ethyl]-2(5H)-furanone as a fluffy white solid after recrystallization from ether and hexanes: 1H NMR (acetone-d6) δ 8.25-8.17 (m, 1H); 7.88-7.38 (m, 4H), 7.01-6.93 (m, 1H); 4.97 (dd, J=4.9, 8.7 Hz, 1H), 4.81-4.55 (m, 2H); 2.62-2.45 (m, 1H), 2.20-1.95 (m, 1H). Anal Calcd for C15H13NO5 +0.5 H2O: C, 60.81; H, 5.10; N, 4.72. Found: C, 61.04; H, 5.04; N, 4.32.
Reaction SMILES: [I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[NH2:9][C:10]1[C:11]2[N:12]([C:16]([CH3:20])=[C:17]([CH3:19])[N:18]=2)[CH:13]=[CH:14][CH:15]=1.[C:21]([O:25][C:26]([NH:28][C:29]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:30]=1[CH2:31]Cl)=[O:27])([CH3:24])([CH3:23])[CH3:22]>CC(C)=O>[C:21]([O:25][C:26]([NH:28][C:29]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:30]=1[CH2:31][NH:9][C:10]1[C:11]2[N:12]([C:16]([CH3:20])=[C:17]([CH3:19])[N:18]=2)[CH:13]=[CH:14][CH:15]=1)=[O:27])([CH3:24])([CH3:23])[CH3:22]
Reactant: Cc1nc2c(N)cccn2c1C
Reactant: Cc1cccc(NC(=O)OC(C)(C)C)c1CCl
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: Cc1cccc(NC(=O)OC(C)(C)C)c1CNc1cccn2c(C)c(C)nc12
Temperature: 25 °C

Procedure:
5.5 g of sodium iodide and 8.0 g of sodium carbonate are added at RT to a solution of 8-amino-2,3-dimethylimidazo[1,2-a]pyridine (4.8 g) and 2-tert-butoxycarbonylamino-6-methylbenzyl chloride (9.2 g) in acetone (250 ml) and the mixture is then heated to boiling under reflux for 6 h. After cooling the solution to RT and concentrating it, the residue is dissolved in a mixture of 200 ml of ethyl acetate and 200 ml of water and the organic phase is separated off. After three further extractions with 100 ml each of ethyl acetate, the combined organic phases are dried over magnesium sulfate and then concentrated. The title compound crystallizes as a slightly yellow solid. After chromatographic purification on silica gel (eluent: toluene/dioxane=20:1) and recrystallization from diisopropyl ether, 7.1 g (62%) of the title compound of m.p. 149-152° C. are obtained.
Reaction SMILES: [Cl:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].O.[NH2:15][C:16]1[NH:20][N:19]=[N:18][N:17]=1>O1CCCC1.O>[Cl:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:15][C:16]1[NH:20][N:19]=[N:18][N:17]=1)=[O:5]
Reactant: Nc1nnn[nH]1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1Cl
Solvent: C1CCOC1
Solvent: O
Product: O=C(Nc1nnn[nH]1)c1cccc([N+](=O)[O-])c1Cl
Reaction time: 1 h

Procedure:
Similarly, a solution of 109 g of 2-chloro-3-nitrobenzoyl chloride in 100 ml of tetrahydrofuran was reacted with a mixture of 103 g of 5-aminotetrazole monohydrate in 1200 ml of hot tetrahydrofuran and 50 ml of water. A voluminous precipitate appeared and, after 1 hour, the mixture was diluted with 2 liters of water and the resulting white solid was collected and oven-dried to give 2-chloro-3-nitro-N-(1H-tetrazol-5-yl)-benzamide melting at about 279° C. with decomposition. In this case, the indicated acid chloride was obtained by the reaction of 2-chloro-3-nitrobenzoic acid with phosphorus pentachloride in cyclohexane. The acid chloride melts at about 57°-59° C.
Reaction SMILES: CO.C[O:4][C:5]([C:7]1[C:8]([C:17]2[C:18]([C:27](OC)=[O:28])=[CH:19][C:20]([O:25][CH3:26])=[CH:21][C:22]=2[O:23][CH3:24])=[C:9]([O:15][CH3:16])[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:4][CH2:5][C:7]1[C:8]([C:17]2[C:22]([O:23][CH3:24])=[CH:21][C:20]([O:25][CH3:26])=[CH:19][C:18]=2[CH2:27][OH:28])=[C:9]([O:15][CH3:16])[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1
Reactant: COC(=O)c1cc(OC)cc(OC)c1-c1c(OC)cc(OC)cc1C(=O)OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(CO)c(-c2c(CO)cc(OC)cc2OC)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.4 %

Procedure:
(6′-Hydroxymethyl-4,6,2′,4% tetramethoxy-biphenyl-2-yl)-methanol: 4,6,4′,6′-tetramethoxy-biphenyl-2,2′-dicarboxylic acid dimethyl ester (2.5 g) was dissolved in THF (96 mL), and 1M LiAlH4 in THF (9.6 mL) was added. After stirring at room temperature for overnight, the mixture was quenched with water and 2N HCl (24 mL) was added. The mixture was evaporated under vacuum and partitioned with DCM (300 mL) and water (200 mL). The organic layer was dried over Na2SO4 and crystallized with DCM to provide (6′-hydroxymethyl-4,6,2′,4′-tetramethoxy-biphenyl-2-yl)-methanol (1.7 g, 77%) as a pale blue white triclinic crystals.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[OH:13])[C:7]([OH:9])=[O:8])[CH3:2].Cl.[CH3:15]O>>[CH3:15][O:8][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:12]([OH:13])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1
Reactant: CO
Reactant: CCOc1cc(C(=O)O)ccc1O
Agent: Cl
Product: CCOc1cc(C(=O)OC)ccc1O
Yield: 91 %

Procedure:
A solution of 3-ethoxy-4-hydroxy-benzoic acid (5.5 g, 30.19 mmol, 1.0 equiv) in methanol (300 mL) was saturated with anhydrous HCl gas and heated to reflux overnight. Evaporation of the solvent and purification of the crude reaction product over a short plug of silica eluting with dichloromethane yielded 5.4 g (91%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.37 (t, J=7.0 Hz, 3H), 3.80 (s, 3H), 4.08 (q, J=7.0 Hz, 2H), 6.11 (s, 1H), 6.86 (d, J=8.3 Hz, 1H), 7.45 (d, J=1.9 Hz, 1H), 7.54 (dd, J=8.3 Hz, J=1.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 14.69, 51.85, 64.74, 112.67, 114.05, 122.21, 124.05, 145.46, 150.20, 166.88. MS (ISN): 195.0 [M−H]−.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][CH2:11][N:12]2[C:16](=[O:17])[CH2:15][CH2:14][C:13]2=[O:18])[CH:5]=[CH:4][N+:3]=1[O-].C(O)C.[C:23]([O:26]C(=O)C)(=[O:25])[CH3:24]>>[C:23]([O:26][CH2:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][CH2:11][N:12]2[C:16](=[O:17])[CH2:15][CH2:14][C:13]2=[O:18])[CH:5]=[CH:4][N:3]=1)(=[O:25])[CH3:24]
Reactant: Cc1c(OCCN2C(=O)CCC2=O)cc[n+]([O-])c1C
Reactant: CC(=O)OC(C)=O
Solvent: CCO
Product: CC(=O)OCc1nccc(OCCN2C(=O)CCC2=O)c1C
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
0.12 g of 2,3-dimethyl-4-(2-succinimidoethoxy)pyridine N-oxide was dissolved in 5 ml of acetic anhydride to obtain a solution. This solution was stirred at 100° C. for 0.5 hour and cooled, followed by the addition of 30 ml of ethanol. The obtained mixture was stirred at a room temperature for 0.5 hour and distilled to remove the solvent. Thus, 0.14 g of crude 2-acetoxymethyl-3-methyl-4-(2-succinimidoethoxy)pyridine was obtained as an oil.
Reaction SMILES: [Br:1][CH2:2]/[CH:3]=[CH:4]/[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1.[N+](=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N-]>ClCCl.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.[Rh].[Rh]>[Br:1][CH2:2][CH:3]1[CH:4]([C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=2)[CH:16]1[C:17]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: O=[N+]([O-])c1cccc(/C=C/CBr)c1
Agent: [Rh]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CCOC(=O)C1C(CBr)C1c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 66 h
Yield: 6.1 %

Procedure:
To a solution of 1-[(E)-3-bromo-1-propenyl]-3-nitrobenzene (Preparation 22, 820 mg, 3.23 mmol) in dichloromethane (3 ml) was added rhodium (II) acetate dimer (20 mg, 0.046 vmnol). To the mixture was added dropwise at room temperature over 3 h a solution of ethyl diazoacetate (0.47 ml, 510 mg, 4.47 mmol) in dichloromethane (3 ml), then the mixture was stirred at room temperature for 66 h. The mixture was purified by silica (100 g) column chromatography eluting with hexane:dichloromethane 100:0 to 50:50. Product containing fractions were combined and concentrated in vacuo to afford the title compound as a colourless oil (65 mg, 7%).