Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[CH2:12][C:13]([N:15]1[CH:20]=[CH:19][C:18](=[O:21])[CH2:17][CH:16]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:14].O.[CH3:29][N:30](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[CH3:11][O:10][C:5]1[C:6]([O:8][CH3:9])=[CH:7][C:2]([C:29]#[N:30])=[C:3]([CH2:12][C:13](=[O:14])[N:15]2[CH:20]=[CH:19][C:18](=[O:21])[CH2:17][CH:16]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:4]=1
Reactant: COc1cc(I)c(CC(=O)N2C=CC(=O)CC2c2ccccc2)cc1OC
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: COc1cc(C#N)c(CC(=O)N2C=CC(=O)CC2c2ccccc2)cc1OC
Temperature: 80 °C
Yield: 20.3 %

Procedure:
1-[2-(2-Iodo-4,5-dimethoxy-phenyl)-acetyl]-2-phenyl-2,3-dihydro-1H-pyridin-4-one (269 mg, 0.56 mmol), zinc cyanide (1.5 eq, 99 mg) and tetrakis(triphenylphosphine)palladium(0) (0.15 eq, 98 mg) were dissolved in DMF. The mixture was heated to 80° C. overnight. Upon cooling, the mixture was poured into water and extracted with EtOAc. The organic extracts were dried over anhydrous sodium sulfate and concentrated en vacuo. The residue was purified by flash chromatography (7:3 Hexanes/Ethyl Acetate) to give 4,5-dimethoxy-2-[2-oxo-2-(4-oxo-2-phenyl-3,4-dihydro-2H-pyridin-1-yl)-ethyl]-benzonitrile (43 mg, 20.3%) viscous oil.
Reaction SMILES: OI1(=O)C2C=CC=CC=2C(=O)O1.[C:13]1([CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([CH2:30][NH:31][C:32]3[NH:36][C:35]4[CH:37]=[CH:38][C:39]([CH2:41][OH:42])=[CH:40][C:34]=4[N:33]=3)[CH2:26][CH2:25]2)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.C(OCC)(=O)C>CS(C)=O>[C:13]1([CH2:23][N:24]2[CH2:25][CH2:26][CH:27]([CH2:30][NH:31][C:32]3[NH:36][C:35]4[CH:37]=[CH:38][C:39]([CH:41]=[O:42])=[CH:40][C:34]=4[N:33]=3)[CH2:28][CH2:29]2)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: OCc1ccc2[nH]c(NCC3CCN(Cc4cccc5ccccc45)CC3)nc2c1
Agent: O=C1OI(=O)(O)c2ccccc21
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: O=Cc1ccc2[nH]c(NCC3CCN(Cc4cccc5ccccc45)CC3)nc2c1
Temperature: 25 °C
Reaction time: 9 h

Procedure:
A solution of 1-hydroxy-1-oxo-1H-1λ5-benzo[d][1,2]iodoxol-3-one (846 mg, 3.02 mmol) in dimethylsulfoxide (10 ml) was added to a solution of {2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazol-5-yl}-methanol (807 mg, 2.01 mmol) in dimethylsulfoxide (10 ml), and the mixture was stirred at room temperature for 9 hours. The reaction mixture was poured into ice water (200 ml) and stirred at room temperature for 30 minutes, after which ethyl acetate was added and stirring was continued vigorously for 10 minutes for extraction. After washing with saturated aqueous sodium bicarbonate and saturated brine, the mixture was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/methanol=9/1). This was further purified by preparative HPLC to obtain 2-[(1-naphthalen-1-ylmethyl-piperidin-4-ylmethyl)-amino]-1H-benzimidazole-5-carboaldehyde.
Reaction SMILES: [CH2:1]([O:9][C:10]1[CH:11]=[N:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]([OH:29])[CH3:28])=[CH:18][CH:17]=2)=[N:14][CH:15]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(N(CC)CC)C.ClCCl.[C:40](Cl)(=[O:43])[CH2:41][CH3:42]>C(Cl)(Cl)Cl>[CH2:1]([O:9][C:10]1[CH:15]=[N:14][C:13]([C:16]2[CH:17]=[CH:18][C:19](/[CH:22]=[CH:23]/[CH2:24][CH2:25][CH2:26][CH:27]([O:29][C:40](=[O:43])[CH2:41][CH3:42])[CH3:28])=[CH:20][CH:21]=2)=[N:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCOc1cnc(-c2ccc(CCCCCC(C)O)cc2)nc1
Reactant: CCC(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCOc1cnc(-c2ccc(/C=C/CCCC(C)OC(=O)CC)cc2)nc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 88.4 %

Procedure:
A reactor was charged with 1.6 g (4 mmol) of the (-)-5-octyloxy-2-{4-(6-hydroxy-heptyl)-phenyl}-pyrimidine obtained in Example 9, 2 g of triethylamine and 30 g of dichloromethane, to which was dropwise added 0.6 g (6 mmol) of propionyl chloride at a temperature not exceeding 10° C. The mixture was reacted first at 0°-10° C. for one hour and thereafter at 20°-30° C. for 2 hours. After the reaction, the reaction mixture was poured into ice water, and the mixture thus obtained was separated into two phases. The organic layer was washed successively with 5% hydrochloric acid, water, 5% aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by silica gel column chromatography gave 1.6 g (yield 85%) of (+)-5-octyloxy-2-{4-(6-propionyloxy-1-trans-heptenyl)-phenyl}-pyrimidine, [α]D20 =+0.96 (c=1.1, CHCl3).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].Cl.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][N:23]([CH3:25])[CH3:24])=[C:11]([CH:14]=1)[CH2:12][OH:13]>C(#N)C.C(N(CC)CC)C>[C:1]([O:13][CH2:12][C:11]1[CH:14]=[C:7]([Cl:6])[CH:8]=[CH:9][C:10]=1[S:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][N:23]([CH3:25])[CH3:24])(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CN(C)Cc1ccccc1Sc1ccc(Cl)cc1CO
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(=O)OCc1cc(Cl)ccc1Sc1ccccc1CN(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 38.2 %

Procedure:
A solution of acetyl chloride (2.5 g) in 50 mL of acetonitrile was added dropwise to a solution of 9.8 g of 5-chloro-2-((2-((dimethylamino)methyl)phenyl)thio)benzyl alcohol (Example 2) in 25 mL of triethylamine and 200 mL of acetonitrile. The reaction mixture was stirred for 3 hr at room temperature, filtered and concentrated in vacuo to give a yellow oil. This oil was chromatographed on silica gel with EtOAc as the eluent. Concentration of solvents afforded 3.8 g (34% yield) of 5-chloro-2-((2-((dimethylamino)methyl)phenyl)thio)benzyl acetate as a light yellow oil. Upon standing, oil crystallized to a beige solid, m.p. 41°-44° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH:5]=O.Cl.[O:12]([NH2:14])[CH3:13]>>[CH3:13][O:12][N:14]=[CH:5][C:4]1[CH:7]=[CH:8][C:9]([CH3:10])=[C:2]([F:1])[CH:3]=1
Reactant: Cc1ccc(C=O)cc1F
Reactant: CON
Agent: Cl
Product: CON=Cc1ccc(C)c(F)c1
Yield: 94 %

Procedure:
Reaction of 3-fluoro-4-methyl-benzaldehyde with methoxylamine hydrochloride as described in the preparation of compound 3-A gave the title oxime ether as a clear oil (94% yield). 1HNMR indicated a 9:1 mixture of E- and Z-isomers. 1HNMR 400 MHz (CDCl3) δ (ppm): (E-isomer) 2.28 (3H, broad s, CH3), 3.97 (3H, s, OCH3), 7.15-7.29 (3H, m, aromatics), 7.99 (1H, s, CH).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH2:9][C:10](=[O:16])[NH:11]3)[CH2:3][CH2:2]1.[CH:17]([C:19]1[NH:20][C:21]2[CH2:22][CH2:23][CH2:24][CH2:25][C:26]=2[C:27]=1[CH2:28][CH2:29][C:30]([OH:32])=[O:31])=O.N1CCCC1.C(O)(=O)C>C(O)C>[O:16]=[C:10]1[C:9](=[CH:17][C:19]2[NH:20][C:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:26]=3[C:27]=2[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[C:8]2[C:12](=[CH:13][CH:14]=[CH:15][C:7]=2[CH:4]2[CH2:3][CH2:2][NH:1][CH2:6][CH2:5]2)[NH:11]1
Reactant: O=Cc1[nH]c2c(c1CCC(=O)O)CCCC2
Reactant: O=C1Cc2c(cccc2C2CCNCC2)N1
Solvent: CC(=O)O
Solvent: CCO
Solvent: C1CCNC1
Product: O=C(O)CCc1c(C=C2C(=O)Nc3cccc(C4CCNCC4)c32)[nH]c2c1CCCC2
Reaction time: 0.17 h

Procedure:
A mixture of 4-piperidin-4-yl-1,3-dihydroindol-2-one (45 mg, 0.2 mmol), 3-(2-formyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-propionic acid (57 mg, 0.23 mmol) and pyrrolidine (0.3 mL) in ethanol (0.5 mL) was heated to reflux for 2 hours. Acetic acid (0.05 mL) was added to the reaction and heating was continued for another 10 minutes. The reaction was cooled and the precipitate which formed was collected by vacuum filtration, washed with ethanol and dried to give the title compound.
Reaction SMILES: FC(F)(F)C([N:5]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([O:32][CH3:33])=[O:31])[C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1)=O.C(N(CC)CC)C.C([O:45][C:46](=[O:50])[C@H:47]([CH3:49])[NH2:48])C>CCOCC>[C:30]([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][NH:5][C:6]1[CH:7]=[CH:8][C:9]([C:10]([NH:48][C@H:47]([C:46]([OH:50])=[O:45])[CH3:49])=[O:11])=[CH:13][CH:14]=1)([O:32][CH3:33])=[O:31]
Reactant: CCOC(=O)[C@H](C)N
Reactant: COC(=O)CCCCCCCCCCCCCCCN(C(=O)C(F)(F)F)c1ccc(C(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: COC(=O)CCCCCCCCCCCCCCCNc1ccc(C(=O)N[C@@H](C)C(=O)O)cc1

Procedure:
A solution of 4.75 g. of N-trifluoroacetyl-4-(15-carbomethoxypentadecylamino)benzoyl chloride and 1.2 g. of triethylamine in 20 ml. of warm ether is treated with 1.55 g. alanine ethyl ester and refluxed for 24 hours. The hot solution is filtered, the residue is washed with hot ether, and the solution is evaporated. After treatment with aqueous methanolic potassium carbonate, the product is precipitated by acidification, filtered, and dried. Crystallization from acetone yields the product as a white, crystalline solid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25]1[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH:30]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([SiH](CC)CC)C>C(Cl)Cl>[CH2:8]([O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[CH:25]1[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CN1CC=C(c2c[nH]c3ccc(OCc4ccccc4)cc23)CC1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN1CCC(c2c[nH]c3ccc(OCc4ccccc4)cc23)CC1
Yield: 93.6 %

Procedure:
By a method similar to Preparation 20, using trifluoroacetic acid (1.6 mL), 5-benzyloxy-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (222 mg, 0.7 mmol), methylene chloride (3 mL) and triethylsilane (111 μL, 0.7 mmol) gave the tile compound as a yellow foam (210 mg) which was crystallized from ethyl acetate to give 160 mg of pale yellow crystals: mp=163-164° C.; MS(m/e): 321 (M+1), 379 (M+59); Calculated for C21H24N2O: Calcd: C, 78.72; H, 7.55; N, 8.74. Found: C, 78.63; H, 7.64; N, 8.78.
Reaction SMILES: [CH3:1][S:2]([CH:5]([CH2:15][CH2:16][CH2:17][CH:18]([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9]CCC(O)=O)(=[O:4])=[O:3].CSC(CCCC(O)CCCCC)CCCC[O:32][CH2:33][C:34]([OH:36])=[O:35]>>[CH3:1][S:2]([CH:5]([CH2:15][CH2:16][CH2:17][CH:18]([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9][O:32][CH2:33][C:34]([OH:36])=[O:35])(=[O:3])=[O:4]
Reactant: CCCCCC(O)CCCC(CCCCOCC(=O)O)SC
Reactant: CCCCCC(O)CCCC(CCCCCCC(=O)O)S(C)(=O)=O
Product: CCCCCC(O)CCCC(CCCCOCC(=O)O)S(C)(=O)=O

Procedure:
This compound is prepared essentially by the method described in Example 2 except that the 8-methylthio-12-hydroxyheptadecanoic acid of Example 2 is replaced by 5-methylthio-9-hydroxytetradecyloxyacetic acid. The product is purified by chromatography on silica gel and is obtained as a very viscous yellowish oil.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH:6]([CH3:15])[CH:7]([CH2:13][CH3:14])[C:8]2=[O:12])=[CH:4][C:3]=1[O:16][CH2:17][C:18]([O:20][CH3:21])=[O:19].C([C:24]([CH3:26])=[O:25])=C.N12CCCC1=NC[CH2:29][CH2:28]2>O1CCCC1>[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH:6]([CH3:15])[C:7]([CH2:28][CH3:29])([CH2:13][CH2:14][C:24](=[O:25])[CH3:26])[C:8]2=[O:12])=[CH:4][C:3]=1[O:16][CH2:17][C:18]([O:20][CH3:21])=[O:19]
Reactant: CCC1C(=O)c2c(cc(OCC(=O)OC)c(Cl)c2Cl)C1C
Reactant: C1CN=C2CCCN2C1
Reactant: C=CC(C)=O
Solvent: C1CCOC1
Product: CCC1(CCC(C)=O)C(=O)c2c(cc(OCC(=O)OC)c(Cl)c2Cl)C1C
Temperature: 0 °C

Procedure:
To a solution of methyl [(6,7-dichloro-2-ethyl-2,3-dihydro-3-methyl-1-oxo-1H-inden-5-yl)oxy]acetate (0.8 g) in tetrahydrofuran (7.5 ml) was added methyl vinyl ketone (0.45 ml) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) (75 μl). The reaction mixture was heated at 60° C. for five hours during which time DBN (2×75 μl) was added. The reaction mixture was poured into ice water, extracted with ether, washed with water, dried over MgSO4 and evaporated in vacuo. Chromatography on silica gel eluting with ethyl acetate-hexane (1:1) gave methyl [(6,7-dichloro-2-ethyl-2,3-dihydro-3-methyl-1-oxo-2-(3-oxobutyl)-1H-inden-5-yl)oxy]acetate which was used in Step B without further purification.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:13]=[C:14]([CH:16]=O)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.[CH3:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.C[Si](Br)(C)C.CO>CN(C=O)C>[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[CH:28][C:19]=1/[CH:18]=[CH:16]/[C:14]1[N:15]=[C:8]2[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[CH:12][CH:11]=[N:10][N:9]2[CH:13]=1
Reactant: Cc1ccc2ccccc2n1
Reactant: O=Cc1cn2nccc(N3CCOCC3)c2n1
Agent: C[Si](C)(C)Br
Solvent: CN(C)C=O
Solvent: CO
Product: C(=C/c1cn2nccc(N3CCOCC3)c2n1)\c1ccc2ccccc2n1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To a solution of compound 5e (10 g, 43 mmol) and 2-methylquinoline (4.6 g, 32 mmol) in DMF (10 mL) was added TMSBr (2.9 g, 19 mmol) dropwise. The reaction mixture was stirred at 80° C. for 2 h. MeOH (10 mL) was added. The solids formed were collected by filtration and washed with Et2O (2×50 mL) to obtain compound 57c as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C21H19N5O: 358.2 (M+H). Found: 358.3.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[CH:8]=[C:7]([CH2:13][CH2:14][CH2:15][C:16]([OH:18])=O)[CH:6]=[CH:5]2>CS(O)(=O)=O>[CH3:12][C:11]1[CH:10]=[C:9]2[C:4](=[CH:3][C:2]=1[CH3:1])[CH:5]=[CH:6][C:7]1[CH2:13][CH2:14][CH2:15][C:16](=[O:18])[C:8]2=1
Reactant: Cc1cc2ccc(CCCC(=O)O)cc2cc1C
Agent: CS(=O)(=O)O
Product: Cc1cc2ccc3c(c2cc1C)C(=O)CCC3
Temperature: 90 °C

Procedure:
4-(6,7-Dimethyl-2-naphthyl)butanoic acid (6.21 g, 0.026 mole) was added to 40 ml of CH3SO3H. The mixture was heated to 90° C. until all solid material disappeared (about 30 min.). The mixture was poured into ice and then extracted twice with ethylacetate. Combined ethylacetate solution was dried over anhydrous Na2SO4 and then concentrated. After flash chromatography on silica gel, 6,7-Dimethyl-4-oxo-1,2,3,4-tetrahydrophenanthrene was obtained as a pale yellow solid material (4.96 g, 0.022 mole, 85% yield). mp 114.0°-115.0° C., 1H NMR (CDCl3) δ2.12-2.20 (m,2H), 2.41 (s,3H), 2.47 (s,3H), 2.77 (t, J=6.4 Hz,2H), 3.09 (t, J=6.4 Hz,2H), 7.21 (d, J=8.3 Hz,1H), 7.54 (s,1H), 7.31 (d, J=8.3 Hz,1H), 9.20 (s,1 H), IR (KBr) cm-1 2930, 1669, 1590, 1510, Anal. Calcd. for C16H16O: C, 85.6: H, 7.19. Found: C, 86.00; H, 7.18.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[O:8][C@:9]3([CH3:49])[O:12][CH:13]=[CH:14][C@H:15]([O:47][CH3:48])[C@@H:16]([CH3:46])[C@@H:17]([O:42][C:43]([CH3:45])=[O:44])[C@H:18]([CH3:41])[C@H:19]([OH:40])[C@H:20]([CH3:39])[C@@H:21]([OH:38])[C@@H:22]([CH3:37])[CH:23]=[CH:24][CH:25]=[C:26]([CH3:36])[C:27]([NH:29][C:30]4[C:34](=[O:35])[C:4](=[C:5]([C:32](=[O:33])[CH:31]=4)[C:6]=2[C:10]3=[O:11])[C:3]=1[OH:50])=[O:28].[N-:51]=[N+]=[N-].[Na+]>CN(C)C=O>[CH3:37][C@@H:22]1[C@H:21]([OH:38])[C@@H:20]([CH3:39])[C@@H:19]([OH:40])[C@@H:18]([CH3:41])[C@H:17]([O:42][C:43]([CH3:45])=[O:44])[C@H:16]([CH3:46])[C@@H:15]([O:47][CH3:48])[CH:14]=[CH:13][O:12][C@:9]2([CH3:49])[C:10](=[O:11])[C:6]3[C:7]([O:8]2)=[C:2]([CH3:1])[C:3]([OH:50])=[C:4]2[C:34](=[O:35])[C:30](=[C:31]([NH2:51])[C:32]([C:5]=32)=[O:33])[NH:29][C:27](=[O:28])[C:26]([CH3:36])=[CH:25][CH:24]=[CH:23]1
Reactant: [N-]=[N+]=[N-]
Reactant: CO[C@H]1C=CO[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C=C(NC(=O)C(C)=CC=C[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Agent: CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C(N)=C(NC(=O)/C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Agent: CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C=C(NC(=O)/C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@H]1C=CO[C@@]2(C)Oc3c(C)c(O)c4c(c3C2=O)C(=O)C(N)=C(NC(=O)C(C)=CC=C[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C4=O
Reaction time: 36 h

Procedure:
50 g rifamycin S were dissolved in 200 ml dimethyl formamide and added with 9 g sodium azide. After 36 hours at a temperature of +5° C, the reaction mixture was treated as in Example 3, to obtain 13 g 3-amino-rifamycin S identical to that described in Example 3.
Reaction SMILES: [C:1]1([S:7]([NH:10][NH2:11])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]([C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1)#[N:13].NN>C(O)C>[C:1]1([S:7]([NH:10][N:11]=[CH:18][C:17]2[CH:20]=[CH:21][C:14]([C:12]#[N:13])=[CH:15][CH:16]=2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NNS(=O)(=O)c1ccccc1
Reactant: N#Cc1ccc(C=O)cc1
Agent: NN
Solvent: CCO
Product: N#Cc1ccc(C=NNS(=O)(=O)c2ccccc2)cc1

Procedure:
Benzenesulfonyl hydrazine (20.5 g, 0.12 mole) was dissolved by warming in 110 ml absolute ethanol. p-Cyanobenzaldehyde (15.6 g, 0.12 mole) was separately dissolved in 50 ml of hot ethanol and added to the hydrazine solution. The resulting slurry was refluxed 0.5 hour, cooled and filtered to yield 28.1 g; m.p. 209°-213°. Recrystallization from CH3CN gave purified title product: 23.7 g; m.p. 210°-213°.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=3)=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.O.[OH-].[Na+]>C(Cl)Cl>[CH3:26][C:22]1[CH:21]=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[N:15][CH:16]=2)[CH:25]=[CH:24][N:23]=1
Reactant: Cc1cc(-c2ccc(C3CCN(C(=O)OC(C)(C)C)CC3)nc2)ccn1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(-c2ccc(C3CCNCC3)nc2)ccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 80.1 %

Procedure:
2″-Methyl-3,4,5,6-tetrahydro-2H-[4,2′;5′,4″]terpyridine-1-carboxylic acid tert-butyl ester (0.54 g, 1.528 mmol) was dissolved in DCM (12 mL), TFA (4mL) was added the reaction mixture was stirred at RT for 2 hours. The reaction mixture was added water and 1N NaOH until pH=12. The organic phase was washed dried with Na2CO3 filtered and evaporation gave 310 mg (80%) yellow crystals.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([N:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=2)=[C:6]([Cl:19])[CH:5]=1.O.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[CH:47](=[O:51])[CH:48]([CH3:50])[CH3:49].O>O1CCCC1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]2[C:7](=[C:6]([Cl:19])[CH:5]=1)[NH:10][CH:11]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=1)[C:48]([CH3:50])([CH3:49])[CH:47]2[OH:51])=[O:20]
Reactant: CC(C)C=O
Reactant: COC(=O)c1ccc(N=Cc2cccc(Br)c2)c(Cl)c1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1cc(Cl)c2c(c1)C(O)C(C)(C)C(c1cccc(Br)c1)N2
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.8 %

Procedure:
To a stirred mixture solution of 4-[(3-bromo-benzylidene)-amino]-3-chloro-benzoic acid methyl ester (39.8 g, 113.2 mmol) and ytterbium(III) triflate hydrate (10.5 g, 16.9 mmol) in dry tetrahydrofuran (100 mL) at 25° C. was added isobutyraldehyde (10.4 mL, 113.2 mmol) and water (2.1 mL, 113.2 mmol) dropwise. The reaction mixture was stirred at 25° C. for 16 h. Then the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-(3-bromo-phenyl)-8-chloro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (48 g, quant.) as a light yellow oil which was used for next step without further purification: LC/MS m/e calcd for C19H19BrClNO3 (M+H)+: 425.73, observed: 405.9 & 407.9.
Reaction SMILES: [C:1]1([CH:9]=[C:7]([OH:8])[CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].C([O:12][C:13]([CH:15]1[CH:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][C:16]1=O)=O)C.Cl>C(O)C>[OH:2][C:1]1[C:9]2[C:16]3[CH2:17][CH2:18][CH2:19][CH:20]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:15]=3[C:13](=[O:12])[O:8][C:7]=2[CH:6]=[C:4]([OH:5])[CH:3]=1
Reactant: Oc1cc(O)cc(O)c1
Reactant: CCOC(=O)C1C(=O)CCCC1c1ccccc1
Agent: Cl
Solvent: CCO
Product: O=c1oc2cc(O)cc(O)c2c2c1C(c1ccccc1)CCC2

Procedure:
A solution of phloroglucinol (0.7 g) and 2-ethoxycarbonyl-3-phenylcyclohexanone (1.5 g) in ethanol was treated with dry HCl as described in example 1a. The product was first recrystallized from ethanol-water (1:1) and then triturated with ether. Yield 0.61 g.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].[C:21]([NH:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)(=[O:23])[CH3:22]>>[C:21]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:27][CH:26]=1)(=[O:23])[CH3:22]
Reactant: CC(=O)Nc1ccc(B(O)O)cc1
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Product: COC(=O)c1cc(C2CC2)c2c(C)c(-c3ccc(NC(C)=O)cc3)ccn2c1=O
Yield: 91.6 %

Procedure:
Methyl 8-(4-acetamido-phenyl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A using methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (77 mg, 0.26 mmol) and (4-acetamido-phenyl)-boronic acid (56 mg, 0.31 mmol). Purification by flash silica column chromatography (CH2Cl2:MeOH) (1:0 to 94:6) afforded the title compound as a yellow solid (93 mg, 90%). ESI-MS m/z: 391 (M+H)+.
Reaction SMILES: C([O:4][CH:5]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16]CC2N=C(C3C=CC=CC=3)OC=2C)=[C:12]([O:30][CH3:31])[CH:11]=1)[C:6]#N)(=O)C.Cl.[O:33]1CCO[CH2:35][CH2:34]1.[OH2:39]>>[OH:4][CH:5]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([O:30][CH3:31])[CH:11]=1)[C:6]([O:33][CH2:34][CH3:35])=[O:39]
Reactant: C1COCCO1
Reactant: O
Reactant: COc1cc(CCC(C#N)OC(C)=O)ccc1OCc1nc(-c2ccccc2)oc1C
Agent: Cl
Product: CCOC(=O)C(O)CCc1ccc(O)c(OC)c1
Reaction time: 4 h
Yield: 60 %

Procedure:
A mixture of 2-acetoxy-4-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)phenyl]butyronitrile (2.0 g), 6 N HCl (24 ml) and dioxane (12 ml) was stirred for 4 hours under reflux. The reaction mixture was poured into water, which was subjected to extraction with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), followed by distilling off the solvent. To the resulting oily product was added ethanolic hydrochloric acid (10%, 24 ml), followed by stirring for 1.5 hours under reflux. The reaction mixture was poured into water, which was subjected to extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), followed by distilling off the solvent. The resulting oily product was subjected to column chromatography on silica gel. From the fraction eluted with ethyl acetate-hexane (1:2, v/v), was obtained ethyl 2-hydroxy-4-(4-hydroxy-3-methoxyphenyl)butanoate (0.73 g, 60%),