Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([CH3:3])[CH3:2].[Br-:11].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl>[Br:11][C:8]1[CH:7]=[CH:6][C:5]([OH:10])=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:9]=1
Reactant: [Br-]
Reactant: CC(C)c1ccccc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(C)c1cc(Br)ccc1O
Yield: 179.9 %

Procedure:
First, 20.4 g of 2-isopropylphenol and 750 ml of chloroform were charged into a reaction vessel, and 80 g of tetra-n-butylammonium tribromide was added at room temperature (about 20° C.) with stirring and the mixture was stirred at room temperature for additional 24 hours. To the reaction solution, 750 ml of a saturated sodium sulfite solution was added, and the mixture was shaken vigorously to concentrate the chloroform layer. To the residue, 500 ml of diethyl ether and 500 ml of 10% hydrochloric acid were added, and the mixture was shaken vigorously. The ether layer was dried over anhydrous magnesium sulfate and concentrated to give 32 g of 4-bromo-2-isopropylphenol (yield, 100%).
Reaction SMILES: [Br:1]Br.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:14](=[O:16])[CH3:15])[CH2:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.O>ClCCl.CO>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2([C:14](=[O:16])[CH2:15][Br:1])[CH2:13][CH2:12][CH2:11]2)=[CH:8][CH:9]=1
Reactant: BrBr
Reactant: CC(=O)C1(c2ccc(Cl)cc2)CCC1
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: O=C(CBr)C1(c2ccc(Cl)cc2)CCC1
Reaction time: 0.25 h

Procedure:
A solution of bromine (8 ml) in dichloromethane (40 ml) was added at 10° C. to a solution of 1-[1-(4-chlorophenyl)cyclobutyl]ethanone (27.8 g) in methanol (30 ml). The mixture was stirred for 15 minutes and poured into a mixture of ice and water. The resulting mixture as extracted with dichloromethane. The extract was washed with water, dried evaporated to yield an oil which was distilled (145°-160° C./1 mm Hg) to give 1-[1-(4-chlorophenyl)cyclobutyl]-2-bromoethanone.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12])[CH3:2].[N:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([C:17]2[CH:18]=[CH:19][N:14]=[CH:15][CH:16]=2)[CH:7]=[CH:6][C:5]=1[N+:11]([O-:13])=[O:12])[CH3:2]
Reactant: OB(O)c1ccncc1
Reactant: CCOc1cc(Br)ccc1[N+](=O)[O-]
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CC(=O)N(C)C
Product: CCOc1cc(-c2ccncc2)ccc1[N+](=O)[O-]
Temperature: 80 °C
Yield: 55.2 %

Procedure:
A solution of 5-bromo-2-nitrophenyl ethyl ether (Example 146, step A) (4.5 g, 18.3 mmol), PdCl2(dppf)*DCM (1.34 g, 1.82 mmol) and 4-pyridylboronic acid (4.5 g, 36.6 mmol) in N,N-dimethylacetamide (110 mL) was deoxygenated by bubbling with N2 (g) for ca 15 min. To this solution was added degassed 1.6 N K2CO3 (aq) (55 mL, 6.0 equiv.) and the resulting slurry was warmed to 80° C. for 24 h. The N,N-dimethylacetamide was removed under reduced pressure and the solids were taken up in EtOAc, filtered to remove insoluble solids, washed with H2O, and dried (Na2SO4). The solvent was rotovaped down and the crude product was purified by flash chromatography to give the title compound of step A (2.46 g, 10.1 mmol, 55%). 1H NMR (400 MHz, CDCl3) δ ppm 8.72 (dd, J=4.67, 1.56 Hz, 2H), 7.93 (d, J=8.06 Hz, 1H), 7.45-7.51 (m, 2H), 7.21-7.26 (m, 2H), 4.26 (q, J=6.96 Hz, 2H), 1.51 (t, J=6.96 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[Br:10][CH2:11][CH2:12][CH2:13]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:10][CH2:11][CH2:12][CH2:13][O:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=1
Reactant: Oc1ccc(F)c(F)c1
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Fc1ccc(OCCCBr)cc1F
Temperature: 75 °C
Yield: 86.6 %

Procedure:
A mixture of 3,4-difluorophenol (2.60 g, 20.0 mmol), 1,3-dibromopropane (20.3 mL, 2001 mmol), and potassium carbonate (2.76 g, 20.0 mmol) in acetonitril (30 mL) was heated at 75° C. overnight. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The crude product was purified by chromatography on silica gel. (Horizon™, flash system from Biotage™. Column: Flash 40+M, 40×150 mm. Eluent: 3% ethyl acetate in heptane. Concentration in vacuo afforded, 4.35 g of the title compound as a colourless oil with a purity of ca. 90%.
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.FC(F)(F)C(NC1SC(Cl)=C(C(=NOCC#C)C(O)=O)N=1)=O.[CH3:28][N+:29]([CH3:32])=[CH:30][Cl:31].[Cl-].C[Si](CC(N)=O)(C)C.[CH3:42][C:43]([O:45][CH2:46][C:47]1[CH2:56][S:55][C@@H:50]2[C@H:51](N)[C:52](=[O:53])[N:49]2[C:48]=1[C:57]([OH:59])=[O:58])=[O:44]>C(OCC)(=O)C.O1CCCC1.O.CN(C)C=O>[CH3:28][N+:29]([CH3:32])=[CH:30][Cl:31].[Cl-:3].[CH3:42][C:43]([O:45][CH2:46][C:47]1[CH2:56][S:55][C@@H:50]2[CH2:51][C:52](=[O:53])[N:49]2[C:48]=1[C:57]([OH:59])=[O:58])=[O:44]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: O=P(Cl)(Cl)Cl
Agent: C#CCON=C(C(=O)O)c1nc(NC(=O)C(F)(F)F)sc1Cl
Agent: C[N+](C)=CCl
Agent: C[Si](C)(C)CC(N)=O
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)C[C@H]2SC1
Reaction time: 0.5 h

Procedure:
Vilsmeier reagent was prepared from phosphorus oxychloride (1.1 g) and N,N-dimethylformamide (0.5 g) in ethyl acetate (2.0 ml) in a conventional manner. 2-[2-(2,2,2-Trifluoroacetamido)-5-chlorothiazol-4-yl]-2-propargyloxyiminoacetic acid (syn isomer, 2.2 g) was added to the stirred suspension of Vilsmeier reagent in tetrahydrofuran (22 ml) under ice cooling and stirred for 20 minutes at same temperature [Solution A]. Trimethylsilylacetamide (5.1 g) was added to the stirred suspension of 7-aminocephalosporanic acid (1.5 g) in tetrahydrofuran (30 ml); and the mixture was stirred for 30 minutes at 35° to 40° C. To the solution was added the solution [Solution A] at -10° C., and the resulting solution was stirred at the same temperature for 30 minutes. Water and ethyl acetate were added to the reaction mixture at -10° C. The organic layer was separated and added to water. The mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated and adjusted to pH 2.0 with 10% hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated under reduced pressure to give 7-[2-(2,2,2-trifluoroacetamido)-5-chlorothiazol-4-yl]-2-propargyloxyiminoacetamido]cephalosporanic acid (syn isomer, 2.51 g).
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([SH:17])=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:18]([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([S:17][CH3:18])=[C:10]([C:13]([F:14])([F:16])[F:15])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CC(=O)N1CCc2cc(S)c(C(F)(F)F)cc21
Agent: [K+]
Solvent: CN(C)C=O
Product: CSc1cc2c(cc1C(F)(F)F)N(C(C)=O)CC2
Temperature: 80 °C
Yield: 96.5 %

Procedure:
A mixture of the thiol (D5) (26 g, 99 mmol), anhydrous K2CO3 (15.12 g, 109 mmol) and indomethane (18.6 ml, 300 mmol) in dry DMF (100 ml) was heated at 80° C. for 1 h. The reaction mixture was cooled, evaporated in vacuo and partitioned between water (200 ml) and dichloromethane (3×200 ml). The combined organics were washed with water (400 ml), dried (Na2S04) and evaporated to yield the title compound (26.3 g, 97%) as a yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:20]2[CH2:19][CH2:18][N:17]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:22][CH2:21]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: BrCc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccc(Br)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 4-bromobenzyl bromide (5 g, 20 mmol) and N-Boc piperazine (4.47 g, 24 mmol) in DMF (25 mL), K2CO3 (5.52 g, 40 mmol) was added and the reaction mixture was stirred for 16 h at room temperature. After completion of reaction (monitored by TLC), the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give crude product, V-1-I. This compound was used for next step without purification.
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].[CH:5]1([CH2:8][O:9][C:10]2[CH:11]=C([CH:15]=[CH:16][C:17]=2[O:18][CH:19]([F:21])[F:20])C=O)[CH2:7][CH2:6]1.S(=O)(=O)(O)N.Cl([O-])=O.[Na+]>O>[CH:5]1([CH2:8][O:9][C:10]2[CH:11]=[C:2]([CH:15]=[CH:16][C:17]=2[O:18][CH:19]([F:20])[F:21])[C:1]([OH:4])=[O:3])[CH2:6][CH2:7]1
Reactant: O=Cc1ccc(OC(F)F)c(OCC2CC2)c1
Reactant: CC(=O)O
Agent: NS(=O)(=O)O
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Product: O=C(O)c1ccc(OC(F)F)c(OCC2CC2)c1
Temperature: 7.5 °C

Procedure:
Glacial acetic acid (5 vol. with respect to 3-cyclopropylmethoxy 4-Difluoromethoxy benzaldehyde) was taken in a vessel and to this mixture of 3-cyclopropylmethoxy 4-Difluoromethoxy benzaldehyde and sulfamic acid (1.35 eq with respect to 3-cyclopropylmethoxy 4-Difluoromethoxy benzaldehyde) was added. The reaction mass was cooled to 5-10° C. under stirring. In another clean reaction vessel sodium chlorite (1.63 eq) was taken in water (1.5 vol. with respect to 3-cyclopropylmethoxy 4-Difluoromethoxy benzaldehyde) and added dropwise to the above prepared reaction solution at temperature below 10° C. The reaction mixture was stirred for 1 hr at 5-10° C. After completion of the reaction, water was added to get a white slurry. The solid was filtered and washed with water and dried under vacuum at 45-50° C. to get 3-cyclopropylmethoxy 4-Difluoromethoxy benzoic acid.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(CC)CC.F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[F:25]>CCOC(C)=O>[F:25][C:17]1[CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=[CH:21][C:16]=1[N:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Reactant: CN1CCNCC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CN1CCN(c2ccc([N+](=O)[O-])cc2F)CC1
Yield: 97.9 %

Procedure:
To a solution of 1-methylpiperazine (6.91 g, 69 mmol) and Et3N (6.98 g, 69 mmol) in EtOAc (60 mL) was added 1,2-difluoro-4-nitrobenzene (10.02 g, 63 mmol) dropwise with stirring and the mixture was stirred at rt overnight. The reaction mixture was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a yellow solid (14.75 g, 98%).
Reaction SMILES: C(O[C:9]([N:11]([CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([CH2:23][CH3:24])[CH:15]=1)C)=O)C1C=CC=CC=1.C(OC(N(CC1C2C(=CC=CC=2)N(CC2C=CC=CC=2)C=1)C)=O)C1C=CC=CC=1>>[CH2:23]([N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([CH2:13][NH:11][CH3:9])=[CH:15]1)[CH3:24]
Reactant: CCn1cc(CN(C)C(=O)OCc2ccccc2)c2ccccc21
Agent: CN(Cc1cn(Cc2ccccc2)c2ccccc12)C(=O)OCc1ccccc1
Product: CCn1cc(CNC)c2ccccc21
Yield: 94.8 %

Procedure:
According to the procedure of Preparation 17 (c), except substituting 3-[N-(benzyloxycarbonyl)-N-methylaminomethyl]-1-ethyl-1H-indole (0.90 g, 2.80 mmole) for the 3-[N-(benzyloxycarbonyl)-N-methylaminomethyl]-1-benzyl-1H-indole, the title compound (0.50 g, 94%) was prepared as a white solid: MS (ES) m/e 189 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CI.[C:17]([O-])([O-])=O.[K+].[K+]>CC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:14])[CH2:9][CH2:10][N:11]([CH3:17])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: OC1(c2ccc(Br)cc2)CCNCC1
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: CN1CCC(O)(c2ccc(Br)cc2)CC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A reaction mixture of 4-(4-bromophenyl)piperidin-4-ol (1.5 g, 5.9 mmol), methyl iodide (0.4 mL, 6.4 mmol), and K2CO3 (1.2 g, 8.8 mmol) in acetone was stirred at rt for 90 min
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:17]=[C:13]([C:14]([OH:16])=[O:15])[C:12]([OH:18])=[C:11]([I:19])[CH:10]=1.[CH2:20](O)[CH3:21]>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:17]=[C:13]([C:14]([O:16][CH2:20][CH3:21])=[O:15])[C:12]([OH:18])=[C:11]([I:19])[CH:10]=1
Reactant: O=C(O)c1cc(-c2ccc(F)cc2F)cc(I)c1O
Reactant: CCO
Product: CCOC(=O)c1cc(-c2ccc(F)cc2F)cc(I)c1O
Temperature: 25 °C

Procedure:
A solution of 5-(2,4-difluorophenyl)-3-iodo-salicylic acid (1.69 g, 4.61 mmol) in ethanol (20 ml) was cooled to 0° C. and a flow of anhydrous hydrochloride gas was bubbled through for 5 min. The solution was heated under reflux for 4 hr and cooled to room temperature, the solvents were evaporated at low pressure. The residue was dissolved in dichloromethane and the product was worked up. The reaction crude was purified by chromatography on silica gel using hexane/ethyl acetate (7:3) as the eluent.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:23]=[O:24].O>O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[N:10]=[CH:11][C:12]([CH:23]=[O:24])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccc(OCc2ccccc2)nc1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: O=Cc1ccc(OCc2ccccc2)nc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 40.1 %

Procedure:
To a solution of 2-benzyloxy-5-bromopyridine (15.1 g, 57.0 mmol) described in Manufacturing Example 12-1-1 in anhydrous tetrahydrofuran (250 mL) were added dropwise n-butyl lithium (2.67 M n-hexane solution, 25.6 mL, 68.4 mmol) under nitrogen atmosphere on a dry ice-ethanol bath (−78° C.), which was stirred for 30 minutes at −78° C. N,N-Dimethylformamide (6.60 mL, 85.5 mmol) was then added thereto at −78° C., and stirred for 30 minutes. Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated after stirring for 10 minutes at room temperature. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:7 then 1:5) to obtain the title compound (4.87 g, 40%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[H-].[Na+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([O:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=[C:4]([CH:3]=1)[C:12]([O:14][CH3:15])=[O:13])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1cc(O)cc(C(=O)OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(OCc2ccccc2)cc(C(=O)OC)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of dimethyl 5-hydroxyisophthalate (1 eq.) in DMF (0.5 M) at 0° C. was added portionwise NaH (1.2 eq.) and stirred for 30 min at 0° C. Benzyl bromide (1.2 eq.) was added and the reaction was stirred at rt for 1.5 h. The reaction was then quenched with water ( 1/7 volume), and the resulting precipitate was filtered and washed with hexane. The filtrate was diluted with ether and washed several times with water and brine. The organic extract was dried over MgSO4 and concentrated in vacuo to give a solid which was combined with the filtered precipitate to give dimethyl 5-(benzyloxy)isophthalate. This compound was subsequently dissolved in THF/MeOH (2:1, 0.5 M), and to this solution was added KOH powder. After stirring for 18 h at rt, the reaction was poured into a solution of ether/water. The two layers were separated and the ethereal layer was discarded. The aqueous layer was acidified to pH <1 with 3 N HCl and extracted with EtOAc. The combined organic extracts were dried over MgSO4 and concentrated in vacuo to afford the title compound as a white solid.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:15][O:16][C:17](=[O:29])[C:18]1[CH:27]=[C:26]([OH:28])[CH:25]=[C:20]([C:21]([O:23][CH3:24])=[O:22])[CH:19]=1>CC(C)=O>[CH3:24][O:23][C:21](=[O:22])[C:20]1[CH:25]=[C:26]([O:28][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:27]=[C:18]([C:17]([O:16][CH3:15])=[O:29])[CH:19]=1
Reactant: COC(=O)c1cc(O)cc(C(=O)OC)c1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1cc(OCc2ccccc2)cc(C(=O)OC)c1
Temperature: 25 °C
Yield: 105.1 %

Procedure:
K2CO3 (21 g, 153 mmol, 2 equiv) and benzyl bromide (11 ml, 92 mmol, 1.2 equiv) were added to a solution of 5-hydroxy-isophthalic acid dimethyl ester (D42) (16.1 g, 76.7 mmol, 1 equiv) in acetone (400 ml) at room temperature. The resulting solution was refluxed for 18 h, cooled to room temperature and concentrated in vacuo. The residue was partitioned between H2O and AcOEt. The aqueous phase was extracted with AcOEt and the combined organic layers were washed with 2N aqueous NaOH solution and brine, dried over MgSO4 and concentrated in vacuo to give 5-benzyloxy-isophthalic acid dimethyl ester (D44) (24.2 g, 105%) as a white solid. [M+H]+=301.0, RT=3.50 min
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[C:7](=[CH:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[CH2:6]2.Cl(O)(=O)(=O)=O>CO.ClCCl.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH:7]([CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[CH2:6]2
Reactant: COc1cc2c(cc1OC)C(=O)C(=Cc1ccncc1)C2
Agent: [Pd]
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: CO
Solvent: ClCCl
Product: COc1cc2c(cc1OC)C(=O)C(Cc1ccncc1)C2

Procedure:
4-[(5,6-Dimethoxy-1-indanon-2-ylidene)methyl]pyridine (50 g) in methanol and dichloromethane (1:1) was hydrogenated in presence of palladium on carbon (5 g) and a catalytic quantity of perchloric acid at 0.5 kg pressure and room temperature. The solvents were evaporated under vacuum and the residue was taken in ethyl acetate (500 ml), washed with water (50 ml), brine (50 ml), dried over anhydrous sodium sulphate and evaporated in vacuum to yield the product. Yield: 49 g.
Reaction SMILES: [C:1]([OH:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].O.O.O.O.O.O.O.O.[OH-].[Sr+2:26].[OH-]>O>[C:1]([O-:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[Sr+2:26].[C:1]([O-:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCC(=O)O
Agent: [OH-]
Agent: [Sr+2]
Solvent: O
Product: CCCCCCCCCCCCCC(=O)[O-]
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
100 of myristic acid which has been granulated from an aqueous emulsion as described in Example 1 (AN 246, titer 53° C. particle size 0.2-0.3 mm.) and 60.2 g strontium hydroxide octahydrate (97% active) are suspended in one liter of water at 50° C. temperature and stirred for 30 minutes at 50° C. followed by 60 minutes of agitation at 70° C. The hollow formed granulate is filtered and dried. The content of free fatty acid amounts to 1.7%.
Reaction SMILES: [C:1]([OH:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[OH-].[Ca+2:18].[OH-]>C(O)(=O)C>[C:1]([O-:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[Ca+2:18].[C:1]([O-:16])(=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCC(=O)O
Agent: [Ca+2]
Agent: [OH-]
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCC(=O)[O-]
Reaction time: 0.05 h

Procedure:
114.5 g of myristic acid and 38.9 g of calcium hydroxide were stirred at 35° to 40° C., and 0.3% acetic acid was added as catalyst. The mass initially underwent slight compaction but then changed into a white voluminous powder. During the reaction, the temperature rose to 70°-80° C. The total stirring time was 3 minutes. A white voluminous powder having a Ca content of 13.6%, a melting temperature of 180° to more than 250° C., and an acid value of 1.6 was obtained.
Reaction SMILES: COC1C=CC(S)=CC=1.B([O-])([O-])OC1C=CC=CC=1.[CH2:20]([NH2:23])[CH2:21][NH2:22].[CH3:24][CH2:25][CH:26]([CH2:28][CH:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]([NH:41][C@@H:42]1[C:73](=[O:74])[NH:72][C@@H:71]([C@H:75]([OH:77])[CH3:76])[C:69](=[O:70])[N:68]2[C@@H:64]([CH2:65][C@@H:66]([OH:78])[CH2:67]2)[C:62](=[O:63])[NH:61][C@@H:60]([C@H:79]([OH:89])[C@@H:80]([OH:88])[C:81]2[CH:86]=[CH:85][C:84]([OH:87])=[CH:83][CH:82]=2)[C:58](=[O:59])[NH:57][C@@H:56]([C@H:90]([OH:95])[CH2:91][C:92]([NH2:94])=O)[C:54](=[O:55])[N:53]2[C@@H:49]([C@@H:50]([OH:96])[CH2:51][CH2:52]2)[C:47](=[O:48])[NH:46][C@H:45](O)[C@H:44]([OH:98])[CH2:43]1)=[O:40])[CH3:30])[CH3:27]>>[CH3:24][CH2:25][CH:26]([CH2:28][CH:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]([NH:41][C@@H:42]1[C:73](=[O:74])[NH:72][C@@H:71]([C@H:75]([OH:77])[CH3:76])[C:69](=[O:70])[N:68]2[C@@H:64]([CH2:65][C@@H:66]([OH:78])[CH2:67]2)[C:62](=[O:63])[NH:61][C@@H:60]([C@H:79]([OH:89])[C@@H:80]([OH:88])[C:81]2[CH:86]=[CH:85][C:84]([OH:87])=[CH:83][CH:82]=2)[C:58](=[O:59])[NH:57][C@@H:56]([C@H:90]([OH:95])[CH2:91][CH2:92][NH2:94])[C:54](=[O:55])[N:53]2[C@@H:49]([C@@H:50]([OH:96])[CH2:51][CH2:52]2)[C:47](=[O:48])[NH:46][C@H:45]([NH:22][CH2:21][CH2:20][NH2:23])[C@H:44]([OH:98])[CH2:43]1)=[O:40])[CH3:30])[CH3:27]
Reactant: CCC(C)CC(C)CCCCCCCCC(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)CCN2C(=O)[C@H]([C@H](O)CC(N)=O)NC(=O)[C@H]([C@H](O)[C@@H](O)c2ccc(O)cc2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@H]([C@@H](C)O)NC1=O
Reactant: NCCN
Agent: COc1ccc(S)cc1
Agent: [O-]B([O-])Oc1ccccc1
Product: CCC(C)CC(C)CCCCCCCCC(=O)N[C@H]1C[C@@H](O)[C@@H](NCCN)NC(=O)[C@@H]2[C@@H](O)CCN2C(=O)[C@H]([C@H](O)CCN)NC(=O)[C@H]([C@H](O)[C@@H](O)c2ccc(O)cc2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@H]([C@@H](C)O)NC1=O

Procedure:
According to WO2010008493A2, Pneumocandin B0 as the starting material reacts with 4-methoxy thiophenol, the resulting product is protected by phenyl borate, the amide group in Pneumocandin B0 is reduced to amine group under the condition of dehydration by 3A molecular sieve, and then the resulting product reacts with ethylenediamine to obtain caspofungin.
Reaction SMILES: [CH:1]#[CH:2].[Cl:3][SiH:4]([CH:6]([SiH:11]([Cl:13])[Cl:12])[Si:7]([Cl:10])([Cl:9])[Cl:8])[Cl:5]>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.C1C=CC=CC=1>[Cl:5][Si:4]1([Cl:3])[CH:2]=[CH:1][Si:11]([Cl:12])([Cl:13])[CH:6]1[Si:7]([Cl:8])([Cl:10])[Cl:9]
Reactant: Cl[SiH](Cl)C([SiH](Cl)Cl)[Si](Cl)(Cl)Cl
Reactant: C#C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: Cl[Si](Cl)(Cl)C1[Si](Cl)(Cl)C=C[Si]1(Cl)Cl
Yield: 50.3 %

Procedure:
Hydrosilation of acetylene with bis(dichlorosilyl)trichlorosilylmethane in the presence of Pd(PPh3)4. Into the same apparatus as described in Example 1 were added 1.01 g of bis(dichlorosilyl)trichlorosilylmethane, 0.103 g of Pd(PPh3)4, and 25 ml of dried benzene to form a mixture. Acetylene gas was blown into the mixture at a rate of 90 ml per minute for 3 hours. The resulting mixture was vacuum distilled at 67 Pa to yield a mixture comprising 0.89 g of 1,1,3,3-tetrachloro-2-trichlorosilyl-1,3-disilacyclopent-4-ene (TCD-GC area 50.3%).