Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]2[S:14][C:13]([NH2:15])=[N:12][CH:11]=2)=[CH:5][CH:4]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH2:23][C:24](O)=[O:25])[CH:17]=1.CCN(CC)CC.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([S:9][C:10]2[S:14][C:13]([NH:15][C:24](=[O:25])[CH2:23][CH2:22][C:18]3[CH:17]=[N:16][CH:21]=[CH:20][CH:19]=3)=[N:12][CH:11]=2)=[CH:7][CH:8]=1
Reactant: O=C(O)CCc1cccnc1
Reactant: COc1ccc(Sc2cnc(N)s2)cc1
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COc1ccc(Sc2cnc(NC(=O)CCc3cccnc3)s2)cc1
Yield: 74.8 %

Procedure:
A solution of 5-(4-methoxy-phenylsulfanyl)-thiazol-2-ylamine (70b, 3.0 g, 12.6 mmol), 3-pyridin-3-yl-propionic acid (2.30 g, 15.1 mmol), NEt3 (6.10 ml, 44.1 mmol), EDC (4.80 g, 25.2 mmol) and HOBt (3.40 g, 25.2 mmol) in DMF (150 mL) was stirred at room temperature for 18 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4(s), and concentrated under reduced pressure to give N-[5-(4-methoxy-phenylsulfanyl)-thiazol-2-yl]-3-pyridin-3-yl-propionamide (70, 3.50 g) in 75% yield: 1H NMR (500 MHz, DMSO) δ 8.45 (d, 1H), 8.39 (m, 1H), 7.64 (m, 2H), 7.29 (m, 3H), 6.92 (t, 2H), 3.73 (t, 3H), 2.90 (t, 2H), 2.77 (t, 2H).
Reaction SMILES: Cl.[CH2:2]([N:6]([S:16]([C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=1)(=[O:18])=[O:17])[C@H:7]([C:13]([OH:15])=[O:14])[CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH:3]([CH3:5])[CH3:4].[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([NH:38][C@H:39]([C:44](O)=[O:45])[CH2:40][C:41](=[O:43])[NH2:42])(=[O:37])=[O:36])=[CH:31][CH:30]=1>>[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([NH:38][C@H:39]([C:44]([NH:12][CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]([N:6]([S:16]([C:19]2[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:2][CH:3]([CH3:5])[CH3:4])[C:13]([OH:15])=[O:14])=[O:45])[CH2:40][C:41]([NH2:42])=[O:43])(=[O:36])=[O:37])=[CH:31][CH:30]=1
Reactant: CC(C)CN([C@@H](CCCCN)C(=O)O)S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Reactant: Cc1ccc(S(=O)(=O)N[C@@H](CC(N)=O)C(=O)O)cc1
Agent: Cl
Product: Cc1ccc(S(=O)(=O)N[C@@H](CC(N)=O)C(=O)NCCCC[C@@H](C(=O)O)N(CC(C)C)S(=O)(=O)c2ccc(N)cc2)cc1

Procedure:
The title compound was prepared from Nα-isobutyl-Nα-(4-nitrobenzenesulfonyl)-L-lysine hydrochloride (400 mg, 1.03 mmol, example 5, step C) as described in general procedure Bc using Nα-(4-methylbenzenesulfonyl)-L-asparagine (286 mg, 1.0 mmol) which was prepared in step A this example. The final product, Nα-isobutyl-Nα-(4-nitrobenzenesulfonyl)-Nε-[N′α-(4-methylbenzenesulfonyl)-L-asparagyl]-L-lysine was subsequently hydrogenolysed following the indications of general procedure E. Purification by HPLC gave the desired material (185 mg, 76%).
Reaction SMILES: [C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]1=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH3:16][O:17][C:18](=[O:29])[C@H:19]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[NH2:20].O.CO>C1(OC)C=CC=CC=1.[Pd]>[CH3:16][O:17][C:18](=[O:29])[CH:19]([NH:20][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1)[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1
Reactant: O=C1CCCCC1C(=O)c1cccnc1
Reactant: COC(=O)[C@@H](N)Cc1ccc(O)cc1
Agent: [Pd]
Solvent: COc1ccccc1
Solvent: CO
Solvent: O
Product: COC(=O)C(Cc1ccc(O)cc1)Nc1ccccc1C(=O)c1cccnc1
Temperature: 80 °C
Reaction time: 48 h
Yield: 38.9 %

Procedure:
To a mixture of 2-nicotinoylcyclohexanone (914.0 g, 0.45 mol), L-tyrosine methyl ester (78.0 g, 0.40 mol) in anisole (1000 ml) is added 5% palladium on carbon (20 g), then the mixture is heated to reflux for 2 h while the resulting water is removed by a Dean-Stark apparatus. The mixture is cooled to 80° C., and the Pd/C is filtered and washed with anisole (3×60 ml). The mixture is cooled to 40° C., hexane (1000 ml) is added and the mixture kept at −20° C. for 48 h. The solid is filtered and washed with hexane (5×200 ml) to yield the crude 2-((2-nicotinoylphenyl)amino)-3-(4-hydroxyphenyl)-propionic acid methyl ester. The crude product is mixed with 250 ml of methanol and is refluxed for 30 min. After cooled to 0° C., the product is filtered, washed with methanol (2×50 ml), and dried under a vacuum to give the title compound (58.6 g, 39.0%).
Reaction SMILES: [Li]CCCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[C:11]1(=[O:15])[CH2:14][CH2:13][CH2:12]1.[NH4+].[Cl-]>CCCCCC.CCOCC>[OH:15][C:11]1([C:7]2[S:6][CH:10]=[CH:9][N:8]=2)[CH2:14][CH2:13][CH2:12]1
Reactant: c1cscn1
Reactant: O=C1CCC1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Solvent: CCCCCC
Product: OC1(c2nccs2)CCC1
Reaction time: 1 h
Yield: 43.2 %

Procedure:
To a solution of n-BuLi (36 mL of a 2.5M solution in hexane, 90 mmol) in anhydrous ether (100 mL) at −78° C. was slowly added a solution of thiazole (6.35 g, 74.6 mmol) in anhydrous ether (60 mL). The resulting mixture was stirred for 1 h and then cyclobutanone (10.4 g, 148 mmol) in ether (20 mL) was added over 5 min. The mixture was stirred for 2 h at −78° C. and then sat. aq. NH4Cl was added and the phases were separated. The aqueous phase was extracted with ethyl acetate (3×) and the combined organics were washed with water, brine, dried (MgSO4) and concentrated. Flash chromatography of the residue (silica gel; hexane/ethyl acetate 4:1 to 7:3) provided 2-[(1-Hydroxy)cyclobutyl]thiazole (5 g).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[CH2:7][CH2:8][CH:9]([CH:11]1[CH2:16][CH:15]2[CH2:17][CH:12]1[CH:13]=[CH:14]2)[OH:10].[C:18](OC(=O)C)(=[O:20])[CH3:19].C(Cl)Cl.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.O>[C:18]([O:10][CH:9]([CH:11]1[CH2:16][CH:15]2[CH2:17][CH:12]1[CH:13]=[CH:14]2)[CH2:8][CH2:7][CH:2]1[O:3][CH2:4][CH2:5][CH2:6][O:1]1)(=[O:20])[CH3:19]
Reactant: OC(CCC1OCCCO1)C1CC2C=CC1C2
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CC(=O)OC(CCC1OCCCO1)C1CC2C=CC1C2
Yield: 95.8 %

Procedure:
To a mixture of 15.0 g of 3-(1,3-dioxan-2-yl)-1-(5-norbornen-2-yl)-1-propanol, 9.6 g of acetic anhydride, 100 mg of 4-dimethylaminopyridine and 50 ml of methylene chloride, 10.2 g of triethylamine was added dropwise over 30 minutes at 20° C. Stirring was continued for 30 minutes whereupon 10 g of water was added to stop reaction. Stirring was continued for a further 30 minutes whereupon water was added to the reaction solution, which was extracted with hexane. The organic layer was successively washed with water and saturated sodium chloride water, dried over anhydrous sodium sulfate, and concentrated in vacuum. It was further purified by vacuum distillation, obtaining 16.9 g of 3-(1,3-dioxan-2-yl)-1-(5-norbornen-2-yl)-1-propyl acetate (boiling point 125° C./53 Pa, yield 96%).
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3.[NH2:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][C:22]1=[O:26]>>[O:26]=[C:22]1[CH2:23][CH2:24][CH2:25][N:21]1[CH2:20][CH2:19][CH2:18][NH:17][C:2]1[CH:16]=[CH:15][C:5]2[C:6](=[O:14])[NH:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[CH:10][N:9]=3
Reactant: NCCCN1CCCC1=O
Reactant: O=c1[nH]c2ncccc2c2cc(Cl)ccc12
Product: O=C1CCCN1CCCNc1ccc2c(=O)[nH]c3ncccc3c2c1
Yield: 6.5 %

Procedure:
The title compound was synthesized according to the procedure described for the preparation of Example 456 using 6 (160 mg, 0.69 mmol) and 1-(3-aminopropyl)pyrrolidin-2-one (395 mg, 2.78 mmol) to provide 479 (15 mg, 7% yield) as a white powder. LC-MS (M+H=337, obsd.=337). 1H NMR (400 MHz, DMSO-D6) δ 11.47 (s, 1H), 8.67 (d, J=7.7, 1H), 8.43 (d, J=3.2, 1H), 7.99 (d, J=8.8, 1H), 7.19 (m, 2H), 6.90 (dd, J=1.9, 8.7, 1H), 6.64 (s, 1H), 3.27 (m, 4H), 3.24 (s, 2H), 2.23 (t, J=8.0, 2H), 1.87 (m, 2H), 1.73 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:38])=[N:4][O:5][C:6]=1[N:7]([CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37])[S:8]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[S:13][C:12]=1[CH:20](O)[C:21]1[C:26]([O:27][CH3:28])=[CH:25][CH:24]=[CH:23][C:22]=1[O:29][CH3:30])(=[O:10])=[O:9].C([SiH](CC)CC)C.B(F)(F)F.CCOCC>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH3:38])=[N:4][O:5][C:6]=1[N:7]([CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37])[S:8]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[CH:17][CH:18]=2)[S:13][C:12]=1[CH2:20][C:21]1[C:26]([O:27][CH3:28])=[CH:25][CH:24]=[CH:23][C:22]=1[O:29][CH3:30])(=[O:9])=[O:10]
Reactant: COCCOCN(c1onc(C)c1Cl)S(=O)(=O)c1c(C(O)c2c(OC)cccc2OC)sc2ncccc12
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: COCCOCN(c1onc(C)c1Cl)S(=O)(=O)c1c(Cc2c(OC)cccc2OC)sc2ncccc12
Yield: 88 %

Procedure:
The title compound was prepared by the method of Example 5(A) using N-(4-chloro-3-methyl-5-isoxazolyl)-N-(methoxyethoxymethyl)-2-(α-hydroxy-2,6-dimethoxybenzyl)thieno[2,3-b]pyridine-3-sulfonamide (0.13 g, 0.22 mmoles), CH2Cl2 (5 ml), triethylsilane (0.35 ml, 2.2 mmoles) and boron trifluoride etherate (0.16 ml, 1.3 mmoles). Flash chromatography (40% EtOAc/hexanes) provided 0.11 g (85%) of the title compound as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:34])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[C:11]([NH2:33])=[CH:12][C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:15]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[C:14]=2[CH:32]=1.[F:35][C:36]1[CH:41]=[CH:40][C:39]([S:42](Cl)(=[O:44])=[O:43])=[CH:38][CH:37]=1>>[CH3:1][O:2][C:3](=[O:34])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[C:11]([NH:33][S:42]([C:39]2[CH:40]=[CH:41][C:36]([F:35])=[CH:37][CH:38]=2)(=[O:44])=[O:43])=[CH:12][C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:15]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[C:14]=2[CH:32]=1
Reactant: COC(=O)CCCCCOc1cc2c(cc1N)nc(-c1ccccc1)n2-c1ccc(OC)cc1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Product: COC(=O)CCCCCOc1cc2c(cc1NS(=O)(=O)c1ccc(F)cc1)nc(-c1ccccc1)n2-c1ccc(OC)cc1

Procedure:
6-[(5-Amino-1-(4-methoxyphenyl)-2-phenyl-1H-benzimidazol-6-yl)oxy]hexanoic acid methyl ester was reacted with 4-fluorobenzenesulfonic acid chloride according to general operating instructions 13.
Reaction SMILES: [NH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)[NH2:2].Br[CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([CH3:22])=[N:20][CH:21]=1>C(N(CC)CC)C>[CH3:22][C:19]1[N:20]=[CH:21][C:16]([CH2:15][CH2:14][N:1]([C:3]2[CH:4]=[CH:5][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:11][CH:12]=2)[NH2:2])=[CH:17][CH:18]=1
Reactant: Cc1ccc(CCBr)cn1
Reactant: COC(=O)c1ccc(NN)cc1
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(N(N)CCc2ccc(C)nc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 28 %

Procedure:
Methyl 4-hydrazinylbenzoate (1 g, 0.005 moles) and 5-(2-bromoethyl)-2-methylpyridine (1 g, 0.005 moles) was taken up in triethylamine (2.1 mL) and stirred at RT for 1 hr. The reaction was heated at 100° C., overnight. LCMS analysis of the reaction mixtures shows the formation of product. The reaction mixture was concentrated, water (20 mL) was added to the reaction mixture and the mixture extracted with ethyl acetate. The crude product was dissolved in ethyl acetate and purified by column chromatography using neutral alumina, using 100% ethyl acetate as the eluent. After chromatography 400 mg of Methyl 4-(1-(2-(6-methylpyridin-3-yl)ethyl)hydrazinyl)benzoate was obtained, 28.5% yield.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C:9](=[O:25])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:24])[CH2:6]1)(=[O:3])[CH3:2]>CCO.[Pd]>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[CH:7]([CH2:8][C:9](=[O:25])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:24])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC(=O)[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C1
Agent: [Pd]
Solvent: CCO
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(CC(=O)[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C1
Reaction time: 2 h
Yield: 59.3 %

Procedure:
A mixture of 3β-acetoxyandrost-5-ene-7,17-dione (7.97 g) and 10% Pd/C (0.80 g) in EtOH (0.5 L) was stirred under H2 at atm pressure for 2 h. The mixture was filtered through Celite and the filtrate evaporated to dryness. The crude product was crystallized from Et2O to give 3β-acetoxyandrostane-7,17-dione (4.75 g, 60%) 1H-NMR (300 MHz, acetone-d6, ppm from TMS): δ 4.57 (1H, m), 2.66-0.96 (20H, m), 1.96 (3H, s), 1.05 (3H, s), 0.77 (3H, s).
Reaction SMILES: C(OC([N:8]1[CH2:22][C:11]2=[C:12]3[N:17]([N:18]=[C:10]2[CH2:9]1)[C:16]([CH3:19])=[C:15]([F:20])[C:14]([CH3:21])=[N:13]3)=O)(C)(C)C.[ClH:23]>C(Cl)Cl>[ClH:23].[F:20][C:15]1[C:14]([CH3:21])=[N:13][C:12]2[N:17]([N:18]=[C:10]3[CH2:9][NH:8][CH2:22][C:11]3=2)[C:16]=1[CH3:19]
Reactant: Cc1nc2c3c(nn2c(C)c1F)CN(C(=O)OC(C)(C)C)C3
Agent: Cl
Solvent: ClCCl
Product: Cc1nc2c3c(nn2c(C)c1F)CNC3
Temperature: 25 °C
Reaction time: 18 h
Yield: 74.2 %

Procedure:
To a solution of 6-fluoro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carboxylic acid tert-butyl ester (3.39 g; 11.1 mmol; 1 eq.) in DCM (20 mL) was added 2M HCl (10 mL; 20 mmol; 1.81 eq.) and the resulting mixture was stirred at room temperature for 18 hours than concentrated in vacuo. The residue was triturated in DCM and the precipitate was filtered off to afford the title compound (2 g, 80%) as a white solid. HPLC (max plot) 99.6%; Rt 1.23 min. UPLC/MS: (MS+) 207.1 ([M+H]+).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:13][CH2:14][C:15]([OH:17])=[O:16])=[C:8]([CH3:12])[C:9]=2[CH3:11])[CH:4]([CH3:18])[CH:3]1[CH2:19][CH3:20].[Cl:21]Cl>Cl.C(O)(=O)C>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:13][CH2:14][C:15]([OH:17])=[O:16])=[C:8]([CH3:12])[C:9]=2[CH3:11])[CH:4]([CH3:18])[C:3]1([CH2:19][CH3:20])[Cl:21]
Reactant: CCC1C(=O)c2c(cc(OCC(=O)O)c(C)c2C)C1C
Reactant: ClCl
Agent: Cl
Solvent: CC(=O)O
Product: CCC1(Cl)C(=O)c2c(cc(OCC(=O)O)c(C)c2C)C1C

Procedure:
By following substantially the procedure described in Example 12, Step B, using as the reactants (1-oxo-2-ethyl-3,6,7-trimethyl-5-indanyloxy)acetic acid (2.76 g., 0.01 mole), glacial acetic acid (50 ml.), chlorine (710 mg., 0.01 mole) and concentrated hydrochloric acid (1 drop) there is obtained (1-oxo-2-ethyl-2-chloro-3,6,7-trimethyl-5-indanyloxy)acetic acid.
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][O:7][C:8]1[CH:21]=[CH:20][C:11]([C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:13])=[CH:10][CH:9]=1.C(C1C(O)=CC(C(C)(C)C)=C(C)C=1)(C)(C)C.[CH2:38]([NH:40][C:41](=[O:44])[CH:42]=[CH2:43])O>>[C:41]([NH:40][CH2:38][C:9]1[CH:10]=[C:11]([CH:20]=[CH:21][C:8]=1[O:7][CH3:6])[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:13])(=[O:44])[CH:42]=[CH2:43]
Reactant: COc1ccc(C(=O)c2ccccc2)cc1
Reactant: C=CC(=O)NCO
Agent: Cc1cc(C(C)(C)C)c(O)cc1C(C)(C)C
Agent: O=S(=O)(O)O
Product: C=CC(=O)NCc1cc(C(=O)c2ccccc2)ccc1OC

Procedure:
A mixture of 1000 g of sulfuric acid, 175.6 g (0.825 mole) of 4-methoxybenzophenone, 0.5 g of 2,5-di-tert-butyl-p-cresol and 86 g (0.851 mole) of N-methylolacrylamide was reacted for 5 hours at 25° C. and then hydrolyzed on ice.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:11]([Cl:12])=[CH:10][C:9](=[O:13])[N:8]([CH3:14])[CH:7]=1)=[O:5])C.C1COCC1.[Li+].[OH-].Cl>CO>[Cl:12][C:11]1[C:6]([C:4]([OH:5])=[O:3])=[CH:7][N:8]([CH3:14])[C:9](=[O:13])[CH:10]=1
Reactant: CCOC(=O)c1cn(C)c(=O)cc1Cl
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cn1cc(C(=O)O)c(Cl)cc1=O
Reaction time: 0.5 h
Yield: 91 %

Procedure:
To a solution of 4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester (0.925 g, 4.29 mmol) in a 4:1 mixture of THF:MeOH (20 mL) was added a 1 M solution of LiOH (8.6 mL). After stirring for 30 minutes, the reaction mixture was acidified to pH 1 with 10% HCl and extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure to give 0.732 g (91%) clean desired product.
Reaction SMILES: [OH:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([SH:11])[N:8]2[N:12]=[C:13]([CH2:15][OH:16])[N:14]=[C:7]2[N:6]=1)=[O:4].CC(O[CH2:21][C:22]1[CH2:31][S:30][C@@H:25]2[C@H:26]([NH2:29])[C:27](=[O:28])[N:24]2[C:23]=1[C:32]([OH:34])=[O:33])=O.B(F)(F)F.CCOCC.ClCCl>S1(CCCC1)(=O)=O.ClCCl>[NH2:29][C@@H:26]1[C:27](=[O:28])[N:24]2[C@@H:25]1[S:30][CH2:31][C:22]([CH2:21][S:11][C:9]1[N:8]3[N:12]=[C:13]([CH2:15][OH:16])[N:14]=[C:7]3[N:6]=[C:5]([C:3](=[O:4])[NH:2][OH:1])[CH:10]=1)=[C:23]2[C:32]([OH:34])=[O:33]
Reactant: O=C(NO)c1cc(S)n2nc(CO)nc2n1
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Solvent: O=S1(=O)CCCC1
Product: N[C@@H]1C(=O)N2C(C(=O)O)=C(CSc3cc(C(=O)NO)nc4nc(CO)nn34)CS[C@H]12
Temperature: 0 °C
Reaction time: 20 h
Yield: 40.4 %

Procedure:
N-Hydroxy-2-(hydroxymethyl)-7-mercapto-s-triazolo[1,5-a]pyrimidine-5-carboxamide (190 mg) (0.79 mmol) and 193 mg (0.71 mmol) of 7-amino-cephalosporanic acid are suspended in 20 ml of sulpholane/dichloromethane (1:1 v/v). 4.2 ml of boron trifluoride diethyl etherate are added thereto at 0° C. The mixture is stirred at 0° C. for 2 hours and at room temperature for 20 hours. 80 ml of dichloromethane are added. The precipitated material is separated and dissolved in water. The mixture is adjusted to pH 4 by the addition of saturated aqueous sodium hydrogen carbonate solution. The precipitated product is filtered off under suction and washed in sequence with water, ethanol and diethyl ether. There are obtained 130 mg of (6R,7R)-7-amino-3-[[[5-(hydroxycarbamoyl)-2-(hydroxymethyl)-s-triazolo[1,5-a]pyrimidin-7-yl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid as a beige powder.
Reaction SMILES: C([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[C:18](C(OCC)=O)=[C:17]([C:24]2[N:25]=[N:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][CH:29]=2)[C:16]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:15]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)[N:14]=1)=O)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[CH2:33]([O:32][C:30]([C:27]1[N:26]=[N:25][C:24]([C:17]2[C:18]3[C:6](=[O:5])[N:8]4[CH:9]([C:13]=3[N:14]=[C:15]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[C:16]=2[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:10][CH2:11][CH2:12]4)=[CH:29][CH:28]=1)=[O:31])[CH3:34]
Reactant: CCOC(=O)c1ccc(-c2c(C(=O)OCC)c(Cc3ccc(F)cc3)nc([C@@H]3CCCN3C(=O)OC(C)(C)C)c2C(=O)OCC)nn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1ccc(-c2c(C(=O)OCC)c(Cc3ccc(F)cc3)nc3c2C(=O)N2CCCC32)nn1
Reaction time: 1 h
Yield: 71.9 %

Procedure:
Diethyl 2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-4-[6-(ethoxycarbonyl)-3-pyridazinyl]-6-(4-fluorobenzyl)-3,5-pyridinedicarboxylate (E, 260 mg crude) was first dissolved in 15 ml mixture of trifluoroacetic acid and dichloromethane (2 to 1 ratio) and stirred for 1 hour followed by the removal of the solvent. To this residue, 15 ml of mixture of triethylamine and dichloromethane (1 to 2 ratio) was added and the mixture was stirred for 2 hours. Upon removal of the solvent, the residue was purified by flash chromatography. 145 mg solid was obtained. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, 1H), 8.03 (d, 1H), 7.18 (t, 2H), 6.90 (t, 2H), 4.75 (m, 1H), 4.54 (q, 2H), 4.42 (m, 2H), 3.96 (q, 2H), 3.65 (m, 1H), 3.38 (m, 1H), 2.45 (m, 1H), 2.32 (m, 2H), 1.45 (t, 3H), 1.40 (m, 1H), 0.92 (t, 3H) ppm. ESI-MS m/z 505 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([CH3:21])[C:5]2[C:11](=S)[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]=2[N:7]=1.[Si:22]([O:29][NH2:30])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>[Hg](OC(C)=O)OC(C)=O.C1(C)C=CC=CC=1>[Si:22]([O:29]/[N:30]=[C:11]1\[NH:10][C@@H:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[Br:20])[CH2:8][C:6]2[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:21])[C:5]\1=2)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)ON
Reactant: Cc1nc(N)nc2c1C(=S)N[C@@H](c1ccc(F)cc1Br)C2
Agent: CC(=O)O[Hg]OC(C)=O
Solvent: Cc1ccccc1
Product: Cc1nc(N)nc2c1/C(=N/O[Si](C)(C)C(C)(C)C)N[C@@H](c1ccc(F)cc1Br)C2
Temperature: 100 °C
Yield: 79.9 %

Procedure:
A mixture of (R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-5(6H)-thione (366 mg, 1.0 mmol), O-(tert-butyldimethylsilyl)hydroxylamine (588 mg, 4.0 mmol), Hg(OAc)2 (640 mg, 2.0 mmol) and toluene (5 mL) was heated at 100° C. for 2 h. The mixture was cooled to r.t. and filtered through celite. Filtrate concentrated and the resulting oily residue was triturated with dry methanol to afford a pale yellow solid. Filtered and dried to afford ((R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-tert-butyldimethylsilyloxime (384 mg, 80%) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.22 (s, 3H), 0.23 (s, 3H) 0.97 (s, 9H) 2.70 (s, 3H) 2.91 (dd, J=16.42, 8.08 Hz, 1H) 3.19 (ddd, J=16.36, 4.86, 1.26 Hz, 1H) 4.99 (ddd, J=7.77, 5.12, 2.02 Hz, 1H) 7.05 (td, J=8.27, 2.65 Hz, 1H) 7.33 (dd, J=8.08, 2.78 Hz, 1H) 7.39 (dd, J=8.72, 5.94 Hz, 1H). MS (ES) [M+H] calculated for C20H28BrFN5OSi, 480.12. found 480.30.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([CH3:12])[Cl:11].C[SiH](C)N(C)C(=O)C>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:10]([CH3:12])([CH3:9])[Cl:11])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: C[SiH](C)Cl
Agent: [Pt]
Agent: CC(=O)N(C)[SiH](C)C
Solvent: Cc1ccccc1
Product: C[Si](C)(Cl)CCc1ccccc1
Yield: 4.4 %

Procedure:
Reaction between styrene and dimethylchlorosilane with platinum catalyst in the presence of N-dimethylsilyl-N-methylacetamide. 526 mg Styrene and 408 mg dimethylchlorosilane were introduced into a glass tube, and 1 mg of N-dimethylsilyl-N-methylacetamide was added. 2.5 mg Of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) were added. The tube was sealed with Teflon tape and a rubber septum and then placed in a 50° C. oil bath where it was heated for 30 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 4.8% and a phenethyldimethylchlorosilane yield of 4.4%. The ratio between the phenethyldimethylchlorosilane and (α-methylbenzyl)dimethylchlorosilane was 15:1.
Reaction SMILES: [O:1]=[S:2]1(=[O:15])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH2:16]([O:29][CH2:30][CH:31]1[O:33][CH2:32]1)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27]>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C>[O:15]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:32][CH:31]([OH:33])[CH2:30][O:29][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])=[CH:12][CH:13]=2)[CH2:6][CH2:7]1
Reactant: CC(C)CCCCCCCCCCOCC1CO1
Reactant: O=S1(=O)CCN(c2ccc(O)cc2)CC1
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Product: CC(C)CCCCCCCCCCOCC(O)COc1ccc(N2CCS(=O)(=O)CC2)cc1
Yield: 49.6 %

Procedure:
4-(1,1-dioxo-thiomorpholin-4-yl)phenol (2.3 g, 10 mmol), isotridecylglycidyl ether (2.6 g, 10 mmol) and ethyltriphenylphosphonium bromide (0.1 g) are reacted and purified as described for compound 102 to afford a light yellow liquid 2.4 g (50%).