Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][Si:16]([CH3:22])([CH3:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:11][C:10]=1[N+:23]([O-])=O)=[O:7])#[N:2].CCO>[Pd].C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[C:6]([NH:8][C:9]1[C:10]([NH2:23])=[CH:11][C:12]([O:15][Si:16]([CH3:21])([CH3:22])[C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][CH:14]=1)=[O:7])#[N:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(NC(=O)c2cccc(C#N)c2)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(C)[Si](C)(C)Oc1ccc(NC(=O)c2cccc(C#N)c2)c(N)c1
Reaction time: 12 h
Yield: 58.7 %

Procedure:
A mixture of N-(3-cyanobenzoyl)-2-nitro-4-(dimethyl-t-butylsiloxy)aniline (5.00 g, 12.6 mmol), 10% Pd/C (2.5 g), EtOH (160 mL), and THF (160 mL) was hydrogenated at 1 atm for 12 h. The reaction was filtered through diatomaceous earth with hot methanolic washes. The filtrate was concentrated and chromatographed (20% EtOAc/hexanes to 30% EtOAc/hexanes) to give the title compound as a solid (2.72 g, 59%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([N+:15]([O-])=O)[N:12]=[CH:11]1)([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([NH2:15])[N:12]=[CH:11]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCCn1cnc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NCCn1cnc(N)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
A flask containing compound 39.2 (400 mg, 1.56 mmol) and 10% (dry basis) palladium on activated carbon (−50% wet, Deguessa, 664 mg, ˜0.312 mmol) in MeOH (6.0 mL) was sealed with a septum and purged with nitrogen followed by hydrogen. The mixture was stirred under hydrogen (balloon pressure) at ambient temperature for 3 hours. After completion of the reaction, the mixture was filtered through a plug of celite and concentrated. The residue was dried under high-vacuum to yield 353 mg (quantitative) of [2-(4-amino-imidazol-1-yl)-ethyl]-carbamic acid tert-butyl ester (compound 39.3) as a solid, ES (+) MS m/e=227 (M+H+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[I:11].[CH3:12][O-].[Na+].CI>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:12])[N:6]=[C:5]2[I:11]
Reactant: C[O-]
Reactant: Brc1ccc2[nH]nc(I)c2c1
Agent: [Na+]
Solvent: CI
Solvent: CO
Product: Cn1nc(I)c2cc(Br)ccc21
Temperature: 65 °C
Reaction time: 0.5 h

Procedure:
A solution of 184.30 g of 5-bromo-3-iodo-1H-indazole [459133-66-5] n 2500 ml of methanol is admixed at 40° C. with 212 ml of a sodium methoxide solution (5.4M in methanol). 90 ml of methyl iodide are then added and the reaction mixture is heated to 65° C. After 30 minutes, the reaction mixture is cooled to room temperature, concentrated to approx. 1000 ml by evaporation, diluted with water and extracted with ethyl acetate (2×). The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a dark brown solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.68 (dichloromethane). Rt=4.94 (gradient I). As a by-product, the 5-bromo-3-iodo-2-methyl-2H-indazole regioisomer is also isolated as a red-orange solid. Rf=0.52 (dichloromethane). Rt=4.58 (gradient I).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:21]([F:24])([F:23])[F:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:25]([NH:29][S:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([NH:29][S:30]([C:33]1[CH:38]=[C:37]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:13]=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=4)[CH:11]=[C:10]([C:21]([F:22])([F:23])[F:24])[N:9]=3)[CH:3]=2)[CH:36]=[CH:35][CH:34]=1)(=[O:32])=[O:31])([CH3:28])([CH3:26])[CH3:27]
Reactant: FC(F)(F)c1cc(-c2ccc(Cl)cc2)nc(-c2cccc(Br)c2)n1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(Cl)cc4)cc(C(F)(F)F)n3)c2)c1

Procedure:
3′-[4-(4-Chloro-phenyl)-6-trifluoromethyl-pyrimidin-2-yl]-biphenyl-3-sulfonic acid tert-butylamide was prepared from 2-(3-bromo-phenyl)-4-(4-chloro-phenyl)-6-trifluoromethyl-pyrimidine (example E.4) (0.41 g, 1.0 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.31 g, 1.2 mmol) according to the general procedure VI. Obtained as white foam (0.47 g), which was subsequently deprotected.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[Br:12]N1C(=O)CCC1=O.C(Cl)(Cl)(Cl)Cl>O>[Br:12][CH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1
Reactant: Cc1ccc(CC(=O)O)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(O)Cc1ccc(CBr)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 50 g (0.33 mol) of 4-methylphenyl acetic acid, 62 g (0.35mol) of N-bromosuccinimide, 200 ml of carbon tetrachloride and 0.1 g of 2,2-azobis(isobutyronitrile) are placed in a 500 ml flask and heated to reflux with stirring for 4 hours. After the reaction mixture is cooled to room temperature, it is poured into 500 ml of water. The obtained precipitate is filtered off, and then washed with water. After drying under an atmosphere of reduced pressure, 55 g of a white powder are obtained (72%).
Reaction SMILES: [NH2:1][C:2]([C:4]1([CH2:17][CH2:18][C:19]#[N:20])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:3].C(O)(=O)C.[H][H]>[Pt]=O.Cl>[NH2:20][CH2:19][CH2:18][CH2:17][C:4]1([C:2]([NH2:1])=[O:3])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2
Reactant: [H][H]
Reactant: N#CCCC1(C(N)=O)c2ccccc2-c2ccccc21
Agent: O=[Pt]
Agent: Cl
Solvent: CC(=O)O
Product: NCCCC1(C(N)=O)c2ccccc2-c2ccccc21

Procedure:
A 3.3 g. portion of 9-aminocarbonyl-9-(2-cyanoethyl)fluorene from Example 27 was hydrogenated in 95 ml. of glacial acetic acid under 4 atmospheres of hydrogen pressure for two hours at 24° C. in the presence of 1.5 g. of platinum oxide catalyst. The reaction mixture was filtered to remove the catalyst and the solvent was removed by evaporation under reduced pressure. The product which remained was dissolved in ethyl acetate and then extracted into 1N hydrochloric acid. The aqueous acid layer was separated, made alkaline with 50% sodium hydroxide, and extracted several times with fresh ethyl acetate. The extracts were combined, washed with water and with brine, dried, and the solvent was removed by evaporation under reduced pressure to provide 2.3 g. of a white solid. The solid was dissolved in 1N hydrochloric acid, filtered, and diluted with water to 100 ml. The aqueous acid solution was lyophilized to provide a white solid, which when crystallized from methanol and ethyl acetate was identified as 1.0 g. of 9-(3-aminopropyl)-9-aminocarbonylfluorene. m.p. 198°-200° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH:11]=1)([O-:3])=[O:2].[Cl-].[Cl-].[Cl-].[Ce+3].[BH4-].[Na+]>CCO>[N+:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[C:10]1[CH2:15][CH2:14][CH2:13][CH:12]([OH:16])[CH:11]=1)([O-:3])=[O:2]
Reactant: O=C1C=C(c2ccncc2[N+](=O)[O-])CCC1
Agent: [BH4-]
Agent: [Ce+3]
Agent: [Cl-]
Solvent: CCO
Product: O=[N+]([O-])c1cnccc1C1=CC(O)CCC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 55.3 %

Procedure:
To a solution of 3-(3-nitropyridin-4-yl)cyclohex-2-en-1-one (1.9 g, 8.7 mmol) and cerium trichloride (4.2 g, 11 mmol) in EtOH (30 mL) at 0° C., sodium tetrahydroborate (0.43 g, 11 mmol) was slowly added. The reaction mixture was stirred at 0° C. for 2 h, then quenched with water (40 mL). After vacuum filtration, the residue was diluted with EtOAc. The aqueous layer was extracted three times with EtOAc. The combined organic layers were dried, filtered and concentrated under reduced pressure to give a crude product, which was further purified by silica gel column chromatography (eluting with 0-30% MeOH in EtOAc) to give the sub-title compound (1.06 g, 55%). LCMS calc. for C11H13NO3 (M+H)+: m/z=221.1. Found: 221.1.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].[CH2:12](O)[CH3:13].CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:12]([O:10][C:9](=[O:11])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])[CH3:13]
Reactant: CCO
Reactant: O=C(O)CCCCCCCBr
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)CCCCCCCBr
Reaction time: 12 h
Yield: 76.1 %

Procedure:
To a solution of 8-bromooctanoic acid (0.20 g, 0.89 mmol), DMAP (0.12 g, 0.99 mmol), and ethanol (0.05 g, 0.99 mmol) in methylene chloride (20 mL) was added EDCI (0.19 g, 0.99 mmol) at room temperature. After stirring for 12 h, the reaction mixture was washed with 1 N NaOH aqueous solution (15 mL) and water (30 mL), and the organic layer was dried over Na2SO4 and evaporated to give 8-bromooctanoic acid ethyl ester (0.17 g, 75%). This bromide reacted with 4-(3-adamantan-1-yl-ureido)butyric acid 822 in the same manner as that used for the preparation of 883 to provide 879 (0.19 g, 65%) as a solid: 1H NMR (CDCl3) 1.26 (3H, t, J=6.9 Hz), 1.32-1.35 (6H, m), 1.59-1.66 (10H, m), 1.82 (2H, quint, J=6.9 Hz), 1.94-1.97 (6H, m), 2.05-2.07 (3H, m), 2.28 (2H, t, J=6.9 Hz), 2.36 (2H, t, J=6.9 Hz), 3.16 (2H, q, J=6.9 Hz), 4.05-4.14 (5H, m), 4.31 (1H, s); LC-MS (ESI) m/z calcd for C25H42N2O5 [M+H]+ 451.31. found [M+H]+ 451.20; mp 58-59 C. Anal. (C25H42N2O5) C, H, N.
Reaction SMILES: [NH2:1][C:2]1[C:11]([C:12]#[N:13])=[C:10]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N:22]([CH3:24])[CH3:23])[CH:8]=2)[N:3]=1.[CH3:25][O:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=1>N1C=CC=CC=1>[CH3:25][O:26][C:27]1[CH:35]=[CH:34][C:30]([C:31]([N:1]([C:31](=[O:32])[C:30]2[CH:34]=[CH:35][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)[C:2]2[C:11]([C:12]#[N:13])=[C:10]([NH:14][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([N:22]([CH3:24])[CH3:23])[CH:8]=3)[N:3]=2)=[O:32])=[CH:29][CH:28]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: CN(C)c1ccc2nc(N)c(C#N)c(NCc3ccccc3)c2c1
Solvent: c1ccncc1
Product: COc1ccc(C(=O)N(C(=O)c2ccc(OC)cc2)c2nc3ccc(N(C)C)cc3c(NCc3ccccc3)c2C#N)cc1
Temperature: 0 °C

Procedure:
To the solution of 0.4 g of 2-amino-3-cyano-4-benzylamino-6-dimethylaminoquinoline in 2 mL of pyridine, 0.4 mL of 4-methoxybenzoyl chloride is added under stirring and cooling. The reaction mixture is stirred at 80° C. for 8 hours, then poured onto 5 mL of ice-water. The precipitated material is filtered off, washed twice with 3 mL of water. After drying 0.53 g of the title compound is obtained, m.p.: 156° C.
Reaction SMILES: C([O:9][C:10]1[C:11]([CH3:17])=[N:12][N:13]([CH3:16])[C:14]=1[CH3:15])(=O)C1C=CC=CC=1.[OH-].[Na+]>C(O)C>[CH3:16][N:13]1[C:14]([CH3:15])=[C:10]([OH:9])[C:11]([CH3:17])=[N:12]1
Reactant: Cc1nn(C)c(C)c1OC(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1nn(C)c(C)c1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.7 %

Procedure:
A flask was charged with 1,3,5-trimethyl-1H-pyrazol-4-yl benzoate (80 g, 347 mmol), and 500 mL ethanol. To the above mixture was added 3M NaOH (174 ml, 521 mmol) and stirred at ambient temperature for 2 hours. The ethanol was removed in vacuo and the aqueous layer was extracted with dichloromethane, ethyl acetate and dichloromethane:isopropyl alcohol (4:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford 1,3,5-trimethyl-1H-pyrazol-4-ol (34 g, 78% yield) as white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[CH2:13][CH2:14][NH:15][C:16]([O:18][C:19](C)([CH3:21])[CH3:20])=[O:17].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[CH2:13][CH2:14][NH:15][C:16]([O:18][CH:19]([CH3:20])[CH3:21])=[O:17]
Reactant: COC(=O)CCc1ccc(O)cc1CCNC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)CCc1ccc(O)cc1CCNC(=O)OC(C)C
Reaction time: 1 h
Yield: 66.4 %

Procedure:
A solution of 3-[2-(2-tert-butoxycarbonylamino-ethyl)-4-hydroxy-phenyl]-propionic acid methyl ester (282 mg, 0.876 mmol; Example 544, Step E) in CH2Cl2 (10 mL) at ambient temperature was treated with TFA (5.0 mL), stirred for 60 min, and concentrated. The residue in CH2Cl2 (10 mL) was treated with triethyl amine (2.0 mL) and iso-propyl chloroformate (0.97 mL, 1.0 M in toluene). The reaction mixture was stirred at ambient temperature for 16 h and concentrated. The crude material was purified using silica gel chromatography (50% EtOAc/hexanes) to yield the title compound (180 mg, 67%).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]=[N:11][C:12]1[CH:22]=[CH:21][C:15]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:14][CH:13]=1.[CH2:23]=[N:24]O.N1C(C)=CC=CC=1C.[N+](C1C=CC=CC=1)([O-])=O>[Cu]I>[C:23]([C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]=[N:11][C:12]1[CH:22]=[CH:21][C:15]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:14][CH:13]=1)#[N:24]
Reactant: CCN(CC)c1ccc(N=Nc2c(C)cc(Br)cc2Br)cc1
Reactant: C=NO
Agent: [Cu]I
Solvent: Cc1cccc(C)n1
Solvent: O=[N+]([O-])c1ccccc1
Product: CCN(CC)c1ccc(N=Nc2c(C)cc(Br)cc2C#N)cc1
Temperature: 95 °C
Yield: 15.1 %

Procedure:
A stirred mixture of 4-(2',4'-dibromo-6'-methylphenylazo)-N,N-diethylaniline (4.25 parts), copper (I) iodide (2.0 parts), formaldoxime trimer (1.75 parts), 2,6-lutidine (2.15 parts), and nitrobenzene (150 parts) was heated to 95° C. for 6 hours when thin layer chromatography showed reaction to be complete. The mixture was cooled, filtered and the nitrobenzene was removed by steam distillation. Crystallisation of the solid product from ethanol gave 4-(2'-cyano-4'-bromo-6'-methylphenylazo)-N,N-diethylaniline (Found: C, 58.2; H, 5.4; Br, 21.7; N, 15.2. C18H19BrN4 requires C, 58.2; H, 5.15; Br, 21.55; N, 15.1%).
Reaction SMILES: [CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:9]=[O:10])(=[O:5])=[O:4].[BH4-].[Na+]>C1COCC1>[CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH2:9][OH:10])(=[O:4])=[O:5]
Reactant: COc1ccc(C=O)cc1S(=O)(=O)N(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(CO)cc1S(=O)(=O)N(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 62.7 %

Procedure:
To a solution of OBS02049 (5.5 g, 21.21 mmol) in anhydrous THF (50 mL) was added sodium borohydride (0.88 g, 23.33 mmol). The mixture was stirred at room temperature for 4 h, quenched with water (CARE!!) and filtered through a Celite pad. The filtrate was concentrated in vacuo and re-dissolved in DCM (200 mL). The organic layer was washed with brine (2×200 mL), dried (Na2SO4) and filtered. Concentration in vacuo of the combined filtrates gave OBS02053 as a golden-yellow oil (3.26 g, 59%). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.36; 1H-NMR (270 MHz, CDCl3)=1.73 (1H, bs, OH), 2.97 (6H, s), 3.88 (3H, s), 4.62 (2H, s), 6.95 (1H, d, J=8.4), 7.23 (1H, dd, J=2.2, 8.4), 7.36 (1H, d, J=2.2). 3-(N,N-Dimethylsulfamoyl)-4-methoxybenzyl chloride (OBS02058)
Reaction SMILES: [CH2:1]([C:3]1[CH2:4][S:5][C@@H:6]2[CH:17]([NH:18][C:19](=[O:26])[CH2:20][C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)[C:16](=[O:27])[N:7]2[C:8]=1[C:9]([O:11]C(C)(C)C)=[O:10])[CH3:2].FC(F)(F)C(O)=O>>[CH2:1]([C:3]1[CH2:4][S:5][C@@H:6]2[CH:17]([NH:18][C:19](=[O:26])[CH2:20][C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)[C:16](=[O:27])[N:7]2[C:8]=1[C:9]([OH:11])=[O:10])[CH3:2]
Reactant: CCC1=C(C(=O)OC(C)(C)C)N2C(=O)C(NC(=O)Cc3cccs3)[C@H]2SC1
Solvent: O=C(O)C(F)(F)F
Product: CCC1=C(C(=O)O)N2C(=O)C(NC(=O)Cc3cccs3)[C@H]2SC1
Yield: 85.7 %

Procedure:
t-Butyl 3-ethyl-7-(2-thienylacetamido)-3-cephem-4-carboxylate (23 mg) was treated with trifluoracetic acid at room temperature for 1 hour. The excess trifluoroacetic acid was distilled off azeotropically with dry benzene to give the free acid (XVII) as a gum (17 mg) νmax (CHCl3) 1770, 1705, 1680 cm-1The minimum inhibitory concentrations of this compound required to inhibit the growth of five typical Gram-positive bacteria are tabulated below:
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([N+:19]([O-:21])=[O:20])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])=[C:7]([N+:19]([O-:21])=[O:20])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C#C[Si](C)(C)C
Reactant: CC(C)(C)c1ccc(OS(=O)(=O)C(F)(F)F)c([N+](=O)[O-])c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)c1ccc(C#C[Si](C)(C)C)c([N+](=O)[O-])c1
Temperature: 90 °C
Yield: 102.3 %

Procedure:
To Trifluoro-methanesulfonic acid 4-tert-butyl-2-nitro-phenyl ester (3.715 g, 11.35 mmol), dichlorobis(triphenylphosphine)palladium(II) (336 mg, 0.478 mmol), cuprous iodide (168 mg, 0.882 mmol) was added dimethylformamide (45 mL), triethylamine (1.72 g, 17.0 mmol), and trimethylsilylacetylene (2.229 g, 22.70 mmol). The resulting mixture was heated at 90° C. under an atmosphere of nitrogen for 15 minutes. This was partitioned between ethylacetate and water. The ethylacetate layer was washed with brine, dried over anhydrous MgSO4, concentrated in vacuo, and purified by flash chromatography with elution with CH2Cl2 to yield (4-tert-Butyl-2-nitro-phenylethynyl)-trimethyl-silane (3.193 g, 11.61 mmol).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[CH:17][CH:16]=2)[CH:7]=1.[CH3:27][N:28]1[CH:32]=[C:31]([S:33](Cl)(=[O:35])=[O:34])[N:30]=[CH:29]1>>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]([S:33]([C:31]2[N:30]=[CH:29][N:28]([CH3:27])[CH:32]=2)(=[O:35])=[O:34])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[CH:17][CH:16]=2)[CH:7]=1
Reactant: Cn1cnc(S(=O)(=O)Cl)c1
Reactant: COC(=O)CCc1cccc(CNCc2ccc(-c3nccs3)cc2)c1
Product: COC(=O)CCc1cccc(CN(Cc2ccc(-c3nccs3)cc2)S(=O)(=O)c2cn(C)cn2)c1

Procedure:
The title compound of Step B was prepared from 3-{3-[(4-thiazol-2-yl-benzylamino)-methyl]-phenyl}-propionic acid methyl ester, of Step A, and 1-methyl-1H-imidazole-4-sulfonyl chloride following the method described in Example 1, Step B. MS 511 (M+1).
Reaction SMILES: [OH:1][C@H:2]1[CH2:34][N:5]2[C:6](=[O:33])[C@@H:7]([NH:24][C:25]([C:27]3[CH:31]=[C:30]([CH3:32])[O:29][N:28]=3)=[O:26])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][C@@H:15]3[CH2:20][C@@:16]3([C:21]([OH:23])=[O:22])[NH:17][C:18](=[O:19])[C@@H:4]2[CH2:3]1.CC(C)([O-])C.[K+].Cl[C:42]1[C:43]([C:53]([F:56])([F:55])[F:54])=[N:44][C:45]2[C:50]([N:51]=1)=[CH:49][C:48]([F:52])=[CH:47][CH:46]=2>CS(C)=O.C1COCC1.CN(C)C=O.CC1CCCO1>[F:52][C:48]1[CH:49]=[C:50]2[C:45]([N:44]=[C:43]([C:53]([F:56])([F:55])[F:54])[C:42]([O:1][C@H:2]3[CH2:34][N:5]4[C:6](=[O:33])[C@@H:7]([NH:24][C:25]([C:27]5[CH:31]=[C:30]([CH3:32])[O:29][N:28]=5)=[O:26])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][C@@H:15]5[CH2:20][C@@:16]5([C:21]([OH:23])=[O:22])[NH:17][C:18](=[O:19])[C@@H:4]4[CH2:3]3)=[N:51]2)=[CH:46][CH:47]=1
Reactant: Fc1ccc2nc(C(F)(F)F)c(Cl)nc2c1
Reactant: Cc1cc(C(=O)N[C@H]2CCCCCC=C[C@@H]3C[C@@]3(C(=O)O)NC(=O)[C@@H]3C[C@@H](O)CN3C2=O)no1
Agent: CC(C)(C)[O-]
Agent: Cc1cc(C(=O)N[C@H]2CCCCC/C=C\[C@@H]3C[C@@]3(C(=O)O)NC(=O)[C@@H]3C[C@@H](O)CN3C2=O)no1
Agent: Cc1cc(C(=O)N[C@H]2CCCCC/C=C\[C@@H]3C[C@@]3(C(=O)O)NC(=O)[C@@H]3C[C@@H](Oc4nc5cc(F)ccc5nc4C(F)(F)F)CN3C2=O)no1
Solvent: CC1CCCO1
Solvent: CN(C)C=O
Solvent: CS(C)=O
Product: Cc1cc(C(=O)N[C@H]2CCCCCC=C[C@@H]3C[C@@]3(C(=O)O)NC(=O)[C@@H]3C[C@@H](Oc4nc5cc(F)ccc5nc4C(F)(F)F)CN3C2=O)no1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
(2R,6S,13aS,14aR,16aS,Z)-2-hydroxy-6-(5-methylisoxazole-3-carboxamido)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (15.2 g) was dissolved in dimethylsulfoxide (122 mL) and a solution of potassium tert-butoxide in THF (1.0M, 68.8 mL) was added dropwise, keeping the temperature to less than 30° C. The resulting solution was added to a solution of 3-chloro-6-fluoro-2-(trifluoromethyl)quinoxaline (8.3 g) in dimethylformamide (152 mL) over 30 min while at 0° C. After stiffing for 30 min, the reaction was diluted with 2-methyltetrahydrofuran (330 mL), quenched with phosphoric acid (29.1 g), and finally diluted with water (441 mL). The layers were separated and the lower layer was extracted with 2-methyltetrahydrofuran (165 mL). The organic layers were combined and extracted twice with water (330 mL each time). The organic layer was concentrated, chased with acetonitrile, and the final volume adjusted to about 900 mL with acetonitrile. The slurry was warmed to 80° C., cooled to 0° C., and filtered. The solid was rinsed with acetonitrile (100 mL) and dried under vacuum at 50° C. (19.5 g, 84% yield)
Reaction SMILES: C([N:20]1[CH:24]=[C:23]([C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[N:22]=[CH:21]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)=O>C(Cl)Cl>[NH:20]1[CH:24]=[C:23]([C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[N:22]=[CH:21]1
Reactant: c1ccc(C(c2ccccc2)(c2ccccc2)n2cnc(-c3cnco3)c2)cc1
Solvent: O=CO
Solvent: ClCCl
Product: c1nc(-c2cnco2)c[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 51.7 %

Procedure:
A solution of 5-(1-trityl-1H-imidazol-4-yl)oxazole (14.5 g, 38.4 mmol) was treated with a 90% aq. solution of formic acid (90 mL) and the mixture was stirred at RT for 18 h. The mixture was then diluted with DCM, and washed with H2O and sat. aq. solution of NaHCO3. The combined aqueous layers were washed with DCM and then concentrated in vacuo. The residue obtained was placed in a Soxlet apparatus and continuously extracted with DCM for 12 h. The organic phase was then concentrated and the crude product was crystallized in DCM to give the title compound (2.68 g). UPLC-MS: MS 136.1 (M+H+); UPLC rt 0.25 min.