Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:37])[C@H:4]([CH3:36])[NH:5][C:6](=[O:35])[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:18]2[C:19](=[O:34])[NH:20][C:21](=[O:33])[C:22]=2[C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([CH3:32])[CH:24]=2)=[CH:10]1.[OH-].[Li+]>O1CCOCC1.O>[CH3:32][N:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:23]([C:22]2[C:21](=[O:33])[NH:20][C:19](=[O:34])[C:18]=2[C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:9]([CH2:8][CH2:7][C:6]([NH:5][C@H:4]([C:3]([OH:37])=[O:2])[CH3:36])=[O:35])[CH:10]=2)=[CH:24]1
Reactant: COC(=O)[C@H](C)NC(=O)CCn1cc(C2=C(c3cn(C)c4ccccc34)C(=O)NC2=O)c2ccccc21
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: C[C@H](NC(=O)CCn1cc(C2=C(c3cn(C)c4ccccc34)C(=O)NC2=O)c2ccccc21)C(=O)O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
3-[3-[4-(1-Methylindol-3-yl)-1H-pyrrole-2,5-dion-3-yl)-indol-1-yl]-propionyl-L-alanine methyl ester 100 mg (0.2 mmol) are dissolved in a mixture of 4 mL dioxane and 1 mL of water, mixed with 36 mg (1.5 mmol) lithium hydroxide, and stirred for 18 hours at ambient temperature. The solvent is subsequently distilled off in a vacuum and the residue is taken up in 30 mL ethylacetate, washed with 1N hydrochloric acid, and dried over anhydrous sodium sulphate. The solvent is then distilled off in a vacuum and the residue separated by thick layer chromatography (silica gel, dichloromethane/methanol saturated with ammonia=90:10%). The product is separated with the first polar fraction, extracted, freed from solvent, and stirred up with a mixture of dichloromethane and diisopropyl ether (1:1). There are obtained 65 mg (67% of theory) of the desired product;
Reaction SMILES: C([C:3]1([C:17]2([OH:28])[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]2)[CH2:8][CH2:7][CH2:6][CH:5]([CH3:9])[N:4]1[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)#N.C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[OH:28][C:17]1([CH:3]2[CH2:8][CH2:7][CH2:6][CH:5]([CH3:9])[N:4]2[CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:18]1
Reactant: CC1CCCC(C#N)(C2(O)CN(C(=O)OC(C)(C)C)C2)N1Cc1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: CC1CCCC(C2(O)CN(C(=O)OC(C)(C)C)C2)N1Cc1ccccc1
Temperature: 70 °C
Reaction time: 8 h
Yield: 35.4 %

Procedure:
To a stirred solution of 1,1-dimethylethyl 3-[2-cyano-6-methyl-1-(phenylmethyl)piperidin-2-yl]-3-hydroxyazetidine-1-carboxylate (180 mg, 0.47 mmol) in ethanol (1 mL) was added acetic acid (53.5 μL, 0.94 mmol) followed by sodium cyanoborohydride (58.7 mg, 0.94 mmol) and the reaction mixture stirred at 70° C. overnight. After cooling to room temperature the suspension was filtered through celite and the solid washed with additional ethanol. The filtrate was concentrated in vacuo and taken up in ethyl acetate (30 mL). The organic layer was washed with 2 M sodium hydroxide solution. The sodium hydroxide layer was separated and washed with ethyl acetate (10 mL). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 1,1-dimethylethyl 3-hydroxy-3-[6-methyl-1-(phenylmethyl)piperidin-2-yl]azetidine-1-carboxylate as yellow oil (60 mg, 36% yield). Crude product was used further without purification. 1H NMR (400 MHz, CDCl3): 7.22-7.35 (m, 5H), 4.08 (d, 1H), 3.85-3.96 (m, 3H), 3.57 (d, 1H), 3.33-3.36 (m, 1H), 2.91-3.06 (m, 2H), 1.63-1.70 (m, 4H), 1.44 (s, 9H), 1.23 (d, 3H), 1.05 (d, 2H); MS (EI) for C21H32N2O3: 361 (MH+).
Reaction SMILES: [CH:1](=[CH:10][C:11]([OH:13])=O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(Cl)([Cl:16])=O>CCCCCC>[CH:1](=[CH:10][C:11]([Cl:16])=[O:13])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=C(O)C=CC=Cc1ccccc1
Reactant: O=S(Cl)Cl
Solvent: CCCCCC
Product: O=C(Cl)C=CC=Cc1ccccc1
Yield: 77.9 %

Procedure:
Preparation of C6H5—CH═CH—CH═CH—CO2PEG-OCH2CH(OC2H5)2: A solution of cinnamylideneacetic acid (1.7 g, 0.01 moles) and thionyl chloride (3 ml, 0.04 moles) in 50 ml of hexane were refluxed under N2 for 4 h, then filtered to remove a small amount of dark solid and the filtrate evaporated under vacuum. The residue was dried under vacuum overnight at room temperature to obtain 1.5 g of cinnamylideneacetyl chloride as a yellow solid, m.p. 51-52° C.)
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[NH2:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]2[S:18][C:17]3[N:19]=[CH:20][CH:21]=[N:22][C:16]=3[N:15]([CH2:23][O:24][CH3:25])[C:14]=2[CH:26]=1.C(OCC)C>ClCCl>[CH3:25][O:24][CH2:23][N:15]1[C:14]2[CH:26]=[C:10]([CH2:9][NH:8][C:5](=[O:7])[CH3:6])[CH:11]=[CH:12][C:13]=2[S:18][C:17]2[N:19]=[CH:20][CH:21]=[N:22][C:16]1=2
Reactant: COCN1c2cc(CN)ccc2Sc2nccnc21
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: CCOCC
Product: COCN1c2cc(CNC(C)=O)ccc2Sc2nccnc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1 ml of acetic anhydride was added to 5 ml of a solution of 350 mg of 8-aminomethyl-10-methoxymethyl-10H-pyrazino[2,3-b][1,4]benzothiazine in dichloromethane and the resulting mixture was stirred at room temperature for 2 hours. After adding diethyl ether, the precipitate thus formed was taken up by filtration to thereby give 350 mg of the title compound as yellow crystals.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([C:20]2[CH:25]=[CH:24][C:23]([S:26](=[O:33])(=[O:32])[N:27]=[CH:28][N:29]([CH3:31])[CH3:30])=[CH:22][CH:21]=2)=[C:5]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[CH3:34][NH:35][CH3:36]>C1C=CC=CC=1>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]2[S:6][C:5]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:4]([C:20]3[CH:21]=[CH:22][C:23]([S:26](=[O:33])(=[O:32])[N:27]=[CH:28][N:29]([CH3:31])[CH3:30])=[CH:24][CH:25]=3)[C:3]=2[CH2:2][N:35]([CH3:36])[CH3:34])=[CH:13][CH:12]=1
Reactant: CCOC(=O)c1sc(-c2ccc(Cl)cc2)c(CBr)c1-c1ccc(S(=O)(=O)N=CN(C)C)cc1
Reactant: CNC
Solvent: c1ccccc1
Product: CCOC(=O)c1sc(-c2ccc(Cl)cc2)c(CN(C)C)c1-c1ccc(S(=O)(=O)N=CN(C)C)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 53.4 %

Procedure:
To a stirred suspension of Ethyl 4-(bromomethyl)-5-(4-chlorophenyl)-3-(4-(N-((dimethylamino)methylene)sulfamoyl)phenyl)thiophene-2-carboxylate (compound 35b, 2.20 g, 3.86 mmol) in benzene (30 ml), dimethyl amine (0.69 g, 7.6 ml 2M solution in THF, 15.4 mmol) was added at 0° C. in a drop wise manner. The reaction mixture was then stirred at room temperature (about 25° C.) for 16 hr. The progress of the reaction was monitored by TLC. The reaction mixture was then concentrated to obtain the crude product as semi-solid (2.38 g). The crude product so obtained was purified by column chromatography over silica gel (100-200 mesh) using 1.2 methanol in DCM as an eluent to obtain the title compound (1.1 g, 53.39%).
Reaction SMILES: Cl[C:2]1[C:3]2[S:18][C:17]([NH2:19])=[N:16][C:4]=2[N:5]=[C:6]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=1.[NH2:20][C@H:21]([CH3:24])[CH2:22][OH:23]>>[NH2:19][C:17]1[S:18][C:3]2[C:2]([NH:20][C@H:21]([CH3:24])[CH2:22][OH:23])=[N:7][C:6]([S:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[N:5][C:4]=2[N:16]=1
Reactant: Nc1nc2nc(SCc3ccccc3)nc(Cl)c2s1
Reactant: C[C@@H](N)CO
Product: C[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(N)sc12

Procedure:
Prepared by the method of example 2 step a), using the product of example 1 step c) and (R)-(−)-2-amino-1-propanol.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[C:18]1[C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:20][C:21]2[C:26]([N:27]=1)=[CH:25][C:24]([C:28]([O:30][CH3:31])=[O:29])=[CH:23][CH:22]=2.CCN(C(C)C)C(C)C>CN(C=O)C>[C:32]1([C:19]2[C:18]([N:12]3[CH2:11][CH2:10][CH:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=4)[CH2:14][CH2:13]3)=[N:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=3)[N:20]=2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: FC(F)(F)c1ccc(C2CCNCC2)cc1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(N3CCC(c4ccc(C(F)(F)F)cc4)CC3)nc2c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 83.2 %

Procedure:
A solution of 4-(4-(trifluoromethyl)phenyl)piperidine (200 mg, 0.87 mmol, 2.00 equiv), methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), and DIEA (169 mg, 1.31 mmol, 3.00 equiv) in DMF (10 mL) was placed in a 20-mL sealed tube and stirred overnight at 100° C. in an oil bath. The resulting mixture was concentrated under vacuum and purified via silica gel column (ethyl acetate/petroleum ether (1:20)), yielding 180 mg (84%) of methyl 2-phenyl-3-(4-(4-(trifluoromethyl)phenyl)piperidin-1-yl)quinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:7]([C:8]([OH:10])=[O:9])[C:6]([NH2:12])=[CH:5][CH:4]=1.[C:13](OC(=O)C)(=O)[CH3:14]>>[CH3:13][C:14]1[O:9][C:8](=[O:10])[C:7]2[CH:11]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[N:12]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(N)c(C(=O)O)c1
Product: COc1ccc2nc(C)oc(=O)c2c1
Yield: 71 %

Procedure:
A solution of 5-methoxyanthranilic acid (Lancaster) (41.8 g, 0.25 mol) was refluxed in acetic anhydride (230 ml) for 3.5 h before being concentrated under reduced pressure. The crude compound was then concentrated twice in the presence of toluene before being filtered and washed twice with ether to yield to the title compound (33.7 g, 71% yield) as a brown solid; LC/MS (Method D): m/z 192 [M+H]+, Rt 1.69 min.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([NH2:9])=[C:4]([I:10])[CH:3]=1.[N:11]([O-])=O.[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[C:4]([I:10])[CH:3]=1)[NH:9][N:11]=[CH:8]2
Reactant: Cc1cc(Br)cc(I)c1N
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Brc1cc(I)c2[nH]ncc2c1
Reaction time: 0.25 h
Yield: 95.1 %

Procedure:
4-bromo-2-iodo-6-methyl-phenylamine (31.08 g, 99.6 mmol) was dissolved in glacial acetic acid (400 mL) in a 1 L round bottom flask equipped with a stir bar. The flask was then charged in one portion with sodium nitrite (7.56 g, 109.6 mmol) dissolved in water (18.7 mL). The mixture was stirred for about 15 minutes then the solvents were removed by evaporation on a rotovap at a bath temperature of about 35° C. The residue was stirred with water (200 mL) for 15 minutes and the resulting solid was collected by filtration and dried to yield 5-bromo-7-iodo-1H-indazole (30.6 g, 95%) as a brownish-tan solid; (DMSO-d6, 400 MHz) δ 13.6 (bs, 1H), 8.24 (s, 1H), 8.04 (d, J=1.54 Hz, 1H), and 7.88 (d, J=1.54 Hz, 1H); RP-HPLC (Table 1, Method e) Rt=3.63 min; m/z: (M−H)− 322.8.
Reaction SMILES: N1C=CC([C:7]2[C:8](=[O:17])[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=CC=1.Cl.[H][H]>[Pd].C(O)C>[N:9]1([C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8](=[O:17])[CH:7]=2)[CH2:10][CH2:15][CH2:16][CH2:7][CH2:8]1
Reactant: [H][H]
Reactant: O=c1[nH]c2ccccc2cc1-c1ccncc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: O=c1cc(N2CCCCC2)c2ccccc2[nH]1

Procedure:
A mixture of 8.6 g (0.0387 mol) of 3-(4-pyridinyl)-2(1H)-quinolone, 1.2 l of ethanol, 39 ml (0.039 mol) of 1N hydrochloric acid and 8.0 g of 10% palladium/charcoal was hydrogenated at a temperature of 40° C. until about 0.08 mol of hydrogen had been taken up. The mixture was freed from catalyst, the filtrate was evaporated down in vacuo, the residue was taken up in 200 ml of water and made ammoniacal. Common salt was added up to saturation point and the mixture was continuously extracted with dichloromethane using a perforator. The dichloromethane phase was evaporated down, the residue remaining was separated from byproducts by chromatography over silica gel using FM1 as eluant. The appropriate fractions were combined, freed from solvent, dissolved in a little isopropanol and converted with ethanolic hydrogen chloride solution into the hydrochloride. Colourless crystals. Yield: 2.68 g (26.2% of theory).
Reaction SMILES: [F:1][C:2]1([F:44])[CH2:7][C@H:6]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([S:16]([N:19](CC3C=CC(OC)=CC=3OC)[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:18])=[O:17])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[F:44][C:2]1([F:1])[CH2:7][C@H:6]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([S:16]([NH:19][C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)(=[O:17])=[O:18])=[C:11]([F:37])[CH:10]=2)[C@@H:5]([C:38]2[N:42]([CH3:43])[N:41]=[CH:40][CH:39]=2)[CH2:4][CH2:3]1
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2c(F)cc(O[C@H]3CC(F)(F)CC[C@@H]3c3ccnn3C)cc2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1nccc1[C@H]1CCC(F)(F)C[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)c(F)c1
Yield: 49.3 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 4-{[(1S*,2R*)-5,5-difluoro-2-(1-methyl-1H-pyrazol-5-yl)cyclohexyl]oxy}-N-(2,4-dimethoxybenzyl)-2,6-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide (120 mg, 0.188 mmol) prepared in Example 109a, triethylsilane (0.15 mL), trifluoroacetic acid (1.5 mL) and dichloromethane (1.5 mL), to yield the title compound (45 mg, 49%) as a colorless solid.
Reaction SMILES: [NH2:1][CH:2]([C:10]1[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[CH:12][C:11]=1[O:18][CH3:19])[CH2:3][CH2:4][CH2:5][C:6]([O:8]C)=O.[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][C:22]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1>>[CH3:19][O:18][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([O:16][CH3:17])[C:10]=1[CH:2]1[N:1]([CH2:25][C:24]2[CH:27]=[CH:28][C:21]([F:20])=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[CH:23]=2)[C:6](=[O:8])[CH2:5][CH2:4][CH2:3]1
Reactant: COC(=O)CCCC(N)c1c(OC)cccc1OC
Reactant: O=Cc1ccc(F)c(-c2ccccn2)c1
Product: COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc(F)c(-c2ccccn2)c1

Procedure:
Prepared according to the described general procedure 1 (GP1) by reaction of methyl 5-amino-5-(2,6-dimethoxyphenyl)pentanoate with 4-fluoro-3-(pyridin-2-yl)benzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.68 min.; [M+H]+: 420.97 g/mol.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]1[CH:21]=[C:20]([C:22]#[C:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[C:19]([O:31]COC)=[CH:18][N:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>ClC(Cl)C>[CH2:8]([O:15][C:16]1[N:17]=[CH:18][C:19]([OH:31])=[C:20]([C:22]#[C:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH:21]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: COCOc1cnc(OCc2ccccc2)cc1C#Cc1ccc(F)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: CC(Cl)Cl
Product: Oc1cnc(OCc2ccccc2)cc1C#Cc1ccc(F)cc1
Reaction time: 5 h
Yield: 100 %

Procedure:
Trifluoroacetic acid (0.95 mL, 12.4 mmol) was added to a stirring solution of 2-(benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine (450 mg, 1.24 mmol) in dichloroethane (5 mL) at room temperature. It was allowed to stir for 5 hours and then concentrated to dryness to give 6-(benzyloxy)-4-((4-fluorophenyl)ethynyl)pyridin-3-ol (395 mg, 1.24 mmol, 100% yield) consistent by LCMS. LC-MS retention time: 2.49 min; m/z (MH+): 320. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.
Reaction SMILES: [C:1]([S:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:52])[C:19]([C:27]3[N:28]=[C:29]([NH:32][C:33]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[S:30][CH:31]=3)=[N:20][O:21]C(C)(OC)C)[C:15](=[O:53])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=[O:3])[CH3:2].C(NCC)C.Cl>CC(C)=O>[C:1]([S:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:52])[C:19]([C:27]3[N:28]=[C:29]([NH:32][C:33]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[S:30][CH:31]=3)=[N:20][OH:21])[C:15](=[O:53])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=[O:3])[CH3:2]
Reactant: COC(C)(C)ON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSC(C)=O)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: Cl
Solvent: CCNCC
Solvent: CC(C)=O
Product: CC(=O)SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NO)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)[C@H]2SC1

Procedure:
The product of Step A was added to a mixture of 10 ml of acetone and 3.5 ml of 2 N hydrochloric acid and the acetone was evaporated. The mixture was extracted with ethyl acetate and the ethyl acetate phase was triturated with ether. The mixture was vacuum filtered to obtain the syn isomer of 3-acetylthiomethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-hydroxyimino-acetamido]-ceph-3-eme-4-carboxylic acid which was then stirred with 4 ml of aqueous formic acid (1 volume water--2 volumes of formic acid) at 45° C. for 10 minutes. The mixture was evaporated to dryness under reduced pressure and the residue was triturated with 5 ml of water. The mixture was vacuum filtered and dried under reduced pressure to obtain 1 g of raw product which was dissolved in 20 ml of ethanol. The mixture was vacuum filtered to remove insolubles and the filtrate was evaporated to half its volume. 20 ml of ethanol were added thereto and the mixture was again evaporated to half its volume. The mixture was vacuum filtered and the product was washed with ethanol and with ether to obtain 0.5 g of purified syn isomer of 3-acetylthiomethyl-7-[2-(2-amino-4-thiazolyl)-2-hydroxyimino-acetamido]-ceph-3-eme-4-carboxylic acid.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[C:10](=[O:11])[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18]O)[CH:13]=2)=[C:8]([CH3:20])[N:7]([CH:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=2)[CH3:22])[CH:6]=1)=[O:4].COCCN(S(F)(F)[F:41])CCOC>ClCCl>[CH3:1][NH:2][C:3]([C:5]1[C:10](=[O:11])[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][F:41])[CH:13]=2)=[C:8]([CH3:20])[N:7]([CH:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=2)[CH3:22])[CH:6]=1)=[O:4]
Reactant: CNC(=O)c1cn(C(C)c2ccc(C#N)cc2)c(C)c(-c2cccc(CO)c2)c1=O
Reactant: COCCN(CCOC)S(F)(F)F
Solvent: ClCCl
Product: CNC(=O)c1cn(C(C)c2ccc(C#N)cc2)c(C)c(-c2cccc(CF)c2)c1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of preparation 31a (60 mg, 149 μmol) and [bis(2-methoxyethyl)amino]sulfur trifluoride (50% in toluene, 74 μL, 202 μmol) in dichloromethane (1 mL) is stirred for 3 h at room temperature. The reaction mixture is quenched with 1N HCl, extracted twice with dichloromethane and the organic phase is concentrated under reduced pressure. The remaining residue is purified by preparative reversed-phase HPLC (Stable Bond, gradient of acetonitrile in water, 0.1% TFA, 60° C.). Yield: 30 mg (50% of theory); ESI mass spectrum: [M+H]+=404; Retention time HPLC: 0.95 min (Z017—504).
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=1)=[O:4].[OH-].[Na+]>CCO.O>[CH3:12][O:11][C:8]1[CH:7]=[C:6]([C:13]2[CH:14]=[CH:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)[C:5]([C:3]([OH:4])=[O:2])=[CH:10][CH:9]=1
Reactant: COC(=O)c1ccc(OC)cc1-c1ccc(C(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc(C(=O)O)c(-c2ccc(C(F)(F)F)cc2)c1
Yield: 95.4 %

Procedure:
5-Methoxy-4′-trifluoromethyl-biphenyl-2-carboxylic acid methyl ester (5.6 g) was placed in suspension in EtOH (80 mL) and a solution of NaOH (2.9 g) in water (40 mL) was added. The mixture was stirred under reflux for 2 hours and EtOH was evaporated under reduced pressure. The aqueous layer was then acidified with concentrated HCl and the resulting solid which formed was filtered, washed with water and dried to give the title compound (5.1 g) as white crystals. m.p.: 232-234° C.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]#[CH:12])[CH2:3][CH2:2]1.[Br:13][C:14]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:15]=1[O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](OS(C(F)(F)F)(=O)=O)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1>>[Br:13][C:14]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:15]=1[O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([C:12]#[C:11][CH2:10][CH2:9][CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1
Reactant: COc1cc2c(Oc3ccc(F)cc3Br)ncnc2cc1OS(=O)(=O)C(F)(F)F
Reactant: C#CCCCCN1CCOCC1
Product: COc1cc2c(Oc3ccc(F)cc3Br)ncnc2cc1C#CCCCCN1CCOCC1

Procedure:
Using an analogous procedure to that described in the second last paragraph of Note [115] above, 6-morpholino-1-hexyne was reacted with 4-(2-bromo-4-fluorophenoxy)-6-methoxy-7-trifluoromethanesulphonyloxyquinazoline to give 4-(2-bromo-4-fluorophenoxy)-6-methoxy-7-(6-morpholino-1-hexynyl)quinazoline; NMR Spectrum: (DMSOd6) 1.63 (m, 4H), 2.33 (m, 6H), 2.55 (m, 2H), 3.56 (m, 4H), 4.0 (s, 3H), 7.35-7.8 (m, 3H), 7.65 (s, 1H), 7.96 (s, 1H), 8.6 (s, 1H); Mass Spectrum: M+H+ 514 and 516.
Reaction SMILES: [C:1]([NH:9][C:10]1[N:11]=[CH:12][N:13]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]2([C:32]([NH:34][CH2:35][C:36]([F:39])([F:38])[F:37])=[O:33])[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:40]C1NC([N+]([O-])=O)=CN=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]([NH:9][C:10]1[N:11]=[C:12]([CH3:40])[N:13]([CH2:15][CH2:16][CH2:17][CH2:18][C:19]2([C:32]([NH:34][CH2:35][C:36]([F:38])([F:37])[F:39])=[O:33])[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Nc1cn(CCCCC2(C(=O)NCC(F)(F)F)c3ccccc3-c3ccccc32)cn1)c1ccccc1
Reactant: Cc1ncc([N+](=O)[O-])[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1nc(NC(=O)c2ccccc2)cn1CCCCC1(C(=O)NCC(F)(F)F)c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 72 h
Yield: 88 %

Procedure:
To a solid mixture of Example 273 Part A(2) compound (1.00 g, 2.35 mmoL), 2-methyl-5-nitroimidazole (400 mg, 3.15 mmol), and K2CO3 (2.82 mmol) was added DMF (5 mL) and the mixture was stirred at room temperature for 3 days. The reaction was partitioned between EtOAc and saturated NaHCO3 and the organic layer was washed successively with H2O and brine. The solution was dried (Na2SO4), filtered, and stripped. The residue was triturated with Et2O/EtOAc/hexane to give title compound (973 mg, 88%) as a white solid. mp 145°-147° C.