Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH3:12])=[C:10]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Br:17]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:17][CH2:12][C:11]1[C:2]([Cl:1])=[C:3]([CH:8]=[CH:9][C:10]=1[S:13]([CH3:16])(=[O:15])=[O:14])[C:4]([O:6][CH3:7])=[O:5]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1ccc(S(C)(=O)=O)c(C)c1Cl
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(S(C)(=O)=O)c(CBr)c1Cl
Yield: 70.4 %

Procedure:
82 g (0.31 mol) of methyl 2-chloro-3-methyl-4-methylsulfonylbenzoate were dissolved in 2 l of carbon tetrachloride and, with exposure to light, admixed a little at a time with 56 g (0.31 mol) of N-bromosuccinimide. The reaction mixture was filtered, the filtrate was concentrated and the residue was taken up in 200 ml of methyl tert-butyl ether. The solution was admixed with petroleum ether and the precipitated solid was filtered off with suction and dried. 74.5 g (70% of theory) of methyl 3-bromomethyl-2-chloro-4-methylsulfonylbenzoate were obtained.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[C:11]([OH:13])=O.[CH2:14]([C:21]1([OH:27])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[CH2:14]([C:21]1([OH:27])[CH2:26][CH2:25][N:24]([C:11]([C:3]2[C:4]3[O:8][CH2:7][O:6][C:5]=3[CH:9]=[CH:10][C:2]=2[Br:1])=[O:13])[CH2:23][CH2:22]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=C(O)c1c(Br)ccc2c1OCO2
Reactant: OC1(Cc2ccccc2)CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(c1c(Br)ccc2c1OCO2)N1CCC(O)(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.6 %

Procedure:
A suspension of 5-bromo-1,3-benzodioxole-4-carboxylic acid (0.50 g), 4-benzyl-4-hydroxypiperidine (0.59 g), HATU (1.2 g) and triethylamine (1.4 mL) in DMF (5.0 mL) was stirred overnight at room temperature. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.85 g).
Reaction SMILES: I(C1C=CC=CC=1C(O)=O)(=O)=[O:2].[C:13]1(C)[CH:18]=[CH:17][C:16]([S:19][C:20]2C=CC(C)=CC=2)=[CH:15][CH:14]=1>[Br-].C([N+](CC)(CC)CC)C.C(Cl)(Cl)Cl.O>[C:16]1([S:19]([CH3:20])=[O:2])[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=1
Reactant: O=C(O)c1ccccc1I(=O)=O
Reactant: Cc1ccc(Sc2ccc(C)cc2)cc1
Agent: CC[N+](CC)(CC)CC
Agent: [Br-]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CS(=O)c1ccccc1
Yield: 99.9 %

Procedure:
To a stirred suspension of iodoxybenzoic acid (3.7 g, 13.2 mmol, 1.1 eq) in 100:1 CHCl3/H2O (25 mL) was added tetraethylammonium bromide (TEAB) (126 mg, 5 mol %), followed by the addition of p-tolyl sulfide (1.66 g, 12 mmol) in one portion. The mixture was stirred at room temperature for approximately 30 minutes until consumption of sulfide was observed (TLC, hexanes/EtOAc 1/1). The residual solids were removed by filtration and washed with CHCl3 (40 mL). The combined filtrate was washed successively with saturated aq. NaHCO3 (30 mL), saturated aq. NaCl (30 mL), dried over sodium sulfate, and concentrated to provide the crude product. Purification by silica gel column chromatography (50% hexanes/EtOAc elution) afforded the title compound (1.68 g, yield 91%). 1H NMR (300 MHz, CDCl3) δ 7.52 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 2.71 (s, 3H), 2.42 (s, 3H); ESI-MS m/z 154.7 (M+H)+.
Reaction SMILES: [CH2:1]([N:8]([CH2:16][CH2:17][OH:18])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH2:1]([N:8]([CH2:16][CH2:17][O:18][C:23]1[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=1)[C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N(CCO)Cc1ccccc1
Reactant: Oc1ccc(F)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N(CCOc1ccc(F)cc1)Cc1ccccc1
Reaction time: 3 h
Yield: 86.9 %

Procedure:
To a solution of 2-(N-benzyl-N-tert-butoxycarbonylamino)ethanol (6.85 g, 27.3 mmol), 4-fluorophenol (3.07 g, 27.3 mmol) and PPh3 (7.83 g, 30.0 mmol) in THF (100 mL) was added DIAD (6.00 mL, 30.0 mmol) at room temperature. After being stirred for 3 hr, the reaction mixture was concentrated. Chromatography of the residue with hexane-EtOAc (8:1, v/v) as eluent gave 1-[2-(N-benzyl-N-tert-butoxycarbonylamino)ethoxy]-4-fluorobenzene (8.19 g, 64%) as a yellow oil. 1H-NMR (CDCl3) δ1.42-1.50 (m, 9H), 3.41-3.67 (m, 2H), 3.92-4.11 (m, 2H), 4.51-4.63 (m, 2H), 6.73-6.85 (m, 2H), 6.89-6.98 (m, 2H), 7.24 (m 5); FAB-MS m/z 346 (M++1).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[N+:22]([O-])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[NH2:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccc(NC2CCN(C(=O)OC(C)(C)C)CC2)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCO
Product: Cc1ccc(NC2CCN(C(=O)OC(C)(C)C)CC2)c(N)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.3 %

Procedure:
To a solution of 4-(4-methyl-2-nitro-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (9.5 g, 28.4 mmol) in ethanol (150 mL) was added 10% Pd/C (125 mg) and the reaction mixture was shaken under H2 (50 psi) at rt for 1 h. The catalyst was then removed by filtration through a pad of Celite® and washed with ethanol. The filtrate was concentrated in vacuo to provide 4-(2-amino-4-methyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (7.83 g) in 90% yield.
Reaction SMILES: [CH3:1][C:2]([S@:5](/[N:7]=[C:8](/[CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)\[CH3:9])=[O:6])([CH3:4])[CH3:3].CO.[BH4-].[Na+]>O1CCCC1>[CH3:1][C:2]([S@:5]([NH:7][CH:8]([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[CH3:9])=[O:6])([CH3:3])[CH3:4]
Reactant: C/C(=N\[S@](=O)C(C)(C)C)C1CCOCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: CC(N[S@](=O)C(C)(C)C)C1CCOCC1
Temperature: -32.5 °C
Reaction time: 2 h
Yield: 95.2 %

Procedure:
To a solution of (R,E)-2-methyl-N-(1-(tetrahydro-2H-pyran-4-yl)ethylidene)propane-2-sulfinamide (1.25 g, 5.4 mmol) in tetrahydrofuran (6 mL) was added methanol (692 mg, 21.6 mmol) and NaBH4 (821 mg, 21.6 mmol) at −65° C. under N2. The reaction was stirred at −65-0° C. for 2 h. Then the reaction was quenched by water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3 and concentrated in vacuo to give crude (R)-2-methyl-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)Propane-2-sulfinamide (1.2 g, 52.1%) as a yellow oil.
Reaction SMILES: [NH2:1][O:2][CH2:3][S:4]([C:7]1[CH:8]=[C:9]([OH:14])[C:10](=[CH:12][CH:13]=1)[OH:11])(=[O:6])=[O:5].[NH2:15][C:16]1[S:17][CH:18]=[C:19]([C:21](=O)[C:22]([NH:24][C@@H:25]2[C:32](=[O:33])[N:31]3[C@@H:26]2[S:27][CH2:28][C:29]([CH2:37][S:38][C:39]2[N:44]4[N:45]=[C:46]([C:48]([O:50][CH3:51])=[O:49])[N:47]=[C:43]4[N:42]=[C:41]([CH3:52])[CH:40]=2)=[C:30]3[C:34]([OH:36])=[O:35])=[O:23])[N:20]=1.[OH-].[Na+:55].O.CO>O.CO>[Na+:55].[NH2:15][C:16]1[S:17][CH:18]=[C:19](/[C:21](=[N:1]/[O:2][CH2:3][S:4]([C:7]2[CH:13]=[CH:12][C:10]([OH:11])=[C:9]([OH:14])[CH:8]=2)(=[O:5])=[O:6])/[C:22]([NH:24][C@@H:25]2[C:32](=[O:33])[N:31]3[C@@H:26]2[S:27][CH2:28][C:29]([CH2:37][S:38][C:39]2[N:44]4[N:45]=[C:46]([C:48]([O:50][CH3:51])=[O:49])[N:47]=[C:43]4[N:42]=[C:41]([CH3:52])[CH:40]=2)=[C:30]3[C:34]([O-:36])=[O:35])=[O:23])[N:20]=1
Reactant: COC(=O)c1nc2nc(C)cc(SCC3=C(C(=O)O)N4C(=O)[C@@H](NC(=O)C(=O)c5csc(N)n5)[C@H]4SC3)n2n1
Reactant: NOCS(=O)(=O)c1ccc(O)c(O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COC(=O)c1nc2nc(C)cc(SCC3=C(C(=O)[O-])N4C(=O)[C@@H](NC(=O)/C(=N\OCS(=O)(=O)c5ccc(O)c(O)c5)c5csc(N)n5)[C@H]4SC3)n2n1

Procedure:
122 mg of 4-[[(aminooxy)methyl]sulphonyl]pyrocatechol were reacted with 236 mg of (6R,7R)-7-(2-amino-4-thiazoleglyoxylamido)-3-[[[2-(methoxycarbonyl)-5-methyl-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 according to the procedure described in Example 7. The crude product obtained was suspended in 10 ml of water and brought into solution by the slow addition of 0.1N sodium hydroxide solution, with care being taken that the pH of the solution did not exceed 7. By chromatography on MCI gel CHP 2OP using water as the elution agent as well as water/methanol mixtures with increasing amounts of methanol and lyophilization of the concentrated product fractions, there was obtained (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2-(methoxycarbonyl)-5-methyl-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 monosodium salt as a white powder.
Reaction SMILES: [CH2:1]([C@:4]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:19])[N:5]1[CH3:20])[CH:2]=[CH2:3].C([C@]1(C2C=CC(F)=CC=2)CCN([C@H](C2C=CC(Br)=CC=2)C)C(=[O:46])N1)C=C>>[Br:18][C:15]1[CH:16]=[CH:17][C:12]([C@@H:10]([N:7]2[CH2:8][CH2:9][C@@:4]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)([CH2:1][CH2:2][CH2:3][OH:46])[N:5]([CH3:20])[C:6]2=[O:19])[CH3:11])=[CH:13][CH:14]=1.[CH2:1]([C@:4]1([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:19])[N:5]1[CH3:20])[CH:2]=[CH2:3]
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)N1
Agent: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(Br)cc2)C(=O)N1C
Product: C[C@@H](c1ccc(Br)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)N(C)C1=O

Procedure:
(R)-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-3-methyltetrahydropyrimidin-2(1H)-one was prepared from (R)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)-3-methyltetrahydropyrimidin-2(1H)-one following a procedure analogous to that described in Example 10. (R)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)-3-methyltetrahydropyrimidin-2(1H)-one was prepared from (R)-4-allyl-1-((S)-1-(4-bromophenyl)ethyl)-4-(4-fluorophenyl)tetrahydropyrimidin-2(1H)-one following a procedure analogous to that described in Example 3. LC-MS Method tR=2.45 min, m/z=471.1; 1H NMR (CDCl3) δ=1.28 (m, 2H), 1.49 (m, 3H), 1.72 (m, 2H), 1.90 (m, 1H), 2.18 (m, 3H), 2.70 (m, 1H), 2.80 (m, 3H), 3.69 (m, 2H), 5.82 (m, 1H), 6.91 (m, 2H), 7.06 (m, 4H), 7.32 (m, 2H).
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([CH2:11][NH2:12])=[CH:6][N:5]=1.C(N(CC)CC)C.[C:20](OC(=O)C)(=[O:22])[CH3:21]>CO>[NH2:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([CH2:11][NH:12][C:20](=[O:22])[CH3:21])=[CH:6][N:5]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(N)ncc1CN
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(=O)NCc1cnc(N)cc1C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-amino-5-aminomethyl-4-methylpyridine dihydrochloride (70 mg, 0.333 mmol) in methanol (2 mL) were added triethylamine (93 uL, 0.667 mmol) and acetic anhydride (47 uL, 0.498 mmol). The reaction mixture was stirred for 2 h at room temperature and then evaporated. The residue was chromatographed on silica gel (10% methanol/methylene chloride) to afford pure title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]1[NH:11][C:12]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[C:13]([C:28]([O:30][CH3:31])=[O:29])[CH:14]([C:20]2[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:27])[C:15]=1[C:16]([O:18][CH3:19])=[O:17].[CH3:37][S:38](Cl)(=[O:40])=[O:39].C(N(CC)CC)C>C(Cl)Cl>[Cl:27][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]([Cl:26])[C:20]=1[CH:14]1[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:10]([CH2:9][CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][S:38]([CH3:37])(=[O:40])=[O:39])[NH:11][C:12]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[C:13]1[C:28]([O:30][CH3:31])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)CC1=C(C(=O)OC)C(c2c(Cl)cccc2Cl)C(C(=O)OC)=C(CCc2ccccc2N)N1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CC1=C(C(=O)OC)C(c2c(Cl)cccc2Cl)C(C(=O)OC)=C(CCc2ccccc2NS(C)(=O)=O)N1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a stirred solution of dimethyl 2-[2-(2-aminophenyl)ethyl]-4-(2,6-dichlorophenyl)-6-(2-methoxy-2-oxoethyl)-1,4-dihydro-3,5-pyridinedicarboxylate (500 mg/0.94 mmol) and methanesulfonyl chloride (107 mg/0.94 mmol) in anhydrous CH2Cl2(15 ml) was added triethylamine (94.7 mg/0.94 mmol) at 0° C. under nitrogen atmosphere. The resulting solution was stirred at room temperature for 1 day. The reaction was quenched with water and the separated organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated to afford a crude mixture. This crude was purified by column chromatography on silica gel (Hexane:EtOAc=3:2) to afford a yellow solid (262 mg/46%).
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[CH:15]=[C:14]([C:16]([O:18]C)=[O:17])[CH:13]=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9])([O-:5])=[O:4]>O1CCOCC1.O>[C:16]([C:14]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([N+:3]([O-:5])=[O:4])[CH:15]=1)([OH:18])=[O:17]
Reactant: COC(=O)c1ccc(C(=O)OC)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C(=O)O)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 71684 %

Procedure:
1N NaOH (50 mL) was slowly added dropwise at room temperature over 30 min to a stirred solution of di-methyl nitroterephthalate (12 g, 0.05 mmol) in dioxane (100 mL). After stirring overnight at room temperature the reaction was diluted with water, washed with ether, acidified with 1N HCl (50 mL) and extracted with ethyl acetate. After drying the ethyl acetate phase (MgSO4) and evaporation, the resulting residue was purified by flash chromatography (silica gel, 98:2:0.1 CHCl3 :MeOH:HOAc) to yield the title compound (8.07 g, 72%).
Reaction SMILES: [CH2:1]([C:3]([C:12]1[CH:25]=[CH:24][C:15]([O:16][CH2:17][C:18]([OH:23])([CH2:21][CH3:22])[CH2:19][CH3:20])=[C:14]([CH3:26])[CH:13]=1)([C:6]1[S:7][CH:8]=[C:9]([CH3:11])[CH:10]=1)[CH2:4][CH3:5])[CH3:2].[Li]CCCC.Cl[C:33]([O:35][CH3:36])=[O:34]>C1COCC1>[CH3:36][O:35][C:33]([C:8]1[S:7][C:6]([C:3]([CH2:4][CH3:5])([C:12]2[CH:25]=[CH:24][C:15]([O:16][CH2:17][C:18]([CH2:21][CH3:22])([OH:23])[CH2:19][CH3:20])=[C:14]([CH3:26])[CH:13]=2)[CH2:1][CH3:2])=[CH:10][C:9]=1[CH3:11])=[O:34]
Reactant: CCC(O)(CC)COc1ccc(C(CC)(CC)c2cc(C)cs2)cc1C
Reactant: COC(=O)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCC(O)(CC)COc1ccc(C(CC)(CC)c2cc(C)c(C(=O)OC)s2)cc1C
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 41 %

Procedure:
3-{4-[1-Ethyl-1-(4-methyl-thiophen-2-yl)-propyl]-2-methyl-phenoxymethyl}-pentan-3-ol, Example 51B (0.50 g, 1.34 mmol) is dissolved in THF (10 mL). The solution is cooled to 0° C., treated with nBuLi (1.6 M, 1.8 mL, 2.95 mmol). It is stirred at 0° C. for 20 min, and methyl chloroformate (113 μL, 1.47 mmol) is added. The reaction is stirred at 0° C. for 10 min and RT for 20 m before it is quenched with satd NH4Cl (5 mL). It is diluted with H2O (10 mL), treated with 0.1 M HCl (10 ml) and extracted with EtOAc (3×15 mL), dried and concentrated. The crude product is purified by chromatography to give the titled compound (0.24 g, 0.56 mmol, 41%). 1H NMR (CD3C3), δ 0.71 (t, J=7.1 Hz, 6H), 0.95 (t, J=7.9 Hz, 6H), 1.64-1.72 (m, 4H), 2.11 (q, J=7.1 Hz, 4H), 2.21 (s, 3H), 2.49 (s, 3H), 3.81 (s, 3H), 6.61 (s, 1H), 6.72 (d, J=8.4 Hz, 1H), 6.85-7.01 (m, 2H). LC/MS (m/z): calcd for C25H40NO4S (M+NH4)+: 450.3; found: 450.3.
Reaction SMILES: [N+:1]([C:4]1[C:9]([NH:10][S:11]([C:14]2[N:18]=[CH:17][NH:16][N:15]=2)(=[O:13])=[O:12])=[C:8]([O:19][CH2:20][C:21]#[CH:22])[CH:7]=[CH:6][CH:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH3:29][O:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[N:34]=[C:33](S(C)(=O)=O)[N:32]=1.Cl>CN(C)C=O>[CH3:29][O:30][C:31]1[CH:36]=[C:35]([O:37][CH3:38])[N:34]=[C:33]([N:16]2[CH:17]=[N:18][C:14]([S:11]([NH:10][C:9]3[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=[CH:7][C:8]=3[O:19][CH2:20][C:21]#[CH:22])(=[O:13])=[O:12])=[N:15]2)[N:32]=1
Reactant: C#CCOc1cccc([N+](=O)[O-])c1NS(=O)(=O)c1nc[nH]n1
Reactant: COc1cc(OC)nc(S(C)(=O)=O)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C#CCOc1cccc([N+](=O)[O-])c1NS(=O)(=O)c1ncn(-c2nc(OC)cc(OC)n2)n1
Temperature: 50 °C
Reaction time: 20 h

Procedure:
A mixture of 3.23 g (10 mmol) N-(6-nitro-2-propargyloxyphenyl)-1H-1,2,4-triazole-3-sulphonamide and 2.76 g (20 mmol) potassium carbonate in 25 ml dimethylformamide was heated under a protective gas for 10 minutes at 50° C. After cooling to 0° C. and addition of 2.18 g (10 mmol) 4,6-dimethoxy-2-methylsulphonylpyrimidine, the mixture was warmed and stirred for 20 hours. It was then stirred into to 300 ml ice-cold saturated aqueous sodium chloride and acidified with hydrochloric acid (pH 4). The crystals were removed by suction filtration and purified by silica gel chromatography using a mixture of hexane and ethyl acetate (0 to 100% ethyl acetate).
Reaction SMILES: [CH3:1][N:2]1[CH:6]([C:7]([OH:9])=O)[CH2:5][NH:4][C:3]1=[O:10].CN1C(C(OC(C)(C)C)=O)CNC1=O.O=C1N(C(OCC2C=CC=CC=2)=O)[C@H](C(O)=O)CN1.C(N1CCOCC1)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[F:75][C:76]1[C:81]([C:82]([F:85])([F:84])[F:83])=[CH:80][CH:79]=[CH:78][C:77]=1[CH2:86][NH2:87]>ClCCl>[F:75][C:76]1[C:81]([C:82]([F:84])([F:85])[F:83])=[CH:80][CH:79]=[CH:78][C:77]=1[CH2:86][NH:87][C:7]([CH:6]1[CH2:5][NH:4][C:3](=[O:10])[N:2]1[CH3:1])=[O:9]
Reactant: NCc1cccc(C(F)(F)F)c1F
Reactant: CN1C(=O)NCC1C(=O)O
Agent: CCN1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: CN1C(=O)NCC1C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O
Product: CN1C(=O)NCC1C(=O)NCc1cccc(C(F)(F)F)c1F
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 8.4 %

Procedure:
A mixture of 3-methyl-2-oxo-4-imidazolidinecarboxylic acid (86 mg, 0.6 mmol) (prepared as described in Example 28 from 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate, itself prepared as described in step (iii) of Example 13, starting originally from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid), N-ethyl morpholine (0.380 ml, 3.00 mmol), 1-hydroxybenzotriazole hydrate (110 mg, 0.720 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.720 mmol) in dichloromethane (9 ml) was stirred at room temperature for 10 minutes, under an argon atmosphere. {[2-Fluoro-3-(trifluoromethyl)phenyl]methyl}amine (0.1 ml, 0.684 mmol) was added and the reaction was stirred overnight under an argon atmosphere. The reaction mixture was diluted with dichloromethane (10 ml) and the solution was washed with saturated sodium hydrogen carbonate solution (10 ml), water (10 ml), citric acid solution (10 ml) and brine (10 ml). The citric acid layer was re-extracted with dichloromethane and the dichloromethane extracts were combined, dried and evaporated. The residue was purified by mass-directed automated HPLC. Fractions containing product were collected and the solvent was evaporated in vacuo to give N-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-4-imidazolidinecarboxamide (16 mg, 8% yield) as a white solid. LC/MS [M+H]+=320, retention time=1.85 minutes.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH:15]2[O:19][C:18](=[O:20])[N:17]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=3)[CH2:16]2)[CH2:10][CH:9]1[C:29]([O:31][CH2:32][CH3:33])=[O:30])=O)(C)(C)C.C(C1C=CC(N2CC(CBr)OC2=O)=CC=1)#N.C(OC(N1CCNCC1C(OCC)=O)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:27]([C:24]1[CH:25]=[CH:26][C:21]([N:17]2[CH2:16][CH:15]([CH2:14][N:11]3[CH2:12][CH2:13][NH:8][CH:9]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:10]3)[O:19][C:18]2=[O:20])=[CH:22][CH:23]=1)#[N:28]
Reactant: CCOC(=O)C1CN(CC2CN(c3ccc(C#N)cc3)C(=O)O2)CCN1C(=O)OC(C)(C)C
Agent: CCOC(=O)C1CNCCN1C(=O)OC(C)(C)C
Agent: N#Cc1ccc(N2CC(CBr)OC2=O)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)C1CN(CC2CN(c3ccc(C#N)cc3)C(=O)O2)CCN1
Reaction time: 1 h

Procedure:
A solution of 1 g of ethyl 1-tert-butoxycarbonyl-4-(3-(4-cyanophenyl)-2-oxo-5-oxazolidinylmethyl)piperazine-2-carboxylate (obtainable by reacting 3-(4-cyanophenyl)-5-bromomethyl-2-oxazolidinone with ethyl 1-tert-butoxycarbonylpiperazine-2-carboxylate in accordance with the method described in Example 3) in 12 ml of dichloromethane and 12 ml of trifluoroacetic acid is left to stand at 20° for 1 h. and then concentrated by evaporation. Ethyl 1-(3-(4-cyanophenyl)-2-oxo-5-oxazolidinylmethyl)piperazine-3-carboxylate is obtained, FAB 359.
Reaction SMILES: CS([O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][CH:7]=1)(=O)=O.C[O-].[Na+].O1CCCC1.Cl>CO>[OH:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:12]([C:9]2[CH:10]=[CH:11][C:6]([OH:5])=[CH:7][CH:8]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:19][CH:20]=1
Reactant: CS(=O)(=O)Oc1ccc(N(Cc2ccc(O)cc2)S(C)(=O)=O)cc1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CS(=O)(=O)N(Cc1ccc(O)cc1)c1ccc(O)cc1
Yield: 60.1 %

Procedure:
A mixture composed of 80 mg of 4-[N-(4-hydroxybenzyl)-N-methylsulfonylamino]phenyl methanesulfonate and 0.5 ml of a 28% methanolic solution of sodium methoxide was stirred in 2 ml of methanol and 1 ml of tetrahydrofuran at 50° C. for 1hour. After hydrochloric acid was added to the reaction mixture, the product was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the solvent was distilled off the resulting crude product was purified by TLC (using a 19:1 mixture of chloroform and methanol as the developing solvent) to obtain 38 mg of N-(4-hydroxybenzyl)-N-(4-hydroxyphenyl)methanesulfonamide.
Reaction SMILES: [CH:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].S(=O)(O)[O-].[Na+].[N+:17]([CH2:20][CH3:21])([O-:19])=[O:18].[OH-].[Na+]>O.C(O)C>[N+:17]([CH:20]([CH3:21])[CH:8]([C:7]1[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:11][CH:10]=1)[OH:9])([O-:19])=[O:18]
Reactant: CC[N+](=O)[O-]
Reactant: CC(C)c1ccc(C=O)cc1
Agent: O=S([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)c1ccc(C(O)C(C)[N+](=O)[O-])cc1

Procedure:
The procedure of Example 1 was followed for the reaction of 74 g of p-isopropylbenzaldehyde and 57 g of sodium bisulfite with 75 g of 1-nitroethane and 40 g of sodium hydroxide. Water and ethanol served as solvents. The product weighed 41 g and was a light yellow oil which slowly crystallized on standing: ir (film) 2.85 (m), 3.35 (m), 6.5 (s), 7.2 (m), 7.35 (m), 9.5 (m), 11.95 (m) microns; nmr (CDCl3) 7.1 (4H, s), 5.0 to 4.6 (2H, m) 3.05 (1H, broad), 2.9 (1H, quintet), 1.3 (6H, d), 1.5 to 1.2 (3H, m) ppm.
Reaction SMILES: N.FC(F)(F)C([N:6]1[CH2:11][C:10]2([CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH2:25][OH:26])[CH:19]=3)[CH2:13][CH2:12]2)[O:9][CH2:8][CH2:7]1)=O>CO>[O:9]1[C:10]2([CH2:12][CH2:13][N:14]([CH2:17][C:18]3[CH:19]=[C:20]([CH2:24][CH2:25][OH:26])[CH:21]=[CH:22][CH:23]=3)[CH2:15][CH2:16]2)[CH2:11][NH:6][CH2:7][CH2:8]1
Reactant: O=C(N1CCOC2(CCN(Cc3cccc(CCO)c3)CC2)C1)C(F)(F)F
Agent: N
Solvent: CO
Product: OCCc1cccc(CN2CCC3(CC2)CNCCO3)c1
Reaction time: 1.5 h

Procedure:
‘880’ Ammonia solution (5 mL) was added to a solution of 2,2,2-trifluoro-1-(9-(3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone (example 12, step e) (2.02 g) in methanol (25 mL). The resulting mixture was stirred for 90 min and the solvent evaporated. The residue was purified by silica gel chromatography eluting with 94.5:5:0.5 to 89:10:1 DCM:methanol:‘880’ aqueous ammonia gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a clear oil. Yield 1.44 g.