Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si](O[CH2:9][C@@H:10]1[O:21][C@H:11]1[CH2:12]OCC1C=CC=CC=1)(C(C)(C)C)(C)C.[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][Mg]Br)[CH:23]=1>>[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH2:12][CH:11]([OH:21])[CH2:10][CH3:9])[CH:23]=1
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1O[C@H]1COCc1ccccc1
Reactant: Cc1cccc(C[Mg]Br)c1
Product: CCC(O)CCc1cccc(C)c1

Procedure:
325 mg of (2S,3S)-4-benzyloxy-2,3-epoxy-1-butanol tert-butyldimethylsilyl ether obtained in Example 53. was subjected to Grignard reaction in the same manner as in Example 53 by using 3-tolylmethyl magnesium bromide (0.8M diethyl ether solution). The product was purificated by silica gel column chromatography to obtain 210 mg of (2R,3R)-4-benzyloxy-1-tert-butyldimethylsilyloxy-3-(3-tolylmethyl-2-butanol as colorless oily substance.
Reaction SMILES: C1(C)C=CC(S([N:10]=[N+:11]=[N-])(=O)=O)=CC=1.[CH3:14][O:15][C:16](=[O:24])[CH2:17][C:18](=[O:23])[CH2:19][CH2:20][CH:21]=[CH2:22].C(N(CC)CC)C>C(#N)C>[CH3:14][O:15][C:16](=[O:24])[C:17](=[N+:10]=[N-:11])[C:18](=[O:23])[CH2:19][CH2:20][CH:21]=[CH2:22]
Reactant: C=CCCC(=O)CC(=O)OC
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C=CCCC(=O)C(=[N+]=[N-])C(=O)OC
Reaction time: 2 h
Yield: 97 %

Procedure:
A solution of p-toluenesulfonyl azide (592 mg; 3 mmol) in 1 ml of acetonitrile was added at room temperature to a solution of 3-oxo-6-heptenoic acid methyl ester (468 mg; 3 mmol) and triethylamine (306 mg; 3 mmol) in 5 ml of acetonitrile. The mixture was stirred for about 2 hours and the solvent was distilled off under a reduced pressure and the product was dissolved in 50 ml of ether. The solution was washed with a 5% aqueous solution of potassium hydroxide until no color remained in the aqueous phase and was further washed with a saturated aqueous solution of sodium chloride. The ether solution was dried over anhydrous magnesium sulfate and was filtered and condensed under a reduced pressure to obtain 530 mg of 2-diazo-3-oxo-6-heptenoic acid methyl ester as a yellow oily product. The crude product can be purified by distillation under reduced pressure.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[S:14][C:13](Cl)=[C:12](Cl)[C:10]1=[O:11]>C1(C)C(C)=CC=CC=1>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[S:14][CH:13]=[CH:12][C:10]1=[O:11]
Reactant: CCCCCCCCn1sc(Cl)c(Cl)c1=O
Solvent: Cc1ccccc1C
Product: CCCCCCCCn1sccc1=O

Procedure:
The core material is prepared as a mixture of 100 grams of Kathon 287T (97%) manufactured by Rohm and Haas and 100 grams of a substituted aromatic solvent, SAS 310 manufactured by Nisseki Chemical and heated to 40° C. The aqueous phase and the core material are added to a 1-quart Waring Blender jar and the slurry is emulsified at moderate speed for about 15 minutes to produce an oil-in-water emulsion of droplets in the size range of about 10 to 40 microns. The emulsion is transferred to a 1-liter beaker. The slurry is slowly agitated using a turbine impellor while maintaining the temperature at about 40° C. A solution of 4 grams of urea and 10 grams of resorcinol in 60 grams of water is slowly added to the emulsion. A solution of 2 grams sodium sulfate in 30 grams of water is subsequently added to the slurry in drop-wise fashion. A 30 ml 37% formaldehyde solution is added drop-wise followed 10 minutes later by the addition of 20 ml of a 10% sulfuric acid solution over a 5-minute period. The slurry is warmed to 45° C. and after about one hour a solution of 4 g of urea, 6 g of resorcinol, 50 g of water and 20 ml of 37% formaldehyde second addition is added drop-wise. This solution may be divided, with half added in 15 minutes followed by a 15-minute hold period prior to adding the second half. One hour later another solution like the proceeding is added to the slurry in the same fashion. The slurry is heated to 55° C. and allowed to stir for 16 hours. The microcapsule slurry is cooled to ambient temperature and pH adjusted to 7.0 using 10% sodium hydroxide solution. The slurry is then diluted with water and strained using a 125-150 um sieve to remove encapsulated air and any debris. The slurry is set aside to allow the microcapsules to settle. The supernatant liquid is decanted and microcapsule concentrate is re-slurried with water. A small amount of Syloid 244 silica from W. R. Grace Company is stirred into the slurry; and the microcapsules are vacuum-filtered using Whatman 4.0 paper and tray dried to produce 230 grams of dry free-flowing powder. The resultant microcapsules are mostly 10-40 microns and can be incorporated in a marine coating composition to impart anti-fouling properties. The microcapsules were tested for stability in xlyene by placing a 50-mg sample into 50 mls of xlyene and periodically analyzing a small aliquot of the xylene spectrophotometrically for the presence of DCOIT to determine the amount diffused through the capsule shell. Samples were tested after room storage. 1.1% DCOIT was released after 56 days at room temperature.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:10][NH:11][C:12](=[O:20])[CH2:13][CH2:14][NH:15][CH2:16][CH:17]([CH3:19])[CH3:18].C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[C:3]([N:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:14][CH2:13][C:12]([NH:11][CH3:10])=[O:20])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: Clc1ncc(Br)c(Cl)n1
Reactant: CNC(=O)CCNCC(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CNC(=O)CCN(CC(C)C)c1nc(Cl)ncc1Br
Temperature: 25 °C

Procedure:
5-Bromo-2,4-dichloropyrimidine (Aldrich; 2.82 g, 12.37 mmol), N-methyl-3-(2-methylpropylamino)propanamide (Intermediate 86; 1.78 g; 11.25 mmol), Triethylamine (1.65 mL, 11.81 mmol) and DCM (40 mL) were combined and stirred over the weekend at room temperature. The reaction mixture was washed saturated aqueous sodium bicarbonate solution and gravity filtered through a PTFE cup and solvent evaporated. The residue was dissolved in DCM and passed through a silica column eluting with a gradient of 30-50% Ethyl Acetate/iso-hexane over 10 column volumes then 50% Ethyl Acetate/iso-hexane. Fractions containing product combined and evaporated to give the title compound as a white solid. (3.26 g, 83%)
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[C@@H:7]([NH:16][C:17]([O:19][CH2:20][CH:21]1[C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C([CH:42](O)[C:43]1[CH:48]=[CH:47][CH:46]=[C:45]([NH2:49])[CH:44]=1)(OC(C)(C)C)=O>>[C:1]([O:5][C:6](=[O:34])[C@@H:7]([NH:16][C:17]([O:19][CH2:20][CH:21]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=2[C:28]2[C:33]1=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:18])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([NH:49][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:34])[CH:44]=2)=[CH:13][CH:14]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)C(O)c1cccc(N)c1
Reactant: CC(C)(C)OC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OCC1c2ccccc2-c2ccccc21
Product: CC(C)(C)OC(=O)Nc1cccc(COc2ccc(C[C@H](NC(=O)OCC3c4ccccc4-c4ccccc43)C(=O)OC(C)(C)C)cc2)c1
Yield: 111.4 %

Procedure:
In a manner similar to that described in Example H, the product from Example G (0.50 g, 1.08 mmol) and BOC-3-aminobenzylalcohol (0.24 g, 1.08 mmol) were converted to the title compound (0.40 g, 60%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[C:11]([OH:17])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:17])[C:12](=[CH:15][CH:16]=1)[CH2:13][OH:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc(OCc2ccccc2)cc1O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OCc1ccc(OCc2ccccc2)cc1O
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 76 %

Procedure:
To an ice cooled suspension of 4-benzyloxy-2-hydroxy-benzaldehyde (0.228 g, 1 mmol) in 10 mL of methanol was slowly added sodium borohydride (0.038 g, 1 mmol). After addition of sodium borohydride, a clear solution was obtained. The reaction was stirred at 0° C. for 20 minutes followed by stirring at RT for 10 minutes. The solvent was evaporated under vacuum. To this solid residue was carefully added 0.1 N H2SO4 until the pH dropped to 6.5 with vigorous stirring. Additional water (ca. 40 mL) was added with continuous stirring which then caused the product to precipitate. The solid was filtered and copiously washed with water to remove all traces of acid (last wash pH>7). The solid was immediately vacuum dried to obtain 0.175 g (76%) white solid: mp 88-90° C.; TLC, Rf0.29, in hexanes:EtOAc (2:1); 1H NMR (600 MHz, DMSO-d6) δ, 9.36 (s, 1H, Ph-OH), 7.43-7.32 (m, 5H, C6H5), 7.14-7.12 (d, 1H, J=8.4 Hz, Ar—H6), 6.44-6.41 (m, 2H, Ar—H5/Ar—H3), 5.01 (s, 2H, PhCH2), 4.8 (t, 1H, CH2OH), 4.39 (s, 2H, CH2OH); 13C NMR (100 MHz, DMSO-d6) δ 158.0, 155.2, 137.3, 128.5, 128.4, 128.3, 127.6, 127.5, 127.3, 121.2, 104.8, 101.8, 68.9, 57.9; analysis calcd. for C14H14O3. C, 73.03; H, 6.13. found: C, 73.16; H, 5.94.
Reaction SMILES: C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:17]=[C:16]([NH:18][C:19]([NH2:26])=[N:20][CH2:21][C:22]([F:25])([F:24])[F:23])[CH:15]=[CH:14][N:13]=1)C1C=CC=CC=1.Cl>CCO.[Pd]>[OH:8][CH2:9][CH2:10][CH2:11][C:12]1[N:17]=[C:16]([NH:18][C:19]([NH2:26])=[N:20][CH2:21][C:22]([F:25])([F:23])[F:24])[CH:15]=[CH:14][N:13]=1
Reactant: NC(=NCC(F)(F)F)Nc1ccnc(CCCOCc2ccccc2)n1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: NC(=NCC(F)(F)F)Nc1ccnc(CCCO)n1
Yield: 7.2 %

Procedure:
A solution of 2-(3-benzyloxypropyl)-4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimidine (3.7 g.) in EtOH (75 ml.) containing concentrated aqueous HCl (1 ml.) was hydrogenated over 5% w/w palladium on carbon (1 g.). The filtrate was evaporated and the residue was partitioned between dilute aqueous NaOH and EtOAc. The EtOAc solution was washed with brine, dried and evaporated and the residue was crystallised from EtOAc to give 2-(3-hydroxypropyl)-4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimidine (0.2 g.), m.p. 136°-138°.
Reaction SMILES: [CH3:1][C:2]([N:6]([CH2:19][CH2:20][CH:21]=[O:22])[C:7]([NH:9][C:10]1[S:11][C:12]([C:15]([F:18])([F:17])[F:16])=[N:13][N:14]=1)=[O:8])([CH3:5])[C:3]#[CH:4].Cl>O>[F:16][C:15]([F:18])([F:17])[C:12]1[S:11][C:10]([N:9]2[CH:21]([OH:22])[CH2:20][CH2:19][N:6]([C:2]([CH3:1])([CH3:5])[C:3]#[CH:4])[C:7]2=[O:8])=[N:14][N:13]=1
Reactant: C#CC(C)(C)N(CCC=O)C(=O)Nc1nnc(C(F)(F)F)s1
Agent: Cl
Solvent: O
Product: C#CC(C)(C)N1CCC(O)N(c2nnc(C(F)(F)F)s2)C1=O

Procedure:
The diethyl acetal of 3-[1-(1,1-dimethylprop-2-ynyl)-3-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)ureido]propionaldehyde (15 grams), water (400 ml) and hydrochloric acid (4 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux for a period of about 15 minutes. The reaction mixture is then filtered while hot and the filtrate is cooled to form a precipitate. The precipitate is recovered by filtration, is dried and is recrystallized to yield the desired product tetrahydro-1-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)-3(1,1-dimethylprop-2-ynyl)-6-hydroxy-2(1H)-pyrimidinone.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:12]2=[N:13][CH:14]=[CH:15][C:16]([CH2:17][NH:18][C@H:19]([CH2:23][C:24]([F:27])([F:26])[F:25])[C:20](O)=[O:21])=[C:11]2[C:10]([C:28]([O:30][CH3:31])=[O:29])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=N[C:42]2[CH:43]=[CH:44][CH:45]=[N:46][C:41]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(N)CCCC1.CN1CCOCC1>C1COCC1>[CH:41]1([NH:46][C:20](=[O:21])[C@H:19]([NH:18][CH2:17][C:16]2[CH:15]=[CH:14][N:13]=[C:12]3[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH:9]=[C:10]([C:28]([O:30][CH3:31])=[O:29])[C:11]=23)[CH2:23][C:24]([F:25])([F:27])[F:26])[CH2:42][CH2:43][CH2:44][CH2:45]1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: COC(=O)c1cn(C(=O)OC(C)(C)C)c2nccc(CN[C@H](CC(F)(F)F)C(=O)O)c12
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CCCC1
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: COC(=O)c1cn(C(=O)OC(C)(C)C)c2nccc(CN[C@H](CC(F)(F)F)C(=O)NC3CCCC3)c12
Temperature: 43 °C
Reaction time: 36 h

Procedure:
To (R)-2-((1-(tert-butoxycarbonyl)-3-(methoxycarbonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methylamino)-4,4,4-trifluorobutanoic acid was added THF (2 mL), HATU (94 mg, 0.246 mmol), cyclopentanamine (70.0 mg, 0.822 mmol) and 4-methylmorpholine (83 mg, 0.822 mmol). The resulting suspension was stirred at 43° C. for 36 h to afford the title compound, which was used in the next step without further purification. [M+H] calc'd for C24H31F3N4O5, 513; found, 513.6.
Reaction SMILES: [CH2:1]([O:8][C:9]1[N:14]=[C:13]([CH2:15]O)[CH:12]=[CH:11][C:10]=1[O:17][CH2:18][CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.[N-:45]=[N+:46]=[N-:47].[Na+]>O.CN(C)C=O>[N:45]([CH2:15][C:13]1[N:14]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:10]([O:17][CH2:18][CH2:19][CH3:20])=[CH:11][CH:12]=1)=[N+:46]=[N-:47]
Reactant: CCCOc1ccc(CO)nc1OCc1ccccc1
Reactant: [N-]=[N+]=[N-]
Agent: BrC(Br)(Br)Br
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Product: CCCOc1ccc(CN=[N+]=[N-])nc1OCc1ccccc1
Temperature: 0 °C

Procedure:
To a mixture of (6-benzyloxy-5-propoxy-pyridin-2-yl)-methanol (1.09 g, 4.0 mmole) and 20 mL of N,N-dimethylformamide stirred and cooled with an ice bath to 0° C. is added triphenylphosphine (1.57 g, 6.0 mmole) followed by carbon tetrabromide (1.99 g, 6.0 mmole). This is stirred for 15 minutes maintaining temperature between 0-5°. Sodium azide is then added (781 mg, 12.0 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature. The reaction mixture is diluted with water and extracted with ether. The combined extracts were dried over sodium sulfate, filtered, evaporated and the residue chromatographed on silica gel eluting with hexane/ethyl acetate to give a-clear liquid, 1.05 g, (88%); MS (ES+): m/z 299.1 (M+H).
Reaction SMILES: [Cl:1][C:2]([Cl:7])([Cl:6])[C:3]([NH2:5])=[NH:4].[C:8](OC)(=[O:13])[CH2:9][C:10]([CH3:12])=O.C(=O)([O-])[O-].[K+].[K+]>O>[OH:13][C:8]1[CH:9]=[C:10]([CH3:12])[N:5]=[C:3]([C:2]([Cl:7])([Cl:6])[Cl:1])[N:4]=1
Reactant: N=C(N)C(Cl)(Cl)Cl
Reactant: COC(=O)CC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Cc1cc(O)nc(C(Cl)(Cl)Cl)n1
Reaction time: 72 h
Yield: 46 %

Procedure:
A mixture of 44.4 g (0.28 mole) trichloroacetamidine, 32.0 g (0.28 mole) methyl acetoacetate, 37.5 g (0.28 mole) potassium carbonate, and 450 ml water was stirred for 3 days. A trace of solid was removed by filtration and the filtrate was made acidic with hydrochloric acid. The product precipitated out to give 28.9 g (46% yield; (mp 173°-174° C.). The structure was confirmed via mp*, infrared and elemental analysis.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH3:11].[NH3:13]>O>[CH3:11][C:7]1[C:6]2[C:10](=[C:2]([NH2:13])[CH:3]=[C:4]([F:12])[CH:5]=2)[NH:9][CH:8]=1
Reactant: N
Reactant: Cc1c[nH]c2c(Br)cc(F)cc12
Solvent: O
Product: Cc1c[nH]c2c(N)cc(F)cc12
Temperature: 170 °C

Procedure:
A mixture of 7-Bromo-5-fluoro-3-methyl-indole (2.5 g), Cu (0.77 g), CuBr (1.57 g) and NH3 (30 mL of a 33% aqueous solution) was heated in an autoclave for 2 h at 170° C. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was dried and the solvent removed to give 3-methyl-5-fluoro-7-amino-indole (1.84 g) as an oil which was used without further purification. UPLC/MS found for C9H9FN2 as (M+H)+ 165.2
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@:8]([OH:36])([CH2:30]OS(C)(=O)=O)[C@H:9]([N:11]1[CH:15]=[CH:14][N:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])=[CH:18][CH:17]=2)[C:12]1=[O:29])[CH3:10].[NH:37]1[CH:41]=[N:40][CH:39]=[N:38]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.C(OC(C)C)(C)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]([OH:36])([CH2:30][N:37]1[CH:41]=[N:40][CH:39]=[N:38]1)[C@H:9]([N:11]1[CH:15]=[CH:14][N:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])=[CH:18][CH:17]=2)[C:12]1=[O:29])[CH3:10]
Reactant: C[C@@H](n1ccn(-c2ccc(OC(F)(F)C(F)F)cc2)c1=O)[C@](O)(COS(C)(=O)=O)c1ccccc1F
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CC(C)OC(C)C
Product: C[C@@H](n1ccn(-c2ccc(OC(F)(F)C(F)F)cc2)c1=O)[C@@](O)(Cn1cncn1)c1ccccc1F
Temperature: 80 °C
Yield: 58.5 %

Procedure:
1-[(1R,2S)-2-(2-Fluorophenyl)-2-hydroxy-3-methanesulfonyloxy-1-methylpropyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (3.6 g) was dissolved in 70 ml of dimethylformamide, to which 2.0 g of 1H-1,2,4-triazole and 7.8 g of potassium carbonate were added. The mixture was heated at 80° C. for 4 hours. The reaction solution was diluted with a mixture of 150 ml of ethyl acetate and 50 ml of diisopropyl ether, and washed with 150 ml of water, 1N-hydrochloric acid (100 ml×2) and 100 ml of an aqueous solution of sodium chloride successively. The organic layer was dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate=1:2 to ethyl acetate). The desired fraction was concentrated and the residue was recrystallized from diisopropyl ether to give 2.0 g of 1-[(1R,2S)-2-(2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (yield: 69%) as a colorless powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[C:15]2[C:6]([O:7][C:8]3[CH:9]=[CH:10][C:11]([C:18]([OH:20])=[O:19])=[CH:12][C:13]=3[C:14]2=[O:17])=[CH:5][CH:4]=1.[CH2:21](O)[CH3:22]>S(=O)(=O)(O)O>[CH3:1][O:2][C:3]1[CH:16]=[C:15]2[C:6]([O:7][C:8]3[CH:9]=[CH:10][C:11]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][C:13]=3[C:14]2=[O:17])=[CH:5][CH:4]=1
Reactant: COc1ccc2oc3ccc(C(=O)O)cc3c(=O)c2c1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc2oc3ccc(OC)cc3c(=O)c2c1
Yield: 84 %

Procedure:
A mixture of 7-methoxy-9-oxoxanthene-2-carboxylic acid in ethanol (100ml) and concentrated sulfuric acid (10 ml) was refluxed under nitrogen for 24 hours. The reaction mixture was concentrated and cooled. The product, which precipitated, was filtered off and recrystallized from ethanol to give white crystals (2.53g, 84%), mp. 170°-172° C.
Reaction SMILES: [CH3:1][C:2]([N:6]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[N:8]=[CH:7]1)([CH3:5])[CH:3]=O.[CH3:14][NH:15][CH3:16]>>[CH3:14][N:15]([CH3:16])[CH2:3][C:2]([CH3:1])([N:6]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[N:8]=[CH:7]1)[CH3:5]
Reactant: CC(C)(C=O)n1cnc([N+](=O)[O-])c1
Reactant: CNC
Product: CN(C)CC(C)(C)n1cnc([N+](=O)[O-])c1

Procedure:
2-Methyl-2-(4-nitro-imidazol-1-yl)-propionaldehyde was reacted with dimethyl amine to provide the title compound: H1 NMR (400 MHz, CDCl3) 1.50 (s, 6H), 2.00 (s, 6H), 2.40 (s, 2H), 7.55 (s, 1H), 7.89 (s, 1H).
Reaction SMILES: [OH-].[K+].C([O:5][C:6](=[O:34])[C:7]([CH3:33])([CH3:32])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15](=[O:31])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][C:23]([C:26]([O:28]CC)=[O:27])([CH3:25])[CH3:24])[CH:17]=2)[CH:10]=1)C>O.C(O)C>[C:26]([C:23]([CH3:25])([CH3:24])[CH2:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[C:15]([C:11]1[CH:10]=[C:9]([CH2:8][C:7]([CH3:33])([CH3:32])[C:6]([OH:34])=[O:5])[CH:14]=[CH:13][CH:12]=1)=[O:31])([OH:28])=[O:27]
Reactant: CCOC(=O)C(C)(C)Cc1cccc(C(=O)c2cccc(CC(C)(C)C(=O)OCC)c2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)(Cc1cccc(C(=O)c2cccc(CC(C)(C)C(=O)O)c2)c1)C(=O)O
Yield: 101.5 %

Procedure:
To a solution of potassium hydroxide (1.57 g, 28 mmol) in water (1.5 mL) and absolute ethanol (5 mL) was added 3-{3-[3-(2-ethoxycarbonyl-2-methyl-propyl)-benzoyl]-phenyl}-2,2-dimethyl-propionic acid ethyl ester (4.38 g, 10 mmol) in portions. The mixture was heated to reflux for 3 h and the ethanol was distilled off under reduced pressure on a water-bath. The residual aqueous solution was extracted with chloroform (2×50 mL), then cooled with an ice-bath, and acidified with hydrochloric acid to pH 1. The mixture was extracted with diethyl ether (3×50 mL). The ethereal extracts were dried over sodium sulfate and concentrated in vacuo to give 3-{3-[3-(2-carboxy-2-methylpropyl)benzoyl]-phenyl}-2,2-dimethyl-propanoic acid (3.88 g, 100%) as a solid. Mp.: 46-48° C. 1H NMR (300 MHz, CDCl3): δ (ppm): 7.8-7.2 (m, 8H), 2.83 (s, 4H), 1.25 (s,12H). 13C NMR (75 MHz, CDCl3): δ (ppm): 198.02, 184.0, 139.2, 137.3, 134.5, 129.5, 128.4, 128.3, 127.6, 43.8, 24.7. HRMS (LSIMS, gly): Calcd. for C23H27O5 (MH+): 383.1858, found: 383.1858.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1>O1CCOCC1.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Reactant: COc1ccc(N)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: C1COCCO1
Solvent: CCOCC
Product: COc1ccc(Nc2ccc([N+](=O)[O-])cc2)cc1
Reaction time: 0.17 h
Yield: 58.5 %

Procedure:
A mixture of palladium acetate (37 mg, 0.165 mmol) and BINAP (154 mg, 0.248 mmol) in 5 mL dioxane was stirred for 10 min under Ar atmosphere. To this mixture was added 1-bromo-4-nitrobenzene (1.11 g, 5.5 mmol), 4-methoxyaniline (745 mg, 6.07 mmol), CsCO3 (2.5 g, 7.73 mmol), and 10 mL of dioxane. The mixture was heated at reflux for 15 h and cooled and diluted with ether (80 mL). The solid was removed through filtration and the filtrate was concentrated. The residue was chromatographed (hexane/EtOAc) to afford 4-methoxy-N-(4-nitrophenyl)aniline as a yellow solid (786 mg, 58%). MS (ESI) m/z 245 (M+H+).
Reaction SMILES: [CH2:1]1[CH:7](O)[NH:6][P:4]([N:9]([CH2:13][CH2:14][Cl:15])[CH2:10][CH2:11][Cl:12])(=[O:5])[O:3][CH2:2]1.[SH:16][CH2:17][CH2:18][S:19]([OH:22])(=[O:21])=[O:20]>O>[Cl:12][CH2:11][CH2:10][N:9]([CH2:13][CH2:14][Cl:15])[P:4]1(=[O:5])[NH:6][CH:7]([S:16][CH2:17][CH2:18][S:19]([OH:22])(=[O:21])=[O:20])[CH2:1][CH2:2][O:3]1
Reactant: O=P1(N(CCCl)CCCl)NC(O)CCO1
Reactant: O=S(=O)(O)CCS
Solvent: O
Product: O=P1(N(CCCl)CCCl)NC(SCCS(=O)(=O)O)CCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
0.8 g (3.0 mmol) of 4-hydroxycyclophosphamide in 3 ml of water were mixed with 420 mg (3.0 mmol) of 2-mercaptoethanesulphonic acid, with ice water cooling. After 1 hour, the mixture was concentrated under high vacuum and was crystallised.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[C:9]2[SH:13])[CH:3]=1.[CH3:14][C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[C:16]=1[S:23]([NH:26][C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29]Cl)(=[O:25])=[O:24]>>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[C:9]2[S:13][CH2:29][C:28]2[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=2[NH:26][S:23]([C:16]2[C:15]([CH3:14])=[CH:20][C:19]([CH3:21])=[CH:18][C:17]=2[CH3:22])(=[O:24])=[O:25])[CH:3]=1
Reactant: Cc1ccnc(-n2ccnc2S)c1
Reactant: Cc1cc(C)c(S(=O)(=O)Nc2ccccc2CCl)c(C)c1
Product: Cc1ccnc(-n2ccnc2SCc2ccccc2NS(=O)(=O)c2c(C)cc(C)cc2C)c1

Procedure:
1.25 g of 1-(4-methyl-2-pyridyl)-2-mercaptoimidazole and o-(2,4,6-trimethylphenyl)sulfonylaminobenzyl chloride are treated in the same manner as described in Example 1-(1) to give 2.19 g of 1-(4-methyl-2-pyridyl)-2-(2-(2,4,6-trimethylphenyl)sulfonylaminobenzylthio)imidazole. (2) The product obtained above is treated in the same manner as described in Example 73 to give 1-(4-methyl-2-pyridyl)-2-(2-methylaminobenzylsulfinyl)imidazole.