Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:4]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:31])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH3:30])=[CH:18][C:17]=2[O:32][CH3:33])=[CH:5][CH:6]=[C:7]2[C:12]=1[NH:11][C:10](=[O:13])[C:9]([CH3:15])([CH3:14])[NH:8]2.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][C:37]=1O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C1CCN(C(/N=N/C(N2CCCCC2)=O)=O)CC1>O1CCCC1>[CH3:33][O:32][C:17]1[CH:18]=[C:19]([O:22][C:23](=[O:31])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH3:30])[CH:20]=[CH:21][C:16]=1[C:4]1[C:3]([CH2:2][O:1][C:37]2[CH:38]=[C:39]([N+:42]([O-:44])=[O:43])[CH:40]=[CH:41][C:36]=2[O:35][CH3:34])=[C:12]2[C:7]([NH:8][C:9]([CH3:14])([CH3:15])[C:10](=[O:13])[NH:11]2)=[CH:6][CH:5]=1
Reactant: COc1ccc([N+](=O)[O-])cc1O
Reactant: COc1cc(OC(=O)c2ccccc2C)ccc1-c1ccc2c(c1CO)NC(=O)C(C)(C)N2
Agent: CCCCP(CCCC)CCCC
Agent: O=C(/N=N/C(=O)N1CCCCC1)N1CCCCC1
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: COc1ccc([N+](=O)[O-])cc1OCc1c(-c2ccc(OC(=O)c3ccccc3C)cc2OC)ccc2c1NC(=O)C(C)(C)N2
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 41.2 %

Procedure:
A mixture of 8-hydroxymethyl-7-[2-methoxy-4-(2-methylbenzoyloxy)phenyl]-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 23, 40.1 mg, 0.0898 mmol), 2-methoxy-5-nitrophenol (22.8 mg, 0.135 mmol), and tri n-butylphosphine (33.7 μL, 0.135 mmol) was dissolved in anhydrous tetrahydrofuran (1 mL), 1,1′-(azodicarbonyl)dipiperidine (34.0 mg, 0.135 mmol) was added thereto, and then the mixture was stirred at room temperature. After 20 minutes, 2-methoxy-5-nitrophenol (23.1 mg, 0.137 mmol), tri n-butylphosphine (33.7 μL, 0.135 mmol), and 1,1′-(azodicarbonyl)dipiperidine (33.9 mg, 0.134 mmol) were added thereto, and after 80 minutes, 2-methoxy-5-nitrophenol (22.9 mg, 0.135 mmol), tri-n-butylphosphine (33.7 μL, 0.135 mmol), and 1,1-(azodicarbonyl)dipiperidine (34.0 mg, 0.135 mmol) were added further. The stir was stopped 3 hours later and the reaction mixture was concentrated. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled compound (22.1 mg) as a pale yellow amorphous product. (Yield 41%)
Reaction SMILES: C(O)(=O)C.[N:5]1[CH:10]=[CH:9][C:8]([CH:11]=O)=[CH:7][CH:6]=1.[C:13]([O:22][CH3:23])(=[O:21])[C:14]1[C:15](=[CH:17][CH:18]=[CH:19][CH:20]=1)[NH2:16].C([BH3-])#N.[Na+]>CO>[N:5]1[CH:6]=[CH:7][C:8]([CH2:11][NH:16][C:15]2[C:14](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:13]([O:22][CH3:23])=[O:21])=[CH:9][CH:10]=1
Reactant: O=Cc1ccncc1
Reactant: COC(=O)c1ccccc1N
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)c1ccccc1NCc1ccncc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
3 mL Acetic acid and 8.6 g 4-pyridinecarbaldehyde are added to a solution of 7.5 g methyl anthranilate in 300 mL methanol. The mixture is stirred for 12 hours under nitrogen atmosphere at room temperature. 5.7 g Sodium cyanotrihydridoborate (85%) is added and the mixture is stirred for 3 hours at room temperature. Additional 1.14 g sodium cyanotrihydridoborate (85%) is added and the mixture is stirred for 12 hours at room temperature. The solvent is evaporated and the residue dissolved in ethyl acetate and washed with saturated NaHCO3 solution and saturated sodium chloride solution. The organic extract is concentrated and purified with hexane/ethyl acetate (1:1) on silica gel to yield methyl N-(4-pyridylmethyl)-anthranilate with m.p. 86° C.
Reaction SMILES: CS(O)(=O)=O.[NH2:6][C:7]1[CH:8]=[CH:9][C:10]([Cl:16])=[C:11]([CH:15]=1)[C:12]([OH:14])=[O:13].[CH3:17][CH:18](O)[CH3:19]>>[NH2:6][C:7]1[CH:8]=[CH:9][C:10]([Cl:16])=[C:11]([CH:15]=1)[C:12]([O:14][CH:18]([CH3:19])[CH3:17])=[O:13]
Reactant: Nc1ccc(Cl)c(C(=O)O)c1
Reactant: CC(C)O
Agent: CS(=O)(=O)O
Product: CC(C)OC(=O)c1cc(N)ccc1Cl
Reaction time: 6 h
Yield: 75 %

Procedure:
Methanesulfonic acid (99%, 318 g, 3.3 mole) was added slowly to a stirred mixture of 5-amino-2-chloro-benzoic acid (85%, 215 g, 1.1 mole) in 2-propanol (about 1100 ml). The mixture was heated under reflux with stirring for 6 hours, then the excess 2-propanol was evaporated under reduced pressure. Water (about 1000 ml) was added to the residue and the mixture was neutralized with solid sodium bicarbonate and extracted with methylene chloride (about 1200 ml). The extract was washed twice with water, dried over magnesium sulfate and evaporated to give a purple oil, which crystallized on seeding. The product was reprecipitated from dilute hydrochloric acid solution by slowly basifying with concentrated ammonium hydroxide and seeding. The resulting crystals after drying melted at 50.5°-52° C. (170 g, 75% yield).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.Cl[CH2:17][C:18]1[N:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[O:20][N:19]=1>>[F:15][C:2]([F:14])([F:1])[C:3]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][N:7]2[CH2:17][C:18]1[N:22]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:27][CH:28]=2)[O:20][N:19]=1
Reactant: FC(F)(F)c1ccc(-c2nc(CCl)no2)cc1
Reactant: N#Cc1ccc2[nH]ccc2c1C(F)(F)F
Product: N#Cc1ccc2c(ccn2Cc2noc(-c3ccc(C(F)(F)F)cc3)n2)c1C(F)(F)F

Procedure:
Synthesized as described in Example 23 using 4-(trifluoromethyl)-1H-indole-5-carbonitrile and 3-(chloromethyl)-5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole: MS (ES) m/z 437 (M+1).
Reaction SMILES: [C:1]1([CH2:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]32[CH2:19][C:18](=[O:20])[NH:17][C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]=2[S:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=CC=C(C(OO)=[O:33])C=1.S([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[C:1]1([CH2:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]32[CH2:19][C:18](=[O:20])[NH:17][C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]=2[S:14]3=[O:33])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1CC2(CCCCC2Cc2ccccc2)Sc2ccccc2N1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=C1CC2(CCCCC2Cc2ccccc2)S(=O)c2ccccc2N1

Procedure:
To a solution of 2'-phenylmethyl-4,5-dihydro-4-oxospiro[1,5-benzothiazepine-2(3H), 1'-cyclohexane] (5.0 g) in methylene chloride (150 ml) was added 80% m-chloroperbenzoic acid (3.9 g) at 0° C. After fifteen minutes, a saturated aqueous solution (150 ml) of sodium sulfite was added to the solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diisopropyl ether to give 2'-phenylmethyl-4,5-dihydro-4-oxospiro[1,5-benzothiazepine-2(3H), 1'-cyclohexane] 1-oxide
Reaction SMILES: C([NH:8]C1C=C(C=C(S(Cl)(=O)=O)C=1C1C=CC=CC=1)C(O)=O)C1C=CC=CC=1.Cl[S:29]([C:32]1[C:33]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[C:34]([O:41][CH2:42][CH2:43][CH3:44])[CH:35]=[C:36]([CH:40]=1)[C:37]([OH:39])=[O:38])(=[O:31])=[O:30]>>[C:45]1([C:33]2[C:32]([S:29](=[O:31])(=[O:30])[NH2:8])=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[CH:35][C:34]=2[O:41][CH2:42][CH2:43][CH3:44])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1
Reactant: CCCOc1cc(C(=O)O)cc(S(=O)(=O)Cl)c1-c1ccccc1
Reactant: O=C(O)c1cc(NCc2ccccc2)c(-c2ccccc2)c(S(=O)(=O)Cl)c1
Product: CCCOc1cc(C(=O)O)cc(S(N)(=O)=O)c1-c1ccccc1

Procedure:
By replacing in Example 1, step G, 3-benzylamino-5-chlorosulfonyl-4-phenylbenzoic acid with 5-chlorosulfonyl-4-phenyl-3-n-propoxybenzoic acid, and following the procedure described, 4-phenyl-3-n-propoxy-5-sulfamylbenzoic acid is obtained with a melting point of 155°-157° C.
Reaction SMILES: [SH2:1].[CH3:2][C:3]1([CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[O:5][CH2:4]1.C(NC(C)C)(C)C>O1CCCC1.CCOCC>[SH:1][CH2:4][C:3]([CH3:2])([OH:5])[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCC1(C)CO1
Reactant: S
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CC(C)NC(C)C
Product: CCCCCC(C)(O)CS
Temperature: 25 °C
Reaction time: 68 h

Procedure:
Hydrogen sulfide gas was bubbled into a solution of 5 (3.84 g, 30 mmol) in tetrahydrofuran (30 mL) containing diisopropylamine (21 mL, 150 mmol) for one hour and the reaction mixture was stirred at room temperature for 68 hours. It was diluted with ether and washed with 10% aqueous hydrogen chloride, saturated sodium bicarbonate solution, and saturated aqueous sodium chloride. The organic layer was dried over magnesium sulfate. The solvent was evaporated in vacuo; 1.2 g of 1-mercapto-2-methylheptan-2-ol 6 was obtained after HPLC purification. IR (neat): 3600-3200 cm-1 (br); PMR (CDCl3): δ 2.67 (s, 1H), 2.57 (s, 1H), 2.17 (s, 1H), 1.70-1.20 (m, 9H), 1.22 (s, 3H), and 0.90 (t, 3H).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16](C(NN)=O)=[N:17][CH:18]=[CH:19][N:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:25]([O-])=O.[Na+].[C:29](=[O:32])(O)[O-].[Na+]>Cl.O>[O:32]=[C:29]1[N:14]([CH:11]2[CH2:10][CH2:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:13][CH2:12]2)[C:15]2=[N:20][CH:19]=[CH:18][N:17]=[C:16]2[NH:25]1
Reactant: O=N[O-]
Reactant: NNC(=O)c1nccnc1NC1CCN(Cc2ccccc2)CC1
Reactant: O=C([O-])O
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=c1[nH]c2nccnc2n1C1CCN(Cc2ccccc2)CC1
Temperature: 180 °C

Procedure:
3-[(1-Benzylpiperidin-4-yl)amino]pyrazine-2-carbohydrazide (3.0 g, 9.2 mmol) was dissolved in 1N HCl (20 mL) and water (40 mL), and cooled to 0° C. To this was added aqueous sodium nitrite (0.8 g, 11.6 mmol) in water (5 mL). After 0.5 h sodium bicarbonate was added and the basic solution extracted with chloroform (5×50 mL), which was dried over magnesium sulfate. The crude acyl azide was dissolved in methoxyethanol (20 mL) and heated at 180° C. for 3 h. The progress of the reaction was monitored by thin layer chromatography (10% methanol in chloroform). The reaction was cooled and concentrated, and the crude product purified by preparative thin layer chromatography (silica gel, 75:25 tetrahydrofuran:hexane) to give the title compound (1.7 g). MS 310 (M+1).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:26]([F:29])([F:28])[F:27])[NH:15][C:16]3=[O:19])=[CH:11][CH:10]=2)[CH2:4]1.[CH3:30][C:31]([O:34][C:35]([N:37]([CH2:39][C:40](O)=[O:41])[CH3:38])=[O:36])([CH3:33])[CH3:32]>C(Cl)Cl>[O:8]=[C:6]1[N:5]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:26]([F:28])([F:27])[F:29])[NH:15][C:16]3=[O:19])=[CH:11][CH:10]=2)[CH2:4][C@H:3]([CH2:2][O:1][C:40](=[O:41])[CH2:39][N:37]([C:35]([O:34][C:31]([CH3:32])([CH3:30])[CH3:33])=[O:36])[CH3:38])[O:7]1
Reactant: CN(CC(=O)O)C(=O)OC(C)(C)C
Reactant: O=C1O[C@@H](CO)CN1c1ccc2cc(-c3ccccc3C(F)(F)F)[nH]c(=O)c2c1
Solvent: ClCCl
Product: CN(CC(=O)OC[C@H]1CN(c2ccc3cc(-c4ccccc4C(F)(F)F)[nH]c(=O)c3c2)C(=O)O1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 15 h
Yield: 100 %

Procedure:
The 7-((R)-5-hydroxymethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (800 mg, 1.98 mmol) obtained in step B of Example 1-14 was dissolved in methylene chloride (10 ml). Thereafter, Boc-sar-OH (449 mg, 2.37 mmol), N,N-dimethylaminopyridine (73 mg, 0.59 mmol), and WSCI (493 mg, 2.57 mmol) were added at 0° C. to the solution. The obtained mixture was stirred at a room temperature for 15 hours. Thereafter, the reaction mixture was concentrated under reduced pressure, and the obtained residue was then purified by silica gel chromatography (methylene chloride:methanol=20:1), so as to obtain N-tert-butoxycarbonyl-N-methylaminoacetic acid (R)-2-oxo-3-[1-oxo-3-(2-trifluoromethylphenyl)-1,2-dihydroisoquinolin-7-yl]oxazolidin-5-ylmethyl ester (1.14 g, 100%) in the form of a colorless foaming substance.
Reaction SMILES: [C:1]([C:3](=[C:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:22][C@H:21]([CH2:23][NH:24][C:25](=[O:27])[CH3:26])[O:20][C:19]3=[O:28])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[C:4]#[N:5])#[N:2].[I-].[CH3:30][S+](C)(C)=O.CC(C)([O-])C.[K+]>CS(C)=O>[C:1]([C:3]1([C:4]#[N:5])[C:6]2([CH2:11][CH2:10][N:9]([C:12]3[CH:13]=[CH:14][C:15]([N:18]4[CH2:22][C@H:21]([CH2:23][NH:24][C:25](=[O:27])[CH3:26])[O:20][C:19]4=[O:28])=[CH:16][CH:17]=3)[CH2:8][CH2:7]2)[CH2:30]1)#[N:2]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(=C(C#N)C#N)CC3)cc2)C(=O)O1
Reactant: C[S+](C)(C)=O
Agent: CC(C)(C)[O-]
Agent: [I-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCC4(CC3)CC4(C#N)C#N)cc2)C(=O)O1
Yield: 52 %

Procedure:
The title compound was prepared by reacting (S)-N-[3-{4-[4-dicyanomethylidenepiperidin-1-yl]-phenyl}-2-oxo-1,3-oxazolidin-5-ylmethyl]-acetamide (1.0 mmol, Example D), trimethyloxosulphonium iodide (1.3 mmol), potassium tert-butoxide (1.3 mmol) in dimethylsulfoxide (10 ml) at a temperature 25° C. for 14 hours in 52% yield.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[NH2:15][C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([N+:26]([O-])=O)=[CH:18][CH:17]=1>>[CH3:3][C:2]1([CH3:11])[NH:26][C:19]2[C:20]3[C:25]([C:16]([N:15]=[N:1][C:2]4[C:11]5[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=5)[CH:5]=[CH:4][C:3]=4[N+:12]([O-:14])=[O:13])=[CH:17][CH:18]=2)=[CH:24][CH:23]=[CH:22][C:21]=3[NH:1]1
Reactant: Nc1ccc([N+](=O)[O-])c2ccccc12
Reactant: Nc1c([N+](=O)[O-])ccc2ccccc12
Product: CC1(C)Nc2cccc3c(N=Nc4c([N+](=O)[O-])ccc5ccccc45)ccc(c23)N1

Procedure:
In the manner described in Example 8, substituting 9.5 grams of 1-amino-2-nitronaphthalene for the 1-amino-4-nitronaphthalene, the desired compound is obtained.
Reaction SMILES: CC(S([NH:7][C@H:8]([C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1)[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=O)(C)C.[ClH:27]>CO.O1CCOCC1>[ClH:27].[C:11]1([CH2:10][CH2:9][C@H:8]([NH2:7])[C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:19][CH:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(C)(C)S(=O)N[C@@H](CCc1ccccc1)c1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: N[C@@H](CCc1ccccc1)c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-methyl-N-{(1S)-3-phenyl-1-[4-(trifluoromethyl)phenyl]propyl}propane-2-sulfinamide (JACS, 2005, 127, 1092-3) (8.3 g, 21.7 mmol) was dissolved in methanol (50 mL) and a 4M solution of HCl in dioxane (10.8 mL) was added. The solution was stirred at RT for 1 h then concentrated. The residue was triturated with isohexane to give a colourless solid which was collected by filtration. 1H NMR (400 MHz), δ (ppm) (DMSO-D6): 8.7 (3H, s), 7.85 (2H, d, J 8.3 Hz), 7.77 ((2H, d, J 8.3 Hz), 7.29-7.26 (2H, m), 7.20-7.13 (3H, m), 4.36 (1H, m), 2.4-2.35 (2H, m), 2.35-2.25 (m, 1H), 2.2-2.1 (1H, m).
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]=[C:5]=[O:6].[CH3:7][C:8]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:9]=1[NH2:10].ClCCNC(N)=O.CO>O1CCCC1.O>[CH3:7][C:8]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:9]=1[NH:10][C:5]1[O:6][CH2:2][CH2:3][N:4]=1
Reactant: Cc1cccc(N)c1C
Reactant: O=C=NCCCl
Agent: NC(=O)NCCCl
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cccc(NC2=NCCO2)c1C
Temperature: 25 °C
Yield: 22.3 %

Procedure:
Chloroethylisocyanate (Compound 5, Aldrich, 346 mg, 3.3 mmol) was added to a stirred solution of 2,3-dimethylaniline (Aldrich, 400 mg, 3.3 mmol) in tetrahydrofuran (5 ml) at room temperature. After 30 minutes a white precipitate formed. The solid chloroethylurea was collected by vacuum filtration yield: 477 mg (64%): mp 145°-146° C. HNMR (300 MHz, CDCl3) σ 7.00 (m, 3H); 6.72 (br, 1H); 5.19 (br, 1H), 3.59 (m, 2H); 3.49 (m, 2H); 2.30 (s, 3H); 2.18 (s, 3H); Mass spectrum m/e 226.0872 (C1H15ClN2O requires 226.0872). The chlorethylurea (199 mg, 0.88 mmol) was suspended in H2O (4 ml) and CH3OH (4 ml) and heated to reflux for 1 hour. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was dissolved in CH2Cl2 and washed with 1N NaOH (to pH 13). The organic layer was dried over Na2CO3 and concentrated in vacuo to yield 140 mg (84%) of the title compound as a white crystalline solid: mp 112°-113.5° C.; 1H NMR (300 MHz, CDCl3) σ 7.19 (m, 1H); 7.09 (m, 1H), 6.91 (m, 1H); 5.00 (br, s, 1H); 4.40 (t, 2H); 3.70 (t, 2H); 2.30 (s, 3H); 2.15 (s, 3H); Mass spectrum m/e 190.1104 (C11H14N2O requires 190.1106).
Reaction SMILES: [C:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[B:16]([OH:17])[O:15][CH2:14][C:13]=3[CH:18]=2)=[C:6]([OH:21])[CH:5]=1)([OH:3])=[O:2].S(=O)(=O)(O)O.O.[CH2:28](O)[CH3:29]>>[CH2:28]([O:2][C:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[B:16]([OH:17])[O:15][CH2:14][C:13]=3[CH:18]=2)=[C:6]([OH:21])[CH:5]=1)=[O:3])[CH3:29]
Reactant: CCO
Reactant: O=C(O)c1ccc(Oc2ccc3c(c2)COB3O)c(O)c1
Agent: O=S(=O)(O)O
Solvent: O
Product: CCOC(=O)c1ccc(Oc2ccc3c(c2)COB3O)c(O)c1
Yield: 77 %

Procedure:
A mixture of 5-(4-carboxy-2-hydroxyphenoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1.95 g, 6.82 mmol) and sulfuric acid (1.5 mL) in ethanol (75 mL) was refluxed for 6 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. Silica gel column (6:4 to 5:5 hexane/acetone) followed by recrystallization from diisopropyl ether gave 5-(4-Ethoxycarbonyl-2-hydroxyphenoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1.65 g, 77%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][CH3:15])[C:11]=1[O:12][CH3:13])[C:6](O)=[O:7].CP(=O)(C)CCCCCCCCCCCC.C(Cl)([Cl:34])=O>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][CH3:15])[C:11]=1[O:12][CH3:13])[C:6]([Cl:34])=[O:7]
Reactant: COc1cc(C(=O)O)cc(OC)c1OC
Reactant: O=C(Cl)Cl
Agent: CCCCCCCCCCCCP(C)(C)=O
Solvent: Cc1ccccc1C
Product: COc1cc(C(=O)Cl)cc(OC)c1OC

Procedure:
A mixture of 100 g of 3,4,5-trimethoxybenzoic acid, 150 g of xylene and 0.1 g of dimethyl-dodecyl-phosphine oxide is treated with phosgene at 100°C in the apparatus described for example 1. After a lapse of abt. 1 hour and phosgene consumption of 140 g the absorption of phosgene is terminated. At the end of a two-hours-postreaction a yellow solution of 3,4,5-trimethoxy-benzoylchloride is obtained. The yield in dissolved acid chloride is approx. 106 g, corresponding to 97.5% of the theoretical yield, calculated on the acid used. The solution may be used directly for further reactions after having eliminated the remaining phosgene by means of nitrogen or by distillation of a part of the solvent. But it is also possible to isolate the trimethoxy-benzoylchloride in its pure form by means of vacuum distillation (boiling point: 137°C/1.5 torr. softening point: 80 to 81°C).
Reaction SMILES: C([O-])(=O)C.[Si:5](Cl)([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6].[Br:13][C:14]1[C:15]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][OH:34])=[CH:16][C:17]2[C:18]([CH3:27])([CH3:26])[CH2:19][CH2:20][C:21]([CH3:25])([CH3:24])[C:22]=2[CH:23]=1.[H-].[Na+]>C1COCC1.C(OCC)(=O)C.O>[Br:13][C:14]1[C:15]([O:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][O:34][Si:5]([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6])=[CH:16][C:17]2[C:18]([CH3:26])([CH3:27])[CH2:19][CH2:20][C:21]([CH3:24])([CH3:25])[C:22]=2[CH:23]=1
Reactant: CC1(C)CCC(C)(C)c2cc(OCCCCCO)c(Br)cc21
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CC(=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC1(C)CCC(C)(C)c2cc(OCCCCCO[Si](C)(C)C(C)(C)C)c(Br)cc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The acetate obtained above is saponified and the resulting hydroxyl group is then protected according to the following procedure: tert-Butyldimethylsilyl chloride (2.64 g) is added to a mixture of 5-(3-bromo-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)pentan-1-ol (4.3 g, 11.7 mmol) and 80% sodium hydride (422 mg) in THF (20 ml). The mixture is stirred at room temperature for 2 h. The solution is poured into a mixture of water and ethyl acetate. The organic phase is washed twice with water, dried over magnesium sulphate and concentrated on a rotary evaporator under vacuum at 40° C. The product is purified by flash chromatography on a column of silica.
Reaction SMILES: C(N)C1C=CC=CC=1.[CH:9]1([CH2:12][CH2:13][NH2:14])[CH2:11][CH2:10]1.[F:15][C:16]1[CH:38]=[CH:37][C:19]([CH2:20][N:21]2[CH2:25][CH2:24][N:23]([C:26]3[CH:27]=[C:28]([CH:33]=[CH:34][N:35]=3)[C:29](OC)=[O:30])[C:22]2=[O:36])=[CH:18][CH:17]=1>>[CH:9]1([CH2:12][CH2:13][NH:14][C:29](=[O:30])[C:28]2[CH:33]=[CH:34][N:35]=[C:26]([N:23]3[CH2:24][CH2:25][N:21]([CH2:20][C:19]4[CH:18]=[CH:17][C:16]([F:15])=[CH:38][CH:37]=4)[C:22]3=[O:36])[CH:27]=2)[CH2:11][CH2:10]1
Reactant: COC(=O)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Reactant: NCCC1CC1
Solvent: NCc1ccccc1
Product: O=C(NCCC1CC1)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Yield: 70 %

Procedure:
Following the procedure as described in Example 15, making variations as required to replace benzylamine with 2-cyclopropylethanamine to react with methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate, N-(2-cyclopropylethyl)-2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinamide was obtained as a colorless solid in 70% yield: mp 123-125° C.; 1H NMR (300 MHz, CDCl3) δ 8.56 (s, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.38 (dd, J=5.1, 1.2 Hz, 1H), 7.29-7.24 (m, 2H), 7.05-7.00 (m, 2H), 6.52 (br s, 1H), 4.44 (s, 2H), 4.05 (t, J=8.1 Hz, 2H), 3.55-3.49 (m, 2H), 3.37 (t, J=8.1 Hz, 2H), 1.54-1.47 (m, 2H), 0.77-0.64 (m, 1H), 0.53-0.45 (m, 2H), 0.11-0.02 (m, 2H); MS (ES+) m/z 383.3 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][NH2:9])[N:3]=1.C([O:12][C:13](=[O:21])[C:14]([C:19]#[N:20])=[CH:15]OCC)C.[CH3:22][CH2:23]O>>[CH2:22]([C:15]1[C:14]([C:13]([OH:12])=[O:21])=[C:19]([NH2:20])[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[N:3]=2)[N:9]=1)[CH3:23]
Reactant: NNc1cccc(Cl)n1
Reactant: CCO
Reactant: CCOC=C(C#N)C(=O)OCC
Product: CCc1nn(-c2cccc(Cl)n2)c(N)c1C(=O)O
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a mixture of 2-chloro-6-hydrazinopyridine (2.00 g, 13.93 mmol) and ethyl-2-cyano-3-ethoxyacrylate (2.36 g, 13.93 mmol) was added EtOH (14 mL) and the resulting suspension was stirred at room temperature. After 5 min, the mixture was heated at reflux. After 2 h, the reaction mixture was allowed to cool to room temperature. The title compound was isolated as a white solid by filtration, and was used without further purification: LCMS m/z 267.0 [M+I-1]+.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[CH2:16])[CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].[H-].[Na+].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C(Cl)Cl>CN(C=O)C.C(C1C=C(O)C=CC=1O)(C)(C)C>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O:8][C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[CH2:16])[CH:10]=2)([C:4]([F:6])([F:5])[F:7])[C:2]([F:17])([F:18])[F:1])(=[O:30])=[O:29])=[CH:24][CH:23]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: C=Cc1cccc(C(O)(C(F)(F)F)C(F)(F)F)c1
Agent: CC(C)(C)c1cc(O)ccc1O
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: C=Cc1cccc(C(OS(=O)(=O)c2ccc(Cl)cc2)(C(F)(F)F)C(F)(F)F)c1
Temperature: 5 °C
Yield: 84.3 %

Procedure:
12 g (44.4 mmol) of 1,1,1,3,3,3-hexafluoro-2-(3-vinyl-phenyl)-propan-2-ol were dissolved in 50 ml of anhydrous DMF, and a spatula tip of 2-tert-butyl-hydroquinone (10 mg) was added for stabilization. 1.5 g (50 mmol) of sodium hydride were then added while stirring and cooling with ice at about 5° C. After everything had dissolved, 9.92 g (47mmol) of 4-chlorobenzenesulfonyl chloride were added at the same temperature. The mixture was stirred for 72 hours at room temperature, methylene chloride was then added and the mixture was washed with water, dried, filtered and evaporated down. The residue obtained was chromatographed with hexane/chloroform over a silica gel column. 16.65 g of 2-(4-chlorobenzenesulfonyloxy)-1,1,1,3,3,3-hexafluoro-2-(3-vinylphenyl)-propane (=2,2,2-trifluoro-1-trifluoromethyl-1-(3-vinylphenyl)-ethyl 4-chlorobenzenesulfonate) were isolated (colorless crystals, m.p.: 70° C.).