Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2.[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[CH2:28]([O:30][C:31](=[O:39])[CH2:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH3:29]>C(C(C)=O)C>[CH2:28]([O:30][C:31](=[O:39])[CH2:32][CH:33]1[CH2:38][CH2:37][N:36]([CH2:2][CH2:3][CH2:4][N:5]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[CH2:9][CH2:8][C:7]3[CH:16]=[CH:17][CH:18]=[CH:19][C:6]2=3)[CH2:35][CH2:34]1)[CH3:29]
Reactant: ClCCCN1c2ccccc2CCc2ccccc21
Reactant: CCOC(=O)CC1CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCOC(=O)CC1CCN(CCCN2c3ccccc3CCc3ccccc32)CC1
Temperature: 75 °C
Reaction time: 8 h

Procedure:
A mixture of 5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine (1.5 g, 0.0055 mol, prepared similarly as described in example 1) and potassium iodide (5.4 g, 0.0327 mol) in methyl ethyl ketone (100 ml) was heated at reflux temperature for 2.5 h. Potassium carbonate (1.5 g, 0.0109 mol) and 4-piperidineacetic acid ethyl ester (1.4 g, 0.0082 mmol, described in J. Am. Chem. Soc., Vol. 75, 6249, 1953) were added and the reaction mixture was stirred at 75° C. overnight. After cooling, the reaction mixture was filtered (Hyflo) and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel (150 g) using a gradient of heptane and ethyl acetate (1:1→3:7), to give 0.6 g of 1-(3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-1-propyl)-4-piperidineacetic acid ethyl ester as an oil.
Reaction SMILES: CO[C:3](=[O:22])[C@H:4]([CH2:7][CH2:8][CH2:9][CH2:10][NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[NH:5][CH3:6].[CH3:23][N:24]=[C:25]=[S:26]>>[CH2:15]([O:14][C:12]([NH:11][CH2:10][CH2:9][CH2:8][CH2:7][CH:4]1[N:5]([CH3:6])[C:25](=[S:26])[N:24]([CH3:23])[C:3]1=[O:22])=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CN=C=S
Reactant: CN[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)OC
Product: CN1C(=O)C(CCCCNC(=O)OCc2ccccc2)N(C)C1=S

Procedure:
Using an analogous procedure to Example 1 Nε-benzyloxycarbonyl-Nα-methyl-L-lysine methyl ester may be reacted with methyl isothiocyanate to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[N:5]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:6]=[CH:7][N:8]=1)([O-])=O.[BH4-].[Na+]>CO.O.[Pd]>[O:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][N:5]2[CH:6]=[CH:7][N:8]=[C:4]2[NH2:1])[CH2:12][CH2:13]1
Reactant: O=[N+]([O-])c1nccn1CCN1CCOCC1
Agent: [Pd]
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Nc1nccn1CCN1CCOCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.2 %

Procedure:
The product from Step 1 (0.64 g, 2.81 mmol) is suspended in methanol (20 mL) and water (2 mL). Palladium on carbon (0.065 g, 0.281 mmol) is added and the mixture is degassed with nitrogen for 10 min before sodium borohydride (0.15 g, 3.93 mmol) is added portion-wise. The reaction is cooled with an ice bath and after 30 mins warmed to room temperature and stirred for 16 h at room temperature. The palladium is filtered through celite and washed with methanol (3×30 mL). The filtrate is concentrated in vacuo and the residue partitioned between dichloromethane (100 mL) and water (10 mL). The aqueous layer is extracted with dichloromethane (5×50 mL+1 mL MeOH). The organic layers are combined, dried (MgSO4) and solvent removed in vacuo to give an orange oil (0.42 g, 77%). NMR (400 MHz, CDCl3) δ=2.47-2.60 (m, 4H), 2.64-2.66 (m, 2H), 3.62-3.72 (m, 4H), 3.77-3.83 (m, 2H), 4.76 (brs, 2H), 6.49 (s, H), 6.61 (s, 1H).
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][C@H:6]([OH:23])[C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[C@@H:9]3[CH2:22][C@@H:10]3[C:11]2=[O:21])[CH2:3]1.C(N(CC)CC)C.[CH2:31]([Si:38](Cl)([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl.CN(C1C=CC=CN=1)C>[CH2:46]([Si:38]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[O:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][C@H:6]([OH:23])[C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[C@@H:9]3[CH2:22][C@@H:10]3[C:11]2=[O:21])[CH2:3]1)[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1
Reactant: Cl[Si](Cc1ccccc1)(Cc1ccccc1)Cc1ccccc1
Reactant: C[C@]12CC[C@H](O)CC1=C[C@H](O)[C@H]1[C@@H]3[C@@H]4C[C@@H]4C(=O)[C@@]3(C)CC[C@@H]12
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@]12CC[C@H](O[Si](Cc3ccccc3)(Cc3ccccc3)Cc3ccccc3)CC1=C[C@H](O)[C@H]1[C@@H]3[C@@H]4C[C@@H]4C(=O)[C@@]3(C)CC[C@@H]12
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 89.8 %

Procedure:
A solution of 15.7 g of 3β,7β-dihydroxy-15β,16β-methylene-5-androsten-17-one in 750 ml of methylene chloride is combined with 9 ml of triethylamine and 200 mg of dimethylaminopyridine and cooled to -20° C. Within 30 minutes, 19.4 g of tribenzylsilyl chloride in 10 ml of methylene chloride is added dropwise thereto. The reaction mixture is stirred for one hour at -20° C. and one hour at 0° C., diluted with methylene chloride, and washed with 1 N hydrochloric acid, saturated sodium bicarbonate solution, and water. After drying over sodium sulfate, the mixture is concentrated under vacuum. Chromatography on silica gel with hexane-acetone yields 27.5 g of 3β-tribenzylsilyloxy-7β-hydroxy-15β,16β-methylene-5-androsten-17-one.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)(=O)=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31].S(O)(O)(=O)=O.[NH2:37][CH2:38][C:39]#[N:40].C(N(CC)CC)C>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:40][CH2:39][C:38]#[N:37])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:31]
Reactant: N#CCN
Reactant: Cc1cc(F)ccc1-c1nc(S(C)(=O)=O)nc2c1ccc(=O)n2-c1c(F)cccc1F
Agent: O=S(=O)(O)O
Solvent: CCN(CC)CC
Product: Cc1cc(F)ccc1-c1nc(NCC#N)nc2c1ccc(=O)n2-c1c(F)cccc1F
Yield: 97.5 %

Procedure:
Following the general procedure outlined in Example 195, the product of Example 48 (500 mg, 1.12 mmol), aminoacetonitrile hydrogen sulfate (1.16 g, 5.6 mmol) and triethylamine (0.78 mL, 5.6 mmol) were reacted at 65° for 2 h to give the crude material 460 mg. LC-MS: 421.8 (MH+, m/z), 2.08 (Rt, min).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]([NH2:13])=[O:12])=[CH:4][CH:3]=1.O[CH2:15][NH:16][C:17](=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].O1CCCC1>Cl.O>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][C:11]([NH:13][CH2:15][NH:16][C:17](=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:12])=[CH:4][CH:3]=1
Reactant: CCCCCCCCCCCCCCCCCC(=O)NCO
Reactant: NC(=O)CCSc1ccc(O)cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCSc1ccc(O)cc1
Temperature: 60 °C
Yield: 72 %

Procedure:
Into a 200-ml flask equipped with a stirrer and a condenser were charged 8.0 g of 3-(p-hydroxyphenylthio)propanamide, 10.6 g of N-hydroxymethyl-n-octadecanamide, 5 drops of concentrated hydrochloric acid and 120 ml of tetrahydrofuran, and stirred with heating at 60° C. for 5 hours. The reaction mixture was cooled to room temperature and then poured into 300 ml of distilled water. The white crystals precipitated were collected by filtration and recrystallized from isopropanol to obtain 12.0 g of the desired compound. Melting point: 172° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:10]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[N:11]=[C:12]3[C:17]=2[CH:16]=[CH:15][CH:14]=[CH:13]3)[CH:5]=[CH:6][CH:7]=1.[CH:25]1([N:31]=[C:32]=[O:33])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]([C:9]2[N:10]([C:18]3[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=3)[N:11]=[C:12]3[C:17]=2[CH:16]=[CH:15][CH:14]=[CH:13]3)[C:32]([NH:31][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:33])[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1ccc(-n2nc3ccccc3c2Nc2cccc(Cl)c2)cc1
Reactant: O=C=NC1CCCCC1
Solvent: Cc1ccccc1
Product: O=C(NC1CCCCC1)N(c1cccc(Cl)c1)c1c2ccccc2nn1-c1ccc(Cl)cc1

Procedure:
In analogy to the procedure described in example 1.2, (3-chloro-phenyl)-[2-(4-chloro-phenyl)-2H-indazol-3-yl]-amine was reacted with cyclohexylisocyanate ([3173-53-3]) in toluene for 3 d under reflux conditions to give the title compound as yellow foam. MS: m/e=479.3 [M+H+].
Reaction SMILES: [C:1]([C:4]1[C:9]([Cl:10])=[N:8][C:7]([Cl:11])=[CH:6][N:5]=1)([OH:3])=[O:2].[C:12](=O)([O-])O.[Na+].CI.CN(C)C=O>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH3:12][O:2][C:1]([C:4]1[C:9]([Cl:10])=[N:8][C:7]([Cl:11])=[CH:6][N:5]=1)=[O:3]
Reactant: O=C(O)c1ncc(Cl)nc1Cl
Reactant: O=C([O-])O
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1ncc(Cl)nc1Cl
Temperature: 25 °C
Reaction time: 14 h

Procedure:
A mixture of 2-carboxy-3,5-dichloropyrazine (prepared in the above (1)) 226 g, sodium hydrogen carbonate 118 mg, methyl iodide 0.5 ml and dimethylformamide 1.8 ml is stirred at room temperature for 14 hours. The mixture is diluted with a 10% aqueous citric acid solution and extracted with ethyl acetate. The combined organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo to give 2-methoxycarbonyl-3,5-dichloropyrazine as a pale brown crystalline powder 245 mg. mp 60-63° C., MS(m/z): 206(M+)
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:18](I)([CH3:20])[CH3:19]>CN(C)C=O>[CH:18]([N:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:11]=2)[CH2:6][CH2:7][CH2:8]1)([CH3:20])[CH3:19]
Reactant: Cc1ccc2c(c1)NCCC2
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)N(C(C)C)CCC2
Temperature: 60 °C
Reaction time: 24 h
Yield: 82.5 %

Procedure:
To a cooled solution of 7-methyl quinoline (5.00 g, 35 mmol) and nickel (II) chloride hexahydrate (1.40 g, 6 mmol) in methanol (130 mL) was added sodium borohydride (5.50 g, 140 mmol) portionwise. The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 3 hours. Hydrochloric acid (2N, 200 mL) was added to the black residue and the mixture stirred at room temperature until disappearance of the black precipitate. The acidic solution was neutralized with concentrated ammonium hydroxide and extracted with ether. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered and evaporated to give 5.28 g of 7-methyl-1,2,3,4-tetrahydro-quinoline (100%), used without further purification. A mixture of 7-methyl-1,2,3,4-tetrahydro-quinoline (1.20 g, 8.2 mmol), potassium carbonate (2.3 g, 16.4 mmol) and isopropyl iodide (3.3 mL, 32.8 mmol) in N,N-dimethylformamide (10 mL) was heated at 60° C. with stirring for 24 hours. The solution was cooled to room temperature and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to give 1.28 g (82%) of 1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline. To a solution of 1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline (1.04 g, 5.5 mmol) in dichloromethane was added tetrabutylammonium tribromide (2.65 g, 5.5 mmol) and the solution stirred at room temperature for 5 hours. The solution was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed and silica gel (ethyl acetate/hexane, 1:9) to give 1.00 g of 6-bromo-1-isopropyl-7-methyl-1,2,3,4-tetrahydro-quinoline (67%).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:40][CH3:41])[CH2:4][NH:5][C:6]([CH:8]([CH2:34][CH2:35][C:36]([OH:39])([CH3:38])[CH3:37])[CH2:9][CH:10]([OH:33])[CH:11]([NH:20][C:21]([C:23]1[CH:32]=[N:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)=[O:22])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)=[O:7].CN(C1C=CC=CN=1)C.[C:51](OC(=O)C)(=[O:53])[CH3:52]>N1C=CC=CC=1.C(Cl)Cl>[CH3:1][O:2][CH:3]([O:40][CH3:41])[CH2:4][NH:5][C:6]([CH:8]([CH2:34][CH2:35][C:36]([OH:39])([CH3:37])[CH3:38])[CH2:9][CH:10]([O:33][C:51](=[O:53])[CH3:52])[CH:11]([NH:20][C:21]([C:23]1[CH:32]=[N:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)=[O:22])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)=[O:7]
Reactant: COC(CNC(=O)C(CCC(C)(C)O)CC(O)C(Cc1cccc(F)c1)NC(=O)c1cnc2ccccc2n1)OC
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccccn1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(CNC(=O)C(CCC(C)(C)O)CC(OC(C)=O)C(Cc1cccc(F)c1)NC(=O)c1cnc2ccccc2n1)OC
Reaction time: 3 h
Yield: 96.2 %

Procedure:
To a solution of quinoxaline-2-carboxylic acid [4-(2,2-dimethoxy-ethylcarbamoyl)-1-(3-fluoro-benzyl)-2,7-dihydroxy-7-methyl-octyl]-amide (192 mg, 0.336 mmol) in pyridine (0.6 mL) was added dimethylaminopyridine (DMAP) (10 mg, 0.082 mmol) and acetic anhydride (0.093 mL, 0.984 mmol). The resulting solution was stirred for 3 hours then diluted with methylene chloride and washed with 1 M hydrochloric acid. The organic layer was dried over sodium sulfate, filtered and concentrated to give the title compound as a white foam (198 mg, 96%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=O.[NH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]=1O>>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:8][C:11]2[CH:12]=[C:13]([C:14]([O:16][CH3:17])=[O:15])[CH:18]=[CH:19][C:10]=2[N:9]=1
Reactant: O=C(O)c1cccs1
Reactant: COC(=O)c1ccc(N)c(O)c1
Product: COC(=O)c1ccc2nc(-c3cccs3)oc2c1

Procedure:
Preparation is carried out analogously to 4.1.a from thiophene-2-carboxylic acid and methyl 4-amino-3-hydroxybenzoate.
Reaction SMILES: O[CH:2]([CH3:34])[CH2:3][N:4]([S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)(=[O:27])=[O:26])[C:5]1[CH:22]=[C:21]([CH3:23])[C:20]([CH3:24])=[CH:19][C:6]=1[O:7][CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1.C(N(S(F)(F)[F:41])CC)C.O>ClCCl>[F:41][CH:2]([CH3:34])[CH2:3][N:4]([S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)(=[O:27])=[O:26])[C:5]1[CH:22]=[C:21]([CH3:23])[C:20]([CH3:24])=[CH:19][C:6]=1[O:7][CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1
Reactant: COC(=O)c1ccc(COc2cc(C)c(C)cc2N(CC(C)O)S(=O)(=O)c2ccccn2)cc1
Reactant: CCN(CC)S(F)(F)F
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1ccc(COc2cc(C)c(C)cc2N(CC(C)F)S(=O)(=O)c2ccccn2)cc1
Yield: 23.6 %

Procedure:
460 mg of methyl 4-({2-[(2-hydroxypropyl)(pyridin-2-ylsulfonyl)amino]-4,5-dimethylphenoxy}methyl)benzoate was dissolved in 4.00 mL of dichloromethane, and 161 mg of diethylaminosulfur trifluoride was added dropwise thereto under ice-cooling, followed by stirring under ice-cooling for 30 minutes. To the reaction liquid was added water, followed by extraction with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 1:1) to obtain 109 mg of methyl 4-({2-[(2-fluoropropyl)(pyridin-2-ylsulfonyl)amino]-4,5-dimethylphenoxy}methyl)benzoate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])[CH2:16][CH2:15][CH:14]([CH2:17][C:18]([C:20]3[O:24][C:23]([CH:25]=[O:26])=[CH:22][CH:21]=3)=[O:19])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.S(=O)(=O)([OH:37])N.Cl([O-])=O.[Na+]>ClCCl.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])[CH2:12][CH2:13][CH:14]([CH2:17][C:18]([C:20]3[O:24][C:23]([C:25]([OH:37])=[O:26])=[CH:22][CH:21]=3)=[O:19])[CH2:15][CH2:16]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: NS(=O)(=O)O
Reactant: O=Cc1ccc(C(=O)CC2CCC(c3cc(F)ccc3F)(S(=O)(=O)c3ccc(Cl)cc3)CC2)o1
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: ClCCl
Product: O=C(O)c1ccc(C(=O)CC2CCC(c3cc(F)ccc3F)(S(=O)(=O)c3ccc(Cl)cc3)CC2)o1
Temperature: 25 °C

Procedure:
To a solution of the product from Example 139 (29 mg, 0.057 mmol) in dichloromethane (2 mL) and water (1 mL) cooled to 0° C. was added sulfamic acid followed by sodium chlorite. The reaction was left to stir, warming to room temperature over 2.5 hours. The layers were separated and the aqueous layer extracted further with dichloromethane. The combined organic layers were dried (MgSO4) and evaporated to a cream foam, which was purified by column chromatography on silica (50% ethyl acetate/49% dichloromethane/1% acetic acid) to obtain a white solid (10 mg).
Reaction SMILES: [OH-].[Na+].[CH2:3]([O:5][P:6]([O:23][CH2:24][CH3:25])([CH:8]([P:15]([O:20][CH2:21][CH3:22])([O:17][CH2:18][CH3:19])=[O:16])[CH2:9][C:10]([O:12]CC)=[O:11])=[O:7])[CH3:4]>O.CCO>[O:20]([P:15]([O:17][CH2:18][CH3:19])([CH:8]([P:6]([O:5][CH2:3][CH3:4])([O:23][CH2:24][CH3:25])=[O:7])[CH2:9][C:10]([OH:12])=[O:11])=[O:16])[CH2:21][CH3:22]
Reactant: CCOC(=O)CC(P(=O)(OCC)OCC)P(=O)(OCC)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCOP(=O)(OCC)C(CC(=O)O)P(=O)(OCC)OCC
Temperature: 80 °C
Yield: 95.6 %

Procedure:
A solution of NaOH (4.00 g, 100 mmol) in water (50 ml) was added to a solution of ethyl 3,3-bis(diethoxyphosphinyl)propionate (32.6 g, 87 mmol) in EtOH (100 ml), and heated at 80° C. for 1 hour. After cooling, the EtOH was evaporated, and the residue was acidified to methyl orange with 12N HCl. The product was extracted into dichloromethane (5×50 ml). The organic layer was dried (Na2SO4) and concentrated to give the title compound (28.8 g, 96%) as a viscous oil.
Reaction SMILES: N([CH2:3]NC(N)=O)=O.[OH-].[K+].[Cl:10][C:11]1[N:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:12]=1[C:13]([OH:15])=[O:14]>C(OCC)C.CO>[Cl:10][C:11]1[N:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:12]=1[C:13]([O:15][CH3:3])=[O:14]
Reactant: O=C(O)c1c(Cl)ccnc1Cl
Reactant: NC(=O)NCN=O
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Product: COC(=O)c1c(Cl)ccnc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 93.2 %

Procedure:
Nitrosomethyl urea (8 g, 78.16 mmol), taken in diethyl ether (30 ml) was cooled to 0° C. and 25% aqueous KOH solution was added slowly under cooling. The ether layer was collected, dried over KOH and added dropwise to a stirring solution of 2,4-Dichloronicotinic acid (3 g, 15.62 mmol) in methanol (5 mL) at 0° C. The reaction mixture was allowed to come to room temperature within 1 hour. The organic solvent was removed under reduced pressure and the crude residue was purified by column chromatography (5-10% EtOAc in hexane) to obtain the pure methyl 2,4-dichloronicotinate (3.00 g, 99%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ 8.34 (d, J=5.3 Hz, 1H), 7.33 (d, J=5.4 Hz, 1H), 3.99 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[C:4]([CH3:10])[C:3]=1[OH:11].C(O)(=[O:14])C>>[CH3:10][C:4]1[C:3](=[O:11])[C:2]([CH3:1])=[C:7]([CH3:8])[C:6](=[O:14])[C:5]=1[CH3:9]
Reactant: CC(=O)O
Reactant: Cc1cc(C)c(C)c(O)c1C
Product: CC1=C(C)C(=O)C(C)=C(C)C1=O
Yield: 53 %

Procedure:
500 mg of 2,3,5,6-tetramethylphenol and 10 mg of RuCl3.3H2O were reacted in 5 ml of acetic acid in the same manner as in Example 1, followed by the same treatment as in Example 1, whereby 288 mg (53% yield) of tetramethylbenzoquinone and 228 mg of a mixture of three unidentified substances were obtained. The tetramethylbenzoquinone was recrystallized from hexane to obtain yellow needle-like crystals having a melting point of from 114° to 115° C.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].C([O:15][CH2:16][CH:17]1[CH2:21][O:20][C:19]([CH3:23])([CH3:22])[O:18]1)(=O)C1C=CC=CC=1>O>[CH3:22][C:19]1([CH3:23])[O:18][C@@H:17]([CH2:16][OH:15])[CH2:21][O:20]1
Reactant: CC1(C)OCC(COC(=O)c2ccccc2)O1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC1(C)OC[C@H](CO)O1
Temperature: 100 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
Then sodium carbonate (24.80 g, 0.234 mol) was added to a mixture of the crude 4-benzoyloxymethyl-2,2-dimethyl-1,3-dioxolane (36.95 g, 0.156 mol) and water (80 ml) and resulting mixture was stirred for 8 hours at 100° C. After cooling the reaction mixture was extracted with methylene chloride. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and condensed in vacuo. The crude product was distilled to give 15.67 g of (S)-2,2-dimethyl-1,3-dioxolane-4-methanol (yield 76%, b.p. 72° C. at 8 mmHg, optical purity 98.6% e.e., specific rotation [α]D20 +11.1°(c=1,MeOH)).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[CH:5]=[CH:4][N:3]=1.[C:10](O)(=O)[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>>[CH3:9][C:6]1[CH:5]=[CH:4][N:3]=[C:2]2[N:1]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[NH:8][C:7]=12
Reactant: Cc1ccnc(N)c1N
Reactant: CCCCCC(=O)O
Product: CCCCCc1nc2nccc(C)c2[nH]1

Procedure:
The title compound was prepared from 2,3-diamino-4-picoline (0.246 g, 2 mmol) and hexanoic acid (0.25 ml, 2 mmols) according to the procedure described in Step 1 of Example 9. The crude product was purified by flash chromatography on silica-gel using EtOAc-MeOH (9:1) to give the pure product (0.28 g, 69%) as a tan colored solid.
Reaction SMILES: [OH:1]C(CCCCC)CCN1C(=O)CS(=O)C1CCCCCCC(O)=O.[OH:26][CH:27]([CH2:46][O:47][CH2:48][CH2:49][CH3:50])[CH2:28][CH2:29][N:30]1[C:34](=[O:35])[CH2:33][S:32](=[O:36])[CH:31]1[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]([OH:45])=[O:44]>>[OH:26][CH:27]([CH2:46][O:47][CH2:48][CH2:49][CH3:50])[CH2:28][CH2:29][N:30]1[C:34](=[O:35])[CH2:33][S:32](=[O:1])(=[O:36])[CH:31]1[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]([OH:45])=[O:44]
Reactant: CCCCCC(O)CCN1C(=O)CS(=O)C1CCCCCCC(=O)O
Reactant: CCCOCC(O)CCN1C(=O)CS(=O)C1CCCCCCC(=O)O
Product: CCCOCC(O)CCN1C(=O)CS(=O)(=O)C1CCCCCCC(=O)O

Procedure:
This compound is prepared essentially by the same procedure as described in Example 3 except that the 7-[3-(3-hydroxyoctyl)-1,4-dioxo-2-thiazolidinyl]heptanoic acid is replaced by 7-[3-(3-hydroxy-4-propoxybutyl)-1,4-dioxo-2-thiazolidinyl]heptanoic acid. Chromatographic purification of the resulting product on silica gel gives the title compound as a viscous, pale yellow oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][CH:32]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([CH3:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)=[N:7]1.[C:33]([CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)#[N:34]>>[CH3:11][C:10]1[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([N:38]3[CH2:39][CH2:40][CH:35]([C:33]#[N:34])[CH2:36][CH2:37]3)[CH:32]=[CH:31][CH:30]=2)[N:7]=[C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([CH3:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)[CH:9]=1
Reactant: N#CC1CCNCC1
Reactant: Cc1cc(-c2nc(-c3ccc(C(C)(C)C(F)(F)F)cc3)no2)nn1Cc1cccc(Br)c1
Product: Cc1cc(-c2nc(-c3ccc(C(C)(C)C(F)(F)F)cc3)no2)nn1Cc1cccc(N2CCC(C#N)CC2)c1

Procedure:
Analogously to the process described in Example 9, 125 mg (0.247 mmol) of the compound from Example 3A and 55 mg (0.495 mmol) of 4-cyanopiperidine were used to obtain 66 mg (50% of theory) of the title compound.