Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]([OH:13])=O)[CH2:7][CH2:6]1)=[O:4].ON1C2C=CC=CC=2N=N1.[CH3:24][N:25]([CH3:30])[CH2:26][CH2:27][NH:28][CH3:29].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[CH3:24][N:25]([CH3:30])[CH2:26][CH2:27][N:28]([CH3:29])[C:11]([C@H:8]1[CH2:7][CH2:6][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10][CH2:9]1)=[O:13]
Reactant: COC(=O)[C@H]1CC[C@H](C(=O)O)CC1
Reactant: CNCCN(C)C
Agent: O=C([O-])O
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@H]1CC[C@H](C(=O)N(C)CCN(C)C)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
trans-4-(Methoxycarbonyl)cyclohexanecarboxylic acid (8.84 g) obtained in Reference Example 1(2) is dissolved in chloroform (100 ml), and thereto are added 1-hydroxybenzotriazole (7.14 g), 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride (10.00 g) and N,N,N′-trimethylethylenediamine (5.33 g) under ice-cooling. The mixture is then stirred at room temperature for 4 hours. Saturated aqueous sodium hydrogen carbonate solution is poured to the reaction solution and the mixture is extracted with chloroform. The organic layer is washed with saturated brine and dried over sodium sulfate. The solvent is concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: chloroform/methanol/28% ammonia water=200/10/1) to give methyl trans-4-{[[2-(dimethylamino)ethyl](methyl)amino]carbonyl}-cyclohexanecarboxylate-(11.98 g). APCI-MS M/Z:271[M+H]+
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:23])[CH2:10][S:11][C:12]2[NH:13][N:14]=[C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[N:16]=2)[CH:5]=[CH:6][CH:7]=1.ClC1C=CC=C(C(OO)=[O:32])C=1>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:23])[CH2:10][S:11]([C:12]2[NH:13][N:14]=[C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[N:16]=2)=[O:32])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(CSc1nc(-c2cccnc2)n[nH]1)Nc1cccc(Cl)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=C(CS(=O)c1nc(-c2cccnc2)n[nH]1)Nc1cccc(Cl)c1
Reaction time: 2 h
Yield: 44.2 %

Procedure:
To a dichloromethane solution (2 mL) of N-(3-chloro-phenyl)-2-(5-pyridin-3-yl-2H-[1,2,4]triazol-3-ylsulfanyl)-acetamide (0.080 g, 0.25 mmol), m-chloroperbenzoic acid (0.25 mmol) was and the mixture was stirred for 2 h. The reaction mixture was quenched with sodium bicarbonate solution and the product extracted in ethyl acetate. The ethyl acetate layer was dried, filtered and evaporated to afford crude residue. This residue was purified by reverse phase HPLC to afford pure title compound (40 mg, 45%). MS (ES) 361.5
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[CH2:8][CH2:7][CH2:6]2.[OH:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[N:19][C:18]1[CH:20]=[CH:21][C:15]([OH:14])=[CH:16][CH:17]=1)[CH2:8][CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCCC2=O
Reactant: Nc1ccc(O)cc1
Product: COc1ccc2c(c1)CCCC2=Nc1ccc(O)cc1
Temperature: 180 °C

Procedure:
A mixture of 6-methoxytetralone (25 g, 142 mmol) and 4-hydroxyaniline (16.3 g, 149 mmol) was heated to 180° C. under a nitrogen stream for 2 h. After cooling to ambient temperature, the solid mass was recrystallized from toluene/methanol: 1H NMR (300 MHz) d 8.15 (d, J=9.7 Hz, 1H), 6.5-7.9 (m, 6H), 3.80 (s, 3H), 2.84 (t, J=7.3 Hz, 2H), 2.51 (t, J=6.8 Hz, 2H), 1.85 (m, 2H).
Reaction SMILES: [N:1]([CH2:4][C:5]1[N:6]=[C:7]([S:17][CH3:18])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][CH:11]=2)[CH:9]=1)=[N+]=[N-].O.O.[Sn](Cl)Cl.[OH-].[Na+]>CCOC(C)=O>[I:16][C:13]1[CH:14]=[CH:15][C:10]([N:8]2[CH:9]=[C:5]([CH2:4][NH2:1])[N:6]=[C:7]2[S:17][CH3:18])=[CH:11][CH:12]=1
Reactant: CSc1nc(CN=[N+]=[N-])cn1-c1ccc(I)cc1
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: CSc1nc(CN)cn1-c1ccc(I)cc1
Yield: 52.6 %

Procedure:
To a solution of 4-(azidomethyl)-1-(4-iodophenyl)-2-(methylthio)-1H-imidazole (0.26 g, 0.70 mmol) in EtOAc (10 mL), Tin(II) chloride dihydrate (0.63 g, 2.8 mmol) was added. The mixture was heated at reflux for 10 min. After being cooled down, 1N NaOH (10 mL) was added. The white precipitate was filtered off through celite. The EtOAc phase was separated, dried over Na2SO4, concentrated in vacuo to give (1-(4-iodophenyl)-2-(methylthio)-1H-imidazol-4-yl)methanamine (127 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][O:29][CH3:30])=S)=[CH:21][CH:20]=1.I([O-])(=O)(=O)=O.[Na+]>CN(C=O)C.O.O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[CH2:17][CH2:16][N:15]([C:26](=[N:28][O:29][CH3:30])[NH:25][C:22]4[CH:21]=[CH:20][C:19]([F:18])=[CH:24][CH:23]=4)[CH2:14][CH2:13]3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: Clc1ccc2c(N3CCNCC3)ccnc2c1
Reactant: CONC(=S)Nc1ccc(F)cc1
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: CN(C)C=O
Solvent: O
Product: CON=C(Nc1ccc(F)cc1)N1CCN(c2ccnc3cc(Cl)ccc23)CC1

Procedure:
7-Chloro-4-(piperazin-1-yl)quinoline (297 mg, 1.2 mmol), N-(4-Fluorophenyl)-N′-methoxythiourea (240 mg, 1.2 mmol), and sodium periodate (278 mg, 1.3 mmol) in DMF-water 1:1 (40 mL) are heated at 85° C. for 1 h. The reaction mixture is diluted with water and extracted with ether. The organic phase is dried (MgSO4) and concentrated. The residue is purified by column chromatography with hexane-EtOAc yielding the title product.
Reaction SMILES: Cl[CH2:2][C:3](=O)[CH3:4].[Li+].[Br-:7].Br[C:9]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][N:10]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[Br:7][C:3]1[C:4]2[N:10]([CH:9]=[C:14]([CH3:15])[CH:13]=2)[CH:11]=[CH:12][CH:2]=1
Reactant: CC(=O)CCl
Reactant: [Br-]
Reactant: Cc1cccnc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Li+]
Solvent: CC#N
Product: Cc1cc2c(Br)cccn2c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of cloroacetone (17 mmol), LiBr (17 mmol) in acetonitrile (10 mL) was stirred at room temperature for 15 min. Then, a solution of 2-bromo-3-methylpyridine (19 mmol) in acetonitrile (10 mL) was added and the resulting mixture was heated at reflux for 24 h. The mixture was cooled to room temperature and the solvent was removed under reduce pressure. The residue was diluted with water extracted with diethylether. The aqueous was treated with K2CO3 (96 mmol) and heated at 80° C. for 2 h. The mixture was cooled to room temperature and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated by rotary evaporation, and purified by column chromatography to give 35. (34%) 1H NMR (400 MHz, CDCl3) δ 7.76 (dt, J=6.9, 0.8 Hz, 1H), 7.20-7.07 (m, 1H), 6.83 (dd, J=7.1, 0.7 Hz, 1H), 6.40 (s, 1H), 6.25 (t, J=7.0 Hz, 1H), 2.39 (s, 3H). LC-MS (ES) for C9H8BrN [M+1]+ 209.11.
Reaction SMILES: [NH3:1].[C:2]([C:5]1[C:19]([OH:20])=[CH:18][C:8]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15](Cl)=[O:16])=[C:7]([CH2:21][CH:22]=[CH2:23])[CH:6]=1)(=[O:4])[CH3:3]>C(Cl)Cl>[C:2]([C:5]1[C:19]([OH:20])=[CH:18][C:8]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([NH2:1])=[O:16])=[C:7]([CH2:21][CH:22]=[CH2:23])[CH:6]=1)(=[O:4])[CH3:3]
Reactant: C=CCc1cc(C(C)=O)c(O)cc1OCCCCCC(=O)Cl
Reactant: N
Solvent: ClCCl
Product: C=CCc1cc(C(C)=O)c(O)cc1OCCCCCC(N)=O
Reaction time: 0.17 h

Procedure:
Ammonia gas was bubbled into a solution of approximately 3 millimoles of the acid chloride from Example 95 in 25 ml of methylene chloride. After 10 minutes, gas introduction was discontinued and the reaction was stirred overnight. The reaction mixture was concentrated in vacuo and then partitioned between ethyl acetate and dilute hydrochloric acid to which sodium chloride had been added. The organic layer was separated, washed with a potassium carbonate solution, dried over sodium sulfate, and concentrated to dryness. The residue was purified by preparative thin layer chromatography eluting with ethyl acetate to provide 110 mg of the desired title product, m.p.=122°-124° C.
Reaction SMILES: Cl[C:2]1[N:7]([CH3:8])[C:6](=[N:9][C:10]2[C:15]([CH3:16])=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=2[CH3:18])[CH:5]=[C:4]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[N:3]=1.[CH3:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(O)C.C(Cl)(Cl)Cl>[CH3:28][O:27][C:21]1[CH:20]=[C:19]([C:4]2[N:3]=[C:2]([N:30]([CH3:29])[CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:7]([CH3:8])[C:6](=[N:9][C:10]3[C:15]([CH3:16])=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[CH3:18])[CH:5]=2)[CH:24]=[CH:23][C:22]=1[O:25][CH3:26]
Reactant: CNCc1ccccc1
Reactant: COc1ccc(-c2cc(=Nc3c(C)cc(C)cc3C)n(C)c(Cl)n2)cc1OC
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: COc1ccc(-c2cc(=Nc3c(C)cc(C)cc3C)n(C)c(N(C)Cc3ccccc3)n2)cc1OC

Procedure:
To a suspension of 2-chloro-3,4-dihydro-6-(3,4-dimethoxyphenyl)-3-methyl-4-(2,4,6-trimethylphenylimino)pyrimidine (1.5 g) in ethanol (15 ml) was added N-methylbenzylamine (1.47 ml). The mixture was refluxed for 5 hours. The resulting suspension was dissolved in chloroform, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The obtained syrup was triturated in diisopropyl ether and filtered to afford 3,4-dihydro-6-(3,4-dimethoxyphenyl)-3-methyl-2-(N-methyl-N-benzylamino)-4-(2,4,6-trimethylphenylimino)pyrimidine (1.18 g).
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].CN(CCN(C)C)C.[CH2:14]([Li])[CH2:15][CH2:16][CH3:17].CN(CCN(C)C)C>>[CH2:1]=[CH:2][CH:3]=[CH2:4].[CH2:4]=[CH:3][C:2]1[CH:1]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: [Li]CCCC
Agent: CN(C)CCN(C)C
Product: C=CC=C
Product: C=Cc1ccccc1

Procedure:
The procedure described in Example 1 was utilized in this example except that 3 mL of 1 M solution of n-butyl lithium (n-BuLi) in hexanes and 5 mL of 1 M solution of TMEDA in hexanes were added to the catalyst system (BaTHFA/MgR2) making the molar ratio (BaTHFA/MgR2/n-BuLi/TMEDA) 1:3:3:5. The styrene-butadiene produced was determined to have a glass transition temperature (Tg) at −76° C. and a melting temperature (Tm) at −11° C. The Mooney viscosity (ML-4) at 100° C. was 48. The GPC measurements indicated that the polymer has a number average molecular weight (Mn) of 175,000 g/mol and a weight average molecular weight (Mw) of 270,000 g/mol. The polydispersity (Mw/Mn) of the resulting polymer was 1.54. Carbon-13 NMR analysis showed a trans 1,4 polybutadiene content of 75%, cis 1,4 polybutadiene content of 19%, a 1,2 polybutadiene content of 6%, and a polystyrene content of 16.5%.
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[C:11]#[N:12])=[CH:4][CH:3]=1.O.[NH2:17][NH2:18]>N1C=CC=CC=1>[NH:17]([C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[C:11]#[N:12])=[CH:4][CH:3]=1)[NH2:18]
Reactant: N#Cc1cccc(-c2ccc(Cl)nn2)c1
Reactant: NN
Solvent: O
Solvent: c1ccncc1
Product: N#Cc1cccc(-c2ccc(NN)nn2)c1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
A solution of 3-(6-chloro-pyridazin-3-yl)-benzonitrile (75.6 g, 350 mmol) in 900 mL of dried pyridine was cooled in an ice bath and 119.2 mL of hydrazine hydrate was added. The cooling was continued so as to keep the temperature below 30° C. at which time yellow needle separated. The mixture was then heated to 65° C. and stirred overnight. Then the mixture was concentrated and the residue was washed with water and Methanol to return the title compound (60 g, 81%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): δ 8.38˜8.39 (m, 1H), 8.32˜8.35 (m, 1H), 8.24 (s, 1H), 7.97˜8.00 (d, 1H), 7.82˜7.85 (m, 1H), 7.64˜7.69 (m, 1H), 7.09˜7.12 (d, 1H), 4.39 (s, 2H); MS (m/z) 212.1 [M++1].
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[C:6](=[O:12])[CH2:7][CH2:8][C:9]=1[CH:10]=O)[CH3:4].[C:13]([OH:16])(=O)[CH3:14].O.[CH3:18]OCCOC>C(O)C>[O:16]=[C:13]([CH3:14])/[CH:18]=[CH:10]/[C:9]1[CH2:8][CH2:7][C:6](=[O:12])[C:5]=1[CH2:3][CH3:4]
Reactant: CCC1=C(C=O)CCC1=O
Reactant: CC(=O)O
Reactant: COCCOC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCC1=C(/C=C/C(C)=O)CCC1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
0.968 (0.023 mole) of a 57% NaH dispersion was transferred into a dry 250 ml flask equipped with a magnetic stirring bar and nitrogen inlet. The NaH was covered with 60 ml of dry DME and a solution of 4.15 g (0.025 mole) of dimethyl (2-oxopropyl) phosphonate in 10 ml of DME was added dropwise. The resulting reaction mixture was stirred for one hour at room temperature. Crude aldehyde 5 supra [from oxidation of 3.4 g (0.025 mole) of the vinyl compound 4] in 15 ml of DME was added dropwise, and the stirring was continued for 2 hours after completion of the addition. The reaction mixture was neutralized with acetic acid and 150 ml of water added. The resulting solution was extracted four times each with 100 ml of ether, and the combined ether extracts back-extracted with 100 ml water and once with 75 ml saturated NaCl. The extracts were dried over MgSO4 and concentrated to yield 3.3 g of crude dione Ib. This material was chromatographed on silicic acid using ethyl acetate-cyclohexane to give a bright yellow liquid: uv (95% ethanol) 293 nm; ir (neat) 1685, 1665, 1640 and 1580 cm-1 (conjugated enone system); ##STR5## and 1.0 (t,3,CH2CH3).
Reaction SMILES: CO[C:3](=[O:13])[C:4]1[C:9]([I:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11]Br.[F:14][C:15]([F:26])([F:25])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][NH2:22])=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[I:10][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:4]=1[C:3](=[O:13])[N:22]([CH2:21][C:20]1[CH:23]=[CH:24][C:17]([O:16][C:15]([F:14])([F:25])[F:26])=[CH:18][CH:19]=1)[CH2:11]2
Reactant: COC(=O)c1c(I)cccc1CBr
Reactant: NCc1ccc(OC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=C1c2c(I)cccc2CN1Cc1ccc(OC(F)(F)F)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 31.3 %

Procedure:
A mixture of 2-bromomethyl-6-iodo-benzoic acid methyl ester (0.245 g, 0.7 mmol), 4-trifluoromethoxy-benzylamine (0.122 mL, 0.8 mmol), and K2CO3 (0.207 g, 1.5 mmol) in toluene (5 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 7-iodo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.095 g, 31%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.21 (s, 2H), 4.82 (s, 2H), 6.84 (d, 2H), 7.14-7.40 (m, 4H), 7.92 (d, 1H). GC-MS: m/z 433 (M)+.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH:11](Br)[C@@H:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][CH2:19][C@@H:20]([F:25])[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2].CC1C=C(C)N=C(C)C=1.C1(C)C(C)=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@:31]2([CH3:32])[C:9](=[CH:10][CH:11]=[C:12]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:33])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:26])[CH2:18][CH2:19][C@@H:20]([F:25])[C:21]([OH:24])([CH3:22])[CH3:23])[CH2:8][C@@H:7]([O:35][C:36](=[O:38])[CH3:37])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1CC2=CC(Br)[C@H]3[C@@H]4CC[C@H]([C@H](C)CC[C@@H](F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Solvent: Cc1ccccc1C
Solvent: Cc1ccccc1
Solvent: Cc1cc(C)nc(C)c1
Product: CC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H]([C@H](C)CC[C@@H](F)C(C)(C)O)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(C)=O)C1
Temperature: 140 °C

Procedure:
A mixture of 0.605 g. (0.0010 mole) of [1α,3β,7ξ,24R]-7-bromo-24-fluorocholest-5-en-1,3,25-triol 1,3-diacetate, 0.6 ml. of s-collidine and 18 ml. of xylene was heated at reflux (140° C.) for 0.5 hr and cooled. The mixture was diluted with 30 ml. of toluene. This solution was washed with 10% aqueous sulfuric acid, and saturated aqueous sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was purified by column chromatography on 0.06-0.20 mm silica gel to yield [1α,3β,24R]-24-fluorocholesta-5,7-dien-1,3,25-triol 1,3-diacetate, [α]D23 -21° (c 0.5, CHCl3).
Reaction SMILES: C(OC([NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][S:19]([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)(=[O:21])=[O:20])[CH:15]=[CH:14][C:12]=2[N:13]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl.O>[NH2:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][S:19]([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)(=[O:21])=[O:20])[CH:15]=[CH:14][C:12]=2[N:13]=1
Reactant: CC(C)(C)OC(=O)Nc1nc2ccc(OS(=O)(=O)c3cccs3)cc2s1
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: Nc1nc2ccc(OS(=O)(=O)c3cccs3)cc2s1
Yield: 79.4 %

Procedure:
A solution of thiophene-2-sulfonic acid 2-tert-butoxycarbonylaminobenzo-thiazol-6-yl ester (intermediate 30) (1.5 g, 3.63 mmol) and trifluoroacetic acid (15 ml, 196 mmol) in 15 ml of dichloromethane and 600 μl of water is stirred for 2 hours at room temperature. The reaction medium is concentrated to dryness to give 900 mg of thiophene-2-sulfonic acid 2-aminobenzothiazol-6-yl ester in the form of the trifluoroacetic acid salt (oil) in a yield of 76%.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][OH:10])=[CH:5][CH:4]=1.ON1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=N1.CN1CC[O:25]CC1.CCN=C=NCCCN(C)C.Cl>>[OH:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:20]([C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:25])=[CH:4][CH:5]=1
Reactant: CN1CCOCC1
Reactant: NCc1ccc(CO)cc1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Product: O=C(NCc1ccc(CO)cc1)c1ccccn1
Yield: 95 %

Procedure:
Using General Procedure F: Reaction of (4-aminomethyl-phenyl)-methanol (200 mg, 1.46 mmol, 1-hydroxybenzotriazole (218 mg, 1.61 mmol), 4-methyl morpholine (241 μL, 2.19 mmol), and EDCl (309 mg, 1.61 mmol) for 2 h at room temperature gave the title compound (335 mg, 95%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 4.67 (d, 2H, J=6.0 Hz), 4.69 (s, 2H), 7.36 (br s, 4H), 7.43-7.44 (m, 1H), 7.85-7.86 (m, 1H), 8.24 (d, 1H, J=9.0 Hz), 8.52 (br s, 1H), 8.52 (d, 1H, J=3.0 Hz). ES-MS m/z 243 (M+H).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:3]=1.[CH2:19]([CH2:21][NH2:22])[OH:20]>>[ClH:1].[C:15]1([CH3:18])[CH:16]=[CH:17][C:12]([C:4]2[CH:3]=[C:2]([NH:22][CH2:21][CH2:19][OH:20])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[CH:13][CH:14]=1
Reactant: Cc1ccc(-c2cc(Cl)c3ccccc3n2)cc1
Reactant: NCCO
Product: Cc1ccc(-c2cc(NCCO)c3ccccc3n2)cc1
Product: Cl

Procedure:
The title compound, m.p. 274-276° C. and MS: m/e=278 (Me), was prepared from 4-chloro-2-p-tolyl-quinoline and ethanolamine.
Reaction SMILES: [NH2:1][N:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([NH:13][CH2:14][CH2:15][C:16]([NH:18][CH2:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:17])=[S:12])=[CH:6][CH:5]=1>[OH-].[Li+].CO>[NH2:1][N:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([NH:13][CH2:14][CH2:15][C:16]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[O:17])=[S:12])=[CH:6][CH:5]=1
Reactant: CCOC(=O)CCNC(=O)CCNC(=S)Nc1ccc(C=NN)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: NN=Cc1ccc(NC(=S)NCCC(=O)NCCC(=O)O)cc1

Procedure:
Ethyl β-[[3-[[[4(aminoiminomethyl)phenyl]amino]thiocarbonyl]aminopropanoyl]amino]propanoate (65 mg; 0.18 mmoles) was treated in 1N lithium hydroxide/methanol (20 ml; 1:1) for 10 min. Methanol was evaporated and the pH of the remaining mixture was adjusted to 5 with 50% acetic acid. The mixture was then purified by HPLC using a linear gradient of acetonitrile/water/0.05% trifluoro-acetic acid (0-20% acetonitrile in 30 min). Yield: 51 mg (85%). FAB-MS: MH+ =338.0.
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].O=[C:19]1[CH2:22][CH:21]([C:23]#[N:24])[CH2:20]1>C1COCC1>[C:7]([CH:9]=[C:19]1[CH2:22][CH:21]([C:23]#[N:24])[CH2:20]1)#[N:8]
Reactant: CCOP(=O)(CC#N)OCC
Reactant: N#CC1CC(=O)C1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: N#CC=C1CC(C#N)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 71.3 %

Procedure:
To a solution of 1 M of potassium tert-butoxide in THF (67.4 mL) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (11.4 mL, 0.0706 mol) in tetrahydrofuran (100 mL, 1 mol). The reaction mixture was warmed up to room temperature and cooled to 0° C. again. To the resulting mixture, a solution of 3-oxocyclobutanecarbonitrile (6.10 g, 0.0641 mol) in tetrahydrofuran (20 mL, 0.2 mol) was added. The reaction mixture was allowed to warm up to room temperature and stirred for 2 hours. After quenching with water, the mixture was extracted with EtOAc. The combined organic layers were dried and concentrated. The residue was purified by flash silica gel column, eluting with 0-10% MeOH/dichloromethane to give the titled product (5.40 g, 71.26%). LCMS (M+Na) 141.3. 1H NMR (400 MHz, CDCl3): δ 5.30 (1H, m), 3.40 (2H, m), 3.14 (3H, m) ppm.
Reaction SMILES: [C:1]([O-:13])(=[O:12])[CH2:2][C:3]([CH2:8][C:9]([O-:11])=[O:10])([C:5]([O-:7])=[O:6])[OH:4].[K+].[K+].[K+]>O>[C:1]([OH:13])(=[O:12])[CH2:2][C:3]([CH2:8][C:9]([OH:11])=[O:10])([C:5]([OH:7])=[O:6])[OH:4]
Reactant: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]
Agent: [K+]
Solvent: O
Product: O=C(O)CC(O)(CC(=O)O)C(=O)O
Reaction time: 0.03 h

Procedure:
Potassium citrate ##STR91## The resulting product is added to 16 ounces of boiling water and stirred for a period of 1.5 minutes. The resulting material is poured into a mold and is permitted to cool. The resulting jell has an excellent "true fruit" flavor with intense blueberry and blackcurrant nuances. Note: CARMEL KOSHER® vegetable jell is produced by Carmel Kosher Food Products, Inc. of Chicago, Ill. 60632.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](C=O)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH:12]([O:17][CH3:18])([O:15][CH3:16])OC.O.[O-2].[O-2].[O-2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.[Al+3].[Al+3]>ClCCl>[CH3:18][O:17][CH:12]([O:15][CH3:16])[C:4]1[C:5]([O:8][CH3:9])=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1
Reactant: COc1ncc(Br)cc1C=O
Reactant: COC(OC)OC
Agent: O=[Si]=O
Agent: [Al+3]
Agent: [O-2]
Solvent: ClCCl
Solvent: O
Product: COc1ncc(Br)cc1C(OC)OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2.58 g of 5-bromo-2-methoxy-3-pyridinecarboxaldehyde was dissolved in 30 ml of dichloromethane, a mixture of 9 ml of trimethyl orthoformate and montmorillonite K-10 (3 g) was added thereto, and the mixture was stirred at room temperature for 2 hours. After filtering the reaction solution, the filtrate was evaporated. To the residue was added ethyl acetate, followed by filtering through alumina. The filtrate was evaporated, to give 3.09 g of the title compound as a yellow oil.
Reaction SMILES: Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=[C:4]([O:19][CH3:20])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:26]1[S:27][CH:28]=[CH:29][N:30]=1)CCC>>[CH3:20][O:19][C:4]1[CH:3]=[C:2]([C:26]2[S:27][CH:28]=[CH:29][N:30]=2)[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Reactant: COc1ccc(-c2nc3cc(OC)cc(Br)c3o2)cc1
Product: COc1ccc(-c2nc3cc(OC)cc(-c4nccs4)c3o2)cc1

Procedure:
The title compound was prepared according to the procedure of Example 53, Step a, from 7-bromo-5-methoxy-2-(4-methoxyphenyl)-1,3-benzoxazole and 2-(tributylstannyl)thiazole. The product was obtained as an off white solid (93% yield, m.p. 132-136° C.); MS m/e 339 (M+H)+.