Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:38](=[N:42][OH:43])[C:39]([OH:41])=[O:40])[C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)=[CH:22][CH:21]=2)=[CH:15][CH:14]=1.C(O)C.C1COCC1.[OH-].[Na+:53]>O>[Na+:53].[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:38](=[N:42][OH:43])[C:39]([O-:41])=[O:40])[C:20]2[CH:21]=[CH:22][C:23]([O:26][CH2:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)=[CH:24][CH:25]=2)=[CH:15][CH:14]=1
Reactant: O=C(O)C(=NO)C(c1ccc(OCc2ccc3ccccc3n2)cc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: O=C([O-])C(=NO)C(c1ccc(OCc2ccc3ccccc3n2)cc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Reaction time: 1 h
Yield: 81.1 %

Procedure:
A mixture of bis(4-(2-quinolylmethoxy)phenyl)methyloximinoacetic acid (570 mg, 1.00 mmol), prepared as in step 1, ethanol (7 mL), dry THF (3 mL), and 1N NaOH (1.10 mL, 1.10 mmol) was stirred for 1 hour. The reaction mixture was diluted with water and the aqueous phase was washed with hexane and concentrated in vacuo. The resulting solid was collected by filtration to provide bis(4-(2-quinolylmethoxy)phenyl)methyloximinoacetic acid sodium salt (0.48 g, 81%): 1H NMR (300 MHz, DMSO-d6)δ4.18 (s, 2H), 5.38 (s, 2H), 5.42 (s, 2H), 7.05 (d, 2H, J=8.8 Hz), 7.10 (d, 2H, J=8.8 Hz), 7.29 (d, 2H, J=8.8 Hz), 7.29 (d, 2H, J=8.8 Hz), 7.57 (d, 2H, J=8.8 Hz), 7.62 (m, 2H), 7.69 (m, 2H), 7.79 (m, 2H), 8.02 (m, 2H), 8.43 (m, 2H); MS (FAB+) m/z: 592 (M+H)+. Anal. Calcd. for C33 H26N3O5Na: C, 69.83; H, 4.61; N, 7.40. Found: C, 68.77; H, 4.29; N, 6.74.
Reaction SMILES: N.[Sn:2](Cl)(Cl)(Cl)Cl.[CH:7]([OH:10])([CH3:9])[CH3:8]>>[CH3:8][CH:7]([CH3:9])[O-:10].[CH3:8][CH:7]([CH3:9])[O-:10].[CH3:8][CH:7]([CH3:9])[O-:10].[CH3:8][CH:7]([CH3:9])[O-:10].[Sn+4:2]
Reactant: Cl[Sn](Cl)(Cl)Cl
Reactant: CC(C)O
Agent: N
Product: CC(C)[O-]
Product: [Sn+4]

Procedure:
Approx. 360 g of ammonia were introduced into a solution of 1000 g of tin tetrachloride in 6650 g of isopropanol. Subsequently, the ammonium chloride was filtered off. An approx. 16% solution of tin tetraisopropoxide in isopropanol was obtained. At a temperature of 70° C., 352 g of N-methyldiethanolamine were added to 6208 g of this solution and the mixture was kept at 70° C. for 1½ h. An approx. 20% solution of the target compound in isopropanol was obtained. Reprecipitation in 1,4-butanediol with distillative removal of isopropanol under reduced pressure afforded the 20% partial solution in 1,4-butanediol.
Reaction SMILES: [CH3:1][SiH:2]([CH:6]([CH3:8])[CH3:7])[CH:3]([CH3:5])[CH3:4].S(Cl)([Cl:12])(=O)=O.Cl.S(=O)=O>>[CH3:1][Si:2]([CH:6]([CH3:8])[CH3:7])([CH:3]([CH3:5])[CH3:4])[Cl:12]
Reactant: O=S(=O)(Cl)Cl
Reactant: CC(C)[SiH](C)C(C)C
Agent: Cl
Agent: O=S=O
Product: CC(C)[Si](C)(Cl)C(C)C

Procedure:
73 g (3.0 mol) magnesium was introduced into a 2 L four-neck flask equipped with a reflux condenser, stirring rod, thermometer, and addition funnel, and was dried under nitrogen. 1,000 mL dry THF was then added. A Grignard reagent was prepared by slowly dripping in 235.6 g (3.0 mol) isopropyl chloride from the addition funnel. 166.8 g (1.45 mol) methyldichlorosilane was then dripped in from the addition funnel. After completion of this addition, the reaction was brought to completion by continuing to stir for 2 hours at the reflux temperature of THF, followed by the addition of 350 mL water, with cooling, for hydrolysis. The reaction solution was recovered by decantation, and the THF was distilled out through a 30 cm Widmer precision distillation column. Continuing with distillation at ambient pressure afforded 160 g (1.2 mol) methyldiisopropylsilane (bp= 122 degrees Centigrade). 26.1 g (0.2 mol) of the methyldiisopropylsilane thus obtained was placed in a 50 mL three-neck flask equipped with a reflux condenser, thermometer, and addition funnel. 27 g (0.2 mol) sulfuryl chloride was carefully dripped in at 60 degrees Centigrade while stirring with a magnetic stirring bar. An exothermic reaction developed with the production of hydrogen chloride and sulfur dioxide. After addition of the entire quantity, the reaction was maintained for 1 hour at 70 degrees Centigrade and then distilled in vacuo. 27 g (0.16 mol) of the target methyldiisopropylchlorosilane (bp=64 degrees Centigrade32 mmHg) was obtained.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([O:17]CC)=[O:16])[C:10]([OH:20])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:22][C:23]1[CH:42]=[CH:41][C:26]([O:27][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[O:32][C:33]=2[CH3:34])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])[C:10]([O:20][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:27][CH2:28][C:29]3[N:30]=[C:31]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[O:32][C:33]=3[CH3:34])=[CH:41][CH:42]=2)=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCc1cn(Cc2ccccc2)nc1O
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(COc2nn(Cc3ccccc3)cc2CCC(=O)O)cc1
Temperature: 60 °C
Reaction time: 5 h
Yield: 89.1 %

Procedure:
A mixture of ethyl 3-(1-benzyl-3-hydroxy-1H-pyrazol-4-yl)propionate (900 mg), 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.06 g), potassium carbonate (690 mg) and N,N-dimethylformamide (10 ml) was stirred at 60° C. for 5 hrs. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and a colorless oil was obtained from a fraction eluted with ethyl acetate-hexane (1:3, volume ratio). A mixture of the obtained colorless oil, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 2 hrs. 1N Hydrochloric acid (5 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained colorless crystals were collected by filtration to give 3-[1-benzyl-3-[-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxy]-1H-pyrazol-4-yl]propionic acid (1.53 g, yield 89%). The crystals were recrystallized from acetone-hexane. melting point: 125–126° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F:24])[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[CH3:25][N:26]1[C:30]([CH3:31])=[CH:29][C:28]([C:32](O)=[O:33])=[N:27]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:21]=[CH:22][C:23]([F:24])=[C:2]([NH:1][C:32]([C:28]5[CH:29]=[C:30]([CH3:31])[N:26]([CH3:25])[N:27]=5)=[O:33])[CH:3]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1
Reactant: Cc1cc(C(=O)O)nn1C
Reactant: Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)ccc1F
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)Nc2cc(Oc3ccc4nc(NC(=O)C5CC5)cn4n3)ccc2F)nn1C
Temperature: 60 °C
Reaction time: 36 h
Yield: 26.3 %

Procedure:
To a solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.61 mmol) in N,N-dimethylformamide (4.0 mL) were added 1,5-dimethyl-1H-pyrazole-3-carboxylic acid (171 mg, 1.22 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (351 mg, 1.83 mmol), 1-hydroxybenzotriazole (248 mg, 1.83 mmol) and triethylamine (256 μL, 1.83 mmol), and the mixture was stirred at 60° C. for 36 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1→ethyl acetate alone) to give the title compound (72 mg, 26%) as a white powder.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][C:28]([O:30][CH3:31])=[O:29])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:32]1([CH:38]=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>O1CCCC1.CCCCCC>[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH:27]([CH:38]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[OH:39])[C:28]([O:30][CH3:31])=[O:29])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=CC1CCCCC1
Reactant: COC(=O)Cc1ccccc1OCc1ccccc1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COC(=O)C(c1ccccc1OCc1ccccc1)C(O)C1CCCCC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 36.3 %

Procedure:
To a dry ice-acetone bath cooled solution of diisopropylamine (4.84 g) in tetrahydrofuran (100 ml) was added a 1.61M solution of n-butyl lithium in n-hexane (24.8 ml) and the mixture was stirred for 30 minutes at the same temperature. Methyl (2-benzyloxyphenyl)acetate (5.12 g) was added and the mixture was stirred at −70° C. for 30 minutes and allowed to warm to 0° C. Cyclohexanecarbaldehyde (2.24 g) was added and the solution was stirred for 30 minutes. The reaction mixture was quenched by 1N aqueous hydrochloric acid solution (80 ml), washed with aqueous sodium bicarbonate solution and brine, dried, and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluting with 20% diethyl ether in hexane) to afford less polar isomer of methyl (2RS,3SR)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate (isomer A) (394 mg) and more polar isomer of methyl (2RS,3RS)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate (isomer B) (2.67 g).
Reaction SMILES: [CH2:1]([C:5]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:39]3[N:43](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:42]=[N:41][N:40]=3)=[CH:29][CH:28]=2)[C:8]2[CH:9]([C:21]([O:23][CH3:24])=[O:22])[N:10]([C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:12][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4].O1CCCC1>C(O)=O>[CH2:1]([C:5]1[N:25]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[C:39]3[NH:43][N:42]=[N:41][N:40]=3)=[CH:31][CH:32]=2)[C:8]2[CH:9]([C:21]([O:23][CH3:24])=[O:22])[N:10]([C:13](=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:12][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2c(n1Cc1ccc(-c3ccccc3-c3nnnn3C(c3ccccc3)(c3ccccc3)c3ccccc3)cc1)C(C(=O)OC)N(C(=O)CC(=O)OCC)CC2
Solvent: C1CCOC1
Solvent: O=CO
Product: CCCCc1nc2c(n1Cc1ccc(-c3ccccc3-c3nnn[nH]3)cc1)C(C(=O)OC)N(C(=O)CC(=O)OCC)CC2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 96.6 %

Procedure:
To a mixture of methyl (+)-2-n-butyl-5-ethoxycarbonylacetyl-3-{2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl}methyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate (395 mg) and tetrahydrofuran (4 ml) is added 90% formic acid (8 ml) under ice-cooling, and the mixture is stirred at room temperature for 30 minutes, and evaporated under reduced pressure to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; chloroform/methanol) to give methyl (+)-2 -n-butyl-5-ethoxycarbonylacetyl-3-{2'-(1H-tetrazol-5-yl)biphenyl-4-yl}methyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate (270 mg) as foam.
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])C.O>ClC1C=CC=CC=1>[CH3:13][C:8]1[C:7]2[S:6][CH:5]=[CH:4][C:12]=2[CH:11]=[CH:10][CH:9]=1
Reactant: CCOC(CSc1ccccc1C)OCC
Solvent: Clc1ccccc1
Solvent: O
Product: Cc1cccc2ccsc12
Yield: 93.8 %

Procedure:
To a solution of intermediate 136, (2,2-diethoxyethyl)(o-tolyl)sulfane (0.58 g, 2.41 mmol) in chlorobenzene (20 mL) was added polyphosphoric acid. The reaction mixture was stirred at reflux for 18 h. Water (100 mL) was then added and the organic material was extracted with CH2Cl2 (2×50 mL). The organic solution was dried (MgSO4) and concentrated in vacuo to afford 335 mg (94% yield) of the title compound: 1H NMR (400 MHz, CDCl3) δ: 7.68 (1H, d, J=7.8 Hz), 7.43 (1H, d, J=5.4 Hz), 7.36 (1H, d, J=5.4 Hz), 7.30 (1H, dd, J=7.8, 7.1 Hz), 7.14 (1H, d, J=7.1 Hz), 2.58 (3H, s); LCMS (M+H)+ m/z 148.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:7]=[C:6]([NH2:29])[CH:5]=1.Br[CH2:32][C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34].CN(C)[C:45]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][C:53]=2N(C)C)C=CC=1.[I-].[Na+]>CN(C=O)C>[C:37]1([CH2:36][O:35][C:33](=[O:34])[CH2:32][N:29]([C:6]2[CH:7]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:9]=[C:4]([C:3]([O:2][CH3:1])=[O:30])[CH:5]=2)[CH2:4][C:3](=[O:2])[O:30][CH2:45][C:54]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(N)cc(C(=O)OC)c1
Reactant: O=C(CBr)OCc1ccccc1
Reactant: CN(C)c1cccc2cccc(N(C)C)c12
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCOc1cc(C(=O)OC)cc(N(CC(=O)OCc2ccccc2)CC(=O)OCc2ccccc2)c1
Yield: 93.8 %

Procedure:
A mixture of 3.25 g (7.74 mmol) of 3-amino-5-(octadecyloxy)benzoic acid methyl ester, 3.7 ml (23 mmol) of benzyl bromoacetate, 4.2 g (19.4 mmol) of 1,8-bis(dimethylamino)naphthalene and 0.3 g (2.2 mmol) of sodium iodide in 65 ml of acetronitrile and 20 ml of DMF was stirred and heated at reflux under argon for 48 hours. The reaction mixture was concentrated at reduced pressure and ethyl acetate was added to the residue. The extract was washed with 0.05N HCl, with saturated NaHCO3 solution, dried and concentrated at reduced pressure to a solid which was purified by HPLC using 15% ethyl acetate-hexane to give 2.6 g (48% yield, mp 62°-63°) of N-[3-(methoxycarbonyl)-5-(octadecyloxy)phenyl]-N-[2-oxo-2-(phenylmethoxy)ethyl]glycine phenylmethyl ester.
Reaction SMILES: [CH3:1][N:2]([CH3:24])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]([NH2:23])=O)[CH:19]=3)[NH:14][N:13]=2)=[CH:8][CH:7]=1.COC(OC)[N:28]([CH3:30])C.[NH2:33]N>C(O)(=O)C>[NH:33]1[C:21]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[C:12]3[C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:24])[CH3:1])=[CH:7][CH:8]=2)=[N:23][CH:30]=[N:28]1
Reactant: NN
Reactant: COC(OC)N(C)C
Reactant: CN(C)CCOc1ccc(-c2n[nH]c3ccc(C(N)=O)cc23)cc1
Solvent: CC(=O)O
Product: CN(C)CCOc1ccc(-c2n[nH]c3ccc(-c4ncn[nH]4)cc23)cc1
Temperature: 93 °C
Yield: 86.6 %

Procedure:
A mixture of 3-{4-[2-(dimethylamino)ethoxy]phenyl}-1H-indazole-5-carboxamide (79 mg, 0.243 mmol) and N,N-dimethylformamide dimethyl acetal (10.0 mL, 75.3 mmol, 310 equiv.) was heated at 93° C. for 3 h and then concentrated. To the concentrate was added 4.0 mL of glacial acetic acid (AcOH), and anhydrous hydrazine (204 mg, 6.36 mmol, 26.2 equiv.). The mixture was heated at 93° C. for 3 h and concentrated. The residue was partitioned between EtOAc and 6.0 N aq. NaOH and the layers separated. The aqueous layer was extracted with 2×EtOAc and then the pH adjusted between 10–11 with 6.0 N aq. HCl to give maximum cloudiness. The mixture was extracted with 3×EtOAc. The combined organics were dried (Na2SO4), filtered, and concentrated to afford the title compound (73.3 mg, 86.5% yield): 1H NMR (DMSO-d6) δ 14.20 (br s, 1H), 13.30 (br s, 1H), 8.65 (s, 1H), 8.37 (br s, 1H), 8.07 (d, 1H), 7.96 (d, 2H), 7.65 (d, 1H), 7.15 d, 2H), 4.14 (t, 2H), 2.67 (t, 2H), 2.24 (s, 6H); ES-MS (m/z) 349 [M+1]+.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][N:9]3[C:12]([C:15]4[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=4)=[CH:13][N:14]=[C:8]3[CH:7]=2)=[CH:2]1.S(C)C.[OH-].[Na+]>C1COCC1>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][N:9]3[C:12]([C:15]4[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=4)=[CH:13][N:14]=[C:8]3[CH:7]=2)=[CH:2]1
Reactant: N#Cc1ccc(-c2cnc3cc(-c4ccsc4)ccn23)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CSC
Product: NCc1ccc(-c2cnc3cc(-c4ccsc4)ccn23)cc1
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
Dissolve 4-(7-thien-3-yl-imidazo[1,2-a]pyridin-3-yl)-benzonitrile (0.087 g, 0.29 mmol) in THF (8 mL). To the solution add a BH3.Me2S solution (2 M, 1.0 mL, 2.0 mmol) at room temperature. Stir the solution for 15 minutes and then heat at 50° C. for 3.5 hours. Cool the mixture at 0° C. and acidify to pH=1 slowly and stir for 30 minutes. Make the reaction mixture basic with solid NaOH to pH=12-14, followed by extraction with ethyl acetate. Wash the extracts with saturated aqueous saturated sodium chloride, dry over MgSO4, filter and evaporate to afford 0.070 g. MS(ES), m/z 306 (M+1).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH3:10])=[O:8])[CH2:3]1.[C:11](=[O:14])([O-])[O-:12].[K+].[K+]>C1COCC1.O>[CH3:10][O:9][C:7]([C@@H:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:11](=[O:14])[O:12][C:4]([CH3:7])([CH3:5])[CH3:3])[CH2:3]1)=[O:8]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)[C@@H]1CC[C@H](N)C1
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)[C@@H]1CC[C@H](NC(=O)OC(C)(C)C)C1
Reaction time: 24 h
Yield: 172.7 %

Procedure:
Boc-anhydride (2.90 ml, 13.1 mmol) was added to a solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (1.70 g, 11.9 mmol) and potassium carbonate (3.29 g, 23.8 mmol) in THF (10 ml), water (20 ml) and stirred for 24 h. The reaction mixture was extracted with DCM (2×50 ml). The combined organic layer was washed with water (20 ml), brine solution (20 ml), dried over anhydrous sodium sulfate, filtered and concentrated under vacuo to afford 2.5 g (87%) of tert-butyl (1S,3R)-3-(methoxycarbonyl)cyclopentylcarbamate as a colorless liquid.
Reaction SMILES: [CH3:1][S:2]([NH:5][CH2:6][CH2:7][CH2:8][C:9]([NH2:11])=[S:10])(=[O:4])=[O:3].Br[CH2:13][C:14](=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16]>CCO>[CH2:18]([O:17][C:15]([C:14]1[N:11]=[C:9]([CH2:8][CH2:7][CH2:6][NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[S:10][CH:13]=1)=[O:16])[CH3:19]
Reactant: CCOC(=O)C(=O)CBr
Reactant: CS(=O)(=O)NCCCC(N)=S
Solvent: CCO
Product: CCOC(=O)c1csc(CCCNS(C)(=O)=O)n1
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 89.3 %

Procedure:
A solution of 4-methanesulfonylamino-thiobutyramide (0.35 g, 1.8 mmol) and ethyl bromopyruvate (0.37 g, 1.9 mmol) in EtOH (50 mL) was stirred at room temperature for 17 h. Additional ethyl bromopyruvate (0.05 g, 0.26 mmol) was added and the reaction mixture was stirred at room temperature for 5.5 h. The reaction mixture was concentrated and was purified by flash chromatography (79:1 to 19:1 EtOAc:MeOH) to afford the title compound (0.47 g). 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 4.40 (q, 2H), 3.24 (t, 2H), 3.17 (t, 2H), 2.96 (s, 3H), 2.10 (t, 2H), 1.39 (t, 3H); MS 293 (M+ +1).
Reaction SMILES: [S:1](S([O-])=O)([O-:3])=[O:2].[Na+].[Na+].Cl[CH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1.O>CN(C=O)C>[C:11]1([CH2:10][S:1]([CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)(=[O:3])=[O:2])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: O=S([O-])S(=O)[O-]
Reactant: ClCc1cccc2ccccc12
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=S(=O)(Cc1cccc2ccccc12)Cc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 12 h
Yield: 100.3 %

Procedure:
To a well-stirred suspension of 7.3 grams (42 mmol) of sodium hydrosulfite (Na2S2O4) in 30 ml DMF was added 5.0 grams (28.3 retool) of 1-chloromethylnaphthalene. The mixture was stirred at room temperature for 12 hours, then brought to 85° C. for 24 hours. The warm mixture was poured onto 400 ml crushed ice, and the total volume brought to 700 ml with water. The precipitated solids were filtered to give 4.91 grams (14.2 mmol, 100% yield) of bis(1-naphthylmethyl) sulfone. Pure material was obtained by recrystallization from toluene (mp 220° C.).
Reaction SMILES: [CH3:1][C:2]1[CH2:3][C:4](=[O:13])[N:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:6]=1.[CH3:14][N:15]([CH3:24])[C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1.N1CCCCC1>C(O)C.O>[CH3:14][N:15]([CH3:24])[C:16]1[CH:23]=[CH:22][C:19](/[CH:20]=[C:3]2/[C:4](=[O:13])[N:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=3)[N:6]=[C:2]/2[CH3:1])=[CH:18][CH:17]=1
Reactant: CC1=NN(c2ccccn2)C(=O)C1
Reactant: CN(C)c1ccc(C=O)cc1
Solvent: C1CCNCC1
Solvent: CCO
Solvent: O
Product: CC1=NN(c2ccccn2)C(=O)/C1=C/c1ccc(N(C)C)cc1

Procedure:
1.3 g (7.42 mmol) of 5-methyl-2-(2-pyridinyl)-2,4-dihydro-3H-pyrazol-3-one and 1.68 g (11.13 mmol) of 4-(dimethylamino)benzaldehyde are stirred under reflux with the addition of 3 ml of piperidine in absolute ethanol for 2 hours. The mixture is then diluted with water and the orange-red precipitate is filtered off, then washed with water and dried under reduced pressure.
Reaction SMILES: C([O:3][C:4](=[O:19])[CH:5]([O:16][CH2:17][CH3:18])[CH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[CH:10]2)C.Cl[CH2:21][C:22]1[N:23]=[C:24]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)[O:25][C:26]=1[CH3:27]>>[Cl:34][C:30]1[CH:29]=[C:28]([C:24]2[O:25][C:26]([CH3:27])=[C:22]([CH2:21][N:12]3[C:13]4[C:9](=[CH:8][C:7]([CH2:6][CH:5]([O:16][CH2:17][CH3:18])[C:4]([OH:3])=[O:19])=[CH:15][CH:14]=4)[CH:10]=[CH:11]3)[N:23]=2)[CH:33]=[CH:32][CH:31]=1
Reactant: CCOC(=O)C(Cc1ccc2[nH]ccc2c1)OCC
Reactant: Cc1oc(-c2cccc(Cl)c2)nc1CCl
Product: CCOC(Cc1ccc2c(ccn2Cc2nc(-c3cccc(Cl)c3)oc2C)c1)C(=O)O
Yield: 21 %

Procedure:
Starting from rac-2-ethoxy-3-(1H-indol-5-yl)-propionic acid ethyl ester and 4-chloromethyl-2-(3-chloro-phenyl)-5-methyl-oxazole, the title compound was obtained in 21% yield as a yellow solid. MS: (M+H)+ 439.3.
Reaction SMILES: P([O-])([O-])([O-])=O.[K+].[K+].[K+].[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]#[N:15].C(#N)C.[OH2:19].CN(C)[C:22](=[O:29])[C:23]1C=C[CH:26]=[CH:25][CH:24]=1>C(#N)C>[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([NH2:15])=[O:29].[S:9]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:22]([OH:29])=[O:19]
Reactant: O
Reactant: N#Cc1cccs1
Reactant: CN(C)C(=O)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: NC(=O)c1cccs1
Product: O=C(O)c1cccs1
Reaction time: 0.5 h

Procedure:
To a 15-mL polypropylene centrifuge tube was added 3.86 mL of 50 mM potassium phosphate buffer (pH 7.0), 1.0 mL of a suspension of 22.1 mg dry cell weight E. coli SW132 wet cells (prepared as described in Example 10) in 50 mM potassium phosphate buffer (pH 7.0), and 0.1691 g of 2-thiophenecarbonitrile. The final concentration of 2-thiophencarbonitrile was 0.307 M. The reaction mixture was mixed on a rotating platform at 27° C. After 30 min, 7.50 mL of 95:5 acetonitrile/water containing 0.30 M N,N-dimethylbenzamide (HPLC external standard) was added to the reaction, the resulting mixture centrifuged, and a 0.100 mL of the supernatant mixed with 0.900 mL of acetonitrile and analyzed by HPLC. The conversion of 2-thiophenecarbonitrile was 99.5%, and the yields of 2-thiophenecarboxamide and 2-thiophenecarboxylic acid were 98% and 0%, respectively.