Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[S:4][C:5]2[C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=[C:8]([O:15][CH3:16])[C:6]=2[N:7]=1)[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[N:28]([CH3:29])[N:27]=[CH:26][C:25]=1[C:30]#[N:31]>ClCCl.CN(C)C=O>[C:30]([C:25]1[CH:26]=[N:27][N:28]([CH3:29])[C:24]=1[NH:23][C:12]([C:11]1[C:5]2[S:4][C:3]([CH2:1][CH3:2])=[N:7][C:6]=2[C:8]([O:15][CH3:16])=[CH:9][CH:10]=1)=[O:14])#[N:31]
Reactant: CCc1nc2c(OC)ccc(C(=O)O)c2s1
Reactant: Cn1ncc(C#N)c1N
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCc1nc2c(OC)ccc(C(=O)Nc3c(C#N)cnn3C)c2s1
Temperature: 25 °C
Reaction time: 16 h
Yield: 61.2 %

Procedure:
To a suspension of 2-ethyl-4-methoxybenzothiazole-7-carboxylic acid (0.1 g) in dichloromethane (10 ml) was added oxalyl chloride (1.0 ml) and dimethylformamide (1 drop). The reaction was stirred at room temperature for 16 hrs, and then the solvent was removed in vacuo to yield a brown solid residue. 5-Amino-1-methyl-1H-pyrazole-4-carbonitrile (0.1 g) was taken up in dichloromethane (10 ml) and sodium hexamethyldisilylamine (1.0M in tetrahydrofuran, 0.84 ml) was added. After 5 minutes the acid chloride was added and the reaction stirred at room temperature for 16 hrs. The solvent was removed in vacuo and the product purified by flash chromatography (eluent 50% ethyl acetatethexane-75% ethyl acetate/hexane) to yield the title compound as an off-white solid (0.088 g). TLC Rf 0.13 (50% ethyl acetate/hexane); Mpt 190-191° C.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH2:10]([O:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][C:16]=1[Cl:24])[CH2:11][CH2:12][CH3:13].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH2:10]([O:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=2)=[CH:17][C:16]=1[Cl:24])[CH2:11][CH2:12][CH3:13]
Reactant: O=Cc1cccc(Br)n1
Reactant: CCCCOc1ccc(B(O)O)cc1Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: CCCCOc1ccc(-c2cccc(C=O)n2)cc1Cl
Temperature: 80 °C
Yield: 82 %

Procedure:
To a solution of 6-bromopicolinaldehyde (4.07 g, 21.88 mmol) in dioxane (40 mL) at ambient temperature was added 4-butoxy-3-chlorophenylboronic acid (5.00 g, 21.9 mmol), 2M cesium carbonate (22.0 mL, 43.8 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.357 g, 0.438 mmol). The mixture was degassed (3× vacuum/purge N2) then heated at 80° C. overnight. The mixture was cooled to room temperature then partioned between water and CH2Cl2. The organic phase was concentrated and purified by chromatography (silica gel, 10% ethyl acetate:hexanes) to provide 5.20 g (82%) of the title compound. MS (DCI+) m/z 290 (M+H).
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][C:11]1[S:15][C:14]2[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=2[C:12]=1[C:20]#[N:21].Cl>N1C=CC=CC=1>[C:1]([NH:10][C:11]1[S:15][C:14]2[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=2[C:12]=1[C:20]#[N:21])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: N#Cc1c(N)sc2c1CCCC2
Agent: Cl
Solvent: c1ccncc1
Product: N#Cc1c(NC(=O)c2ccccc2)sc2c1CCCC2
Reaction time: 2 h
Yield: 97 %

Procedure:
4.7 ml (40 mmol) of benzoyl chloride were added to a solution of 5.34 g (30 mmol) of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene in 50 ml of pyridine. Stirring was carried out for 2 hours at 80° C. after which 150 ml of 10 mol % aqueous hydrochloric acid were added to the mixture. The solid formed was isolated in a conventional manner. Yield: 97%; mp.: 168°-170° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:18]([F:21])([F:20])[F:19])=[C:13](I)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:23]=1.C([Sn](CCCC)(CCCC)CCCC)=C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][C:10]2[C:15](=[CH:14][C:13]([CH:22]=[CH2:23])=[C:12]([C:18]([F:21])([F:20])[F:19])[CH:11]=2)[CH2:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: c1ccc([As](c2ccccc2)c2ccccc2)cc1
Reactant: CC(C)(C)OC(=O)N1Cc2cc(I)c(C(F)(F)F)cc2C1
Agent: [Pd+2]
Agent: C=C[Sn](CCCC)(CCCC)CCCC
Agent: CC(=O)[O-]
Solvent: C1COCCO1
Product: C=Cc1cc2c(cc1C(F)(F)F)CN(C(=O)OC(C)(C)C)C2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 93 %

Procedure:
To a stirred solution 0.61 mmol 5-iodo-6-trifluoromethyl-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (Example A35(d)) in 3 ml dioxane were added 0.04 mmol palladium(II) acetate and 0.18 mmol triphenylarsine and the mixture was stirred at RT for 10 min. 0.91 mmol vinyltributylstannane was then added and the mixture was heated at 100° C. for 16 h. The reaction mixture was then cooled to room temperature, filtered, and the filtrate was concentrated in vacuo. The residue was purified by chromatography (SiO2, heptane/ethyl acetate) to yield the title compound as a yellow solid (93% yield). MS (m/e): 258.0 ([M+H−Me2C═CH2]+, 100%).
Reaction SMILES: [CH3:1][N:2]([C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:22]=1[NH:21][C:20]([C:23]1[S:24][CH:25]=[CH:26][N:27]=1)=[CH:19]2)[S:3]([C:6]1[CH:10]=[CH:9][S:8][C:7]=1[C:11](O)=[O:12])(=[O:5])=[O:4].N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.Cl>CN(C)C=O>[CH3:1][N:2]([C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:22]=1[NH:21][C:20]([C:23]1[S:24][CH:25]=[CH:26][N:27]=1)=[CH:19]2)[S:3]([C:6]1[CH:10]=[CH:9][S:8][C:7]=1[C:11]([N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1)=[O:12])(=[O:5])=[O:4]
Reactant: C1COCCN1
Reactant: CN(c1cccc2cc(-c3nccs3)[nH]c12)S(=O)(=O)c1ccsc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CN(c1cccc2cc(-c3nccs3)[nH]c12)S(=O)(=O)c1ccsc1C(=O)N1CCOCC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 52 %

Procedure:
To a solution of 3-({methyl[2-(1,3-thiazol-2-yl)-1H-indol-7-yl]amino}sulfonyl)thiophene-2-carboxylic acid (100 mg), 1H-1,2,3-benzotriazol-1-ol (46 mg) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (58 mg) in N,N-dimethylformamide (2 mL) was added morpholine (100 μL), and the mixture was stirred at room temperature for 12 hr. To the reaction mixture was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was crystallized from diethyl ether-hexane to give the title compound (61 mg, yield 52%) as colorless crystals. melting point 190° C.
Reaction SMILES: C(OC([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[CH:14]=2)[CH2:9]1)=O)(C)(C)C.[C:25]([OH:31])([C:27]([F:30])([F:29])[F:28])=[O:26]>C(Cl)Cl>[F:28][C:27]([F:30])([F:29])[C:25]([OH:31])=[O:26].[N:19]1([C:17]([C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[CH2:9][NH:8][CH2:16]3)=[O:18])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1
Reactant: CC(C)(C)OC(=O)N1Cc2ccc(C(=O)N3CCOCC3)cc2C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(c1ccc2c(c1)CNC2)N1CCOCC1

Procedure:
A solution of N-t-butoxycarbonyl-5-[(morpholin-4-yl)carbonyl] isoindoline (D19) (300 mg) in DCM (5 ml) at rt was treated with TFA (2 ml) for 1 h and then evaporated. The residue was re-evaporated from DCM/toluene to give the title compound (D20) (305 mg). MS electrospray (+ion) 233 (MH+). 1H NMR δ (CDCl3): 10.10 (1H, m), 7.25 (3H, m), 4.64 (2H, m), 4.53 (2H, m), 3.54 (8H, m).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH:8]=O)=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1.[OH-].[K+].[CH3:14][C:15]([CH3:17])=O>>[CH3:17][C:15]1[CH:14]=[CH:8][C:7]2[CH:6]=[N:5][C:4]([S:10][CH3:11])=[N:3][C:2]=2[N:1]=1
Reactant: CSc1ncc(C=O)c(N)n1
Reactant: CC(C)=O
Agent: [K+]
Agent: [OH-]
Product: CSc1ncc2ccc(C)nc2n1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Treat a solution of 4-amino-2-(methylthio)pyrimidine-5-carbaldehyde (10 g, 59.1 mmol) in acetone (100 mL) with KOH (3.32 g, 59.1 mmol), stir at RT for 10 min, then concentrate to dryness. Treat the residue with EtOAc, wash with saturated. Aqueous NaHCO3, then brine, dry over Na2SO4 and concentrate to obtain 7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidine. MS (m/z): 192.1 (M+1). Add a solution of methylamine in ethanol (33%, 80 mL) and heat at 110° C. overnight in a pressure tube. Remove the solvent under reduced pressure and purify the crude product by silica gel chromatography (50-100% EtOAc/Hexanes) to obtain the title compound (6.73 g, 65%, over two steps). MS (m/z): 175.1 (M+1).
Reaction SMILES: ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[N+:23]([C:26]1[N:27]=[C:28]2[N:33]([CH:34]=1)[CH2:32][CH2:31][C@H:30]([CH2:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)=[CH:39][CH:38]=1)[O:29]2)([O-:25])=[O:24].[F:49][C:50]([F:62])([F:61])[C:51]1[CH:52]=[C:53]([OH:60])[C:54](=[CH:58][CH:59]=1)[C:55](O)=[O:56]>O.CN(C=O)C>[OH:60][C:53]1[CH:52]=[C:51]([C:50]([F:49])([F:61])[F:62])[CH:59]=[CH:58][C:54]=1[C:55]([N:46]1[CH2:47][CH2:48][N:43]([C:40]2[CH:41]=[CH:42][C:37]([O:36][CH2:35][C@@H:30]3[O:29][C:28]4=[N:27][C:26]([N+:23]([O-:25])=[O:24])=[CH:34][N:33]4[CH2:32][CH2:31]3)=[CH:38][CH:39]=2)[CH2:44][CH2:45]1)=[O:56]
Reactant: O=[N+]([O-])c1cn2c(n1)O[C@@H](COc1ccc(N3CCNCC3)cc1)CC2
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: O=C(c1ccc(C(F)(F)F)cc1O)N1CCN(c2ccc(OC[C@H]3CCn4cc([N+](=O)[O-])nc4O3)cc2)CC1
Temperature: 25 °C
Reaction time: 11 h
Yield: 68.9 %

Procedure:
1-Hydroxybenzotriazole (0.19 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.24 g) were added to a DMF solution (5 ml) of (R)-2-nitro-7-(4-piperazin-1-ylphenoxymethyl)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (0.40 g) and 4-(trifluoromethyl)salicylic acid (0.25 g), and the mixture was stirred at room temperature for 11 hours. Water was added to the reaction mixture. After stirring the mixture for a while, the precipitate was collected by filtration. The resulting crude product was purified by silica gel column chromatography (methylene chloride:methanol=90:10) and recrystallized from ethanol-acetone to afford the title compound as a white powder (0.42 g).
Reaction SMILES: S([O-])([O-])(=O)=O.[NH4+].[NH4+].S([O-])([O-])(=O)=O.CO.[CH2:15]([OH:37])[C@H:16]1[O:21][C@H:20]([O:22][C@H:23]2[C@H:28]([OH:29])[C@@H:27]([OH:30])[C@H:26]([OH:31])[O:25][C@@H:24]2[CH2:32][OH:33])[C@H:19]([OH:34])[C@@H:18]([OH:35])[C@@H:17]1[OH:36].O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O>C(O)CCC.N1C=CC=CC=1.O>[CH2:15]([OH:37])[C@H:16]1[O:21][C@H:20]([O:22][CH2:23][C@H:24]2[O:25][CH:26]([OH:31])[C@H:27]([OH:30])[C@@H:28]([OH:29])[C@@H:32]2[OH:33])[C@H:19]([OH:34])[C@@H:18]([OH:35])[C@@H:17]1[OH:36]
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=S(=O)([O-])[O-]
Agent: [NH4+]
Solvent: CO
Solvent: CCCCO
Solvent: c1ccncc1
Product: OC[C@H]1O[C@H](OC[C@H]2OC(O)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 100 °C

Procedure:
Bacillus circulans PP710, FERM BP-10771, was cultivated by the method in Experiment 1-1, and about 3 L of the resulting culture supernatant was salted out using ammonium sulfate. Then, the resulting precipitated was dissolved in water, dialyzed against 20 mM Tris-HCl buffer containing 1 mM CaCl2, and about 40 ml of the resulting dialyzate was collected as a crude enzyme solution. The crude enzyme solution was admixed with 2% (w/v) of soluble starch solution or 2=% (w/v) of pullulan solution, and followed by the enzyme reaction at pH 6.0 and 40° C. for 16 hours. After stopping the reaction by heating at 100° C. for 10 min, the reaction mixture was subjected to TLC using “SILICAGELM 60F254”, a TLC plate (10×20 cm) commercialized by Merck. TLC was carried out using a solvent (n-butanol/pyridine/water, volume ratio of 6:4:1) and two-times ascending method. The products on the plate were detected by visualizing the spots by spraying 20% sulfate-methanol solution and heating at 100° C. for 5 min. By the TLC analyses, it was revealed that maltose and α-1,4 glucan having a glucose polymerization degree of 3 or higher were formed from soluble starch, and slight amounts of isomaltose and panose were formed from pullulan. It was revealed that an amylase which hydrolyzes starch and pullulan was present in the crude enzyme from Bacillus circulans PP710, FERM BP-10771, as a concomitant enzyme.
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4]([C:14]2[CH:15]=[C:16]3[C:24](=[CH:25][CH:26]=2)[NH:23][C:22]2[CH:21]=[C:20]4[C:27]([CH3:35])([CH3:34])[C:28]5[C:33]([C:19]4=[CH:18][C:17]3=2)=[CH:32][CH:31]=[CH:30][CH:29]=5)=[CH:3][CH:2]=1.[H-].[Na+].Cl[C:39]1[N:44]=[C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[N:42]=[C:41]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[N:40]=1>CN(C)C=O>[CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]=2[C:4]([C:14]2[CH:15]=[C:16]3[C:24](=[CH:25][CH:26]=2)[N:23]([C:39]2[N:44]=[C:43]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[N:42]=[C:41]([C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)[N:40]=2)[C:22]2[CH:21]=[C:20]4[C:27]([CH3:35])([CH3:34])[C:28]5[C:33]([C:19]4=[CH:18][C:17]3=2)=[CH:32][CH:31]=[CH:30][CH:29]=5)=[CH:3][CH:2]=1
Reactant: CC1(C)c2ccccc2-c2cc3c(cc21)[nH]c1ccc(-c2cccc4c2oc2ccccc24)cc13
Reactant: Clc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)c2ccccc2-c2cc3c4cc(-c5cccc6c5oc5ccccc56)ccc4n(-c4nc(-c5ccccc5)nc(-c5ccccc5)n4)c3cc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
16.6 g (58.78 mmol) of 7-dibenzofuran-4-yl-12,12-dimethyl-10,12-dihydro-10-azaindeno[2,1-b]fluorene are dissolved in 225 ml of dimethylformamide under a protective-gas atmosphere, and 2.8 g of 60% NaH in mineral oil (70 mmol) are added. After 1 h at room temperature, a solution of 2-chloro-4,6-diphenyl-1,3,5-triazine (18.6 g, 66.2 mmol) in 75 ml of dimethylformamide is added dropwise. The reaction mixture is stirred at room temperature for 12 h. After this time, the reaction mixture is poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene, recrystallised from dichloromethane/isopropanol and finally sublimed in a high vacuum, the purity is 99.9%. The yield is 18.3 g (27 mmol, 45.7%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][CH2:20][C:21]2[O:25][C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:23][C:22]=2[CH2:32][OH:33])=[CH:17][CH:16]=1>[O-2].[O-2].[Mn+4].O1CCCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][CH2:20][C:21]2[O:25][C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[N:23][C:22]=2[CH:32]=[O:33])=[CH:17][CH:16]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(OCc2oc(-c3ccccc3)nc2CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(OCc2oc(-c3ccccc3)nc2C=O)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 89.1 %

Procedure:
A mixture of [5-({4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenoxy}methyl)-2-phenyl-1,3-oxazol-4-yl]methanol (3.10 g), activated manganese dioxide (10.0 g) and tetrahydrofuran (300 mL) was stirred at room temperature for 15 hrs. Manganese dioxide was removed by filtration, and the filtrate was concentrated. The obtained crystals were collected by filtration and washed with hexane to give 5-({4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenoxy}methyl)-2-phenyl-1,3-oxazole-4-carbaldehyde (2.75 g, yield 89%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 127-128° C.
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:8][O:9][C:10]1[CH:15]=[C:14]([CH2:16][NH:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH2:27][CH2:28][CH2:29][NH2:30])[CH:13]=[CH:12][C:11]=1[OH:31].[CH2:32]([O:39][CH:40]1[C:45](=[O:46])[C:44]2[CH:47]=[CH:48][C:49]([C:51]([CH3:59])([CH3:58])[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])=[CH:50][C:43]=2[O:42][C:41]1([CH3:61])[CH3:60])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[OH-].[NH4+]>COCOC.[Zn]>[CH3:8][O:9][C:10]1[CH:15]=[C:14]([CH2:16][NH:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH2:27][CH2:28][CH2:29][NH2:30])[CH:13]=[CH:12][C:11]=1[OH:31].[CH2:32]([O:39][CH:40]1[C:45]([CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])([OH:46])[C:44]2[CH:47]=[CH:48][C:49]([C:51]([CH3:59])([CH3:58])[CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])=[CH:50][C:43]=2[O:42][C:41]1([CH3:60])[CH3:61])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: CCOC(=O)CBr
Reactant: CCCCCCC(C)(C)c1ccc2c(c1)OC(C)(C)C(OCc1ccccc1)C2=O
Agent: COc1cc(CNCCCNCCCCNCCCN)ccc1O
Agent: [NH4+]
Agent: [OH-]
Solvent: COCOC
Product: CCCCCCC(C)(C)c1ccc2c(c1)OC(C)(C)C(OCc1ccccc1)C2(O)CC(=O)OCC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Zinc metal (13 g, 0.2 mole) is covered with a small amount of dimethoxymethane. The mixture is heated at reflux and a solution of 16.7 g (0.1 mole) ethyl bromoacetate in 75 ml of dimethoxymethane is added over 20 minutes. After refluxing for 30 minutes, the mixture is cooled to 0°-5° C. and 40.85 g (0.10 mole) dl-5-benzyloxy-2,2-dimethyl-7-(1,1-dimethylheptyl)-3,4-dihydro-2H-benzopyran-4-one is added dropwise. The mixture is stirred at 0°-5° C. for one hour, allowed to warm to room temperature and stirred overnight. Ammonium hydroxide, 25 ml, is added, the mixture extracted with ethyl ether and isolated as described in Part A above, to afford the desired product.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[CH:21]([NH:23][CH2:24][CH2:25][CH:26]1[O:31][CH2:30][CH2:29][NH:28][CH2:27]1)=[O:22]>>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11]([N:28]4[CH2:29][CH2:30][O:31][CH:26]([CH2:25][CH2:24][NH:23][CH:21]=[O:22])[CH2:27]4)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:2][CH2:3]1
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Reactant: O=CNCCC1CNCCO1
Product: O=CNCCC1CN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2F)CCO1

Procedure:
By the use of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2-(2-formylaminoethyl)morpholine, the reaction is similarly carried out as Example 11 to give 1-cyclopropyl-6,8-difluoro-7-[2-(2-formylaminoethyl)morpholino]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].N[C@H](C1C=CC=C([N+]([O-])=O)C=1)CC(O)=O.S(Cl)([Cl:36])=O>>[ClH:36].[NH2:2][C@@H:3]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: CCOC(=O)C[C@H](N)c1cccc([N+](=O)[O-])c1
Reactant: O=S(Cl)Cl
Agent: Cl
Agent: N[C@@H](CC(=O)O)c1cccc([N+](=O)[O-])c1
Product: CCOC(=O)C[C@@H](N)c1cccc([N+](=O)[O-])c1
Yield: 99 %

Procedure:
Using a procedure analogous to that used to prepare 34A, (S)-3-amino-3-(3-nitrophenyl)propanoic acid (2.1 g, 10 mmol) was reacted with thionyl chloride to 10 afford 39A (2.75 g, 99%) as a white solid. MS (ESI) m/z 239.08 (M+H)+.
Reaction SMILES: [OH:1][N:2]1[C:6]2[CH:7]=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:5]=2[N:4]=[C:3]1[C:18]([F:21])([F:20])[F:19].[CH2:22](I)[CH3:23].[O-]CC.[Na+]>CO>[CH2:22]([O:1][N:2]1[C:6]2[CH:7]=[C:8]([C:14]([F:15])([F:16])[F:17])[CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:5]=2[N:4]=[C:3]1[C:18]([F:19])([F:21])[F:20])[CH3:23]
Reactant: CCI
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cc2c1nc(C(F)(F)F)n2O
Agent: CC[O-]
Agent: [Na+]
Solvent: CO
Product: CCOn1c(C(F)(F)F)nc2c([N+](=O)[O-])cc(C(F)(F)F)cc21

Procedure:
A 6 g. portion of 1-hydroxy-4-nitro-2,6-bis(trifluoromethyl)benzimidazole was mixed with 50 ml. of methanol, 10 ml. of ethyl iodide, and 2.5 g. of sodium ethoxide. The mixture was heated at reflux temperature overnight with stirring, and was then cooled and evaporated to dryness. The residue was taken up in ether, and the ether solution was washed with water. The ether layer was then evaporated to dryness, and the residue was recrystallized from petroleum ether to produce the desired 1-ethoxy-4-nitro-2,6-bis(trifluoromethyl)benzimidazole, m.p. 94°-96°C.
Reaction SMILES: [C:1]1([N:11]=[C:12]2[CH:17]=[CH:16][C:15](=[O:18])[CH:14]=[CH:13]2)[C:10]2[C:5](=CC=CC=2)[CH:4]=[CH:3][CH:2]=1.C1C2C(=CC=CC=2)C=CC=1N=C1C=CC(=O)C=C1>>[C:1]1([N:11]=[C:12]2[CH:13]=[CH:14][C:15](=[O:18])[CH:16]=[CH:17]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:10]=1
Reactant: O=C1C=CC(=Nc2cccc3ccccc23)C=C1
Agent: O=C1C=CC(=Nc2ccc3ccccc3c2)C=C1
Product: O=C1C=CC(=Nc2ccccc2)C=C1

Procedure:
4-(1-naphthylimino)-2,5-cyclohexadien-1-one; 4-(2-naphthylimino)-2,5-cyclohexadien-1-one;
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[S:27])=[CH:21][CH:20]=1.C1(C)C=CC=CC=1>CCOCC>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([F:16])[C:10]=1[CH2:9][O:8][C:7]1[C:2]([NH:1][C:26]([NH:25][C:22]2[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=2)=[S:27])=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1ncccc1OCc1c(F)cccc1Cl
Reactant: Cc1ccc(N=C=S)cc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: Cc1ccc(NC(=S)Nc2ncccc2OCc2c(F)cccc2Cl)cc1

Procedure:
A mixture of 2-amino-3-(2-chloro-6-fluorobenzyloxy)pyridine (2g, 0.008 mol), 4methylphenyl isothiocyanate (1.43g, 0.0096 mol) and toluene (10 ml) was heated under reflux for 5 hours, then cooled and diluted with ether to induce crystallisation of the product. Yield 2.61g (82%) m.p. 138°-140 ° C.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10](Br)[CH:9]=1)(=[O:3])[CH3:2].[C:27]([C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)#[N:28]>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:32]2[CH:33]=[N:34][C:29]([C:27]#[N:28])=[CH:30][CH:31]=2)[CH:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cccc(Br)c1
Reactant: N#Cc1ccc(B(O)O)cn1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cccc(-c2ccc(C#N)nc2)c1
Yield: 45 %

Procedure:
By carrying out the operation analogously to example 3, starting from 3-bromophenyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, obtained according to preparation VII, and 6-cyano-3-pyridineboronic acid, the expected product is obtained in the form of a white solid with a yield of 45%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH:4]([CH2:8][NH:9][C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5](=[O:7])[CH3:6].CCN(CC)CC>C(Cl)Cl>[C:10]([NH:9][CH2:8][C@@H:4]([C@H:5]([OH:7])[CH3:6])[C:3]([O:2][CH3:1])=[O:18])(=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COC(=O)C(CNC(=O)c1ccccc1)C(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@@H](CNC(=O)c1ccccc1)[C@@H](C)O
Yield: 89.5 %

Procedure:
In a 100 ml autoclave was put a solution of 2.5 g (10 mmol) of methyl-2-(N-benzoylamino)methyl-3-oxobutyrate and 173 mg (0.102 mmol) of Ru2Cl4((R)-BINAP)2.NEt3 in 17.5 ml of methylene chloride, and the mixture was stirred at 50° C. under a hydrogen pressure of 10000 kPa for 20 hours. The solvent was removed by evaporation under reduced pressure, and the residue was purified by column chromatography to furnish 2.25 g (90%) of the title compound. Optical purity: 98%e.e.