Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C@@H:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[C:14]([N+:21]([O-:23])=[O:22])[CH:13]=2)[CH:8]=[CH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:25][SiH:26]([CH3:28])[Cl:27]>ClCCl.C(O)(C)C>[C:1]1([C@@H:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[C:14]([N+:21]([O-:23])=[O:22])[CH:13]=2)[CH2:8][CH2:9][Si:26]([Cl:27])([CH3:28])[CH3:25])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C=C[C@H](NC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)c1ccccc1
Reactant: C[SiH](C)Cl
Solvent: CC(C)O
Solvent: ClCCl
Product: C[Si](C)(Cl)CC[C@H](NC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)c1ccccc1
Reaction time: 6 h

Procedure:
1 g (3.06 mmol) of amide 5 was dispersed in an inert atmosphere in 10 ml of dry dichloromethane. 12 mg of H2PtCl6.xH2O was dispersed in 0.25 ml isopropanol and the obtained brown suspension was added to the reaction mixture. Afterwards, 10 ml of dimethylchlorosilane (92 mmol) was added and the reaction mixture was stirred on a reflux temperature for six hours. The transparent yellow solution was evaporated to paste remain which was dissolved in 5 ml of dry dichloromethane and again evaporated until dry.
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3](N)=O.F[B-](F)(F)F.C([O+](CC)CC)C.[N:19]1([C@@H:24]2[CH2:29][CH2:28][C@H:27]([NH:30][C:31]3[C:36]([NH2:37])=[CH:35][N:34]=[C:33]4[CH:38]=[CH:39][S:40][C:32]=34)[CH2:26][CH2:25]2)[CH:23]=[N:22][CH:21]=[N:20]1>O1CCCC1.C(O)C>[N:19]1([C@@H:24]2[CH2:29][CH2:28][C@H:27]([N:30]3[C:31]4=[C:32]5[S:40][CH:39]=[CH:38][C:33]5=[N:34][CH:35]=[C:36]4[N:37]=[C:3]3[C@H:2]([OH:1])[CH3:6])[CH2:26][CH2:25]2)[CH:23]=[N:22][CH:21]=[N:20]1
Reactant: Nc1cnc2ccsc2c1N[C@H]1CC[C@@H](n2cncn2)CC1
Reactant: C[C@@H](O)C(N)=O
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: CCO
Solvent: C1CCOC1
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@@H](n2cncn2)CC1
Reaction time: 0.25 h

Procedure:
A mixture of (2R)-2-hydroxypropanamide (28 mg, 0.32 mmol) and triethyloxonium tetrafluoroborate (60 mg, 0.32 mmol) in tetrahydrofuran (0.4 mL) became a solution after stirring for 15 min. After another 45 min, this solution was added to a mixture of N7-[cis-4-(1H-1,2,4-triazol-1-yl)cyclohexyl]thieno[3,2-b]pyridine-6,7-diamine (25 mg, 0.080 mmol) in ethanol (0.8 mL) and heated at reflux overnight. The resulting mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (1.7 mg, 5.8%). LCMS calculated for C18H21N6OS (M+H)+: m/z=369.1. Found: 369.1.
Reaction SMILES: Cl[C:2]1[N:12]2[C:13]3[C:8]([CH2:9][CH2:10][CH2:11]2)=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=1.[N:14]1([CH:20]=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1>>[N:3]1[C:4]2=[C:13]3[C:8](=[CH:7][CH:6]=[CH:5]2)[CH2:9][CH2:10][CH2:11][N:12]3[C:2]=1[N:17]1[CH2:18][CH2:19][N:14]([CH:20]=[O:21])[CH2:15][CH2:16]1
Reactant: Clc1nc2cccc3c2n1CCC3
Reactant: O=CN1CCNCC1
Product: O=CN1CCN(c2nc3cccc4c3n2CCC4)CC1
Yield: 64.5 %

Procedure:
A solution of 2-chloro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline (20.00 g) in 1-piperazinecarboxaldehyde (25.00 g) was stirred at 120° C., under nitrogen, for 1.5 hrs. The reaction mixture was quenched with dilute sodium bicarbonate solution (300 ml) and extracted with chloroform. The organic extracts were combined, washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated. The residue was purified by flash chromatography (silica gel; 25:1 dichloromethane-methanol). The appropriate fractions were collected and evaporated. The residue was recrystallized twice from ethyl acetate to give 18.1 g (64%) of product, mp 138°-139° C.
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[O:3].N[C:6]([NH:8][C:9](N)=[O:10])=[O:7]>>[NH:1]1[C:9](=[O:10])[NH:8][C:6](=[O:7])[NH:4][C:2]1=[O:3]
Reactant: NC(N)=O
Reactant: NC(=O)NC(N)=O
Product: O=c1[nH]c(=O)[nH]c(=O)[nH]1

Procedure:
As set forth above the process of the invention is directed to heating urea and/or biuret dissolved in the reaction medium containing a dissolved acid or a corresponding anhydride or ammonium salt to produce cyanuric acid, vapor being discharged during the reaction.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:39])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:38])[CH:13]([N:20]2[C:24]3[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:23]=3[N:22]=[C:21]2[C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:7][CH:6]=1)C.[Cl:40]C1C=CC(C2N(C(C3CCCCC3)C(O)=O)C3C=C(F)C(F)=CC=3N=2)=CC=1.NC1C=CC(C(OC)=O)=CC=1Cl>>[CH3:1][O:3][C:4](=[O:39])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:38])[CH:13]([N:20]2[C:24]3[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:23]=3[N:22]=[C:21]2[C:31]2[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:7]([Cl:40])[CH:6]=1
Reactant: O=C(O)C(C1CCCCC1)n1c(-c2ccc(Cl)cc2)nc2cc(F)c(F)cc21
Reactant: CCOC(=O)c1ccc(NC(=O)C(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)cc1
Agent: COC(=O)c1ccc(N)c(Cl)c1
Product: COC(=O)c1ccc(NC(=O)C(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)c(Cl)c1

Procedure:
This compound was prepared in analogy to example 22, intermediate d, from [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid and methyl 4-amino-3-chlorobenzoate.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](CC(O)=O)[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([N+:16]([O-])=O)[CH:10]=1.CO.[C:26](=O)([O-])O.[Na+].[C:31]([O:34]CC)(=[O:33])[CH3:32]>S(Cl)(Cl)=O>[C:31]([O:34][C:4]1[CH:5]=[C:6]([Cl:19])[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([NH2:16])[CH:10]=2)=[C:2]([Cl:1])[C:3]=1[CH3:26])(=[O:33])[CH3:32]
Reactant: O=C([O-])O
Reactant: Nc1ccc(Oc2c(Cl)cc(CC(=O)O)cc2Cl)cc1[N+](=O)[O-]
Reactant: CCOC(C)=O
Agent: [Na+]
Solvent: O=S(Cl)Cl
Solvent: CO
Product: CC(=O)Oc1cc(Cl)c(Oc2ccc(N)c(N)c2)c(Cl)c1C
Temperature: 25 °C

Procedure:
3,5-Dichloro-4-(4-amino-3-nitrophenoxy)phenylacetic acid (50 mg), methanol (20 mL) and thionyl chloride (2 drops) was heated at reflux for two hours. After cooling down to room temperature, the reaction mixture was partioned between an aqueous solution of sodium hydrogencarbonate (saturated) and ethyl acetate. The organic phase was washed with brine and concentrated. This gave 45 mg of methyl(3,5-dichloro-4-(4-amino-3-nitro-phenoxy)phenyl) acetate which was reduced using the method described in Example 1(f), to give 40 mg of methyl(3,5-dichloro-4-(3,4-diaminophenoxy)phenyl) acetate.
Reaction SMILES: [CH3:1][N:2]([CH2:10][CH:11]([OH:15])[CH2:12][C:13]#[N:14])CC1C=CC=CC=1.[H][H].[ClH:18]>C(O)(C)C.[Pd]>[ClH:18].[CH3:1][NH:2][CH2:10][CH:11]([OH:15])[CH2:12][C:13]#[N:14]
Reactant: CN(Cc1ccccc1)CC(O)CC#N
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CC(C)O
Product: CNCC(O)CC#N

Procedure:
4-(N-Methyl-N-benzylamino)-3-hydroxybutyronitrile, 5.1 g (0.02 mole) was dissolved in 40 ml of isopropanol and 0.5 g of 5% palladium on carbon was added to the solution. The mixture was subjected to hydrogen gas under about 55 psi for 18 hr at 60° C. Mass spectrometry of a sample taken from the mixture indicated no reduction had occurred. About 2.1 ml (ca. 0.02 mole) of 37% hydrochloric acid and 0.5 g of 5% palladium on carbon were added and the mixture was subjected to hydrogen gas under 50 psi for 18 hr at room temperature. Approximately 0.02 molar equivalents of hydrogen was absorbed. A sample taken for mass spectroscopy showed product (m/e 115) and a small amount of starting material (m/e 205) unreacted. The mixture was filtered and the filtrate was concentrated to a light yellow liquid weighing 4.73 g. Proton NMR analysis showed mainly 4-methylamino-3-hydroxybutyronitrile and a small amount of starting benzyl compound and solvent was present, NMR analysis is as follows: (D2O, ppm): 4.40 (multiplet, methine proton on carbon 3), 3.20 (multiplet, methylene protons on carbon 4 bearing the protonated amino groups), 2.80 (multiplet, methylene protons on carbon 2 and methyl protons on the amino group).
Reaction SMILES: [C-:1]#[N:2].[K+].CS(O[CH2:9][CH2:10][CH:11]([C:24]1[CH:34]=[CH:33][C:27]2[O:28][C:29]([F:32])([F:31])[O:30][C:26]=2[CH:25]=1)[C:12]1[C:20]2[C:15](=[C:16]([CH2:21][S:22][CH3:23])[CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)(=O)=O.C(OCC)(=O)C>CS(C)=O>[F:32][C:29]1([F:31])[O:28][C:27]2[CH:33]=[CH:34][C:24]([CH:11]([C:12]3[C:20]4[C:15](=[C:16]([CH2:21][S:22][CH3:23])[CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)[CH2:10][CH2:9][C:1]#[N:2])=[CH:25][C:26]=2[O:30]1
Reactant: CSCc1cccc2c(C(CCOS(C)(=O)=O)c3ccc4c(c3)OC(F)(F)O4)c[nH]c12
Reactant: [C-]#N
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CSCc1cccc2c(C(CCC#N)c3ccc4c(c3)OC(F)(F)O4)c[nH]c12
Temperature: 80 °C
Reaction time: 3 h

Procedure:
0.37 g (5.76 mmol) of potassium cyanide was added to 1.35 g (2.88 mmol) of the compound from Example 112A in 26 ml of DMSO. The mixture was stirred at 80° C. for 3 h, ethyl acetate was added to the reaction solution, and the mixture was washed twice with water and once with saturated aqueous sodium chloride solution. The combined organic phases were freed of solvent, and the crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient). 0.90 g (78% of theory) of the target compound was obtained.
Reaction SMILES: [CH2:1](CC(O)=O)[CH3:2].[C:7]([O:10][CH2:11][C:12]1[CH2:13][S:14][C@@H:15]2[C@H:22]([NH:23][C:24](=[O:34])[C:25](=[N:32][OH:33])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:21](=[O:35])[N:16]2[C:17]=1[C:18]([OH:20])=[O:19])(=[O:9])[CH3:8].[N-:36]=[C:37]=[O:38]>>[C:7]([O:10][CH2:11][C:12]1[CH2:13][S:14][C@@H:15]2[C@H:22]([NH:23][C:24](=[O:34])[C:25](=[N:32][O:33][C:37](=[O:38])[NH:36][CH2:1][CH3:2])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:21](=[O:35])[N:16]2[C:17]=1[C:18]([OH:20])=[O:19])(=[O:9])[CH3:8]
Reactant: [N-]=C=O
Reactant: CCCC(=O)O
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)C(=NO)c3ccccc3)[C@H]2SC1
Product: CCNC(=O)ON=C(C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(C)=O)CS[C@H]12)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47 %

Procedure:
To ethyl ioscyanate (5 ml.) was added (3-acetoxymethyl-7β-(2-hydroxyimino-2-phenylacetamido)ceph-3-em-4-carboxylic acid ethyl acetate solvate (syn-isomer) (0.9 g.) and the mixtue stirred for one hour at room temperature. Two further portions of the isocyanate (5 ml.) were added, over a period of 2 hours. The mixture was then allowed to stand for 1 hour, and poured into petroleum (b.p. 40°-60°; 250 ml.) and the resulting precipitate collected, washed thoroughly with petroleum and dried. The solid was dissolved in ethyl acetate and extracted into sodium bicarbonate solution; the bicarbonate solution was then washed with ethyl acetate, acidified (2N-hydrochloric acid) and extracted with ethyl acetate. The combined extracts were dried and concentrated, and the concentrate (ca. 5 ml.) added dropwise to petroleum spirit with vigorous stirring. The precipitate formed was filtered and dried, giving the title acid (0.4 g., 47%), [α]D + 50° (c 0.85, DMSO), νmax. (pH 6 buffer) 257.5 nm (ε 21,200), νmax. (Nujol) 1782 (β-lactam), 1675 and 1520 cm.-1 (CONH), τ (DMSO-d6) values include 0.04 (doublet J 8 Hz; NH), 2.0-2.6 (multiplet; aromatic protons), 6.7-7.1 (multiplet; NHCH2CH3) and 8.89 (triplet, J 9 Hz; (CH2CH3).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11].[C:12](=O)([O-])[O-].[K+].[K+].CO>CC(C)=O>[CH3:12][O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11]
Reactant: O=C([O-])[O-]
Reactant: O=C1CCc2c(O)cccc21
Agent: [K+]
Solvent: CC(C)=O
Solvent: CO
Product: COc1cccc2c1CCC2=O
Reaction time: 10 h
Yield: 79.4 %

Procedure:
To a mixture of 4-hydroxy-indan-1-one (14.5 g, 0.0979 mol) and 27.08 g (0.195 mol) of potassium carbonate was added 500 ml of acetone and 48.7 ml (0.78 mol) of methanol with stirring and the resulting mixture was heated to reflux for 4 h, cooled, and allowed to stand at room temperature for 10 h. The above mixture was filtered concentrated under vacuo, the solid residue was dissolved in methanol, heated and filtered. The filtrate was concentrated to a volume of 100 ml, cooled and filtered to afford 12.6 g (79%) of 4-methoxy-indan-1-one.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[Cl:16][C:17]1[CH:35]=[C:34]([N+:36]([O-:38])=[O:37])[CH:33]=[CH:32][C:18]=1[O:19][C:20]1[C:25]([Cl:26])=[CH:24][C:23]([S:27](Cl)(=[O:29])=[O:28])=[CH:22][C:21]=1[Cl:31].[OH:39][C@@H:40]([CH2:53][NH2:54])[CH2:41][O:42][C:43]1[C:51]2[NH:50][C:49](=[O:52])[NH:48][C:47]=2[CH:46]=[CH:45][CH:44]=1>>[Cl:31][C:21]1[CH:22]=[C:23]([S:27]([NH:2][C:3]2[CH:8]=[CH:7][C:6]([N:9]3[CH2:14][CH2:13][CH:12]([NH:54][CH2:53][C@H:40]([OH:39])[CH2:41][O:42][C:43]4[C:51]5[NH:50][C:49](=[O:52])[NH:48][C:47]=5[CH:46]=[CH:45][CH:44]=4)[CH2:11][CH2:10]3)=[CH:5][CH:4]=2)(=[O:29])=[O:28])[CH:24]=[C:25]([Cl:26])[C:20]=1[O:19][C:18]1[CH:32]=[CH:33][C:34]([N+:36]([O-:38])=[O:37])=[CH:35][C:17]=1[Cl:16]
Reactant: O=[N+]([O-])c1ccc(Oc2c(Cl)cc(S(=O)(=O)Cl)cc2Cl)c(Cl)c1
Reactant: NC[C@H](O)COc1cccc2[nH]c(=O)[nH]c12
Reactant: Nc1ccc(N2CCC(=O)CC2)cc1
Agent: Cl
Product: O=c1[nH]c2cccc(OC[C@@H](O)CNC3CCN(c4ccc(NS(=O)(=O)c5cc(Cl)c(Oc6ccc([N+](=O)[O-])cc6Cl)c(Cl)c5)cc4)CC3)c2[nH]1

Procedure:
The title compound was prepared from 1-(4-aminophenyl)-4-piperidone hydrochloride (which was obtained in Example 224), 4-(2-chloro-4-nitrophenoxy)-3,5-dichlorobenzenesulfonyl chloride, and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (U.S. Pat. No. 5,786,356/1998) according to the procedure of Example 346; MS (ES) m/z: 777.2, 779.2 (MH+).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH:4]=[O:5].[CH2:11](I)[CH3:12].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:11]([O:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH:4]=[O:5])[CH3:12]
Reactant: CCI
Reactant: O=Cc1cc(O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1ccc(O)cc1C=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 35.6 %

Procedure:
A mixture of 2,5-dihydroxybenzaldehyde (9.81 g), ethyl iodide (13.29 g), anhydrous potassium carbonate (14.72 g) and N,N-dimethylformamide (100 mL) was stirred at room temperature for 1 hr. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column a chromatography to give crystals (4.20 g, 36%) of 2-ethoxy-5-hydroxybenzaldehyde from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave pale-yellow prism crystals. melting point: 108-109° C.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]([C:14]([O:16]C)=[O:15])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])([O-:3])=[O:2].[OH-].[Na+]>O1CCOCC1.O>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:12]([C:14]([OH:16])=[O:15])=[CH:13][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: COC(=O)c1ccc(C(=O)OC)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C(=O)O)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 71.7 %

Procedure:
To a stirred solution of di-methyl nitroterephthalate ((5), 12g, 50 mMol) in dioxane (100 mL) at room temperature was slowly added dropwise aq. 1N NaOH (50 mL) over 30 minutes. After stirring for 16 h at room temperature the reaction was diluted with water, washed with ether, acidified with aq. 1N HCl (50 mL) then extracted with 10% n-BuOH in ethyl acetate (2×100 mL). After drying (MgSO4) over ethyl acetate and evaporation under reduced pressure the resulting residue was purified by flash chromatography on silica gel eluted with (98:2:0.1) CHCl3, MeOH, HOAc to give product (6) (8.07 g, 72%) as a white solid.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[OH:12].[Br:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Br>C(O)C>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[O:12][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][Br:13]
Reactant: BrCCCCCCBr
Reactant: COc1ccc(O)c(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(OCCCCCCBr)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 29.6 g. (0.74 mole) sodium hydroxide pellets in 400 ml. absolute ethanol was prepared with stirring at room temperature and a solution of 108.0 g. (0.68 mole) 2-chloro-4-methoxyphenol in 200 ml. absolute ethanol was added in a fine stream. The solution was stirred at room temperature for 15 minutes, then warmed gently in a steam bath for one-half hour. The reaction mixture was chilled to about 5° C. in an ice bath and 500 g. (2.05 moles) 1,6-dibromohexane was added. The reaction was stirred and allowed to warm to room temperature, then stirred for 6 hours at room temperature and boiled overnight at reflux.
Reaction SMILES: [CH3:1][O:2][CH:3]1[C@@H:8]([OH:9])[C@@H:7]([OH:10])[CH:6]([OH:11])[C@H:5]([OH:12])[C@H:4]1[OH:13]>CO>[CH3:1][O:2][C@@H:3]1[C@@H:4]([OH:13])[C@@H:5]([OH:12])[C@H:6]([OH:11])[C@H:7]([OH:10])[C@H:8]1[OH:9]
Reactant: COC1[C@@H](O)[C@@H](O)C(O)[C@H](O)[C@H]1O
Solvent: CO
Product: CO[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H]1O
Temperature: 70 °C
Yield: 47.4 %

Procedure:
3-O-methyl-D-chiro-inositol (D-pinitol) (283 mg, 1.457 mmol, 1 equiv) was dissolved in methanol (15 mL), then 1,2-cyclohexane diacetal (507 mg, 2.458 mmol, 1.7 equiv), trimethyl orthoformiate (200 mL, 1.752 mmol, 1.2 equiv) and 1-(S)-(+)-10-camphorsulfonic acid (24 mg, 0.102 mmol, 0.07 equiv) were added. The reaction mixture was heated at 70° C. for 24 h whereupon it was diluted with MeOH and quenched with solid NaHCO3. The residue was concentrated and purified by flash chromatography (Hex/EtOAc 1:15) to give 6 (222 mg, 0.664 mmol, 45%; 89% based on 134 mg of recovered D-pinitol). Rf (Hex/EtOAc 1:20): 0.22; [α]20 D −22.9 (c=1.05, CHCl3); 1H NMR (CDCl3, 300 MHz): d=4.12 (Ys, 1H, H1), 4.10 (s, 2H, H4, H5), 4.07 (Ys, 1H, H6), 3.81 (dt, 1H, J2-3=9.0 Hz, J2-1=3.6 Hz, J2-OH=1.8 Hz, H2), 3.47 (t, 1H, J=9.0 Hz, H3), 3.23 (s, 3H, OCH3), 3.21 (s, 3H, OCH3), 2.76 (d, 1H, JOH-2=1.8 Hz, OH2), 2.60 (s, 1H, OH1), 2.56 (s, 1H, OH−6), 1.86-1.78 (m, 1H, CDA), 1.77-1.66 (m, 3H, CDA), 1.57-1.50 (m, 2H, CDA), 1.42-1.34 (m, 2H, CDA); 13C-NMR (CDCl3, 75 MHz); d=98.9 (C), 98.0 (C), 80.2 (C3), 71.5(C2) 70.8, 70.4, 70.3 (C1, C4, C6), 68.7 (C5), 61.1 (OCH3), 47.0(OCH3, CDA), 46.8 (OCH3, CDA), 27.1 (CH2), 27.0 (CH2), 21.5 (CH2), 21.4 (CH2); HRFABMS Calcd. for C15H26O8: 357.3571. found: 357.1528. MALDI-TOF Calcd. for C15H26O8+Na+: 357.4. found: 357.5. calcd. for C15H26O8+K+: 373.5. found: 374.1.
Reaction SMILES: [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[S:12]1[C:16]([C:17]([NH:19][NH2:20])=[O:18])=[CH:15][C:14]2[CH:21]=[CH:22][CH:23]=[CH:24][C:13]1=2>>[CH2:2]([N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)/[C:4](=[N:20]/[NH:19][C:17]([C:16]2[S:12][C:13]3[CH:24]=[CH:23][CH:22]=[CH:21][C:14]=3[CH:15]=2)=[O:18])/[C:2]1=[O:3])[CH2:4][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: NNC(=O)c1cc2ccccc2s1
Reactant: O=C1Nc2ccccc2C1=O
Product: CCCCCCN1C(=O)/C(=N\NC(=O)c2cc3ccccc3s2)c2ccccc21
Yield: 82 %

Procedure:
The title compound was prepared as a yellow solid, using isatin 3 and Benzo[b]thiophene-2-carboxylic hydrazide according to the synthetic method E. The resulting solid was washed with ethanol. Yield: 82%. 1H NMR (DMSO-d6): δ 0.86 (t, J=6.9 Hz, 3H), 1.26-1.36 (m, 6H), 1.64-1.66 (m, 2H), 3.79 (t, J=7.2 Hz, 2H), 7.19-7.27 (m, 2H), 7.48-7.59 (m, 3H), 7.75 (d, J=7.5 Hz, 1H), 8.13 (d, J=7.5 Hz, 2H), 8.31 (br s, 1H), 13.65 (br s, 1H). 13C NMR (DMSO-d6): δ 14.33 (CH3), 22.44 (CH2), 26.40 (CH2), 27.41 (CH2), 31.34 (CH2), 39.81 (CH2), 110.71 (CH), 115.52 (C), 119.55 (C), 121.52 (CH), 123.35 (CH), 123.69 (CH), 125.75 (CH), 126.51 (CH), 127.83 (CH), 132.38 (CH), 143.64 (C═N), 161.60 (C═O). HRMS (ES+) calcd for C23H24N3O2S (M+H+), m/e, 406.1596. found, 406.1584.
Reaction SMILES: COC(OC)[N:4]([CH3:6])C.[Cl:9][C:10]1[CH:30]=[CH:29][C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22](=[N:26][O:27][CH3:28])[C:23]([NH2:25])=O)=[CH:12][CH:11]=1.[CH3:31][NH:32]N.C(O)(=O)C>CCOCC>[CH3:28][O:27][N:26]=[C:22]([C:23]1[N:4]([CH3:6])[N:32]=[CH:31][N:25]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][O:14][C:13]1[CH:29]=[CH:30][C:10]([Cl:9])=[CH:11][CH:12]=1
Reactant: CNN
Reactant: CON=C(C(N)=O)c1ccccc1COc1ccc(Cl)cc1
Reactant: COC(OC)N(C)C
Solvent: CCOCC
Solvent: CC(=O)O
Product: CON=C(c1ccccc1COc1ccc(Cl)cc1)c1ncnn1C
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 57.9 %

Procedure:
Dimethylformamide dimethylacetal (0.53 g, 4.5 mmol) was added to 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (0.48 g, 1.5 mmol), and the mixture was stirred under reduced pressure (ca. 40 mmHg) at 60° C. for 0.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and a mixture of methylhydrazine (0.08 g, 1.8 mmol) and acetic acid (3 ml) was added to the residue. The mixture was stirred at 90° C. for 1 hour. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1-methyl-1H-1,2,4-triazol-5-yl ketone O-methyloxime (0.31 g, 57.9%) as colorless crystals.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:16]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][OH:25])[CH2:17][CH2:18][CH3:19].C[Si](C)(C)[N-][Si](C)(C)C.[K+].O>O1CCOCC1.C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:19][CH2:18][CH2:17][CH2:16][NH:20][CH2:21][CH2:22][CH2:23][CH2:24][OH:25])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1cccc(OCc2ccccc2)c1
Reactant: CCCCNCCCCO
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Solvent: O
Product: OCCCCNCCCCc1cccc(OCc2ccccc2)c1
Temperature: 100 °C
Yield: 34.4 %

Procedure:
In 75 ml of dioxane were dissolved 5.19 g (19.7 mmol) of 3-benzyloxybromobenzene and 3.72 g (25.6 mmol) of 4-butylamino-1-butanol. To this mixture was added 5.89 g (29.5 mmol) of potassium hexamethyldisilazide and the mixture was stirred with heating at 100° C. for 22 hours. After the reaction mixture was poured into 200 ml of water, extraction with chloroform, washing with a saturated saline solution, drying over anhydrous sodium sulfate, and concentration were performed. The residue was purified by silica gel column chromatography to give 2.22 g of a light brown oily matter (yield: 34.4%).