Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]1[C:14](=[O:15])[N:13]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:12]2[C:7]1=[N:8][C:9]([C:24]1[C:32]3[C:27](=[N:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[F:40])[N:25]=1)=[N:10][CH:11]=2.C([SiH](CC)CC)C.O.C(=O)([O-])O.[Na+]>FC(F)(F)C(O)=O.C(OCC)(=O)C>[F:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH2:33][N:26]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:32]2[C:24]([C:9]2[N:8]=[C:7]3[C:12]([N:13]([CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[C:14](=[O:15])[NH:6]3)=[CH:11][N:10]=2)=[N:25]1
Reactant: COc1ccc(Cn2c(=O)n(CCN3CCOCC3)c3cnc(-c4nn(Cc5ccccc5F)c5ncccc45)nc32)c(OC)c1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: CCOC(C)=O
Product: O=c1[nH]c2nc(-c3nn(Cc4ccccc4F)c4ncccc34)ncc2n1CCN1CCOCC1
Yield: 69.8 %

Procedure:
101 mg (0.16 mmol) of the compound from example 87A were dissolved in 10 ml of trifluoroacetic acid, 188 mg (1.62 mmol) of triethylsilane were added and the mixture was heated to reflux for 18 h. The reaction mixture was admixed with water and ethyl acetate, and neutralized with saturated aqueous sodium hydrogencarbonate solution. The organic phase was dried over sodium sulfate and concentrated on a rotary evaporator. The residue was dried under high vacuum, and purified by means of preparative HPLC (eluent: methanol/water with 0.1% trifluoroacetic acid, gradient 30:70→90:10). 53 mg of the title compound were obtained (69% of theory).
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([NH:18][C:19](=[O:36])[N:20]([C:22]3[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=3)[CH3:21])[C@H:14]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=3)[CH2:13]2)=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH2:45](I)[CH3:46]>>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([N:18]([CH2:45][CH3:46])[C:19]([N:20]([C:22]3[CH:23]=[C:24]([C:32]([F:35])([F:33])[F:34])[CH:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=3)[CH3:21])=[O:36])[C@H:14]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=3)[CH2:13]2)=[O:11])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCC(C(=O)N2CC[C@@H](NC(=O)N(C)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1
Reactant: CCI
Product: CCN(C(=O)N(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)[C@@H]1CCN(C(=O)C2CCN(C(C)=O)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1

Procedure:
By reaction and purification in the same manner as in the method described in Example 2 and using the compound obtained in Example 40 and ethyl iodide, the title compound was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][C:17]=1Cl)[C:7]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8])([O-:3])=[O:2].[NH3:19]>C(O)C>[N+:1]([C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][C:17]=1[NH2:19])[C:7]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8])([O-:3])=[O:2]
Reactant: N
Reactant: O=C(c1cccnc1)c1ccc(Cl)c([N+](=O)[O-])c1
Solvent: CCO
Product: Nc1ccc(C(=O)c2cccnc2)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A suspension of 63 g. (0.24 mol) of 3-(3-nitro-4-chlorobenzoyl)pyridine in 3 liters of a saturated solution of ammonia in ethanol was autoclaved at 100° C. for 24 hours. The mixture was concentrated in vacuo and the resulting residue dissolved in 1.5 liters of warm 5N HCl. The solution was cooled to room temperature and neutralized with concentrated ammonium hydroxide. The resulting product was collected as yellow-orange prisms, mp. 229° -230° C. (dimethylformamide-2-propanol).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13](=[O:15])[CH3:14])[CH2:10][CH2:9][C:8]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][C:6]=2[CH:20]=1.[CH2:21](O)[CH2:22][OH:23]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]3([CH3:14])[O:23][CH2:22][CH2:21][O:15]3)[CH2:10][CH2:9][C:8]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][C:6]=2[CH:20]=1
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(CC(C)=O)CC1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COC(=O)C1=Cc2cc(Br)ccc2N(CC2(C)OCCO2)CC1
Temperature: 25 °C
Yield: 68 %

Procedure:
A solution of methyl 7-bromo-1-(2-oxopropyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1.29 g), ethylene glycol (2.3 g) and p-toluenesulfonic acid monohydrate (36 mg) in toluene (10 ml) was heated to reflux for 3 days while removing water. After cooled to room temperature, an aqueous solution of sodium hydrogen carbonate was added to alkaline, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified with column chromatography (ethyl acetate:hexane=1:4) to give methyl 7-bromo-1-[(2-methyl-1,3-dioxolan-2-yl)methyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylate (992 mg).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)=[O:4].[C:14]1([S:20]([NH2:23])(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[C:14]1([S:20]([NH:23][C:9]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=2)=[O:11])(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Reactant: NS(=O)(=O)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C(=O)NS(=O)(=O)c2ccccc2)cc1
Reaction time: 18 h
Yield: 97.3 %

Procedure:
4-Methoxycarbonyl-benzoic acid (from Preparation 11) (5.0 g, 28 mmol) was dissolved in 100 mL of anhydrous dichloromethane. After the addition of DMAP (3.39 g, 28 mmol) and benzenesulfonamide (4.36 g, 28 mmol), EDCI (5.85 g, 31 mmol) was gradually added to the stirred mixture. After 18 hours at room temperature, rotary evaporation of the mixture gave a residue which was mixed with ethyl acetate and 1N HCl. The organic phase was washed with water (1×) and brine (2×), dried (Na2SO4), rotary evaporated, and dried at high vacuum to afford 8.7 g (98%) of methyl 4-phenylsulfonamidocarbonyl-benzoate (4--C6H5SO2 --NHCO--C6H4 --COOCH3) as a white solid. A solution of this material (3.2 g, 10 mmol) in 130 mL of dioxane/water (3:1) was cooled to 0° C. 1N Sodium hydroxide was added dropwise, followed by vigorous stirring at 0° C. for 20 minutes, then at room temperature for 2 hours. The mixture was again cooled to 0° C., and then acidified to pH 2 by gradual addition of 1N HCl. The mixture was rotary evaporated, and the aqueous residue was extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried (Na2SO4), rotary evaporated, and dried at high vacuum to afford the product (4--C6H5SO2NHCO--C6H4 --COOH), m.p. 267°-270° C.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH2:10])=[CH:7][CH:6]=1)([O-:4])=[O:3].C(N(C(C)C)CC)(C)C.[NH:22](C(OC(C)(C)C)=O)[CH2:23][C:24]([O:26]N1C(=O)CCC1=O)=[O:25]>ClCCl>[NH2:22][CH2:23][CH:24]([OH:26])=[O:25].[ClH:1].[N+:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][NH-:10])=[CH:11][CH:12]=1)([O-:4])=[O:3]
Reactant: CC(C)(C)OC(=O)NCC(=O)ON1C(=O)CCC1=O
Reactant: NCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: [NH-]Cc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-Nitrobenzylamine hydrochloride (1 g; 5.3 mmol) and diisopropylethylamine (1.8 ml; 10.6 mmol) were dissolved in 70 ml of dichloromethane at RT. BOC-Gly-OSu (1.44 g; 5.3 mmol) was added and the solution was stirred at RT overnight. After evaporating the solvent in a rotary evaporator, the residue was taken up in 50 ml of ethyl acetate and extracted in each case 2× with 5% KHSO4, 5% NaHCO3 and distilled water. The organic phase was dried over Na2SO4, the solvent was evaporated and toluene was then added and evaporated in a rotary evaporator. The resultant oil was dissolved, without further work-up, directly in 15 ml of 4M HCl/dioxane and stirred at RT. After a short time, the product starts to precipitate. After 1 h, the solvent was evaporated, the solid was suspended in 100 ml of ethyl acetate, filtered off and washed with petroleum ether. The white solid was dried under vacuum.
Reaction SMILES: [CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([S:15][C:16]4[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=4[C:18](O)=[O:19])=[N:11][N:10]3[CH:25]=2)=[O:5])[CH2:3][CH2:2]1.[F:26][C:27]([F:36])([F:35])[C:28]1[CH:29]=[C:30]([CH:32]=[CH:33][CH:34]=1)[NH2:31].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([S:15][C:16]4[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=4[C:18]([NH:31][C:30]4[CH:32]=[CH:33][CH:34]=[C:28]([C:27]([F:26])([F:35])[F:36])[CH:29]=4)=[O:19])=[N:11][N:10]3[CH:25]=2)=[O:5])[CH2:2][CH2:3]1
Reactant: Nc1cccc(C(F)(F)F)c1
Reactant: O=C(O)c1ccccc1Sc1ccc2nc(NC(=O)C3CC3)cn2n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1ccccc1Sc1ccc2nc(NC(=O)C3CC3)cn2n1
Yield: 99.5 %

Procedure:
In the same manner as in Example 278 and using 2-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}thio)benzoic acid (150 mg, 0.42 mmol), 3-(trifluoromethyl)aniline (191 mg, 1.2 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (230 mg, 0.6 mmol), N,N-diisopropylethylamine (160 mg, 1.3 mmol) and N,N-dimethylformamide (5 mL) as starting materials, the title compound (208 mg, 99%) was obtained as a white solid.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8][CH2:7]2)([OH:3])=[O:2].O[N:16]1[C:20](=[O:21])[CH2:19][CH2:18][C:17]1=[O:22].C1(N=C=NC2CCCCC2)CCCCC1>O1CCOCC1>[NH:10]1[C:11]2[C:6](=[CH:5][C:4]([C:1]([OH:3])=[O:2])=[CH:13][CH:12]=2)[CH2:7][CH2:8][C:9]1=[O:14].[C:17]1(=[O:22])[NH:16][C:20](=[O:21])[CH2:19][CH2:18]1
Reactant: O=C1CCC(=O)N1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1CCc2cc(C(=O)O)ccc2N1
Solvent: C1COCCO1
Product: O=C1CCC(=O)N1
Temperature: 25 °C

Procedure:
10 Grams of 6-carboxy-3,4-dihydrocarbostyril and 6.0 g of N-hydroxysuccinimide were suspended in 200 ml of dioxane. Then a solution containing 12.4 g of dicyclohexylcarbodiimide in 50 ml of dioxane was added dropwise thereto under ice-cooled condition with stirring. The reaction mixture was further stirred for 4 hours at 90° C. After the reaction was completed, the reaction mixture was allowed to stand to cool at room temperature, and the crystals precipitated were removed by filtration, then the filtrate obtained was concentrated to dryness. The residue was recrystallized from dimethylformamide-ethanol to obtain 10.8 g of succinimide 3,4-dihydrocarbostyril-6-carboxylate in the form of colorless flake-like crystals.
Reaction SMILES: [C:1]([C:5]1[C:6]([OH:40])=[C:7]([C:29]([CH3:39])([CH3:38])[CH2:30][O:31]C2CCCCO2)[CH:8]=[C:9]([CH:28]=1)[CH:10]=[C:11]1[C:16](=[O:17])[N:15]([CH2:18][C:19]2[NH:23][N:22]=[N:21][N:20]=2)[C:14]2[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=2[S:12]1)([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl-].[Na+]>CO.C(Cl)(Cl)Cl>[C:1]([C:5]1[C:6]([OH:40])=[C:7]([C:29]([CH3:39])([CH3:38])[CH2:30][OH:31])[CH:8]=[C:9]([CH:28]=1)[CH:10]=[C:11]1[C:16](=[O:17])[N:15]([CH2:18][C:19]2[NH:23][N:22]=[N:21][N:20]=2)[C:14]2[CH:24]=[CH:25][CH:26]=[CH:27][C:13]=2[S:12]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc(C=C2Sc3ccccc3N(Cc3nnn[nH]3)C2=O)cc(C(C)(C)COC2CCCCO2)c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CC(C)(C)c1cc(C=C2Sc3ccccc3N(Cc3nnn[nH]3)C2=O)cc(C(C)(C)CO)c1O
Temperature: 60 °C
Reaction time: 3 h
Yield: 60.7 %

Procedure:
2-[5-tert.-Butyl-4-hydroxy-3-[1,1-dimethyl-2-(tetrahydropyran-2-yloxy)ethyl]benzylidene]-3,4-dihydro-3-oxo-4-(1H-tetrazol-5-ylmethyl)-2H-1,4-benzothiazine (compound No. 2-2, 0.31 g) was dissolved in a mixture of methanol (5 ml) and chloroform (1 ml). To the mixture, p-toluenesulfonic acid monohydrate (0.05 g) was added and the mixture was stirred for 3 hours at 60° C. Saturated sodium chloride solution was added to the mixture and the whole was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue was purified by silica gel column chromatography to give 0.16 g (60.7%) of the titled compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[C:10](Cl)(=[O:13])[CH2:11][CH3:12]>N1C=CC=CC=1.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[O:9][C:10](=[O:13])[CH2:11][CH3:12]
Reactant: Oc1cc(F)ccc1F
Reactant: CCC(=O)Cl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCC(=O)Oc1cc(F)ccc1F

Procedure:
At 0° C.-5° C., a solution of 100 g of 2,5-difluorophenol in 66.5 g of pyridine is added dropwise in the course of 2 hours to a solution of 71.2 g of propionic acid chloride in 800 ml of toluene and stirring is then carried out at room temperature for a further hour. The reaction mixture is then diluted with ethyl acetate, washed twice with water and once with saturated sodium chloride solution and the organic phase is separated off, dried with sodium sulfate and concentrated by evaporation in vacuo. The crude product is processed further without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[CH:3]=1.[N:12]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[CH2:26]=O>C(O)C>[OH:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=[O:9])[CH2:7][O:8][C:4]=2[C:3]=1[CH2:26][N:15]1[CH2:16][CH2:17][CH2:18][N:12]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:13][CH2:14]1
Reactant: CC(C)(C)OC(=O)N1CCCNCC1
Reactant: O=C1COc2cc(O)ccc21
Reactant: C=O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCCN(Cc2c(O)ccc3c2OCC3=O)CC1
Yield: 16.1 %

Procedure:
A solution of 6-hydroxybenzofuran-3(2H)-one (0.150 g, 1.00 mmol) in ethanol (1 mL) was added with tert-butyl 1,4-diazepane-1-carboxylate (0.200 g, 1.00 mmol) and paraformaldehyde (0.0300 g, 1.00 mmol) at room temperature, and the mixture was refluxed for 3 hours by heating. The reaction mixture was concentrated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain tert-butyl 4-[(6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl]-1,4-diazepane-1-carboxylate (0.0583 g, 16%).
Reaction SMILES: O=O.O.[C:4](=[O:6])=[O:5].[C:7]1(C)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[CH:4](=[O:6])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:4]([OH:6])(=[O:5])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C=O
Reactant: Cc1ccccc1
Agent: O=O
Solvent: O
Product: O=C(O)c1ccccc1
Product: O=Cc1ccccc1

Procedure:
The reactor is heated to, and maintained at, 140°, when a stream of 300 mmoles/hr. nitrogen, 100 mmoles/hr. oxygen, 180 mmoles/hr. water and 17 mmoles/hr. toluene is passed through the catalyst bed. The exhaust gases are passed through a trap cooled by dry ice, followed by a carbon dioxide absorbing solution. Gas chromatographic and titrimetric analyses on the product of a 5 hour operation indicate product yields of 2.6 mole % benzaldehyde, 0.6 mole % benzoic acid and 0.8 mole % toluene converted to carbon dioxide. The conversion is 4.0% with a benzaldehyde selectivity of 65%.
Reaction SMILES: [C:1]1([C:6]([C:8]2[CH:18]=[CH:17][C:11]([CH:12]([CH3:16])[C:13]([OH:15])=[O:14])=[CH:10][CH:9]=2)=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:21][CH2:22][CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH3:26]>CN(C)P(N(C)C)(N(C)C)=O>[ClH:21].[C:1]1([C:6]([C:8]2[CH:18]=[CH:17][C:11]([CH:12]([CH3:16])[C:13]([O:15][CH2:22][CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])=[O:14])=[CH:10][CH:9]=2)=[O:7])[S:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCN(CC)CCCl
Reactant: CC(C(=O)O)c1ccc(C(=O)c2cccs2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCN(CC)CCOC(=O)C(C)c1ccc(C(=O)c2cccs2)cc1
Product: Cl
Temperature: 50 °C
Reaction time: 8 h

Procedure:
A mixture of 10.4 parts of p-(2-thenoyl)hydratropic acid in 75 parts of hexamethylphosphoramide is heated to 50° C and there are added 1.3 parts of sodium hydride dispersion 78.3%. When the reaction is ceased, there are added 10 parts of N-(2-chloroethyl)-N,N-diethylamine and the whole is stirred overnight at 50° C. The reaction mixture is cooled and extracted with 240 parts of benzene and 100 parts of water. The organic layer is washed with diluted sodium hydroxide solution and with water, dried and evaporated. The oily residue is converted into the hydrochloride salt in 2-propanol. After cooling to -20° C, the precipitated salt is filtered off and dried, yielding 2-(diethylamino)ethyl p-(2-thenoyl)hydratropate hydrochloride; mp. 126.4° C.
Reaction SMILES: Br[CH:2]([CH3:12])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=O.[NH2:13][C:14]([NH2:16])=[S:15]>CCO>[CH3:12][C:2]1[S:15][C:14]([NH2:16])=[N:13][C:3]=1[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1
Reactant: Cc1ccc(C(=O)C(C)Br)cc1
Reactant: NC(N)=S
Solvent: CCO
Product: Cc1ccc(-c2nc(N)sc2C)cc1
Yield: 98.5 %

Procedure:
A mixture of 2-bromo-1-(p-tolyl)propan-1-one (6.88 g, 30.3 mmol) and thiourea (2.54 g, 33.4 mmol) in 95% EtOH (43 mL) was heated at reflux for 60 min. The solution was concentrated and added with water (100 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene. The solids were filtered and dried under vacuum to give 5-methyl-4-(p-tolyl)thiazol-2-amine (6.10 g) as white solids in 99% yield: 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J=8.0 Hz, 2 H), 7.23 (d, J=8.0 Hz, 2 H), 3.18 (bs, 2 H), 2.37 (s, 3 H), 2.35 (s, 3 H).
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10](=[N:14]O)[C:11](=O)[CH3:12].[ClH:16].C(OC(C)C)(C)C>C(O)(=O)C>[Cl:16][CH2:9][C:10]1[N:14]=[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:8][C:11]=1[CH3:12]
Reactant: Cl
Reactant: O=Cc1ccccc1
Reactant: CC(=O)C(C)=NO
Solvent: CC(=O)O
Solvent: CC(C)OC(C)C
Product: Cc1oc(-c2ccccc2)nc1CCl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Benzaldehyde (342 g) and acetic acid (800 ml) were added to 2,3-butanedione oxime (300 g), and the mixture was stirred for dissolution at room temperature, followed by cooling. Hydrochloric acid gas was started to be blown into the mixture at 5° C., and hydrochloric acid gas was continuously blown at 10-25° C. for 5 hr. Diisopropyl ether (1200 ml) was added at 10-15° C. over about 1 hr, and the mixture was aged at 5-10° C. for 1 hr. The precipitated solid was collected by filtration and washed twice with diisopropyl ether (400 ml) to give a pale-yellow white solid (not dried, 527 g) . 120 g therefrom was suspended in tetrahydrofuran (360 ml), cooled, and a solution of thionyl chloride (117 ml, 191 g) in tetrahydrofuran (240 ml) was added at 3-6° C. over about 40 min. The mixture was heated to 25° C. over about 1 hr, stirred with heating under reflux (66° C.) for 6 hr. The mixture was cooled to 27° C. over about 1 hr, and stirred under ice-cooing at 5-10° C. for 1 hr. The precipitated solid was collected by filtration and washed with tetrahydrofuran (24 ml×2) to give 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole (not dried, 119 g) as a pale-yellow white solid. Acetonitrile (57.9 ml) was added (suspended) to 23.7 g therefrom and pure water (9.7 ml) was added for dissolution at 21° C. Pure water (96.5 ml) was added at 21-24° C. over about 1 hr, and the mixture was cooled and stirred at 5-10° C. for 3 hr. The precipitated solid was collected by filtration, washed with pure water (20 ml×2) and dried under reduced pressure (40° C.) to give 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole (15.9 g) as a pale-yellow white solid in a yield of 56.7%.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][O:10][NH:11][CH3:12].[Cl:13][C:14]1[C:15]([CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=2)=[N:16][C:17]([Cl:20])=[CH:18][CH:19]=1>N1C=CC=CC=1>[Cl:13][C:14]1[C:15]([CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:31])[N:11]([O:10][CH3:9])[CH3:12])=[CH:25][CH:24]=2)=[N:16][C:17]([Cl:20])=[CH:18][CH:19]=1
Reactant: CNOC
Reactant: O=C=Nc1ccc(OCc2nc(Cl)ccc2Cl)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: CON(C)C(=O)Nc1ccc(OCc2nc(Cl)ccc2Cl)cc1
Temperature: 60 °C

Procedure:
Triethylamine (4.55 grams; 0.045 mole) was added to a solution of O,N-dimethylhydroxyamine hydrochloride (4.1 grams; 0.042 mole) in 40 ml. of dry pyridine. 3,6-dichloro-2-((4-isocyanatophenoxy)methyl)pyridine (12.4 grams; 0.042 mole) was added thereto and the resulting mixture heated for 20 minutes at about 60°C. The reaction mixture was then mixed with ice and the resulting precipitate recovered by filtration and recrystallized from a benzenehexane (90:10) mixture. As a result of such operations, the desired N'-(4-((3,6-dichloro-2-pyridinyl)methoxy)phenyl)-N-methoxy-N-methyl urea compound was recovered as a crystalline solid having a melting point of 152°-153.5°C.
Reaction SMILES: [C:1]([C:5]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:6]=1[OH:7])([CH3:4])([CH3:3])[CH3:2].[C:17](Cl)(=[O:26])[CH:18]=[CH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>[OH-].[Na+].C(O)C.C1C=CC=CC=1>[C:17]([O:12][C:10]1[CH:11]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]([OH:7])=[C:8]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:9]=1)(=[O:26])[CH:18]=[CH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(Cl)C=Cc1ccccc1
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccccc1
Solvent: CCO
Product: CC(C)(C)c1cc(OC(=O)C=Cc2ccccc2)cc(C(C)(C)C)c1O
Reaction time: 0.5 h

Procedure:
3,5-di tert. butyl-4-hydroxyphenyl cinnamate was prepared by dissolving 22.2 grams of 2,6-di tert.butyl hydroquinone in a solution of 4 grams of sodium hydroxide in 100 milliliters of ethanol and adding drop wise to this solution a solution of 18.2 grams of cinnamoyl chloride in 50 milliliters of benzene. The addition was completed in 30 minutes and the reaction mixture was stirred for an additional 45 minutes. The reaction mixture was then poured into 150 milliliters of water and the layers were separated. The organic layer was washed three times with 10 per cent sodium hydroxide solution, once with water, dried over sodium sulfate, and then evaporated to dryness. The residue, after washing with cold hexane, yielded 10 grams of product which after recrystallization from hexane melted at 123.5° C. to 125.5° C.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6]Cl.[OH:8][CH2:9][C:10]1[CH:11]=[C:12]([Si:15]([CH3:18])([CH3:17])[CH3:16])[O:13][CH:14]=1.CN(C)C1C=CC=CC=1>ClCCl>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:8][CH2:9][C:10]1[CH:11]=[C:12]([Si:15]([CH3:18])([CH3:17])[CH3:16])[O:13][CH:14]=1
Reactant: C[Si](C)(C)c1cc(CO)co1
Reactant: COCCOCCl
Solvent: CN(C)c1ccccc1
Solvent: ClCCl
Product: COCCOCOCc1coc([Si](C)(C)C)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2-Methoxyethoxymethyl chloride (0.11 ml, 0.96 mmol) was added to a solution of 4-hydroxymethyl-2-trimethylsilylfuran, also known as (2-trimethylsilyl-4-furyl)methanol, (162.8 mg, 0.96 mmol) and dimethylaniline (0.13 ml, 0.1 mmol) in dichloromethane (5 ml) at 0°. After stirring at room temperature overnight (ca. 16 hours), the reaction mixture was washed successively with water, dilute hydrochloric acid and water. Evaporation of the dried (magnesium sulfate) dichloromethane layer gave an oil, which was purified by preparative silica TLC (developed with 30% ethyl ether/hexane) to give the title ether as a colorless oil.