Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH:4]=O.[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[BH4-].[Na+]>CO.C(O)(=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH2:4][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1
Reactant: O=Cc1cc(O)ccc1Cl
Reactant: C1COCCN1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Oc1ccc(Cl)c(CN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 51.9 %

Procedure:
To a mixture of 2-chloro-5-hydroxybenzaldehyde (200 mg, 1.27 mmol, intermediate 28a) and morpholine (280 mg, 3.21 mmol) in methanol (10 mL) was added 2 drops of acetic acid and the mixture was stirred at room temperature for 2 h. To the mixture, sodium borohydride (97 mg, 2.56 mmol) was added and the resulting mixture was stirred at room temperature for 4 h. The mixture was quenched with dilute hydrochloride acid and concentrated to give crude product. This crude material was purified by silica gel chromatography eluting with petroleum ether/ethyl acetate (5:1 to 1:1) to give 4-chloro-3-(morpholinomethyl)phenol (150 mg, 51.8% yield) as white solid. LCMS retention time 0.378; LCMS MH+ 228.
Reaction SMILES: [O-]CC.[Na+].CS([C:9]1[N:10]([CH2:22][CH2:23][NH:24]C(=O)OC(C)(C)C)[C:11]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:21]=1)(=O)=O>C(O)C>[N:19]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:20]=1[C:11]1[N:10]3[CH2:22][CH2:23][NH:24][C:9]3=[N:21][C:12]=1[CH:13]=[N:14]2
Reactant: CC(C)(C)OC(=O)NCCn1c(S(C)(=O)=O)nc2cnc3cccnc3c21
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: c1cnc2c(c1)ncc1nc3n(c12)CCN3
Yield: 69.1 %

Procedure:
Sodium ethoxide (4.2 g, 61 mmol) was added in one portion to a solution of tert-butyl 2-[2-(methylsulfonyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]ethylcarbamate (20 g, 50 mmol) in ethanol (200 mL), and the resulting mixture was heated at reflux for four hours. Analysis by LC/MS indicated that no reaction had taken place, and additional sodium ethoxide (4.2 g, 61 mmol) was added. The mixture was heated at reflux overnight. Analysis by LC/MS indicated the presence of starting material, and a solution of sodium ethoxide (21% in ethanol, 150 mL) was added to the mixture. The reaction was heated at reflux for two hours and then concentrated under reduced pressure. Water was added, and the mixture was extracted with dichloromethane. A precipitate formed in the aqueous layer; the precipitate was isolated by filtration and washed with water to provide 7.3 g of 9,10-dihydro-8H-imidazo[1′,2′:1,2]imidazo[4,5-c][1,5]naphthyridine as a white solid.
Reaction SMILES: [CH2:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[OH:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:15][CH2:16][CH2:17][CH2:18]Br>>[CH2:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH2:18][CH2:17][CH2:16][Br:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1ccccc1Cc1ccccc1
Reactant: BrCCCBr
Product: BrCCCOc1ccccc1Cc1ccccc1

Procedure:
By following similar procedure as described in Preparation 89, O-alkylation of 2-benzylphenol with 1,3-dibromopropane gives the title-compound as oil. EIMS: m/z 304 (M+, 79Br), 306 (M+, 81Br).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([N:8]2[CH:12]=[C:11]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=3)[N:10]=[C:9]2[CH3:22])[N:3]=1.[CH3:23][Zn]C.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH3:23][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([N:8]2[CH:12]=[C:11]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=3)[N:10]=[C:9]2[CH3:22])[N:3]=1
Reactant: C[Zn]C
Reactant: Cc1cc(C#Cc2cn(-c3cncc(Cl)n3)c(C)n2)ccn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cc(C#Cc2cn(-c3cncc(C)n3)c(C)n2)ccn1

Procedure:
2-Chloro-6-[2-methyl-4-(2-methyl-pyridin-4-ylethynyl)-imidazol-1-yl]-pyrazine (27)(300 mg, 0.968 mmol) was dissolved in 5 mL dry tetrahydrofuran. Dimethylzinc (1.2 mL, 2M in toluene) and tetrakis(triphenylphosphin)palladium (23 mg, 0.02 mmol) were added. The reaction mixture was refluxed for 2 h and poured into 50 mL sat. sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate (50 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→90:10 gradient) and the desired product was obtained as a light yellow solid (240 mg, 85%), MS: m/e=290.1 (M+H+).
Reaction SMILES: [OH:1][C@@H:2]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:19]2[C:18](=[O:24])[CH2:17][C@@:16]2([CH3:25])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:15])[CH:13]=[CH2:14])[CH2:3]1.[CH2:26]([SH:28])[CH3:27]>>[CH2:26]([S:28][CH2:14][CH2:13][C:12](=[O:15])[C@@H:11]1[C@:16]2([CH3:25])[C@H:8]([C@H:7]3[C@H:19]([C:18](=[O:24])[CH2:17]2)[C@:20]2([CH3:23])[C@H:4]([CH2:3][C@H:2]([OH:1])[CH2:22][CH2:21]2)[CH2:5][CH2:6]3)[CH2:9][CH2:10]1)[CH3:27]
Reactant: C=CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: CCS
Product: CCSCCC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reaction time: 24 h

Procedure:
3α-Hydroxy-21-methylene-5α-pregnane-11,20-dione (250 mg. ) was dissolved in ethanethiol (2 ml) and the solution kept at room temperature for 24 hours. The excess ethanethiol was removed in vacuo and the residue partitioned between ether and water. The ethereal solution was washed with water, dried over anhydrous sodium sulphate and evaporated to a foam which was purified by preparative t.l.c. to give title compound (150 mg) as a glass [α]D + 83.3° (c = 0.12)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12](O)=[O:13])=[CH:5][CH:4]=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([S:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[CH2:12][OH:13])=[CH:7][CH:8]=1
Reactant: COc1ccc(Sc2ccccc2C(=O)O)cc1
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Agent: [Na+]
Product: COc1ccc(Sc2ccccc2CO)cc1
Yield: 84.7 %

Procedure:
2-(4-Methoxyphenylsulfanyl)benzoic acid was reduced with sodium bis-(methoxyethoxy)-aluminum hydride to provide in 84.7% yield 2-(4-methoxyphenylsulfanyl)benzyl alcohol. This compound was without purification treated with thionyl chloride to provide in 95.0% yield 2-(4-methoxyphenylsulfanyl)benzyl chloride, m.p. 76-78° C. For C14H13ClOS (264.8) calculated: 63.51% C, 4.95% H, 13.39% Cl, 12.11% S; found: 63.43% C, 5.05% H, 13.16% Cl, 12.10% S. This compound was treated with sodium cyanide to provide in 94.6% yield 2-(4-methoxyphenylsulfanyl)phenylacetonitrile, m.p. 65-67° C. Alkaline hydrolysis of this nitrile provided after work-up 69.7% yield of 2-(4-methoxyphenyl-sulfanyl)phenylacetic acid, m.p. 177-179° C. Demethylation with pyridine hydrochloride provided in 82.5% yield 2-(4-hydroxyphenylsulfanyl)phenylacetic acid, m.p. 163-165° C. This acid was esterified with methanol in the presence of sulfuric acid to give the required ester in 77.8% yield, m.p. 126-128° C. For C15H14O3S (274.3) calculated: 65.69% C, 5.15% H, 11.67% S; found: 65.17% C, 5.14% H, 11.69% S. 1H NMR spectrum (CDCl3): H(O) 5.17 bs; CH2 3.85 s; aromatic H on the phenolic nucleus: H(3,5) 6.73 d, J=8.8 Hz.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7].N1C=CC=CC=1.C(Cl)Cl.Cl[C:23]([O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:24]>CCOC(C)=O>[F:1][C:2]([F:11])([F:12])[O:3][C:4]1[CH:5]=[C:6]([NH:7][C:23](=[O:24])[O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:8]=[CH:9][CH:10]=1
Reactant: Nc1cccc(OC(F)(F)F)c1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(Nc1cccc(OC(F)(F)F)c1)Oc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 89.3 %

Procedure:
Add 3-(trifluoromethoxy)aniline (1.0 g, 5.65 mmol), pyridine (0.89 g, 11.3 mmol) to DCM (20 mL) and cool to 0° C. Add dropwise phenyl chloroformate (1.15 g, 7.34 mmol). After addition, stir for 1 hr. TLC (PE:EtOAc=3:1) shows the reaction is complete. Add water to the mixture, extract with DCM (10 mL×3), combine the organic layer, wash with 1N HCl solution, brine sequentially, and dry over anhydrous Na2SO4. Concentrate under reduced pressure to get the product (1.50 g, 89%).
Reaction SMILES: [CH:1]1[C:13]2[C:12](=O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[C:4](C(Cl)=O)=[CH:3][CH:2]=1.C1C2C(C3C=CC(OCCO)=CC=3)(C3C=CC([O:35]CCO)=CC=3)C3C(=CC=CC=3)C=2C=CC=1.C(N(CC)CC)C>O1CCCC1>[C:1]1(=[O:35])[C:13]2[C:5]([C:6]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)=[CH:4][CH:3]=[CH:2]1
Reactant: O=C(Cl)c1cccc2c1-c1ccccc1C2=O
Reactant: OCCOc1ccc(C2(c3ccc(OCCO)cc3)c3ccccc3-c3ccccc32)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C1C=CC=C2C1=Cc1ccccc12
Reaction time: 0.5 h

Procedure:
A 10.0 g quantity of 9-fluorenone-4-carbonyl chloride (0.04 mole, obtained from Aldrich Chemicals Co, Milwaukee, Wis. 53201, USA) and 100 ml of tetrahydrofuran (obtained from Aldrich) were added to a 250 ml, 3-neck round bottom flask equipped with a reflux condenser and a mechanical stirrer. The solution was stirred for about ½ hour, and then 9.04 g of 4.4′-(9-fluorenylidene)-bis(2-phenoxyethanol) (0.02 mole, obtained from Aldrich) in 50 ml of tetrahydrofuran were added, followed by the addition of 4.17 g of triethylamine (0.04 mole, obtained from Aldrich). The solution was refluxed for 6 hours, filtered hot to remove triethylamine hydrochloride salt byproduct, and the filtrate was evaporated to dryness to obtain the crude product. The crude product was recrystallized from tetrahydrofuran with activated charcoal. The product was dried at 60° C. in a vacuum oven for 6 hours to yield a fourth dimeric fluorenone derivative, which was a yellow solid (9.0 g, 51% yield). The product had a melting point of 137–138° C. A 1H-NMR (300 MHz) spectrum in CDCl3 yielded chemical shifts (ppm) of: 4.25–4.34 (t, 4H); 4.67–4.77 (t, 4H); 6.71–6.86 (m, 4H); 7.06–7.17 (m, 4H); 7.19–7.48 (m, 12H); 7.65–7.72 (td, 2H); 7.72–7.79 (d, 2H); 7.78–7.84 (dd, 2H); 7.86–7.95 (dd, 2H); 8.22–8.33 (d, 2H).
Reaction SMILES: [Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]2[N:6]([C@@H:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]3[OH:15])[CH:7]=[N:8][C:4]=2[CH:3]=1.N1C=CC=CC=1.[C:25](OC(=O)C)(=[O:27])[CH3:26]>>[C:25]([O:15][C@@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[N:6]1[C:5]2[CH:16]=[C:17]([Cl:18])[C:2]([Cl:1])=[CH:3][C:4]=2[N:8]=[CH:7]1)(=[O:27])[CH3:26]
Reactant: O[C@@H]1CCCC[C@H]1n1cnc2cc(Cl)c(Cl)cc21
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)O[C@@H]1CCCC[C@H]1n1cnc2cc(Cl)c(Cl)cc21
Yield: 97 %

Procedure:
(±)-trans-2-(5,6-Dichloro-1H-benzimidazol-1-yl)cyclohexanol (part a of this example, 6.25 g, 21.9 mmol) was stirred in acetic anhydride (3 ml)-pyridine (50 ml) for 18 h. Volatiles were evaporated and the residue partitioned between chloroform and saturated aqueous sodium bicarbonate. The chloroform solution was filtered through Celite/charcoal and evaporated to give title compound as an off-white solid (6.92 g, 97%), m.p. 145-147° C.
Reaction SMILES: C([N:8]1[C:12]2[N:13]=[C:14]([NH:27][C:28]3[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=3)[N:15]=[C:16]([O:17][C:18]3[C:23]([CH3:24])=[CH:22][C:21]([CH3:25])=[CH:20][C:19]=3[CH3:26])[C:11]=2[CH:10]=[CH:9]1)C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC1C=CC=CC=1Cl>[CH3:26][C:19]1[CH:20]=[C:21]([CH3:25])[CH:22]=[C:23]([CH3:24])[C:18]=1[O:17][C:16]1[C:11]2[CH:10]=[CH:9][NH:8][C:12]=2[N:13]=[C:14]([NH:27][C:28]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=2)[N:15]=1
Reactant: Cc1cc(C)c(Oc2nc(Nc3ccc(C#N)cc3)nc3c2ccn3Cc2ccccc2)c(C)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1Cl
Product: Cc1cc(C)c(Oc2nc(Nc3ccc(C#N)cc3)nc3[nH]ccc23)c(C)c1
Temperature: 160 °C
Reaction time: 4 h
Yield: 48.9 %

Procedure:
To a solution of 4-[7-benzyl-4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile (38 mg, 0.083 mmol) in 1,2-dichlorobenzene (1 mL) was added aluminum chloride (55 mg, 0.42 mmol). The reaction mixture was stirred at 160° C. for 4 h and cooled to room temperature. The mixture was poured into ice water and extracted with CH2Cl2 (2×10 mL). The combined organic solution was washed with brine (10 mL), dried with Na2SO4, and concentrated to dryness. Silica gel chromatography (Hexanes:EtOAc 50:50) yielded 15 mg (49%) of 4-[4-(2,4,6-trimethyl-phenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino]-benzonitrile as a tan solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1)#[N:2].Br[CH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]1=O>C(O)C>[CH3:14][C:12]1[N:11]=[CH:10][N:9]([C:8]2[CH:7]=[CH:6][C:5]([NH:15][C:16]3[S:17][C:28]4[CH2:29][CH2:30][CH2:31][CH:26]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:20][CH:21]=5)[C:27]=4[N:18]=3)=[CH:4][C:3]=2[C:1]#[N:2])[CH:13]=1
Reactant: Cc1cn(-c2ccc(NC(N)=S)cc2C#N)cn1
Reactant: O=C1C(Br)CCCC1c1ccccc1
Solvent: CCO
Product: Cc1cn(-c2ccc(Nc3nc4c(s3)CCCC4c3ccccc3)cc2C#N)cn1
Temperature: 25 °C
Yield: 87.5 %

Procedure:
A suspension of [3-cyano-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (64.3 mg, 0.25 mmol) and of 2-bromo-6-phenyl-cyclohexanone (63.3 mg, 0.25 mmol) in ethanol (2 mL) was heated to reflux under an atmosphere of nitrogen for 2 days. After cooling to room temperature the solvent was evaporated under reduced pressure. The residue was suspended in dichloromethane/diethyl ether. The precipitated solid was filtered off, washed with diethyl ether and dried under reduced pressure to yield the title compound (90 mg, 88%) as a pale-brown solid. MS ISP (m/e): 412.2 (100) [(M+H)+]. 1H NMR (DMSO-D6, 300 MHz): δ (ppm)=10.75 (s, 1H), 9.31 (s, 1H), 8.16 (s, 1H), 7.78 (m, 2H), 7.65 (d, 1H), 7.30 (t, 2H), 7.17 (m, 3H), 4.08 (m, 1H), 2.75 (m, 2H), 2.34 (s, 3H), 2.15 m, 2H), 1.76 (m, 2H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=2[OH:20])[N:3]=1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C>C(Cl)Cl>[F:19][C:18]1[C:13]([C:4]2[N:3]=[C:2]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:11]3[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=3)[N:5]=2)=[C:14]([OH:20])[CH:15]=[CH:16][CH:17]=1
Reactant: C1CNCCN1
Reactant: Cc1ccc2c(Cl)nc(-c3c(O)cccc3F)nc2c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc2c(N3CCNCC3)nc(-c3c(O)cccc3F)nc2c1
Yield: 84.3 %

Procedure:
2-(4-Chloro-7-methylquinazolin-2-yl)-3-fluorophenol (4.37 g, 15.14 mmol) was suspended in CH2Cl2 (65 mL) under an N2 atmosphere and placed into an ice water bath. To this solution was added a solution of piperazine (4.00 g, 45.42 mmol) and triethylamine (4.2 mL, 30.28 mmol) in CH2Cl2 (15 mL) in one portion. After stirring the reaction for 30 minutes, it was partitioned between CH2Cl2 and H2O and separated, and the aqueous layer was extracted twice more with CH2Cl2. The organic phase was dried over Na2SO4, filtered, and concentrated to a bright yellow solid which was purified via silica gel chromatography using a 95%/5% mixture of CH2Cl2/MeOH to afford 3-fluoro-2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (4.32 g, 85%) as a bright yellow solid. LC/MS: m/z 339.3 (M+H)+ at 1.80 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([CH:8]=[C:9]2[S:13][C:12](=[O:14])[NH:11][C:10]2=[O:15])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:18]N(C)C=O.[H-].[Na+].IC>O>[CH3:18][N:11]1[C:10](=[O:15])[C:9](=[CH:8][C:7]2[CH:16]=[CH:17][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[S:13][C:12]1=[O:14]
Reactant: O=C1NC(=O)C(=Cc2ccc([N+](=O)[O-])cc2)S1
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CI
Product: CN1C(=O)SC(=Cc2ccc([N+](=O)[O-])cc2)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 95 %

Procedure:
To a mixture of 5-(4-nitrobenzylidene)-1,3-thiazolidine-2,4-dione (4.0 g) and N,N-dimethylformamide (100 mL) was added sodium hydride (60% in oil, 0.7 g) at room temperature. The reaction mixture was stirred at room temperature for 30 min. and iodomethane (6.81 g) was added to the reaction mixture. The mixture was further stirred at room temperature for 15 hrs. Water was added to the reaction mixture and the precipitated crystals were collected by filtration to give 3-methyl-5-(4-nitrobenzylidene)-1,3-thiazolidine-2,4-dione as yellow crystals (4.02 g, yield 95%). Recrystallization thereof from tetrahydrofuran-hexane gave yellow prism crystals. melting point: 233-234° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:12]1([CH2:18][SH:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)C(C)C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH2:18]([S:19][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: SCc1ccccc1
Reactant: COc1cc(Br)cnc1OC
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: COc1cc(SCc2ccccc2)cnc1OC
Temperature: 120 °C
Yield: 105.7 %

Procedure:
To a solution of 5-bromo-2,3-dimethoxypyridine (1.2 g, 5.50 mmol) in toluene (18 ml) was added phenylmethanethiol (0.71 ml, 6.05 mmol), N-ethyl-N-isopropylpropan-2-amine (2.00 ml, 12.1 mmol), Pd2(dba)3 (0.20 g, 0.22 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (0.26 g, 0.44 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was irradiated in the microwave with heating to 120° C. for 1 hour before being filtered through a pad of celite and washed with ethyl acetate (25 ml). The filtrate was concentrated to give an orange oil which was purified by column chromatography (SiO2; 0-15% ethyl acetate in petrol) gave 5-(benzylsulfanyl)-2,3-dimethoxypyridine as an orange oil (1.52 g, 75%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][C:13]([F:16])([F:15])[F:14])[CH3:2].[Li]C(CC)C.[I:23]I.[Cl-].[NH4+]>C1COCC1.C1CCCCC1.O>[CH2:1]([O:3][C:4](=[O:17])[NH:5][C:6]1[C:7]([O:12][C:13]([F:14])([F:16])[F:15])=[CH:8][CH:9]=[CH:10][C:11]=1[I:23])[CH3:2]
Reactant: II
Reactant: CCOC(=O)Nc1ccccc1OC(F)(F)F
Agent: [Cl-]
Agent: [Li]C(C)CC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: C1CCCCC1
Solvent: O
Product: CCOC(=O)Nc1c(I)cccc1OC(F)(F)F
Reaction time: 1 h
Yield: 94.4 %

Procedure:
(2-Trifluoromethoxy-phenyl)-carbamic acid ethyl ester (42.4 g, 0.17 mol) was dissolved in THF (800 mL) and cooled to −70 ° C. sec-BuLi in cyclohexane (280 mL, 1.3 M) was added dropwise at this temperature with stirring. Stirring was continued for 1 h after addition was complete. A solution of iodine (43.2 g, 0.17 mol) in THF (160 mL) was added dropwise at −70 ° C. Stirring was continued for 1 h after addition was complete and the mixture was hydrolysed with saturated ammonium chloride solution. Water was added and the mixture was extracted with diethyl ether. The organic phases were washed with 40% sodium bisulfite, water, brine, pooled and dried with MgSO4. Evaporation of the solvent yielded the title compound, (60.2 g, 94%) as a colorless amorphous solid. (EI-MS: m/e=374.9 (M+))
Reaction SMILES: [Zn:1].[F-].F[Si-2](F)(F)(F)(F)F.[P:10]([O-:14])([O-:13])([O-:12])=[O:11].[N+]([O-])([O-])=O.N([O-])=O.[OH:22][P:23]([OH:26])([OH:25])=[O:24]>[Ni].O>[P:10]([O-:14])([O-:13])([O-:12])=[O:11].[Zn+2:1].[P:23]([O-:26])([O-:25])([O-:24])=[O:22].[Zn+2:1].[Zn+2:1]
Reactant: O=P(O)(O)O
Reactant: [Zn]
Agent: [Ni]
Agent: O=N[O-]
Agent: O=P([O-])([O-])[O-]
Solvent: O
Product: [Zn+2]
Temperature: 65.55555555555556 °C

Procedure:
An aqueous acidic zinc phosphate coating solution was prepared in a five-gallon laboratory spray tank to contain 1.2 g/l zinc ions, 1.0 g/l nickel ions, 1.0 g/l fluoride added as silicofluoride, 5.0 g/l phosphate ions, 2.0 g/l nitrate ions, and 0.1 g/l nitrite ions. This solution, when heated to 150° F., and when titrated in the conventional manner, was found to have a total acid of between 13.0 and 14.6 points, and a free acid of between 1.0 and 1.3 points. In a second spray tank, a conventional alkaline cleaner was prepared at a concentration of one ounce per gallon and was heated to 145°-150° F. A third spray tank was used to contain the melamine-formaldehyde resin/tannin post-treatment solutions detailed in Table XVIII. A number of 4 × 12 inch SAE 1010, cold rolled steel panels (CRS) and 4 × 12 inch minimum spangle commercial hot-dipped galvanized panels (GALV), temper rolled one percent, were sprayed in the sequence one minute cleaner, one-half minute fresh warm water spray rinse, 1 minute zinc phosphate solution, one-half minute cold water rinse, and one-half minute melamine-formaldehyde resin/tannin solution detailed in the table, after which they were dried in a circulating air oven for 5 minutes at 325° F. Control panels were prepared in the same manner except that they were oven dried following a one-half minute tap water rinse and a one-half minute deionzed water rinse, or alternatively treated in a commercial post-treatment solution containing about 0.04% chromic acid at a pH of about 4 at 80° F. for one-half minute following the cold water rinse and oven dried. Other control panels were prepared in the same manner except that they were treated in a solution containing 0.25 g/l of tannin T9 at a pH of 4.6 (adjusted with H3PO4) at 80° F. for one-half minute following the cold water rinse and oven dried. In this example, all panels were oven dried for 5 minutes at 325° F.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[NH:7][C:6]=2[CH:13]=1.Cl[C:15]1[N:20]=[C:19]([NH:21][C:22]2[CH:31]=[CH:30][C:29]([N:32]([CH3:34])[CH3:33])=[CH:28][C:23]=2[C:24]([NH:26][CH3:27])=[O:25])[C:18]([Cl:35])=[CH:17][N:16]=1>>[Cl:35][C:18]1[C:19]([NH:21][C:22]2[CH:31]=[CH:30][C:29]([N:32]([CH3:33])[CH3:34])=[CH:28][C:23]=2[C:24]([NH:26][CH3:27])=[O:25])=[N:20][C:15]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[NH:7][C:6]=3[CH:13]=2)=[N:16][CH:17]=1
Reactant: CNC(=O)c1cc(N(C)C)ccc1Nc1nc(Cl)ncc1Cl
Reactant: Nc1ccc2c(c1)NC(=O)CCC2
Product: CNC(=O)c1cc(N(C)C)ccc1Nc1nc(Nc2ccc3c(c2)NC(=O)CCC3)ncc1Cl

Procedure:
2-[5-Chloro-2-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-5-dimethylamino-N-methyl-benzamide was prepared from 8-amino-1,3,4,5-tetrahydro-benzo[b]azepin-2-one and 2-(2,5-dichloro-pyrimidin-4-ylamino)-5-dimethylamino-N-methyl-benzamide in an analogous manner to Example 1410. Product isolated as a yellow solid (155 mg, 81%). m.p.=253-255° C.; LCMS (m/e) 480 (M+H); HNMR (d6-DMSO, 400 MHz) δ 11.46 (bs, 1H), 9.80-9.66 (m, 1H), 9.51 (s, 1H), 8.87-8.77 (m, 1H), 8.53-8.40 (m, 1H), 8.21 (s, 1H), 7.34 (s, 1H), 7.29-7.09 (m, 1H), 7.25 (d, 1H, J=8.0 Hz), 7.17 (d, 1H, J=8.5 Hz), 7.03-6.81 (m, 1H), 2.99 (s, 6H), 2.81 (d, 3H, J=3.8 Hz), 2.65 (t, 2H, J=6.8 Hz), 2.24-2.15 (m, 2H), 2.15-2.04 (m, 2H).