Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4]1[C:5](=[C:10]([NH2:14])[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7].[O:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[CH:21]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:5](=[C:10]([NH:14][CH2:21][C:17]2[O:16][CH:20]=[CH:19][CH:18]=2)[CH:11]=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]
Reactant: O=Cc1ccco1
Reactant: COC(=O)c1cccc(N)c1C(=O)OC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COC(=O)c1cccc(NCc2ccco2)c1C(=O)OC
Reaction time: 0.08 h
Yield: 109.2 %

Procedure:
To a stired solution of 3-amino-phthalic acid dimethyl ester (8.23 g, 39.32 mmol) in methylene chloride (200 ml) under a nitrogen atmosphere, 2-furaldehyde (8.14 ml, 98.30 mmol) and acetic acid (13.57 ml, 235.92 mmol) were added. The mixture was stirred for 5 minutes, followed by addition of sodium triacetoxyborohydride (25 g, 117.96 mmol). The reaction was sitirred overnight, washed with water (2×200 ml), saturated aqueous sodium bicarbonate (2×200 ml), and brine (200 ml), and dried over MgSO4. The solvent was evaporated in vacuo to give a brown oil (12.42 g), which was used directly without purification.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[C:7]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1.Br[C:23]1[C:24]([NH2:29])=[N:25][CH:26]=[CH:27][CH:28]=1.O>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:7]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:10]([C:23]2[C:24]([NH2:29])=[N:25][CH:26]=[CH:27][CH:28]=2)=[CH:9][CH:8]=1
Reactant: Nc1ncccc1Br
Reactant: OB(O)c1ccc(-c2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Nc1ncccc1-c1ccc(-c2ccccc2)cc1
Yield: 65.5 %

Procedure:
A mixture of 2M aqueous sodium carbonate solution (6.64 mL), tetrakis(triphenylphosphine)palladium(0) (0.512 g), biphenyl-4-ylboronic acid (2.28 g) and 3-bromopyridin-2-amine (1.532 g) in dehydrated THF (30 mL) was heated under reflux overnight. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a solid. The obtained solid was crystallized from toluene, diisopropyl ether and acetonitrile to give the title compound (1.428 g) as a white solid.
Reaction SMILES: [C:1]1([CH3:16])[CH:6]=[CH:5][C:4]([C:7]2[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)=[CH:3][CH:2]=1.[Br:17]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[Br:17][CH2:16][C:1]1[CH:2]=[CH:3][C:4]([C:7]2[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)=[CH:5][CH:6]=1
Reactant: Cc1ccc(-c2nc3ccccc3o2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: BrCc1ccc(-c2nc3ccccc3o2)cc1

Procedure:
2-(p-Tolyl)benzoxazole was reacted with N-bromosuccinimide in the presence of benzoyl peroxide by the standard procedure to produce the known compound, 2-(4-bromomethylphenyl)benzoxazole (A). 2-(2,4-Dihydroxyphenyl)benzotriazole (B) (0.1 mole) and 2-(4-bromomethylphenyl)benzoxazole (A) (0.1 mole) was stirred in a mixture of 2-butanone (300 ml.) and potassium carbonate (100 g.). After refluxing 16 hr., the mixture was poured onto 1000 g. ice/water. Filtration, washing with water and recrystallization from methyl cellosolve/ isopropyl alcohol gave the tan, crystalline product I.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9](=[O:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:3]=1.Cl.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1.N1C=CC=CC=1>O>[C:18]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[C:9](=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1
Reactant: O=C(Cl)c1cccnc1
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1O
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C(Oc1ccc(Cl)cc1C(=O)c1ccccc1)c1cccnc1
Temperature: 40 °C
Reaction time: 24 h

Procedure:
15 g (64.5 mmol) of p-chlorobenzoylphenol and 12 g (68 mmol) of nicotinic acid chloride hydrochloride was mixed with 200 ml dry pyridine and stirred for 24 hours at 40° C. After cooling 200 ml water were added and the precipitated product washed twice with 80 ml of water and recrystallized from methanol.
Reaction SMILES: [NH3:1].[CH2:2]([O:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[C:15]([I:23])=[CH:14]2)[CH2:9][CH2:8]1)=[O:6])[CH3:3]>CC(O)C>[CH2:2]([O:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH2:1])[C:16]=3[C:15]([I:23])=[CH:14]2)[CH2:9][CH2:8]1)=[O:6])[CH3:3]
Reactant: CCOC(=O)[C@H]1CC[C@@H](n2cc(I)c3c(Cl)ncnc32)CC1
Reactant: N
Solvent: CC(C)O
Product: CCOC(=O)[C@H]1CC[C@@H](n2cc(I)c3c(N)ncnc32)CC1
Temperature: -78 °C

Procedure:
Gaseous ammonia was bubbled into an iPrOH (1 mL) solution of cis-4-(4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclohexanecarboxylic acid ethyl ester (30 mg, 70% pure by HPLC peak area, 0.048 mmol) in a glass pressure tube, cooled to −78° C. in a dry ice/acetone bath, for 15 min. The tube was equipped with a Teflon washer, sealed and heated to 110° C. for 7 h. After that time, the excess NH3 and the solvent were evaporated. The residue was used for the next reaction without purification. A portion of above crude material were purified by HPLC to give the title compound as pale yellow oil. 1H NMR (CDCl3, 400 MHz): δ=1.31 (t, 3H, J=7.6 Hz), 1.63-1.98 (m, 6H), 2.29-2.35 (m, 2H), 2.73 (m, 1H), 4.22 (q, 2H, J=7.6 Hz), 4.64-4.71 (m, 1H), 5.58 (brs, 2H), 7.11 (s, 1H), 8.26 (s, 1H). MS (ES+): 415.0 [MH+]. tR=2.7 min (polar—5 min).
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: Cc1ccc2c(Cl)nc(-c3c(O)cccc3F)nc2c1
Reactant: C1CNCCN1
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: [OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18]([O:20]C)=O.[CH3:22][C:23]1[S:27][C:26]([NH2:28])=[N:25][CH:24]=1>>[OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18]([NH:28][C:26]1[S:27][C:23]([CH3:22])=[CH:24][N:25]=1)=[O:20]
Reactant: Cc1cnc(N)s1
Reactant: COC(=O)C1=C(O)c2sc3ccccc3c2S(=O)(=O)N1C
Product: Cc1cnc(NC(=O)C2=C(O)c3sc4ccccc4c3S(=O)(=O)N2C)s1
Yield: 46 %

Procedure:
Prepared analogous to Example 1 from methyl 4-hydroxy-2-methyl-2H-[1]benzothieno[2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide and 5-methyl-2-thiazolamine with a yield of 46% of theory.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][CH2:7][C:8]([C:10]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:11]=1[CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[O:9])(=[O:3])[CH3:2].S(Cl)(Cl)=O.O[CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>C(Cl)Cl>[C:1]([NH:4][CH2:5][CH2:6][CH2:7][C:8]([C:10]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:11]=1[CH2:12][CH2:13][C:14]([O:16][CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1)=[O:15])=[O:9])(=[O:3])[CH3:2]
Reactant: OCc1cccnc1
Reactant: CC(=O)NCCCC(=O)c1ccc(Cl)cc1CCC(=O)O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: CC(=O)NCCCC(=O)c1ccc(Cl)cc1CCC(=O)OCc1cccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.00 g (0.006 mol) of 2-(4-acetamidobutyryl)-5-chlorohydrocinnamic acid and 0.5 ml (0.006 mol) of thionyl chloride in 20 ml of methylene chloride are stirred at room temperature for 5 minutes and, then a solution of 2.2 ml (0 023 mol) of 3-hydroxymethylpyridine in 20 ml of methylene chloride is added thereto at 0°. After stirring at room temperature for 1 hour, the solution is concentrated, extracted with methylene chloride/water, dried with magnesium sulfate and the solvent is distilled in a vacuum. Chromatography on aluminum oxide with ethyl acetate gives 3-pyridylmethyl 2-(4-acetamidobutyryl)-5chlorohydrocinnamate as a beige oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8]C)=[C:4]([CH2:10][CH3:11])[CH:3]=1.B(Br)(Br)Br.CO>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH2:10][CH3:11])[CH:3]=1
Reactant: CCc1cc(Cl)ccc1OC
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CO
Product: CCc1cc(Cl)ccc1O
Reaction time: 2 h
Yield: 57.6 %

Procedure:
To a solution of 4-chloro-2-ethyl-1-methoxybenzene (Preparation 5, 7.0 g, 41.0 mmol) in dichloromethane (20 mL) at 0° C. was added a 1M solution of boron tribromide in dichloromethane (20.5 mL, 20.5 mmol). After 2 hours, further boron tribromide solution (20 mL, 20.0 mmol) was added. After a further 2 hours, methanol was added and the reaction mixture concentrated in vacuo. The residue was purified by silica gel column chromatography (5%-40% ethyl acetate in heptane) to afford the title compound (3.7 g, 58%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][CH:6]=[C:5]([C:10]2[C:14]3[CH:15]=[C:16]([N:19]4[C:24](=[O:25])[CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[N:21]([CH3:30])[C:20]4=[O:31])[CH:17]=[CH:18][C:13]=3[S:12][N:11]=2)[CH:4]=1.[I:32]I>C(Cl)Cl.FC(F)(F)C([O-])=O.[Ag+]>[I:32][C:6]1[C:5]([C:10]2[C:14]3[CH:15]=[C:16]([N:19]4[C:24](=[O:25])[CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[N:21]([CH3:30])[C:20]4=[O:31])[CH:17]=[CH:18][C:13]=3[S:12][N:11]=2)=[CH:4][C:3]([O:2][CH3:1])=[C:8]([CH3:9])[CH:7]=1
Reactant: II
Reactant: COc1cc(-c2nsc3ccc(-n4c(=O)cc(C(F)(F)F)n(C)c4=O)cc23)ccc1C
Agent: [Ag+]
Agent: O=C([O-])C(F)(F)F
Solvent: ClCCl
Product: COc1cc(-c2nsc3ccc(-n4c(=O)cc(C(F)(F)F)n(C)c4=O)cc23)c(I)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.2 %

Procedure:
A mixture of 3-[3-(6-methoxy-p-tolyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione (1.34 g, 0.00300 mol), silver trifluoroacetate and methylene chloride is treated with iodine (1.14 g, 0.00450 mol) in portions, stirred overnight at room temperature, diluted with methylene chloride, washed with 1M sodium thiosulfate and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to a brown oil which solidifies on standing. Recrystallization from ether affords the title compound as a light yellow crystalline solid (1.50 g, 87.2%, mp 210-212° C.).
Reaction SMILES: [CH3:1][CH2:2][C:3](=[O:9])[CH2:4][CH2:5][CH:6]=[CH:7][CH3:8]>C(OCC)(=O)C.[Pd]>[C@@H:5]12[CH2:6][CH2:7][CH2:8][C@@H:1]1[CH2:2][C:3](=[O:9])[CH2:4]2
Reactant: CC=CCCC(=O)CC
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C1C[C@H]2CCC[C@H]2C1
Yield: 104.7 %

Procedure:
A solution of the cis-bicyclo[3.3..0]oct-6-ene-3-one (6.2 g 0.05 mol) in 150 mL of ethyl acetate containing 0.50 g of 10% Pd/C was hydrogenated at 25 psi for 11/2 hours. The catalyst was removed by filtering through Celite and the solvent evaporated to give 6.5 g of cis-bicyclo[3.3.0]-octane-3-one (100%). TLC (SiO2, CH2Cl2) Rf =0.35 (I2, brown).
Reaction SMILES: [CH2:1]([SH:3])[CH3:2].[H-].[Na+].Br[C:7]([F:14])([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9]>CS(C)=O>[CH2:1]([S:3][C:7]([F:14])([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:2]
Reactant: CCS
Reactant: CCOC(=O)C(F)(F)Br
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCOC(=O)C(F)(F)SCC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 66.7 %

Procedure:
Ethyl mercaptan (6.8 g, 109.7 mmol) was added dropwise to a solution of 60% sodium hydride (2.6 g, 65 mmol) in dimethyl sulfoxide (80 ml) under cooling with ice, and the mixture was stirred at room temperature for 10 minutes. A solution of ethyl bromodifluoroacetate (11.2 g, 55.2 mmol) in dimethyl sulfoxide (20 ml) was added dropwise to this solution under cooling with ice, and the resultant mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was poured into ice water to conduct extraction with ether. The solvent was distilled out of the resultant extract under reduced pressure. The resultant residue was distilled under reduced pressure to obtain the intended product (6.8 g; yield: 66.7%) as a colorless oil.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[N:5][N:4]=[C:3]1[CH:8]1[C:17](=O)[C:16]2[C:15]([C:19]([O:21]CC)=O)=[CH:14][CH:13]=[CH:12][C:11]=2[NH:10][CH:9]1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.O.[NH2:32][NH2:33]>CO>[CH3:1][N:2]1[C:6]([CH3:7])=[N:5][N:4]=[C:3]1[CH:8]1[C:17]2=[N:32][NH:33][C:19](=[O:21])[C:15]3[CH:14]=[CH:13][CH:12]=[C:11]([C:16]=32)[NH:10][CH:9]1[C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1
Reactant: CCOC(=O)c1cccc2c1C(=O)C(c1nnc(C)n1C)C(c1ccc(F)cc1)N2
Reactant: NN
Solvent: O
Solvent: CO
Product: Cc1nnc(C2c3n[nH]c(=O)c4cccc(c34)NC2c2ccc(F)cc2)n1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 26 %

Procedure:
A mixture of ethyl 3-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-2-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (170 mg) in 85% hydrazine monohydrate (1 mL) and methanol (3 mL) was stirred at 25° C. for 3 h. The mixture was purified by prep-HPLC to obtain the title compound as a yellow solid (40 mg, yield: 26%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 2.23 (s, 3H), 3.38 (s, 3H), 4.78-4.80 (d, J=11.0 Hz, 1H), 4.99-5.02 (d, J=11.0 Hz, 1H), 7.11-7.18 (m, 3H), 7.35-7.40 (m, 2H), 7.47-7.51 (m, 2H), 7.57-7.61 (t, J=7.6 Hz, 1H), 12.19 (s, 1H); LC-MS (ESI) m/z: 377 (M+1)+.
Reaction SMILES: [CH3:1][N:2]([CH3:26])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:19]2[CH:20]=[C:21]([CH3:25])[CH:22]=[CH:23][CH:24]=2)[CH2:10][C:11]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=O)=[CH:5][CH:4]=1.Cl.[NH2:28][OH:29].C([O-])(O)=O.[Na+]>>[CH3:1][N:2]([CH3:26])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:19]2[CH:20]=[C:21]([CH3:25])[CH:22]=[CH:23][CH:24]=2)[CH2:10][C:11]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[N:28][OH:29])=[CH:5][CH:4]=1
Reactant: Cc1cccc(C(CC(=O)c2ccncc2)c2ccc(N(C)C)cc2)c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1cccc(C(CC(=NO)c2ccncc2)c2ccc(N(C)C)cc2)c1

Procedure:
In analogy to example 1, step 2, from 3-(4-dimethylamino-phenyl)-1-pyridin-4-yl-3-m-tolyl-propan-1-one and hydroxylamine hydrochloride in the presence of NaHCO3 was prepared the title compound as a mixture of E and Z isomers (3:1) as a yellow foam, MS (ESI+): m/z=360.1 ([M+H]+).
Reaction SMILES: [S:1]1[CH2:5][CH2:4][N:3]=[CH:2]1.[Cl:6]([O-:10])(=[O:9])(=[O:8])=[O:7].CS[C:13]1[S:17][CH:16]=[CH:15][S+:14]=1>>[Cl:6]([O-:10])(=[O:9])(=[O:8])=[O:7].[S:14]1[CH:15]=[CH:16][S:17][C:13]1=[N+:3]1[CH2:4][CH2:5][S:1][CH2:2]1
Reactant: CSc1scc[s+]1
Reactant: C1=NCCS1
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: c1csc(=[N+]2CCSC2)s1

Procedure:
1.0 g of thiazoline and 2.5 g of 2-methylthio-1,3-dithiolium perchlorate were treated in the same manner as in Example 26, and the product was recrystallized from ethanol, whereby 2.3 g (yield: 79.3%) of 3-(1,3-dithiol-2-ylidene)thiazolidinium perchlorate (Compound No. 36) was obtained as crystals having a melting point of from 179° to 180° C.
Reaction SMILES: [Si]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][C:21](=[O:33])[N:22]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])=[C:18]([C:34]([O:36]CC)=O)[N:17]=1)(C(C)(C)C)(C)C.[NH2:39]C1C(C(OCC)=O)=NC(NC2C=CC=CC=2O[Si](C(C)(C)C)(C)C)=NC=1NC1C=CC=CC=1OC.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl>[OH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][C:21](=[O:33])[N:22]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])=[C:18]([C:34]([NH2:39])=[O:36])[N:17]=1
Reactant: CCOC(=O)c1nc(Nc2ccccc2O[Si](C)(C)C(C)(C)C)nc2c1[nH]c(=O)n2-c1ccccc1OC
Reactant: CCOC(=O)c1nc(Nc2ccccc2O[Si](C)(C)C(C)(C)C)nc(Nc2ccccc2OC)c1N
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: COc1ccccc1-n1c(=O)[nH]c2c(C(N)=O)nc(Nc3ccccc3O)nc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
Ethyl 2-(2-(tert-butyldimethylsilyloxy)phenylamino)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxylate. Ethyl 5-amino-2-(2-(tert-butyldimethylsilyloxy)phenyl amino)-6-(2-methoxyphenylamino)pyrimidine-4-carboxylate (232.6 mg, 0.456 mmol) was dissolved in methylene chloride (5 mL) and 1,1′-carbonyldiimidazole (740 mg, 4.56 mmol) was added. The reaction was refluxed for 1H and then stirred at room temperature overnight. Solvent was removed under reduced pressure and crude was purified by column chromatography (50% ethyl acetate in hexanes). Fractions containing product were combined and the solvent evaporated to provide the title compound (235.2 mg, 0.439 mmol, 96% yield) as a yellow solid. MS (ESI) m/z 536.4 [M+1]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10](O)=[O:11])=[CH:4][C:3]=1[O:13][CH3:14].C(N(CC)CC)C.C1C=CC(P([N:36]=[N+:37]=[N-:38])(C2C=CC=CC=2)=O)=CC=1>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([N:36]=[N+:37]=[N-:38])=[O:11])=[CH:4][C:3]=1[O:13][CH3:14]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: COc1cc(/C=C/C(=O)O)ccc1F
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: COc1cc(/C=C/C(=O)N=[N+]=[N-])ccc1F
Reaction time: 18 h
Yield: 70.9 %

Procedure:
To a solution of (E)-3-(4-fluoro-3-methoxyphenyl)acrylic acid (5 g, 25.5 mmol) in benzene (30 ml) was added triethylamine (5.16 g, 51 mmol) followed by DPPA (7.01 g, 25.5 mmol) at room temperature. The reaction mass was stirred at the same temperature for 18 h. The solvent was evaporated under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to get crude compound. The crude compound was purified by conventional column chromatography (Silica gel, 60-120 mesh) using 10% ethyl acetate in pet ether as mobile phase to get the desire compound as white solid (4 g, 71%). 1H NMR (400 MHz, CDCl3): δ ppm 7.70-7.66 (d, J=16 Hz, 1H), 7.12-7.07 (m, 3H), 6.35-6.31 (d, J=16 Hz, 1H), 3.92 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@H:12]3[O:16][C:15](=[O:17])[NH:14][CH2:13]3)=[CH:11][C:5]=2[CH2:4][O:3]1.[H-].[Na+].Br[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([N+:39]([O-:41])=[O:40])[CH:34]=1.P([O-])([O-])([O-])=O>CN(C=O)C.O>[CH3:1][C:2]1([CH3:18])[O:7][C:6]2[CH:8]=[CH:9][C:10]([CH:12]3[O:16][C:15](=[O:17])[N:14]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([N+:39]([O-:41])=[O:40])[CH:34]=4)[CH2:13]3)=[CH:11][C:5]=2[CH2:4][O:3]1
Reactant: CC1(C)OCc2cc([C@@H]3CNC(=O)O3)ccc2O1
Reactant: O=[N+]([O-])c1cccc(COCCOCCCCCCBr)c1
Agent: O=P([O-])([O-])[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OCc2cc(C3CN(CCCCCCOCCOCc4cccc([N+](=O)[O-])c4)C(=O)O3)ccc2O1
Reaction time: 0.67 h
Yield: 101.8 %

Procedure:
A solution of (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (4.40 g) in anhydrous DMF (75 ml) was treated under nitrogen at 0° with sodium hydride (60% dispersion in mineral oil, 1.04 g) and the mixture stirred for 40 min. A solution of 1-[(2-[(6-bromohexyl)oxy]ethoxy)methyl]-3-nitrobenzene (8.12 g) in DMF (10 ml) was added and the mixture stirred at 20° for 2 h. Phosphate buffer (pH 6.5, 100 ml) and water (100 ml) were added and the product extracted with EtOAc (4×100 ml). The combined organic layer was washed with water (3×100 ml) and dried (Na2SO4). The solvent was removed in vacuo to give a residue that was purified by Biotage. Elution with EtOAc-PE (1:1 then 3:2) followed by solvent evaporation in vacuo gave the title compound (9.50 g). LCMS RT=3.75 min, ES+ve 529 (MH)+.
Reaction SMILES: C(N)C1C=CC=CC=1.[F:9][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[CH2:13][NH2:14].[CH2:18]([N:25]1[CH2:29][CH2:28][N:27]([C:30]2[S:31][C:32]([C:36](O)=[O:37])=[C:33]([CH3:35])[N:34]=2)[C:26]1=[O:39])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([N:25]1[CH2:29][CH2:28][N:27]([C:30]2[S:31][C:32]([C:36]([NH:14][CH2:13][C:12]3[CH:15]=[CH:16][CH:17]=[C:10]([F:9])[CH:11]=3)=[O:37])=[C:33]([CH3:35])[N:34]=2)[C:26]1=[O:39])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Cc1nc(N2CCN(Cc3ccccc3)C2=O)sc1C(=O)O
Reactant: NCc1cccc(F)c1
Solvent: NCc1ccccc1
Product: Cc1nc(N2CCN(Cc3ccccc3)C2=O)sc1C(=O)NCc1cccc(F)c1
Yield: 14 %

Procedure:
Following the procedure as describe in Example 8, making variations as required to replace benzylamine with 3-fluorobenzylamine to react with 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a white powder in 14% yield: mp 169-171° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.51 (t, J=5.7 Hz, 1H), 7.50-7.00 (m, 9H), 4.54-4.34 (m, 4H), 3.97 (t, J=7.5 Hz, 2H), 3.42 (t, J=7.5 Hz, 2H), 2.44 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 164.2, 162.3, 161.0, 157.8, 155.5, 151.6, 143.1, 130.6, 129.1, 128.2, 127.9, 123.6, 118.0, 114.4, 114.1, 47.3, 42.6, 42.4, 42.0, 17.5; MS (ES+) m/z 425.3 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[NH:11][N:10]=2)=[C:5]([CH3:22])[CH:4]=1.[H-].[Na+].[CH2:25](Br)[CH:26]=[CH2:27]>>[CH:26]([N:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:19])[F:20])[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[CH3:22])=[N:10]1)([CH3:27])[CH3:25]
Reactant: COc1ccc(-c2n[nH]c3c(C(F)(F)F)cccc23)c(C)c1
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Product: COc1ccc(-c2nn(C(C)C)c3c(C(F)(F)F)cccc23)c(C)c1
Yield: 39.7 %

Procedure:
Prepared according to Method D step B from 3-(4-methoxy-2-methylphenyl)-7-(trifluoro-methyl)-1H-indazole (0.150 g, 0.52 mmol), sodium hydride (60% in oil, 0.025 g, 1.04 mmol) and allyl bromide (0.07 mL, 0.7 mmol) to give the title compound (0.072 g) as a white solid.
Reaction SMILES: [N+:1]([C:4]1[C:5]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([NH2:17])[CH2:13][CH2:12]2)=[N:6][CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl[C:19]1[NH:23][C:22]2[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=2[N:20]=1>CN1CCCC1=O.O>[NH:20]1[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=[C:19]1[NH:17][CH:14]1[CH2:15][CH2:16][CH:11]([NH:10][C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=[CH:7][N:6]=2)[CH2:12][CH2:13]1
Reactant: Clc1nc2ccccc2[nH]1
Reactant: NC1CCC(Nc2ncccc2[N+](=O)[O-])CC1
Solvent: CN1CCCC1=O
Solvent: O
Product: O=[N+]([O-])c1cccnc1NC1CCC(Nc2nc3ccccc3[nH]2)CC1
Temperature: 180 °C
Yield: 53.6 %

Procedure:
A mixture of N1-(3-nitropyridin-2-yl)cyclohexane-1,4-diamine (500 mg, 2.11 mmol) and 2-chloro-1H-benzoimidazole (320 mg, 2.11 mmol) in N-methylpyrrolidinone (5 mL) was heated at 180° C. in microwave for 2 hours. The mixture was diluted with water (60 mL), and extracted with ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated to give N1-(1H-benzo[d]imidazol-2-yl)-N4-(3-nitropyridin-2-yl)cyclohexane-1,4-diamine (400 mg, 1.13 mmol, 53.8% yield) which was used in the next step without further purification.