Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[Cl:17])[C:7](=O)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:19]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].C(Cl)Cl.Cl>[Ti](Cl)(Cl)(Cl)Cl.N1C=CC=CC=1>[Cl:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[Cl:17])[C:7](=[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:19]([O:27][CH2:28][CH3:29])=[O:26])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C1c2cccc(Cl)c2C(=O)c2c(Cl)cccc21
Reactant: CCOC(=O)CC(=O)OCC
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOC(=O)C(C(=O)OCC)=C1c2cccc(Cl)c2C(=O)c2c(Cl)cccc21

Procedure:
In a 250 milliliter round-bottomed flask equipped with a pressure equalizing dropping funnel, there was discharged 10 grams of 1,8-dichloroanthraquinone, 16.5 milliliters of diethyl malonate, and 150 milliliters of methylene chloride under a nitrogen atmosphere. The resulting mixture was then mechanically stirred and cooled with an ice bath. Thereafter, 24 milliliters of titanium tetrachloride was added dropwise through the dropping funnel over a period of 20 minutes, followed by the addition of 45 milliliters of pyridine. The reaction mixture was then stirred at room temperature for 65 hours. Subsequently, 150 milliliters of a dilute aqueous hydrochloric acid solution was slowly added with stirring. The organic phase resulting was separated, washed twice with water, and dried with anhydrous magnesium sulfate. Evaporation of the dried organic solution yielded a yellowish solid which when recrystallized from methanol afforded 7.5 grams of the pure Compound (VIII), mp., 166°-167° C.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]2[C:23]([S:28][CH2:29][C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)=[N:24][CH:25]=[CH:26][CH:27]=2)=[O:21])=[CH:15][CH:14]=1>C(Cl)(Cl)Cl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]2[C:23]([S:28]([CH2:29][C:30]3[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=3)=[O:6])=[N:24][CH:25]=[CH:26][CH:27]=2)=[O:21])=[CH:15][CH:14]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(Nc1ccc(Cl)cc1)c1cccnc1SCc1ccncc1
Solvent: ClC(Cl)Cl
Product: O=C(Nc1ccc(Cl)cc1)c1cccnc1S(=O)Cc1ccncc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 69 %

Procedure:
A solution of m-chloroperoxybenzoic acid (65%, 160 mg, 0.60 mmol) in chloroform (2 mL) was added to a solution of N-(4-chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (300 mg, 0.84 mmol, Compound No. 1-1) in chloroform (18 mL) under ice-cooling, then the mixture was stirred at room temperature for 2 hours. The precipitated solid in the reaction mixture was filtered off, and dried under reduced pressure to give 220 mg of the target compound as a pale yellow solid. (Yield 69%)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]([C:13]3[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([N+:20]([O-])=O)[CH:14]=3)[CH2:11][CH2:10][CH:9]2[C:23]2[CH:29]=[CH:28][C:26]([NH2:27])=[C:25]([N+:30]([O-])=O)[CH:24]=2)=[CH:4][CH:3]=1.C1COCC1>CN(C=O)C.[Pt]=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:9]([C:23]3[CH:24]=[C:25]([NH2:30])[C:26]([NH2:27])=[CH:28][CH:29]=3)[CH2:10][CH2:11][CH:12]2[C:13]2[CH:14]=[C:15]([NH2:20])[C:16]([NH2:17])=[CH:18][CH:19]=2)=[CH:6][CH:7]=1
Reactant: Nc1ccc(C2CCC(c3ccc(N)c([N+](=O)[O-])c3)N2c2ccc(F)cc2)cc1[N+](=O)[O-]
Agent: O=[Pt]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: Nc1ccc(C2CCC(c3ccc(N)c(N)c3)N2c2ccc(F)cc2)cc1N
Temperature: 25 °C
Reaction time: 20 h

Procedure:
The product from Example 29C (0.218 g, 0.50 mmol) was dissolved in DMF (5 mL) then platinum oxide (0.226 g, 0.99 mmol) was added via THF slurry. The flask was evacuated and purged with nitrogen twice, then evacuated and opened to hydrogen balloon. The mixture was stirred at room temperature for 20 h. The solution was taken on to the next step without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][OH:12])=[CH:5][CH:4]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH:11]=[O:12])=[CH:5][CH:4]=1
Reactant: COc1ccc(CCCO)cc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: COc1ccc(CCC=O)cc1
Reaction time: 2 h
Yield: 45.9 %

Procedure:
A solution of 3-(4-methoxyphenyl)propan-1-ol (15.02 g) in dichloromethane (100 ml) was added to a stirred suspension of pyridinium chlorochromate (29 g) in dichloromethane (250 ml). The mixture was stirred for 2 hours then filtered through a kieselguhr pad. The residue was washed with ether (3×500 ml) and the combined liquors were evaporated under reduced pressure. The residual oil was purified by vacuum distillation to give the subtitle compound (6.81 g) as an oil.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH:29]=[CH:28][C:20]3[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=3[CH:18]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[Cl:1][C:2]1[N:7]=[C:6]([C:17]2[CH:29]=[CH:28][C:20]3[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=3[CH:18]=2)[CH:5]=[CH:4][N:3]=1
Reactant: CC(=O)Nc1nc2ccc(B3OC(C)(C)C(C)(C)O3)cc2s1
Reactant: Clc1ccnc(Cl)n1
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: C1COCCO1
Product: CC(=O)Nc1nc2ccc(-c3ccnc(Cl)n3)cc2s1
Temperature: 25 °C
Yield: 59 %

Procedure:
2,4-Dichloropyrimidine (1.060 g, 7115 μmol) and N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide (2.86 g, 8988 μmol) were suspended in 1,4-dioxane (40 mL) to which palladium tetrakis (triphenylphosphine) (782 mg, 677 μmol) was added, followed by 2 mL of 1,4-dioxane and sodium carbonate (7.1 mL, 2.0 M in water, 14200 μmol). Argon was bubbled through the solution for about 1 minute, and the flask was fit with a reflux condensor and placed in a preheated oil bath (95 C) and heated while stirring under argon. When LCMS indicated a complete reaction, the reaction flask was cooled to RT and filtered through Celite® (diatomaceous earth). The Celite® (diatomaceous earth) pad was washed with 1,4-dioxane, and 1:1 DCM/MeOH. The filtrate was concentrated, treated with DCM, and filtered. The solid was washed with DCM, collected, and dried under vacuum to afford the desired product (1.28 g, 4.20 mmol, 95% purity, 56% yield). MS (ESI pos. ion) m/z: 305. Calculated exact mass for C13H9ClN4OS: 304.
Reaction SMILES: [C:1]([NH:9][NH:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]1([N:24]=[C:25]=[S:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CCOCC>[C:1]([NH:9][NH:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:25]([NH:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[S:26])=[CH:15][CH:16]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: S=C=Nc1ccccc1
Reactant: Nc1ccc(NNC(=O)c2ccccc2)cc1
Solvent: CCOCC
Product: O=C(NNc1ccc(NC(=S)Nc2ccccc2)cc1)c1ccccc1

Procedure:
1-Benzoyl-2-(4-aminophenyl)hydrazine (1.14 g, 0.005 mole) and phenyl isothiocyanate (2.7 g, 0.02 mole) were mixed together and heated until contents became fluid. Gentle warming was continued for a few minutes and the reaction mixture was then chilled and diluted with ether. After some stirring and scratching, the product precipitated from solution. It was filtered off, washed thoroughly with ether and dried. Yield 1.7 g (94%), m.p. 149°-151° C.
Reaction SMILES: [CH2:1]([C:3]([C:12]1[CH:25]=[CH:24][C:15]([O:16][CH2:17][C:18]([OH:23])([CH2:21][CH3:22])[CH2:19][CH3:20])=[C:14]([CH3:26])[CH:13]=1)([C:6]1[S:7][CH:8]=[C:9]([CH3:11])[CH:10]=1)[CH2:4][CH3:5])[CH3:2].[Li]CCCC.Cl[C:33]([O:35][CH3:36])=[O:34]>C1COCC1>[CH3:36][O:35][C:33]([C:8]1[S:7][C:6]([C:3]([CH2:4][CH3:5])([C:12]2[CH:25]=[CH:24][C:15]([O:16][CH2:17][C:18]([CH2:21][CH3:22])([OH:23])[CH2:19][CH3:20])=[C:14]([CH3:26])[CH:13]=2)[CH2:1][CH3:2])=[CH:10][C:9]=1[CH3:11])=[O:34]
Reactant: COC(=O)Cl
Reactant: CCC(O)(CC)COc1ccc(C(CC)(CC)c2cc(C)cs2)cc1C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCC(O)(CC)COc1ccc(C(CC)(CC)c2cc(C)c(C(=O)OC)s2)cc1C
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 41 %

Procedure:
3-{4-[1-Ethyl-1-(4-methyl-thiophen-2-yl)-propyl]-2-methyl-phenoxymethyl}-pentan-3-ol, Example 51B (0.50 g, 1.34 mmol) is dissolved in THF (10 mL). The solution is cooled to 0° C., treated with nBuLi (1.6 M, 1.8 mL, 2.95 mmol). It is stirred at 0° C. for 20 min, and methyl chloroformate (113 μL, 1.47 mmol) is added. The reaction is stirred at 0° C. for 10 min and RT for 20 m before it is quenched with satd NH4Cl (5 mL). It is diluted with H2O (10 mL), treated with 0.1 M HCl (10 ml) and extracted with EtOAc (3×15 mL), dried and concentrated. The crude product is purified by chromatography to give the titled compound (0.24 g, 0.56 mmol, 41%). 1H NMR (CD3C3), δ 0.71 (t, J=7.1 Hz, 6H), 0.95 (t, J=7.9 Hz, 6H), 1.64-1.72 (m, 4H), 2.11 (q, J=7.1 Hz, 4H), 2.21 (s, 3H), 2.49 (s, 3H), 3.81 (s, 3H), 6.61 (s, 1H), 6.72 (d, J=8.4 Hz, 1H), 6.85-7.01 (m, 2H). LC/MS (m/z): calcd for C25H40NO4S (M+NH4)+: 450.3; found: 450.3.
Reaction SMILES: [Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:11])[N:7]([CH2:12][CH2:13][CH2:14][CH2:15]C(OCC)=O)[C:6](=[O:21])[N:5]([CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:4]=2[N:3]=1.CC[O-].[Na+].[Cl:31][C:32]1[CH:33]=[C:34]([CH2:38]/[C:39](=[N:42]/[H])/[NH:40][OH:41])[CH:35]=[CH:36][CH:37]=1>CCO>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:11])[N:7]([CH2:12][CH2:13][CH2:14][C:15]3[O:41][N:40]=[C:39]([CH2:38][C:34]4[CH:35]=[CH:36][CH:37]=[C:32]([Cl:31])[CH:33]=4)[N:42]=3)[C:6](=[O:21])[N:5]([CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C:4]=2[N:3]=1
Reactant: CCCCCn1c(=O)n(CCCCC(=O)OCC)c(=O)c2[nH]c(Cl)nc21
Reactant: [H]/N=C(/Cc1cccc(Cl)c1)NO
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCCCn1c(=O)n(CCCc2nc(Cc3cccc(Cl)c3)no2)c(=O)c2[nH]c(Cl)nc21
Temperature: 140 °C
Yield: 49.3 %

Procedure:
Ethyl 5-(8-chloro-2,6-dioxo-3-pentyl-2,3,6,7-tetrahydro-1H-purin-1-yl)pentanoate (70 mg, 0.19 mmol) was dissolved in EtOH. The solution was treated with a 21% solution of NaOEt in EtOH (78 μl, 0.21 mmol) and (1Z)-2-(3-chlorophenyl)-N-hydroxyethanimidamide (38 mg, 0.21 mmol). The reaction was heated in the microwave at 140° C. for 10 min. The mixture was partitioned between EtOH and 2M HCl (aq). The organic layer was decanted off and concentrated. The crude product was purified on the MDAP. The product fractions were combined and concentrated to give the title compound as a white solid (46 mg, 49%).
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([C:13]([OH:19])=[C:14]([C:17]#[N:18])[C:15]#[N:16])[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:20](OC)(OC)OC>>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]([O:19][CH3:20])=[C:14]([C:15]#[N:16])[C:17]#[N:18])[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#CC(C#N)=C(O)c1cnn(Cc2ccccc2)c1
Reactant: COC(OC)OC
Product: COC(=C(C#N)C#N)c1cnn(Cc2ccccc2)c1
Yield: 51.8 %

Procedure:
A solution of 2-((1-benzyl-1H-pyrazol-4-yl)(hydroxy)methylene)malononitrile (26.5 g, 106 mmol) in CH(OMe)3 (250 mL) was heated to 75° C. for 16 hr. Then the solution was concentrated. The residue was washed with MeOH (50 mL) to give 14.5 g (51.8%) of 2-((1-benzyl-1H-pyrazol-4-yl)(methoxy)methylene)malononitrile as an off-white solid. 1H NMR (DMSO-d6) δ 8.71 (s, 1H), 8.08 (s, 1H), 7.42-7.24 (m, 5H), 5.46 (s, 2H), 4.12 (s, 3H). MS (ESI) m/e [M+1]+ 264.9.
Reaction SMILES: I[C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][NH:9][C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[CH:27][C:28]([C:31]#[CH:32])=[N:29][CH:30]=2)=[CH:21][CH:20]=1>>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[CH:26]=[CH:27][C:28]([C:31]#[C:32][C:2]3[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH2:8][NH:9][C:10]4[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=4)=[CH:4][CH:3]=3)=[N:29][CH:30]=2)=[CH:23][CH:24]=1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Reactant: Ic1ccc(OCCNc2ccncc2)cc1
Product: Clc1ccc(-c2ccc(C#Cc3ccc(OCCNc4ccncc4)cc3)nc2)cc1

Procedure:
Prepared according to general working method I from [2-(4-iodo-phenoxy)-ethyl]-pyridin-4-yl-amine (95 mg, 0.28 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (70 mg, 0.33 mmol).
Reaction SMILES: C([O:3][C:4]([C:6]1[S:10][C:9]([Cl:11])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:5])C>O1CCCC1.[OH-].[Na+]>[Cl:11][C:9]1[S:10][C:6]([C:4]([OH:5])=[O:3])=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:8]=1
Reactant: CCOC(=O)c1sc(Cl)nc1-c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1sc(Cl)nc1-c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.6 %

Procedure:
A mixture of 2-Chloro-4-phenyl-thiazole-5-carboxylic acid ethyl ester (1 g, 3.74 mmol) in tetrahydrofuran (10 ml) and NaOH (15%, 4.8 ml) was stirred at room temperature for 2 hr. After removal of tetrahydrofuran, the aqueous was neutralized with aqueous hydrochloric acid (3 N) to ˜pH=3. The solid was filtered and washed with water, dried in air to give 2-chloro-4-phenyl-thiazole-5-carboxylic acid (0.83 g). The acid was then dissolved in acetonitrile, and EDC (0.62 g, 4 mmol) was added. The mixture was stirred under an ammonia balloon for 2 hrs. Acetonitrile was removed, the residue was diluted with ethyl acetate and washed with water. Ethyl acetate solution was dried over MgSO4. After removal of MgSO4 and solvent, the residue was diluted with tetrahydrofuran (10 ml), followed by adding triethyl amine (0.5 ml). The mixture was cooled in ice, and trifluoroacetic anhydride (0.85 ml) was added dropwise. After the addition, the reaction mixture was stirred overnight at RT. The mixture was then diluted with ethyl acetate and washed with sat. sodium bicarbonate, dried over MgSO4. After removal of the magnesium sulfate and solvent, the residue was purified on Isco (0-20% gradient ethyl acetate in hexane) to give product (287.9 mg, yield 35% overall). 1H-NMR (CDCl3) 8.07-8.13 (m, 2H); 7.47-7.53 (m, 3H); 4.11 (q, 1H); 1.22 (t, 3H). MS M/z 221 (M+1)
Reaction SMILES: O.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].CO[CH:12]1[CH2:16][CH2:15][CH:14](OC)O1>C(O)(=O)C>[N:2]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[CH:12]=[CH:16][CH:15]=[CH:14]1
Reactant: Nc1ccccc1O
Reactant: COC1CCC(OC)O1
Solvent: O
Solvent: CC(=O)O
Product: Oc1ccccc1-n1cccc1
Temperature: 100 °C
Yield: 74.1 %

Procedure:
A 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, a heating mantle, a water cooled reflux condenser, a temperature probe/controller and a nitrogen inlet/outlet. The vessel was charged with (50 g, 0.46 mol) of 2-aminophenol and acetic acid (750 mL) which provided a very dark solution. Stirring was commenced and the vessel was charged with 2,5-dimethoxytetrahydrofuran (59.4 mL, 0.458 mol) dropwise over 2 minutes. The dark mixture was then heated at 100° C. for 15 min. The mixture was allowed to cool to room temperature and was filtered through a pad of Celite to remove residual solids. The filtrate was concentrated under reduced pressure azeotroping with toluene. The residual oil was dissolved in ethyl acetate (1000 mL) and was partitioned with water (500 mL). The organic layer was separated and was washed with water (500 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to provide 2-(1H-pyrrol-1-yl)phenol (54 g, 74%) as a dark oil. ESI-MS m/z calc. 159.1. found 160.2 (M+1)+. Retention time: 2.67 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.37-7.23 (m, 2H), 7.13-6.97 (m, 2H), 6.91 (t, J=1.9 Hz, 2H), 6.43 (t, J=1.9 Hz, 2H), 5.35 (s, 1H). 3-(1H-Pyrrol-1-yl)pyridin-2-ol was also synthesized using the procedure described above.
Reaction SMILES: Cl.Cl[C:3](=[C:8](Cl)[C:9]([F:12])([F:11])[F:10])[C:4]([F:7])([F:6])[F:5]>>[F:5][C:4]([F:7])([F:6])/[CH:3]=[CH:8]\[C:9]([F:12])([F:11])[F:10]
Reactant: FC(F)(F)C(Cl)=C(Cl)C(F)(F)F
Agent: Cl
Product: FC(F)(F)/C=C\C(F)(F)F

Procedure:
Additional products of the reaction may include partially hydrodechlorinated intermediates; saturated hydrogenated compounds; various partially chlorinated intermediates or saturated compounds; and hydrogen chloride (HCl). For example, wherein the chlorofluoroalkene is 2,3-dichloro-1,1,1,4,4,4-hexafluoro-2-butene (CFC-1316mxx, E- and/or Z-isomers), the compounds formed in addition to E- and/or Z-1,1,1,4,4,4-hexafluoro-2-butene (E- and/or Z-HFC-1336mzz) may include, 1,1,1,4,4,4-hexafluorobutane (HFC-356mff), pentafluorobutane (HFC-1345, different isomers), 2-chloro-1,1,1,4,4,4-hexafluorobutane (HFC-346mdf), E and/or Z-2-chloro-1,1,1,4,4,4-hexafluoro-2-butene (E- and/or Z-HCFC-1326mxz), and 1,1,1,4,4,4-hexafluoro-2-butyne (HFB).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10](=[O:19])[C:11]1[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=1.ClC1C=C(C=CC=1)C(OO)=[O:25]>C(Cl)(Cl)Cl>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[NH:9][C:10](=[O:19])[C:11]1[CH:12]=[CH:13][C:14]([S:17]([CH3:18])=[O:25])=[CH:15][CH:16]=1
Reactant: CSc1ccc(C(=O)Nc2c(C)cccc2C)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: Cc1cccc(C)c1NC(=O)c1ccc(S(C)=O)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
Ten grams of N-(2,6-dimethylphenyl)-4-(methylthio)benzamide were dissolved in a small volume of chloroform and chilled to 0° C. A solution of 7.9 g of m-chloroperoxybenzoic acid in chloroform was added in dropwise fashion. The reaction was stirred at room temperature for 1 hour, washed with a sodium bicarbonate solution, water, and a saturated chloride solution, dried over sodium sulfate and evaporated in vacuo. The resulting foam was chromatographed over silica gel eluting with an ethyl acetate in hexane gradient. The appropriate fractions were combined and the solvent removed in vacuo and the resulting residue was crystallized from ethyl acetate/hexane providing the desired title product in 59% yield, m.p. 144-146° C.
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)[N:3]=1.[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>ClCCl.N1C=CC=CC=1>[CH3:1][C:2]1[C:7]([NH:8][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:6][CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)[N:3]=1
Reactant: Cc1nc(N2CC[C@H](N3CCC[C@@H]3C)C2)ccc1N
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1nc(N2CC[C@H](N3CCC[C@@H]3C)C2)ccc1NC(=O)c1ccccc1

Procedure:
The title compound was synthesized substantially in the same manner as Example 3 by coupling of 2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamine (0.025 g, 0.096 mmol) with benzoyl chloride (0.041 g, 0.288 mmol) in dichloromethane (3 mL) and pyridine (0.5 mL) to obtain 0.0084 (24% yield) of the title compound.
Reaction SMILES: CON(C)[C:4]([C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[O:23][C:24]([F:27])([F:26])[F:25])[CH:14]=[CH:15][CH:16]=2)[CH:10]=1)=[O:5].Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1>>[N:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C:4]([C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[O:23][C:24]([F:26])([F:25])[F:27])[CH:14]=[CH:15][CH:16]=2)[CH:10]=1)=[O:5]
Reactant: CON(C)C(=O)c1cn(-c2cccc(-c3ccccc3OC(F)(F)F)c2)cn1
Reactant: Brc1ccccn1
Product: O=C(c1ccccn1)c1cn(-c2cccc(-c3ccccc3OC(F)(F)F)c2)cn1

Procedure:
This compound is prepared by method C using compound 12f and 2-bromopyridine
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21]([C:24]([NH:26][CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[O:25])=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[CH2:34]([NH2:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[CH2:34]([NH:41][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21]([C:24]([NH:26][CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[O:25])=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:4][CH:3]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: NCc1ccccc1
Reactant: O=C(NCc1cccnc1)c1ccc2n1Cc1ccccc1N(C(=O)c1ccc(Cl)nc1)C2
Solvent: ClCCl
Product: O=C(NCc1cccnc1)c1ccc2n1Cc1ccccc1N(C(=O)c1ccc(NCc3ccccc3)nc1)C2
Temperature: 100 °C
Yield: 46.6 %

Procedure:
A mixture of 10-[(6-chloropyridin-3-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 117 (0.100 g, 0.219 mmol) and benzylamine (0.12 mL, 1.094 mmol) was heated to 100° C. in a sealed tube for 17 hours. The cooled reaction mixture was then diluted with dichloromethane (10 mL), washed with saturated aqueous sodium bicarbonate solution (10 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a yellow semi-solid. Purification by flash chromatography using a solvent gradient of 1 to 5% methanol in dichloromethane gave a white solid that was triturated with diethyl ether to afford the title compound (0.054 g, 47%) as a white solid.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[CH:17]=1.[CH3:29][CH:30](Cl)[CH2:31][N:32]([CH3:34])[CH3:33]>>[F:28][C:2]([F:1])([F:27])[C:3]1[CH:26]=[CH:25][CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([O:15][CH:30]([CH3:29])[CH2:31][N:32]([CH3:34])[CH3:33])[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[CH:17]=1
Reactant: Cc1cccc(-c2nc3ccc(O)cc3n2Cc2ccccc2C(F)(F)F)c1
Reactant: CC(Cl)CN(C)C
Product: Cc1cccc(-c2nc3ccc(OC(C)CN(C)C)cc3n2Cc2ccccc2C(F)(F)F)c1

Procedure:
The title compound was prepared essentially as described above except that the compound of Example 120 was reacted with 1-methyl-2-(N,N-dimethylamino)ethyl chloride, yielding the title product as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=1.[CH2:13](O)[CH2:14][CH2:15][OH:16]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH:9]([CH3:10])[CH3:11])[O:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)c1ccc(Br)cc1
Reactant: OCCCO
Product: CC(C)C1(c2ccc(Br)cc2)OCCCO1
Yield: 42 %

Procedure:
Using an analogous procedure to that described in Example 62, part (i), but starting from 1-bromo-4-(2-methylpropanoyl)benzene and 1,3-propanediol there was thus obtained (in 42% yield) 2-(4-bromophenyl)-2-isopropyl-1,3-dioxane (4.25 g), b.p. 116° C. at 0.4 mm Hg 1H NMR (acid free CDCl3): 0.8 (d, 3H), 1.15-1.25 (m, 1H), 1.85 (m, 2H), 2.0-2.1 (m, 1H), 3.68 (d of t, 2H), 3.75-3.85 (m, 2H) 7.15-7.25 (m, 2H), 7.45-7.55 (m, 2H): mass spectrum (CI+) 285 (M+H)+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH2:7]([O:9][C:10]1[N:15]=[C:14](SC)[N:13]=[C:12]([N:18]2[CH2:23][CH2:22][S:21](=[O:24])[CH2:20][CH2:19]2)[C:11]=1[N+:25]([O-:27])=[O:26])[CH3:8]>O1CCOCC1>[CH2:7]([O:9][C:10]1[N:15]=[C:14]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)[N:13]=[C:12]([N:18]2[CH2:19][CH2:20][S:21](=[O:24])[CH2:22][CH2:23]2)[C:11]=1[N+:25]([O-:27])=[O:26])[CH3:8]
Reactant: CCOc1nc(SC)nc(N2CCS(=O)CC2)c1[N+](=O)[O-]
Reactant: C1CNCCN1
Solvent: C1COCCO1
Product: CCOc1nc(N2CCNCC2)nc(N2CCS(=O)CC2)c1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
52 gm (0.6 mol) of piperazine were dissolved in 120 ml of boiling dioxane. 61.5 gm (0.18 mol) of 6-ethoxy-2-methylthio-5-nitro-4-(1-oxido-thiomorpholino)-pyrimidine were added over a period of 30 minutes to this solution. After refluxing for 45 minutes, the reaction mixture was poured into 1.5 liters of ice-water, and the yellow precipitate formed thereby was suction-filtered off, washed and recyrstallized from ethanol. Yield: 45.1 gm (65.8% of theory; m.p. 222°-223°C.