Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S.[C:2]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH:13]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:18]=3)[O:12][C:11]2=[O:28])=[CH:6][CH:5]=1)#[N:3].[N:29]1C=CC=CC=1>C(N(CC)CC)C>[C:2]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:14][CH:13]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:18]=3)[O:12][C:11]2=[O:28])=[CH:8][CH:9]=1)(=[NH:29])[NH2:3]
Reactant: c1ccncc1
Reactant: COC(=O)Cc1ccc(OCC2CN(c3ccc(C#N)cc3)C(=O)O2)cc1
Agent: S
Solvent: CCN(CC)CC
Product: COC(=O)Cc1ccc(OCC2CN(c3ccc(C(=N)N)cc3)C(=O)O2)cc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
H2S gas is passed, at -10°, into a solution of 1.2 g of 3-p-cyanophenyl-5-(p-methoxycarbonylmethylphenoxymethyl)oxazolidin-2-one (obtainable in accordance with Example 1) in 50 ml of pyridine and 7 ml of triethylamine. The mixture is subsequently stirred at room temperature for 14 h and concentrated by evaporation; the residue is dissolved in 50 ml of acetone and treated with 9 ml of methyl iodide. After this mixture has been stirred for a further 6 h, it is filtered and the residue is washed with 5 ml of acetone and dissolved in 30 ml of methanol; 4.6 g of ammonium acetate are added to this solution, which is stirred at room temperature for 24 h. Following the customary working-up, 3-p-amidinophenyl-5-(p-methoxycarbonylmethylphenoxymethyl)oxazolidin-2-one (semihydriodide) is obtained, M.p. 151-152°.
Reaction SMILES: [NH2:1][C:2]1[C:7]2=[C:8]([C:24]3[CH:25]=[CH:26][C:27]4[C:31]([CH:32]=3)=[N:30][N:29]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:28]=4)[CH:9]=[C:10]([C:11]3(O)[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:22])[CH2:18][N:19]([CH3:21])[CH3:20])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl.CCO>[CH2:33]([N:29]1[CH:28]=[C:27]2[C:31]([CH:32]=[C:24]([C:8]3[CH:9]=[C:10]([C:11]4[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:22])[CH2:18][N:19]([CH3:20])[CH3:21])[CH:12]=4)[N:6]4[C:7]=3[C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)[CH:25]=[CH:26]2)=[N:30]1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: CN(C)CC(=O)N1CCCC(O)(c2cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c3c(N)ncnn23)C1
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: CCO
Solvent: ClCCl
Product: CN(C)CC(=O)N1C=C(c2cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c3c(N)ncnn23)CCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 73.6 %

Procedure:
To a cooled (0° C.) mixture of 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-1-(N,N-dimethylglycyl)piperidin-3-ol (58 mg, 0.11 mmol) and N,N-diisopropylethylamine (58 μL, 0.33 mmol) in CH2Cl2 (2 mL) was added trifluoroacetic anhydride (31 μL, 0.22 mmol), dropwise. The ice bath was removed and the mixture was stirred at rt for 2 h. The reaction was cooled (0° C.) and additional N,N-diisopropylethylamine (58 μL) and trifluoroacetic anhydride (31 μL) was added. The ice bath was removed and the reaction was stirred at rt for 5 h. Water (5 mL) was added and the layers were separated. The aqueous phase was extracted with CH2Cl2 (2×5 mL) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated. To a solution of the residue in EtOH (3 mL) was added NaOH (66 mg, 1.66 mmol). The mixture was stirred at rt for 17 h. The mixture was partitioned between EtOAc (10 mL) and H2O (10 mL). The layers were separated and the organic phase was washed with H2O (10 mL), brine, dried (Na2SO4) and concentrated. The material was crystallized from EtOAc/hexanes to afford 41 mg (73%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.66-8.70 (m, 1H,) 8.55 (s, 1 H), 7.94-7.98 (m, 1 H), 7.81 (d, 1 H), 7.61 (s, 1 H), 7.27-7.36 (m, 5 H), 7.15 (dd, 1 H), 6.76-6.80 (m, 1 H), 5.65 (s, 2 H), 3.56-3.79 (m, 2 H), 3.22-3.28 (m, 2 H), 2.48-2.59 (m, 2 H), 2.17-2.25 (m, 6 H), 1.85-1.94 (m, 2 H); ES-MS m/z 507.13 [M+H]+, HPLC RT (min) 2.31.
Reaction SMILES: [CH2:1]1[CH2:11][C:9](=O)[C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2]1.Cl.[NH2:13][OH:14]>CO>[C:9]1(=[N:13][OH:14])[C:8]2[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:2][CH2:1][CH2:11]1
Reactant: O=C1CCCc2ccccc21
Reactant: NO
Agent: Cl
Solvent: CO
Product: ON=C1CCCc2ccccc21
Temperature: 22 °C
Yield: 63.9 %

Procedure:
To a solution of α-tetralone (100.0 g, 0.68 mol) in 300 mL of methanol was added hydroxylamine hydrochloride (71.0 g, 1.03 mol) and the resulting solution was stirred at reflux for 2 hours. The mixture was allowed to cool to 20-24° C. and was concentrated under reduced pressure. The resulting mixture was diluted with 1 L of water and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was crystallized from isopropanol to provide 70.0 g (63%) of the desired compound as an off-white solid.
Reaction SMILES: [O:1]([C:8]1[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:16]1[CH2:22][C:20](=[O:21])[NH:19][C:17]1=[S:18].C([O-])(=O)C.[Na+].C(O)(=O)C>O>[O:1]([C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[C:22]2[S:16][C:17](=[S:18])[NH:19][C:20]2=[O:21])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CSC(=S)N1
Reactant: O=Cc1ccc(Oc2ccccc2)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: O=C1NC(=S)SC1=Cc1ccc(Oc2ccccc2)cc1
Yield: 54.9 %

Procedure:
A mixture of 9.9 g (50.0 mmol) of 4-phenoxybenzaldehyde, 6.8 g (51.1 mmol) of rhodanine, 15.5 g of sodium acetate and 60 ml of acetic acid was heated on a steam bath for two hours. The reaction solution was then poured into water causing crude product to precipitate. The precipitate was filtered and then washed successively with water followed by diethyl ether to provide 8.6 g of title product, m.p. 195°-200° C.
Reaction SMILES: [C:1]([O:4][CH2:5]/[CH:6]=[C:7](/[CH3:27])\[CH2:8][CH2:9]/[CH:10]=[C:11](\[CH3:26])/[CH2:12][CH2:13][CH:14]([O:18][Si](C(C)(C)C)(C)C)[C:15]([CH3:17])=[CH2:16])(=[O:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:4][CH2:5]/[CH:6]=[C:7](/[CH3:27])\[CH2:8][CH2:9]/[CH:10]=[C:11](\[CH3:26])/[CH2:12][CH2:13][CH:14]([OH:18])[C:15]([CH3:17])=[CH2:16])(=[O:3])[CH3:2]
Reactant: C=C(C)C(CC/C(C)=C/CC/C(C)=C\COC(C)=O)O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C=C(C)C(O)CC/C(C)=C/CC/C(C)=C\COC(C)=O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
The purified product obtained, (2Z,6E)-10-(tert.-butyldimethylsilyloxy)-3,7,11-trimethyl-2,6,11-dodecatrienyl acetate, is dissolved in 5 ml of tetrahydrofuran and treated with 320 mg of tetrabutylammonium fluoride. The solution is stirred at room temperature for 16 hours. After removing the solvent on a rotary evaporator the residue is chromatographed on silica gel with ether-hexane 1:1. There is obtained (2Z,6E)-10-hydroxy-3,7,11-trimethyl-2,6,11-dodecatrienyl acetate which exhibits the following bands in the IR spectrum: 3454 cm-1, 1739 cm-1, 1651 cm-1, 1446 cm-1, 1236 cm-1, 1023 cm-1, 955 cm-1, 898 cm-1.
Reaction SMILES: [ClH:1].[CH2:2]([N:9](C)[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=[O:12])C1C=CC=CC=1>[Pd].C(O)(=O)C>[ClH:1].[F:19][C:16]1[CH:15]=[CH:14][C:13]([C:11](=[O:12])[CH2:10][NH:9][CH3:2])=[CH:18][CH:17]=1
Reactant: CN(CC(=O)c1ccc(F)cc1)Cc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Product: CNCC(=O)c1ccc(F)cc1

Procedure:
1.2 g of 10% palladium on charcoal is added under a nitrogen atmosphere to a solution of 10 g (31 mmol) of the compound from Example 1 in 200 ml of glacial acetic acid. After hydrogenation in a shaking apparatus (hydrogen uptake about 700 ml), the catalyst is filtered off, the solvent is removed by distillation and the product is washed with water and dried.
Reaction SMILES: [CH3:1][N:2]([OH:14])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=1[Cl:13])=[O:4].C(=O)([O-])[O-].[K+].[K+].CS(C)=O.Cl[CH:26](Cl)[CH3:27]>O>[CH3:1][N:2]1[C:3](=[O:4])[N:5]([C:6]2[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=2[Cl:13])[CH2:27][CH2:26][O:14]1
Reactant: CC(Cl)Cl
Reactant: CN(O)C(=O)Nc1ccc(Cl)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CN1OCCN(c2ccc(Cl)cc2Cl)C1=O
Temperature: 20 °C
Reaction time: 0.33 h
Yield: 65.5 %

Procedure:
A mixture of 11 g of N-methyl-N-hydroxy-N'-(2,4-dichlorophenyl)-urea, 55 g of potassium carbonate and 66 ml of dimethylsulfoxide was stirred for 20 minutes at 20° C and then 11 g of dichloroethane were added. The mixture was stirred for 16 hours at 20°-25° C and was then poured into water. The mixture was vacuum filtered and the recovered precipitate was taken up in ethyl acetate. The solution was dried and evaporated to dryness under reduced pressure. The residue was crystallized from isopropyl ether to obtain 8 g of 2-methyl-4-(2',4'-dichlorophenyl)-3-oxo-5,6-dihydro-1,2,4-oxadiazine melting at 94°-95° C.
Reaction SMILES: C(N(CC)C(C)C)(C)C.[C:10](Cl)(=[O:13])[CH:11]=[CH2:12].[CH3:15][O:16][CH2:17][CH2:18][NH2:19]>ClCCl>[CH3:15][O:16][CH2:17][CH2:18][NH:19][C:10](=[O:13])[CH:11]=[CH2:12]
Reactant: C=CC(=O)Cl
Reactant: COCCN
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CC(=O)NCCOC
Temperature: 25 °C
Reaction time: 0.03 h

Procedure:
N,N-Diisopropylethylamine (3.21 g, 25 mmol) was added to a stirred, ice-cooled solution of acryloyl chloride (2.25 g, 25 mmol) in dichloromethane (30 ml) under nitrogen followed, 2 minutes later, by 2-methoxyethylamine (1.92 g, 25.6 mmol) added dropwise over 1 hour. The cooling bath was removed, then the reaction mixture stirred for 18 hours at room temperature and washed twice with water. The combined aqueous washings were saturated with sodium chloride and exhaustively extracted with dichloromethane. All the dichloromethane solutions were combined, washed twice with 2M aqueous sodium carbonate solution, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a solvent gradient of ethanol: dichloromethane (0:100 to 5:95), to yield the required amide as an oil. Rf 0.63 (SS 7). Found: C,54.97; H,9.24; N,10.68. C6H11NO2 ; 0.10 H2O requires C,55.04; H,8.62; N,10.70%. LRMS: m/z 130.4 (M+1)+.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[CH:4][N:3]=1.[F:17][C:18]1[CH:33]=[CH:32][C:21]([O:22][C:23]2[N:28]=[CH:27][C:26]([C@@H:29]([NH2:31])[CH3:30])=[CH:25][CH:24]=2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:22][C:23]2[N:28]=[CH:27][C:26]([C@@H:29]([NH:31][C:2]3[N:7]=[C:6]([N:8]4[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]4=[O:16])[CH:5]=[CH:4][N:3]=3)[CH3:30])=[CH:25][CH:24]=2)=[CH:32][CH:33]=1
Reactant: CC(C)[C@H]1COC(=O)N1c1ccnc(Cl)n1
Reactant: C[C@H](N)c1ccc(Oc2ccc(F)cc2)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(Oc3ccc(F)cc3)nc2)n1
Temperature: 107.5 °C
Yield: 14 %

Procedure:
To (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (28 mg, 0.116 mmol) was added (S)-1-(6-(4-fluorophenoxy)pyridin-3-yl)ethanamine (46.7 mg, 0.174 mmol), DMSO (0.6 ml) and Hunig's Base (0.071 ml, 0.406 mmol). The reaction was heated at 105-110° C. for 24 hours or until done by LCMS. The reaction was let cool, 0.5 ml of DMSO was added, filtered, purified by prep LC and lyophilized to give 7.1 mg of (S)-3-(2-((S)-1-(6-(4-fluorophenoxy)pyridin-3-yl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one as the TFA Salt. LCMS m/z 438.2 (M+H)+, Rt 0.82 min.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[C:15]2[O:14][CH2:13][C:12](=[O:16])[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)([O-:5])=[O:4].[CH3:17]I.O>CN(C)C=O>[CH3:17][N:11]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([N+:3]([O-:5])=[O:4])[C:15]=2[O:14][CH2:13][C:12]1=[O:16]
Reactant: O=C1COc2c(cccc2[N+](=O)[O-])N1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN1C(=O)COc2c1cccc2[N+](=O)[O-]
Reaction time: 0.17 h

Procedure:
Sodium hydride (60%) (300 mg, 7.50 mmol) was added to a solution of 8-nitro-2 H-1,4-benzoxazin-3(4 H)-one (971 mg, 5.00 mmol) in N,N-dimethylformamide (15 mL) at room temperature, the mixture was stirred for 10 min, and then methyl iodide (374 μL, 6.00 mmol) was added dropwise thereto. The mixture was stirred at room temperature for 3 hr and water was added to the reaction mixture. The resulting precipitate was collected by filtration, washed with ethyl acetate and water, and then dried at 60° C. under reduced pressure to afford 4-methyl-8-nitro-2 H-1,4-benzoxazin-3(4 H)-one as a pale yellow amorphous substance (453 mg).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[NH:13][C:12](=[S:14])[N:11]([CH3:15])[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:8]=2[CH:22]=1.[CH3:23]I>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]=[C:12]([S:14][CH3:23])[N:11]([CH3:15])[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:8]=2[CH:22]=1
Reactant: CN1N=C(c2ccccc2)c2cc(Cl)ccc2NC1=S
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NN1C
Temperature: 6 °C

Procedure:
The reaction vessel was charged with 11.5 grams (479 moles) of sodium hydride (99%) and 850 ml of dry N,N-dimethylformamide. To this mixture, 132 grams (437 moles) of 7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,3,4-benzotriazepine-2-thione (Example 15) was added with stirring using a screw feed solid addition apparatus while the system was flushed with dry nitrogen. Thirty minutes after addition was completed, the resulting reaction mass was cooled to about 6° C. and 30.0 ml (482 moles) of methyl iodide was added quickly with stirring. The temperature of the reaction mixture rose to about 20° C. The reaction mass was stirred for an additional 30 minutes in an ice bath and for about two hours at ambient temperature. The reaction mixture was poured into about 7 liters of ice water. The yellow precipitate which formed was collected, washed with water, and dissolved in about 1 liter of diethyl ether. The ether solution was washed with water, dried with magnesium sulfate, and concentrated in vacuo on a rotary evaporator. The title compound was left as a viscous yellow-orange oil which solidified on triturating with 100 ml of hexane. The resulting yellow product had a melting point of 100° C. to 102° C. Elemental analysis was used to confirm the structure.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10]C)[CH:7]=[CH:6][C:4]=1[NH2:5].C[O:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=1[O:23]C)C(O)=O>>[OH:10][C:8]1[CH:7]=[CH:6][C:4]2[N:5]=[C:1]([C:20]3[CH:21]=[C:22]([OH:23])[C:14]([OH:13])=[CH:15][CH:16]=3)[O:2][C:3]=2[CH:9]=1
Reactant: COc1ccc(C(=O)O)cc1OC
Reactant: COc1ccc(N)c(OC)c1
Product: Oc1ccc2nc(-c3ccc(O)c(O)c3)oc2c1

Procedure:
The title compound was prepared in substantially the same manner as described in Example 1, from 2,4-dimethoxyaniline, and 3,4-dimethoxybenzoic acid and was obtained as a white solid, m.p. 282–284° C.; MS m/e 242 (M−H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([N:14]3[CH2:19][CH2:18][N:17]([S:20]([CH2:23][C@H:24]([CH:29]([CH3:31])[CH3:30])[C:25]([NH:27][OH:28])=[O:26])(=[O:22])=[O:21])[CH2:16][CH2:15]3)=N[CH:13]=2)=[CH:4][CH:3]=1.F[C:33]1C=CC(C2C=CC(N3CCN(S(C[C@H](C(C)C)C(O)=O)(=O)=O)CC3)=NC=2)=CC=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:33][C:11]([N:14]3[CH2:19][CH2:18][N:17]([S:20]([CH2:23][C@H:24]([CH:29]([CH3:31])[CH3:30])[C:25]([NH:27][OH:28])=[O:26])(=[O:22])=[O:21])[CH2:16][CH2:15]3)=[N:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ncc(-c3ccc(F)cc3)cn2)CC1)C(=O)NO
Reactant: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ccc(-c3ccc(F)cc3)cn2)CC1)C(=O)O
Product: CC(C)[C@@H](CS(=O)(=O)N1CCN(c2ccc(-c3ccc(F)cc3)cn2)CC1)C(=O)NO
Yield: 61 %

Procedure:
Prepared according to the method for the preparation of 2-(R)-{4-[5-(4-fluorophenyl)pyrimidin-2-yl]piperazine-1-sulfonylmethyl}-N-hydroxy-3-methyl-butyramide, from 2-(R)-{4-[5-(4-fluorophenyl)pyridin-2-yl]piperazine-1-sulfonyl-methyl}-3-methylbutyric acid (0.072 g), to give the title compound as a white solid (0.047 g, 61%).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:16]1[CH:28]=[CH:27][C:19]([C:20]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[I-].[Na+].C(N(CC)CC)C.[F:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][CH:46]=1)[CH2:42]Br.FC(Br)C1C=CC=CC=1>C(#N)C>[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:42][C:41]2[CH:44]=[CH:45][CH:46]=[C:39]([F:38])[CH:40]=2)[C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:16]1[CH:17]=[CH:18][C:19]([C:20]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[O:21])=[CH:27][CH:28]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CCN(CC)C(=O)c1ccc([C@H](c2ccccc2)N2C[C@@H](C)NC[C@@H]2C)cc1
Reactant: Fc1cccc(CBr)c1
Agent: FC(Br)c1ccccc1
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCN(CC)C(=O)c1ccc([C@H](c2ccccc2)N2C[C@@H](C)N(Cc3cccc(F)c3)C[C@@H]2C)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.9 %

Procedure:
A solution of 4-((alpha-S)-alpha-((2S,5R)-2,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide (9.128 g, 24.05 mmol) in acetonitrile (150 mL)) was added to sodium iodide (360 mg, 2.4 mmol) and stirred under nitrogen during the addition of triethylamine (12 mL, (8.76 g), 86.6 mmol), followed by 3-fluorobenzyl bromide (5.9 mL, (9.09 g), 48.1 mmol). An immediate turbidity was observed on addition of the fluorobenzyl bromide, thickening to a white crystalline precipitate over one hour. The reaction mixture was stirred under nitrogen overnight at room temperature. The solvent was removed by evaporation, and saturated sodium bicarbonate solution (25 mL) added to the residue. The copious white precipitate was filtered off, washed well with water and dried under vacuum at room temperature to give 4-((alpha-S)-alpha-((2S,5R)-2,5-dimethyl-4-(3-fluorobenzyl)-1-piperazinyl)benzyl)-N,N-diethylbenzamide (10.54 g, 89.2%). Calc. for C31H38FN3O 0.2 H2O: C, 75.79; H, 7.88; N, 8.55; F, 3.87. Found C, 75.80; H, 7.78; N, 8.49; F, 3.75%.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[CH2:9][CH2:8][C@H:7]([C:10]([OH:12])=[O:11])[CH2:6]1)=[N+]=[N-].ClCCl>CO.CN(C)C=O.[Pd]>[NH2:1][CH2:4][C@@H:5]1[CH2:9][CH2:8][C@H:7]([C:10]([OH:12])=[O:11])[CH2:6]1
Reactant: [N-]=[N+]=NC[C@@H]1CC[C@H](C(=O)O)C1
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Solvent: CN(C)C=O
Product: NC[C@@H]1CC[C@H](C(=O)O)C1

Procedure:
A mixture of cis-3-azidomethylcyclopentancarboxylic acid (0.9 g, 5.3 mmol) in methanol (about 30 mL) was hydrogenated at about 50 psi and room temperature in the presence of 10% Pd on carbon (about 40 mg) for about 1 h. The catalyst was removed by filtration and the filtrate concentrated to give a syrup. When the syrup was dissolved in dimethylformamide and dichloromethane for acetylation (next step), formation of some white precipitate occurred. The precipitate was collected by filtration, washed with dichloromethane and dried to give cis-3-aminomethylcyclopentanecarboxylic acid as a white powder, mp 186-188° C. The yield of syrup was 0.7 g (100%). The white solid obtained was about 0.35 g. The remainder of the material from the dimethylformamide and dichloromethane mixture was not recovered, but was used for the acetylation step.
Reaction SMILES: C([O-])(O)=O.[Na+].[C:6]1([CH3:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:13]1([CH3:22])[CH:18]=[CH:17][C:16]([C:19](O)=[O:20])=[CH:15][CH:14]=1>O>[CH3:12][C:6]1[CH:11]=[CH:10][C:9]([C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:22])=[CH:14][CH:15]=2)=[O:20])=[CH:8][CH:7]=1
Reactant: Cc1ccc(C(=O)O)cc1
Reactant: Cc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1ccc(C(=O)c2ccc(C)cc2)cc1
Yield: 28 %

Procedure:
The three water extracts from Example 4 (excluding the NaHCO3 extracts) were charged into a 200 mL flask along with toluene (50 mL) and para-toluic acid (1.36 g). The mixture was heated and water was removed azeotropically as in Example 3;once approximately 40 mL of water had been removed a further 50 mL toluene was added. Then, when a total of 75 mL of water had been removed, a final 25 mL toluene was added. The reflux was terminated after 18 hours. After workup (as in Example 3) the reaction gave crude 4,4′-dimethylbenzophenone (0.58 g, 28% yield), which was again practically pure by 1H NMR (M.P. 86.5-87.5° C.). Removal of water from the three water extracts recovered 3.40 g cerium (III) trifluoromethanesulfonate as a damp, off-white solid).
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][O:4][CH:3]=1.C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].[C:19]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>CCO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:19]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:24]=[CH:23][C:22]([C:2]2[CH:6]=[CH:5][O:4][CH:3]=2)=[CH:21][CH:20]=1
Reactant: Brc1ccoc1
Reactant: OB(O)c1ccc(-c2ccccc2)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: c1ccccc1
Product: c1ccc(-c2ccc(-c3ccoc3)cc2)cc1
Temperature: 80 °C
Yield: 75.9 %

Procedure:
A biphasic mixture of 3-bromofuran (2.90 mL, 32.1 mmol), benzene (70 mL), and 2N aqueous Na2CO3 (50 mL) was degassed and purged with argon. Tetrakis(triphenylphosphine) palladium(0) (3.7 g, 3.2 mmol) arid a solution of 4-biphenylboronic acid (6.3 g, 32.1 mmol) in EtOH (50 mL) were added sequentially. The mixture was heated at 80° C. for 18 hours, allowed to cool, and partitioned between CH2Cl2 and H2O. The aqueous layer was separated and extracted with CH2Cl2 two times. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to a crude product, which was dissolved in a minimal amount of CH2Cl2 and applied to a flash chromatography column packed with hexanes. Elution with 10% CH2Cl2/hex led to some mixed fractions, which were rechromatographed. A total of 5.37 g (76%) of 3-(biphenyl-4-yl)furan was obtained as a pale yellow oil.
Reaction SMILES: C(C1C=CC=CC=1C(C1OC=CC=1)C)C.[Cl:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[C:24]([C:26]1[O:27][CH:28]=[CH:29][CH:30]=1)=[CH2:25]>>[Cl:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[CH:24]([C:26]1[O:27][CH:28]=[CH:29][CH:30]=1)[CH3:25]
Reactant: C=C(c1ccco1)c1cccc(Cl)c1Cl
Agent: CCc1ccccc1C(C)c1ccco1
Product: CC(c1ccco1)c1cccc(Cl)c1Cl

Procedure:
(±) 2-[1-(2,3Dichlorophenyl)ethyl]furan (b.p. 108°-112° C./0.3 mm.Hg) was prepared in a manner similar to that described in Example 3(m) for the preparation of (±) 2-[1-(2-ethylphenyl)ethyl]furan but replacing the 1-(2-ethylphenyl)-1-(2-furyl)ethylene by 1(2,3-dichlorophenyl)-1-(2-furyl)ethylene.
Reaction SMILES: [N+]([O-])(O)=O.[N+:5]([C:8]1[CH:9]=[C:10]([NH:14][C:15]([NH2:17])=[NH:16])[CH:11]=[CH:12][CH:13]=1)([O-:7])=[O:6].[OH-].[Na+].CN(C)[CH:22]=[CH:23][C:24]([C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1)=O>C(O)(C)C>[N+:5]([C:8]1[CH:9]=[C:10]([NH:14][C:15]2[N:17]=[C:24]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)[CH:23]=[CH:22][N:16]=2)[CH:11]=[CH:12][CH:13]=1)([O-:7])=[O:6]
Reactant: CN(C)C=CC(=O)c1ccncc1
Reactant: N=C(N)Nc1cccc([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: CC(C)O
Product: O=[N+]([O-])c1cccc(Nc2nccc(-c3ccncc3)n2)c1

Procedure:
1.38 g (5.68 mmol) of 3-nitrophenyl-guanidine nitrate and 0.25 g (6.24 mmol) of sodium hydroxide are added to a solution of 1 g (5.68 mmol) of 3-dimethylamino-1-(4-pyridyl)-2-propen-1-one [U.S. Pat. No. 4,281,000] in 8 ml of isopropanol. The yellow suspension is heated at reflux for 20 hours and then cooled to 0°. After washing with 30 ml of isopropanol the filtration residue is made into a slurry in succession in 15 ml of ethanol and then in 15 ml of water and filtered each time. Drying under HV yields N-(3-nitrophenyl)-4-(4-pyridyl)-2-pyrimidine-amine; m.p. 282°-284°.