Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:17])[CH:10](Br)[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.COC(=O)[C@@H](C)N.CN1CCOCC1.O>CS(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:13][C:12]([CH3:15])([CH3:14])[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:17]
Reactant: CC(C)(C)CC(Br)C(=O)OCc1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: COC(=O)[C@@H](C)N
Agent: Cl
Solvent: CS(C)=O
Solvent: CN1CCOCC1
Solvent: O
Product: CC(C)(C)C=CC(=O)OCc1ccccc1
Temperature: 25 °C
Yield: 95.9 %

Procedure:
Benzyl-2-bromo-4,4-dimethylpentanoate (20 g) in dry dimethyl sulphoxide (250 ml) was treated with D-alanine methylester hydrochloride (9.33 g), N-methyl morpholine (6.78 g) and tetrabutyl ammonium iodide (24.7 g) at 90° under an atmosphere of argon for 2 days. The reaction mixture was allowed to cool to room temperature, poured into water (500 ml) and the products recovered by extraction into dichloromethane (3×250 ml). The material isolated from the organic extracts was purified by chromatography on silica developed in a gradient of hexane-ether. Elution with 30% ether-hexane afforded benzyl 4,4-dimethylpent-2-enoate (14 g). Elution with 40% ether in hexane afforded the title compound (350 mg) as a gum; (Found: [m+1]+ =322.2022. C18H27N1O4 requires [m+1]+ =322.2018); νmax (film) 1735 cm-1 ; δ(CDCl3) 0.90 (9H,s,C(CH3)3); 1.28 (3H,d,J=7 Hz CHCH3); 2.46 and 2.68 (2H, each dd,J=12 and 5 Hz,CH2 (CH3)3); 3.30 (1H,q,J=5 Hz CH--CH3); 3.36 (1H,t,J=5 Hz, CH--CH2); 3.66 (3H,s,OCH3); 5.12 (2H,s,OCH2) and 7.36 (5H,s,C6H5). Elution with 45% ether in hexane afforded benzyl 2-(R)-N-(1-(R)-methoxycarbonylethyl)-amino-4,4-dimethylpentanoate (340 mg); (Found: [m+1]+ =322.2022. C11H27NO4 requires 322.2018); νmax (film) 3360 and 1735 cms-1 ; δ(CDCl3) 0.90 (9H,s, C(CH3)3); 1.28 (3H,d,J=6 Hz, CHCH3); 1.44 and 1.72 (2H, each dd,J=5 and 12.5 Hz,CH2); 3.32 (1H,q,J=7 Hz, CHCH3); 3.44 (1H,t,J=6 Hz, CHCH2); 3.69 (3H,s,OCH3), 5.24 (2H,s,OCH2) and 7.36 (5H,m,C6H5).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:20]=[CH:19][C:18]([O:21][CH2:22]/[CH:23]=[C:24](/[CH2:26][CH2:27][CH:28]=[C:29]([CH3:31])[CH3:30])\[CH3:25])=[CH:17][C:13]=1[C:14](O)=[O:15])/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])\[CH3:4].[NH2:32][CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][N:35]1[CH2:39][CH3:40]>>[CH2:39]([N:35]1[CH2:36][CH2:37][CH2:38][CH:34]1[CH2:33][NH:32][C:14](=[O:15])[C:13]1[CH:17]=[C:18]([O:21][CH2:22]/[CH:23]=[C:24](/[CH2:26][CH2:27][CH:28]=[C:29]([CH3:30])[CH3:31])\[CH3:25])[CH:19]=[CH:20][C:12]=1[O:11][CH2:1]/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])\[CH3:4])[CH3:40]
Reactant: CCN1CCCC1CN
Reactant: CC(C)=CCC/C(C)=C/COc1ccc(OC/C=C(\C)CCC=C(C)C)c(C(=O)O)c1
Product: CCN1CCCC1CNC(=O)c1cc(OC/C=C(\C)CCC=C(C)C)ccc1OC/C=C(\C)CCC=C(C)C
Yield: 55 %

Procedure:
In a manner identical to Example 15, 2,5-digeranyloxybenzoic acid (2.13 g) was subjected to a condensation reaction with 2-aminomethyl-1-ethylpyrrolidine (0.7 ml), thereby yielding 1.47 g (55%) of the aimed compound
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[O:6][CH:7]([C:17](O)=[O:18])[O:8][C:9]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:10]=3[CH2:11][C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[NH2:26][CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>C1C=CC=CC=1>[Cl:16][C:13]1[CH:14]=[CH:15][C:9]2[O:8][CH:7]([C:17]([NH:26][CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)=[O:18])[O:6][C:5]3[CH:20]=[CH:21][C:2]([Cl:1])=[CH:3][C:4]=3[CH2:11][C:10]=2[CH:12]=1
Reactant: NCc1cccnc1
Reactant: O=C(O)C1Oc2ccc(Cl)cc2Cc2cc(Cl)ccc2O1
Solvent: O=S(Cl)Cl
Solvent: c1ccccc1
Product: O=C(NCc1cccnc1)C1Oc2ccc(Cl)cc2Cc2cc(Cl)ccc2O1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 15 g of 2,10-dichloro-12H-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid was added 75 ml of thionyl chloride, and the heterogenous mixture was refluxed with occasional stirring until it became homogenous. The mixture was refluxed for an additional 2 hours after which the thionyl chloride was distilled off under reduced pressure affording a solid residue which was dissolved in 300 ml of dry benzene by warming on a steam bath. The benzene was distilled off under reduced pressure affording a white crystalline residue to which was added 500 ml of dry benzene. The mixture was stirred at room temperature until homogenous then 35 g of 3-aminomethylpyridine was added. After standing at room temperature for 2 hours the mixture was heated to reflux for an additional 3 hours, cooled to room temperature, poured into ice water and separated. Methanol was added to aid the solubility of the product in the organic layer. The organic layer was washed with water and distilled under reduced pressure resulting in a residue which was dried and recrystallized twice from methanol-acetone (1:1) to give the desired product, M.P. 225°-226°C.
Reaction SMILES: [N:1]1([C:6]2[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=2[CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=[N:2]1.[F:14][C:15]([Si](C)(C)C)([F:17])[F:16]>C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:14][C:15]([F:17])([F:16])[CH:8]([C:7]1[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=1[N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1)[OH:9]
Reactant: O=Cc1ccccc1-n1cccn1
Reactant: C[Si](C)(C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: OC(c1ccccc1-n1cccn1)C(F)(F)F
Temperature: 25 °C
Reaction time: 6 h
Yield: 92.9 %

Procedure:
To 2-pyrazol-1-yl-benzaldehyde (0.344 g, 2 mmol) in THF (8 ml) was added trifluoromethyl trimethyl silane (0.341 g, 2.4 mmol). The mixture was cooled to 0-5° C. (ice water bath) and tetra-n-butyl ammonium fluoride (0.035 ml, 0.035 mmol, 1M in THF) was added. The ice bath was removed, and the mixture was stirred at room temperature for 6 h. 2N HCl (5 ml) was added and the reaction mixture was further stirred at room temperature for 3 h. Solvent was removed on the rotavap under reduced pressure. The residue was dissolved in DCM (30 ml), washed with water (20 ml), brine (20 ml) and dried over sodium sulfate. The solvent was removed in vacuo to give crude 2,2,2-trifluoro-1-(2-pyrazol-1-yl-phenyl)-ethanol (0.45 g, 93%) which was directly used in the following experiment.
Reaction SMILES: [C:1]([CH:4]=[CH:5][C:6]1[CH:20]=[CH:19][C:9]([O:10][C:11]2[C:16](=[O:17])[C:15]([Cl:18])=[N:14][S:13][N:12]=2)=[CH:8][CH:7]=1)([OH:3])=[O:2].[CH2:21](N(CC)CC)[CH3:22].C(O)C>S(Cl)(Cl)=O.C(Cl)Cl.O>[Cl:18][C:15]1[C:16](=[O:17])[C:11]([O:10][C:9]2[CH:19]=[CH:20][C:6]([CH:5]=[CH:4][C:1]([O:3][CH2:21][CH3:22])=[O:2])=[CH:7][CH:8]=2)=[N:12][S:13][N:14]=1
Reactant: O=C(O)C=Cc1ccc(Oc2nsnc(Cl)c2=O)cc1
Reactant: CCN(CC)CC
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)C=Cc1ccc(Oc2nsnc(Cl)c2=O)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 51.4 %

Procedure:
A stirred solution of 15.5 grams (0.05 mole) of 3-[4-(2-carboxyethenyl)phenoxy]-5-chloro-4H-1,2,6-thiadiazin-4-one in 150 ml of thionyl chloride was heated under reflux for 16 hours, then allowed to cool to ambient temperature. The excess thionyl chloride was removed under reduced pressure to give a residual solid. The solid was dissolved in 300 ml of methylene chloride. To the resulting solution was carefully added 6.1 grams (0.06 mole) of triethylamine; then, dropwise, 4.6 grams (0.1 mole) of absolute ethanol. The reaction mixture was stirred at ambient temperature for 2.5 hours, then diluted with 150 ml of water. The organic layer was separated and washed with 200 ml of water, then 150 ml of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to a solid residue. The solid was recrystallized twice with ethanol to give 8.7 grams (51%) of 3 -chloro-5-[4-(2-ethoxycarbonylethenyl)phenoxy]-4H-1,2,6-thiadiazin-4-one; mp 126°-127.5° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:21])=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1.[O:22]1[CH2:26]C[CH2:24][CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>COCCO>[Br:1][C:2]1[C:3]([O:21][CH2:24][CH2:23][O:22][CH3:26])=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1
Reactant: O=C1CN=C(c2ccccc2Cl)c2cc(Br)c(O)cc2N1
Reactant: C1CCOC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: COCCO
Product: COCCOc1cc2c(cc1Br)C(c1ccccc1Cl)=NCC(=O)N2
Reaction time: 8 h

Procedure:
To a stirred mixture of 0.300 g (0.00082 mole) 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-hydroxy-2H-1,4-benzodiazepin-2-one (Ipp) prepared in Example 28, 60 mL of tetrahydrofuran, 0.070 mL of 2-methoxy ethanol, and 0.2586 g of triphenyl phosphine was added 0.194 mL (0.00099 mole) of diisopropyl azodicarboxylate. The mixture was stirred overnight; then, an additional 0.2586 g of triphenyl phosphine, 0.070 mL of 2-methoxy ethanol and 0.194 mL of diisopropyl azodicarboxylate was added. The mixture stirred for an additional hour and then concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with dichloromethane-methanol (98:2) to yield 0.212 g of 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-methoxyethoxy-2H-1,4-benzodiazepin-2-one (Inn). MH+/Z=423.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=3)[CH2:13][C:14]([NH:16][CH3:17])=O)=[CH:9][CH:10]=2)[NH:5][N:4]=1.C(O)(C(F)(F)F)=O.N1C2C(=CC=CC=2C(C2C=CC=CC=2)CCNC)C=C1>>[CH3:1][O:2][C:3]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=3)[CH2:13][CH2:14][NH:16][CH3:17])=[CH:9][CH:10]=2)[NH:5][N:4]=1
Reactant: CNC(=O)CC(c1ccc2c(OC)n[nH]c2c1)c1cccc(C)n1
Agent: CNCCC(c1ccccc1)c1cccc2cc[nH]c12
Solvent: O=C(O)C(F)(F)F
Product: CNCCC(c1ccc2c(OC)n[nH]c2c1)c1cccc(C)n1

Procedure:
[3-(3-Methoxy-1H-indazol-6-yl)-3-(6-methyl-pyridin-2yl)-propyl]-methyl-amine CCXLVI was prepared from 3-(3-methoxy-1H-indazol-6-yl)-N-methyl-3-(6-methyl-pyridin-2yl)-propionamide and TFA as a bis-trifluoroacetate using the procedure described for preparation of [3-(1H-Indol-7-yl)-3-phenyl-propyl]-methyl-amine XX (Example 4). MS (M+H)=MS 311.
Reaction SMILES: C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl.[CH2:13]([C:16]1[C:37]2[CH2:36][C:35]3[C:22](=[C:23]([CH2:53][CH2:54][CH3:55])[C:24]4[C:33]([C:34]=3[CH2:38][CH2:39][CH3:40])=[CH:32][C:31]3[C:26](=[C:27]([CH2:50][CH2:51][CH3:52])[C:28]([CH2:47][CH2:48][CH3:49])=[C:29]([CH2:44][CH2:45][CH3:46])[C:30]=3[CH2:41][CH2:42][CH3:43])[CH:25]=4)[CH2:21][C:20]=2[C:19]([CH2:56][CH2:57][CH3:58])=[C:18]([C:59]([O:61][CH3:62])=[O:60])[C:17]=1[C:63]([O:65][CH3:66])=[O:64])[CH2:14][CH3:15]>C1C=CC=CC=1>[CH2:13]([C:16]1[C:37]2[C:20](=[CH:21][C:22]3[C:35]([CH:36]=2)=[C:34]([CH2:38][CH2:39][CH3:40])[C:33]2[C:24](=[CH:25][C:26]4[C:31]([CH:32]=2)=[C:30]([CH2:41][CH2:42][CH3:43])[C:29]([CH2:44][CH2:45][CH3:46])=[C:28]([CH2:47][CH2:48][CH3:49])[C:27]=4[CH2:50][CH2:51][CH3:52])[C:23]=3[CH2:53][CH2:54][CH3:55])[C:19]([CH2:56][CH2:57][CH3:58])=[C:18]([C:59]([O:61][CH3:62])=[O:60])[C:17]=1[C:63]([O:65][CH3:66])=[O:64])[CH2:14][CH3:15]
Reactant: CCCc1c2c(c(CCC)c(C(=O)OC)c1C(=O)OC)Cc1c(c(CCC)c3cc4c(CCC)c(CCC)c(CCC)c(CCC)c4cc3c1CCC)C2
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: c1ccccc1
Product: CCCc1c(CCC)c(CCC)c2cc3c(CCC)c4cc5c(CCC)c(C(=O)OC)c(C(=O)OC)c(CCC)c5cc4c(CCC)c3cc2c1CCC
Yield: 32.8 %

Procedure:
Chloranil (0.054 g, 0.22 mmol) was added to a solution of dimethyl 5,14-dihydro-1,4,6,8,9,10,11,13-octapropylpentacene-2,3-dicarboxylate (0.147 g, 0.2 mmol) obtained in REFERENCE EXAMPLE 6 in benzene (5 ml). The mixture was then refluxed for 24 hours. After concentration, chloroform was added to the residue followed by filtration. After concentration, the concentrate was recrystallized from benzene to give 0.048 g of the title compound as a blue solid. The isolation yield was 33%.
Reaction SMILES: C(OC([N:8]1[CH2:14][CH2:13][CH2:12][CH:11]([O:15][CH2:16][C:17]2[C:18]([C:25]3[C:30]([Cl:31])=[CH:29][CH:28]=[CH:27][C:26]=3[Cl:32])=[N:19][O:20][C:21]=2[CH:22]2[CH2:24][CH2:23]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH:22]1([C:21]2[O:20][N:19]=[C:18]([C:25]3[C:26]([Cl:32])=[CH:27][CH:28]=[CH:29][C:30]=3[Cl:31])[C:17]=2[CH2:16][O:15][CH:11]2[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]2)[CH2:23][CH2:24]1
Reactant: CC(C)(C)OC(=O)N1CCCC(OCc2c(-c3c(Cl)cccc3Cl)noc2C2CC2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Clc1cccc(Cl)c1-c1noc(C2CC2)c1COC1CCCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.7 %

Procedure:
A solution of 56 g (116.32 mmol) of 4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepane-1-carboxylic acid tert-butyl ester in 150 mL of dichloromethane at 0° C. (ice bath) is treated with trifluoroacetic acid (150 mL, 1.98 mol). The mixture is stirred at room temperature under nitrogen for 2 hours. The reaction mixture is concentrated. The crude product is dissolved with EtOAc (300 mL), washed with a solution 2N—NaOH (2×100 mL) and washed with brine (1×100 mL). The organics are dried (Na2SO4), filtered and concentrated to afford 38 g of the desired compound as a yellow oil (86%). MS (m/e): 381 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=[O:9])=[C:4]([NH:11][C:12]([C:14]([O:16]CC)=O)=[O:13])[CH:3]=1.C(O)C>CN(C)C=O.[Ni]>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[N:8]([OH:9])[C:14](=[O:16])[C:12](=[O:13])[NH:11]2
Reactant: CCOC(=O)C(=O)Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CCO
Solvent: CN(C)C=O
Product: O=c1[nH]c2cc(Cl)ccc2n(O)c1=O
Yield: 33.4 %

Procedure:
A solution of 0.5 g (1.83 mmol) 1-chloro-3-ethoxalylamino-4-nitrobenzene in 15 ml dimethylformamide was hydrogenated at atm. pressure by using 0.5 g Ra-Ni as a catalyst. The residue was stirred with ethanol to give 0.13 g (30%) of 6-chloro-1-hydroxyquinoxaline-2,3(1H,4H)-dione. M.p. decomp. 1H-NMR (DMSO-d6): 11.8 (1H, broad s), 7.17 (3H, m). MS (m/e): 212 (M30 , 60%).
Reaction SMILES: C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[C:16](=[CH:18][CH:19]=[C:20]([OH:36])[C:21]=1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33](O)=[O:34])[OH:17].[H-].[Al+3].[Li+].[H-].[H-].[H-].[H][H].Cl>O1CCCC1.O.C(O)C>[C:20]1([C:21]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][OH:34])=[C:15]([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:2])[C:16](=[CH:18][CH:19]=1)[OH:17])[OH:36]
Reactant: COC(=O)CCCCCCCCCCCc1c(O)ccc(O)c1CCCCCCCCCCCC(=O)O
Reactant: [H][H]
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: OCCCCCCCCCCCCc1c(O)ccc(O)c1CCCCCCCCCCCCO
Temperature: 25 °C

Procedure:
The desired nonionic gemini surfactant, hydroquinone bislauryl alcohol was prepared as follows. Hydroquinone bislauric acid methyl ester (5.25 g) was dissolved in dry tetrahydrofuran (THF) at 0° C. Lithium aluminum hydride (LAH) (1.07 g) was added to the solution slowly. A large amount of hydrogen was generated. The reaction temperature was then raised to 25° C. After the reaction was stirred for an hour at this temperature, the reaction was stopped by adding ethanol to deactivate the excess LAH. The solution was mixed with water and then acidified with concentrated HCl. The final product was extracted twice with ether. The crude hydroquinone bislauryl alcohol was dried under vacuum. The product is an oily liquid (4.2 g) whose NMR spectrum agrees with the structure of the expected gemini compound. The reaction can be summarized as follows.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17](=[NH:19])[NH2:18])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:20]([F:23])([F:22])[F:21].C([O-])([O-])=O.[K+].[K+].[CH:30]([CH:32]([CH2:37][C:38]1[CH:39]=[N:40][CH:41]=[N:42][CH:43]=1)[C:33](OC)=O)=[O:31]>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][C:17]3[NH:18][CH:33]=[C:32]([CH2:37][C:38]4[CH:43]=[N:42][CH:41]=[N:40][CH:39]=4)[C:30](=[O:31])[N:19]=3)=[CH:13][CH:14]=2)=[CH:4][C:3]=1[C:20]([F:21])([F:22])[F:23]
Reactant: COC(=O)C(C=O)Cc1cncnc1
Reactant: N=C(N)CCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: O=c1nc(CCc2ccc(Oc3ccc(Cl)c(C(F)(F)F)c3)cc2)[nH]cc1Cc1cncnc1
Temperature: 120 °C

Procedure:
A mixture of 3-(4-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)propanimidamide (150 mg, 0.316 mmol), K2CO3 (131 mg, 0.949 mmol) and methyl 2-formyl-3-(5-pyrim-idinyl)propanoate (188 mg, 0.633 mmol) in NMP (1.5 mL) was heated with a microwave reactor at 120° C. for 2 h. Purification via a reverse phase Biotage then afforded the title compound as a white solid. LCMS: rt=3.13 min, [M+H+]=487
Reaction SMILES: [Na].Cl[C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][C:6]([CH3:12])=[CH:5][N:4]=1.[CH3:13][OH:14]>>[CH3:13][O:14][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][C:6]([CH3:12])=[CH:5][N:4]=1
Reactant: Cc1cnc(Cl)c([N+](=O)[O-])c1
Reactant: CO
Agent: [Na]
Product: COc1ncc(C)cc1[N+](=O)[O-]
Yield: 92 %

Procedure:
To a solution of sodium (2.31 g, 0.1 mol) dissolved in methanol (100 mL) at room temperature, 2-chloro-5-methyl-3-nitro-pyridine (17.2 g, 0.1 map was added. The reaction mixture was refluxed for 4 h under N2 atmosphere. After evaporated to dryness, the residue was diluted with water (100 mL) and extracted (2×50 mL CH2Cl2). The combined extracts were washed with brine, dried on MgSO4, and filtered. The solvent was evaporated and the residue was crystallized from a mixture of water (300 mL) and ethanol (20 mL) to yield 2-methoxy-5-methyl-3-nitro-pyridine as a light orange solid (15.4 g, 92%). 1H-NMR (DMSO-d6): δ 2.31 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 8.30 (d, 1H, J=2.0 Hz, Py-H), 8.35 (d, 1H, J=2.0 Hz, Py-H); 13C-NMR (DMSO-d6): δ 16.80, 54.86, 127.36, 133.7, 135.91, 152.03, 154.27; HR-MS (ESI+) m/z 169.0570 [M+H]+; C7H8N2O3 requires 168.0535.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[C:3]([C:14]([OH:16])=[O:15])[CH:2]=1.[C:17]([O-])([O-])=O.[K+].[K+].CI>CC(C)=O>[CH3:17][N:12]1[C:13]2[CH:1]=[CH:2][C:3]([C:14]([OH:16])=[O:15])=[CH:4][C:5]=2[C:6]2[C:11]1=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: O=C(O)c1ccc2[nH]c3ccccc3c2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: Cn1c2ccccc2c2cc(C(=O)O)ccc21
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 87.5 %

Procedure:
A mixture of 9H-carbazole-3-carboxylic acid (300 mg, 1.42 mmol), K2CO3 (800 mg) and methyl iodide (1 mL) in 25 mL of acetone was heated under reflux overnight, then cooled and evaporated in vacuo. A mixture of the resultant residue and NaOH (170 mg) in aqueous MeOH (90%, 25 mL) was stirred at 50° C. for 30 minutes. The reaction mixture was concentrated and acidified with diluted HCl. The solids were collected by filtration and dried to give the title compound (280 mg, 87%).
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[N:12]=[CH:11][N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CN([CH:33]=[O:34])C>C1COCC1>[CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([CH:33]=[O:34])[N:10]([CH2:14][CH:15]=[CH2:16])[C:9]=2[C:8](=[O:17])[N:7]([CH3:18])[C:6]1=[O:19])[CH2:2][CH2:3][CH3:4]
Reactant: C=CCn1cnc2c1c(=O)n(C)c(=O)n2CCCC
Reactant: CN(C)C=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCn1c(C=O)nc2c1c(=O)n(C)c(=O)n2CCCC
Temperature: -75 °C
Yield: 105.8 %

Procedure:
A pre-dried flask was charged with 3-butyl-1-methyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (300 mg, 1.14 mmol) and anhydrous THF (6 ml), cooled to −75° C. under nitrogen, then treated with LiHMDS (1.37 ml of a 1.0M solution in THF). The resulting solution was allowed to warm to −60° C. over 1.5 hours before the addition of anhydrous DMF (177 ul, 2.29 mmol). The solution was allowed to warm to −10° C. over 3 hours then it was quenched with sat. NH4Cl (aq) solution. The mixture was partitioned between 1M HCl (aq) and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4) and concentrated giving a brown oil (350 mg). The product was purified by SPE (Si, 10 g) eluting with EtOAc/cyclohexane mixtures to give the title compound as a white solid (131 mg, 39%); NMR; δH (400 MHz, d6-DMSO) 0.91 (t, 3H, J=7.5 Hz), 1.28-1.39 (m, 2H), 1.63-1.73 (m, 2H), 3.25 (s, 3H), 4.02 (t, 2H, J=7.5 Hz), 5.03 (dd, 1H, J=17 and 1 Hz), 5.17 (dd, 1H, J=10 and 1 Hz), 5.31 (app. d, 2H, J=5.5 Hz), 5.98-6.09 (m, 1H), 9.88 (s, 1H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4]([CH3:7])(=[O:6])=[O:5].Cl[C:9]1[N:14]=[C:13]([C:15]2[S:19][C:18]([N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[N:17][C:16]=2[C:25]2[CH:26]=[C:27]([NH:31][S:32]([C:35]3[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=3[F:42])(=[O:34])=[O:33])[CH:28]=[CH:29][CH:30]=2)[CH:12]=[CH:11][N:10]=1>>[F:42][C:36]1[CH:37]=[CH:38][CH:39]=[C:40]([F:41])[C:35]=1[S:32]([NH:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([C:16]2[N:17]=[C:18]([N:20]3[CH2:21][CH2:22][CH2:23][CH2:24]3)[S:19][C:15]=2[C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:1][CH2:2][CH2:3][S:4]([CH3:7])(=[O:6])=[O:5])[N:14]=2)[CH:26]=1)(=[O:34])=[O:33]
Reactant: CS(=O)(=O)CCN
Reactant: O=S(=O)(Nc1cccc(-c2nc(N3CCCC3)sc2-c2ccnc(Cl)n2)c1)c1c(F)cccc1F
Product: CS(=O)(=O)CCNc1nccc(-c2sc(N3CCCC3)nc2-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2)n1

Procedure:
Following a procedure analogous to the procedure described in Example 1 using 2-aminoethyl-methyl-sulfone (923 mg, 7.49 mmol) and N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide (400 mg, 0.749 mmol) the title compound was obtained as a white solid (27 mg, 4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.87-11.12 (m, 1H) 7.75 (d, J=5.4 Hz, 1H) 7.55-7.72 (m, 1H) 7.24-7.38 (m, 1H) 7.10-7.25 (m, 4H) 7.08 (d, J=7.8 Hz, 1H) 5.57-5.85 (m, 1H) 3.54-3.70 (m, 2H) 3.29-3.43 (m, 7H) 2.88-3.05 (m, 4H) 1.86-2.04 (m, 3H). MS (ESI): 621.1 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5](Cl)=[CH:4][CH:3]=1.[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:11])[CH3:10].P.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(Cl)C=CC1C=CC=CC=1.[Pd]>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:11])=[CH:4][CH:3]=1
Reactant: CC(=O)c1ccccc1
Reactant: Cc1ccc(Cl)cc1
Agent: [Pd]
Agent: ClCC=Cc1ccccc1
Agent: O=P([O-])([O-])[O-]
Solvent: Cc1ccccc1
Product: Cc1ccc(CC(=O)c2ccccc2)cc1
Yield: 66.8 %

Procedure:
This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are p-methylphenyl chloride (125.6 mg, 1.0 mmol), acetophenone (300.1 mg, 2.5 mmol), palladium cinnamyl chloride (7.8 mg, 0.015 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino)phenyldicyclohexyl)phosphine (18.3 mg, 0.045 mmol), K3PO4:3H2O (665.8 mg, 2.5 mmol) in 3 mL dry toluene at 110° C. for 12 h. 2-(4′-Methylphenyl)-1-phenyl-1-ethanone (140.5 mg) was obtained with a yield of 67% as solid. m.p.: 95.8-96.1° C. (n-hexane); 1H NMR (300 MHz, CDCl3) δ 8.07-8.00 (m, 2H, ArH), 7.62-7.53 (m, 1H, ArH), 7.52-7.43 (m, 2H, ArH), 7.22-7.13 (m, 4H, ArH), 4.27 (s, 2H, CH2), 2.35 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 197.7, 136.5, 136.3, 133.0, 131.3, 129.3, 129.2, 128.5, 45.0, 21.0; IR (KBr) v (cm−1) 3051, 3024, 2896, 1686, 1592, 1578, 1515, 1448, 1406, 1335, 1221, 1209, 1197, 1181; MS (70 eV, EI) m/z (%): 211 (M++1, 0.65), 210 (M+, 3.47), 105 (100).