Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][N:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:64]([S:71][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][N:3]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1
Reactant: SCc1ccccc1
Reactant: Oc1ccnc2cc(Cl)ncc12
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: Oc1ccnc2cc(SCc3ccccc3)ncc12
Temperature: 80 °C
Yield: 22.6 %

Procedure:
A screw cap vial was charged with 7-chloro-1,6-naphthyridin-4-ol (0.500 g, 2.77 mmol), Xantphos (0.080 g, 0.138 mmol), tris(dibenzylideneacetone)dipalladium (0.063 g, 0.069 mmol), 1,4-dioxane (5.54 mL) and DIPEA (0.963 mL, 5.54 mmol). The vial was purged with argon, sealed and heated to 80° C. for 10 minutes. The reaction was cooled to room temperature and benzyl mercaptan (0.385 mL, 3.25 mmol) was added and the reaction was continued heating at 80° C. for an additional 30 minutes. The reaction was cooled to room temperature, diluted with water and extracted with DCM (3×). The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting material was concentrated, dissolved in minimal DCM and purified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane) to afford 0.168 g of 7-(benzylthio)-1,6-naphthyridin-4-ol. m/z (ESI) 269.1 (M+H)+.
Reaction SMILES: [I-].[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([Zn+])=[CH:9][CH:8]=1)=[O:6])[CH3:3].[CH:14]1([C:17](Cl)=[O:18])[CH2:16][CH2:15]1>>[CH:14]1([C:17]([C:10]2[CH:11]=[CH:12][C:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])=[CH:8][CH:9]=2)=[O:18])[CH2:16][CH2:15]1
Reactant: CCOC(=O)c1ccc([Zn+])cc1
Reactant: O=C(Cl)C1CC1
Agent: [I-]
Product: CCOC(=O)c1ccc(C(=O)C2CC2)cc1

Procedure:
Intermediate i-3a was prepared from 4-ethoxycarbonylphenyl zinc iodide and cyclopropanecarbonyl chloride following the above procedure as described for intermediate i-1a. m/z (ES) 219 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.17 (d, 2H, J=8.5 Hz), 8.08 (d, 2H, J=8.4 Hz), 4.44 (q, 2H, J=7.1 Hz), 2.71 (m, 1H), 1.45 (t, 3H, J=7.1 Hz), 1.31 (m, 2H), 1.13 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](/[CH:15]=[CH:16]/[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.[H][H]>[Pd].C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1
Reactant: [H][H]
Reactant: N#Cc1c(/C=C/c2ccccc2)nc(N)nc1-c1ccco1
Agent: [Pd]
Solvent: C1CCOC1
Product: N#Cc1c(CCc2ccccc2)nc(N)nc1-c1ccco1

Procedure:
From (E)-2-Amino-4-furan-2-yl-6-styryl-pyrimidine-5-carbonitrile, hydrogen and palladium on charcoal in THF. ES-MS m/e (%): 291 (M+H+, 100).
Reaction SMILES: [N:1]1[C:8]([Cl:9])=[N:7][C:5]([Cl:6])=[N:4][C:2]=1Cl.[CH2:10]([NH2:22])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].O>CC(C)=O>[Cl:6][C:5]1[N:7]=[C:8]([Cl:9])[N:1]=[C:2]([N:22]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:2]2[N:1]=[C:8]([Cl:9])[N:7]=[C:5]([Cl:6])[N:4]=2)[N:4]=1
Reactant: CCCCCCCCCCCCN
Reactant: Clc1nc(Cl)nc(Cl)n1
Solvent: CC(C)=O
Solvent: O
Product: CCCCCCCCCCCCN(c1nc(Cl)nc(Cl)n1)c1nc(Cl)nc(Cl)n1
Reaction time: 4 h

Procedure:
To a solution of cyanuric chloride (38.0 g) in acetone (350 ml) was added dropwise a suspension of dodecylamine (18.5 g) in acetone (40 ml) at 10° C. After addition, the mixture was stirred for 4 hours at that temperature. The reaction mixture was poured into water (2 l) and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and ethyl acetate was distilled off. The resulting oil was purified with silica gel column chromatography (eluent=benzene:n-hexane=4:1) to afford N,N-bis-(2,4-dichloro-1,3,5-triazine-6-yl)-n-dodecylamine as white crystals melting at 50°-53° C.
Reaction SMILES: [N+]([C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1/[CH:17]=[CH:18]/[N:19](C)C)([O-])=O>[Ni].C(O)C>[F:16][C:13]([F:14])([F:15])[C:7]1[CH:6]=[C:5]2[C:4](=[CH:9][C:8]=1[NH2:10])[NH:19][CH:18]=[CH:17]2
Reactant: CN(C)/C=C/c1cc(C(F)(F)F)c([N+](=O)[O-])cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CCO
Product: Nc1cc2[nH]ccc2cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 5 h
Yield: 14.5 %

Procedure:
A suspension of (E)-2-(2,4-dinitro-5-(trifluoromethyl)phenyl)-N,N-dimethylethenamine (2.1 g, 6.9 mmol) and Raney Nickel (1 g) in ethanol (80 mL) was stirred under H2 (1 atm) at room temperature for 5 h. The catalyst was filtered off and the filtrate was concentrated to dryness. The residue was purified by column on silica gel to give 5-(trifluoromethyl)-1H-indol-6-amine (200 mg, 14%). 1H NMR (DMSO-d6) δ 10.79 (br s, 1H), 7.55 (s, 1H), 7.12 (s, 1H), 6.78 (s, 1H), 6.27 (s, 1H), 4.92 (s, 2H); MS (ESI) m/e (M+H+): 200.8.
Reaction SMILES: C(Cl)(=O)C1C(=CC=CC=1)C(Cl)=O.C1(=O)OC(=O)C2=CC=CC=C12.[CH2:24]([N:28]([CH2:32][CH2:33][CH2:34][CH3:35])[C:29](Cl)=[O:30])[CH2:25][CH2:26][CH3:27]>>[CH2:24]([N:28]([CH2:32][CH2:33][CH2:34][CH3:35])[CH:29]=[O:30])[CH2:25][CH2:26][CH3:27]
Reactant: CCCCN(CCCC)C(=O)Cl
Agent: O=C(Cl)c1ccccc1C(=O)Cl
Agent: O=C1OC(=O)c2ccccc21
Product: CCCCN(C=O)CCCC

Procedure:
The crude product remains as a dark oil. According to HPLC analysis, it contains 83.8% by weight of phthaloyl chloride, 2.4% by weight of phthalic anhydride, and, according to GC analysis, 0.9 area % of N,N-dibutylcarbamoyl chloride. Based on the product, this corresponds to a crude yield of 97.8% of theory.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][NH2:8].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:19]2[C@H:28]3[C@H:23]([CH2:24][CH2:25][CH2:26][CH2:27]3)[C:22](=[O:29])N(CCO)N=2)[CH:14]=[CH:15][C:16]=1[O:17][CH3:18]>>[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:19]2[C@H:28]3[C@H:23]([CH2:24][CH:25]=[CH:26][CH2:27]3)[C:22](=[O:29])[N:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[N:8]=2)[CH:14]=[CH:15][C:16]=1[O:17][CH3:18]
Reactant: NNc1ccccn1
Reactant: COc1ccc(C2=NN(CCO)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Product: COc1ccc(C2=NN(c3ccccn3)C(=O)[C@H]3CC=CC[C@@H]23)cc1OC

Procedure:
Prepared from compound C and 2-pyridylhydrazine as described for compound 35. Purified by chromatography (ethyl acetate) and crystallized from ethyl acetate/diethyl ether. M.p. 147°-148° C.
Reaction SMILES: [CH2:1]([N:4]1[C:12](=[O:13])[C:11]2[C:6](=[N:7][C:8](SC)=[N:9][CH:10]=2)[N:5]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])[N:17]=1)[CH:2]=[CH2:3].[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][C:41]([N:43]([CH3:45])[CH3:44])=[O:42])[CH2:36][CH2:35]2)=[CH:30][CH:29]=1>>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C:18]1[N:17]=[C:16]([N:5]2[C:6]3=[N:7][C:8]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([N:34]5[CH2:39][CH2:38][N:37]([CH2:40][C:41]([N:43]([CH3:45])[CH3:44])=[O:42])[CH2:36][CH2:35]5)=[CH:30][CH:29]=4)=[N:9][CH:10]=[C:11]3[C:12](=[O:13])[N:4]2[CH2:1][C:2]#[CH:3])[CH:21]=[CH:20][CH:19]=1
Reactant: CN(C)C(=O)CN1CCN(c2ccc(N)cc2)CC1
Reactant: C=CCn1c(=O)c2cnc(SC)nc2n1-c1cccc(CC(C)(C)O)n1
Product: C#CCn1c(=O)c2cnc(Nc3ccc(N4CCN(CC(=O)N(C)C)CC4)cc3)nc2n1-c1cccc(CC(C)(C)O)n1

Procedure:
27 mg of the entitled compound was obtained as a yellow solid in the same manner as in Example 113-1 to 113-2, for which, however, 2-allyl-1-[6-(2-hydroxy-2-methylpropyl)pyridin-2-yl]-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one obtained in Example 81-2 was used in place of 2-allyl-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one used in Example 113-1, and 2-[4-(4-aminophenyl)piperazin-1-yl]-N,N-dimethylacetamide was used in place of 4-(4-methylpiperazin-1-yl)aniline used in Example 113-2.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([OH:13])=O.C(Cl)(=O)C(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]2[C:3]=1[CH2:9][CH2:10][C:11]2=[O:13]
Reactant: O=C(O)CCc1cccc(F)c1F
Agent: O=C(Cl)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C1CCc2c1ccc(F)c2F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 2,3-difluorocinnamic acid (2.8 g, 15.2 mol) (commercially available from Lancaster) (Intermediate TWENTY-1) in ethanol (100 mL) was hydrogenated with H2 (balloon) and 10% Pd/C (0.3 g) at rt for 16 h. The mixture was filtered through Celite® and the solvent was evaporated to give 3-(2,3-difluoro-phenyl)-propionic acid as a solid, 2.68 g (98%). A mixture of 3-(2,3-difluoro-phenyl)-propionic acid (2.7 g, 14.4 mmol) in CH2Cl2 at 0° C. was treated with oxalyl chloride (8.7 mL, 2 M in CH2Cl2) and a few drops of DMF. The reaction mixture was stirred for 2 h at rt. The solution was decanted from the dark colored residues and the solvent was removed under vacuum. The residue was dissolved in CH2Cl2 (20 mL) and added to a mixture of AlCl3 (1.92 g, 14.4 mmol) in CH2Cl2 (25 mL). The mixture was heated at 50° C. for 16 h. The entire mixture was poured into ice water. The aqueous phase was removed and extracted with CH2Cl2. The organic layers were combined, washed with sat. NaHCO3 solution, brine, and dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified by chromatography on silica gel with 20% EtOAc:hexane to give 4,5-difluoro-indan-1-one (Intermediate TWENTY-2), 1.65 g (68%).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6][C:7](=[CH:9][CH:10]=O)[CH3:8])[CH3:3].O.[OH-].[Li+].P(=O)(O)(O)O.[CH3:20][C:21]([CH3:23])=[O:22]>>[CH3:3][C:2]([CH3:1])=[CH:4][CH2:5][CH2:6]/[C:7](/[CH3:8])=[CH:9]/[CH:10]=[CH:20]/[C:21]([CH3:23])=[O:22]
Reactant: CC(C)=CCCC(C)=CC=O
Reactant: CC(C)=O
Agent: O=P(O)(O)O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Product: CC(=O)/C=C/C=C(\C)CCC=C(C)C

Procedure:
500 g citral (75%) and 2008 g acetone were heated at reflux (50° - 60° C.) in the presence of 5 g lithium hydroxide monohydrate until 1% citral remained. The crude oil was neutralized with 8% aqueous phosphoric acid, stripped of acetone, and washed with water and aqueous sodium bicarbonate to give ann 85% molar yield of pseudoionone. The product contained 1% of isocitral aldol impurities as compared with 3% isocitral aldols in the prior art sodium hydroxide process.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:30]=[CH:29][C:15]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([CH3:28])([CH3:27])[C:22]([O:24]CC)=[O:23])=[CH:14][CH:13]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[OH-].[Na+]>CO.O>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:30]=[CH:29][C:15]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([CH3:27])([CH3:28])[C:22]([OH:24])=[O:23])=[CH:14][CH:13]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CCOC(=O)C(C)(C)CCCCOc1ccc(OCCCCCn2ccnc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(CCCCOc1ccc(OCCCCCn2ccnc2)cc1)C(=O)O
Yield: 82.2 %

Procedure:
To a solution of 3 g ethyl 6-[p-[5-(1-imidazolyl)pentyloxy]phenoxy]-2,2-dimethylhexanoate in 15 ml methanol, was added a solution of 580 mg sodium hydroxide in 6 ml water, and the mixture was heated under reflux for 5 hours. Methanol was distilled off under reduced pressure, and dilute hydrochloric acid was added to the remaining aqueous solution to lower its pH down to about 5. The solid which separated out was collected by filtration, washed with water, and recrystallized from methanol, affording 2.3 g of 6-[p-[5-(1-imidazolyl)pentyloxy]phenoxy]-2,2-dimethylhexanoic acid.
Reaction SMILES: F[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C@H:11]1([OH:18])[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13][CH2:12]1>>[N+:8]([C:7]1[C:2]([O:17][C@H:14]2[CH2:15][CH2:16][C@H:11]([OH:18])[CH2:12][CH2:13]2)=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O[C@H]1CC[C@H](O)CC1
Reactant: O=[N+]([O-])c1cccnc1F
Product: O=[N+]([O-])c1cccnc1O[C@H]1CC[C@H](O)CC1

Procedure:
Prepared analogously to III.1 from 4.054 g 2-fluoro-3-nitropyridine and 2.266 g trans-1,4-cyclohexanediol
Reaction SMILES: [CH3:1][S:2][C:3]1[S:7][C:6]2[C:8]([CH2:12][NH:13][CH3:14])=[CH:9][CH:10]=[CH:11][C:5]=2[C:4]=1Br.CCOCC.C([Li])CCC.Cl>CCCCCC>[CH3:1][S:2][C:3]1[S:7][C:6]2[C:8]([CH2:12][NH:13][CH3:14])=[CH:9][CH:10]=[CH:11][C:5]=2[CH:4]=1
Reactant: CNCc1cccc2c(Br)c(SC)sc12
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CNCc1cccc2cc(SC)sc12

Procedure:
To a solution of 0.3 g of N-(2-methylthio-3-bromo-7-benzo[b]thienylmethyl)methylamine in abs. ether are added dropwise under inert gas at -70°, 1.4 ml of a 15% solution of n-butyllithium in n-hexane and stirring continued at -70° for half an hour. The mixture is then poured into ice-cooled 2N HCl, shaken and the acidic phase separated, made alkaline with NaOH and extracted with ether. The ether phase is dried, concentrated in vacuum and the resulting oil directly further reacted.
Reaction SMILES: FC(F)(F)C([NH:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]#[C:16][C:17]([OH:24])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[CH:10]=1)=O.C(Cl)Cl.N>CO>[NH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:10]=[C:11]([C:15]#[C:16][C:17]([CH:21]([CH3:23])[CH3:22])([OH:24])[CH:18]([CH3:20])[CH3:19])[CH:12]=[CH:13][CH:14]=1
Reactant: CC(C)C(O)(C#Cc1cccc(CCCNC(=O)C(F)(F)F)c1)C(C)C
Agent: N
Solvent: CO
Solvent: ClCCl
Product: CC(C)C(O)(C#Cc1cccc(CCCN)c1)C(C)C

Procedure:
Deprotection of 2,2,2-trifluoro-N-(3-(3-(3-hydroxy-3-isopropyl-4-methylpent-1-ynyl)phenyl)propyl)acetamide following the method used in Example 2 followed by flash chromatography (9:1 CH2Cl2: 7 M NH3 in MeOH) gave 1-(3-(3-aminopropyl)phenyl)-3-isopropyl-4-methylpent-1-yn-3-ol as a clear oil. Yield (0.835 g, 82%): 1H NMR (400 MHz, DMSO-d6) δ 7.15-7.26 (m, 4H), 4.82 (br s, 1H), 2.56 (t, J=7.6 Hz, 2H), 2.47-2.52 (m, 2H), 1.86 (quint, J=6.8 Hz, 2H), 1.59 (quint, J=6.8 Hz, 2H), 1.56 (br.s, 2H), 1.05 (d, J=6.8 Hz, 6H), 1.03 (d, J=6.8 Hz, 6H).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[CH3:16])[C:12](=[O:17])[CH2:11][CH2:10]2)(=O)=O.[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[F-].[K+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:15]=2[CH3:16])[C:12](=[O:17])[CH2:11][CH2:10]3)=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: OB(O)c1ccc(OCc2ccccc2)cc1
Reactant: Cc1cc2c(cc1OS(=O)(=O)C(F)(F)F)CCC2=O
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: C1CCOC1
Product: Cc1cc2c(cc1-c1ccc(OCc3ccccc3)cc1)CCC2=O
Reaction time: 0.08 h
Yield: 119.4 %

Procedure:
A solution of 5-(trifluoromethanesulfonyloxy)-6-methyl-1-indanone 0.15 g, 0.51 mmol, from Step A), 4-benzyloxyphenyl boronic acid (0.17 g, 0.77 mmol), palladium acetate (5.7 mg, 0.025 mmol), tricyclohexylphosphine (8.6 mg, 0.030 mmol) and potassium fluoride (0.098 g, 1.68 mmol) in tetrahydrofuran (2.5 mL) was stirred at rt. After 5 min, the reaction was loaded onto silica gel and the product eluted with 25% ethyl acetate/hexanes to give a yellow solid (0.20 g): ESI-MS 329.1 (M+H).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40]O)=[CH:33][C:32]=2[CH3:42])=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=O)C.[CH3:46][N:47]([CH3:64])[CH2:48][CH2:49][CH2:50][NH:51]S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O.CC(NS(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)(C)C(N)=O>>[C@@H:6]1([O:24][C:25]2[C:29]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH:51][CH2:50][CH2:49][CH2:48][N:47]([CH3:64])[CH3:46])=[CH:33][C:32]=3[CH3:42])=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=2)[O:7][C@H:8]([CH2:19][OH:20])[C@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CN(C)CCCNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCCO)cc2C)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: CC(C)(NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(N)=O
Product: Cc1cc(OCCCNCCCN(C)C)ccc1Cc1c(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)n[nH]c1C(C)C

Procedure:
The title compound was prepared in a similar manner to that described in Example 51 using 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-{[4-(3-hydroxypropoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole and N,N-dimethyl-N′-(2-nitrobenzenesulfonyl)-1,3-diaminopropane instead of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-hydroxypropoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole and 2-methyl-2-(2-nitrobenzenesulfonylamino)-propionamide, respectively.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:17]([CH2:20][C:21]([O:23][CH3:24])=[O:22])=[N+:18]=[N-:19].C[O-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[C:20]([N:17]=[N+:18]=[N-:19])[C:21]([O:23][CH3:24])=[O:22])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)CN=[N+]=[N-]
Reactant: O=Cc1ccc(OCc2ccccc2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)C(=Cc1ccc(OCc2ccccc2)cc1)N=[N+]=[N-]
Reaction time: 2 h

Procedure:
4-Benzyloxybenzaldehyde (10.0 g) and methyl azidoacetate (21.7 g) are dissolved in 157 ml of methanol and cooled to -10° (ice-acetone bath). Then sodium methoxide (43.1 ml, 25% in methanol) is added dropwise such that the reaction temperature does not rise above -5°. After 2 hr, the cooling bath is removed and the reaction is warmed to 20°-25°. When no starting material remains by TLC, the reaction is diluted with ether and washed with saturated aqueous ammonium chloride. The organic layer is washed with water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (hexane to 5% ethyl acetate/hexane) gives the title compound.
Reaction SMILES: Cl[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([O:13][CH2:14][CH3:15])[CH:3]=1.[C:16]1(OB(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.O>[CH2:14]([O:13][C:4]1[CH:3]=[C:2]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[CH:11][C:5]=1[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:15]
Reactant: CCOC(=O)c1ccc(Cl)cc1OCC
Reactant: OB(O)Oc1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CCOC(=O)c1ccc(-c2ccccc2)cc1OCC
Temperature: 95 °C
Reaction time: 1 h

Procedure:
0.50 g of ethyl 4-chloro-2-ethoxybenzoate, 0.31 g of phenylboric acid, 85 mg of 1,1-bis(diphenylphosphino)ferrocene dichloronickel and 1.4 g of potassium phosphate were dissolved in 8 ml dioxane, followed by stirring at 95° C. for 1 hour in a nitrogen atmosphere. After cooling the reaction solution to room temperature, ethyl acetate and water were added thereto. The mixture was filtered through Celite, and the mother liquor was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was subjected to silica gel column chromatography, and from fractions eluted with hexane-ethyl acetate (9:1), ethyl 2-ethoxy-4-phenylbenzoate was obtained. Then, the resulting ethyl 2-ethoxy-4-phenylbenzoate was dissolved in 4 ml ethanol, and 2 ml of 1N sodium hydroxide was added thereto, followed by stirring at room temperature for 6 hours. The reaction mixture was ice-cooled and neutralized with 1N hydrochloric acid, followed by extracting with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and the solvent was evaporated, to give 0.22 g of 2-ethoxy-4-phenylbenzoic acid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]=[CH:11][C:12]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]#[N:18])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].C1(P(=[CH:41][C:42]([O:44][CH3:45])=[O:43])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[C:17]([C:16]1[CH:15]=[C:14]([C:12]([CH:11]=[CH:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[CH:41][C:42]([O:44][CH3:45])=[O:43])[CH:21]=[CH:20][CH:19]=1)#[N:18]
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: N#Cc1cccc(C(=O)C=Cc2ccc([N+](=O)[O-])cc2)c1
Solvent: Cc1ccccc1
Product: COC(=O)C=C(C=Cc1ccc([N+](=O)[O-])cc1)c1cccc(C#N)c1
Temperature: 25 °C
Yield: 73.7 %

Procedure:
Part B. 3-[3-(4-nitrophenyl)-1-oxo-2-propenyl]benzonitrile (0.500 gm, 1.79 mmol) was suspended in toluene and methyl (triphenylphosphoranylidene)acetate (0.600 gm, 1.79 mmol) was added. The suspension was heated to reflux (at which point the solution becomes homogeneous) for 5 hrs. The reaction was cooled to room temperature and the solvent removed under vacuum. The residue was chromatographed on silica gel (20% ethyl acetate/toluene) to afford methyl 3-(3-cyanophenyl)-5-(4-nitrophenyl)-2,4-pentadienoate 0.441 gm (74%) as a mixture of the E/Z isomers. MS: 335(M+H)+ ; 1H NMR (CDCl3): 3.6 (s, 3H), 3.8 (s, 3H), 5.9 (s, 1H), 6.25 (m, 2H), 6.6 (d, 1H), 7.15 (m, 2H), 7.6 (m, 11H), 8.2 (d, 4H), 8.65 (d, 1H).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH:14]([CH:22]([OH:37])[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)[C:15]([O:17]C(C)(C)C)=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>ClCCl>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH:14]([CH:22]([OH:37])[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[CH:27][CH:26]=1)[C:15]([OH:17])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)C(CCNC(=O)OCc1ccccc1)C(O)CCc1ccc(-c2ccccc2)cc1
Solvent: ClCCl
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(NCCC(C(=O)O)C(O)CCc1ccc(-c2ccccc2)cc1)OCc1ccccc1
Reaction time: 4 h
Yield: 70.3 %

Procedure:
To a solution of the compound (40 mg) obtained from step 2 above in dry dichloromethane (10 ml) at 0° C. was added trifluoroacetic acid (0.5 ml) and anisole (0.05 ml) and stirred for 4 hours. The solvent and excess reagents were evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 60% ethyl acetate in hexane as eluant to furnish the title compound (25 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:31]1[CH2:30][CH2:29][N:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[O:21][CH3:20])[CH2:33][CH2:32]1)=[O:19])=[N:5]2
Reactant: CCOC(=O)Nc1nc2cc(F)ccc2nc1OC
Reactant: COc1ccccc1N1CCNCC1
Product: COc1ccccc1N1CCN(C(=O)Nc2nc3cc(F)ccc3nc2OC)CC1
Yield: 84 %

Procedure:
Ethyl N-(6-fluoro-2-methoxyquinoxalin-3-yl)carbamate and 1-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound (yield, 84%). 1H NMR (200 MHz, CDCl3): δ 3.15 (s, 4H), 3.79-3.87 (m, 6H), 4.11 (s, 4H), 6.86-7.02 (m, 4H), 7.18-7.22 (m, 1H), 7.39-7.50 (m, 1H), 7.65-7.72 (m, 1H).