Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N+:11]([O-])=O)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1>C1COCC1.[Pd]>[CH3:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1
Reactant: Cc1cc2c(c([N+](=O)[O-])c1)OCC2
Agent: [Pd]
Solvent: C1CCOC1
Product: Cc1cc(N)c2c(c1)CCO2
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of 5-methyl-7-nitro-2,3-dihydrobenzofuran (1c) (0.30 g, 1.7 mmol) and Pd/C (150 mg, 50%) in THF (5 mL) was introduced H2. It was stirred at ambient temperature for 12 h. The mixture was filtered through celite and concentrated to give the title compound (1d) as a solid. MS-ESI (m/z): 150 (M+1)+.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]2.CC1(C)COB([C:23]2[CH:24]=[CH:25][C:26]([F:36])=[C:27]([CH:35]=2)[CH2:28][N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)OC1>>[F:36][C:26]1[CH:25]=[CH:24][C:23]([C:2]2[CH:11]=[CH:10][N:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]3)=[CH:35][C:27]=1[CH2:28][N:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1
Reactant: CC1(C)COB(c2ccc(F)c(CN3CCOCC3)c2)OC1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2n1
Product: Fc1ccc(-c2ccnc3nc(C(F)(F)F)ccc23)cc1CN1CCOCC1
Yield: 11.6 %

Procedure:
5-Chloro-2-trifluoromethyl[1,8]naphthyridine (50 mg, 0.22 mmol) was coupled to 4-[5-(5,5-dimethyl[1,3,2]dioxaborinan-2-yl)-2-fluorobenzyl]morpholine (86 mg, 0.28 mmol) as described in Example 7 part g), affording 5-(4-fluoro-3-morpholin-4-ylmethylphenyl)-2-trifluoromethyl[1,8]naphthyridine (10 mg, 12%). δH (360 MHz, CDCl3) 2.54 (4H, t, J 4.2), 3.68 (2H, s), 3.71 (4H, t, J 4.4), 7.26 (1H, t, 8.8), 7.37 (1H, m), 7.55-7.58 (2H, m), 7.82 (1H, d, J 8.4), 8.49 (1H, d, J 8.4), 9.27 (1H, d, J 4.2). m/z (ES+) 392 [MH]+.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[NH:7][CH2:6][C:5]=12.[Cl:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][N:17]=1>ClCCl>[Cl:15][C:16]1[N:17]=[CH:18][C:19]([C:20]([N:7]2[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[CH2:10][N:4]3[CH:3]=[CH:2][CH:1]=[C:5]3[CH2:6]2)=[O:21])=[CH:23][CH:24]=1
Reactant: O=C(Cl)c1ccc(Cl)nc1
Reactant: c1ccc2c(c1)Cn1cccc1CN2
Solvent: ClCCl
Product: O=C(c1ccc(Cl)nc1)N1Cc2cccn2Cc2ccccc21
Reaction time: 1 h

Procedure:
A solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (100 mmol) and N,N′-diisopropylethyl amine (130 mmol) in dichloromethane (500 mL) was cooled to 0° C. 6-Chloronicotinoyl chloride (130 mmol) was added dropwise under nitrogen. The solution was stirred for one hour as it returned to room temperature. The reaction mixture was filtered through a sica gel pad, washed with 0.5 N sodium hydroxide and water, dried over anhydrous magnesium sulfate. The solution was again filtered through a silica gel pad and evaporated to dryness in vacuo. The residual oil crystallized from diethyl ether to provide the title compound as a colorless crystalline solid, m.p. 165–167° C.
Reaction SMILES: [OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:11](=[O:24])/[CH:12]=[CH:13]/[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([F:23])([F:22])[F:21]>CS(C)=O.O1CCOCC1>[N+:8]([C:7]1[CH:6]=[CH:5][CH:4]=[C:3]2[C:2]=1[O:1][C:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]([F:21])([F:22])[F:23])=[CH:12][C:11]2=[O:24])([O-:10])=[O:9]
Reactant: O=C(/C=C/c1ccccc1C(F)(F)F)c1cccc([N+](=O)[O-])c1O
Solvent: C1COCCO1
Solvent: CS(C)=O
Product: O=c1cc(-c2ccccc2C(F)(F)F)oc2c([N+](=O)[O-])cccc12
Temperature: 25 °C
Yield: 92.3 %

Procedure:
A solution of (E)-1-(2-hydroxy-3-nitrophenyl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one 9 (1.4 g, 4.2 mmol) and SeO2 (1.4 g, 12.5 mmol) in DMSO/dioxane (35 ml, 1:15) was heated at reflux for 12 h. After cooling to room temperature, the reaction mixture was passed through a filter and the filtrate was concentrated to dryness. The crude residue was suspended in H2O and collected by filtration to give 10 as a yellow solid (1.3 g, 92% yield).
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.CI.[C:13]([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:13])[CH:6]=[CH:5]2
Reactant: O=C([O-])[O-]
Reactant: Ic1ccc2[nH]ccc2c1
Agent: [K+]
Solvent: CI
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cn1ccc2cc(I)ccc21

Procedure:
5-Iodoindole (4.8 g, 20 mmol) was stirred in dry DMF (20 ml) containing MeI (8.5 g, 60 mmol) and K2CO3 (13.8 g, 100 mmol) for overnight at 55° C. The reaction mixture was diluted with EtOAc and passed through celite plug. The illiterate was evaporated to dryness and then oil was further purified by small flash column, Yield (90%). 1H NMR (300 MHz, CDCl3) δ: 3.75 (s, 3H, NMe), 6.39 (d, J=3.0, 1H), 6.98 (d, J=3.0, 1H), 7.07 (d, J=9.0, 1H), 7.44 (dd, J1=9.0, J2=1.2, 1H), 7.93 (d, J=1.2, 1H).
Reaction SMILES: [CH3:1][C:2]([CH:8]1[C:21]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[O:15][C:14]2[C:9]1=[CH:10][CH:11]=[C:12](B1OC(C)(C)C(C)(C)O1)[CH:13]=2)([CH3:7])[C:3]([O:5][CH3:6])=[O:4].Br[C:32]1[CH:42]=[CH:41][C:35]([C:36]([N:38]([CH3:40])[CH3:39])=[O:37])=[CH:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.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>[CH3:39][N:38]([CH3:40])[C:36]([C:35]1[CH:41]=[CH:42][C:32]([C:12]2[CH:13]=[C:14]3[C:9]([CH:8]([C:2]([CH3:1])([CH3:7])[C:3]([O:5][CH3:6])=[O:4])[C:21]4[C:16]([O:15]3)=[N:17][CH:18]=[CH:19][CH:20]=4)=[CH:10][CH:11]=2)=[CH:33][CH:34]=1)=[O:37]
Reactant: CN(C)C(=O)c1ccc(Br)cc1
Reactant: COC(=O)C(C)(C)C1c2ccc(B3OC(C)(C)C(C)(C)O3)cc2Oc2ncccc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)(C)C1c2ccc(-c3ccc(C(=O)N(C)C)cc3)cc2Oc2ncccc21
Temperature: 100 °C
Yield: 73 %

Procedure:
A mixture of the product from Step 5 (65 mg, 0.159 mmol), 4-bromo-N,N-dimethylbenzamide (72.4 mg, 0.318 mmol), 2.0 M aqueous potassium phosphate (0.397 mL, 0.794 mmol) and Pd(Ph3P)4 (27.5 mg, 0.024 mmol) in DMF (3 mL) was purged with N2, heated to 100° C. for 15 h, and cooled to room temperature. After addition of ethyl acetate (80 mL), the mixture was washed with water (10 mL), brine (10 mL), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography (silica, 30-100% ethyl acetate in hexanes) to provide methyl 2-(8-(4-(dimethylcarbamoyl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoate (50 mg, 73%). MS (ES+) m/z: 431 (M+H).
Reaction SMILES: I[C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[C:9]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[N:8]=2)[CH:6]=1.[C:27]([NH:31][S:32]([C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)(=[O:34])=[O:33])([CH3:30])([CH3:29])[CH3:28]>>[C:27]([NH:31][S:32]([C:35]1[CH:36]=[CH:37][CH:38]=[C:39]([C:2]2[N:3]=[CH:4][N:5]([C:7]3[CH:12]=[C:11]([C:13]([F:14])([F:16])[F:15])[CH:10]=[C:9]([C:17]4[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=4)[N:8]=3)[CH:6]=2)[CH:40]=1)(=[O:34])=[O:33])([CH3:30])([CH3:28])[CH3:29]
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)cc(-n3cnc(I)c3)n2)cc1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cn(-c3cc(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)n3)cn2)c1

Procedure:
The title compound was prepared from 2-(4-iodo-imidazol-1-yl)-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyridine (example E.23) (0.483 g, 1.0 mmol) and commercially available 3-(tert-butylsulfamoyl)-benzeneboronic acid (0.334 g, 1.3 mmol) according to the general procedure VI. Obtained as a white solid (0.126 g, 22%). MS (ISP) 539.3 [(M+H)+].
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[N:10]([CH:14]=[CH:15][N:16]=3)[CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>C(Cl)Cl>[CH3:17][S:18]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]3[N:10]([CH:14]=[CH:15][N:16]=3)[CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=1)(=[O:20])=[O:19]
Reactant: Nc1ccc(-c2cccn3ccnc23)cc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CS(=O)(=O)Nc1ccc(-c2cccn3ccnc23)cc1
Temperature: 5 °C
Reaction time: 12 h

Procedure:
Dissolve 4 g (19.1 mmol) of the product from Example 20, in 100 ml of methylene chloride and cool to 0° C. Add 1.6 ml of methanesulfonyl chloride slowly, maintaining the temperature at 5° C. Stir at r.t. for 12 hr. Extract the reaction mixture with 100 ml of 10% sodium hydroxide. Wash with 100 ml of methylene chloride and with 100 ml of ether. Treat with charcoal and neutralize with ammonium chloride. The resulting precipitate is filtered and washed with water to provide the title compound.
Reaction SMILES: [CH3:1][C:2]1[C:11]([N+:12]([O-])=O)=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]>C(O)(=O)C>[CH3:1][C:2]1[C:11]([NH2:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1C
Solvent: CC(=O)O
Product: COC(=O)c1cccc(N)c1C
Reaction time: 1.5 h
Yield: 101.6 %

Procedure:
Methyl 2-methyl-3-nitrobenzoate (10.0 g) is dissolved in acetic acid (50 ml) and thereto 5% Pd--C (1 g) is added to carry out catalytic reduction at room temperature under 1 atm. After 1.5 hours, the catalyst is filtered off. The reaction mixture is concentrated, and thereto is added water, and the mixture is made alkaline with potassium carbonate, followed by extraction with dichloromethane. The solvent is concentrated to give methyl 2-methyl-3-aminobenzoate (8.6 g).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:10])[C:7]([OH:9])=[O:8].[CH3:11][C:12](=[CH2:14])[CH3:13].S(=O)(=O)(O)O>CCOCC>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:10])[C:7]([O:9][C:12]([CH3:14])([CH3:13])[CH3:11])=[O:8]
Reactant: O=C(O)C(=O)c1ccco1
Reactant: C=C(C)C
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: CC(C)(C)OC(=O)C(=O)c1ccco1
Reaction time: 72 h

Procedure:
Fur-2-ylglyoxylic acid (12.5g) and liquid isobutylene (ca 25 ml) were added to a cooled stirred solution of sulphuric acid (10 ml) in anhydrous ether (100 ml) and the solution was kept at 3° C for 3 days. Ether (150 ml) was added, the solution washed with aqueous sodium bicarbonate solution until free from acid, dried over sodium sulphate and evaporated, giving a brown oil. The oil was distilled at 76°-82° C/0.3 mm, giving t-butyl fur-2-ylglyoxylate (11.6g) λmax (EtOH) 233 (ε2,080) and 286 nm (ε11,700), νmax (CHBr3) 1718 (CO2But) and 1664 cm-1 (=C-CO-), τ (DMSO.d 6; 60 MHz) 1.80, 2,32, 3.15 (furyl protons) and 8.41 (But).
Reaction SMILES: CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)[N:8]=1)=O.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][NH2:33])[CH:27]=1>>[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][C:17]([O:20][C:21]([F:22])([F:23])[F:24])=[CH:16][CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:33]2)[CH:27]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2ccc(OC(F)(F)F)cc2)ccc1=O
Reactant: NNc1cccnc1
Product: O=c1ccn(-c2ccc(OC(F)(F)F)cc2)nc1-c1ccnn1-c1cccnc1

Procedure:
The product was obtained starting from 3-((E)-3-Dimethylamino-acryloyl)-1-(4-trifluoromethoxy-phenyl)-1H-pyridazin-4-one (A-8) and pyridine-3-yl-hydrazine according to the method described for example 43. MS: M=400.1 (M+H)+
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][N:3]=1.[C:11]1([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:11]1([N:17]2[CH2:22][CH2:21][N:20]([C:2]3[N:3]=[CH:4][C:5]([NH2:8])=[CH:6][CH:7]=3)[CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Product: Nc1ccc(N2CCN(c3ccccc3)CC2)nc1

Procedure:
Intermediate B-12 was prepared by the general procedure for intermediate B-2, by using 2-chloro-5-nitropyridine and 1-phenylpiperazine as starting materials. LCMS (ESI) calcd for [M+1]+ 255.2. found 255.1.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]#[CH:16])[CH:6]=1)=[O:4].C#CCCCCCC.[I:27][C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1.IC1C=C2C(=CC=1)CN(C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C2>>[F:18][C:2]([F:1])([F:17])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]#[C:16][C:31]2[CH:32]=[CH:33][C:28]([I:27])=[CH:29][CH:30]=2)[CH:6]=1)=[O:4]
Reactant: Ic1ccc(I)cc1
Reactant: C#CCn1cc(C(=O)C(F)(F)F)c2ccccc21
Agent: C#CCCCCCC
Agent: Ic1ccc2c(c1)CN(C(c1ccccc1)(c1ccccc1)c1ccccc1)C2
Product: O=C(c1cn(CC#Cc2ccc(I)cc2)c2ccccc12)C(F)(F)F
Yield: 51 %

Procedure:
When the product of Step B was substituted for 1-octyne and 1,4 diiodobenzene was substituted for 5-iodo-2-tritylisoindoline in Example 2, Step D, the similar process afforded the title compound in 51% yield, as light yellow solid. 1H-NMR (CDCl3) 5.16 (s, 2H); 7.14 (d, 2H, J=8.30 Hz); 7.38-7.44 (m, 2H); 7.51-7.55 (m, 1H); 7.66 (tr, 2H, J=8.36 Hz); 8.12 (b, 1H); 8.40-8.43 (m, 1H).
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2[O:19][CH:20]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:21]([OH:24])[CH2:22][N:23]=2)[CH:14]=[CH:15][C:16]=1[Cl:17]>ClCCCl>[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2[O:19][CH:20]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:21]([O:24][C:8](=[O:9])[NH:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:22][N:23]=2)[CH:14]=[CH:15][C:16]=1[Cl:17]
Reactant: OC1CN=C(c2ccc(Cl)c(Cl)c2)OC1c1ccccc1
Reactant: O=C=Nc1ccccc1
Solvent: ClCCCl
Product: O=C(Nc1ccccc1)OC1CN=C(c2ccc(Cl)c(Cl)c2)OC1c1ccccc1
Yield: 63.5 %

Procedure:
Phenyl isocyanate (1.7 g) is added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of (5RS, 6SR)-2-(3,4-dichlorophenyl)-6-phenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (4.7 g) in 1,2-dichloroethane (50 cc). The solution obtained is heated to reflux for 3 hours and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by chromatography on silica (0.063-0.2 mm; 100 g) contained in a column 2.5 cm in diameter [eluent: cyclohexane/ethyl acetate (7:3 by volume)], collecting 20-cc fractions. Fractions 2 to 10 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in diisopropyl ether, (5RS, 6SR)-2-(3,4-dichlorophenyl)-6-phenyl-5-phenylcarbamoyloxy-5,6-dihydro-4H-1,3-oxazine (4 g), m.p. 130° C., is obtained.
Reaction SMILES: [C:1]([C@:3]1([CH2:17][O:18][C:19](=[O:21])[CH3:20])[O:7][C@@H:6]([N:8]2[CH:15]=[CH:14][C:12](=[O:13])[NH:11][C:9]2=[O:10])[CH2:5][C@@H:4]1[OH:16])#[N:2].[C:22](OC(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1>[C:1]([C@:3]1([CH2:17][O:18][C:19](=[O:21])[CH3:20])[O:7][C@@H:6]([N:8]2[CH:15]=[CH:14][C:12](=[O:13])[NH:11][C:9]2=[O:10])[CH2:5][C@@H:4]1[O:16][C:22](=[O:24])[CH3:23])#[N:2]
Reactant: CC(=O)OC[C@@]1(C#N)O[C@@H](n2ccc(=O)[nH]c2=O)C[C@@H]1O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OC[C@@]1(C#N)O[C@@H](n2ccc(=O)[nH]c2=O)C[C@@H]1OC(C)=O

Procedure:
A solution of 2'-deoxy-4'-cyano-5'-O-acetyl uridine (24 mg, 0.08 mM) and acetic anhydride (20μl) in pyridine (0.2 ml) was stirred at room temperature for 5 h. The solvent was removed by evaporation and the residue was chromatographed on silica gel eluting with 5% CH3OH/CH2Cl2 to give 2'-deoxy-4'-cyano-3'O,5'O-diacetyl uridine (23 mg, 0.07 mM). Accurate Mass Calcd. for C14H15N3O7 : 337.0910. Found: 337.0911
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:22])[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:15][C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][CH:13]=3)=[CH:4][CH:3]=1.C[O:24][C:25](=[O:47])[C@H:26]([CH2:45]O)[NH:27]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([O:22][CH2:45][C@@H:26]([C:25]([OH:47])=[O:24])[NH2:27])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[O:15][C:16]3[C:21]2=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:6][CH:7]=1
Reactant: COC(=O)[C@H](CO)NC(=O)OCC1c2ccccc2-c2ccccc21
Reactant: OC1(c2ccc(F)cc2)c2ccccc2Oc2ccccc21
Product: N[C@@H](COC1(c2ccc(F)cc2)c2ccccc2Oc2ccccc21)C(=O)O

Procedure:
from 9-(4-fluorophenyl)-9H-xanthen-9-ol (Example 1 m) and Nα -(9-fluorenylmethoxycarbonyl)-L-serine methyl ester;
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=1.[Li]CCCC.[CH3:15][C:16]1([CH3:28])[C:20](=[O:21])[C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:18][CH2:17]1>C1COCC1>[CH3:15][C:16]1([CH3:28])[C:20]([C:2]2[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=2)([OH:21])[C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:18][CH2:17]1
Reactant: CSc1ccc(Br)cc1
Reactant: CC1(C)CC=C(c2ccccc2)C1=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CSc1ccc(C2(O)C(c3ccccc3)=CCC2(C)C)cc1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 87.5 %

Procedure:
To a −78° C. solution of p-bromothioanisole (5 g) in 100 mL of THF was added a solution n-BuLi (10 mL, 2.5 M in hexane). After stirring for 45 min. at −78° C., a solution of the product of Step 3 (2.4 g) in 10 mL of THF was added dropwise. The reaction mixture was stirred for 10 min. and then quenched with 100 mL of saturated solution of NH4Cl. The product was extracted with 300 mL of 2:1 hexanes/EtOAc. The extract was dried over Na2SO4 and concentrated. Th e residue was purified by chromatography eluting with 10:1 hexane/EtOAc to give 3.5 g of the title compound.
Reaction SMILES: [N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[NH2:23])=[CH:6][CH:5]=1)([O-])=O.CCOC(C)=O.C(Cl)Cl.[H][H]>CO.[Pt]>[NH2:1][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[NH2:23])=[CH:6][CH:5]=1
Reactant: Nc1cnccc1CCOc1ccc([N+](=O)[O-])c2ccccc12
Reactant: [H][H]
Agent: [Pt]
Solvent: CO
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Nc1cnccc1CCOc1ccc(N)c2ccccc12
Yield: 96.8 %

Procedure:
A solution of 4-(2-(4-nitronaphthalen-1-yloxy)ethyl)pyridin-3-amine (26) (700 mg, 2.263 mmol) in a mixture of MeOH (50 mL), EtOAc (25 mL), and DCM (25 mL) was passed through a Thales H-cube (10% Pt/C, 30 mm, 1.0 mL·min−1, 40° C., full hydrogen mode). The solvent was removed in vacuo to give the title compound (27) as a brown solid (612 mg, 92%). m/z 280 (M+H)+ (ES+).
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)=O.[CH3:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=O.O.C1(C)C(S(O)(=O)=O)=CC=CC=1>O>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]2[CH:17]=[C:4]([C:6]3[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=3)[C:3]3[C:2](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:1]=2)=[CH:21][CH:22]=1
Reactant: CC(=O)c1ccc(F)cc1
Reactant: Nc1ccccc1C(=O)c1ccc(F)cc1
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: O
Product: Fc1ccc(-c2cc(-c3ccc(F)cc3)c3ccccc3n2)cc1
Temperature: 200 °C

Procedure:
A flask is loaded with (17) (21.5 g, 0.1 mol), 4-fluoroacetophenone (13.8 g, 0.1 mol), and toluene sulfonic acid monohydrate (3.8 g, 0.02 mol). The flask is heated to 200° C. and the water of condensation removed. After water evolution ceased, the mixture is cooled and the crude solid product is crushed and washed with hot ethanol The product is further recrystallized from toluene.
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:8]=[C:7]([N+:17]([O-:19])=[O:18])[C:5]=1N)([O-:3])=[O:2].N([O-])=O.[Na+].[S-:24][C:25]#[N:26].[K+].C(=O)([O-])O.[Na+]>S(=O)(=O)(O)O.O.[Cu]SC#N>[N+:1]([C:4]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:8]=[C:7]([N+:17]([O-:19])=[O:18])[C:5]=1[S:24][C:25]#[N:26])([O-:3])=[O:2]
Reactant: Nc1c([N+](=O)[O-])cc(-c2cccnc2)cc1[N+](=O)[O-]
Reactant: N#C[S-]
Agent: N#CS[Cu]
Agent: O=C([O-])O
Agent: O=N[O-]
Solvent: O
Product: N#CSc1c([N+](=O)[O-])cc(-c2cccnc2)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A suspension of 2,6-Dinitro-4-pyridin-3-yl-aniline (1.24 g, 4.76 mmol) in aqueous sulfuric acid (50% v/v, 12 ml) was stirred at ambient temperature for 1 h before being cooled in an ice bath and treated over 5 min with an aqueous sodium nitrite solution (20% w/v, 2.0 ml). The mixture was stirred in the cold for 1.5 h before being treated with a solution of potassium thiocyanate (0.6 g) in water (1.4 ml) in one portion. The resultant mixture was stirred in the cold for 15 min and then added to a suspension of copper (I) thiocyanate (1.0 g) in water (4 ml) whilst cooling in an ice-bath. The mixture was stirred in the cold for 2 h and then heated to 70° C. for 20 min. After cooling to ambient temperature, the mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate (200 ml) and extracted with ethyl acetate (3×100 ml) which was washed with brine (200 ml) and dried (MgSO4). The solvent was removed in vacuo to give a residue which was purified by flash chromatography (silica) eluting with 80% to 100% ethyl acetate in 40-60 petroleum ether. The 3-(3,5-Dinitro-4-thiocyanato-phenyl)-pyridine was obtained as a yellow solid (1.07 g, 74%).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]12[CH2:21][CH:16]([C:17]([CH3:20])([CH3:19])[O:18]1)[CH2:15][CH2:14][CH:13]2[OH:22].C(N(CC)CC)C>C(Cl)Cl>[CH3:11][C:12]12[CH2:21][CH:16]([C:17]([CH3:19])([CH3:20])[O:18]1)[CH2:15][CH2:14][C:13]2=[O:22]
Reactant: CC1(C)OC2(C)CC1CCC2O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CC12CC(CCC1=O)C(C)(C)O2
Temperature: -60 °C
Reaction time: 0.17 h
Yield: 122.4 %

Procedure:
To a solution of 6.72 g of oxalyl chloride in 150 ml of methylene chloride at -60° C. was added dropwise 8.24 g of dimethyl sulfoxide in 20 ml of methylene chloride. After stirring for 10 minutes at -60° C. under a nitrogen atmosphere, a solution of 7.50 g of 5,7,7-trimethyl-6-oxabicyclo[3.2.1]octan-4-ol in 40 ml of methylene chloride was added dropwise. A white precipitate formed. After stirring in the cold for 15 minutes, 22.22 g of triethylamine was added in a stream via syringe. The reaction mixture was allowed to rise to room temperature and after 15 minutes was poured into 200 ml of ice water. The resulting phases were separated and the aqueous phase was extracted with two 100 ml portions of methylene chloride. The combined organic phases were washed twice with 100 ml portions of saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo to leave 9.07 g of an orange liquid containing some beige solid. This crude mixture was diluted with hexane and filtered. The filtrate was dried (MgSO4) and concentrated in vacuo to leave 8.06 g of orange liquid. Vacuum distillation of the liquid gave two fractions of the desired product; 4.35 g, b.p. 78°-85° C. (4 mm) of 82% purity by GLC and 1.86 g, b.p. 85°-93° C. (4 mm) of 95% purity by GLC.
Reaction SMILES: Br[C:2]1[C:3]([CH3:19])=[C:4]([CH3:18])[C:5]2[O:9][C:8]([CH2:11][O:12][CH2:13][O:14][CH3:15])([CH3:10])[CH2:7][C:6]=2[C:16]=1[CH3:17].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1>>[CH3:15][O:14][CH2:13][O:12][CH2:11][C:8]1([CH3:10])[CH2:7][C:6]2[C:16]([CH3:17])=[C:2]([N:31]3[CH2:30][CH2:29][N:28]([C:25]4[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=4)[CH2:33][CH2:32]3)[C:3]([CH3:19])=[C:4]([CH3:18])[C:5]=2[O:9]1
Reactant: COCOCC1(C)Cc2c(C)c(Br)c(C)c(C)c2O1
Reactant: COc1ccc(N2CCNCC2)cc1
Product: COCOCC1(C)Cc2c(C)c(N3CCN(c4ccc(OC)cc4)CC3)c(C)c(C)c2O1
Yield: 47.5 %

Procedure:
By using 5-bromo-2-[(methoxymethoxy)methyl]-2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran (1.62 g, 4.92 mmol) synthesized in Reference Example 163 and 1-(4-methoxyphenyl)piperazine (1.89 g, 9.84 mmol), the reaction was carried out in the same manner as Example 1 to synthesize 1.03 g of the title compound (yield 48%).