Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH2:8][S:9]([C:11]2[N-:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)=[O:10])=[N:6][CH:5]=[CH:4][C:3]=1[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25].[Na+].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH3:1][C:2]1[C:7]([CH2:8][S+:9]([O-:10])[C:11]2[NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[N:19]=2)=[N:6][CH:5]=[CH:4][C:3]=1[O:20][CH2:21][CH2:22][CH2:23][O:24][CH3:25]
Reactant: COCCCOc1ccnc(CS(=O)c2nc3ccccc3[n-]2)c1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COCCCOc1ccnc(C[S+]([O-])c2nc3ccccc3[nH]2)c1C
Temperature: 25 °C
Reaction time: 25 h

Procedure:
100 g of rabeprazole sodium salt (amorphous) is dissolved at approximately 25° C. in 450 ml of ethyl acetate. The solution is kept at approximately 25° C. and 8 ml of sodium bicarbonate saturated solution is added. The mixture is kept under stirring at approximately 25° C. for 25 hours. The resulting white solid is filtered by suction, washed with 100 ml of ethyl acetate and dried under vacuum at 45° C. The resulting product has the same physical characteristics of the product obtained in example 1.
Reaction SMILES: [CH2:1]([P:3]([CH2:10][CH2:11][CH2:12][NH2:13])(=[O:9])[O:4]CCCC)[CH3:2].O>C(O)CCC.O>[CH2:1]([P:3]([CH2:10][CH2:11][CH2:12][NH2:13])(=[O:4])[OH:9])[CH3:2]
Reactant: CCCCOP(=O)(CC)CCCN
Solvent: O
Solvent: CCCCO
Product: CCP(=O)(O)CCCN
Reaction time: 4 h
Yield: 97.9 %

Procedure:
414 g (2 mol) of butyl ethyl(3-aminopropyl)phosphinate (produced as in Example 6) are initially charged to a 1 l five-neck flask equipped with thermometer, reflux condenser, high-performance stirrer and dropping funnel. At 160° C., during 4 h, 500 ml of water are metered in and a butanol-water mixture is distilled off. The solid residue is recrystallized from acetone to obtain 296 g (98% of theory) of ethyl(3-aminopropyl)phosphinic acid as colorless solid.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][CH2:11][CH2:12][OH:13])[N:5]=1)(=[O:3])[CH3:2].[F:14][C:15]([F:31])([F:30])[C:16]1[O:20][N:19]=[C:18]([C:21]2[CH:26]=[C:25]([CH3:27])[C:24](O)=[C:23]([CH3:29])[CH:22]=2)[N:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>CN(C=O)C.O>[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][CH2:11][CH2:12][O:13][C:24]2[C:23]([CH3:29])=[CH:22][C:21]([C:18]3[N:17]=[C:16]([C:15]([F:14])([F:31])[F:30])[O:20][N:19]=3)=[CH:26][C:25]=2[CH3:27])[N:5]=1)(=[O:3])[CH3:2]
Reactant: Cc1cc(-c2noc(C(F)(F)F)n2)cc(C)c1O
Reactant: CC(=O)c1cccc(CCCO)n1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1cccc(CCCOc2c(C)cc(-c3noc(C(F)(F)F)n3)cc2C)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 0.1 g (0.55 mmol) of 2-acetyl-6-(3-hydroxypropyl)-pyridine, 0.14 g of 4-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-2,6-dimethylphenol, 0.175 g (1.2 eq) of triphenylphosphine in DMF under nitrogen at 0° C. was added dropwise a solution of 0.097 g (1.2 eq) of DEAD in DMF. The bright red solution was stirred at room temperature overnight, diluted with water, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and the residue was purifed by MPLC to afford 2-acetyl-6-[3-[4-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-2,6-dimethylphenoxy]-propyl]-pyridine.
Reaction SMILES: [C:1]1([NH:7][N:8]=[C:9]([C:12]#[N:13])[C:10]#[N:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(O)(O)(=O)=O.[CH3:19][NH:20][NH2:21]>>[CH3:19][N:20]1[C:10]([NH2:11])=[C:9]([N:8]=[N:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:12]([NH2:13])=[N:21]1
Reactant: CNN
Reactant: N#CC(C#N)=NNc1ccccc1
Agent: O=S(=O)(O)O
Product: Cn1nc(N)c(N=Nc2ccccc2)c1N

Procedure:
1-methyl-4-phenylazo-1H-pyrazole-3,5-diamine was prepared using 2-phenylhydrazonomalononitrile (425 mg) and methylhydrazine sulfate (720 mg). The compound was purified by column chromatography and afforded a yellow solid.
Reaction SMILES: CC(C)([O-])C.[Na+].[C:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([CH3:18])[C:11]=1[NH:19][C:20]([C:22]1[S:23][CH:24]=[C:25]([CH:27]([CH3:29])[CH3:28])[N:26]=1)=O)(=[O:9])[CH3:8]>C(O)(C)(C)C.C(OCC)(=O)C>[CH:27]([C:25]1[N:26]=[C:22]([C:20]2[CH:8]=[C:7]([OH:9])[C:10]3[C:11](=[C:12]([CH3:18])[C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[N:19]=2)[S:23][CH:24]=1)([CH3:29])[CH3:28]
Reactant: COc1ccc(C(C)=O)c(NC(=O)c2nc(C(C)C)cs2)c1C
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CC(C)(C)O
Solvent: CCOC(C)=O
Product: COc1ccc2c(O)cc(-c3nc(C(C)C)cs3)nc2c1C
Temperature: 90 °C
Reaction time: 4 h
Yield: 108.3 %

Procedure:
Sodium tert-butoxide (3.20 g, 28.6 mmol., 2.1 eq.) was added portion wise, at ambient temperature, to a solution of 1-acetyl-2-[(4-isopropyl-thiazol-2-yl)-carbonylamino]-3-methyl-4-methoxy-benzene (4.52 g, 13.6 mmol., 1.0 eq.) in dry tert-butanol (45 mL). The reaction mixture was stirred at 90° C. for 4 hours. LCMS analysis showed the reaction to be complete. The reaction mixture was left to cool to ambient temperature and then diluted with ethyl acetate (100 mL). The organic layer was washed with 1M aqueous potassium hydrogen sulphate (75 mL), water (50 mL), brine (50 mL), dried over sodium sulphate, filtered and the solvent removed under vacuum to give 4.63 g (99%) of the title compound as an off white solid. 1H NMR (500 MHz, CDCl3) δ ppm 9.59 (br. s, 1 H), 8.26 (d, J=9.16 Hz, 1 H), 7.10 (s, 1 H), 7.03 (d, J=9.16 Hz, 1 H), 6.77 (s, 1 H), 3.98 (s, 3 H), 3.20 (spt, J=6.87 Hz, 1 H), 2.43 (s, 3 H), 1.39 (d, J=7.02 Hz, 6 H). LC-MS: 95% (UV), tR 2.24 min, m/z [M+1]+ 315.15.
Reaction SMILES: [CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([O:20]CC)=[O:19])=[O:15])[C:10](=[O:23])[NH:9][C:8]2=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[F:40])[CH2:35]Br.Cl>CC(N(C)C)=O>[CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])[C:10](=[O:23])[N:9]([CH2:35][C:34]3[CH:37]=[CH:38][C:39]([F:40])=[C:32]([F:31])[CH:33]=3)[C:8]2=[O:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Fc1ccc(CBr)cc1F
Reactant: CCOC(=O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)[nH]c1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: O=C(O)CNC(=O)c1c(O)n(C2CCCCC2)c(=O)n(Cc2ccc(F)c(F)c2)c1=O
Reaction time: 8 h
Yield: 31.6 %

Procedure:
A mixture of ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate (340 mg, 1.0 mmoles), pulv. potassium carbonate (750 mg, 5.35 mmoles) and 3,4-difluorobenzyl bromide (256 uL, 2.0 mmoles) in dimethylacetamide (5 mL) was vigorously stirred at 100° C. for 3 hours. The mixture was poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The combined organic solutions were washed with 1 molar hydrochloric acid and evaporated. The residue was purified by flash chromatography (10-50% ethyl acetate in hexane), the required fractions evaporated, dissolved in ethanol (5 mL) and 1 molar sodium hydroxide solution (3.0 mL) added. The mixture was stirred overnight, acidified and extracted with ethyl acetate (×2), the combined extracts washed with 1 molar hydrochloric acid, dried and evaporated. Recrystallization from ethanol-water gave the title compound (138 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.11 (br. s., 1 H), 10.12 (br. s., 1 H), 7.28-7.52 (m, 2 H), 7.05-7.23 (m, J=5.43, 3.16 Hz, 1 H), 4.96 (s, 2 H), 4.63 (t, J=12.00 Hz, 1 H), 4.13 (d, J=5.81 Hz, 2 H), 2.25 (q, 2 H), 1.78 (d, J=12.88 Hz, 2 H), 1.63 (s, 3 H), 1.28 (q, J=12.97 Hz, 2 H), 1.11 (q, 1 H)
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7](=[O:43])[N:8]([C@@H:10]2[O:32][C@H:31]([CH2:33][O:34]C(=O)C3C=CC=CC=3)[C@@H:21]([O:22]C(=O)C3C=CC=CC=3)[C@H:11]2[O:12]C(=O)C2C=CC=CC=2)[CH:9]=1)([O-:3])=[O:2]>N>[C@@H:10]1([N:8]2[CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]2=[O:43])[O:32][C@H:31]([CH2:33][OH:34])[C@@H:21]([OH:22])[C@H:11]1[OH:12]
Reactant: O=C(OC[C@H]1O[C@@H](n2cc([N+](=O)[O-])ccc2=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Agent: N
Product: O=c1ccc([N+](=O)[O-])cn1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of 5-nitro-1-(2′,3′,5′-tri-O-benzoyl-β-ribofuranosyl)-2-pyridone (10, R=Bz, Y=H, Z=CH; 100 mg, 0.17 mmol) and saturated methanolic ammonia (10 mL) was stirred at room temperature for 12 h. The mixture was concentrated to dryness, and the residue triturated with EtOH to precipitate 10 (R=Y=H, Z=CH), which was collected and recrystallized from water (37 mg, 81%) as a white solid. 1H NMR (DMSO-d6+D2O) δ 3.64 (m, 1H), 3.90 (m, 1H), 4.01 (m, 3H), 5.89 (s, 1H), 6.48 (d, J=10.4 Hz, 1H), 8.12 (dd, J=3.2, 10 Hz, 1H), 9.65 (d, J=3.2 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[NH2:27][CH2:28][C:29]1[CH:30]=[N:31][C:32]([CH2:35][O:36][CH:37]([CH3:39])[CH3:38])=[CH:33][CH:34]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:27][CH2:28][C:29]1[CH:30]=[N:31][C:32]([CH2:35][O:36][CH:37]([CH3:39])[CH3:38])=[CH:33][CH:34]=1
Reactant: O=C(N1CCc2ccc(Cl)c(OS(=O)(=O)C(F)(F)F)c2CC1)C(F)(F)F
Reactant: CC(C)OCc1ccc(CN)cn1
Solvent: Cc1ccccc1
Product: CC(C)OCc1ccc(CNc2c(Cl)ccc3c2CCN(C(=O)C(F)(F)F)CC3)cn1

Procedure:
Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (408 mg, 0.96 mmol) with 3-aminomethyl-6-(iso-propoxy)methyl-pyridine (190 mg, 1.05 mmol) in toluene (8 mL). Purify the crude mixture by chromatography on silica gel eluting with isohexane/EtOAc (1:0 to 1:1 gradient) to obtain 7-chloro-6-[(6-iso-propoxymethyl-pyridin-3-ylmethyl)-amino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine. MS (ES+) m/z: 456 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[O:6][C:5]2=O.O.[NH2:14][NH2:15]>C(O)(C)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:15][NH:14][C:5]2=[O:6]
Reactant: O=C1OC(=O)c2cc(Br)ccc21
Reactant: NN
Solvent: O
Solvent: CC(C)O
Product: O=c1[nH][nH]c(=O)c2cc(Br)ccc12
Yield: 72.3 %

Procedure:
A mixture of 5-Bromo-isobenzofuran-1,3-dione (6.0 g, 26.4 mmol) and hydrazine hydrate (1.51 mL, 32.4 mmol) in isopropanol (120 mL) was heated at reflux for 4 h. The mixture was allowed to cool and the precipitate was filtered and washed with water (50 mL). The filter cake was dried to afford the title compound (4.6 g, 72.3%) as a white solid. m/z (M+1)=241.05
Reaction SMILES: [CH2:1]([C@@:4]1([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[N:21][C:22](N)=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].N([O-])=[O:34].[Na+].[OH-].[Na+]>OS(O)(=O)=O>[CH2:1]([C@@:4]1([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22](=[O:34])[NH:21][CH:20]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(-c3ccc(N)nc3)cc2)C(=O)O1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(-c3ccc(=O)[nH]c3)cc2)C(=O)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 59 %

Procedure:
To a solution of (R)-6-allyl-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (1.5 g, 3.47 mmol.) in 3.5 M H2SO4 (25 mL) was added 2 M NaNO2 (15 mL) at 0° C. The reaction mixture was stirred at rt overnight. The reaction was treated with aqueous NaOH solution (8%), and the mixture was extracted with CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated to give crude product, which was purified by preparative TLC to give (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (891 mg, 59%). 1H NMR (CDCl3): δ=1.52 (d, 3H), 2.15-2.38 (m, 3H), 2.51-2.60 (m, 2H), 2.94 (m, 1H), 4.99-5.11 (m, 2H), 5.65-5.74 (m, 2H), 6.67 (m, 1H), 6.89 (d, 2H), 7.00 (t, 2H), 7.13-7.20 (m, 2H), 7.20-7.27 (d, 2H), 7.33 (m, 1H), 7.46 (m, 1H), 7.77 (m, 1H).
Reaction SMILES: [N:1]([C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]([C:13]2[N:14]=[CH:15][S:16][CH:17]=2)=[O:12])=[N:8][CH:9]=1)=[C:2]=[S:3].[CH3:18][C@@H:19]([C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[NH2:20]>C(#N)C>[F:28][C:27]([F:29])([F:30])[C:25]1[CH:26]=[C:21]([C@@H:19]([NH:20][C:2]([NH:1][C:4]2[CH:5]=[CH:6][C:7]([NH:10][C:11]([C:13]3[N:14]=[CH:15][S:16][CH:17]=3)=[O:12])=[N:8][CH:9]=2)=[S:3])[CH3:18])[CH:22]=[C:23]([C:31]([F:32])([F:33])[F:34])[CH:24]=1
Reactant: O=C(Nc1ccc(N=C=S)cn1)c1cscn1
Reactant: C[C@H](N)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: CC#N
Product: C[C@H](NC(=S)Nc1ccc(NC(=O)c2cscn2)nc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 12 h

Procedure:
A mixture of N-(5-isothiocyanato-2-pyridinyl)-1,3-thiazole-4-carboxamide (0.36 g) and (S)-alpha-methyl-3,5-bis(trifluoromethyl)-benzenemethanamine (0.36 g) is heated with acetonitrile (10 mL) until all solids are dissolved. The solution is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.40 g). ]M+H] 520.
Reaction SMILES: [OH:1][NH2:2].C([O:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)C>CO.CN(C=O)C>[OH:1][NH:2][C:6](=[O:5])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: CCOC(=O)CCCCCCN(c1ccccn1)c1ccc(C)cn1
Reactant: NO
Solvent: CO
Solvent: CN(C)C=O
Product: Cc1ccc(N(CCCCCCC(=O)NO)c2ccccn2)nc1
Reaction time: 72 h
Yield: 75 %

Procedure:
HONH2 (50% aqueous, 1 mL) was added to II (50 mg, 0.15 mmol) in MeOH (1 mL) and DMF (0.5 mL) at rt. The reaction mixture was stirred for 72 h, after which the solvents were evaporated under reduced pressure. The resulting residue was dissolved and co-evaporated with toluene (3×5 mL) then was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (100:2 to 100:8) to furnish III as a pale brown oil (37 mg, 75%).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([NH:8][CH2:9][CH:10]([O:34][CH3:35])[CH2:11][O:12][C:13](=[O:33])[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])(=[O:7])=[O:6].[I-:36].[Na+]>C(C(C)=O)C>[I:36][CH2:2][CH2:3][CH2:4][S:5]([NH:8][CH2:9][CH:10]([O:34][CH3:35])[CH2:11][O:12][C:13](=[O:33])[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])(=[O:7])=[O:6]
Reactant: CCCCCCCCCCCCCCCCCCNC(=O)OCC(CNS(=O)(=O)CCCCl)OC
Reactant: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: CCCCCCCCCCCCCCCCCCNC(=O)OCC(CNS(=O)(=O)CCCI)OC
Yield: 85.5 %

Procedure:
To a solution of 972 mg (1.8 mM) of 3-(3-chloropropylsulfonylamino)-2-methoxy-1-octadecylcarbamoyloxypropane IIIa1 in 10 ml of methyl ethyl ketone is added 500 mg (3.38 mM) of sodium iodide and the mixture is refluxed for 3 hours with stirring. After the solvent is evaporated, the residue is purified by the column chromatography on silica gel with a n-hexane-ethyl acetate (1:1) mixture as an eluent. The product is recrystallized from chloroform-n-hexane to give 972 mg (1.54 mM) of 3-(3-iodopropylsulfonylamino)-2-methoxy-1-octadecylcarbamoyloxypropane IIa1 in 86% yield.
Reaction SMILES: [CH2:1]([NH2:4])[C:2]#[CH:3].C(N(C(C)C)CC)(C)C.Cl[C:15]([O:17][CH2:18][CH:19]1[C:31]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16]>CN(C)C=O>[CH:30]1[C:31]2[CH:19]([CH2:18][O:17][C:15](=[O:16])[NH:4][CH2:1][C:2]#[CH:3])[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:26]=2[CH:27]=[CH:28][CH:29]=1
Reactant: C#CCN
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C#CCNC(=O)OCC1c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of propargylamine (250 μL, 3.645 mmol) in diisopropylethylamine (1.273 mL, 7.290 mmol), was added 9-fluorenylmethyl chloroformate (Fmoc), dissolved in 7 mL dimethylformamide. The mixture was stirred under argon overnight at room temperature. After completion, the solution was reduced in vacuo. An ethyl acetate/water extraction procedure was performed to isolate the product; MS: 278.10 (m/z).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]>[Pd].CO>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)N1CCN(c2ccc(N)cc2)CC1
Temperature: 25 °C
Reaction time: 2.7 h

Procedure:
A suspension of 1-isopropyl-4-(4-nitro-phenyl)-piperazine (5.18 g, 20.80 mmol) and 5% palladium on carbon (0.5 g) in MeOH (100 mL) is stirred for 2.7 h at RT, under a hydrogen atmosphere. The reaction mixture is filtered through a pad of celite and concentrated to afford the title compound as a violet solid: ESI-MS: 220.1 [MH]+; tR=0.95 min (system 1).
Reaction SMILES: [I:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[NH:7][C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:9]2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:20])=O>>[Cl:20][C:6]1[C:5]2[C:10](=[CH:11][C:2]([I:1])=[CH:3][CH:4]=2)[N:9]=[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:7]=1
Reactant: CCOC(=O)c1nc2cc(I)ccc2c(=O)[nH]1
Reactant: O=P(Cl)(Cl)Cl
Product: CCOC(=O)c1nc(Cl)c2ccc(I)cc2n1
Temperature: 110 °C
Yield: 48 %

Procedure:
A suspension of ethyl 7-iodo-4-oxo-3,4-dihydroquinazoline-2-carboxylate (1.0 g, 2.90 mmol) in phosphorus oxychloride (10 mL) was heated at 110° C. under argon for 12 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was purified by column chromatography using silica gel eluting with 30% EtOAc/hexanes to afford ethyl 4-chloro-7-iodoquinazoline-2-carboxylate as a white solid (0.510 g, 48%). 1H NMR (300 MHz, DMSO-d6) δ 1.32 (t, 3H), 4.48 (q, 2H), 7.88 (d, 1H), 7.92 (d, 1H), 8.25 (s, 1H); LC-MS (ESI) m/z 363 (M+H)+.
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([C:7]2[O:11][C:10]3[C:12]4[C:17]([CH:18]=[CH:19][C:9]=3[CH:8]=2)=[CH:16][CH:15]=[CH:14][CH:13]=4)=[CH:3][CH:2]=1.[CH:21](=NC1C=CC=CC=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:1]1([CH:20]=[CH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:2]=[CH:3][C:4]([C:7]2[O:11][C:10]3[C:12]4[C:17]([CH:18]=[CH:19][C:9]=3[CH:8]=2)=[CH:16][CH:15]=[CH:14][CH:13]=4)=[CH:5][CH:6]=1
Reactant: Cc1ccc(-c2cc3ccc4ccccc4c3o2)cc1
Reactant: C(=Nc1ccccc1)c1ccccc1
Product: C(=Cc1ccc(-c2cc3ccc4ccccc4c3o2)cc1)c1ccccc1

Procedure:
Following the procedure given in Example 1b the above-named 2-(p-tolyl)-naphtho-[1,2-b]furan was interacted with an equimolar quantity of benzalaniline to produce 2-(4-stilbenyl)naphtho[1,2-b]furan which, when crystallized from xylene and further purified by sublimation, melted at 228°-228.5° C. The wavelength of maximum excitation of this compound was 370 nm., and the wavelength of maximum emission was 426.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].I[CH3:8].[CH:9]1([NH:15][C:16]2[C:17]([NH2:22])=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.O>CN(C=O)C>[CH:9]1([NH:15][C:16]2[C:17]([NH:22][CH3:8])=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CI
Reactant: Nc1ccccc1NC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CNc1ccccc1NC1CCCCC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 39 %

Procedure:
Potassium carbonate (2.45 g, 17.7 mmol) and iodomethane (0.81 ml, 13.0 mmol) were added to a solution of N-cyclohexyl-benzene-1,2-diamine from Example E26.2 (2.25 g, 11.8 mmol) in DMF (10 ml). The mixture was stirred for 6 h at room temperature then poured into water and extracted with EtOAc. The organic layer was washed with water then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% EtOAc:95% hexane) to yield the title compound (950 mg, 39%).
Reaction SMILES: [CH3:1][C@H:2]([CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:3](O)=[O:4].C(Cl)(=O)C([Cl:16])=O>CN(C=O)C>[CH3:1][C@H:2]([CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[C:3]([Cl:16])=[O:4]
Reactant: O=C(Cl)C(=O)Cl
Reactant: C[C@H](CC1CCCCC1)C(=O)O
Solvent: CN(C)C=O
Product: C[C@H](CC1CCCCC1)C(=O)Cl
Reaction time: 2 h
Yield: 98.4 %

Procedure:
To a solution of α(R)-methylcyclohexane-propionic acid (2.4 g, 14 mmol) in dry CH2Cl12 (30 mL) was added DMF (1 drop) and oxalyl chloride (2 g, 15 mmol). After 2 h at room temperature, the mixture was concentrated. The residue was dissolved in Et2O (10 mL). This solution was filtered. The filtrate was concentrated to provide α(R)-methylcyclohexanepropionic acid chloride as a clear yellow liquid (2.6 g, 98% yield). 1H NMR (400 MHz, CDCl3) 3.02-2.91 (m, 1H), 1.80-1.63 (m, 6H), 1.39-1.10 (m, 5H), 1.28 (d, J=7 Hz, 3H), 0.99-0.85 (m, 2H). This material was used without further purification in the coupling reaction described in the following example.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH3:12])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[O:16]1[CH2:20][CH2:19][CH2:18][CH:17]1[CH2:21][NH2:22]>>[CH2:11]([S:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:22][CH2:21][CH:17]2[CH2:18][CH2:19][CH2:20][O:16]2)=[C:3]([N+:13]([O-:15])=[O:14])[CH:4]=1)(=[O:10])=[O:9])[CH3:12]
Reactant: CCS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: NCC1CCCO1
Product: CCS(=O)(=O)c1ccc(NCC2CCCO2)c([N+](=O)[O-])c1

Procedure:
The title compound was prepared according to the procedure described in Step A of Example 5 from 1-chloro-4-(ethylsulfonyl)-2-nitrobenzene (Step C of Example 2) and 1-(tetrahydrofuran-2-yl)methanamine (tetrahydrofurfurylamine available from Acros Organics).
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[CH2:6]([NH:10][CH3:11])[CH2:7][CH2:8][CH3:9]>CCOCC.O>[Br:1][CH2:2][C:3]([N:10]([CH2:6][CH2:7][CH2:8][CH3:9])[CH3:11])=[O:4]
Reactant: O=C(Br)CBr
Reactant: CCCCNC
Solvent: CCOCC
Solvent: O
Product: CCCCN(C)C(=O)CBr
Reaction time: 0.5 h

Procedure:
To a solution cooled to -20° C. of 11.9 ml of bromoacetyl bromide in 180 ml of ether there were added 26 g of butylmethyl amine in solution in 120 ml of ether and then the temperature returned to 20° C. The mixture was stirred for 30 minutes diluted with water and extracted with ether. The ether phase was evaporated to dryness under reduced pressure and the 27.4 g of residue were distilled under reduced pressure (0.05 mbar) at 79/83° C. to obtain. 19.36 g of the desired product.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.ON1C(=O)CCC1=O.CN(C1C=CC=CN=1)C.C1(N=C=NC2CCCCC2)CCCCC1.[C:44]([NH2:48])([CH3:47])([CH3:46])[CH3:45]>ClCCl>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([NH:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:6]
Reactant: Nc1ccc(F)cc1C(=O)O
Reactant: CC(C)(C)N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccccn1
Agent: O=C1CCC(=O)N1O
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1cc(F)ccc1N
Yield: 73.2 %

Procedure:
Stir and cool to 0° C. a solution of 2-amino-5-fluorobenzoic acid (7.75 g, 50 mmol), N-hydroxysuccinimide (6.9 g, 60 mmol) and dimethylaminopyridine (1.0 g) in dichloromethane (200 mL). Add, dropwise, a 1M solution of dicyclohexylcarbodiimide in dichloromethane (60 mL, 60 mmol), and stir at 0° C. for 1H. Add tert-butyl amine (20 mL, 190.3 mmol) by syringe and stir at 0° C. for 3 h and then at ambient temperature overnight. Pour onto a pad of silica gel and elute with 5% ethyl acetate/dichloromethane. Combine like fractions and concentrate to obtain a crude solid. Triturate the solid with heptane and filter to obtain 7.7 g (73%) of the title compound: MS 211(M+H), m.p. 77–78° C.