Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:17]2[CH:18]=[CH:19][C:20]([N+:22]([O-:24])=[O:23])=[CH:21][C:16]=2[Cl:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=[N+]([O-])c1ccc(O)c(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc([N+](=O)[O-])cc2Cl)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 80.4 %

Procedure:
To a solution of 1-t-butoxycarbonyl-4-hydroxypiperidine (3.32 g), 2-chloro-4-nitrophenol (2.36 g) and triphenylphosphine (5.11 g) in dichloromethane (60 ml) was added dropwise diethyl azodicarboxylate (3.1 ml) in an ice bath and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using hexane/ethyl acetate=5/2 as an eluant to give the desired compound (3.90 g, yield 76%) as a pale yellow solid.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9](Cl)([Cl:11])=[O:10]>>[Cl:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10]
Reactant: OCc1ccccc1
Reactant: O=C(Cl)Cl
Product: O=C(Cl)OCc1ccccc1

Procedure:
324.4 Parts of benzyl alcohol are reacted with phosgene to give 505 parts of benzyl chloroformate as a colourless liquid b.p. 78° C/2.0 mm.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([S:33](=[O:36])(=[O:35])[NH2:34])[C:17]=1[O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25]CC2C=CC=CC=2)=[CH:21][CH:20]=1)[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[H][H]>O>[CH2:1]([NH:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([S:33](=[O:36])(=[O:35])[NH2:34])[C:17]=1[O:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1)[C:12]([OH:14])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: NS(=O)(=O)c1cc(C(=O)O)cc(NCc2ccccc2)c1Oc1ccc(OCc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: NS(=O)(=O)c1cc(C(=O)O)cc(NCc2ccccc2)c1Oc1ccc(O)cc1

Procedure:
A suspension of 3-benzylamino-4-(4-benzyloxyphenoxy)-5-sulphamyl-benzoic acid (0.5 g) in water (5 ml) was adjusted to a pH of 11 by addition of 1N sodium hydroxide. The resulting solution was hydrogenated at room temperature and 1.1 atmospheres hydrogen pressue after addition of Pd-on-carbon powder catalyst (0.025 g catalyst containing 10% of Pd). After the hydrogen uptake had become negligible, the catalyst was removed by filtration, and from the filtrate the 3-benzylamino-4-(4-hydroxyphenoxy)-5-sulphamyl-benzoic acid was precipitated by addition of 4N hydrochloric acid until a pH of 2. After isolation by filtration and recrystallization from aqueous ethanol, the compound was obtained with a melting point of 276°-277° C (decomp.).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH2:18])([CH:14]([CH3:17])[CH2:15]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.Cl[C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]>ClCCl.O.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]2([N:18]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[CH2:15][CH:14]2[CH3:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(CO)C1(N)CCCN(C(=O)OC(C)(C)C)C1
Reactant: O=C(Cl)OCc1ccccc1
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC1CN(C(=O)OCc2ccccc2)C12CCCN(C(=O)OC(C)(C)C)C2
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of an optically-active compound of 3-amino-3-(2-hydroxy-1-methylethyl)piperidine-1-carboxylic acid tert-butyl ester (258 mg), triphenylphosphine (472 mg) and triethylamine (502 μl) in dichloromethane (7.7 ml) cooled to 0° C. was added carbon tetrabromide (596 mg). The reaction mixture was stirred at room temperature for 2.5 hours and cooled to 4° C. Then, thereto were added triethylamine (279 μl) and benzyl chloroformate (267 μl), and the mixture was stirred for 40 minutes. To the mixture was added water, and the mixture was extracted with ethyl acetate. The separated organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1 to 2/1) to give the titled compound (85 mg).
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[N:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:18]([C:27]([O:29][CH3:30])=[O:28])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[CH3:32][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[O:29]([C:27]([C@:18]1([CH3:32])[CH2:17][CH2:16][C@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:14][CH:13]=2)[N:19]1[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])=[O:28])[CH3:30]
Reactant: COC(=O)[C@@H]1CC[C@H](c2ccc(OCc3ccccc3)cc2)N1C(=O)OC(C)(C)C
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: COC(=O)[C@]1(C)CC[C@H](c2ccc(OCc3ccccc3)cc2)N1C(=O)OC(C)(C)C
Temperature: -20 °C
Reaction time: 0.67 h
Yield: 78.1 %

Procedure:
To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D6, 1.52 g, 3.7 mmol) in dry THF (27 ml) at −78° C. was added LiHMDS (4.0 ml, 4.0 mmol, 1M solution in THF). The mixture was allowed to warm to −20° C. and was stirred for 40 min at that temperature. Then the mixture was again cooled to −78° C. and methyl iodide (3.15 g, 22.1 mmol) was added. The mixture was left stirring for another 30 min at the same temperature. After standard work up, the organic layer was evaporated. The crude material was purified by chromatography on silica gel using cyclohexanes and ethyl acetate (1:0 to 9:1) affording the title compound (1.23 g, 78%); Rt (HPLC): 6.76 min; MS: (ES/+) m/z: 448 [M+Na+]; C25H31NO5 requires 425; 1H NMR (400 MHz, CDCl3) δ(ppm): 7.45-7.38 (m, 4H); 7.35 (t, 2H); 7.29 (t, 1H); 6.90 (d, 2H); 5.04 and 5.01 (s, s, 2H); 4.98 and 4.79 (d, d, 1H); 3.79 (s, 3H); 2.50-2.35 (m, 1H); 2.34-2.22 (m, 1H); 1.87-1.73 (m, 2H); 1.58 and 1.55 (s, s, 3H); 1.37 and 1.09 (s, s, 9H). NOE between the methyl group and the proton at C5 could be observed.
Reaction SMILES: Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].O1CCCCC1[N:35]1[C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][CH:37]=[N:36]1>>[OH:28][CH2:27][C@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:37]3[NH:36][N:35]=[CH:39][CH:38]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1
Reactant: CC1(C)OB(c2ccnn2C2CCCCO2)OC1(C)C
Reactant: O=C(Nc1ccc(SC(F)(F)F)cc1)c1cnc(N2CC[C@H](CO)C2)c(Br)c1
Product: O=C(Nc1ccc(SC(F)(F)F)cc1)c1cnc(N2CC[C@H](CO)C2)c(-c2ccn[nH]2)c1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 10 using (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 12.1) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to afford a pale yellow powder. UPLC-MS (Condition 3) tR=0.99 min, m/z=464.2 [M+H]+, m/z=462.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) d ppm 1.48-1.64 (m, 1H) 1.76-1.93 (m, 1H) 2.15-2.27 (m, 1H) 3.04 (dd, J=11.49, 7.09 Hz, 1H) 3.18-3.26 (m, 2H) 3.27-3.29 (m, 1H) 3.32-3.41 (m, 2H) 4.60 (br. s, 1H) 6.39 (d, J=1.71 Hz, 1H) 7.67 (d, J=8.56 Hz, 2H) 7.80 (br. s, 1H) 7.87-7.99 (m, 2H) 8.04 (d, J=2.45 Hz, 1H) 8.74 (br. s, 1H) 10.28 (s, 1H) 12.76-13.20 (m, 1H).
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:22])=[C:7]([NH:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][N:14]([CH3:20])[C:13]3=[O:21])[CH:8]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C:34]([C:35](O)=[O:36])=[CH:33][C:32]([S:38]([CH3:41])(=[O:40])=[O:39])=[N:31]2)=[CH:26][CH:25]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C:34]([C:35]([NH:2][C:3]3[CH:4]=[CH:5][C:6]([CH3:22])=[C:7]([NH:9][C:10]4[CH:11]=[C:12]5[C:17](=[CH:18][CH:19]=4)[N:16]=[CH:15][N:14]([CH3:20])[C:13]5=[O:21])[CH:8]=3)=[O:36])=[CH:33][C:32]([S:38]([CH3:41])(=[O:39])=[O:40])=[N:31]2)=[CH:26][CH:25]=1
Reactant: CS(=O)(=O)c1cc(C(=O)O)n(-c2ccc(F)cc2)n1
Reactant: Cc1ccc(N)cc1Nc1ccc2ncn(C)c(=O)c2c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(NC(=O)c2cc(S(C)(=O)=O)nn2-c2ccc(F)cc2)cc1Nc1ccc2ncn(C)c(=O)c2c1
Reaction time: 20 h
Yield: 20.5 %

Procedure:
6-(5-Amino-2-methyl-phenylamino)-3-methyl-3H-quinazolin-4-one HCl salt (138 mg, 0.49 mmol) was dissolved in DMF (2 mL) with 2-(4-fluoro-phenyl)-5-methanesulfonyl-2H-pyrazole-3-carboxylic acid (140 mg, 0.49 mmol) at RT. HATU (186 mg, 0.54 mmol) was added, followed by DIEA (0.21 mL, 1.2 mmol). The mixture was stirred for 20 h. Water (10 mL) was added and the mixture was extracted with EtOAc (20 mL). The organic layer was concentrated and the residue was dissolved in minimum amount of DMSO and purified by prep HPLC. 55 mg of title compound was obtained after lyophilization of pure fractions. LC-MS [M+H] 547.2.
Reaction SMILES: I[C:2]1[Se:3][CH:4]=[CH:5][CH:6]=1.[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[C:12]([F:19])[C:11]=1[F:20])[CH3:8].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CC(OC)(C)C>[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:2]2[Se:3][CH:4]=[CH:5][CH:6]=2)=[C:12]([F:19])[C:11]=1[F:20])[CH3:8]
Reactant: CCOc1ccc(B(O)O)c(F)c1F
Reactant: Ic1ccc[se]1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOc1ccc(-c2ccc[se]2)c(F)c1F

Procedure:
A mixture of 34.8 g (0.14 mol) of 2-iodoselenophene, 32.8 g (0.16 mol) of 4-ethoxy-2,3-difluorophenylboronic acid, 8.10 g (77.01 mmol) of tetrakis -(triphenylphosphine)palladium(0) and 300 ml of 2 N sodium carbonate soln. in 800 ml of toluene/ethanol (1:1) is heated under reflux for 23 h. The mixture is diluted with MTBE and washed with water. The aqueous phase is extracted with MTBE, and the combined organic phases are washed with 2 N hydrochloric acid and sat. sodium chloride soln. The solution is dried using sodium sulfate and concentrated to dryness. The residue is purified by column chromatography (SiO2, n-heptane:EtOAc=15:1-10:1→5:1). Further purification is carried out by recrystallisation from n-heptane; 2-(4-ethoxy-2,3-difluorophenyl)selenophene is obtained as a beige solid.
Reaction SMILES: [CH3:1][C:2]([CH3:15])([CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3](O)=[O:4].C(Cl)(=O)C([Cl:19])=O>CN(C)C=O.ClCCl>[CH3:1][C:2]([CH3:15])([CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([Cl:19])=[O:4]
Reactant: CC(C)(COCc1ccccc1)C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(COCc1ccccc1)C(=O)Cl
Temperature: 0 °C
Reaction time: 5 h

Procedure:
Adapting procedures or variations thereof according to Lopez et al., Bioorg. & Med. Lett. 2003, 13(11), 1873-1878, a 500 mL round-bottomed flask equipped with a magnetic stirring bar was charged with 5.7 g (27.6 mmol) of 2,2-dimethyl-3-(phenylmethoxy)propanoic acid (26b), 20 mL of anhydrous dichloromethane (DCM), and 3 drops of N,N-dimethylformamide (DMF). Four-point-eight (4.8) mL (7.1 g, 55.2 mmol) of neat oxalyl chloride was slowly added to the solution. The reaction mixture was stirred at ca. 0° C. (ice-bath) for 5 hours. The solvents were removed under reduced pressure to provide the crude title compound (26c), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3): δ=1.34 (s, 6H), 3.54 (s, 2H), 4.56 (s, 2H), 7.29-7.37 (m, 5H) ppm. The analytical data was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:32](=[O:33])[N:13]2[CH2:14][CH:15]3[CH2:20][CH2:19][C:18]([NH:21][C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])([C:12]2=[N:11][C:10]=1[C:34](O)=[O:35])[CH2:17][CH2:16]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:43][NH2:44].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[CH2:25]([O:24][C:22](=[O:23])[NH:21][C:18]12[CH2:17][CH2:16][CH:15]([CH2:20][CH2:19]1)[CH2:14][N:13]1[C:32](=[O:33])[C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:10]([C:34]([NH:43][NH2:44])=[O:35])[N:11]=[C:12]21)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(NC12CCC(CC1)Cn1c2nc(C(=O)O)c(OCc2ccccc2)c1=O)OCc1ccccc1
Reactant: NN
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: NNC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CC1CCC2(NC(=O)OCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid, Intermediate 4 (1 g, 2.043 mmol) in CH2Cl2 (20 mL) was added oxalyl chloride (0.286 mL, 3.27 mmol). A few drops of DMF were added and the mixture stirred at room temperature for 2 h. Solvent was then removed under reduced pressure. The crude acid chloride was then diluted with dichloromethane (10 mL)) and added to a stirred solution of hydrazine (0.641 mL, 20.43 mmol) and triethylamine (2.85 mL, 20.43 mmol) in CH2Cl2 (20 mL) and the resulting solution stirred at room temperature. After 16 h the reaction mixture was poured into sat. NaHCO3 and extracted with dichloromethane (50 mL×3), dried (Na2SO4), filtered and concentrated to give a yellow oil which was used in the next step without further purification. LCMS (M+H)=504.10.
Reaction SMILES: [C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[CH:19][C:20]3[N:21]([CH:23]=[CH:24][N:25]=3)[N:22]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[Br:31]Br>CC(O)=O>[C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([CH2:26][CH:27]([CH3:28])[CH3:29])[C:9]([N:11]1[CH2:12][CH2:13][N:14]([C:17]2[CH:18]=[CH:19][C:20]3[N:21]([C:23]([Br:31])=[CH:24][N:25]=3)[N:22]=2)[CH2:15][CH2:16]1)=[O:10])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(c2ccc3nccn3n2)CC1
Reactant: BrBr
Solvent: CC(=O)O
Product: CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(c2ccc3ncc(Br)n3n2)CC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To 104 mg (0.25 mmol) of (S)-tert-butyl(1-(4-(imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-4-methyl-1-oxopentan-2-yl)carbamate dissolved in 5 mL of AcOH was added bromine (48 mg, 0.3 mmol) and the resulting mixture was stirred at room temperature. After 0.25 hr, the reaction was done, and concentrated by rotavap and then by high vacuum pump to obtain 139 mg (100% yield) of mono-acetic acid salt of the desired product.
Reaction SMILES: [O:1]1[CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2]1.[CH3:12][C:13]([NH2:24])([CH3:23])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1>>[OH:1][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2][NH:24][C:13]([CH3:23])([CH3:12])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1
Reactant: CCCCCCCCC1CO1
Reactant: COc1ccc(CC(C)(C)N)cc1
Product: CCCCCCCCC(O)CNC(C)(C)Cc1ccc(OC)cc1
Yield: 21.8 %

Procedure:
Using the method of Example 5, supra, 1,2-epoxydecane (204 mg, 1.0 mmol) and 1,1-dimethyl-2-(4-methoxyphenyl)ethylamine (197 mg, 1.1 mmol) were used to prepare 73 mg of the title compound as a clear, colorless oil: GC/EI-MS, m/z (rel. int.) 214 (M-121, 100), 196 (27.8), 163 (10), 121 (2.2); 1H-NMR (CDCl3) δ 7.08 (2H, d, J=8.6), 6.83 (2H, d, J=8.6), 3.79 (3H, s), 3.53 (1H, m), 2.79 (1H, dd, J=11.7 and 2.9), 2.67 (2H, s), 2.42 (1H, dd, J=12.6 and 9.6), 1.26 (18 H, m), 1.08 (3H, s), 0.88 (3H, t, J=6.6); 13C-NMR (CDCl3) δ 158.2, 131.4, 129.8, 113.5, 77.2, 69.8, 55.2, 53.8, 47.8, 46.5, 35.1, 31.9, 29.8, 29.7, 29.6, 29.3, 26.6, 26.4, 25.7, 22.7, 14.1; FT-IR (film) cm-1 3399 (broad s), 1612, 1512, 1246, 1039, 823.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl[S:18]([C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:18]([C:21]2[CH:22]=[CH:23][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=2)(=[O:20])=[O:19])=[CH:5][CH:4]=1
Reactant: COC(=O)c1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1ccc(N)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1ccc(S(=O)(=O)Nc2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 29.1 %

Procedure:
To 4-methoxybenzenamine (580 mg, 4.71 mmol) and triethylamine (1.48 mL, 10.7 mmol) in dichloromethane (10 mL) was added methyl 4-(chlorosulfonyl)benzoate (1.00 g, 4.28 mmol). This mixture was stirred for 16 hours at room temperature. The reaction was diluted with dichloromethane (50 mL) and washed consecutively with water, 10% citric acid, and brine. The organics were dried over sodium sulfate and concentrated via rotovap. The resulting crude material was chromatographed on silica gel using 100% dichloromethane as eluent affording Methyl 4-(N-(4-methoxyphenyl)sulfamoyl)benzoate as a white crystalline solid (400 mg, 30% yield)
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N+:9]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([OH:21])(=[O:20])=[O:19])=[CH:15][CH:16]=2)[C:11]([CH3:29])([CH2:22][CH2:23][CH2:24][S:25]([OH:28])(=[O:27])=[O:26])[C:10]=1/[CH:30]=[CH:31]/NC1C=CC=CC=1)([OH:3])=[O:2].[CH3:39][O:40][CH2:41][CH2:42][O:43][CH2:44][CH2:45][N+:46]1[C:54]2[C:49](=[CH:50][C:51]([S:55]([OH:58])(=[O:57])=[O:56])=[CH:52][CH:53]=2)[C:48]([CH3:66])([CH2:59][CH2:60][CH2:61][S:62]([OH:65])(=[O:64])=[O:63])[C:47]=1[CH3:67].C([O-])(=O)C.[Na+:72].C(OCC)C>C(O)(=O)C.C(OC(=O)C)(=O)C>[Na+:72].[Na+:72].[Na+:72].[C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([OH:21])(=[O:20])=[O:19])=[CH:15][CH:16]=2)[C:11]([CH3:29])([CH2:22][CH2:23][CH2:24][S:25]([OH:28])(=[O:26])=[O:27])/[C:10]/1=[CH:30]\[CH:31]=[CH:67]\[C:47]1[C:48]([CH3:66])([CH2:59][CH2:60][CH2:61][S:62]([OH:65])(=[O:64])=[O:63])[C:49]2[C:54](=[CH:53][CH:52]=[C:51]([S:55]([OH:58])(=[O:56])=[O:57])[CH:50]=2)[N+:46]=1[CH2:45][CH2:44][O:43][CH2:42][CH2:41][O:40][CH3:39])([OH:3])=[O:2]
Reactant: CC1(CCCS(=O)(=O)O)C(/C=C/Nc2ccccc2)=[N+](CCCCCC(=O)O)c2ccc(S(=O)(=O)O)cc21
Reactant: COCCOCC[N+]1=C(C)C(C)(CCCS(=O)(=O)O)c2cc(S(=O)(=O)O)ccc21
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Solvent: CCOCC
Product: COCCOCC[N+]1=C(/C=C/C=C2/N(CCCCCC(=O)O)c3ccc(S(=O)(=O)O)cc3C2(C)CCCS(=O)(=O)O)C(C)(CCCS(=O)(=O)O)c2cc(S(=O)(=O)O)ccc21
Temperature: 25 °C

Procedure:
Both 1 mmol 1-(5-carboxypentyl)-3-methyl-2-((E)-2-phenylamino-vinyl)-5-sulfo-3-(3-sulfopropyl)-3H-indolium and 1 mmol 1-[2-(2-methoxy-ethoxy)-ethyl]-2,3-dimethyl-5-sulfo-3-(3-sulfo-propyl)-3H-indolium were dissolved in 20 ml acetic acid/acetic anhydride (1/1) followed by the addition of 200 mg sodium acetate. The solution was stirred under reflux for 15 min. After cooling to room temperature, 20 ml diethylether was added. The resulting precipitate (mixture of the diastereomers 550-1 compound 2 and 550-2 compound 2) was extracted by suction, washed with ether and dried.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[O:6][C@H:5]([C@@H:7]([NH:11]C(=O)OCC2C=CC=CC=2)[CH2:8][S:9][CH3:10])[CH2:4][O:3]1>C(O)(C)C.[OH-].[K+]>[CH3:1][C:2]1([CH3:22])[O:6][C@H:5]([C@@H:7]([NH2:11])[CH2:8][S:9][CH3:10])[CH2:4][O:3]1
Reactant: CSC[C@H](NC(=O)OCc1ccccc1)[C@@H]1COC(C)(C)O1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: CSC[C@H](N)[C@@H]1COC(C)(C)O1
Yield: 77.4 %

Procedure:
A stirred solution of the product from Example 27.3 (2.007 g, 6.17 mmol) in isopropanol (34 ml) and 2M potassium hydroxide (15 ml) was heated at 80° C. for 64 h. The reaction mixture was concentrated to remove isopropanol. The residue was diluted with water and extracted with diethyl ether (3×), dried (MgSO4) and evaporated. The residue was chromatographed on silica gel (ethyl acetate-petrol, 2:1 then methanol-ethyl acetate, 2:98) giving a pale yellow oil (0.913 g, 77%). 1H NMR (CDCl3) δ 4.06 (m, 2H), 3.79 (m, 1H), 2.90 (m, 1H), 2.61 (dd, J=13.2, 4.5 Hz, 1H), 2.44 (dd, J=13.2, 8.7 Hz, 1H), 2.12 (s, 3H), 1.43 (s, 3H), 1.36 (s, 3H). 13C NMR (CDCl3) δ 109.5, 79.0, 66.9, 52.7, 39.9, 26.9, 25.6, 16.3, 14.6.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[CH:9][C:8]=1[C:17]([CH2:19][C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[CH:22][CH:21]=1)=[O:18])(=[O:3])[CH3:2].[N+:30]([O-])([OH:32])=[O:31].O>C(O)(=O)C>[C:1]([NH:4][CH2:5][CH2:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[CH:9][C:8]=1[C:17]([CH2:19][C:20]1[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[CH:22][C:21]=1[N+:30]([O-:32])=[O:31])=[O:18])(=[O:3])[CH3:2]
Reactant: COc1ccc(CC(=O)c2cc(OC)c(OC)cc2CCNC(C)=O)cc1OC
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Solvent: O
Product: COc1cc(CCNC(C)=O)c(C(=O)Cc2cc(OC)c(OC)cc2[N+](=O)[O-])cc1OC

Procedure:
To a solution of 200 g of 2-(2-acetamidoethyl)-4,4', 5,5'-tetramethoxydeoxybenzoin in 2000 ml of acetic acid was slowly added 60 ml of 70% nitric acid at 0° C. Immediately after the addition, the mixture was poured into water and extracted with methylene chloride. The extract was neutralized with a sodium hydrogencarbonate aqueous solution and washed with a saturated sodium chloride aqueous solution. The solvent was removed under reduced pressure, and the residue was recrystallized from ethanol to yield 196 g of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[NH:9][C:8](=[O:15])[CH:7]=[C:6]2[C:16]([F:19])([F:18])[F:17].[N+:20]([O-])([OH:22])=[O:21].S(=O)(=O)(O)O.ClCCl.CC(C)=O>CS(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[NH:9][C:8](=[O:15])[C:7]([N+:20]([O-:22])=[O:21])=[C:6]2[C:16]([F:19])([F:18])[F:17]
Reactant: O=[N+]([O-])O
Reactant: COc1cc2[nH]c(=O)cc(C(F)(F)F)c2cc1OC
Agent: O=S(=O)(O)O
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: COc1cc2[nH]c(=O)c([N+](=O)[O-])c(C(F)(F)F)c2cc1OC
Temperature: 25 °C
Yield: 70 %

Procedure:
3.5 g of 6,7-dimethoxy-4-trifluoromethyl-2-(1H)-quinolone are nitrated with 50 ml of a semi-concentrated mixture of nitric acid and sulphuric acid under ice cooling. The mixture is heated to room temperature and poured on water. The precipitation formed is cleaned with Flash Chromatography (silica gel, dichloromethane:acetone 9:1). Yield 70%, melting point 270° C., UV λ max 391 nm (DMSO), IR (KBR) CO: 1670cm-1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[N:7]=[C:6](Cl)[CH:5]=1>O1CCOCC1.C1COCC1>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[N:7]=[C:6]([CH:4]([CH2:9][CH3:8])[CH2:5][CH3:6])[CH:5]=1
Reactant: COC(=O)c1cc(Cl)nc(OC)c1
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: CCC(CC)c1cc(C(=O)OC)cc(OC)n1
Temperature: 85 °C
Reaction time: 16 h
Yield: 99.4 %

Procedure:
Under argon, Pd(dppf) (83 mg, 101 μmol) is added to a solution of 2-chloro-6-methoxy-isonicotinic acid methyl ester (2.00 g, 9.92 mmol, see preparation of 2-isobutyl-6-methoxy-isonicotinic acid) in dioxane (30 mL). To this mixture, a solution of 1-ethyl-propyl zinkbromide (1.17 g, 9.92 mmol, 20 mL of a 0.5 M solution in THF) is added. The mixture is stirred at 85° C. for 16 h before the reaction is carefully quenched with water and extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid methyl ester (1.17 g) as a pale yellow oil; LC-MS: tR=1.08 min; [M+1]+=238.03.