Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:11]/[O:12][C:13]([CH3:22])([CH3:21])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])/[C:8]([OH:10])=[O:9])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][S:30](Cl)(=[O:32])=[O:31].Cl>C(OCC)(=O)C.CN(C)C(=O)C>[CH3:29][S:30]([O:9][C:8](=[O:10])/[C:7](/[C:4]1[N:3]=[C:2]([NH2:1])[S:6][N:5]=1)=[N:11]\[O:12][C:13]([CH3:22])([CH3:21])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])(=[O:32])=[O:31]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)C(C)(C)O/N=C(\C(=O)O)c1nsc(N)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)C(C)(C)O/N=C(\C(=O)OS(C)(=O)=O)c1nsc(N)n1
Temperature: 3.5 °C
Yield: 96.7 %

Procedure:
A 5.0 liter reactor was charged with N,N-dimethylacetamide (1.4 L). Solid (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)acetic acid (250 g, 1 eq., prepared according to the method disclosed in U.S. Pat. No. 7,129,232) was added to the reactor at ambient temperature and the mixture was stirred until the solid was dissolved. The solution was cooled to about 4° C. (target: 2-5° C.) and stirred for another 10-15 minutes. Potassium carbonate (106.7 g, 184.9 mmol, 1.1 eq.) was added to the reactor in one portion. Methanesulfonyl chloride (118.0 mL, 2.2 eq.) was added to the reactor at a rate of about 5 mL/min while maintaining the batch temperature <10° C. The reaction was stirred for 1-2 hours at about 6° C., then cooled to about 0-5° C. Ethyl acetate (2.5 L, 10 volumes) was added to the reactor while maintaining a temperature of about 0-5° C. 1.6% HCl (aq) (1.35 L) was added to the reactor, maintaining a temperature of about 10-15° C. The biphasic mixture was agitated and the layers were then separated. The organic layer was washed with sodium chloride solution, dried with sodium sulfate and concentrated under reduced pressure to obtain crude material. The crude material was dissolved in ethyl acetate (150 mL) and filtered over silica gel. The filtrate was concentrated under reduced pressure to yield the title compound (299 g, 96.7%) as a colorless solid. Exact Mass: 408.08. HRMS: 409.0846 (M+1).
Reaction SMILES: [C:1](=[O:15])([O:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11](=[O:14])[CH:12]=[CH2:13])[O:2][CH2:3]Cl.[C:16]([O-:20])(=[O:19])[CH:17]=[CH2:18].[K+]>CN(C)C=O.C1OCCOCCOCCOCCOCCOC1>[C:1](=[O:15])([O:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11](=[O:14])[CH:12]=[CH2:13])[O:2][CH2:3][O:20][C:16](=[O:19])[CH:17]=[CH2:18]
Reactant: C=CC(=O)OCCCCOC(=O)OCCl
Reactant: C=CC(=O)[O-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CC(=O)OCCCCOC(=O)OCOC(=O)C=C
Yield: 91.1 %

Procedure:
Chloromethyl 4-acryloyloxybutyl carbonate (1.183 g, 5.00 mmol) prepared as described in Preparation 9 is added to a suspension of freeze dried potassium acrylate (0.606 g, 5.50 mmol) and 18-crown-6 (0.066 g, 0.25 mmol) in dimethylformamide (50 ml) under a dry N2 atmosphere. After 5 days at 20° C. the solvent is removed under reduced pressure and the residue dissolved by adding dichloromethane (60 ml) and water (30 ml). After separating the phases the aqueous layer is extracted with dichloromethane (3×30 ml) and the combined organic phase washed with saturated aqueous sodium hydrogen carbonate (50 ml). The organic phase is dried (MgSO4) and the solvent removed under reduced pressure to give 1.24 g (91%) of the title product. 1H NMR (60 MHz, CDCl3): δ 1.82 (4 H, m, CH2 --CH2), 4.23 (4 H, m, 2× CH2 --O), 5.88 (2 H, s, O--CH2 --O), 5.7-6.8 (6 H, 2×CH=CH2).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH2:9][CH2:8][CH2:7]2)([O-])=O.[N+](C1C=CC=C2C=1CCCC2)([O-])=O.[H][H]>CO.[Pd]>[CH:5]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=[CH:13][C:4]=1[NH2:1]
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc2c(c1)CCCC2
Agent: [Pd]
Agent: O=[N+]([O-])c1cccc2c1CCCC2
Solvent: CO
Product: Nc1ccc2c(c1)CCCC2
Temperature: 25 °C
Reaction time: 16 h
Yield: 40 %

Procedure:
To a solution of 6-nitro-1,2,3,4-tetrahydronaphthalene and 5-nitro-1,2,3,4-tetrahydronaphthalene (5.5 g, 31.1 mmol) in MeOH (50 mL) was added 10% palladium on carbon (3.18 g, 3.0 mmol) under nitrogen, then replaced with hydrogen atmosphere (2 L). The resulting mixture was stirred at room temperature for 16 h, and filtered through Celite. The filtrate was concentrated, and the residue was purified by silica gel column (PE/EtOAc v/v 10:1) to give 5,6,7,8-tetrahydronaphthalen-2-amine as a white solid (2 g, 40% yield). ESI MS: m/z 148 [M+H]+. 1H NMR (400 MHz, CDCl1): δ 6.88 (d, J=8.0 Hz, 1H), 6.49 (dd, J=2.0 Hz, J=8.0 Hz, 1H), 6.44 (d, J=2.0 Hz, 1H), 3.49 (s, 2H), 2.69-2.67 (m, 4H), 1.78-1.75 (m, 4H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH:7]=O.[NH2:13][C:14]1[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][C:15]=1[F:25]>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)/[CH:7]=[N:13]/[C:14]1[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][C:15]=1[F:25]
Reactant: CCOC(=O)c1ccc(N)c(F)c1
Reactant: O=Cc1cc(Br)ccc1[N+](=O)[O-]
Solvent: CCO
Product: CCOC(=O)c1ccc(/N=C/c2cc(Br)ccc2[N+](=O)[O-])c(F)c1

Procedure:
A mixture of 5-bromo-2-nitrobenzaldehyde (2.79 g, 12.13 mmol) and ethyl 4-amino-3-fluorobenzoate (2.22 g, 12.12 mmol) in ethanol (60 mL) was stirred at reflux for 2 h. After the solvent was removed under reduced pressure, the reaction mixture was purified by silica gel column chromatography to give (E)-ethyl 4-(5-bromo-2-nitrobenzylideneamino)-3-fluorobenzoate as pale yellow solid: 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.47 (d, J=2.0 Hz, 1H), 8.02 (d, J=8.6 Hz, 1H), 7.91 (dd, J=1.6, 2.3, 9.0 Hz, 1H), 7.85 (dd, J=1.6, 11.0 Hz, 1H), 7.80 (dd, J=2.3, 8.6 Hz, 1H), 7.24 (t, J=8.0 Hz, 1H), 4.40 (q, J=7.0 Hz, 2H), 1.42 (t, J=7.0 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −125.6.
Reaction SMILES: COC[O:4][C:5]1[C:22]([O:23][CH2:24][CH3:25])=[CH:21][C@H:20]2[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:26]COC)[CH:6]=1.Cl>C1COCC1.[Cl-].[Na+].O>[CH2:24]([O:23][C:22]1[C:5]([OH:4])=[CH:6][C:7]2[CH2:8][CH2:9][C@@H:10]3[C@@H:19]([C:20]=2[CH:21]=1)[CH2:18][CH2:17][C@@:15]1([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]1[OH:26])[CH3:25]
Reactant: CCOC1=C[C@H]2C(=CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](OCOC)CC[C@@H]32)C=C1OCOC
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
Temperature: 25 °C
Reaction time: 6 h
Yield: 86.3 %

Procedure:
To a solution of 2 (6.0 g, 14.8 mmol) in THF (100 ml) was added 6 N HCl (100 ml) at room temperature and the resulting solution was stirred at room temperature for 6 hr. The reaction mixture was poured into brine (200 ml) and the products were extracted with ethyl acetate (3×100 ml). The ethyl acetate layers were washed with saturated sodium bicarbonate (100 ml) and brine (100 ml), combined and dried over sodium sulfate, and evaporated to dryness. Chromatography of the residue (silica gel 230-400 mesh, methylene chloride:ethyl acetate 9:1 by volume) gave compound 3 (4.04 g, 85%), which was crystallized from ethyl acetate/hexane to afford white crystals: mp 151-150° C. (lit.4 mp 154-155° C.); 1H NMR (CDCl3) δ6.95 (s, 1 H), 6.65 (s, 1 H), 4.08 (qd, J=6.8 Hz, J=1.5 Hz, 2 H), 3.73 (t, J=8.4 Hz, 1 H), 2.73 (m, 2 H), 2.30-1.20 (m, 18 H), 0.81 (s,3 H).
Reaction SMILES: CS(Cl)(=O)=O.[CH3:6][O:7][C:8](=[O:20])[C@H:9]([CH2:18]O)[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(N(CC)CC)C.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>ClCCl>[C:14]([O:13][C:11]([NH:10][C@@H:9]([CH2:18][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:8]([O:7][CH3:6])=[O:20])=[O:12])([CH3:17])([CH3:16])[CH3:15]
Reactant: COC(=O)[C@H](CO)NC(=O)OC(C)(C)C
Reactant: C1COCCN1
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](CN1CCOCC1)NC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
Methanesulphonyl chloride (0.86 mL, 11 mmol) was added dropwise to a cooled (0° C.), stirred solution of Boc-L-serine methyl ester (2.10 g, 9.6 mmol) and triethylamine (1.53 mL, 11 mmol) in dichloromethane (20 mL) under nitrogen. The mixture was stirred for 45 min, then morpholine (4.5 mL, 52 mmol) was added and the mixture stirred for a further 30 min at 0° C. followed by 1 h at room temperature. Solvent was removed in vacuo and the residue partitioned between ethyl acetate and aq. Na2CO3 solution. The layers were separated and the organic phase concentrated. The residue was azeotroped with toluene and the resulting title compound used without further purification. m/z (ES+) 289 (M+H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][N:15]=2)[CH2:10][CH:9]1[C:26](=[O:36])[NH:27][C:28]1([C:33]([OH:35])=O)[CH2:30][CH:29]1[CH2:31][CH3:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:37]([C:40]1([O:43][S:44](=[O:47])(=[O:46])[NH2:45])[CH2:42][CH2:41]1)([CH3:39])[CH3:38]>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][N:15]=2)[CH2:10][CH:9]1[C:26](=[O:36])[NH:27][C:28]1([C:33]([NH:45][S:44]([O:43][C:40]2([CH:37]([CH3:39])[CH3:38])[CH2:42][CH2:41]2)(=[O:47])=[O:46])=[O:35])[CH2:30][CH:29]1[CH2:31][CH3:32])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCC1CC1(NC(=O)C1CC(Oc2nccc3cc(OC)ccc23)CN1C(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)C1(OS(N)(=O)=O)CC1
Product: CCC1CC1(NC(=O)C1CC(Oc2nccc3cc(OC)ccc23)CN1C(=O)OC(C)(C)C)C(=O)NS(=O)(=O)OC1(C(C)C)CC1

Procedure:
2-[2-Ethyl-1-(1-isopropyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester was prepared according to the method presented in Example 27. Treatment of 2-(1-carboxy-2-ethyl-cyclopropylcarbamoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 mmol) occurred under the same conditions, adjusted for scale with the exception of utilizing sulfamic acid 1-isopropyl-cyclopropyl ester to afford acylsulfamate (185 mg, 56%): LCMS found 660.9 [M+H]+.
Reaction SMILES: [CH2:1]1[CH:6]2[C:7]3[N:8]([CH:16]=[CH:17][CH:18]=3)[CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:5]2[CH2:4][CH2:3][NH:2]1.Br[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)=[O:22]>CN(C)C=O.C(N(CC)CC)C.C(OCC)C>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C:21]([CH2:20][N:2]2[CH2:3][CH2:4][N:5]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[CH2:9][N:8]4[CH:16]=[CH:17][CH:18]=[C:7]4[CH:6]3[CH2:1]2)=[O:22])=[CH:24][CH:25]=1
Reactant: c1ccc2c(c1)Cn1cccc1C1CNCCN21
Reactant: O=C(CBr)c1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: CN(C)C=O
Product: O=C(CN1CCN2c3ccccc3Cn3cccc3C2C1)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To the solution of 500 mg of 1,3,4,14b-tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine in 7.5 ml of dimethylformamide and 350 mg of triethylamine, 470 mg of α-bromo-p-chloroacetophenone are added and the mixture is stirred at room temperature for 2 hours. It is diluted with 60 ml of diethyl ether, washed with water, dried and evaporated. The residue is taken up in 15 ml of chloroform and the solution again evaporated, to yield the 2-(p-chlorobenzoylmethyl)-1,3,4,14b-tetrahydro-10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine melting at 71°-74°.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17](=O)[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[CH:14][CH:15]=3)[O:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1>C(O)C.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:17][C:16]3[C:11](=[CH:12][C:13]([OH:19])=[CH:14][CH:15]=3)[O:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=c1c(-c2cccc(F)c2)coc2cc(O)ccc12
Agent: [Pd]
Solvent: CCO
Product: Oc1ccc2c(c1)OCC(c1cccc(F)c1)C2
Reaction time: 6 h

Procedure:
3-(3-Fluorophenyl)-7-hydroxychromen-4-one (160 mg) was dissolved in ethanol (40 ml) and 10% palladium on carbon (400 mg) was added. The reaction mixture was hydrogenated for 6 hours at normal pressure and room temperature. It was then filtered through Celite and washed with ethanol. The solvent was evaporated under reduced pressure to give 3-(3-fluorophenyl)chroman-7-ol. 1H NMR (400 MHz, d6-DMSO) δ: 9.19 (br s, 1H), 7.38 (m, 1H), 7.17-7.21 (m, 2H), 7.08 (m, 1H), 6.88 (d, 1H, J 8.2 Hz), 6.30 (dd, 1H, J 8.2, 2.4 Hz), 6.20 (d, 1H, J 2.4 Hz), 4.22 (dd, 1H, J 10.3, 3.6 Hz), 4.02 (t, 1H, 10.3 Hz), 3.20 (m, 1H), 2.90 (m, 2H).′
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([O-:3])=[O:2].C1(C)C=CC(S(O[CH2:21][C:22]([F:25])([F:24])[F:23])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:23][C:22]([F:25])([F:24])[CH2:21][O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)OCC(F)(F)F)cc1
Reactant: O=[N+]([O-])c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccccc1OCC(F)(F)F
Temperature: 140 °C
Yield: 86.7 %

Procedure:
A mixture of 2-nitrophenol (18.8 g, 135 mmol), 2,2,2-trifluoroethyl para-toluenesulfonate (34.36 g, 135 mmol), potassium carbonate (18.7 g, 135 mmol) and DMF (200 mL) was heated 16 hours at 140° C. The reaction mixture then was cooled, diluted with water (600 mL) and extracted with ether/hexanes (1:1; 3×400 mL). The combined extracts were washed with saturated sodium bicarbonate (3×100 mL) and brine, dried (Na2SO4), filtered and concentrated to give 1-(2,2,2-trifluoroethoxy)-2-nitrobenzene (27 g, 117 mmol) as an oil.
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])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([CH3:23])[C:17]=1[CH3:24].C1(C)C=CC=CC=1.C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl.[F:51][C:52]([F:63])([F:62])[C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[CH:56]([OH:58])[CH3:57]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:40](=[O:42])[O:58][CH:56]([C:55]2[CH:59]=[CH:60][CH:61]=[C:53]([C:52]([F:62])([F:63])[F:51])[CH:54]=2)[CH3:57])=[C:18]([CH3:23])[C:17]=1[CH3:24]
Reactant: COc1cc2nccc(Oc3ccc(N)c(C)c3C)c2cc1OC
Reactant: CC(O)c1cccc(C(F)(F)F)c1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc(NC(=O)OC(C)c4cccc(C(F)(F)F)c4)c(C)c3C)c2cc1OC
Temperature: 25 °C
Yield: 75 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (110 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-trifluoromethyl-α-methylbenzyl alcohol (70 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (90 mg, yield 68%).
Reaction SMILES: [Br:1][C:2]1[C:3]([I:11])=[C:4]([OH:10])[C:5]([I:9])=[CH:6][C:7]=1[I:8].[F:12][C:13]([F:24])([C:17]([F:23])([Br:22])[C:18]([F:21])([F:20])[Br:19])[C:14](Cl)=[O:15]>N1C=CC=CC=1>[I:11][C:3]1[C:2]([Br:1])=[C:7]([I:8])[CH:6]=[C:5]([I:9])[C:4]=1[O:10][C:14](=[O:15])[C:13]([F:12])([F:24])[C:17]([F:23])([Br:22])[C:18]([F:21])([F:20])[Br:19]
Reactant: O=C(Cl)C(F)(F)C(F)(Br)C(F)(F)Br
Reactant: Oc1c(I)cc(I)c(Br)c1I
Solvent: c1ccncc1
Product: O=C(Oc1c(I)cc(I)c(Br)c1I)C(F)(F)C(F)(Br)C(F)(F)Br

Procedure:
20.3 grams of 3-bromo-2,4,6-triiodophenol (m.p. 155°-157°C.) were dissolved in 50 ml of pyridine. 13.0 grams of 2,2,3,4,4-pentafluoro-3,4-dibromo-butyryl chloride were added dropwise through a dropping funnel with stirring. The mixture was stirred overnight at room temperature. The mixture was washed in a separatory funnel twice with 250 ml of DI water, then filtered through a column of silica and the solvent evaporated. The material was then chromatographed on a column of silica using FREON 113 (trichlorotrifluroethane) as eluent. The sample (25 grams), which slowly crystallized at room temperature, was shown to be pure ester (97%) by gc/ms. It is suitable for use as a fluid above its melting point of 56°-57°C. m/e (chemical ionization) 129 (21%, CF2Br); 131 (100%, CF2Br and C3F5); 140 (13%, C5HBr); 142 (13%, C5HBr); 188 (14%, C5HI); 267, 269 (11%, 10% C5BrIH); 315 (4%, C5I2H); 422, 424 (6%, 7%, C6I2HBrO); 549, 551 (5%, 4%, C6I3HBrO); 866, 868, 870, 872 (0.2%, 0.6%, 0.4%, 0.2%, molecular ion). I.R. ν=3080 (Ar-H); 1800 (C=O); 1550, 1520 (Ar C=C).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([NH2:10])[CH2:8][CH3:9].[CH:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][C:12]=1[O:21][CH2:22][CH2:23][CH2:24][CH2:25]Cl>CS(C)=O.O>[CH2:7]([NH:10][CH2:25][CH2:24][CH2:23][CH2:22][O:21][C:12]1[CH:13]=[CH:14][C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:11]=1)[CH2:8][CH3:9]
Reactant: ClCCCCOc1ccc2ccccc2c1
Reactant: CCCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCCNCCCCOc1ccc2ccccc2c1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and n-propyl amine (0.26 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 4-(2-naphthyloxy)-1-chlorobutane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 7 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to oily compound which was later crystallized by benzene hexane to get N-(n-propyl)-(4-(naphthalen-2-yloxy)butyl)amine, solid, m.p. 118° C., (yield 0.51 gm, 93.2%).
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.C(N(CC)CC)C.[CH3:25][C:26]1[CH:36]=[CH:35][CH:34]=[CH:33][C:27]=1[CH:28]=[CH:29][C:30](O)=[O:31].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH3:25][C:26]1[CH:36]=[CH:35][CH:34]=[CH:33][C:27]=1[CH:28]=[CH:29][C:30]([NH:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)=[O:31]
Reactant: Cc1ccccc1C=CC(=O)O
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)C=Cc1ccccc1C
Yield: 98.4 %

Procedure:
The same procedures as in Example 146 were carried out from methyl L-tryptophanate hydrochloride (3.0 g), triethylamine (2.0 mL), 2-methylcinnamic acid (2.3 g), WSC.HCl (2.7 g), and methylene chloride (80 mL), to give the captioned compound (4.2 g, 98%) as an oily product.
Reaction SMILES: C([O:9][C:10]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:21])[CH:17]=2)[N:12]([CH3:22])[CH:11]=1)(=O)C1C=CC=CC=1.N1CCCCC1>ClCCl>[F:21][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:22])[CH:11]=[C:10]([OH:9])[C:19]2=[O:20]
Reactant: Cn1cc(OC(=O)c2ccccc2)c(=O)c2cc(F)ccc21
Solvent: C1CCNCC1
Solvent: ClCCl
Product: Cn1cc(O)c(=O)c2cc(F)ccc21
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 6-fluoro-1 -methyl-4-oxo-1 ,4-dihydro-quinol-3-yl benzoate (1.90 g), piperidine (0.9 ml) and dry dichloromethane (50 ml) was stirred under nitrogen for 24 hours at ambient temperature. The solvent was removed by distillation and the residue triturated with diethyl ether (100 ml). The resultant solid was collected by filtration to give the novel compound 6-fluoro-3-hydroxy-1-methyl-4-quinolone, m.pp. 104°-106°.
Reaction SMILES: [CH3:1][NH:2][CH3:3].Cl[CH2:5][CH2:6][CH:7]1[N:20]([CH3:21])[C:12]2=[N:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:11]2[C:10](=[O:22])[N:9]([CH3:23])[CH2:8]1>CO>[OH2:22].[CH3:1][N:2]([CH3:3])[CH2:5][CH2:6][CH:7]1[N:20]([CH3:21])[C:12]2=[N:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:11]2[C:10](=[O:22])[N:9]([CH3:23])[CH2:8]1
Reactant: CN1CC(CCCl)N(C)c2nc3ccccc3n2C1=O
Reactant: CNC
Solvent: CO
Product: CN(C)CCC1CN(C)C(=O)n2c(nc3ccccc32)N1C
Product: O
Reaction time: 144 h

Procedure:
To 90 mL of freshly collected dimethylamine and 10 mL of methanol was added 3.25 g (0.011 mol) of 2-(2-chloroethyl)-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]triazepino[3,2-a]benzimidazol-5(2H)-one. The reaction flask was sealed and left standing at room temperature for 6 days. The dimethylamine was then allowed to evaporate at room temperature and the residue partitioned between 75 mL of 1N NaOH and 75 mL of CH2Cl2. The organic phase was washed with another 50 mL of 1N NaOH. The combined organic layers were dried over Na2SO4, filtered, and concentrated by rotary evaporation. The solid residue was recrystallized from isopropyl ether to give 2.8 g of white analytically pure crystals, mp 91°-95° C.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12]3[C:15]4[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[CH:20][C:16]=4[O:17][C:18](=[O:19])[C:11]=3[CH2:10]2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C(N(CC)CC)C>C(O)C>[ClH:28].[ClH:28].[ClH:28].[CH3:27][O:26][C:21]1[C:22]([O:24][CH3:25])=[CH:23][C:15]2[C:12]3[CH2:13][CH2:14][N:9]([CH2:8][CH2:7][N:1]4[CH2:6][CH2:5][N:4]([CH2:29][CH2:30][N:31]5[CH2:36][CH2:35][O:34][CH2:33][CH2:32]5)[CH2:3][CH2:2]4)[CH2:10][C:11]=3[C:18](=[O:19])[O:17][C:16]=2[CH:20]=1
Reactant: ClCCN1CCOCC1
Reactant: COc1cc2oc(=O)c3c(c2cc1OC)CCN(CCN1CCNCC1)C3
Solvent: CCO
Solvent: CCN(CC)CC
Product: COc1cc2oc(=O)c3c(c2cc1OC)CCN(CCN1CCN(CCN2CCOCC2)CC1)C3
Product: Cl

Procedure:
A mixture of 0.01m of 3-[2-(1-piperazinyl)ethyl]-1,2,3,4-tetrahydro-8,9-dimethoxy-5H-[1]benzopyrano[3,4-c]pyridin-5-one, 0.011m of N-2-chloroethylmorpholine and 0.011m of triethylamine in 200ml of ethanol was refluxed for 6 hours. The mixture was filtered while hot and treated immediately with excess HCl gas. Recrystallization of the crude product from 4:1 methanol-water afforded pure material, m.p. 262°-4° C.
Reaction SMILES: [C:1]([N+:8]1([O-])[CH2:12][CH:11]=[CH:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[N-:14]=[N+:15]=[N-:16].[Na+].[NH4+].[Cl-].C[OH:21].O>>[C:1]([N:8]1[CH2:12][C@@H:11]([OH:21])[C@H:10]([N:14]=[N+:15]=[N-:16])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CO
Reactant: CC(C)(C)OC(=O)[N+]1([O-])CC=CC1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Product: CC(C)(C)OC(=O)N1C[C@@H](O)[C@H](N=[N+]=[N-])C1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
A mixture of N-Boc-3-pyrroline oxide (0.925 g, 5.0 mmol), NaN3 (0.65 g, 10 mmol), and NH4Cl (5.0 mmol) in MeOH—H2O (6:1, 16 mL) was stirred at 65° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was extracted thoroughly with ethyl acetate. The combined ethyl acetate extract was washed with water and sat. brine, dried over anhydrous Na2SO4, and evaporated. The crude azidoalcohol was purified by recrystallization from ether-hexane: mp 34-36° C.; 1H NMR (300 MHz, CD3OD) δ 4.16 (m, 1H), 3.95 (m, 1H), 3.62 (m, 1H), 3.51 (m, 1H), 3.35 (m, 2H), 1.47 (s, 9H).