Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(=O)(=O)(O)[OH:2].[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([NH:13][C:14]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[NH:23][C:24]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:37])(=[N:34][C:35]#[N:36])=[O:33])=[CH:28][CH:27]=2)=[O:25])=[O:15])=[N:11][CH:12]=1>O>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([NH:13][C:14]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[NH:23][C:24]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:37])(=[N:34][C:35](=[O:2])[NH2:36])=[O:33])=[CH:28][CH:27]=2)=[O:25])=[O:15])=[N:11][CH:12]=1
Reactant: O=S(=O)(O)O
Reactant: CS(=O)(=NC#N)c1ccc(C(=O)Nc2ccc(Cl)cc2C(=O)Nc2ccc(Cl)cn2)cc1
Solvent: O
Product: CS(=O)(=NC(N)=O)c1ccc(C(=O)Nc2ccc(Cl)cc2C(=O)Nc2ccc(Cl)cn2)cc1
Temperature: 27.5 °C
Reaction time: 3 h
Yield: 45 %

Procedure:
Sulfuric acid (0.5 mL) was cooled to 5-10° C. To this was added product of Example 15 (150 mg, 0.38 mmol) and reaction mixture was stirred at 25-30° C. for 3 hr. Above reaction mixture was slowly poured in chilled water. Precipitated product was filtered and washed with water. Drying afforded 70 mg of titled compound in 45% yield.
Reaction SMILES: O.[OH-].[Li+].[NH2:4][C:5]([NH:7][C:8]1[NH:9][C:10]2[C:15]([C:16]=1[C:17]([NH2:19])=[O:18])=[CH:14][CH:13]=[C:12]([C:20]([O:22]C)=[O:21])[CH:11]=2)=[O:6]>O1CCCC1.CO.O>[NH2:4][C:5]([NH:7][C:8]1[NH:9][C:10]2[C:15]([C:16]=1[C:17](=[O:18])[NH2:19])=[CH:14][CH:13]=[C:12]([C:20]([OH:22])=[O:21])[CH:11]=2)=[O:6]
Reactant: COC(=O)c1ccc2c(C(N)=O)c(NC(N)=O)[nH]c2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: NC(=O)Nc1[nH]c2cc(C(=O)O)ccc2c1C(N)=O
Temperature: 65 °C
Reaction time: 7 h
Yield: 99.6 %

Procedure:
Lithium hydroxide monohydrate (1.5 g, 36 mmol) was added to a solution mixture of 2-aminocarbonylamino-6-methoxycarbonylindole-3-carboxamide (Compound 2-17, 1.0 g, 3.6 mmol) in tetrahydrofuran, methanol and water (tetrahydrofuran/methanol/water=3/1/1, 50 mL), and the mixture was stirred at 65° C. for 7 hours. After the reaction mixture was concentrated under reduced pressure, 6 N hydrochloric acid (4 mL) was added to the residue under ice-cooling. The precipitated solid was washed with water (20 mL), chloroform (20 mL), and dried under reduced pressure to give the title compound (0.94 g) as a colorless solid (yield 99%).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.[NH2:24][C@@H:25]([CH2:28][CH3:29])[CH2:26][OH:27]>>[OH:27][CH2:26][C@@H:25]([NH:24][C:19](=[O:21])[C:18]1[CH:22]=[CH:23][C:15]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:16][CH:17]=1)[CH2:28][CH3:29]
Reactant: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)O)cn1
Reactant: CC[C@H](N)CO
Product: CC[C@@H](CO)NC(=O)c1ccc(OCc2c(-c3ccccc3)noc2C)nc1
Yield: 85 %

Procedure:
As described for example 191, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.65 mmol) was converted, using (S)-(+)-2-amino-1-butanol instead of 2-aminoethyl isopropylether, to the title compound (210 mg, 85%) which was obtained as a white solid. MS: m/e=380.2 [M−H]−.
Reaction SMILES: [C:1]([OH:11])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].CN(C)C=O.C(Cl)(=O)C([Cl:20])=O>ClCCl>[C:1]([Cl:20])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCC(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCCCCCCCC(=O)Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 15.80 g (0.10 mol) of nonanoic acid in 150 mL of dichloromethane at 0° C. was added 0.1 mL of N,N-dimethylformamide and 9.59 mL (0.11 mol) of oxalyl chloride. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was then concentrated in vacuo, diluted with hexanes and filtered. The filtrate was concentrated in vacuo to provide 17.67 g (100%) of nonanoyl chloride which was used without further purification in the next step.
Reaction SMILES: C([O:4][C@H:5]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:28]2[C:27](=[O:33])[C@H:26]([O:34]C(=O)C)[C@@:25]2([CH3:38])[C@H:11]3[CH2:12][C@@H:13]3[O:18][C@@:17]4([O:24][CH2:23][C@H:21]([CH3:22])[CH2:20][CH2:19]4)[C@@H:15]([CH3:16])[C@@H:14]32)[CH2:6]1)(=O)C.[C-]#N.[K+]>O.CO.C1COCC1>[CH3:16][C@@H:15]1[C@:17]2([O:24][CH2:23][C@H:21]([CH3:22])[CH2:20][CH2:19]2)[O:18][C@H:13]2[CH2:12][C@@H:11]3[C@@:25]([CH3:38])([C@@H:14]12)[C@@H:26]([OH:34])[C:27](=[O:33])[C@H:28]1[C@H:10]3[CH2:9][CH2:8][C@@H:7]2[C@:29]1([CH3:32])[CH2:30][CH2:31][C@H:5]([OH:4])[CH2:6]2
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2C(=O)[C@H](OC(C)=O)[C@]2(C)[C@@H]4[C@H](C[C@@H]32)O[C@]2(CC[C@@H](C)CO2)[C@H]4C)C1
Agent: [C-]#N
Agent: [K+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O)CC[C@]5(C)[C@H]4C(=O)[C@H](O)[C@]3(C)[C@H]1[C@@H]2C

Procedure:
Using the procedure described in Syn., 1973, 790, (3β,5α, 12α,25R)-3,12-di(acetoxy)spirostan-11-one was saponified with potassium cyanide in water, methanol and THF to give the title compound.
Reaction SMILES: [C:1]1([C:7]([CH:9]2[CH2:11][CH2:10]2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:18].[Na+]>CO>[CH:9]1([CH:7]([NH2:18])[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:11][CH2:10]1
Reactant: [BH3-]C#N
Reactant: O=C(c1ccccc1)C1CC1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: NC(c1ccccc1)C1CC1
Yield: 76 %

Procedure:
Stir 100 g of cyclopropyl phenyl ketone in 2000 ml of methanol with 500 g of previously dried ammonium acetate and 50 g of sodium cyanoborohydride at 50° C. for 4 days under argon in the presence of 4 Å molecular sieve. After cooling, filter off the molecular sieve and then add concentrated hydrochloric acid to take the pH to 2. Evaporate the solution to dryness under vacuum and take up the residue in water. The aqueous phase is washed with ethyl ether and then alkalinised by adding concentrated potassium hydroxide solution so that the pH is above 10. Extract twice with methylene chloride, wash with saturated sodium chloride solution, dry over anhydrous magnesium sulphate and then concentrate under vacuum to obtain α-cyclopropylbenzylamine, which is used without any further purification in the next step.
Reaction SMILES: CC([Si](C)(C)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][O:13][C:14]([NH:16][C@H:17]([C:21]([NH:23][C@H:24]([C:33]([O:35][CH3:36])=[O:34])[CH2:25][O:26][CH2:27][CH:28]([O:31][CH3:32])[O:29][CH3:30])=[O:22])[CH2:18][CH2:19][OH:20])=[O:15])(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:32][O:31][CH:28]([O:29][CH3:30])[CH2:27][O:26][CH2:25][C@@H:24]([C:33]([O:35][CH3:36])=[O:34])[NH:23][C:21](=[O:22])[C@H:17]([CH2:18][CH2:19][OH:20])[NH:16][C:14]([O:13][CH2:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:6]=1)=[O:15]
Reactant: COC(=O)[C@H](COCC(OC)OC)NC(=O)[C@H](CCO)NC(=O)OCc1ccccc1[Si](C)(C)C(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(=O)[C@H](COCC(OC)OC)NC(=O)[C@H](CCO)NC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 89.8 %

Procedure:
A solution of N-[0-[(1,1-dimethylethyl)dimethylsilyl]-N-[(phenylmethoxy)carbonyl]-L-homoseryl]-O-(2,2-dimethoxyethyl)-L-serine, methyl ester [5.56 g, 10 mmol, prepared as described in Example 10(h)] in methanol (65 ml) was cooled to 0° C. (ice salt bath), treated with p-toluenesulfonic acid monohydrate (386 mg, 2.0 mmol) and stirred at 0° C. for 1.5 hours. The reaction was quenched with sodium bicarbonate solution (198 mg. in 20 ml water), stirred for 5 minutes then evaporated to remove the methanol. The aqueous phase was extracted with ethyl acetate (2×200 ml) and the combined organic extract was washed with water (110 ml), 5% sodium bicarbonate (80 ml) and brine (80 ml), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product was chromatographed on silica gel column (Merck), eluting the column with ethyl acetate:hexane (2:1) and ethyl acetate:methanol (98:2) to give 3.975 g of title product as a syrup. TLC (ethyl acetate:hexane, 4:1) Rf =0.17.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=[O:7].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[N+:26]([C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=1)[CH:32]=O)([O-:28])=[O:27].[OH-].[Na+]>ClCCCl>[OH:11][C:4]1[CH:3]=[C:2]([NH:1][CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[C:29]([N+:26]([O-:28])=[O:27])[CH:30]=2)[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7]
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: Nc1ccc(C(=O)O)c(O)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCCl
Product: O=C(O)c1ccc(NCc2cccc([N+](=O)[O-])c2)cc1O
Yield: 55.5 %

Procedure:
To a solution of 4-amino salicylic acid (153 mg; 1 mmol) in 1,2-dichloroethane (4 mL) under argon atmosphere was added sodium triacetoxyborohydride (317 mg; 1.5 mmol) and 3-nitrobenzaldehyde (226 mg; 1.5 mmol). The mixture was stirred at room temperature under argon overnight after which time 1 M NaOH (sq.; 5 mL) was added and the two layers separated. The aqueous layer was acidified with 2 M HCl (aq) and the precipitate formed filtered off and dried to yield 160 mg (55%) of a yellowish powder with satisfactorily purity. Mp. 189° C. (decomposes); MS (ESI−): 287 (MH−).
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:33])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].[NH2:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38].C[O-].[Na+]>>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:33])[C:5]([C:3]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:4])=[N:14][CH:13]=2)[CH:8]=[C:9]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[C:10]1=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)c1ncc2c(cc(-c3ccc(S(C)(=O)=O)cc3)c(=O)n2Cc2ccccc2)c1O
Reactant: NCCC(=O)O
Agent: C[O-]
Agent: [Na+]
Product: CS(=O)(=O)c1ccc(-c2cc3c(O)c(C(=O)NCCC(=O)O)ncc3n(Cc3ccccc3)c2=O)cc1
Temperature: 25 °C
Yield: 62.8 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-3-(4-methanesulfonyl-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (27 mg, 0.058 mmol), β-alanine (689 mg, 7.7 mmol) and NaOMe solution (12 mL, 5.8 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 19 mg of the title compound as a yellow solid. MS: (+) m/z 522.23 (M+1).
Reaction SMILES: [CH3:1][N:2]([CH3:28])[CH2:3][CH2:4][CH2:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]([C:17]3[CH:18]=[C:19]([CH:24]=[CH:25][C:26]=3[CH3:27])[C:20]([O:22]C)=[O:21])[C:13]2=[O:16])=[CH:8][CH:7]=1.[OH-].[Na+].Cl>CO>[CH3:28][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]([C:17]3[CH:18]=[C:19]([CH:24]=[CH:25][C:26]=3[CH3:27])[C:20]([OH:22])=[O:21])[C:13]2=[O:16])=[CH:8][CH:7]=1
Reactant: COC(=O)c1ccc(C)c(-n2ccc3ccc(CCCN(C)C)cc3c2=O)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1ccc(C(=O)O)cc1-n1ccc2ccc(CCCN(C)C)cc2c1=O

Procedure:
Methyl 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoate (176 mg) was stirred in a solution of methanol (2 ml) and 1N NaOH solution (0.57 ml) at 65° C. for 1 hour and then neutralised with 2N HCl (0.28 ml). The reaction mixture was concentrated and the residue was purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to yield 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid as a cream coloured solid (155 mg); NMR Spectrum: (DMSOd6) 1.81 (m, 2H), 2.12 (s, 3H), 2.24 (s, 6H), 2.38 (t, 2H), 2.76 (t, 2H), 6.71 (d, 1H), 7.29 (d, 1H), 7.51 (d, 1H), 7.66 (m, 2H), 7.76 (s, 1H), 7.94 (d, 1H), 8.08 (s, 1H); Mass Spectrum: M+H+ 365.
Reaction SMILES: CN(C)C=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([OH:27])=[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:35]([CH3:41])([CH3:40])[C:36](OC)=[O:37]>O>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[O:27][C:35]([CH3:41])([CH3:40])[C:36](=[O:37])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]3)[C:11]=2[CH:12]=1
Reactant: COC(=O)C(C)(C)Br
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2cc(Cl)ccc2O)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(N2C(=O)C(C)(C)Oc3ccc(Cl)cc32)CC1
Temperature: 140 °C
Reaction time: 2 h

Procedure:
To a N,N-dimethylformamide solution (23 ml) of tert-butyl 4-[(5-chloro-2-hydroxyphenyl)amino]piperidine-1-carboxylate (1.15 g) were added at room temperature cesium carbonate (5.73 g) and methyl 2-bromo-2-methylpropanoate (1.27 g), followed by stirring at 140° C. for 2 hours. After the reaction solution was cooled to room temperature, water was added, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford tert-butyl 4-(6-chloro-2,2-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)piperidine-1-carboxylate.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.F[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].CS(C)=O>[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1
Reactant: OCCN1CCNCC1
Reactant: O=Cc1ccc(F)cc1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: CS(C)=O
Product: O=Cc1ccc(C2CNCCN2CCO)cc1
Temperature: 95 °C

Procedure:
A two liter three necked flask fitted with a mechanical stirrer, thermometer and condenser is charged with 304 g of 2-hydroxyethylpiperazine, 74.4 g of 4-fluorobenzaldehyde, 1 ml of Aliquat 336, 750 ml of dimethylsulfoxide, and 82.8 g of anhydrous potassium carbonate. The mixture is heated at 95° C. for three days. The reaction mixture then is cooled and poured into 3 liters of ice water. The resultant solid precipitate is filtered, washed with water, and vacuum dried. The crude solid is recrystallized from toluene: m.p. 105°-107° C.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[C:10]([NH:15][CH2:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[CH:11]=[CH:12][C:13]=1[Cl:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[F:29][C:30]([F:37])([F:36])[CH2:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[CH2:1]([C:8]1[CH:9]=[C:10]([N:15]([CH2:16][C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[S:32]([CH2:31][C:30]([F:37])([F:36])[F:29])(=[O:34])=[O:33])[CH:11]=[CH:12][C:13]=1[Cl:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=S(=O)(Cl)CC(F)(F)F
Reactant: Clc1ccc(NCc2cccnc2)cc1Cc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(CC(F)(F)F)N(Cc1cccnc1)c1ccc(Cl)c(Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-(3-benzyl-4-chlorophenyl)pyrid-3-ylmethylamine (0.04 g, 0.13 mmol)and pyridine (1 ml) was dissolved in DCM. The reaction was cooled in an ice-bath to which was added dropwise 2,2,2-trifluoroethylsulfonyl chloride (0.59 g, 0.32 mmol). The mixture was stirred at room temperature overnight. After evaporation of solvent, the residue was dissolved in EtOAc and washed with cold NaHCO3 and brine, and evaporated to dryness. Chromatography gave the title compound. 1H NMR: 8.51 (d,1H,J=3.9 Hz), 8.27 (s,1H), 7.59 (d,1H,J=7.8 Hz), 7.34 (t,1H,J=8.3 Hz), 7.28 (d,2H,J=7.8 Hz), 7.21 (m,2H), 8.03 (m,3H), 6.89 (d,1H,J=2.4 Hz), 4.78 (s,2H), 4.01 (s,2H), 3.73 (q,2H,J=9.3 Hz). MS calcd 454.1; MS (M+1) 455.0.
Reaction SMILES: [CH3:1][NH:2][C:3](=[S:5])[S-:4].C([NH+](CC)CC)C.Br[CH:14]([CH3:23])[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=O>CC#N>[CH3:1][N:2]1[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:14]([CH3:23])[S:5][C:3]1=[S:4]
Reactant: CC(Br)C(=O)c1ccccc1
Reactant: CNC(=S)[S-]
Agent: CC[NH+](CC)CC
Solvent: CC#N
Product: Cc1sc(=S)n(C)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.7 %

Procedure:
To a 100 mL flask was added freshly prepared triethylammonium methyldithiocarbamate (2.0 g, 9.5 mmol), anhydrous MeCN (50 mL), and 2-bromopropiophenone (2.04 g, 9.5 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure and the resulting crude residue was treated with conc H2SO4 (5 mL) with stirring at room temperature. After 20 min, the reaction mixture was diluted with water (75 mL) and then mixed with DCM (75 mL). The layers were separated and the aqueous layer extracted once more with DCM (75 mL). The combined organic layers were washed with water (3×50 mL) and then brine (50 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure to afford the title product (1.95 g, 92%) as an off-white solid, which was used without further purification. 1H-NMR (CDCl3): δ 7.50 (2H, m), 7.27 (2H, m), 3.45 (3H, s), 2.06 (3H, s).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23](O)=[O:24].[CH2:37]([O:39][CH2:40][CH2:41][CH2:42][NH2:43])[CH3:38]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23]([NH:43][CH2:42][CH2:41][CH2:40][O:39][CH2:37][CH3:38])=[O:24]
Reactant: COc1ccc(CC2c3cc(OC)c(OC)cc3CCCN2C(C(=O)O)c2ccccc2)cc1OC
Reactant: CCOCCCN
Product: CCOCCCNC(=O)C(c1ccccc1)N1CCCc2cc(OC)c(OC)cc2C1Cc1ccc(OC)c(OC)c1

Procedure:
prepared by reaction of [1-(3,4-dimethoxy-benzyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl]-phenyl-acetic acid with 3-ethoxypropylamine.
Reaction SMILES: [C:1]([NH:4][CH2:5][C@@H:6]1[CH2:10][CH2:9][N:8]([C@H](C2C=CC=CC=2)C)[C@@H:7]1[C:19]([NH2:21])=[O:20])(=[O:3])[CH3:2].O>CO.[Pd]>[C:1]([NH:4][CH2:5][C@@H:6]1[CH2:10][CH2:9][NH:8][C@@H:7]1[C:19]([NH2:21])=[O:20])(=[O:3])[CH3:2]
Reactant: CC(=O)NC[C@@H]1CCN([C@@H](C)c2ccccc2)[C@@H]1C(N)=O
Agent: [Pd]
Solvent: O
Solvent: CO
Product: CC(=O)NC[C@@H]1CCN[C@@H]1C(N)=O

Procedure:
A mixture of (2S,3S)-3-(acetylamino-methyl)-1-((S)-1-phenyl-ethyl)-pyrrolidine-2-carboxylic acid amide (Stage 36.2) (0.48 mmol) and 10% Pd on charcoal, wet with 50% H2O (Aldrich 330108) (0.096 mmol) in MeOH (5 mL) was hydrogenated for 6.5 h at rt. The reaction mixture was then filtered through a Fluoropore Membrane Filter (0.2 μm FG) and evaporated. The residue was dissolved in CH2Cl2 and evaporated to dryness to afford the title compound as an off-white solid. ESI-MS: [M+H]+ 186; TLC: Rf=0.08 (200:20:1 CH2Cl2/MeOH/conc. NH4OH).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=O)[NH:8][C:9]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:10]([N+:17]([O-:19])=[O:18])[C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:5])[CH3:2].CN(C=O)C.P(Cl)(Cl)([Cl:34])=O>>[Cl:34][C:7]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]([N+:17]([O-:19])=[O:18])=[C:9]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:8]=1
Reactant: CCOC(=O)c1c([N+](=O)[O-])c(-c2ccccc2)[nH]c(=O)c1C(=O)OCC
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(Cl)nc(-c2ccccc2)c([N+](=O)[O-])c1C(=O)OCC
Temperature: 100 °C

Procedure:
In 6.5 ml of phosphorus oxychloride was dissolved 2.5 g of 3,4-diethoxycarbonyl-5-nitro-6-phenyl-2pyridone, followed by addition of 1 ml of DMF. The mixture was heated at 100° C. for 30 minutes. After the reaction mixture was concentrated under reduced pressure, an aqueous solution of sodium hydrogencarbonate was added to the residue for neutralization, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After the solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent:ethyl acetate/hexane 1:2), to give 1.9 g of the title compound as yellow needles.
Reaction SMILES: Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[O:8]1[C:13]2[CH:14]=[CH:15][C:16]([NH2:18])=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>[N+](CC)([O-])=O>[CH2:10]1[CH2:9][O:8][C:13]2=[CH:14][C:15]3[S:2](=[O:4])(=[O:3])[NH:5][C:6](=[O:7])[NH:18][C:16]=3[CH:17]=[C:12]2[O:11]1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: Nc1ccc2c(c1)OCCO2
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC[N+](=O)[O-]
Product: O=C1Nc2cc3c(cc2S(=O)(=O)N1)OCCO3
Temperature: 0 °C
Yield: 51.9 %

Procedure:
This compound was prepared according to the method of Girard et. al., J. Chem. Soc., Perkin I; 1979, 1043-1047, incorporated by reference herein in its entirety. To a solution of chlorosulfonyl isocyanate (5.6 g, 40.0 mmol) in nitroethane (35 ml) at -40° C. was added dropwise over five minutes a solution of 1,4-benzodioxan-6-amine (5.0 g, 33.1 mmol) in nitroethane (5 ml). The mixture was allowed to warm to 0° C. and stirred for one hour at which time anhydrous aluminum chloride was added. The mixture was warmed to 110° C. and stirred for 30 minutes (copious HCl evolution) and allowed to cool to ambient temperature before being added dropwise to a vigorously stirred ice-water (~150 g) mixture. The resulting precipitate was collected by suction filtration, washed with water and air-dried to give 4.4 g (52%) of the title compound as a light gray powder; MS: 255 m/z (M-H)-.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([NH:13][C:14](=[O:16])[CH3:15])[CH2:7][CH2:6]2.B(Br)(Br)Br.C(Cl)Cl>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([NH:13][C:14](=[O:16])[CH3:15])[CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC(NC(C)=O)C2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(=O)NC1CCc2cc(O)ccc2C1
Temperature: -60 °C
Reaction time: 0.5 h
Yield: 76.5 %

Procedure:
To a suspension of N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide (1.57 g; 7.2 mmol) in CH2Cl2 (70 mL), cooled to −60° C., is added a solution of boron tribromide-CH2Cl2 (36 mL), dropwise to maintain the reaction temperature between −50 to −60° C. The gelatinous suspension is allowed to warm to RT and stir for 30 min. The reaction is cooled to 0° C., quenched with satd NaHCO3 and stirred for 30 min at RT. The mixture is extracted with CH2Cl2 (2×), the extracts combined, dried over Na2SO4, filtered and evaporated under reduced pressure to provide a crude solid, which was purified by flash chromatography (SiO2) eluting with a CH2Cl2-MeOH gradient to afford 1.13 g (76%) of N-(6-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide as a beige solid.