Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)(O)[O-].[Na+].[CH3:6][C:7]1[S:11][C:10]([S:12][CH2:13][C:14]2[CH2:21][S:20][CH:19]3[N:16]([C:17](=[O:23])[CH:18]3[NH2:22])[C:15]=2[C:24]([OH:26])=[O:25])=[N:9][N:8]=1.C1(N=C=NC2CCCCC2)CCCCC1.[N:42]1([CH2:47][C:48](O)=[O:49])[CH:46]=[CH:45][CH:44]=[CH:43]1.N=C=N>O1CCOCC1.O>[N:42]1([CH2:47][C:48]([NH:22][CH:18]2[C:17](=[O:23])[N:16]3[CH:19]2[S:20][CH2:21][C:14]([CH2:13][S:12][C:10]2[S:11][C:7]([CH3:6])=[N:8][N:9]=2)=[C:15]3[C:24]([OH:26])=[O:25])=[O:49])[CH:46]=[CH:45][CH:44]=[CH:43]1
Reactant: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)C(N)C3SC2)s1
Reactant: O=C(O)Cn1cccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: N=C=N
Agent: O=C([O-])O
Solvent: C1COCCO1
Solvent: O
Product: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)C(NC(=O)Cn4cccc4)C3SC2)s1
Reaction time: 8 h

Procedure:
(1-Pyrryl)acetic is added to water, the pH of which is adjusted to about 6.5 by the addition of sodium bicarbonate. This solution is cooled in an ice bath and to it is added one equivalent of 3-[[(5 methyl - 1, 3, 4-thiadiazol-2-yl) thio]methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (7-ATDCA) followed by N, N'-dicyclohexylcarbodiimide in cold dioxane. The mole ratio of (1-pyrryl) acetic acid/7-ATDCA/carbodiimide is 3/1/1. After standing overnight at ice bath temperature, the reaction mixture is filtered to remove solids. The filtrate is evaporated to dryness, the solids taken up in ethyl acetate, dried over magnesium sulfate and filtered. The ethyl acetate solution is concentrated and then treated with hexane. The title compound precipitates from solution is filtered and dried. EXAMPLE 6
Reaction SMILES: [CH2:1]([C@@H:3]1[CH2:8][N:7](CC2C=CC=CC=2)[C@H:6]([CH3:16])[CH2:5][N:4]1[CH3:17])[CH3:2]>CO>[CH2:1]([C@@H:3]1[CH2:8][NH:7][C@H:6]([CH3:16])[CH2:5][N:4]1[CH3:17])[CH3:2]
Reactant: CC[C@@H]1CN(Cc2ccccc2)[C@H](C)CN1C
Solvent: CO
Product: CC[C@@H]1CN[C@H](C)CN1C
Yield: 149.6 %

Procedure:
(2R,5R)-2-Ethyl-1,5-dimethyl-4-(phenylmethyl)piperazine (873 mg, 3.76 mmol) was dissolved in 50 mL of MeOH, degassed and placed under argon. 10% Pd/C (175 mg) was added, and the contents were thoroughly degassed and placed under a hydrogen balloon for approximately 3 hrs. The contents were then degassed and filtered through Celite, and the Celite pad was washed with DCM and MeOH. After 7.9 mL 1N HCl was added, the resulting filtrate was concentrated in vacuo to provide the hydrochloride salt of (2R,5R)-2-ethyl-1,5-dimethylpiperazine (800 mg, 100%). LCMS: (M+H)+: 143.1.
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[CH:20]=O)([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[CH:9][CH:8]=2)[N:6]=1.[CH3:27][NH:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.C(O)(=O)C.ClCCCl>[NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:13][CH:14]([F:15])[F:16])=[CH:11][CH:12]=2)([C:17]2[CH:24]=[CH:23][CH:22]=[C:19]([CH2:20][N:28]([CH3:29])[CH3:27])[CH:18]=2)[N:6]=1
Reactant: CN1C(=O)C(c2ccc(OC(F)F)cc2)(c2cccc(C=O)c2)N=C1N
Reactant: CNC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CN(C)Cc1cccc(C2(c3ccc(OC(F)F)cc3)N=C(N)N(C)C2=O)c1
Yield: 43 %

Procedure:
A small vial (10 ml) was charged with 3-[2-Amino-4-(4-difluoromethoxy-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-benzaldehyde (69 mg, 192 μmol) and 1,2-dichloroethane (DCE, 1 ml). To this was added a 2M solution of dimethylamine in THF (1 ml). After stirring overnight at room temperature sodium triacetoxyborohydride (58 mg, 270 μmol) was added followed by 1 drop of glacial acetic acid (˜12 mg), then after another 20 hours 1N sodium hydroxide (1 ml) was added and the mixture extracted with diethyl ether. The ethereal layer was concentrated by rotary evaporation, diluted with methanol and re-concentrated (repeated three times). Finally the oily residue was redissolved in diethylether/hexanes and concentrated, twice then placed under vacuum to give a white foam 32 mg (43%) 1H NMR (400 MHz, DMSO-d6) δ ppm 2.04 (s, 6H) 2.93 (s, 3H) 3.26 (s, 2H, partially obscured by solvent) 6.62 (br. s., 4H) 7.04-7.09 (m, 3H) 7.12 (t, J=74.18 Hz 1H) 7.18 (t, J=7.6 Hz, 1H) 7.27 (d, J=7.9 Hz, 1H) 7.35 (s, 1H) 7.40 (d, J=8.8 Hz, 2H); MS (APPI) m/z 389 [M+H]+
Reaction SMILES: O[CH:2]1[C:6]([CH3:8])([CH3:7])[CH2:5][C:4]([C:9]#[N:10])=[CH:3]1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1>ClCCl.CN(C)C=O.C(OCC)(=O)C>[F:25][C:26]1[CH:27]=[CH:28][C:29]([N:32]2[CH2:37][CH2:36][N:35]([CH:2]3[C:6]([CH3:8])([CH3:7])[CH2:5][C:4]([C:9]#[N:10])=[CH:3]3)[CH2:34][CH2:33]2)=[CH:30][CH:31]=1
Reactant: CC1(C)CC(C#N)=CC1O
Reactant: Fc1ccc(N2CCNCC2)cc1
Agent: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C)CC(C#N)=CC1N1CCN(c2ccc(F)cc2)CC1
Temperature: 2.5 °C
Reaction time: 3 h
Yield: 7.9 %

Procedure:
To a stirred solution of 3-hydroxy-4,4-dimethylcyclopent-1-enecarbonitrile (1.5 g, 10.93 mmol) in dichloromethane (20 ml) was added diisopropylethylamine, (5.73 ml, 32.8 mmol) under nitrogen atmosphere. Reaction mixture was cooled to 0-5° C. Methane sulfonyl chloride (1.278 ml, 16.40 mmol) in 2 ml dichloromethane was added drop wise at 0-5° C. in 10 mins. Reaction mixture was stirred at 0-5° C. for 3 h. Progress of reaction was monitored by TLC. Reaction mixture was diluted with dichloromethane (20 ml) and washed with water (2×10 ml), organic layer was dried on sodium sulfate and concentrated under reduced pressure to get sticky compound which was dissolved in dry N,N-dimethylformamide (15 ml) and cooled to 0-5° C. followed by addition of diisopropylethylamine (5.73 ml, 32.8 mmol) and 1-(4-fluorophenyl)piperazine (1.971 g, 10.93 mmol) under nitrogen atmosphere. Reaction mixture was gradually warmed to 25-30° C. and stirring continued for 16 h. Progress of reaction was monitored by TLC. Reaction mixture was concentrated under reduced pressure to obtain crude product which was dissolved in ethyl acetate (100 ml) and washed with water (3×25 ml). Combined organic layer was dried on sodium sulphate and concentrated under reduced pressure to get crude oily product. Crude compound was purified over silica gel (100-200 mesh) by flash column chromatography using 20% ethyl acetate in hexane to obtain title compound (0.260 g).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:3]=1[O:4][CH2:5][CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C=O.[BH3-][C:22]#N.[Na+]>CC#N>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:3]=1[O:4][CH2:5][CH:6]1[CH2:7][CH2:8][N:9]([CH3:22])[CH2:10][CH2:11]1
Reactant: [BH3-]C#N
Reactant: O=[N+]([O-])c1ccc(Cl)c(OCC2CCNCC2)c1
Agent: C=O
Agent: [Na+]
Solvent: CC#N
Product: CN1CCC(COc2cc([N+](=O)[O-])ccc2Cl)CC1
Reaction time: 4 h

Procedure:
4-(2-Chloro-5-nitro-phenoxymethyl)-piperidine (4 g, 14.8 mmol) was dissolved in CH3CN (20 ml), and formaldehyde (5.9 ml, 37% aqueous) and NaBH3CN (1.49 g, 23.68 mmol) were added. After 4 h, the mixture was concentrated in vacuo and the residue was dissolved in EtOAc, washed with brine. The EtOAc portion was dried with Na2SO4, and evaporated. The title compound was purified by column chromatography using 0-75% of a 90:10:1 (CH2Cl2:MeOH: NH4OH) solution as the eluent to yield a yellow solid. MS(MH+)=NA; Calc'd 284.09 for C13H17ClN2O3.
Reaction SMILES: Cl.Cl[C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[CH:5][C:4]=1[N+:13]([O-:15])=[O:14].[NH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[N+:13]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:3]=1[NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-:15])=[O:14]
Reactant: NCCCCCCNC(=O)c1ccccc1
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Agent: Cl
Product: O=C(NCCCCCCNc1c([N+](=O)[O-])cnc2ccccc12)c1ccccc1

Procedure:
Using the general method of Example 9 Part B, 4-chloro-3-nitroquinoline hydrochloride (10 g, 41 mnmol) was reacted with N-(6-aminohexyl)benzamide to provide 12.85 g of N1-{6-[(3-nitroquinolin-4-yl)amino]hexyl}benzamide as a yellow crystalline solid.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[OH:14].F[C:16]1[CH:17]=[CH:18][C:19]([N+:29]([O-:31])=[O:30])=[C:20]([CH:28]=1)[C:21]([N:23]=[S:24]([CH3:27])([CH3:26])=[O:25])=[O:22]>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[C:8]([C:10]([F:12])([F:13])[F:11])[CH:7]=[CH:6][C:5]=1[O:14][C:16]1[CH:17]=[CH:18][C:19]([N+:29]([O-:31])=[O:30])=[C:20]([CH:28]=1)[C:21]([N:23]=[S:24]([CH3:27])([CH3:26])=[O:25])=[O:22]
Reactant: Oc1ccc(C(F)(F)F)cc1Cl
Reactant: CS(C)(=O)=NC(=O)c1cc(F)ccc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(C)(=O)=NC(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 1 h
Yield: 23 %

Procedure:
0.48 g of sodium hydride is placed in 10 ml of absolute dimethylformamide. 1.96 g of o-chloro-p-trifluoromethyl-phenol are added dropwise and the mixture is stirred for 1 hour. 2.6 g of N-(5-fluoro-2-nitrobenzoyl)-S,S-dimethyl-sulphoximine are added and the mixture is heated to 100° C. for 90 minutes. The mixture is then cooled, poured on to 100 ml of ice-water and extracted with 50 ml of ethyl acetate. The ethyl acetate phase is washed with water, dried and evaporated, and the residue is purified by chromatography and crystallized from diethyl ether. There is obtained 1 g of N-[5-(o-chloro-p-trifluoromethyl-phenoxy)-2-nitrobenzoyl]-S,S-dimethyl-sulphoximine, m.p. 122° C.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[SH2:10].O>N1C=CC=CC=1.C(N(CC)CC)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]([NH2:7])=[S:10])=[CH:4][CH:3]=1
Reactant: S
Reactant: N#Cc1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: c1ccncc1
Product: NC(=S)c1ccc(Cl)cc1
Reaction time: 0.5 h

Procedure:
68.8 g (0.5 mol) of 4-chlorobenzonitrile were dissolved in a mixture of 100 ml pyridine and 50 ml triethylamine. Whilst stirring, an even flow of 15 l (0.67 mol/hour) of hydrogen sulphide was introduced at room temperature, then 11 l (0.5 mol/hour) for 30 min at 50° C., i.e. a total of 1.25 mol. This was then stirred for a further 30 min at 50° C. and then mixed into 1.5 liters of water. The crystallate was drawn off, washed with plenty of water and dried,
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:16]#[N:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][OH:15])[CH:9]=2)=[CH:6][N:7]=1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23]([NH:25][NH2:26])=O.C[O-].[Na+]>CO>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=2)=[N:4][C:3]=1[C:16]1[NH:26][N:25]=[C:23]([C:19]2[S:18][CH:22]=[CH:21][CH:20]=2)[N:17]=1
Reactant: N#Cc1nc(-c2cccc(CO)c2)cnc1N
Reactant: NNC(=O)c1cccs1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Nc1ncc(-c2cccc(CO)c2)nc1-c1nc(-c2cccs2)n[nH]1
Yield: 6.1 %

Procedure:
To a solution of 3-amino-6-[3-(hydroxymethyl)phenyl]pyrazine-2-carbonitrile (149 mg, 0.74 mmol) was added thiophene-2-carboxylic acid hydrazide (94 mg, 0.66 mmol), sodium methoxide (53 mg, 0.996 mmol) in MeOH (5 mL). After reflux for 4 days, the reaction mixture was extracted with ethyl acetate (10 mL×3) and dried over MgSO4. Filteraction and concentration in vacuo gave a crude product, which was purified by preparative HPLC (0.1% TFA in water/0.1% TFA in CH3CN). The product fractions were neutralized by aqueous saturated sodium bicarbonate solution and partitioned with ethyl acetate. The aqueous phase was extracted once with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo gave the (3-{5-amino-6-[3-(2-thienyl)-1H-1,2,4-triazol-5-yl]pyrazin-2-yl } phenyl)methanol (14 mg, yield): 1H NMR (400 MHz, CD3OD): δ 8.65 (s, 1H), 8.14 (s, 1H), 8.02 (d, 1H), 7.77 (m, 1H), 7.53 (m, 1H), 7.47 (m, 1H), 7.38 (m, 1H), 7.17 (m, 1H), 4.72 (s, 2H); MS (EI) for C17H14N6O: 351.10 (MH+).
Reaction SMILES: BrC(F)(F)C(Cl)(F)C=C.[F:10][C:11]([F:25])([C:21]([F:24])([F:23])[F:22])[C:12]([F:20])([F:19])[C:13]([O:16][CH2:17]C)([F:15])[F:14]>C(Cl)(F)(F)C(Cl)(Cl)F>[F:10][C:11]([F:25])([C:21]([F:22])([F:24])[F:23])[C:12]([F:19])([F:20])[C:13]([O:16][CH3:17])([F:15])[F:14]
Reactant: CCOC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: C=CC(F)(Cl)C(F)(F)Br
Solvent: FC(F)(Cl)C(F)(Cl)Cl
Product: COC(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
Solvency tests with 50% by volume 4-bromo-3-chloro-3,4,4-trifluorobutene and 50% by volume ethyl nonafluorobutyl ether were performed. The solvency characteristics of these mixtures matched or exceeded that of CFC-113 with Krytox and Jet Lube. The solvency of the individual components was inferior to that of CFC-113 toward Krytox and Jet Lube, illustrating the effectiveness of using mixtures as taught by this invention. Similarly, mixtures of 4-bromo-3,3,4,4-trifluorobutene and methyl nonafluorobutyl ether produced solvency characteristic that met or exceeded those of CFC-113.
Reaction SMILES: Cl.[CH2:2]([O:9][NH2:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:11]1[CH:20]=[C:19]2[C:21]([O:23][C:24](=O)[C:17]3=[C:18]2[C:13](=[CH:14][C:15]([Br:26])=[CH:16]3)[CH:12]=1)=[O:22]>N1C=CC=CC=1>[CH2:2]([O:9][N:10]1[C:24](=[O:23])[C:17]2[CH:16]=[C:15]([Br:26])[CH:14]=[C:13]3[C:18]=2[C:19](=[CH:20][CH:11]=[CH:12]3)[C:21]1=[O:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: O=C1OC(=O)c2cc(Br)cc3cccc1c23
Reactant: NOCc1ccccc1
Agent: Cl
Solvent: c1ccncc1
Product: O=C1c2cccc3cc(Br)cc(c23)C(=O)N1OCc1ccccc1
Yield: 89.1 %

Procedure:
O-Benzyl hydroxylamine hydrochloride (0.9 g, 5.6 mmol) and 3-bromo-1,8-naphthalic anhydride (1.3 g, 4.7 mmol, from Example N) were reacted in pyridine (30 mL) following the procedure of Example D to give 1.6 g of the title compound.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1>O1CCOCC1>[N:1]1([CH2:7][CH2:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: BrCCc1c[nH]c2ccccc12
Reactant: C1CCNC1
Solvent: C1COCCO1
Product: c1ccc2c(CCN3CCCC3)c[nH]c2c1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
Pyrrolidine (3.17 g, 3.7 ml, 44.6 mmol) was dissolved in abs. dioxane (100 ml), 3-(2-bromo-ethyl)-1H-indole (5 g, 22.3 mmol) was added at RT and the mixture was stirred at 70° C. for 8 h. The solution was concentrated, the residue was taken up in CHCl3 (150 ml) and the mixture was washed with water (2×50 ml). The organic phase was dried over Na2SO4, filtered and concentrated i. vac.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:33])[C:7]([C:16]3[CH:32]=[CH:31][C:19]([C:20]([NH:22][NH:23]C(OC(C)(C)C)=O)=[O:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.Cl.CO>>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:33])[C:7]([C:16]3[CH:32]=[CH:31][C:19]([C:20]([NH:22][NH2:23])=[O:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:14])([F:15])[F:13])[O:9]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NNC(=O)c1ccc(-c2c(C(F)(F)F)oc3cc(O)ccc3c2=O)cc1
Agent: Cl
Solvent: CO
Product: NNC(=O)c1ccc(-c2c(C(F)(F)F)oc3cc(O)ccc3c2=O)cc1

Procedure:
tert-Butyl 2-(4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzoyl)hydrazinecarboxylate is treated with HCl/MeOH overnight. Solvent is removed under reduced pressure to give the product.
Reaction SMILES: [CH2:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH2:2][CH2:3][CH3:4].[H-].[Na+].Br[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>O1CCCC1>[CH2:23]([O:22][C:20](=[O:21])[CH2:19][N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[S:6]([C:9]1[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=1)(=[O:7])=[O:8])[CH3:24]
Reactant: CCOC(=O)CBr
Reactant: CCCCNS(=O)(=O)c1ccc(C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCN(CC(=O)OCC)S(=O)(=O)c1ccc(C)cc1

Procedure:
Dissolve N-butyl-4-methyl-benzenesulfonamide (10 mmol) in tetrahydrofuran (50 mL) and treat with sodium hydride (10 mmol). Stir the reaction for 30 minutes and add ethyl bromoacetate (10 mmol). Stir the reaction at reflux for 18 hours. Then add methylene chloride (100 mL) and rinse with water (100 mL), brine (100 mL), dry over anhydrous sodium sulfate, filter and concentrate to provide crude ethyl-[butyl-(toluene-4-sulfonyl)-amino]-acetate.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[C:10]([O:12]C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[OH-].[Li+].O1CCOCC1.Cl>O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: COC(=O)[C@H](Cc1ccnc(OC)c1)NC(=O)OC(C)(C)C
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1COCCO1
Product: COc1cc(C[C@H](NC(=O)OC(C)(C)C)C(=O)O)ccn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(2-methoxypyridin-4-yl)propanoate (1.42 g, 4.58 mmol) was mixed with methanol (10.0 mL) and a solution of lithium hydroxide (0.66 g, 14 mmol) in water (5.0 mL). The mixture was stirred at rt for 1 h. The mixture was then acidified with 4 N HCl dioxane solution and condensed under vacuum directly to give the white solid mixture, which was used directly in the next step. LC-MS found: 297.1 (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[C:16]([NH2:23])[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(O)=O.C([O-])(O)=O.[Na+].CC(=O)OCC>CCO.C1COCC1.[Zn].O>[NH2:23][C:16]1[CH:15]=[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:19]=[CH:18][C:17]=1[NH2:20]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])c(N)c2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Zn]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(N)c(N)c2)CC1
Yield: 59.5 %

Procedure:
A mixture of tert-butyl-4-(3-amino-4-nitrophenyl)piperazine-1-carboxylate (13 g, 46 mmol), Zn (8.9 g, 140 mmol), and HOAc (8.4 g, 140 mmol) in EtOH/THF (250 ml) was refluxed for 20 mins. After adjusted its PH to 8 by NaHCO3, EA and H2O were added resulting in a precipitate. The solid was filtered off under vacuum. The combined organic layers were dried by anhydrous Na2SO4 and concentrated in vacuo to afford tert-butyl 4-(3,4-diaminophenyl)piperazine-1-carboxylate as a black solid (8 g, yield: 60%).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:7][CH:8]=1.[CH3:22][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI.[Cl-].[NH4+]>O1CCCC1>[CH3:22][C:9]([C:6]1[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:8][N:7]=1)([CH2:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CCOC(=O)C(CC1CCOCC1)c1ccc(SC)cn1
Agent: [Cl-]
Agent: [Li+]
Agent: [NH4+]
Solvent: CI
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(CC1CCOCC1)c1ccc(SC)cn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
To a solution of ethyl 2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate (1.18 g) in dry tetrahydrofuran (7.6 mL) was added lithium hexamethyldisilazide (1.1M tetrahydrofuran solution, 4.49 mL), and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added methyl iodide (473 μL), and the mixture was stirred at room temperature for 30 min. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the title compound (1.11 g, yield 90%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (1:2, volume ratio).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:17]([O-:19])=[O:18])=[C:6]([CH:16]=1)[O:7][C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[CH:10]=[O:11].C([O:22]CC)C.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.OS(O)(=O)=O>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:17]([O-:19])=[O:18])=[C:6]([CH:16]=1)[O:7][C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[C:10]([OH:22])=[O:11]
Reactant: O=Cc1ccccc1Oc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: CCOCC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)(O)O
Agent: [OH-]
Solvent: O
Product: O=C(O)c1ccccc1Oc1cc(Cl)ccc1[N+](=O)[O-]
Reaction time: 2 h

Procedure:
The 2-(5'-chloro-2-nitrophenoxy)benzoic acid was prepared as follows: Crude 2-(5-chloro-2-nitrophenoxy)benzaldehyde was heated under reflux with 200 ml of diethylether, 120 ml of water, 41.1 g of Na2Cr2O7 ·2H2O and 6.0 g of a 40% tetra-n-butylammonium hydroxide solution, and to it was added 63 ml of 9M H2SO4 over three hours. Heating was continued for an additional two hours, and the aqueous layer was extracted with ether and evaporated to dryness to provide the product.
Reaction SMILES: ClC1C=C2C(C(=O)CCN2)=CC=1.[Cl:13][C:14]1[CH:15]=[C:16]([CH:23]=[CH:24][CH:25]=1)[NH:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21].[C:26](Cl)([Cl:28])=[O:27]>>[Cl:28][C:26]([N:17]([CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:16]1[CH:23]=[CH:24][CH:25]=[C:14]([Cl:13])[CH:15]=1)=[O:27]
Reactant: O=C(O)CCNc1cccc(Cl)c1
Reactant: O=C(Cl)Cl
Agent: O=C1CCNc2cc(Cl)ccc21
Product: O=C(O)CCN(C(=O)Cl)c1cccc(Cl)c1

Procedure:
A process of the preparation of 7-chloro-1,2,3,4-tetrahydro-4-quinolinone which comprises treating 3-(m-chloro-anilino)propionic acid with phosgene to produce N-chloroformyl-3-(m-chloroanilino)propionic acid, converting the said product, by the action of an organic base or by heating, into 3-(m-chlorophenyl)-2,6-dioxo-1,3-perhydrooxazine, and treating the latter with aluminium chloride in an inert organic solvent or with a strong acid, to provide 7-chloro-1,2,3,4-tetrahydro-4-quinolinone.
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][SH:4].[C:8]([C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]=1[OH:20])[CH:15]=O)([CH3:11])([CH3:10])[CH3:9]>CO>[C:21]([C:18]1[CH:17]=[C:14]([CH:15]2[NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][S:4]2)[CH:13]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:19]=1[OH:20])([CH3:24])([CH3:23])[CH3:22]
Reactant: N[C@@H](CS)C(=O)O
Reactant: CC(C)(C)c1cc(C=O)cc(C(C)(C)C)c1O
Solvent: CO
Product: CC(C)(C)c1cc(C2N[C@H](C(=O)O)CS2)cc(C(C)(C)C)c1O
Temperature: 25 °C
Yield: 22.5 %

Procedure:
A mixture of cysteine (Aldrich, 2.0 g, 17.1 mmol) and 3,5-di-tert-butyl-4-hydroxybenzaldehyde (Aldrich, 4.0 g, 17.1 mmol) in methanol (100 mL) was warmed at reflux for 2.25 h. The reaction mixture was cooled to ambient temperature and the solid that formed upon cooling was collected by filtration. The solid was washed with methanol and recrystallized from a mixture of ethanol/ethyl acetate. Recrystallization from ethanol gave 1.3 g (22% yield) of (4R)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-thiazolidine carboxylic acid as an off white solid, m.p. 163°-165° C.