Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:3]([O:24][CH3:25])=[CH:4][C:5]2[CH2:14][CH:13]3[N:8]([CH2:9][CH2:10][C:11]4[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH3:22])=[CH:15][C:12]=43)[CH2:7][C:6]=2[CH:23]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>N1C=CC=CC=1>[CH3:22][O:21][C:16]1[C:17]([O:19][CH3:20])=[CH:18][C:11]2[CH2:10][CH2:9][N:8]3[CH:13]([CH2:14][C:5]4[CH:4]=[C:3]([O:24][CH3:25])[C:2]([O:1][C:26](=[O:28])[CH3:27])=[CH:23][C:6]=4[CH2:7]3)[C:12]=2[CH:15]=1
Reactant: COc1cc2c(cc1O)CN1CCc3cc(OC)c(OC)cc3C1C2
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: COc1cc2c(cc1OC)C1Cc3cc(OC)c(OC(C)=O)cc3CN1CC2
Yield: 33.3 %

Procedure:
0.8 g. of 10-hydroxy-2,3,11-trimethoxy-5,6,13,13a-tetrahydro-8H-dibenzo[a, g]quinolizine was dissolved in 8 ml of anhydrous pyridine. To the resulting solution 2 ml of acetic anhydride was added dropwise with stirring, while cooling in an ice-bath. After the mixture was stirred at room temperature for 5 hours, the excessive acetic anhydride was distilled off under reduced pressure, and the residue obtained was extracted with chloroform. The chloroform layer was washed with a 1N-sodium hydroxide solution and then with water, dried over potassium carbonate and evaporated to dryness. Recrystallization of the residue from ethanol-petroleum ether afforded 0.3 g. (33.3% yield) of 5,6,13,13a-tetrahydro-2,3,11-trimethoxy-10-acetoxy-8H-dibenzo [a,g]quinolizine as colorless needles having a melting point of 162° to 164°C.
Reaction SMILES: C(S)C.C([Li])CCC.[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:18]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27]C)=[CH:23][CH:22]=3)=[O:20])=[C:17]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[S:16][C:15]=2[CH:37]=1.Cl>O1CCCC1.CN(C)C=O>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:18]([C:19]([C:21]3[CH:22]=[CH:23][C:24]([OH:27])=[CH:25][CH:26]=3)=[O:20])=[C:17]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[S:16][C:15]=2[CH:37]=1
Reactant: COc1ccc(C(=O)c2c(-c3ccc(OC)cc3)sc3cc(OC)ccc23)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCS
Solvent: CN(C)C=O
Product: COc1ccc(-c2sc3cc(OC)ccc3c2C(=O)c2ccc(O)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of ethanethiol (538 mL, 7.27 mmol) in 1.88 mL of tetrahydrofuran, cooled to −30° C. was added n-butyllithium (2.57 mL, 2.5 M, 6.42 mmol) and the reaction was warmed to room temperature. Dimethylformamide (1 mL) was added then the product from Step 1 (1.73 g, 4.3 mmol) in 2.7 mL of dimethylformamide. The reaction was heated at 58° C. for two hours then at 80° C. for 1 hour. The cooled reaction was poured into 33 mL oh 1N hydrochloric acid and extracted with ethyl acetate. The combined organic layers was washed with brine and dried over anhydrous magnesium sulfate. After filtration, concentration and silica gel column chromatography using 15% ethyl acetate -hexanes as eluant the title compound (1.17 g) was obtained.
Reaction SMILES: [N+:1]([CH:4]=[CH:5][C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)([O-:3])=[O:2].[CH3:11][N:12]([CH3:16])[C:13](=[S:15])[S-:14].C[NH2+]C>C(=S)=S>[CH3:11][N:12]([CH3:16])[C:13](=[S:14])[S:15][CH:5]([CH2:4][N+:1]([O-:3])=[O:2])[C:6]1[S:7][CH:8]=[CH:9][CH:10]=1
Reactant: O=[N+]([O-])C=Cc1cccs1
Reactant: CN(C)C(=S)[S-]
Agent: C[NH2+]C
Solvent: S=C=S
Product: CN(C)C(=S)SC(C[N+](=O)[O-])c1cccs1

Procedure:
As in Example 17, reaction of 2-(2-nitrovinyl)thiophene with dimethylammonium dimethyldithiocarbamate in the presence of carbon disulfide gave α-(nitromethyl)-2-thenyl dimethyldithiocarbamate melting at 88° C.-90° C. when recrystallized without heating from acetone-ethanol solution.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:6]=[C:7]([C:9]([Cl:13])=[CH:10][C:11]=1[Cl:12])[NH2:8])[CH:2]=C.[C:14]1(=O)OC(=O)C2=CC=CC=C12.C(OC1C=C(C(F)=CC=1Cl)N)C=C.C1(=O)NC(=O)C2=CC=CC=C12.NC1(F)C2CC(C)OC2=C(Cl)C=C1>>[NH2:8][C:7]1[C:6]2[CH2:14][CH:1]([CH3:2])[O:4][C:5]=2[C:11]([Cl:12])=[CH:10][C:9]=1[Cl:13]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: C=CCOc1cc(N)c(Cl)cc1Cl
Agent: C=CCOc1cc(N)c(F)cc1Cl
Agent: CC1CC2C(=C(Cl)C=CC2(N)F)O1
Agent: O=C1NC(=O)c2ccccc21
Product: CC1Cc2c(N)c(Cl)cc(Cl)c2O1

Procedure:
4-amino-5,7-dichloro-2,3-dihydro-2-methylbenzofuran (38A) was prepared as an orange oil in four steps from 3-(allyloxy)-4,6-dichloroaniline and phthalic anhydride by the procedures described for preparing Example 19 from 19A, followed by hydrazinolysis of the phthalimide intermediate as described for the preparation of 37A.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH:10]2[CH2:15][CH2:14][N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C1(O)C=CC=CC=1.[BrH:33]>O>[BrH:33].[Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Cc1ccc(S(=O)(=O)N2CCC(Sc3ccc(Cl)c(Cl)c3)CC2)cc1
Agent: Br
Solvent: O
Solvent: Oc1ccccc1
Product: Clc1ccc(SC2CCNCC2)cc1Cl
Temperature: 25 °C

Procedure:
A solution of 20.84 g (0.0502 mole) of 4-[(3,4-dichlorophenyl)thio]-1-[(4-methylphenyl)sulfonyl]piperidine, 36.58 g (0.338 mole) of phenol and 200 ml of 48% hydrobromic acid was heated at reflux for 25 hr. The reaction mixture was cooled to room temperature and diluted with water. The aqueous phase was extracted with benzene. The resulting aqueous acidic phase was made alkaline with 10% aqueous sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulfate, filtered and evaporated to give a residue, the free base of the title compound. The free base was converted to the hydrobromide salt. The salt was recrystallized from methylene chloride-methanol diethyl ether to give 3.6 g (4.4%) of white solid, m.p. 125°-128° C.
Reaction SMILES: O1CCCCC1[O:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22]([O:24][CH3:25])=[O:23])=[CH:11][CH:10]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[OH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22]([O:24][CH3:25])=[O:23])=[CH:13][CH:14]=1
Reactant: COC(=O)Nc1ccccc1-c1ccc(COC2CCCCO2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)Nc1ccccc1-c1ccc(CO)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.7 %

Procedure:
The crude 4-(tetrahydropyranyloxy)methyl-2'-(methoxycarbonyl)amino-1,1'-biphenyl (250 mg) dissolved in 4 mL of methanol was treated with 1 mL of 10% methanolic p-toluenesulfonic acid. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was made basic by the addition of saturated aqueous sodium bicarbonate, then diluted with ethyl acetate. The organic layer was washed with water (2×), dried over magnesium sulfate and evaporated under vacuum. The residue was purified by preparative thin layer chromatography on silica gel, eluting with methylene chloride/methanol (100:3) to give 137 mg of the product. FAB-MS (Li+ spike): calculated for C15H15NO3 (257); found 264 (M+Li). 1H NMR (200 MHz, CDCl3): 3.51 (s, 3H), 4.75 (s, 2H), 6.62 (br s, 1H), 7.14 (dd, 2H), 7.34 (dd, 1H), 7.4 (dd, 4H).
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][CH2:5][CH2:6]Cl.[NH2:8][C@@H:9]([CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:10]([O:12][CH3:13])=[O:11].O>C(N(C(C)C)CC)(C)C>[C:19]([O:18][C:16]([NH:15][CH2:14][C@H:9]([N:8]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)[C:10]([O:12][CH3:13])=[O:11])=[O:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: ClCCOCCCl
Reactant: COC(=O)[C@@H](N)CNC(=O)OC(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: COC(=O)[C@H](CNC(=O)OC(C)(C)C)N1CCOCC1
Temperature: 127 °C
Reaction time: 18 h
Yield: 24.3 %

Procedure:
2.8 g (20 mmol) of 1-chloro-2-(2-chloroethoxy)ethane are added to a solution of 5 g (20 mmol) of commercial methyl(S)-2-amino-3-tert-butoxycarbonylaminopropanoate in 65 ml of diisopropylethylamine. The reaction mixture is stirred at 127° C. for 18 h. After the addition of water, the reaction medium is extracted with ethyl acetate. The organic phases are combined, dried over sodium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on silica gel, elution being carried out with a 70/30 heptane/ethyl acetate mixture. 1.4 g (24%) of methyl(S)-3-tert-butoxycarbonylamino-2-morpholin-4-ylpropanoate are obtained in the form of an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([C:20]([F:23])([F:22])[F:21])=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([NH:15][C:16](=[O:19])[O:17][CH3:18])=[O:14])=[CH:8][CH:7]=[CH:6]2.[H-].[Na+].Br[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>O1CCCC1>[CH3:1][O:2][C:3]1[C:4]([C:20]([F:22])([F:21])[F:23])=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([N:15]([C:16]([O:17][CH3:18])=[O:19])[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:14])=[CH:8][CH:7]=[CH:6]2
Reactant: CC(C)(C)OC(=O)CBr
Reactant: COC(=O)NC(=O)c1cccc2c(C(F)(F)F)c(OC)ccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)N(CC(=O)OC(C)(C)C)C(=O)c1cccc2c(C(F)(F)F)c(OC)ccc12
Yield: 70.8 %

Procedure:
N-[[6-Methoxy-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]carbamic acid, methyl ester (2.2 g, 6.72 mmol) was added to a suspension of sodium hydride (60% in oil, 0.29 g, 7.25 mmol) in tetrahydrofuran (anhydrous, 150 mL) and the mixture stirred for 1.5 hours at 20° C. tert-Butyl bromoacetate (1.20 mL, 7.40 mmol) was added and the resultant solution was stirred for 20 hours at 20° C. The solvent was evaporated and the residual solid triturated with hexanes (3×20 mL), to yield the pure product (2.1 g, 71.2%) as a white crystalline solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:10][CH:11]=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH2:18].C([BH3-])#N.[Na+]>CO>[CH3:14][O:15][C:16](=[O:19])[CH2:17][NH:18][CH2:11][CH2:10][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:9]
Reactant: CN(CC=O)C(=O)OC(C)(C)C
Reactant: COC(=O)CN
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: COC(=O)CNCCN(C)C(=O)OC(C)(C)C
Reaction time: 8 h
Yield: 48.8 %

Procedure:
To a solution of N-t-butoxycarbonylsarcosinal (1.50 g) and glycine methyl ester hydrochloride (1.63 g) in methanol (60 ml) was added a solution of sodium cyanoborohydride (544 mg) in methanol (10 ml) at ambient temperature. The mixture was stirred overnight at the same temperature. After evaporation of the solvent, the residue was dissolved in ethyl acetate (50 ml), and the solution was washed with 1 M sodium bicarbonate solution and water successively, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (chloroform as eluent) to give N-[2-(N-t-butoxycarbonyl-N-methylamino)ethyl]glycine methyl ester (1.04 g) as an oil.
Reaction SMILES: [CH2:1]([O:5][C:6]([C:8]1[C:9]([OH:19])=[C:10]2[C:17]([CH3:18])=[N:16][S:15][C:11]2=[C:12](Br)[N:13]=1)=[O:7])[CH2:2][CH2:3][CH3:4].[CH2:20]([Sn](CC)(CC)CC)[CH3:21]>>[CH2:1]([O:5][C:6]([C:8]1[C:9]([OH:19])=[C:10]2[C:17]([CH3:18])=[N:16][S:15][C:11]2=[C:12]([CH2:20][CH3:21])[N:13]=1)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)c1nc(Br)c2snc(C)c2c1O
Reactant: CC[Sn](CC)(CC)CC
Product: CCCCOC(=O)c1nc(CC)c2snc(C)c2c1O

Procedure:
The title compound was synthesized in analogy to Example 28 from 7-bromo-4-hydroxy-3-methyl-isothiazolo[5,4-c]pyridine-5-carboxylic acid butyl ester and tetraethyltin: MS (m/z) 295.2 (M+1).
Reaction SMILES: O=[C:2]([CH2:11][CH2:12][CH3:13])[CH2:3][C:4]([O:6]CCC#N)=[O:5].[NH2:14]/[C:15](/[CH3:21])=[CH:16]\[C:17]([O:19][CH3:20])=[O:18].[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1>C(O)(C)C>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]2[C:16]([C:17]([O:19][CH3:20])=[O:18])=[C:15]([CH3:21])[NH:14][C:2]([CH2:11][CH2:12][CH3:13])=[C:3]2[C:4]([OH:6])=[O:5])=[CH:25][CH:24]=1
Reactant: COC(=O)/C=C(/C)N
Reactant: CCCC(=O)CC(=O)OCCC#N
Reactant: O=Cc1ccc(Cl)cc1
Solvent: CC(C)O
Product: CCCC1=C(C(=O)O)C(c2ccc(Cl)cc2)C(C(=O)OC)=C(C)N1
Reaction time: 0.5 h

Procedure:
A mixture of 2-cyanoethyl 3-oxohexanoate (11.9 mmol), methyl 3-aminocrotonate (11.9 mmol), and 4-chlorobenzaldehyde in 25 mL of isopropanol is heated at reflux temperature for 16 h, cooled, and the solvent is removed under reduced pressure. The residue is dissolved in 15 mL of dioxane and 626 mg of NaOH in 15 mL of water is added to the reaction mixture. After 0.5 hrs, the solution its concentrated to a small volume under reduced pressure, partitioned between 50 mL of water and 50 mL of ethyl acetate, separated, and the aqueous solution is washed with 2×20 mL of ethyl acetate. The organic solutions are discarded. The aqueous extract is acidified with concentrated HCl (pH=2), and the precipitated oil. is extracted with ethyl acetate (2×40 mL). The combined organic extracts are dried (MgSO4), and the solvent is removed in vacuo to give a residue, which is characterized spectroscopically.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[NH:18][C:19]4[CH:29]=[CH:28][C:27]5[C:22](=[C:23]([OH:33])[CH:24]=[C:25]([C:30](O)=[O:31])[CH:26]=5)[C:20]=4[N:21]=3)[CH:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.C([O:39][C:40](=[O:50])[C@H:41]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[NH2:42])(C)(C)C.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C=O.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[NH:18][C:19]4[CH:29]=[CH:28][C:27]5[C:22](=[C:23]([OH:33])[CH:24]=[C:25]([C:30]([NH:42][C@@H:41]([CH2:43][C:44]6[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=6)[C:40]([OH:50])=[O:39])=[O:31])[CH:26]=5)[C:20]=4[N:21]=3)[CH:12]=2)=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)[C@@H](N)Cc1ccccc1
Reactant: CC(C)(C)c1ccc(-c2cccc(-c3nc4c(ccc5cc(C(=O)O)cc(O)c54)[nH]3)c2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)(C)c1ccc(-c2cccc(-c3nc4c(ccc5cc(C(=O)N[C@@H](Cc6ccccc6)C(=O)O)cc(O)c54)[nH]3)c2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To the 2-(4′-tert-butylbiphenyl-3-yl)-9-hydroxy-3H-naphtho[1,2-d]imidazole-7-carboxylic acid (0.047 g, 0.1 mmol) in dimethylformamide (0.5 mL)at room temperature was added phenylalanine tert butyl ester hydrochloride (0.11 mmol). A cocktail solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.021 g, 0.11 mmol), triethylamine (0.3 mmol) in DMF (0.5 mL) was added and the reaction was agitated at room temperature for 18 hours. 1 ml water was added to the reaction mixture resulting in the formation of a tan precipitate. the mixture was filtered and allowed to dry. The solid mass was transferred into vial and dissolved in 1 ml of 90% trifluoroacetic acid. The solutions were agitated for 6 hrs then concentrated under reduced pressure. The residures were taked up in DMSO and subjected to Gilson HPLC purification. The title compound was abtained as solid.(0.016 g, 28%). MS(ES) m/z 584 [M+H].
Reaction SMILES: CC1(C)[N:6](C(OC(C)(C)C)=O)[C@:5]([CH3:20])([C:14]2[S:15][C:16]([CH3:19])=[N:17][N:18]=2)[CH2:4][O:3]1.[F:22][C:23]([F:28])([F:27])[C:24]([OH:26])=[O:25]>ClCCl>[F:22][C:23]([F:28])([F:27])[C:24]([OH:26])=[O:25].[NH2:6][C@@:5]([C:14]1[S:15][C:16]([CH3:19])=[N:17][N:18]=1)([CH3:20])[CH2:4][OH:3]
Reactant: Cc1nnc([C@]2(C)COC(C)(C)N2C(=O)OC(C)(C)C)s1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1nnc([C@@](C)(N)CO)s1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 1.2 g of tert-butyl (4S)-2,2,4-trimethyl-4-(5-methyl-1,3,4-thiadiazol-2-yl)-1,3-oxazolidine-3-carboxylate in 12 ml of dichloromethane was added 4 ml of trifluoroacetic acid, followed by stirring at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was azeotropic distilled with methanol to obtain 1.59 g of (2S)-2-amino-2-(5-methyl-1,3,4-thiadiazol-2-yl)propan-1-ol trifluoroacetate as a crude product.
Reaction SMILES: [CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].Cl.[F:9][C:10]([F:27])([S:23]([O-:26])(=[O:25])=[O:24])[CH:11]([O:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:12]([F:15])([F:14])[F:13].[Na+].ClCCl>O.C(OCC)C>[F:27][C:10]([F:9])([S:23]([O-:26])(=[O:24])=[O:25])[CH:11]([O:16][C:17](=[O:22])[C:18]([CH3:20])([CH3:21])[CH3:19])[C:12]([F:13])([F:15])[F:14].[CH2:1]([NH+:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2]
Reactant: CCN(CC)CC
Agent: CC(C)(C)C(=O)OC(C(F)(F)F)C(F)(F)S(=O)(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOCC
Solvent: O
Product: CC[NH+](CC)CC

Procedure:
Triethylamine was dissolved in cold water, and hydrochloric acid was added thereto to adjust the pH of the reaction liquid to fall within a range of 1 to 3. Then sodium 1,1,3,3,3-pentafluoro-2-(pivaloyloxy)propanesulfonate and dichloromethane were added thereto and stirred. The separated organic layer was washed with water, and dichloromethane was removed under reduced pressure from the washed organic layer. To the residue thus obtained, diethyl ether was added for recrystallization. The resultant was filtrated and dried to obtain a desired product at a yield of 75%. The structure of the obtained product was identified using 1H-NMR, IR and TOFMS spectra.
Reaction SMILES: [NH2:1][C:2]([CH3:9])([CH3:8])[CH2:3][NH:4][CH2:5][CH2:6][NH2:7].[CH3:10][C:11](=O)[CH2:12][CH3:13].[H][H]>[Pt].CO>[CH3:10][CH:11]([NH:7][CH2:6][CH2:5][NH:4][CH2:3][C:2]([NH2:1])([CH3:9])[CH3:8])[CH2:12][CH3:13]
Reactant: [H][H]
Reactant: CCC(C)=O
Reactant: CC(C)(N)CNCCN
Agent: [Pt]
Solvent: CO
Product: CCC(C)NCCNCC(C)(C)N
Yield: 69.5 %

Procedure:
A mixture of 146 g (1.1 moles) of N-(2-amino-2-methylpropyl)-1,2-ethanediamine, 84.4 (1.17 moles) of 2-butanone, 300 ml methanol, and 3.0 g of 10% platinum on carbon were reacted in a 1 liter autoclave at 80° C. under 800 pounds per square inch (psi) hydrogen pressure. After two hours the reaction mixture was cooled, then filtered to remove the catalyst. The filtrate was stripped to give 205.3 g of water-white clear liquid which was fractionally distilled under reduced pressure. The desired product recovered was found to weigh 144.5 g (69.5% yield), and has a boiling point (b.p.) of 62°-64° C./0.15 mm Hg.
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:8][C:9]1[N:10]=[N:11][C:12](Cl)=[CH:13][CH:14]=1>CC1C=CC=CC=1>[ClH:8].[Cl:8][C:9]1[N:10]=[N:11][C:12]([N:1]2[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[CH:13][CH:14]=1
Reactant: C1CNCCNC1
Reactant: Clc1ccc(Cl)nn1
Solvent: Cc1ccccc1
Product: Cl
Product: Clc1ccc(N2CCCNCC2)nn1
Yield: 22 %

Procedure:
To a stirred solution of 300 parts of hexahydro-1H-1,4-diazepine in 900 parts of methylbenzene were added 75 parts of 3,6-dichloropyridazine. The whole was stirred and refluxed for 4 hours. The reaction mixture was evaporated. Water was added to the residue. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was converted into the hydrochloride salt in 2-propanol and ethanol. The salt was filtered off and dried, yielding 28 parts (22%) of 1-(6-chloro-3-pyridazinyl)-hexahydro- 1H-1,4-diazepine monohydrochloride (compound 215).
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][NH:17][CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[C:5]([F:21])[CH:4]=1.C(N(CC)C(C)C)(C)C.[C:31](Cl)(=[O:34])[CH2:32][CH3:33]>ClCCl>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:16]3)=[N:12][NH:11][C:10]2=[O:20])=[C:5]([F:21])[CH:4]=1
Reactant: O=c1[nH]nc(C[C@@H]2CCNC2)n1-c1ccc(Br)cc1F
Reactant: CCC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCC(=O)N1CC[C@@H](Cc2n[nH]c(=O)n2-c2ccc(Br)cc2F)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.2 %

Procedure:
Into a 4 mL screwcap vial was placed 4-(4-bromo-2-fluorophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (0.318 mmol). Added to the vial in succession was dichloromethane (3 mL), N,N-diisopropylethylamine (0.916 mmol), and propanoyl chloride (0.319 mmol). The vial was capped and stirred at room temperature overnight. The solution was concentrated in vacuo and the residue was purified by reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA). The combined product fractions were concentrated in vacuo for 1 h to remove the acetonitrile. The aqueous solution was neutralized with the addition of saturated aqueous sodium bicarbonate, and extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (100 mg, 79% yield). MS(ES)+ m/e 397.0, 399.1 [M+H]+.
Reaction SMILES: O[C:2]1[N:3]=[C:4](C)[CH:5]=[C:6]2[CH2:11][CH2:10][O:9][C:8](=[O:12])[C:7]=12.[C:14](=[O:17])([O-])[O-].[K+].[K+].I[CH3:21]>CN(C)C=O>[CH3:21][O:17][CH2:14][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH2:11][CH2:10][O:9][C:8](=[O:12])[C:7]=12
Reactant: O=C([O-])[O-]
Reactant: CI
Reactant: Cc1cc2c(c(O)n1)C(=O)OCC2
Agent: [K+]
Solvent: CN(C)C=O
Product: COCc1nccc2c1C(=O)OCC2
Temperature: 70 °C
Reaction time: 4 h
Yield: 62 %

Procedure:
8-hydroxy-6methyl-3,4-dihydro-pyrano[3,4-c]pyridine-1-on (324 mg, 1.809 mmol) and anhydrous potassium carbonate were suspended in anhydrous dimethylformamide (DMF, 10 mL) and then dropwisely added with iodomethane (1.13 mL, 18.09 mmol) and stirred for about 4 hours at 70° C. under the nitrogen atmosphere. The mixture was concentrated under reduced pressure, added with 50 mL of distilled water and then extracted six times with 40 mL of 10% MeOH/MC. The resulting organic layer was dried using anhydrous sodium sulfate, filtered and concentrated. A silica gel column chromatography (10% MeOH/MC) was performed on the resulting residue and 215 mg (62%) of 8-methoxymethyl-3,4-dihydro-pyrano[3,4-c]pyridine-1-on was obtained in pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:13](O)[CH3:14])[CH:5]=[C:6]([Br:12])[C:7]=1[O:8]C(=O)C>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([Br:12])[C:7]=1[OH:8])[CH:13]=[CH2:14]
Reactant: CC(=O)Oc1c(Br)cc(C(C)O)cc1Br
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Solvent: Cc1ccccc1
Product: C=Cc1cc(Br)c(O)c(Br)c1
Yield: 70.5 %

Procedure:
5 g 1-(3',5'-dibromo-4-acetoxyphenyl)ethanol are dissolved in 50 g of toluene, to which mixture are added 0.25 g of anhydrous copper(II)sulfate.The mixture is refluxed for 2 hours and the toluene then removed on a rotary evaporator. A yellow oil remains which after recrystallization frompetrol ether yields 2.9 g of 3,5-dibromo-4-hydroxystyrene as white crystals, mp. 75° C.
Reaction SMILES: [C:1]([NH:4][C:5]12[CH2:14][C:9]3([CH3:15])[CH2:10][CH:11]([CH2:13][C:7]([CH3:16])([CH2:8]3)[CH2:6]1)[CH2:12]2)(=[O:3])[CH3:2].S(=O)(=O)(O)O.[OH-:22].[Na+].[C:24](#[N:26])[CH3:25]>>[C:1]([NH:4][C:5]12[CH2:14][C:9]3([CH3:15])[CH2:10][C:11]([NH:26][C:24](=[O:22])[CH3:25])([CH2:13][C:7]([CH3:16])([CH2:8]3)[CH2:6]1)[CH2:12]2)(=[O:3])[CH3:2]
Reactant: [OH-]
Reactant: CC(=O)NC12CC3CC(C)(CC(C)(C3)C1)C2
Reactant: CC#N
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CC(=O)NC12CC3(C)CC(C)(C1)CC(NC(C)=O)(C3)C2
Temperature: 0 °C
Reaction time: 1 h

Procedure:
1-Acetamido-3,5-dimethyladamantane (2) (10 g) was added slowly to concentrated sulfuric acid (120 mL) cooled to 0° C. in a salt-ice bath. The solution was stirred at 0° C. for 1 h. Acetonitrile (23 mL) was then added dropwise. The reaction mixture was stirred at 0° C. for 2 h, and then at room temperature for 1 h. The reaction mixture was poured into ice-water. Saturated sodium hydroxide solution was added with cooling. The precipitate (dark solid) was filtered, and discarded. The off-white solid was collected by filtration. Recrystallization afforded 3 as a white solid (6.3 g).