Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:28]([OH:30])=O)[CH2:7][CH2:6]1)=[O:4].S(Cl)(Cl)=O.[CH3:35][N:36]([CH:38]=O)[CH3:37]>>[CH3:1][O:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)=[CH:20][CH:21]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:28]([NH:5][C:11]2[CH:12]=[CH:13][C:14]([CH2:38][N:36]([CH3:35])[CH:37]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:15][CH:10]=2)=[O:30])[CH2:7][CH2:6]1)=[O:4]
Reactant: CN(C)C=O
Reactant: COC(=O)N1CCC(C(=O)O)=Cc2cc(-c3ccc(N4CCOCC4)cc3)ccc21
Solvent: O=S(Cl)Cl
Product: COC(=O)N1CCC(C(=O)Nc2ccc(CN(C)C3CCOCC3)cc2)=Cc2cc(-c3ccc(N4CCOCC4)cc3)ccc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
In DMF (8 ml) was dissolved 1-methoxycarbonyl-7-(4-morpholinophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.15 g). To the solution was added, under ice-cooling, thionyl chloride (0.07 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was suspended in THF (25 ml). The suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.12 g) and triethylamine (0.26 ml) in THF (5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature for 4 hours. Under reduced pressure, the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (elution solvent: methanol/triethylamine/ethyl acetate) to give crude crystals, which were recrystallized from ethyl acetate/hexane to give 1-methoxycarbonyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-(4-morpholinophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.14 g) as colorless crystals.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]#[C:19][Si](C)(C)C)[CH:16]=3)[C:11](=[O:24])[C:10]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:9]2)=[CH:4][CH:3]=1.[F-].[K+]>C(O)C>[C:18]([C:15]1[CH:16]=[C:17]2[C:12]([C:11](=[O:24])[C:10]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:9][N:8]2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:13][CH:14]=1)#[CH:19]
Reactant: CCOC(=O)c1cn(-c2ccc(F)cc2)c2cc(C#C[Si](C)(C)C)ccc2c1=O
Agent: [F-]
Agent: [K+]
Solvent: CCO
Product: C#Cc1ccc2c(=O)c(C(=O)OCC)cn(-c3ccc(F)cc3)c2c1
Yield: 73.1 %

Procedure:
A mixture of 23.3 g ethyl 1,4-dihydro-1-(4-fluorophenyl)-4-oxo-7-(trimethylsilylethynyl)-3-quinolinecarboxylate, 10.5 g potassium fluoride and 700 ml ethanol was heated at reflux for 4 hrs. The reaction mixture was concentrated in vacuo and the residue triturated with chloroform. The chloroform-soluble fraction was isolated and recrystallized from ethyl acetate to give 14.02 g ethyl 1,4-dihydro-7-ethynyl-1-(4-fluorophenyl)-4-oxo-3quinolinecarboxylate, m.p. 227°-229° C. d) 1,4-dihydro-1-(4-fluorophenyl)-7-(3-methyl-5
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1)=O)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:12][N:9]1[CH2:10][CH2:11][CH:6]([CH2:4][OH:3])[CH2:7][CH2:8]1
Reactant: CCOC(=O)C1CCN(C)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CN1CCC(CO)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 72.4 %

Procedure:
To an ice-cooled solution of 1-methyl-piperidine-4-carboxylic acid ethyl ester (0.855 g, 5 mmol) in THF (30 ml) was added dropwise a 1M solution of LiAlH4 in THF (20 ml, 20 mmol). The reaction mixture was then stirred for 18 h whilst warming to ambient temperature, and then quenched by careful addition of water (0.75 ml), 10% aqueous NaOH (0.75 ml) then water (3×0.75 ml) and stirred at ambient temperature for 2 h. The resultant mixture was reduced in vacuo, shaken with ethyl acetate and filtered to remove inorganic residues. The filtrate was reduced in vacuo to give (1-methyl-piperidin-4-yl)-methanol as a colourless oil (0.468 g, 73%). (LC/MS: Rt 0.33, [M+H]+ 130.20).
Reaction SMILES: [Cl:1]C1C=CC(OC)=C(C=1)C(Cl)=O.[CH2:13]([NH2:21])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1C=CC=CC=1>[ClH:1].[CH2:13]([NH2:21])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COc1ccc(Cl)cc1C(=O)Cl
Agent: NCCc1ccccc1
Solvent: c1ccccc1
Product: Cl

Procedure:
5-Chloro-2-methoxybenzoyl chloride (15g.), dissolved in benzene, was added slowly to a solution of phenethylamine (18 g.) in benzene. Phenethylamine hydrochloride formed was filtered off, and the benzene removed from the filtrate. The residual oil was distilled to give an oil (19.4 g., 90%) b.p. 205° at 0.2 mm., which crystallized on standing m.p. 60°-63°.
Reaction SMILES: [F:1][CH:2]([F:12])[CH2:3][N:4]1[CH:8]=[C:7]([N+:9]([O-])=O)[CH:6]=[N:5]1>CO>[F:1][CH:2]([F:12])[CH2:3][N:4]1[CH:8]=[C:7]([NH2:9])[CH:6]=[N:5]1
Reactant: O=[N+]([O-])c1cnn(CC(F)F)c1
Solvent: CO
Product: Nc1cnn(CC(F)F)c1
Yield: 93.5 %

Procedure:
1-(2,2-difluoroethyl)-4-nitro-pyrazole (235 mg, 1.33 mmol) was dissolved in methanol (50 mL) and hydrogenated on H-Cube at 50° C. and 40 bar pressure to give 1-(2,2-difluoroethyl)pyrazol-4-amine (183 mg, 93%).
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([F:30])[CH:20]=[C:21]([C:22]4[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=4[Cl:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:31][NH2:32]>>[Cl:29][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([Cl:28])[C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][NH:32][CH3:31])[CH2:17][C:16]=2[CH:18]=[C:19]([F:30])[CH:20]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(F)cc(-c4c(Cl)cccc4Cl)c3O2)cc1
Product: CNCC1Cc2cc(F)cc(-c3c(Cl)cccc3Cl)c2O1

Procedure:
The title compound was prepared (0.081 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.43 mmol) and methylamine (0.133 g, 4.3 mmol). mp 196-198° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([NH2:10])=O)[CH:5]=[C:4]([CH3:11])[N:3]=1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[N:10])[CH:5]=[C:4]([CH3:11])[N:3]=1
Reactant: Cc1cc(C(N)=O)cc(Cl)n1
Solvent: C1CCOC1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Product: Cc1cc(C#N)cc(Cl)n1
Temperature: 25 °C
Yield: 93.9 %

Procedure:
To a mixture of 2-chloro-6-methylpyridine-4-carboxamide (5.1 g, 30 mmol) obtained above, pyridine (7.3 mL, 90 mmol) and tetrahydrofuran (50 mL) was added dropwise a solution of trifluoroacetic anhydride (6.4 mL, 45 mmol) in tetrahydrofuran (10 mL) under ice-cooling, and the mixture was stirred under ice-cooling for 0.5 hr and at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, aqueous sodium bicarbonate solution was added to the obtained residue, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→10/90). The obtained solution was concentrated under reduced pressure to give the title compound (4.3 g, 95%) as a colorless solid.
Reaction SMILES: C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C(#[N:18])C.O.[CH2:20]([O:27][C:28]([NH:30][C@H:31]([CH2:35]C(N)=O)[C:32]([OH:34])=[O:33])=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)(=O)C>[CH2:20]([O:27][C:28]([NH:30][C@@H:31]([C:32]([OH:34])=[O:33])[CH2:35][NH2:18])=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC#N
Reactant: NC(=O)C[C@@H](NC(=O)OCc1ccccc1)C(=O)O
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: NC[C@@H](NC(=O)OCc1ccccc1)C(=O)O
Temperature: 5 °C
Reaction time: 3 h

Procedure:
To a stirred solution of iodobenzene diacetate (7.26 g) in a mixture of ethyl acetate (44 ml), acetonitrile (44 ml) and water (22 ml) was added 2(R)-benzyloxycarbonylamino-succinamic acid (5.0 g) at ambient temperature. After stirred for 3 hours, the reaction mixture was cooled to 5° C., followed by stirring for 2 hours. Insoluble material was collected by filtration, washed with ethyl acetate, and dried under reduced pressure to give 2(R)-benzyloxycarbonylamino-β-alanine (4.15 g) as a white solid.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH:8]([CH:9]=[C:10]([Br:18])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[C:7]1([CH3:20])[CH3:19])=[O:5])C.[OH-].[Na+]>C(O)C.O>[CH3:19][C:7]1([CH3:20])[CH:8]([CH:9]=[C:10]([Br:18])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH:6]1[C:4]([OH:5])=[O:3]
Reactant: CCOC(=O)C1C(C=C(Br)c2ccc(Cl)cc2)C1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC1(C)C(C=C(Br)c2ccc(Cl)cc2)C1C(=O)O
Yield: 81.9 %

Procedure:
50 g (0.14 mol) of 2,2-dimethyl-3-(2-bromo-2-(4-chloro-phenyl)-vinyl)-cyclopropanecarboxylic acid ethyl ester were dissolved in 100 ml of ethanol, a solution of 6 g (0.15 mol) of sodium hydroxide in 100 ml of water was then added and the mixture was heated to the reflux temperature for 4 hours, while stirring. The ethanol was then distilled off under a waterpump vacuum, the residue was taken up in 300 ml of warm water and the mixture was extracted once with 300 ml of methylene chloride. The aqueous phase was separated off, acidified with concentrated hydrochloric acid and then extracted with 2 portions of 300 ml of methylene chloride. The organic phase was then separated off and dried over magnesium sulphate and the solvent was distilled off under a waterpump vacuum. Last residues of solvent were removed by brief incipient distillation under 2 mm Hg at a bath temperature of 60° C. 37.8 g (81.9% of theory) of 2,2-dimethyl-3 -(2-bromo-2-(4-chlorophenyl)-vinyl)-cyclopropanecarboxylic acid (cis and trans, E and Z isomer mixture) were then obtained as a very viscous yellow oil. The structure was confirmed by the 1H-NMR spectrum.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]([CH:14]([CH3:16])[CH3:15])=[CH:10][C:11]([O-:13])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[Mg].II.[Cl-].[NH4+].[CH3:22]O>>[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:14]([CH3:16])[CH3:15])[CH2:10][C:11]([O:13][CH3:22])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CC(C)C(=CC(=O)[O-])c1ccc(Cl)c(N)c1
Reactant: CO
Agent: II
Agent: [Cl-]
Agent: [Mg]
Product: COC(=O)CC(c1ccc(Cl)c(N)c1)C(C)C
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
At RT, a solution of 6.77 g (26.7 mmol) of methyl 2E/Z)-3-(3-amino-4-chlorophenyl)-4-methylpent-2-enoate in 130 ml of methanol was added to 2.2 g (90.7 mmol) of magnesium turnings and a few grains of iodine. After about 30 min, the internal temperature increased to about 60° C. After the reaction solution had cooled to room temperature, stirring at room temperature was continued for another 2 h. 50 ml of saturated aqueous ammonium chloride solution were then added slowly to the dark reaction mixture, and the mixture was extracted repeatedly with diethyl ether. The combined organic phases were washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue obtained was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1). This gave 2.95 g (40% of theory) of the title compound as an oil.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][SH:7])(=[O:3])[CH3:2].[OH-].[K+:9].[C:10](=[S:12])=[S:11]>C(O)C>[C:1]([NH:4][CH2:5][CH2:6][S:7][C:10](=[S:11])[S-:12])(=[O:3])[CH3:2].[K+:9]
Reactant: S=C=S
Reactant: CC(=O)NCCS
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CC(=O)NCCSC(=S)[S-]
Reaction time: 0.5 h

Procedure:
A solution of 1.708 g (14.35 mmole) of 2-acetylaminoethyl mercaptan in 2 ml of absolute ethanol is added dropwise over the course of 0.5 hours, while stirring and cooling to 10°-15°, to a solution of 0.80 g (14.35 mmole) of potassium hydroxide in 5 ml of absolute ethanol. After a further half hour, a solution of 1.09 g (14.35 mmole) of carbon disulphide in 3 ml of absolute ethanol is added, the temperature being maintained at 10°-15°. The reaction mixture is further stirred for 3 hours at room temperature and cooled in an ice bath for 20 minutes. The yellow crystalline precipitate is filtered off, washed once with absolute ethanol and yields potassium (2-acetylaminoethyl)-trithiocarbonate having a melting point of 171°-174°.
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([N:12]([CH3:21])[CH2:13][C:14]([O:16]C(C)(C)C)=[O:15])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[C:1]([O:4][CH2:5][CH:6]([N:12]([CH3:21])[CH2:13][C:14]([OH:16])=[O:15])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC(COC(C)=O)N(C)CC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(=O)OCC(COC(C)=O)N(C)CC(=O)O

Procedure:
Tert-butyl 2-{[1,3-bis(acetyloxy)propan-2-yl](methyl)amino}acetate (1.32 g, 4.3 mmol) was stirred in a solution of 20% TFA:dichloromethane (20 ml) for 5 hours. Upon completion of reaction (assessed by LC-MS) the reaction was concentrated in vacuo and re-dissolved in dichloromethane (10 ml). The HCl salt was treated with polymer supported-diisopropylamine (3.5 g) for 18 hours and the resin removed by filtration. The resin was washed with MeCN (3×10 ml) and the title compound isolated by concentration in vacuo. (1.0 g, 93%) 1H NMR (500 MHz, CHLOROFORM-d) δ 4.18 (4H, d, 6.4 Hz), 3.41 (2H, s), 3.17-3.29 (1H, m), 2.50 (3H, s), 2.11 (6H, s).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=O)[CH:2]=1.C(N(CC)C(C)C)(C)C.[CH3:21][C:22]1[C:27]([NH2:28])=[C:26]([CH3:29])[CH:25]=[C:24]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[N:23]=1.C(OCC)(=O)C>CN(C)C=O>[CH3:21][C:22]1[C:27]([NH:28][C:8](=[O:10])[CH2:7][C:3]2[CH:2]=[C:1]([CH3:11])[CH:6]=[CH:5][CH:4]=2)=[C:26]([CH3:29])[CH:25]=[C:24]([N:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)[N:23]=1
Reactant: Cc1cccc(CC(=O)O)c1
Reactant: Cc1cc(N2CCOCC2)nc(C)c1N
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: Cc1cccc(CC(=O)Nc2c(C)cc(N3CCOCC3)nc2C)c1
Reaction time: 0.03 h
Yield: 14 %

Procedure:
m-Tolylacetic acid (0.33 g), N,N-diisopropyl-ethylamine (0.90 mL) and N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-yl-methylene]-N-methyl-methanaminium hexafluoro-phosphate N-oxide (1.00 g) were mixed in dry N,N-dimethylformamide (3 mL) and stirred under argon for 2 minutes. 2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-ylamine (0.30 g) dissolved in dry N,N-dimethylformamide (2 mL) was added to the reaction mixture, which was stirred at 25° C. under argon for 16 hours. Ethyl acetate (20 mL) was added and the organic phase was washed with saturated aqueous ammonium chloride/water (1:1, 20 mL), water (20 mL), brine/water (1:1, 20 mL), dried over sodium sulfate, concentrated in vacuo and purified by flash chromatography (SiO2, heptane/ethylacetate 3:1) to furnish 0.069 g (14% yield) of the title compound as a white solid. LC-MS (m/z) 340 (MH+); tR=1.42, (UV, ELSD) 96%, 100%. 1H NMR (500 MHz, DMSO-d6): 2.00 (s, 3H), 2.11 (s, 3H), 2.29 (s, 3H), 3.37 (m, 4H), 3.56 (s, 2H), 3.67 (m, 4H), 6.52 (s, 1H), 7.06 (d, 1H), 7.15 (m, 2H), 7.21 (t, 1H), 9.30 (s, 1H).
Reaction SMILES: O1C2C=CC=CC=2N=C1[S:10][CH2:11][CH2:12][CH2:13][CH2:14]CN1C(=O)C2=CC=CC=C2C1=O.O1C2C=CC=CC=2N=[C:28]1[S:36][CH2:37][CH2:38][CH2:39][N:40]1C(=O)C2=CC=CC=C2C1=O>>[S:10]1[CH:11]=[CH:12][CH:13]=[C:14]1[CH2:28][S:36][CH2:37][CH2:38][CH2:39][NH2:40]
Reactant: O=C1c2ccccc2C(=O)N1CCCCCSc1nc2ccccc2o1
Reactant: O=C1c2ccccc2C(=O)N1CCCSc1nc2ccccc2o1
Product: NCCCSCc1cccs1
Yield: 78 %

Procedure:
The same reaction as in Reference Example 4 was repeated except that the N-[5-(2-benzoxazolylthio)pentyl]phthalimide was replaced by N-[3-(2-benzoxazolylthio)propyl]phthalimide, to obtain the title compound at a yield of 78%.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[N:7]([CH2:9][C:10]1[C:11]2[C:16]([C:17]([CH:24]=O)=[C:18]3[C:23]=1[CH:22]=[CH:21][CH:20]=[CH:19]3)=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:27][NH2:28].[BH4-].[Na+]>C1COCC1.CO>[C:1]([O:5][C:6](=[O:26])[N:7]([CH3:8])[CH2:9][C:10]1[C:11]2[C:16]([C:17]([CH2:24][NH:28][CH3:27])=[C:18]3[C:23]=1[CH:22]=[CH:21][CH:20]=[CH:19]3)=[CH:15][CH:14]=[CH:13][CH:12]=2)([CH3:2])([CH3:4])[CH3:3]
Reactant: CN(Cc1c2ccccc2c(C=O)c2ccccc12)C(=O)OC(C)(C)C
Reactant: CN
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CNCc1c2ccccc2c(CN(C)C(=O)OC(C)(C)C)c2ccccc12
Temperature: 25 °C
Reaction time: 12 h
Yield: 83 %

Procedure:
Compound 4 (2.29 g, 6.56 mmol) was dissolved in the mixture of THF (50 mL) and MeOH (50 mL). To this solution was added the aqueous solution of methylamine (40%, wt, 20 mL), the reaction mixture was stirred at room temperature under nitrogen for 12 h. Sodium borohydride (1.00 g, 26.3 mmol) was added, and stirred for 30 min. After removal of the solvent in vacuo, the resulting residue was dissolved in ethyl acetate (100 mL), washed with water (3×50 mL), and dried over MgSO4. Solvent evaporation gave a crude product, which was purified on a silica gel column, eluting with MeOH/CH2Cl2 (1/2), giving compound 5 as a yellow solid (2.00 g, 83%). 1H NMR (CDCl3) δ 8.44-8.39 (m, 4H), 7.56-7.53 (m, 4H), 5.51 (s, 2H), 4.71 (s, 2H), 2.69 (s, 3H), 2.46 (s, 3H), 1.55 (s, 9H). 13C NMR (CDCl3) δ 155.6, 132.5, 131.0, 130.0, 125.8, 125.7, 125.4, 125.3, 124.9, 79.7, 47.8, 42.6, 36.9, 31.6, 28.6. IR (cm−1): 1686. HRMS (FAB) calcd for C23H28N2O2 (M+) 364.2151, found 364.2159. Anal. calcd for C23H28N2O2: C, 75.79; H, 7.74; N, 7.69. Found: C, 75.64; H, 7.71; N, 7.53.
Reaction SMILES: [SH:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([CH3:18])[C:3]=1[C:19]#[N:20].Cl[CH2:22][C:23]([NH2:25])=[O:24].CC[O-].[Na+]>C(O)C>[NH2:20][C:19]1[C:3]2[C:4]([CH3:18])=[N:5][C:6]([C:8]3[CH:9]=[CH:10][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:12][CH:13]=3)=[N:7][C:2]=2[S:1][C:22]=1[C:23]([NH2:25])=[O:24]
Reactant: Cc1nc(-c2ccc(OC(C)C)cc2)nc(S)c1C#N
Reactant: NC(=O)CCl
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1nc(-c2ccc(OC(C)C)cc2)nc2sc(C(N)=O)c(N)c12
Yield: 31.3 %

Procedure:
4.0 g (14 mmol) 6-mercapto-4-methyl-2-(4-iso-propoxy-phenyl)-pyrimidine-5-carbonitrile and 1.6 g (17 mmol) 2-chloroacetamide are suspended in 100 ml ethanol and 1.9 g (28 mmol) sodium ethylate is admixed. The reaction mixture is refluxed for 3 h. It is filtrated, washed with ethanol and water and dried. 1.5 g (31%) 5-amino-4-methyl-2-(4-iso-propoxy-phenyl)-thieno[2,3-d]pyrimidine-6-carboxamide is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C.Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)CBr
Reactant: COc1cccc(C2=CCc3ccccc32)c1
Agent: [Li]N([Si](C)(C)C)[Si](C)(C)C
Solvent: C1CCOC1
Product: CCOC(=O)CC1C=C(c2cccc(OC)c2)c2ccccc21
Reaction time: 2.5 h
Yield: 19.8 %

Procedure:
To a cold solution of 3-(3-methoxyphenyl)indene (4 g, 18 mmol), prepared by the method of J. Med. Chem. 1981, 24, 998, in THF (15 mL) at 0° C. was added dropwise a solution of LiN(TMS)2 (20 mL, 1M in THF) over 5 min. The resulting solution was added dropwise to a solution of ethyl bromoacetate (3.34 g, 20 mmol) in THF (15 mL) at −78° C. over 30 min. After 2.5 h, the mixture was quenched with saturated ammonium chloride solution and the layers were separated. The organic layer was dried over MgSO4 and concentrated to give the crude product which was purified by column chromatography (SiO2/2-4% EtOAc/hexane) to give title compound (1.1 g): 1H NMR (400 MHz, CDCl3) δ1.30 (t, 3H), 2.50 (m, 1H), 2.85 (m, 1H), 3.85 (s, 3H), 4.0 (m, 1H), 4.20 (q, 2H), 6.6 (s, 1H), 6.9 (m, 1), 7.2 (s, 1H), 7.35 (m, 6H).
Reaction SMILES: [C:1]1([C:7](=O)[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3]C=1>[Cl-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)Cl>[C:8]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)(=[O:9])[C:7]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:1]=1
Reactant: O=C(Oc1ccccc1)C(=O)c1ccccc1
Agent: [Cl-]
Agent: c1ccc([P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: O=C(Oc1ccccc1)c1ccccc1

Procedure:
The decarbonylation reaction of phenyl phenylglyoxylate (PPG) was repeated in the manner as described in Example 79, except that neither tetraphenylphosphonium chloride nor chloroform was employed. The results are also set forth in Table 12.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][C:11]([CH2:16][CH:17]2[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]2)([CH3:15])[C:12](=[O:14])[N:13]=1.Cl>CCOC(C)=O>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[NH:8][C:9]1[S:10][C:11]([CH3:15])([CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[C:12](=[O:14])[N:13]=1
Reactant: CC(C)(C)OC(=O)N1CCC(CC2(C)SC(N[C@H]3CC4CCC3C4)=NC2=O)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: CC1(CC2CCNCC2)SC(N[C@H]2CC3CCC2C3)=NC1=O
Reaction time: 4 h
Yield: 99.7 %

Procedure:
A mixture of tert-butyl 4-((2-((2S)-bicyclo[2.2.1]heptan-2-ylamino)-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl)methyl)piperidine-1-carboxylate (1.42 g, 3.37 mmol, 1.0 eq) in 50 mL of a 4.7 M HCl solution in EtOAc was stirred at roomtemperature. After 4 h, the reaction mixture was concentrated in vacuo. Aqueous Na2CO3 (2.0 M, 20 mL) was then added, and water was removed in vacuo. The residue was then triturated with 10% MeOH—CH2Cl2 (6×100 mL), and the combined triturating solution were concentrated in vacuo. The crude product was dissolved in CH2Cl2, filtered, and concentrated in vacuo to afford the title compound as a light orange solid (1.08 g). MS (ESI, pos. ion) m/z: 322 (M+H).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[N:11]=[CH:12][N:13]2[C:18](=[O:19])[N:17]([CH2:20][S:21][CH3:22])[N:16]=[N:15][C:14]=12.[OH:23]OS([O-])=O.[K+]>CN(C=O)C.O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[N:11]=[CH:12][N:13]2[C:18](=[O:19])[N:17]([CH2:20][S:21]([CH3:22])=[O:23])[N:16]=[N:15][C:14]=12
Reactant: CSCn1nnc2c(-c3nc4ccccc4s3)ncn2c1=O
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CS(=O)Cn1nnc2c(-c3nc4ccccc4s3)ncn2c1=O
Temperature: 0 °C
Yield: 98 %

Procedure:
To a 0° C. solution of 8-(benzo[d]thiazol-2-yl)-3-(methylthiomethyl)imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one (0.23 mmol, 75 mg, 1 eq.) in DMF (4.5 mL) was added slowly drop wise Oxone™ (0.25 mmol, 77 mg, 1.1 eq.) dissolved in water (0.75 mL). The formed suspension was stirred at 0° C. and stepwise additions of Oxone™ in water were made until reaction completion. The reaction mixture was filtered and the obtained solid washed with water, acetonitrile, ethyl acetate and ether, and dried under vacuum to give the title compound. Yield: 98%. δH (DMSO-d6) 9.07 (1H, s), 8.22 (1H, m), 8.16 (1H, m), 7.60 (1H, m), 7.52 (1H, m), 5.63 (1H, d, J=13.2), 5.50 (1H, d, J=13.2), 2.79 (3H, s).