Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([F:15])=[CH:13][C:12](Br)=[CH:11][C:10]=1[F:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.CN(C)[CH:25]=[O:26]>O1CCCC1>[CH2:1]([O:8][C:9]1[C:14]([F:15])=[CH:13][C:12]([CH:25]=[O:26])=[CH:11][C:10]=1[F:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([O:8][C:9]1[C:14]([F:15])=[C:13]([CH:12]=[CH:11][C:10]=1[F:17])[CH:25]=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN(C)C=O
Reactant: Fc1cc(Br)cc(F)c1OCc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=Cc1cc(F)c(OCc2ccccc2)c(F)c1
Product: O=Cc1ccc(F)c(OCc2ccccc2)c1F
Temperature: -78 °C
Reaction time: 1 h

Procedure:
Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-(benzyloxy)-5-bromo-1,3-difluorobenzene (7.0 g, 23.40 mmol, 1.00 equiv) in tetrahydrofuran (20 mL) at −78° C. To the resulting mixture was then added n-BuLi (11.3 mL). The resulting mixture was stirred for 1 h at −78° C. To the resulting mixture was then added N, N-dimethylformamide (6 mL). The resulting solution was stirred for 1 h at −78° C. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (3×20 mL) and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out and the resulting mixture was then concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:8) to yield 4-(benzyloxy)-3,5-difluorobenzaldehyde/3-(benzyloxy)-2,4-difluorobenzaldehyde as colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([CH2:9][CH2:10][OH:11])[C:4](=[O:12])[N:3]=1.[C:13]1([CH3:24])[CH:18]=[CH:17][C:16]([S:19]([O:22]C)(=[O:21])=[O:20])=[CH:15][CH:14]=1>C(#N)C>[C:13]1([CH3:24])[CH:14]=[CH:15][C:16]([S:19]([O-:22])(=[O:20])=[O:21])=[CH:17][CH:18]=1.[OH:11][CH2:10][CH2:9][NH+:5]1[C:6]([CH3:8])=[CH:7][CH:2]([CH3:1])[N:3]([CH3:13])[C:4]1=[O:12]
Reactant: COS(=O)(=O)c1ccc(C)cc1
Reactant: Cc1cc(C)n(CCO)c(=O)n1
Solvent: CC#N
Product: CC1=CC(C)N(C)C(=O)[NH+]1CCO
Product: Cc1ccc(S(=O)(=O)[O-])cc1
Temperature: 0 °C

Procedure:
Under a protective-gas atmosphere, a mixture of 9.2 g (0.055 mol) of 4,6-dimethyl-1-(2-hydroxyethyl)pyrimidin-2(1H)-one and 13.1 g (0.068 mol) of methyl p-toluenesulfonate in 700 ml of acetonitrile was heated under reflux for 12 hours. After cooling, about ⅔ of the solvent was removed on a rotary evaporator, the remaining residue was mixed with the same amount of diethyl ether and cooled to 0° C. At low temperature, firstly an oil separated off, which crystallized out after some time. The crystalline product was filtered off.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[OH:12].C([Sn](CCCC)(CCCC)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)CCC>C1(C)C=CC=CC=1.CN(C=O)C>[N:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[OH:12]
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Reactant: Oc1ncnc2ccc(Br)cc12
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: Oc1ncnc2ccc(-c3ccccn3)cc12
Temperature: 25 °C
Yield: 61.7 %

Procedure:
Preparation D12, Step 2: A mixture of 6-bromoquinazolin-4-ol (173 mg, 0.77 mmol) and 2-tributylstannylpyridine (850 mg, 2.30 mmol) in toluene (10 mL), plus a few drops of DMF to improve solubility, was degassed under vacuum/argon, then a catalytic amount of tetrakis(triphenylphosphine)palladium(0) was added, the mixture was degassed again, and then heated at reflux for 4 h. The reaction was cooled to room temperature, and some solids were removed by filtration. Analysis by LC/MS indicated that the desired product was present in both the solids and the filtrate. The solids were slurried in 8:2 methylene chloride/methanol, the mixture was filtered, the filtrate was combined with the original filtrate, and this mixture was concentrated in-vacuo. The residue was purified over silica gel, eluting with 50% EtOAc/hexanes, 75% EtOAc/hexanes, 100% EtOAc, 5% MeOH/EtOAc, to yield 106 mg of 6-(pyridin-2-yl)quinazolin-4-ol as a colorless solid. MS (ES+)=224 (M+H+).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:30](=[O:31])[N:13]3[C:14]([C:27]([OH:29])=[S:28])=[C:15]([C:18]4[S:19][CH:20]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[N:22]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+:33]>O.CO.CC(C)=O>[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:30](=[O:31])[N:13]3[C:14]([C:27]([O-:29])=[S:28])=[C:15]([C:18]4[S:19][CH:20]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[N:22]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+:33].[Na+:33].[C:1]1([CH2:7][C:8]([NH:10][C@@H:11]2[C:30](=[O:31])[N:13]3[C:14]([C:27]([O-:29])=[S:28])=[C:15]([C:18]4[S:19][CH:20]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[N:22]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)Cc1csc(C2=C(C(O)=S)N3C(=O)[C@@H](NC(=O)Cc4ccccc4)[C@H]3SC2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: CC(C)=O
Product: O=C(O)Cc1csc(C2=C(C([O-])=S)N3C(=O)[C@@H](NC(=O)Cc4ccccc4)[C@H]3SC2)n1
Temperature: 30 °C
Reaction time: 2 h

Procedure:
To a solution of 7β-(2-phenylacetamido)-3-(4-carboxymethylthiazol-2-yl)thio-3-cephem-4-carboxylic acid (100 mg) in water (50 ml) was added 0.1 mol/l-sodium hydroxide solution (4.06 ml). The solution was lyophilized. The above obtained powder was dissolved in a mixture of methanol (0.5 ml) and acetone (1.3 ml) under stirring at 30° C. The stirring was continued for 2 hours at room temperature to give crystals, which were collected by filtration and dried to give disodium 7β-(2-phenylacetamido)-3-(4-carboxymethylthiazol-2-yl)thio-3-cephem-4-carboxylate (69.1 mg).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7]O)[CH2:3][CH2:2]1.CS(Cl)(=O)=O.C(N(CC)CC)C.S([O-])(=O)(=O)C.[N-:26]=[N+:27]=[N-:28].[Na+]>CN(C=O)C.ClCCl>[N:26]([CH2:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[N+:27]=[N-:28]
Reactant: OCC1CCOCC1
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: CS(=O)(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: [N-]=[N+]=NCC1CCOCC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a 25 mL round bottom flask is placed (tetrahydro-2H-pyran-4-yl)methanol (350 mg, 3 mmol), followed by dichloromethane (DCM, 15 mL). The solution is cooled to 0° C. and is then treated with methanesulfonyl chloride (0.24 mL, 3.15 mmol) and triethylamine (0.88 mL, 6.3 mmol). The reaction is complete after 30 min. and is then quenched with water and diluted with DCM (10 mL). The layers are then partitioned, and the aqueous layer is extracted with DCM (3×10 mL). The combined organics are dried over Na2SO4, filtered and concentrated. The crude mesylate is then dissolved in DMF (10 mL), to which sodium azide (410 mg, 6.3 mmol) is added and then heated to 75° C. for 4 h. The reaction is then cooled to room temperature, quenched with water (10 mL) and extracted with diethyl ether (3×20 mL). The combined organics are then washed with water (3×10 mL), dried over MgSO4, filtered, and concentrated to give 4-(azidomethyl)-tetrahydro-2H-pyran as a colorless liquid. 1H NMR (CDCl3, 400 MHz) δ 4.01-3.97 (m, 2H), 3.39 (td, J=11.9, 2.1 Hz, 2H), 3.18 (d, J=6.8 Hz, 2H), 1.86-1.75 (m, 1H), 1.67-1.64 (m, 2H), 1.40-1.29 (m, 2H).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:21][CH:22]([CH3:24])[CH3:23])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:36][S:37]([C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1)(=[O:39])=[O:38].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20]([C:43]2[CH:44]=[CH:45][C:40]([S:37]([CH3:36])(=[O:39])=[O:38])=[CH:41][CH:42]=2)=[CH:21][CH:22]([CH3:23])[CH3:24])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CS(=O)(=O)c1ccc(B(O)O)cc1
Reactant: Cc1ccc(S(=O)(=O)OC(=CC(C)C)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CC(C)C=C(c1ccc(S(C)(=O)=O)cc1)c1cc2cc(F)cnc2n1S(=O)(=O)c1ccccc1
Yield: 90.3 %

Procedure:
To a mixture of toluene-4-sulfonic acid 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methyl-but-1-enyl ester (1 g, 2 mmol), 4-(methanesulfonyl)phenylboronic acid (1 g, 5 mmol) and dichlorobis(triphenylphosphine)palladium (II) (140 mg, 0.2 mmol) in dioxane (8 mL) was added an aqueous sodium carbonate solution (2 M, 2.5 mL). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (100 mL), washed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 50% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-5-fluoro-2-[1-(4-methanesulfonyl-phenyl)-3-methyl-but-1-enyl]-1H-pyrrolo[2,3-b]pyridine (0.9 g, 92%) as a white solid: LC/MS m/e calcd for C25H23FN2O4S2 [M+H]+ 499.60, observed 498.8.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([O:46][CH3:47])=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([C:13]1[S:14][CH:15]=[C:16]([CH:18]([CH3:20])[CH3:19])[N:17]=1)[CH:9]=[C:8]2[O:21][CH:22]1[CH2:39][CH:38]2[CH:24]([C:25](=[O:45])[N:26]([CH3:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]=[CH:32][CH:33]3[C:35]([C:41]([OH:43])=O)([NH:36][C:37]2=[O:40])[CH2:34]3)[CH2:23]1)[CH3:2].[CH:48]1([S:51]([NH2:54])(=[O:53])=[O:52])[CH2:50][CH2:49]1.ClC1C(OC)=CC=C2C=1N=C(C1SC=C(C(C)C)N=1)C=C2OC1CC2C(C(=O)N(C)CCCCC=CC3C(C(NS(C4CC4)(=O)=O)=O)(NC2=O)C3)C1>>[CH2:1]([C:3]1[C:4]([O:46][CH3:47])=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([C:13]1[S:14][CH:15]=[C:16]([CH:18]([CH3:20])[CH3:19])[N:17]=1)[CH:9]=[C:8]2[O:21][CH:22]1[CH2:39][CH:38]2[CH:24]([C:25](=[O:45])[N:26]([CH3:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]=[CH:32][CH:33]3[C:35]([C:41]([NH:54][S:51]([CH:48]4[CH2:50][CH2:49]4)(=[O:53])=[O:52])=[O:43])([NH:36][C:37]2=[O:40])[CH2:34]3)[CH2:23]1)[CH3:2]
Reactant: CCc1c(OC)ccc2c(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)C4C3)cc(-c3nc(C(C)C)cs3)nc12
Reactant: NS(=O)(=O)C1CC1
Agent: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)C4C3)cc(-c3nc(C(C)C)cs3)nc2c1Cl
Product: CCc1c(OC)ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)C4C3)cc(-c3nc(C(C)C)cs3)nc12

Procedure:
The title compound was prepared from 17-[8-ethyl-2-(4-isopropylthiazole-2-yl)-7-methoxyquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]-octadec-7-ene-4-carboxylic acid (70) and cyclopropylsulfonamide following the procedure reported for the preparation of N-[17-[8-chloro-2-(4-isopropylthiazole-2-yl)-7-methoxyquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]-octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (56): m/z=764 (M+H)+.
Reaction SMILES: [CH2:1]([N:3]([CH2:22][CH3:23])[C:4]1[CH:20]=[CH:19][C:7]([C:8]([C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12]([OH:14])=[O:13])=[O:9])=[C:6]([OH:21])[CH:5]=1)[CH3:2].Cl.CN(C)[CH2:27][CH2:28][CH2:29]N=C=NCC.C(N(C(C)C)C(C)C)C.C(OCC)(=O)C>CN(C=O)C>[CH2:29]([O:13][C:12](=[O:14])[C:11]1[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=1[C:8](=[O:9])[C:7]1[CH:19]=[CH:20][C:4]([N:3]([CH2:1][CH3:2])[CH2:22][CH3:23])=[CH:5][C:6]=1[OH:21])[C:28]#[CH:27]
Reactant: CCN=C=NCCCN(C)C
Reactant: CCN(CC)c1ccc(C(=O)c2ccccc2C(=O)O)c(O)c1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C#CCOC(=O)c1ccccc1C(=O)c1ccc(N(CC)CC)cc1O

Procedure:
A solution of 200 mmol 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid, 500 mmol propargylic alcohol, 220 mmol 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), and 500 mmol N-ethyldiisopropylamine in 600 mL DMF is stirred at room temperature for 2 h. 1 L of ethyl acetate is added and the solution extracted with 1 L water. The organic layer is separated, dried (Na2SO4), and the solvent evaporated. The crude product is purified via FC (n-hexane/EtOAC 2:1) yielding 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid prop-2-ynyl ester. MS (EI): 374 (18%, M+Na+), 352 (100%, M+H+), 296 (17%). UV (EtOH): λmax=356 nm (ε=31'648).
Reaction SMILES: C([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)(=O)C.[NH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].[CH3:21][C:22](O)=O.[BH4-].[Na+]>C1(C)C=CC=CC=1>[C:8]([C:7]1[CH:10]=[C:11]([CH:21]([NH:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH3:22])[CH:4]=[CH:5][CH:6]=1)#[N:9]
Reactant: CC(=O)O
Reactant: CC(=O)c1ccc(C#N)cc1
Reactant: CC(C)(C)OC(=O)CN
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(NCC(=O)OC(C)(C)C)c1cccc(C#N)c1
Temperature: 0 °C
Yield: 80.9 %

Procedure:
4-Acetylbenzonitrile (1.0 g; 6.9 mmol) and tert-butyl glycinate (1.2 g; 9.0 mmol) were dissolved in toluene (20 mL). The mixture was stirred at reflux with a Dean-Stark trap. AcOH (207 μL; 3.4 mmol) was added and the mixture was further heated overnight. Solvents were evaporated. The crude was dissolved in MeOH (35 mL). The solution was cooled down to 0° C. and sodium borohydride (781 mg; 21 mmol) was added in portions. The reaction was stirred at 0° C. for 1 h and was let stirred at RT overnight. Solvents were evaporated. The crude residue was suspended in EtOAc, washed with NH4Cl saturated solution, NaHCO3 saturated solution, brine and dried over MgSO4. After evaporation of the solvents the resulting yellow oil was purified by flash chromatography affording the title compound 716 mg as a colorless oil. LC/MS (Method B): 261.0 (M+H)+. HPLC (Method A) Rt 2.79 min (Purity: 99.2%).
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][OH:29])(=[O:3])[CH3:2].[C:30](OC(=O)C)(=[O:32])[CH3:31]>N1C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30](=[O:32])[CH3:31])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@H]2[C@@H]3[C@H](CCCCCO)CC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OCCCCC[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@]3(C)[C@@H](OC(C)=O)CC[C@H]3[C@H]12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 37.7 g of 17β-acetoxy-7α-(5-hydroxypentyl)-estr-4-en-3-one in 160 ml of pyridine is slowly mixed with 80 ml of acetic anhydride and stirred for 16 hours at 25° C. Then, it is diluted with ethyl acetate, and the organic phase, after washing with sodium bicarbonate solution, is dried and concentrated by evaporation. The residue is chromatographed on silica gel, and 26.6 g of 17β-acetoxy-7α-(5-acetoxypentyl)-estr-4-en-3-one is obtained as oil. [α]D22 =+20.0° (c=0.51% in chloroform)
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:12]([O-])=O)[CH:8]=2)[N:3]=1.[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([CH2:32][C:33](O)=[O:34])[CH2:28][CH2:27]1>>[CH3:15][O:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH:20][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:12][C:33](=[O:34])[CH2:32][N:29]3[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]3)[CH:8]=2)[N:3]=1
Reactant: O=[N+]([O-])c1ccc2nc(Cl)ccc2c1
Reactant: COc1ccccc1CN
Reactant: CN1CCN(CC(=O)O)CC1
Product: COc1ccccc1CNc1ccc2cc(NC(=O)CN3CCN(C)CC3)ccc2n1

Procedure:
The title compound, MS: m/e=420.0 (M+H+), was prepared in accordance with the general method of example 16 from 2-chloro-6-nitro-quinoline, 2-methoxy-benzylamine and 4-methyl-piperazin-1-yl acetic acid.
Reaction SMILES: Cl[C:2]1[C:7]([N:8]([CH3:10])[CH3:9])=[N:6][CH:5]=[CH:4][N:3]=1.[CH2:11]([OH:14])[CH:12]=[CH2:13].[H-].[Na+]>CN(C)P(=O)(N(C)C)N(C)C>[CH2:11]([O:14][C:2]1[C:7]([N:8]([CH3:10])[CH3:9])=[N:6][CH:5]=[CH:4][N:3]=1)[CH:12]=[CH2:13]
Reactant: C=CCO
Reactant: CN(C)c1nccnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: C=CCOc1nccnc1N(C)C
Temperature: 0 °C
Reaction time: 15 h

Procedure:
47 g of 2-chloro-3-dimethylamino-pyrazine and 35 g of allyl alcohol are dissolved in 300 ml of hexamethylphosphoric acid triamide. 14.4 g of sodium hydride are introduced into this solution at 0° C. over the course of 30 minutes. The mixture is then stirred for a further hour at 0° C. and for 15 hours at room temperature. The reaction mixture is then poured into 2 liters of ice water. After excess sodium hydride has been decomposed, the mixture is extracted by shaking with ether. The ether extracts are washed with water until neutral, dried over sodium sulphate and evaporated in a waterpump vacuum. The residue is distilled under reduced pressure. 2-Allyloxy-3-dimethylamino-pyrazine, boiling point 110°-115° C./10 mm Hg, is thus obtained.
Reaction SMILES: [C:1](#[N:4])[CH:2]=[CH2:3].Cl[C:6]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:9].CCOCC.[ClH:26]>C(#N)C.O>[Cl:26][CH:2]([CH2:3][C:6]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:7]=1[C:8](=[O:9])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:1]#[N:4]
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1Cl
Reactant: Cl
Reactant: C=CC#N
Solvent: CCOCC
Solvent: O
Solvent: CC#N
Product: N#CC(Cl)Cc1ccc(Cl)cc1C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 92.7 g (0.4 mole) of 2-amino-5-chlorobenzephenone in 250 ml of acetonitrile was added to a mixture of 70 g (0.52 mole) of cupric chloride, 65 g (0.63 mole) of t-butylnitrile, 500 ml of acrylonitrile, and 500 ml of acetonitrile. When the addition was complete stirring at room temperature was continued for 2 hr. The mixture was diluted with 80 ml of 6 N hydrochloric acid and 1500 ml of water, extracted with ether and dried over anhydrous sodium sulfate. The ether solution was concentrated at reduced pressure to give a brown oil, which contained the end product and 2,5-dichlorobenzophenone. Trituration of the oil with a mixture of ether and petroleum ether gave the end product as a tan solid. Recrystallization of a small portion of the end product from a mixture of ether and petroleum ether gave pale yellow needles, mp 69°-71°.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:10][C:9](=[O:16])[CH2:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:17][O:18][CH:19](OC)OC>CN(C)C=O.C(OC(=O)C)(=O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:10][C:9](=[O:16])[C:8]2=[CH:17][O:18][CH3:19])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc2c(c1)CC(=O)NC2=O
Reactant: COC(OC)OC
Solvent: CC(=O)OC(C)=O
Solvent: CN(C)C=O
Product: COC=C1C(=O)NC(=O)c2ccc(C(C)(C)C)cc21
Temperature: 120 °C

Procedure:
6-tert-Butyl-4H-isoquinoline-1,3-dione (45 mg, 0.21 mmol) is dissolved in N,N-dimethylformamide (1 mL) and acetic anhydride (2 mL). Trimethylorthoformate (0.2 mL) is added and the mixture is heated to 120° C. for 1 hour. The volatiles were removed under vacuum and the residue passed through a column to afford the crude product, is used directly in the next step. MS (ESI): 258.3 (M−1)−1.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:25])[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.CCO.[Pd]>[CH3:25][N:8]([C@@H:9]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(C(=O)OC(C)(C)C)[C@@H]1CCCN(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CCO
Solvent: CO
Product: CN(C(=O)OC(C)(C)C)[C@@H]1CCCNC1
Reaction time: 1 h
Yield: 81.6 %

Procedure:
A solution of (R)-benzyl 3-(tert-butoxycarbonyl(methyl)amino)piperidine-1-carboxylate (4.00 g, 11.5 mmol) in methanol (10 mL) was slowly added to a suspension of 5% Pd on activated carbon (2.44 g, 1.15 mmol) in EtOH (20 mL). The reaction mixture was evacuated and back filled with N2 (3 cycles). The reaction vessel was then evacuated and back filled with H2 (3 cycles) using a H2 balloon. The mixture was stirred under H2 atmosphere for 1 hour and filtered through a pad of celite, washing with additional 10% MeOH/EtOAc (3×20 mL). The filtrate collected was concentrated in vacuo to provide (R)-tert-butyl methyl(piperidin-3-yl)carbamate (2.01 g, 82% yield) as an oil. LCMS (APCI+) m/z 215 (M+H)+.
Reaction SMILES: C[CH:2]1[N:7]=[C:6]([NH:8][CH2:9][CH3:10])[C:5]([N+:11]([O-:13])=[O:12])=[C:4]([NH:14][CH:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[N:3]1S.[CH3:21][O-:22].[Na+].C(N(CC)CC)C>CO>[CH3:21][O:22][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH3:10])[C:5]([N+:11]([O-:13])=[O:12])=[C:4]([NH:14][CH:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[N:3]=1
Reactant: CCNC1=NC(C)N(S)C(NC(CC)CC)=C1[N+](=O)[O-]
Reactant: C[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CO
Product: CCNc1nc(OC)nc(NC(CC)CC)c1[N+](=O)[O-]
Yield: 74.5 %

Procedure:
30 g (0.1 mol) of 2-methyl-mercapto-4-ethylamino-5-nitro-6-(3-pentyl-amino)-pyrimidine are dissolved in 400 ml of methanol. A solution of 8.1 g (0.15 mol) of sodium methylate in 100 ml of methanol is added together with 20 ml of triethylamine to the previously prepared solution. The mixture is refluxed for 16 hours, evaporated, and the residue is treated with 200 ml of water. After extracting 3 times with ether, the extracts are dried over MgSO4, dried, filtered, and the ethereal solution is evaporated, to leave as residue 21.1 g of 2-methyoxy-4-ethylamino-5-nitro-6-(3-pentylamino)-pyrimidine with a boiling point of 162° C/0.001 Torr (74.5% of theory).
Reaction SMILES: [C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].[OH-].[NH4+]>[Rh].O>[OH:15][CH:14]1[CH2:16][CH2:17][N:10]([C@@H:1]2[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]2[OH:3])[C:11](=[O:12])[NH:13]1.[C@@H:1]1([N:10]2[CH2:17][CH2:16][CH2:14][NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3]
Reactant: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Agent: [Rh]
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: O=C1NC(O)CCN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Product: O=C1NCCCN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Procedure:
In the manner given in Example 2B, uridine was directly reduced with a rhodium on alumina catalyst in a solvent medium consisting of 1 part concentrated ammonium hydroxide and 99 parts water to give 4-hydroxy-1-β-D-ribofuranosyl-tetrahydro-2(1H)-pyrimidinone and 1-β-D-ribofuranosyl-tetrahydro-2(1H)-pyrimidinone.
Reaction SMILES: [CH3:1][SiH:2]([Cl:4])[Cl:3].[SiH:5]([Cl:8])([CH3:7])[CH3:6].[CH2:9]([Cl:12])[CH:10]=[CH2:11]>>[CH3:1][Si:2]([CH2:11][CH2:10][CH2:9][Cl:12])([Cl:4])[Cl:3].[Si:5]([CH2:11][CH2:10][CH2:9][Cl:12])([CH3:7])([CH3:6])[Cl:8]
Reactant: C[SiH](Cl)Cl
Reactant: C[SiH](C)Cl
Reactant: C=CCCl
Product: C[Si](C)(Cl)CCCCl
Product: C[Si](Cl)(Cl)CCCCl
Temperature: 45 °C
Yield: 22.6 %
Yield: 31.3 %

Procedure:
In a 100 ml apparatus, there were combined 8.6 g (0.075 mol) of MeSiHCl2, 7.1 g (0.075 mol) of Me2SiHCl, and 5.7 g (0.075 mol) of allyl chloride. Pt catalyst solution (0.01 ml) was added at 37° C., followed by heating up to 45° C. over 1 hr. Vacuum distillation yielded 31.3% of MeSiCl2CH2CH2CH2Cl and 22.6% of Me2SiClCH2CH2CH2Cl. This example shows that neither Me2SiHCl nor MeSiHCl2 is a very effective promoter at the equimolar level for reactions of the other with allyl chloride.