Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH:3]([O:9][CH3:10])[C:4]1[CH:8]=[CH:7][S:6][CH:5]=1.C([Li])CCC.[F:16][C:17]1[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=1[C:19](Cl)=[O:20].[Cl-].[NH4+]>O1CCCC1.CCOCC>[CH3:1][O:2][CH:3]([O:9][CH3:10])[C:4]1[CH:8]=[CH:7][S:6][C:5]=1[C:19](=[O:20])[C:18]1[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=1[F:16]
Reactant: O=C(Cl)c1ccccc1F
Reactant: COC(OC)c1ccsc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COC(OC)c1ccsc1C(=O)c1ccccc1F
Temperature: 0 °C

Procedure:
To 3-thiophenecarboxaldehyde dimethylacetal (50.6 g) and ether (500 ml) was added n-butyllithium (132 ml, 2.5M in hexanes) at a rate so as to maintain gentle reflux of the mixture. The reaction mixture was heated at reflux an additional 30 mins, diluted with tetrahydrofuran (600 ml), and cooled to 0° C. A solution of 2-fluorobenzoyl chloride (44.0 ml, 368 mmol) and tetrahydrofuran (500 ml), precooled to -78° C., was added with stirring. The mixture was stirred at -78° C. for 1 hr and then allowed to warm to room temperature overnight. Dilute aqueous ammonium chloride solution and ether were added and the layers were separated. The organic layer was washed with dilute aqueous sodium bicarbonate solution, and the combined aqueous layers were back-extracted with ether. The combined organic layers were washed with brine, dried over anhydrous potassium carbonate, filtered, and concentrated to give 2-(2-fluorobenzoyl)-3-thiophenecarboxaldehyde dimethylacetal.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])=[C:4]([C:16](=[N:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[CH2:17][CH3:18])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:35](Cl)(=[O:37])[CH3:36]>CC(C)=O>[C:35]([N:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[C:16](=[N:19][O:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[CH2:17][CH3:18])[S:9]([C:12]([F:15])([F:14])[F:13])(=[O:10])=[O:11])(=[O:37])[CH3:36]
Reactant: CC(=O)Cl
Reactant: CCC(=NOCc1ccc(Cl)cc1)c1cc(Cl)ccc1NS(=O)(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCC(=NOCc1ccc(Cl)cc1)c1cc(Cl)ccc1N(C(C)=O)S(=O)(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.1 %

Procedure:
To a mixture of N-{4-chloro-2-[1-(4-chlorobenzyloxyimino)propyl]phenyl}trifluoromethanesulfonamide (compound 11) (150 mg, 0.33 mmol) and K2CO3 (137 mg, 0.99 mmol) in acetone (5 mL) was added acetyl chloride (70 μL, 0.99 mmol), and the reaction allowed to stir at RT for 2 hours. The reaction mixture was concentrated under vacuum and the residue dissolved in CHCl3 (20 mL), washed with H2O (15 mL) dried over MgSO4 and concentrated under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with EtOAc/PE, 1:19) to afford N-acetyl-N-{4-chloro-2-[1-(4-chlorobenzyloxyimino)propyl]phenyl}trifluoromethanesulfonamide 307 (156 mg, 95%), as a pale yellow solid. M.p. 64-66° C. 1H n.m.r. (400 MHz, CDCl3) δ 7.51, d, J=2.4 Hz, 1H; 7.42, dd, J=2.4 and 8.8 Hz, 1H, 7.30, m, 4H, 7.23, d, J=2.4 Hz, 1H, 5.12, m, 2H, 2.83, m, 1H, 2.67, m, 1H, 1.91, s, 3H, 1.18, t, J=7.6 Hz, 3H.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](SC)=[CH:10][N+:11]([O-:13])=[O:12])=[CH:4][CH:3]=1.[CH3:16][NH2:17]>CCO.CO>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([NH:17][CH3:16])=[CH:10][N+:11]([O-:13])=[O:12])=[CH:4][CH:3]=1
Reactant: CSC(=C[N+](=O)[O-])Nc1ccc(Cl)nc1
Reactant: CN
Solvent: CO
Solvent: CCO
Product: CNC(=C[N+](=O)[O-])Nc1ccc(Cl)nc1

Procedure:
In 25 ml of EtOH was dissolved 0.42 g (0.00171 mole) of 1-(6-chloro-3-pyridyl)amino-1-methylthio-2-nitroethylene, followed by addition of 0.2 g of a 40% solution of methylamine in methanol. The mixture was refluxed for 1.5 hours. The solvent was distilled off and the crystalline residue was washed with AcOEt and dried to recover 0.33 g of the title compound as white crystals.
Reaction SMILES: [CH3:1][CH:2]([CH3:18])[CH2:3][C@H:4]([NH2:17])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH2:33][C:34](O)=[O:35])[CH:25]=[CH:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:20]>>[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH2:33][C:34]([NH:17][CH:4]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:3][CH:2]([CH3:18])[CH3:1])=[O:35])[CH:25]=[CH:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:20]
Reactant: CC(C)C[C@H](N)c1ccccc1N1CCCCC1
Reactant: CCOC(=O)c1ccc(CC(=O)O)cc1OCC
Product: CCOC(=O)c1ccc(CC(=O)NC(CC(C)C)c2ccccc2N2CCCCC2)cc1OCC

Procedure:
Prepared from (S)-3-Methyl-1-(2-piperidino-phenyl)-1-butyl-amine and 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid analogously to Example 1.
Reaction SMILES: [CH2:1]([O:15][CH2:16][C@H:17]([CH2:19][OH:20])[OH:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[C:21]1([C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)Cl)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>N1C=CC=CC=1>[CH2:1]([O:15][CH2:16][C@H:17]([CH2:19][O:20][C:27]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[OH:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCOC[C@@H](O)CO
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCOC[C@@H](O)COC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
In 30 ml of dry pyridine, 2.82 g of 1-tetradecyl-sn-glycerol is allowed to react 3.27 g of triphenylchloromethane to give 1-tetradecyl-3-trityl-sn-glycerol. This compound is subjected to methylation with methyl iodide and deprotection to give 2 g of 1-tetradecyl-2-methyl-sn-glycerol.
Reaction SMILES: [H-].[Na+].O1CCCC1.[CH3:8][C:9]1[CH:13]=[C:12]([CH3:14])[NH:11][N:10]=1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23](Cl)=[C:24]([Cl:29])[N:25]=[N:26][C:27]=2[CH3:28])=[CH:18][CH:17]=1>C(OCC)(=O)C>[Cl:29][C:24]1[N:25]=[N:26][C:27]([CH3:28])=[C:22]([C:19]2[CH:18]=[CH:17][C:16]([Cl:15])=[CH:21][CH:20]=2)[C:23]=1[N:10]1[C:9]([CH3:8])=[CH:13][C:12]([CH3:14])=[N:11]1
Reactant: Cc1cc(C)[nH]n1
Reactant: Cc1nnc(Cl)c(Cl)c1-c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1cc(C)n(-c2c(Cl)nnc(C)c2-c2ccc(Cl)cc2)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
29 mg of sodium hydride (55% oil dispersion) was added to tetrahydrofuran. Into this, a tetrahydrofuran solution of 3,5-dimethylpyrazole was added dropwise. The resultant mixture was added dropwise into 0.20 g of 5-(4-chloro-phenyl)-3,4-dichloro-6-methylpyridazine while cooling with ice. The mixture was stirred overnight at room temperature. To the reaction mixture was added ethyl acetate, and the mixture was washed with dilute hydrochloric acid water and brine sequentially. The organic layer was dried over anhydrous magnesium sulfate, then, concentrated under reduced pressure. 0.27 g of the resultant residue was subjected to silica gel column chromatography, to obtain 50 mg of 3-chloro-5-(4-chlorophenyl)-4-(3,5-dimethyl-1-pyrazolyl)-6-m ethylpyridazine (hereinafter, described as compound (2) of the present invention) and 59 mg of 4-chloro-5-(4-chlorophenyl)-3-(3,5-dimethyl-1-pyrazolyl)-6-m ethylpyridazine.
Reaction SMILES: [Cl:1][C:2]1[C:3]([I:14])=[C:4]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:18][CH2:19][O:20][CH2:21][CH2:22]Br>CN(C=O)C>[Cl:1][C:2]1[C:3]([I:14])=[C:4]([C:8]2([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:5]=[CH:6][CH:7]=1
Reactant: BrCCOCCBr
Reactant: CCOC(=O)Cc1cccc(Cl)c1I
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1(c2cccc(Cl)c2I)CCOCC1
Temperature: 25 °C

Procedure:
A mixture of ethyl 2-(3-chloro-2-iodophenyl)acetate (1.3 g, 4.0 mmol) in 6 mL DMF was stirred at room temperature and treated with sodium hydride (0.23 g, 10 mmol). The mixture turned orange, was stirred for 10 minutes, and was treated with 1-bromo-2-(2-bromoethoxy)ethane (1.2 g, 5.2 mmol) in 6 mL DMF dropwise. The mixture was then stirred at room temperature for 2.5 hours. The mixture was carefully quenched with 20 mL H2O and extracted with ether (3×100 mL). The combined organic layers were washed with water (3×50 mL), 20 mL saturated NaCl, dried over anhydrous Na2SO4, and concentrated. The crude product was purified by column eluting with (10-20% EtOAc/hexane) to give the title compound in 0.57 g. MS m/e: (M+H)+ 395.
Reaction SMILES: [CH3:1][O-:2].[Na+].CO.[NH2:6][C:7]1[C:12]([N+:13]([O-:15])=[O:14])=[CH:11][CH:10]=[C:9](Cl)[N:8]=1>O>[NH2:6][C:7]1[C:12]([N+:13]([O-:15])=[O:14])=[CH:11][CH:10]=[C:9]([O:2][CH3:1])[N:8]=1
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Reactant: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc([N+](=O)[O-])c(N)n1
Temperature: 15 °C
Yield: 86.5 %

Procedure:
Sodium methoxide, 7.78 gm (0.144 mole) and methanol 50.0 ml were mixed and cooled to 15° C. To this solution, 25.0 gm of 2-amino-6-chloro-3-nitropyridine (0.144 mole) was added while maintaining the temperature at 15° C. by external cooling. The resulting mixture was heated to 25°–30° C. and maintained at this temperature for 4–5 hrs with constant stirring. The completion of reaction was monitored by TLC. After the completion of reaction, the reaction mixture was poured in water. The precipitate thus obtained was filtered and washed with water. On drying 21.0 gm of 2-amino-3-nitro-6-methoxypyridine (86.5% yield) was obtained, with the HPLC purity of 99.0%. Melting point 167°–169° C.; 1HNMR (CDCl3) δ3.89 ppm (s, -3H, OCH3), 66.14–6.16 ppm (d, 1H), 68.24–8.27 ppm (d, 1H), 68.16 ppm (s, -2H, —NH2)
Reaction SMILES: [CH:1]([O:4][CH2:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14](N)=[CH:13][CH:12]=2)=[CH:8][CH:7]=1)([CH3:3])[CH3:2].S(O)(O)(=O)=O.Cl[C:26]1[NH:27][CH2:28][CH2:29][N:30]=1>C(O)(C)C>[CH:1]([O:4][CH2:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:26]3[NH:30][CH2:29][CH2:28][N:27]=3)=[CH:13][CH:12]=2)=[CH:8][CH:7]=1)([CH3:3])[CH3:2]
Reactant: CC(C)OCc1ccc(Cc2ccc(N)cc2)cc1
Reactant: ClC1=NCCN1
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: CC(C)OCc1ccc(Cc2ccc(C3=NCCN3)cc2)cc1
Temperature: 80 °C
Reaction time: 3 h
Yield: 95.6 %

Procedure:
To a solution of 4-(4-isopropoxymethylbenzyl)-phenylamine (400 mg, 1.57 mmol) in isopropanol (4.8 mL) at 20° C. under argon atmosphere was added 2-chloro-2-imidazoline sulfate (382 mg, 1.88 mmol). The mixture was heated to 80° C. and stirred for 3 hours. The solvent was evaporated in vacuo, and water and 10% sodium hydroxide was added to pH 11–12. The basic aqueous phase was extracted with dichloromethane (3×20 mL), and the combined organic layers were washed with water, dried (Na2SO4), and evaporated in vacuo. The crude product was purified by flash chromatography, washed with 0.07M potassium carbonate, and concentrated to give pure 2-[4-(4-isopropoxymethyl-benzyl)-phenyl]-imidazoline (463 mg, 91%) as a clear oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][N:12]=1)=[O:10].[O:17]1[C:21]([C:22]2[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=2)=[CH:20][N:19]=[CH:18]1>>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:28]([C:25]2[CH:26]=[CH:27][C:22]([C:21]3[O:17][CH:18]=[N:19][CH:20]=3)=[CH:23][CH:24]=2)(=[O:29])=[O:30])=[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][N:12]=2)=[O:10])[CH:4]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccncn1
Reactant: O=S(=O)(Cl)c1ccc(-c2cnco2)cc1
Product: O=C(c1ccncn1)c1cc(Cl)ccc1NS(=O)(=O)c1ccc(-c2cnco2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 116 mg of (2-Amino-5-chloro-phenyl)-pyrimidin-4-yl-methanone and 122 mg of 4-oxazol-5-yl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 7.43 (s, 1H), 7.53 (dd, 1H, J=8.8 Hz, 2.4 Hz), 7.62 (m, 2H), 7.75 (m, 2H), 7.80 (m, 3H), 7.98 (s, 1H), 8.99 (d, 1H, J=5.2 Hz), 9.25 (b, 1H), 10.29 (b, 1H). MS: m/z 441.9 (M++1).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:10].F[B-](F)(F)F.[O:16]=[N+:17]=[O:18]>C(#N)C.O>[OH:1][C:2]1[C:9]([N+:17]([O-:18])=[O:16])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:10]
Reactant: Cc1cc(C#N)ccc1O
Reactant: O=[N+]=O
Agent: F[B-](F)(F)F
Solvent: O
Solvent: CC#N
Product: Cc1cc(C#N)cc([N+](=O)[O-])c1O
Reaction time: 1 h
Yield: 94 %

Procedure:
A stirred solution of 4-hydroxy-3-methylbenzonitrile (3.1 g, 23.3 mmol) in 60 mL of anhydrous acetonitrile was cooled to −30° C. and treated with nitronium tetrafluoroborate (3.4 g, 25.6 mmol) in portions. After 60 minutes, the reaction mixture was diluted with 100 mL of water. The resulting light yellow precipitate was filtered, washed with water, and dried to give 3.9 g of 4-hydroxy-3-methyl-5-nitrobenzonitrile (94% yield).
Reaction SMILES: [NH:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:3][CH2:2]1.Cl[CH2:17][CH2:18][C:19]1[C:24](=[O:25])[N:23]2[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:22]2=[N:21][C:20]=1[CH3:31].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[NH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([C:4]2[CH2:3][CH2:2][N:1]([CH2:17][CH2:18][C:19]3[C:24](=[O:25])[N:23]4[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:22]4=[N:21][C:20]=3[CH3:31])[CH2:6][CH:5]=2)=[CH:8]1
Reactant: C1=C(c2c[nH]c3ccccc23)CCNC1
Reactant: Cc1nc2c(C)cccn2c(=O)c1CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: Cc1nc2c(C)cccn2c(=O)c1CCN1CC=C(c2c[nH]c3ccccc23)CC1

Procedure:
A solution of 3-(1,2,3,6-tetrahydropyridin-4-yl)indole (25 g, 0.126 mol), 3-(2-chloroethyl)-2,9-dimethyl-4H-pyrido[1,2-a]pyrimidin-4-one (33 g, 0.139 mol) and potassium carbonate (17.5 g, 0.127 mol) in acetonitrile (500 ml) and water (100 ml) was heated under reflux for 18 h. After cooling the precipitate was collected and washed with water, isopropyl alcohol and petroleum ether respectively. Yield 38 g (76%) of a pale yellow solid. M.p.: 210-212° C.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]1[O:18][C@H:17]2[C@H:13]([N:14]=[C:15]([N:19]([CH2:27][CH2:28][CH3:29])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[S:16]2)[C@@H:12]([OH:30])[C@@H:11]1[OH:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1>CN(C=O)C>[Si:1]([O:8][CH2:9][C@H:10]1[O:18][C@H:17]2[C@H:13]([N:14]=[C:15]([N:19]([CH2:27][CH2:28][CH3:29])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[S:16]2)[C@@H:12]([O:30][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[C@@H:11]1[O:31][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]
Reactant: CCCN(C(=O)OC(C)(C)C)C1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@@H]2S1
Reactant: COc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCN(C(=O)OC(C)(C)C)C1=N[C@@H]2[C@@H](OCc3ccc(OC)cc3)[C@H](OCc3ccc(OC)cc3)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@@H]2S1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 66.4 %

Procedure:
To a solution of tert-butyl (3aR,5R,6S,7R,7aR)-5-((tert-butyldimethylsilyloxy)methyl)-6,7-dihydroxy-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl(propyl)carbamate (20 g, 42 mmol) in DMF (300 mL) was added sodium hydride (10 g, 417 mmol) at 15° C. in portions, followed by addition of 1-(bromomethyl)-4-methoxybenzene (33.8 g, 168 mmol). The resulting solution was stirred for 1.5 h at room temperature, quenched by addition of cold water (100 mL), and extracted with dichloromethane (5×100 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to provide a residue, which was purified by silica gel column, eluted with 10-25% ethyl acetate in petroleum ether to give compound 18 as a yellow oil (20 g, 64.8%). (ES, m/z): 717.1; 1H NMR (300 MHz, CDCl3) δ 7.32-7.35 (d, J=8.7 Hz, 2H), 7.19-7.22 (d, J=8.7 Hz, 2H), 6.83-6.92 (m. 4H), 6.05-6.07 (d, J=6.9 Hz, 1H), 4.57-4.74 (m, 3H), 4.30-4.39 (m, 2H), 4.14-4.17 (t, J=4.2 Hz, 1H), 3.68-3.84 (m, 11H), 3.41-3.45 (m, 1H), 1.67-1.74 (m, 2H), 1.53 (s, 9H), 0.89 (s, 9H), 0.84 (m, 3H), 0.08 (s, 6H).
Reaction SMILES: Cl[C@H:2]1[C@H:14]2[C@H:10]([N:11]=[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:13]2)[CH2:9][C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[Li].C[O:23]CCO>O>[C:15]1([C:12]2[O:13][C@H:14]3[CH:2]([OH:23])[C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=4[CH2:9][C@H:10]3[N:11]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COCCO
Reactant: Cl[C@@H]1c2ccccc2C[C@H]2N=C(c3ccccc3)O[C@@H]12
Agent: [Li]
Solvent: O
Product: OC1c2ccccc2C[C@H]2N=C(c3ccccc3)O[C@@H]12
Temperature: 90 °C

Procedure:
To a solution of (±)-(3aR,9R, 9aR)-9-chloro-3a, 4,9,9a-tetrahydro-2-phenyl-naphth[2,3-d]oxazole (360 mg) in 2-methoxyethanol (10 ml) was added a solution of lithium hydroxyde monohydrate (67 mg) in water (2 ml). The mixture was warmed at 90° C. for 1/2 hour and the title compound was precipitated by addition of water. Filtration, washing with water and drying in vacuo gave the title compound as a yellow solid (205 mg).
Reaction SMILES: [N:1]1[CH2:6][CH2:5][CH2:4][NH:3][C:2]=1[SH:7].Br[CH2:9][CH2:10][CH2:11]Br>>[S:7]1[CH2:11][CH2:10][CH2:9][N:1]2[CH2:6][CH2:5][CH2:4][N:3]=[C:2]12
Reactant: SC1=NCCCN1
Reactant: BrCCCBr
Product: C1CN=C2SCCCN2C1

Procedure:
3,4,7,8-Tetrahydro-2H,6H-pyrimido[2,1-b]-[1,3]-thiazine was prepared by the above-described reaction scheme wherein n=2 and m=2. The starting materials were 3,4,5,6-tetrahydro-2-pyrimidinethiol and 1,3-dibromopropane (both obtained from Aldrich Chemical Company, Milwaukee, Wis.), and the remainder of the preparation process was essentially the same as described above. The resulting crude product was 93 percent (%) pure and was used directly for catalysis.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][O:7][NH:8]C(=O)OC(C)(C)C)=[CH:4][CH:3]=1>Cl.O1CCOCC1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][O:7][NH2:8])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NOCc1ccc(Cl)cc1
Agent: Cl
Solvent: C1COCCO1
Product: NOCc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 98.6 %

Procedure:
A mixture of tert-butyl 4-chlorobenzyloxycarbamate (1.28 g, 4.97 mmol) in 15 mL of 4 M HCl-dioxane was stirred at ambient temperature for 1.5 hours. The reaction was concentrated to provide O-(4-chlorobenzyl)hydroxylamine (0.95 g, 4.90 mmol).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:28])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3Br)[C:18]2=[O:27])=[CH:12][CH:11]=1.[CH3:29][O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[O:37][CH3:38]>>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:28])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[C:34]3[CH:33]=[CH:32][C:31]([O:30][CH3:29])=[C:36]([O:37][CH3:38])[CH:35]=3)[C:18]2=[O:27])=[CH:12][CH:11]=1
Reactant: COc1ccc(B(O)O)cc1OC
Reactant: Nc1ccccc1NC(=O)c1ccc(CN2Cc3c(Br)cccc3C2=O)cc1
Product: COc1ccc(-c2cccc3c2CN(Cc2ccc(C(=O)Nc4ccccc4N)cc2)C3=O)cc1OC
Yield: 91 %

Procedure:
The procedure of Example 2 was repeated except for using N-(2-aminophenyl)-4-((4-bromo-1-oxoisoindolin-2-yl)methyl)benzamide obtained in Example 9 instead of N-(2-aminophenyl)-4-((4-bromo-5,6-dimethoxy-1-oxoisoindolin-2-yl)methyl)benzamide, and 3,4-dimethoxyphenyl boronic acid instead of phenyl boronic acid to obtain the title compound (91%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]2[C:13]([O:15][CH3:16])=[O:14])=[CH:5][CH:4]=1.[CH3:17]I.[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][C:10]2([C:13]([O:15][CH3:16])=[O:14])[CH3:17])=[CH:5][CH:4]=1
Reactant: CI
Reactant: COC(=O)C1CCCc2ccc(OC)cc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1(C)CCCc2ccc(OC)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 42.7 %

Procedure:
7-Methoxytetralin-1-yl-carboxylic acid, methyl ester (0.4 g; 1.8 mmol; from step (i) above) and MeI (0.13 mL, 2.0 mmol) were added to a slurry of NaH (55% in oil; 87 mg; 2.0 mmol) in DMF (5 mL) and the mixture was stirred at RT overnight. The resultant mixture was poured onto water, and the water mixture was extracted with EtOAc:toluene 3 times. The combined organic layer was washed with water, dried (Na2SO4), and concentrated. Flash chromatography (Si-gel; heptane:EtOAc; 4:1) yielded 0.18 g (42%) of the sub-title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:29]2[CH2:33][C@H:32]([CH2:34][NH:35][C:36](=[O:38])[CH3:37])[O:31][C:30]2=[O:39])[CH:5]=[CH:6][C:7]=1[C:8]1[C:9](OC)=[N:10][C:11]([O:14][C@@H:15]2[CH2:20][O:19][C:18]3=[N:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][N:17]3[CH2:16]2)=[N:12][CH:13]=1.BrC1[C:42](N(C)C)=[N:43][C:44](O[C@@H]2COC3=NC([N+]([O-])=O)=CN3C2)=NC=1>>[CH3:42][N:43]([CH3:44])[C:9]1[C:8]([C:7]2[CH:6]=[CH:5][C:4]([N:29]3[CH2:33][C@H:32]([CH2:34][NH:35][C:36](=[O:38])[CH3:37])[O:31][C:30]3=[O:39])=[CH:3][C:2]=2[F:1])=[CH:13][N:12]=[C:11]([O:14][C@@H:15]2[CH2:20][O:19][C:18]3=[N:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][N:17]3[CH2:16]2)[N:10]=1
Reactant: COc1nc(O[C@@H]2COc3nc([N+](=O)[O-])cn3C2)ncc1-c1ccc(N2C[C@H](CNC(C)=O)OC2=O)cc1F
Reactant: CN(C)c1nc(O[C@@H]2COc3nc([N+](=O)[O-])cn3C2)ncc1Br
Product: CC(=O)NC[C@H]1CN(c2ccc(-c3cnc(O[C@@H]4COc5nc([N+](=O)[O-])cn5C4)nc3N(C)C)c(F)c2)C(=O)O1

Procedure:
(S,S)—N-(3-{3-Fluoro-4-[4-methoxy-2-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yloxy)-pyrimidin-5-yl]-phenyl}-2-oxo-oxazolidin-5-ylmethyl)-acetamide. The title compound was prepared by following the same procedure as described in the preparation of Example 7, except [5-bromo-2-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6(S)-yloxy)-pyrimidin-4-yl]-dimethyl-amine was used in place of 6-(5-bromo-pyridin-2-yloxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine. ESI MS m/z 557.4 (M+H+).
Reaction SMILES: Cl[C:2]([Cl:12])(OC(=O)OC(Cl)(Cl)Cl)Cl.OC[CH:15]1[CH2:21][S:20][CH2:19][C:18](=[CH2:22])[CH2:17][S:16]1.C(N(CC)CC)C>ClCCl>[Cl:12][CH2:2][CH:15]1[CH2:21][S:20][CH2:19][C:18](=[CH2:22])[CH2:17][S:16]1
Reactant: C=C1CSCC(CO)SC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=C1CSCC(CCl)SC1
Reaction time: 1 h
Yield: 198.9 %

Procedure:
Triphosgene (0.843 g, 2.84 mmoles) was dissolved in 20 mL of dichloromethane. 2-(Hydroxymethyl)-6-methylene-1,4-dithiepane (1.5 g, 8.52 mmoles) and triethyl amine (1.185 mL, 0.86 g) were dissolved in ca. 5 mL of dichloromethane and added dropwise to the triphosgene solution. After ca. one hour the reaction was largely complete. A little more triphosgene was added and the solution was stirred overnight. The reaction was worked up by evaporation of solvent, addition of water and extraction with ether. The extracts were dried and evaporated and the resulting oil was chromatographed on silica gel to give 1.1 g (67%) of clear oil.
Reaction SMILES: O[C:2]1[CH:7]=[C:6]([CH3:8])O[C:4](=[O:9])[CH:3]=1.[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH2:16])=[CH:13][CH:12]=1>C(O)CCC>[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][N:16]2[C:6]([CH3:8])=[CH:7][C:2]([NH:16][CH2:15][C:14]3[CH:17]=[CH:18][C:11]([F:10])=[CH:12][CH:13]=3)=[CH:3][C:4]2=[O:9])=[CH:13][CH:12]=1
Reactant: NCc1ccc(F)cc1
Reactant: Cc1cc(O)cc(=O)o1
Solvent: CCCCO
Product: Cc1cc(NCc2ccc(F)cc2)cc(=O)n1Cc1ccc(F)cc1
Yield: 30.1 %

Procedure:
A mixture of 4-hydroxy-6-methylpyrone (5.0 g, 0.04 mol) and 4-fluorobenzylamine (10.0 g. 0.08 mol) in n-butanol (25.0 mL) was heated to reflux for 24 hours under argon atmosphere. The resulting solution was concentrated to dryness under reduced pressure. The residue was triturated with ethyl acetate and filtered. It was thoroughly washed with ethyl acetate and dried to afford the title compound as a pale yellow powder (4.1 g. 30%). 1H-NMR (CD3OD, 400 MHz) δ 7.33 (q, 2H), 7.04 (m, 5H), 5.85 (d, 1H, J=2.0 Hz), 5.44 (d, 2H, J=2.4 Hz), 5.20 (s, 1H), 4.29 (s, 2H), 2.17 (s, 3H); ES-HRMS m/z 341.1488 (M+H calculated for C20H19N2OF2 requires 341.1460).