Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][S:6][C:7]1[CH:8]=[C:9]([O:15][CH3:16])[C:10]([O:13][CH3:14])=[N:11][CH:12]=1.BrCC1C=CC=C([C:28]([F:31])([F:30])[F:29])C=1>>[CH3:14][O:13][C:10]1[C:9]([O:15][CH3:16])=[CH:8][C:7]([S:6][CH2:5][C:4]2[CH:17]=[CH:18][CH:19]=[C:2]([C:28]([F:31])([F:30])[F:29])[CH:3]=2)=[CH:12][N:11]=1
Reactant: COc1cc(SCc2cccc(Cl)c2)cnc1OC
Reactant: FC(F)(F)c1cccc(CBr)c1
Product: COc1cc(SCc2cccc(C(F)(F)F)c2)cnc1OC

Procedure:
Prepared as described for 5-(3-chlorobenzylthio)-2,3-dimethoxypyridine (Intermediate 8) but using 1-(bromomethyl)-3-trifluoromethylbenzene instead of 1-(bromomethyl)-3-chlorobenzene.
Reaction SMILES: N[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[CH:8]=2)[N:5]=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([NH2:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[N:3]=1.CC(O)C.N(OCCC(C)C)=O>C1COCC1>[Cl:13][C:9]1[CH:8]=[C:7]([N:6]2[CH:2]=[N:3][C:4]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([S:21]([NH2:24])(=[O:22])=[O:23])=[CH:19][CH:20]=3)=[N:5]2)[CH:12]=[CH:11][N:10]=1
Reactant: Nc1nc(Nc2ccc(S(N)(=O)=O)cc2)nn1-c1ccnc(Cl)c1
Agent: CC(C)CCON=O
Solvent: CC(C)O
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccc(Nc2ncn(-c3ccnc(Cl)c3)n2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 49.4 %

Procedure:
To a solution of 250 mg of 4-[5-amino-1-(2-chloro-pyridin-4-yl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonamide (0.686 mmol, 1 equiv) in 40 mL of 1:1 THF:iPrOH, 160 mg of isoamyl nitrite (1.37 mmol, 2 equiv) was added. The dark yellow solution was stirred for 12 h at 25° C. and then heated under reflux for 6 h. The reaction mixture was cooled and concentrated in vacuo. The resulting yellow solid was triturated with methanol and filtered to give the title compound as a yellow solid (118.9 mg, 50%); 1H NMR (400 MHz, (CD3)2SO) ∂ 10.20 (1H, s), 9.42 (1H, s), 8.55 (1H, d, J=5.6), 8.07 (1H, m), 7.95 (1H, dd, J=5.6 and 1.8), 7.77 (4H, m) and 7.18 (2H, s); MS (ES+) m/e 351.36, (ES−) m/e 349.48
Reaction SMILES: C[O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([CH3:10])[N:7]=[C:6]([CH2:11][OH:12])[CH:5]=1.[ClH:14]>>[ClH:14].[OH:12][CH2:11][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([CH3:10])[N:7]=1)[C:3]([OH:13])=[O:2]
Reactant: COC(=O)c1cc(C)nc(CO)c1
Agent: Cl
Product: Cc1cc(C(=O)O)cc(CO)n1

Procedure:
A solution of 2-hydroxymethyl-6-methyl-isonicotinic acid methyl ester (500 mg, 2.76 mmol) in 32% aq. HCl (10 mL) is stirred at 60° C. for 5 h. The solvent is removed and the residue is dried to give 2-hydroxymethyl-6-methyl-isonicotinic acid hydrochloride (480 mg) as a yellow solid; LC-MS: tR=0.15 min, [M+1]+=168.04.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@H:7]([OH:8])[CH2:6][C@@H:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.CCN(CC)CC.[CH2:23]([O:30][C:31](ON1C(=O)CCC1=O)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl>[OH:8][C@H:7]1[C@@H:3]([CH2:2][NH:1][C:31]([O:30][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:32])[CH2:4][C@H:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6]1
Reactant: CC(C)(C)OC(=O)[C@H]1C[C@H](CN)[C@H](O)C1
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)[C@H]1C[C@H](CNC(=O)OCc2ccccc2)[C@H](O)C1
Reaction time: 18 h
Yield: 89.7 %

Procedure:
To a solution of (±)-1,1-dimethylethyl (1S,3R,4R)-3-(aminomethyl)-4-hydroxycyclopentanecarboxylate (7.9 g, 37.0 mmole) in DCM (100 mL) at RT was added Et3N (6.7 mL, 48.4 mmole) and N-(benzyloxycarbonyloxy)succinimide (12.1 g, 48.4 mmole). After 18 h, the DCM was removed under vacuum and the residue purified on silica (1:1, hexanes/EtOAc) to give the title compound (11.6 g, 89%) as a white solid: LC-MS (ES) m/e 350 (M+H)+.
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[O:8])=[CH:5][N:6]=1.[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.C(N(CC)C(C)C)(C)C.O>O1CCCC1>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:24][C:2]2[S:3][C:4]([C:7]([C:9]3[C:17]4[C:12](=[N:13][CH:14]=[CH:15][CH:16]=4)[NH:11][CH:10]=3)=[O:8])=[CH:5][N:6]=2)=[CH:21][CH:20]=1
Reactant: NCc1ccc(Cl)cc1
Reactant: O=C(c1cnc(Br)s1)c1c[nH]c2ncccc12
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: C1CCOC1
Product: O=C(c1cnc(NCc2ccc(Cl)cc2)s1)c1c[nH]c2ncccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 27.1 %

Procedure:
A mixture of (2-Bromo-thiazol-5-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (99, 5 mg, 0.02 mmol), p-chlorobenzylamine (61, 10 mg, 0.08 mmol), and N,N-Diisopropylethylamine (10 μL, 0.08 mmol) in tetrahydrofuran (10 mL), in a sealed reaction vessel, was stirred room temperature overnight. The reaction mixture was poured into iced water, extracted with ethyl acetate, washed with brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a light yellow solid (P-0077, 2 mg, 30%). MS (ESI) [M+H+]=305.90, 307.88.
Reaction SMILES: CO[C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:11]N=[CH:9][N:8]=1.S1C(N)=N[CH:20]=N1.S1C=CN=C1N>>[CH3:17][O:16][C:14]1[CH:13]=[CH:12][C:4]([CH2:5][NH:6][C:7]2[S:11][CH:20]=[CH:9][N:8]=2)=[CH:3][CH:15]=1
Reactant: Nc1ncns1
Reactant: COc1ccc(CNc2ncns2)c(OC)c1
Agent: Nc1nccs1
Product: COc1ccc(CNc2nccs2)cc1

Procedure:
N-(4-methoxybenzyl)thiazol-2-amine (INTERMEDIATE W) was prepared in a manner analogous to INTERMEDIATE A wherein 1,2,4-thiadiazol-5-amine was replaced with thiazole-2-amine
Reaction SMILES: [C:1]1(=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=N)[NH:12]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=N)[NH:2]1.[CH3:21][N:22]1[C:29](=[O:30])[CH2:28][C:26](=[O:27])[N:25]([CH3:31])[C:23]1=[O:24]>CN1C(=O)CCC1.C(O)(=O)C>[CH3:31][N:25]1[C:26](=[O:27])[C:28](=[C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11](=[C:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:3](=[C:28]4[C:29](=[O:30])[N:22]([CH3:21])[C:23](=[O:24])[N:25]([CH3:31])[C:26]4=[O:27])[NH:2]3)[NH:12]2)[C:29](=[O:30])[N:22]([CH3:21])[C:23]1=[O:24]
Reactant: N=C1NC(=C2NC(=N)c3ccccc32)c2ccccc21
Reactant: CN1C(=O)CC(=O)N(C)C1=O
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Product: CN1C(=O)C(=c2[nH]c(=c3[nH]c(=C4C(=O)N(C)C(=O)N(C)C4=O)c4ccccc34)c3ccccc23)C(=O)N(C)C1=O
Temperature: 25 °C

Procedure:
10 g of [1,1′]biisoindolylidene-3,3′-diimine and 18.1 g of 1,3-dimethyl-barbituric acid are stirred in a mixture of 160 ml of NMP and 40 ml of glacial acetic acid at reflux for 5 hours. After cooling to room temperature the suspension is filtered and the filter product is washed with ethanol and then water and dried at 60° C. This gives 14.5 g (70%) of a virtually black powder of a compound of the following formula
Reaction SMILES: [CH3:1][C:2]([CH3:14])([S:4]([NH:6][C:7]([CH3:13])([CH3:12])[C:8](=[N:10][OH:11])[NH2:9])=[O:5])[CH3:3].[CH2:15](OC(OCC)OCC)C>CC(O)=O>[O:11]1[CH:15]=[N:9][C:8]([C:7]([NH:6][S:4]([C:2]([CH3:14])([CH3:1])[CH3:3])=[O:5])([CH3:13])[CH3:12])=[N:10]1
Reactant: CCOC(OCC)OCC
Reactant: CC(C)(NS(=O)C(C)(C)C)C(N)=NO
Solvent: CC(=O)O
Product: CC(C)(NS(=O)C(C)(C)C)c1ncon1
Temperature: 25 °C
Reaction time: 16 h
Yield: 72 %

Procedure:
2-(1,1-dimethylethylsulfinamido)-N′-hydroxy-2-methylpropanimidamide (1.0 g, 4.5 mmol) in triethoxymethane (7.5 ml, 45 mmol) was treated with AcOH (7.5 ml) at rt. The reaction was allowed to stir at rt for 16 h. The reaction was then concentrated to dryness azeotroping with toluene 3×. The resulting yellow oil was purified on silica gel (Biotage, EtOAc/hexanes gradient) to give the expected product N-(2-(1,2,4-oxadiazol-3-yl)propan-2-yl)-2-methylpropane-2-sulfinamide (750 mg, 3.24 mmol, 72% yield) consistent by LCMS and NMR. LC-MS retention time: 0.987 min; m/z (MH+): 232. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1H), 5.54 (s, 1H), 1.65 (s, 3H), 1.59 (s, 3H), 1.08 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1I.C(=O)([O-])O.[Na+].[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CCOCC>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1I
Reactant: OB(O)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccccc1
Reaction time: 8 h

Procedure:
To a rapidly stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.25 g) in toluene (2 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.02 g) was added saturated aqueous sodium hydrogen carbonate solution (1 ml) and a solution of phenylboronic acid (0.1 g) in ethanol (1 ml). The mixture was heated under reflux for 1 hour, then left at room temperature overnight and then poured into ether (25 ml) and water (25ml). The organic layer was separated, dried (MgSO4) and evaporated. The residue was taken up the minimum amount of ethyl acetate and purified by column chromatography on silica gel (20 g) eluted with dichloromethane hexane (1:1). Combination and evaporation of suitable fractions followed by recrystallisation from ether/hexane gave the title compound as a white solid, m.p. 198-9° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([Cl:12])[C:6]=2[CH2:13]Cl.Cl.[NH2:16]O.C([O-])=O.[Na+]>C(O)=O.O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([Cl:12])[C:6]=2[C:13]#[N:16]
Reactant: NO
Reactant: ClCc1c(Cl)ccc2cc(Cl)cnc12
Agent: Cl
Agent: O=C[O-]
Agent: [Na+]
Solvent: O
Solvent: O=CO
Product: N#Cc1c(Cl)ccc2cc(Cl)cnc12

Procedure:
28.1 parts of 3,7-dichloro-8-chloromethylquinoline (Example 1), 6.95 parts of hydroxylamine hydrochloride and 13.6 parts of sodium formate in 200 ml of formic acid and 60 ml of water were stirred at 100° C. for 12 hours. The reaction solution was poured onto ice and the precipitated solid was filtered off with suction, washed neutral with water and dried. 19 parts of 3,7-dichloro-8-cyanoquinoline of melting point 222° C. were obtained. The yield corresponds to 78.5% of theory.
Reaction SMILES: Cl[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([F:13])=[CH:5][CH:4]=1.[C-:14]#[N:15].[Na+].O>CN(C)C=O>[F:13][C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([CH2:2][C:14]#[N:15])=[CH:4][CH:5]=1
Reactant: Fc1ccc(CCl)c2ccccc12
Reactant: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#CCc1ccc(F)c2ccccc12
Temperature: 70 °C

Procedure:
A solution of 1-chloromethyl-4-fluoronaphthalene (5.45 g, 5.66 mmol), sodium cyanide (333 mg, 6.79 mmol), and water (2 mL) in N,N-dimethylformamide (30 mL) is stirred for 8 h, then heated at 70° C. for 15 h. The mixture is cooled to room temperature and partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic portion is washed with three portions of water, one portion of brine, dried (sodium sulfate), filtered and evaporated. The residue is chromatographed on SiO2 (30% ethyl acetate/hexane) to yield the title compound, 4.67 g (90%), as a light brown solid. 1H NMR (CDCl3): δ 8.19 (d, J=8 Hz, 1H), 7.87 (d, J=8 Hz, 1H), 7.68 (ddd, J=8, 7, 1 Hz, 1H), 7.63 (ddd, J=8, 7, 1 Hz, 1H), 7.51 (dd, J=8, 5 Hz, 1H), 7.14 (dd, J=10, 8 Hz, 1H), 4.09 (s, 2H).
Reaction SMILES: [F:1][C:2]1[C:3]([N+:16]([O-])=O)=[CH:4][C:5]([O:14][CH3:15])=[C:6]([N:8]2[CH:12]=[N:11][C:10]([CH3:13])=[N:9]2)[CH:7]=1>[Pd].CO>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:12]=[N:11][C:10]([CH3:13])=[N:9]2)[C:5]([O:14][CH3:15])=[CH:4][C:3]=1[NH2:16]
Reactant: COc1cc([N+](=O)[O-])c(F)cc1-n1cnc(C)n1
Agent: [Pd]
Solvent: CO
Product: COc1cc(N)c(F)cc1-n1cnc(C)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 96 %

Procedure:
10% Palladium on carbon (0.523 g, 4.92 mmol) was added under an atmosphere of nitrogen to a chilled (ice-water bath) solution of 1-(5-fluoro-2-methoxy-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole (1.24 g, 4.92 mmol) dissolved in methanol (100 mL). The flask was repeatedly evacuated and flushed with hydrogen gas (double balloon). The resulting mixture was allowed to warm to rt and left to stir for 18 h under the hydrogen atmosphere. The vessel was subsequently purged with nitrogen gas. The crude reaction mixture was filtered through a short diatomaceous earth (Celite®) plug. The reaction vessel and plug were rinsed with fresh methanol. The combined filtrates were concentrated in vacuo. The residue was dried on high vacuum overnight to afford 2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (1.05 g, 96% yield) as a gray solid. LC-MS (M+H)+223.1. 1H NMR (500 MHz, CDCl3) δ ppm 8.46 (s, 1H) 7.39 (d, J=11.29 Hz, 1H) 6.44 (d, J=7.63 Hz, 1H) 3.89 (br. s., 2H) 3.83 (s, 3H) 2.47 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([N+:16]([O-])=O)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]>CO.[C].[Pd]>[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([NH2:16])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1ccc(F)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NCc1ccc(F)c(N)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 99 %

Procedure:
To a solution of tert-butyl(4-fluoro-3-nitrophenyl)methylcarbamate (1.0 g, 3.70 mmol) in methanol (4 mL) was added 10% palladium-carbon (150 mg), and the mixture was stirred under a hydrogen atmosphere (1 atm) at room temperature for 18 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate), and the obtained solution was concentrated under reduced pressure to give the title compound (0.88 g, 99%) as a brown oil.
Reaction SMILES: [C@@H:1]1([NH:12][C:13]([NH:15][CH3:16])=[O:14])[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@@H:2]1[OH:3].[N:17]([O-])=[O:18].[Na+]>C(O)(=O)C.O>[C@@H:1]1([NH:12][C:13]([N:15]([CH3:16])[N:17]=[O:18])=[O:14])[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@@H:2]1[OH:3]
Reactant: CNC(=O)N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CN(N=O)C(=O)N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 3 h
Yield: 80.2 %

Procedure:
1-(β-D-mannopyranosyl)-3-methyl-urea (200 mg) was dissolved in a mixture of 1.5 ml of glacial acetic acid and 3.5 ml of water, and the resulting solution was admixed with 99 mg of sodium nitrite. The mixture so obtained was agitated for 3 hours at ambient temperature to effect the nitrosation. The reaction mixture was treated with Amberlite IR-120 (H+ form) to remove sodium cation therefrom. The reaction mixture so treated was then concentrated by distillation under reduced pressure at a temperature of less than 30° C to remove the solvent, so that a crystalline product was deposited. This crystalline product was collected by filtration and washed with n-propanol, affording 180 mg of the titled compound. Yield 78%. mp. 103° C (with decomposition). [α]D26 -12.6° (c 0.99, H2O).
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[C:6]([CH3:8])([CH3:7])[O:5][BH:4][O:3]1.[CH2:10]([O:12][C:13]#[CH:14])[CH3:11]>ClCCl.[Cl-].C1([Zr+2]C2C=CC=C2)C=CC=C1.[Cl-]>[CH2:13]([O:12]/[CH:10]=[CH:11]/[B:4]1[O:5][C:6]([CH3:8])([CH3:7])[C:2]([CH3:9])([CH3:1])[O:3]1)[CH3:14]
Reactant: CC1(C)OBOC1(C)C
Reactant: C#COCC
Agent: C1=CC([Zr+2]C2C=CC=C2)C=C1
Agent: [Cl-]
Solvent: ClCCl
Product: CCO/C=C/B1OC(C)(C)C(C)(C)O1
Temperature: 25 °C
Reaction time: 16 h
Yield: 78 %

Procedure:
Di(cyclopenta-2,4-dien-1-yl)zirconium(IV) chloride (0.685 g, 2.344 mmol) was added to a solution of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.0 g, 39.1 mmol) in dichloromethane (15 mL) followed by ethoxyethyne (3.01 g, 43.0 mmol) at 0° C., and the mixture was stirred for 16 h at 25° C. Insoluble solids were filtered off, and filtrate was concentrated. Residue was partitioned between ethyl acetate and water. Organic layer was separated, washed with brine, dried over sodium sulphate, filtered and concentrated in vacuo to afford title compound (6.04 g, 78.13%) as oil. 1H NMR (400 MHz, CDCl3): δ 7.04 (d, J=14.0 Hz, 1H), 4.43 (d, J=14.8 Hz, 1H), 3.84 (q, J=7.2 Hz, 2H), 1.32-1.2 (m, 15H).
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[NH:12]1)[CH2:8]2.[Br:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH2:21]Br>>[Br:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH2:21][N:12]1[C:13]([CH3:17])([CH3:16])[C:14](=[O:15])[N:11]1[CH:2]1[CH:3]2[CH2:4][CH:5]3[CH2:6][CH:7]([CH2:8][CH:1]1[CH2:10]3)[CH2:9]2
Reactant: BrCc1ccccc1Br
Reactant: CC1(C)NN(C2C3CC4CC(C3)CC2C4)C1=O
Product: CC1(C)C(=O)N(C2C3CC4CC(C3)CC2C4)N1Cc1ccccc1Br

Procedure:
2-(Adamantan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one and 2-bromobenzyl bromide were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a white crystalline powder.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([OH:17])=[CH:15][CH:14]=1.[OH-].[K+]>[Cu]>[CH3:11][O:12][C:13]1[CH:19]=[CH:18][C:16]([O:17][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Reactant: COc1ccc(O)cc1
Agent: [Cu]
Agent: [K+]
Agent: [OH-]
Product: COc1ccc(Oc2ccc([N+](=O)[O-])cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 30.9 %

Procedure:
4-Bromonitrobenzene (4.0 g), hydroquinone monomethyl ether (3.1 g), potassium hydroxide (1.5 g) and copper powder (0.1 g) were mixed and the reaction was carried out at 160° C. to 200° C. for 3 hours. After cooling to room temperature, the reaction mixture was extracted with benzene (100 ml), and the extract was washed with 1N sodium hydroxide, water, and saturated aqueous sodium chloride. After drying over magnesium sulfate, the solvent was evaporated under a reduced pressure and the residue obtained was purified by medium pressure column chromatography using silica gel, to obtain 4-(4-nitrophenoxy)phenol methyl ether (1.5 g).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH2:5][N:6]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].Br[CH2:22][CH2:23][CH2:24][CH2:25][B:26]1[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:34])([CH3:33])[O:27]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(OCC)(=O)C>[C:8]1([C:7](=[N:6][CH:5]([CH2:22][CH2:23][CH2:24][CH2:25][B:26]2[O:30][C:29]([CH3:32])([CH3:31])[C:28]([CH3:33])([CH3:34])[O:27]2)[C:4]([O:3][CH2:1][CH3:2])=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(=O)CN=C(c1ccccc1)c1ccccc1
Reactant: CC1(C)OB(CCCCBr)OC1(C)C
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)C(CCCCB1OC(C)(C)C(C)(C)O1)N=C(c1ccccc1)c1ccccc1
Temperature: 50 °C
Yield: 64.3 %

Procedure:
A solution of N-(diphenylmethylene)glycine ethyl ester (8.24 g, 30.8 mmol) and 2-(4-bromobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.92 g, 33.9 mmol) in freshly distilled THF (77 mL, 0.4 M) was cooled to −78° C. and treated with lithium bis(trimethylsilyl)amide (32.3 mL, 1.0 M in THF). Once the addition was complete, the reaction was warmed to 50° C. and heated for 8 h. After being complete by TLC, the reaction mixture was cooled to 0° C., diluted with ethyl acetate and washed successively with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Rapid purification by MPLC (1-15% ethyl acetate in heptane with 0.5% triethylamine over 6 CV) gave ethyl 2-(diphenylmethyleneamino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate as a colorless oil (8.9 g, 64%). Rf 0.40 (30% ethyl acetate in heptane).
Reaction SMILES: C([NH:8][CH:9]1[CH2:18][CH2:17][C:12]2([O:16][CH2:15][CH2:14][O:13]2)[CH2:11][CH2:10]1)C1C=CC=CC=1>CCO>[O:13]1[C:12]2([CH2:17][CH2:18][CH:9]([NH2:8])[CH2:10][CH2:11]2)[O:16][CH2:15][CH2:14]1
Reactant: c1ccc(CNC2CCC3(CC2)OCCO3)cc1
Solvent: CCO
Product: NC1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 8 h
Yield: 81.9 %

Procedure:
Benzyl-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine (6.4 mmol) was dissolved in EtOH (10 ml) and hydrogenated under nitrogen with Pd(C) 340 mg (0.32 mmol) with stirring overnight at RT. The reaction mixture was filtered out over Celite and washed with CH2Cl2. After removal of the solvent, the product 1,4-dioxa-spiro[4.5]dec-8-ylamine 824 mg (82% of theoretical) was obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH:12]([N:14]1[CH2:19][CH2:18][N:17]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:16][CH2:15]1)[CH3:13])[N:6]([CH3:31])[C:5]2=[O:32].[C:33](Cl)(=[O:35])[CH3:34]>CN(C=O)C>[CH3:30][O:29][C:26]1[CH:27]=[CH:28][C:23]([S:20]([N:17]2[CH2:16][CH2:15][N:14]([CH:12]([C:7]3[N:6]([CH3:31])[C:5](=[O:32])[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:33](=[O:35])[CH3:34])[CH:3]=4)[N:8]=3)[CH3:13])[CH2:19][CH2:18]2)(=[O:22])=[O:21])=[CH:24][CH:25]=1
Reactant: COc1ccc(S(=O)(=O)N2CCN(C(C)c3nc4ccc(N)cc4c(=O)n3C)CC2)cc1
Reactant: CC(=O)Cl
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)N2CCN(C(C)c3nc4ccc(NC(C)=O)cc4c(=O)n3C)CC2)cc1
Reaction time: 2 h
Yield: 15.1 %

Procedure:
To the 1 ml DMF solution of 6-Amino-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-3H-quinazolin-4-one (50.0 mg, 0.11 mmol) was added acetyl chloride (9.44 mg, 0.12 mmol). The reaction was stirred for 2 hours. The solvent was removed by reduce pressure and extracted with Na2CO3 aqueous and ethyl acetate, dried over anhydrous MgSO4, and concentrated by rotary evaporation. Purification was accomplished by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase). The product was collected and dried under reduced pressure to give the N-(2-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3-methyl-4-oxo-3,4-dihydro-quinazolin-6-yl)-acetamide (Yield 8.29 mg, 14.9%). 1H NMR (400 MHz, MeOD-d4): δ 1.70 (d, 3H, J=6.57 Hz), 2.18 (s, 3H), 3.57-3.43 (m, 8H), 3.64 (s, 3H), 3.93 (s, 3H), 4.84 (q, 1H, J=6.57, 6.06 Hz), 7.19 (d, 2H, J=9.09 Hz), 7.64 (d, 1H, J=8.34 Hz), 7.79 (d, 2H, J=9.09 Hz), 7.98 (dd, 1H, J=8.59, 2.78 Hz), 8.46 (d, J=2.27 Hz). MS m/z calc. 499.2 found (ESI); 500.2 (M+1)+. Retention time 2.42 minutes.