Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[Si](C)(C)C.BrCCBr.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1.ClCCl.Br[C:26]1[CH:27]=[CH:28][C:29]2[O:38][CH2:37][CH2:36][C:35]3[S:34][C:33]([C:39]4[N:40]([CH:44]([CH3:46])[CH3:45])[N:41]=[CH:42][N:43]=4)=[N:32][C:31]=3[C:30]=2[CH:47]=1>CC(N(C)C)=O.[Zn].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[C:18]([O:17][C:15]([N:13]1[CH2:14][CH:11]([C:26]2[CH:27]=[CH:28][C:29]3[O:38][CH2:37][CH2:36][C:35]4[S:34][C:33]([C:39]5[N:40]([CH:44]([CH3:45])[CH3:46])[N:41]=[CH:42][N:43]=5)=[N:32][C:31]=4[C:30]=3[CH:47]=2)[CH2:12]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)OC(=O)N1CC(I)C1
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(Br)cc1-2
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: [Fe+2]
Solvent: CC(=O)N(C)C
Solvent: ClCCl
Solvent: BrCCBr
Product: CC(C)n1ncnc1-c1nc2c(s1)CCOc1ccc(C3CN(C(=O)OC(C)(C)C)C3)cc1-2
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Zinc (151 mg, 2.31 mmol) was stirred in DMA (0.4 mL) under an atmosphere of argon. Chlorotrimethylsilane (25 uL, 0.20 mmol) and 1,2-dibromoethane (20 uL, 0.2 mmol) were added (gentle exotherm) and the mixture stirred at room temperature for 15 min. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (0.5 g, 1.8 mmol) in DMA (1 mL) was introduced and the reaction was allowed to stir at room temperature for an additional 30 min. Meanwhile, [1,1′-Bis(diphenylphosphino)ferrocen]dichloropalladium(II), in complex with dichloromethane (1:1) (68 mg, 0.083 mmol), copper(I) iodide (32 mg, 0.166 mmol) and 9-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene from Example 6 (0.65 g, 1.66 mmol) were mixed in DMA (2.5 mL) and stirred under argon for 10 min. Subsequently, the organozinc reagent solution was transferred to this mixture via syringe. The resulting green reaction mixture was stirred at 80° C. whereupon it turned yellow. Stirring was continued for 20 h. At this point, LCMS indicated approximately 33% conversion to the title compound. The mixture was diluted with EtOAc (25 mL) and 1 N HCl (25 mL) and the layers were partitioned. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic portions were washed once with brine. The extract was dried over MgSO4 and concentrated in vacuo. The residue was purified by rp-HPLC to give 236 (35 mg, 5% yield). LC/MS (ESI+): m/z 468.2 (M+H). 1H NMR (400 MHz, DMSO) δ 1.22 8.47 (d, J=2.0 Hz, 1H), 8.10 (s, 1H), 7.20 (dd, J=8.2, 2.1 Hz, 1H), 7.03 (d, J=8.2 Hz, 1H), 5.84 (dt, J=13.2, 6.5 Hz, 1H), 4.35 (dd, J=17.3, 12.5 Hz, 4H), 3.82 (s, 3H), 3.44 (t, J=4.9 Hz, 2H), 1.58 (t, J=9.5 Hz, 6H), 1.41 (s, 9H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[N-:11]=[N+:12]=[N-:13].[Na+]>CN(C)C=O.O>[N:11]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[N+:12]=[N-:13]
Reactant: CCOC(=O)CCCCBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCN=[N+]=[N-]
Yield: 95 %

Procedure:
Ethyl 5-bromovalerate (2.1 g; 10 mmol; Aldrich) was added to a stirred suspension of sodium azide (1.3 g, 20 mmol; Fisher) in 5 ml dimethylformamide and 5 ml water, and the reaction mixture was heated 12 h at 80° Cs. The reaction was partitioned between diethyl ether (100 ml) and water (100 ml), and the resulting organic layer was washed with water (100 ml) and brine (100 ml), dried over sodium sulfate, and dried in vacuo. Yield: 1.6 g (9.3 mmol, 95% yield).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[C:9]1([C@H:15]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33]OS(C)(=O)=O)=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH3:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH:39]1[CH2:42][CH2:41][CH2:40]1>C(#N)C.C(Cl)Cl.CO>[C:9]1([C@H:15]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:31][CH2:32][CH2:33][N:39]4[CH2:42][CH2:41][CH2:40]4)=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH3:16])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: C[C@@H](Nc1ncnc2cc(OCCOS(C)(=O)=O)c([N+](=O)[O-])cc12)c1ccccc1
Reactant: C1CNC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CO
Solvent: ClCCl
Product: C[C@@H](Nc1ncnc2cc(OCCN3CCC3)c([N+](=O)[O-])cc12)c1ccccc1
Temperature: 70 °C

Procedure:
221 mg of dried potassium carbonate and 50 mg of sodium iodide were given to 600 mg of 4-[(R)-(1-phenylethyl)amino]-7-[2-methanesulfonyloxyethoxy]-6-nitroquinazoline and 0.34 ml of azetidine in 5.0 ml of acetonitrile. The reaction mixture was heated up to 70° C. with stirring. Subsequently 3 ml of acetonitrile were added after one hour and the mixture was stirred for further about 40 hours at 70° C. The solvent was removed in vacuo and the obtained residue was mixed with ice water. The precipitate was suction filtered and dried. The aqueous phase was extracted with methylene chloride and evaporated. The combined precipitates were dissolved in ethyl acetate and stirred together with a little of silica gel and 120 mg of charcoal for further purification. The obtained suspension was filtered and evaporated yielding a yellow resin. Yield: 518 mg (95% of theory); Rf value: 0.40 (silica gel, methylene chloride/methanol/concentrated aqueous ammonia solution=90:10:0.1); mass spectrum (ESI+): m/z=394 [M+H]+.
Reaction SMILES: C[O:2][C:3]([C:5]1[O:6][C:7]2[CH:13]=[C:12]([CH2:14][CH2:15][CH2:16][CH3:17])[CH:11]=[CH:10][C:8]=2[CH:9]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>CCOCC>[CH2:14]([C:12]1[CH:11]=[CH:10][C:8]2[CH:9]=[C:5]([CH2:3][OH:2])[O:6][C:7]=2[CH:13]=1)[CH2:15][CH2:16][CH3:17]
Reactant: CCCCc1ccc2cc(C(=O)OC)oc2c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CCCCc1ccc2cc(CO)oc2c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 81.6 %

Procedure:
Methyl-6-butylbenzofuran-2-carboxylate (118 mg, 0.51 mmol) was dissolved in 2 mL of anhydrous ether, flushed with argon and cooled to 0° C. Powdered lithium aluminum hydride (21 mg, 0.56 mmol) was added and the resulting suspension stirred vigorously for 2 h at 0° C. The mixture was poured into 25 mL of 1 N hydrochloric acid and extracted with ether (3×20 mL). The combined ether extracts were dried over magnesium sulfate, filtered and concentrated. The crude mixture was subjected to chromatography on silica gel with gradient elution (5-20% ethyl acetate in hexanes) to give (6-butylbenzofuran-2-yl)methanol (85 mg, 82%) as an oil. Used without further characterization.
Reaction SMILES: COCCOCCN(CCOCCOC)CCOCCOC.Br[C:24]1[C:25](I)=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([OH:29])=[O:28].C[C:35]1[C:40](C)=[CH:39][CH:38]=[CH:37][C:36]=1[OH:42]>Cl[Cu]>[O:42]([C:25]1[CH:24]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([OH:29])=[O:28])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:35]=1
Reactant: Cc1cccc(O)c1C
Reactant: O=C(O)c1cccc(Br)c1I
Agent: Cl[Cu]
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Product: O=C(O)c1ccccc1Oc1ccccc1

Procedure:
As shown in the Scheme, at the presence of 10% by mole of CuCl and 10% by mole of tris(2-(2-methoxyethoxy)ethyl) amine (TDA-1), 3-bromo-2-iodo benzoic acid was contacted with 2,3-dimethylphenol to yield phenoxybenzoic acid. Without purification, the phenoxybenzoic acid was directly dehydrated and cyclized by reagents such as sulfuric acid, methanesulfonic acid, polyphosphoric acid, or polyphosphate to yield dimethylxanthone. Diethyl malonate was arylated by the dimethylxanthone under catalysis of palladium to yield 5,6-dimethylxanthone-4-ethyl acetate which was hydrolyzed to yield DMXAA.
Reaction SMILES: N(C(OCC)=O)=N[C:3](OCC)=[O:4].[CH3:13][C:14]([O:17][C:18](=[O:26])[NH:19][C@H:20]1[CH2:24][CH2:23][C@@H:22]([OH:25])[CH2:21]1)([CH3:16])[CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O>>[CH3:16][C:14]([O:17][C:18](=[O:26])[NH:19][C@H:20]1[CH2:24][CH2:23][C@H:22]([O:25][CH:3]=[O:4])[CH2:21]1)([CH3:13])[CH3:15]
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](O)C1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O=CO
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](OC=O)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 50.1 %

Procedure:
Diethyl azodicarboxylate (0.164 ml, 1.23 mmol) was added dropwise to a stirred solution of (1S-cis)-(3-hydroxycyclopentyl)carbamic acid 1,1-dimethylethyl ester (0.124 g, 0.61 mmol), triphenylphosphine (0.323 g, 1.23 mmol) and formic acid (0.046 ml, 1.23 mmol) and the solution was stirred at room temperature for 2h. The solution was then concentrated and purified by column chromatography on flash silica eluting with 10-30% ethyl acetate in cyclohexane to give the title compound (0.07 g) as white needles from diisopropyl ether m.p.84-85° C., [α]D -12.7° (CHCl3 c=0.55%).
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[CH2:4][O:5][C:6]1[CH:17]=[CH:16][C:9]2[C@H:10]([CH2:13][CH2:14]O)[CH2:11][O:12][C:8]=2[CH:7]=1.C1COCC1.CS(Cl)(=O)=O.[C:33](=[S:36])([O-:35])[CH3:34].[K+]>CN(C=O)C.CCN(CC)CC>[C:33](=[O:35])([S:36][CH2:14][CH2:13][C@H:10]1[C:9]2[CH:16]=[CH:17][C:6]([O:5][CH2:4][C:3]3[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:2]=3[Cl:1])=[CH:7][C:8]=2[O:12][CH2:11]1)[CH3:34]
Reactant: OCC[C@@H]1COc2cc(OCc3ccc(Cl)cc3Cl)ccc21
Reactant: CC([O-])=S
Agent: CS(=O)(=O)Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(=O)SCC[C@@H]1COc2cc(OCc3ccc(Cl)cc3Cl)ccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.9 %

Procedure:
To a mixture of 2-((3S)-6-((2,4-dichlorobenzyl)oxy)-2,3-dihydro-1-benzofuran-3-yl)ethanol (678 mg) and THF (dry) (20 mL) were added methanesulfonyl chloride (0.310 mL) and Et3N (0.279 mL). The mixture was stirred at room temperature for 30 min. And then DMF (dry) (20.00 mL) and potassium ethanethioate (228 mg) were added to the mixture. The volatiles (THF) were removed by evaporation. The resulting mixture was stirred at 70° C. for 2 h. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (570 mg).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([O:26][C@@H:27]1[C@@H:32]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@H:31]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:30]([CH2:49][O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:29][C@H:28]1[C:58]1[CH:63]=[CH:62][CH:61]=[C:60]([CH2:64][O:65][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:59]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[OH-].[Na+].O>C1COCC1>[CH2:19]([O:26][C@@H:27]1[C@@H:32]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C@H:31]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:30]([CH2:49][O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:29][C@H:28]1[C:58]1[CH:63]=[CH:62][CH:61]=[C:60]([CH2:64][OH:65])[CH:59]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)(C)[Si](OCc1cccc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c1)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cccc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c1
Reaction time: 2 h
Yield: 56.7 %

Procedure:
A 1.0 M THF solution of tetrabutylammonium fluoride (3.8 ml) was added to a solution of (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[3-([[t-butyl(diphenyl)silyl]oxy]methyl) phenyl]-D-glucitol (1.7 g) in THF (10.0 ml) at room temperature and the mixture was stirred for two hours. 10% aqueous solution of sodium hydroxide (3.0 ml) was further added to the reaction mixture and the mixture was refluxed with stirring for one hour. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[3-(hydroxymethyl)phenyl]-D-glucitol (0.7 g).
Reaction SMILES: [CH2:1]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[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].[OH:30]O>C(O)CC>[CH2:16]([N:15]([CH2:1][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])[OH:30])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCCCCCCCNCCCCCCCCCCCCCC
Reactant: OO
Solvent: CCCO
Product: CCCCCCCCCCCCCCN(O)CCCCCCCCCCCCCC

Procedure:
The general procedure of Example 5 is followed using, at 50 to 55° C., 50 grams (0.12 mol) of ditetradecylamine, 200 ml of n-propanol and 8.3 grams (0.12 mol) of 50% aqueous hydrogen peroxide solution. The above-named product is obtained in a yield of 33.4 grams (64%) as white needles melting at 97-99° C.
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]=1[C:21](=[O:26])[C:22]([F:25])([F:24])[F:23].C(=O)([O-])[O-].[K+].[K+].[CH2:33](Br)[CH:34]=[CH2:35].O>CN(C)C=O>[C:19]([C:4]1[C:3]([C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])=[C:2]([NH:1][CH2:35][CH:34]=[CH2:33])[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:15])([F:16])[F:17])=[CH:9][C:8]=2[Cl:18])[N:5]=1)#[N:20]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1C(=O)C(F)(F)F
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCNc1c(C(=O)C(F)(F)F)c(C#N)nn1-c1c(Cl)cc(C(F)(F)F)cc1Cl
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoroacetylpyrazole (1 g) in anhydrous N,N-dimethylformamide (4 ml) at room temperature was added potassium carbonate (0.7 g), then allyl bromide (165 μl). The mixture was stirred at room temperature for 40 minutes. Water (50 ml) was then added, and the mixture was extracted with ether (50 ml, ×2). The combined organic layers were washed with water (50 ml), dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography on silica gel (50 g) eluted with dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a very pale yellow/white solid, m.p 115-116° C.
Reaction SMILES: [CH2:1]([N:3]([CH2:36][CH3:37])[CH2:4][CH2:5][CH2:6][NH:7][C:8]1[N:9]=[C:10]([C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=2)[C:30](O)=[O:31])[C:11]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:12]=2[N:13]=1)[CH3:2].CN(C(O[N:46]1N=N[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.NC1C=CC=CC=1>CN(C=O)C>[CH2:1]([N:3]([CH2:36][CH3:37])[CH2:4][CH2:5][CH2:6][NH:7][C:8]1[N:9]=[C:10]([C:27]2[CH:28]=[C:29]([CH:33]=[CH:34][CH:35]=2)[C:30]([NH:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:31])[C:11]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=3[F:25])[C:12]=2[N:13]=1)[CH3:2]
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CCN(CC)CCCNc1nc(-c2cccc(C(=O)O)c2)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: Nc1ccccc1
Solvent: CCN(CC)CC
Product: CCN(CC)CCCNc1nc(-c2cccc(C(=O)Nc3ccccc3)c2)c2ccc(=O)n(-c3c(F)cccc3F)c2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.2 %

Procedure:
To the compound 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]benzoic acid (30 mg, 0.06 mmol) in DMF (0.5 mL) were added HBTU (27 mg, 0.072 mmol), triethylamine (16.9 uL, 0.12 mmol) and aniline (8.21 uL, 0.09 mmol). The mixture was stirred at rt overnight. Separation by HPLC with TFA, followed by neutralization with SPE amine cartridge afforded the title compound (17.2 mg, 49%). LC-MS m/z 583 (M+H)+.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[S:5][C@H:6]2[O:12][C@H:11]([C:13](N(OC)C)=[O:14])[C@@H:10]([OH:19])[C@H:9]([OH:20])[C@H:7]2[N:8]=1)[CH3:2].C([AlH]CC(C)C)C(C)C>C1(C)C=CC=CC=1.O1CCCC1>[CH2:1]([NH:3][C:4]1[S:5][C@H:6]2[O:12][C@H:11]([CH:13]=[O:14])[C@@H:10]([OH:19])[C@H:9]([OH:20])[C@H:7]2[N:8]=1)[CH3:2]
Reactant: CCNC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](C(=O)N(C)OC)O[C@@H]2S1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCNC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](C=O)O[C@@H]2S1
Temperature: -78 °C
Reaction time: 3 h

Procedure:
In a dry sealed vial was added (3aR,5S,6S,7R,7aR)-2-(ethylamino)-6,7-dihydroxy-N-methoxy-N-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]thiazole-5-carboxamide (70.00 mg; 0.23 mmol; 1.00 eq.) in toluene (1.00 ml) and tetrahydrofuran (1.00 ml). The clear solution was cooled to −78° C. before hydrido(diisobutyl)aluminum (962.81 μl; 1.00 M; 0.96 mmol; 4.20 eq.) was added slowly. The obtained solution was stirred at −78° C. for 3 h before the reaction was quenched by addition of 1 mL H2O at −78° C. The obtained mixture was stirred at this temperature for 5 min before it is warmed up to room temperature. The mixture was filtered and the obtained filtrated was dried with lyophilize to afford the title compound as white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]([C:20]3[NH:29][C:28](=O)[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[CH3:19])[CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:33])=O>>[Cl:33][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([CH:18]([N:15]2[CH2:16][CH2:17][N:12]([S:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)(=[O:11])=[O:10])[CH2:13][CH2:14]2)[CH3:19])[N:29]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc(S(=O)(=O)N2CCN(C(C)c3nc4ccccc4c(=O)[nH]3)CC2)cc1
Product: COc1ccc(S(=O)(=O)N2CCN(C(C)c3nc(Cl)c4ccccc4n3)CC2)cc1
Temperature: 90 °C
Yield: 100 %

Procedure:
In a flask containing of 2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one (380.0 mg, 0.89 mmol) in phosphorus oxychloride (20 ml) was heated to 90° C. for 2 hours, then the solvent was concentrated under reduced pressure to give 4-Chloro-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-quinazoline (Yield 394.2 mg, 100%) that was used directly without further purification. 1H NMR (400 MHz, CDCl-3): δ 1.93 (d, 3H, J=6.82 Hz), 3.23-3.04 (m, 3H), 3.54-3.34 (m, 1H), 3.87-3.65 (m, 4H), 3.90 (s, 3H), 4.77 (q, 1H, J=14.15, 6.82 Hz), 7.05 (d, 2H, J=8.84), 7.69 (d, 2H, J=8.84), 7.87 (t, H, J=7.84), 8.10 (t, 1H, J=8.34 Hz), 8.18 (d, 1H, 8.34 Hz), 8.35 (d, 1H, 8.34 Hz). MS m/z calc. 446.12, found (ESI); 447.4 (M+1)+. Retention time 2.67 minutes.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9](=O)[CH3:10])=[CH:4][C:3]=1[CH3:12].Cl.[NH2:14][O:15][CH2:16][CH2:17][O:18][C:19]1[CH:32]=[CH:31][C:22]([CH2:23][CH:24]2[S:28][C:27](=[O:29])[NH:26][C:25]2=[O:30])=[CH:21][CH:20]=1>>[OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9](=[N:14][O:15][CH2:16][CH2:17][O:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:23][CH:24]3[S:28][C:27](=[O:29])[NH:26][C:25]3=[O:30])=[CH:31][CH:32]=2)[CH3:10])=[CH:4][C:3]=1[CH3:12]
Reactant: CC(=O)c1cc(C)c(O)c(C)c1
Reactant: NOCCOc1ccc(CC2SC(=O)NC2=O)cc1
Agent: Cl
Product: CC(=NOCCOc1ccc(CC2SC(=O)NC2=O)cc1)c1cc(C)c(O)c(C)c1
Yield: 55.8 %

Procedure:
Following a procedure similar to that described in Example 46, but using 0.22 g of 4'-hydroxy-3',5'-dimethylacetophenone and 0.40 g of 5-[4-(2-aminooxyethoxy)benzyl]thiazolidine-2,4-dione hydrochloride [prepared as described in Example 40(e)], 0.30 g of the title compound was obtained as an amorphous powder, melting at 53-65° C. (softening point).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:10][C@H:9]2[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:4][N:3]=1.[CH:16]([NH2:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:16]([NH:19][C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:10][C@H:9]2[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:4][N:3]=1)([CH3:18])[CH3:17]
Reactant: CCOC(=O)[C@@H]1C[C@H]1c1ccnc(Cl)c1
Reactant: CC(C)N
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CCOC(=O)[C@@H]1C[C@H]1c1ccnc(NC(C)C)c1
Temperature: 100 °C
Reaction time: 14 h
Yield: 36 %

Procedure:
To a dioxane (5 mL) solution of ethyl trans-2-(2-chloropyridin-4-yl)cyclopropanecarboxylate (250 mg, 1.1 mmol) and isopropylamine (393 mg, 6.7 mmol) were added cesium carbonate (1.1 g, 3.3 mmol), Xantophos (224 mg, 0.4 mmol) and palladium acetate (50 mg, 0.2 mmol) at room temperature respectively. The mixture was sealed and stirred at 100 ° C. for 14 hours. After being filtered off, the filtrate was concentrated under reduced pressure, the residue was applied to a silica gel chromatography column and eluted with a hexane/ethyl acetate =6/1 to furnish 100 mg (36% yield) of the title as a colorless oil.
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6]/[C:7](=[CH:9]/[CH2:10][OH:11])/[CH3:8])[CH3:3].[CH3:12][C:13]([CH3:17])=[CH:14][CH:15]=O.C(O)(=O)CC>>[CH3:12][C:13]([CH3:17])=[CH:14][CH2:15][CH2:3]/[C:2](/[CH3:1])=[CH:4]/[CH2:5][CH2:6]/[C:7](/[CH3:8])=[CH:9]/[CH:10]=[O:11]
Reactant: CC(C)=CCC/C(C)=C/CO
Reactant: CC(C)=CC=O
Solvent: CCC(=O)O
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/C=O
Yield: 84 %

Procedure:
100 parts of geraniol, 30 parts of 3,3-dimethylacrolein and 2.5 parts of propionic acid are heated together at refluxing temperature for four hours while stirring. The product is distilled. 83.5 parts of farnesal is obtained having a boiling point of 120° to 123°C at 0.2 mm. The yield is 84% of theory at a conversion of 63% (based on 3,3-dimethylacrolein).
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8].Cl[C:10]([O:12][CH2:13][CH:14]=[CH2:15])=[O:11].C(N(CC)CC)C>O1CCCC1>[C:10](=[O:11])([O:1][N:2]1[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8])[O:12][CH2:13][CH:14]=[CH2:15]
Reactant: C=CCOC(=O)Cl
Reactant: O=C1CCC(=O)N1O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C=CCOC(=O)ON1C(=O)CCC1=O
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A mixture of N-hydroxysuccinimide (4.78 g, 0.042 mol) and allyl chloroformate (5.0 g, 4.40 ml, 0.042 mmol) in dry tetrahydrofuran (60 ml) was cooled to 0° C. under nitrogen. A solution of triethylamine (4.2 g, 5.78 ml, 0.042 mol) in tetrahydrofuran (20 ml) was added dropwise over 20 minutes. After completion of the addition, the mixture was stirred at room temperature for 4 hours, and then filtered and concentrated. Ethyl acetate (200 ml) was added and the resulting solution was washed sequentially with water (3×), saturated sodium bicarbonate solution and water (3×). Drying (MgSO4) and removal of the solvent in vacuo gave the title compound as a clear, colourless oil. (D23).
Reaction SMILES: [N+](=[C:3]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[N-].[CH3:17][OH:18]>C1C=CC=CC=1.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.[Rh].[Rh]>[OH:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][CH:3]([O:18][CH3:17])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:11][CH:12]=1
Reactant: CO
Reactant: CCOC(=O)C(Cc1ccc(O)cc1)=[N+]=[N-]
Agent: [Rh]
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CCOC(=O)C(Cc1ccc(O)cc1)OC
Temperature: 25 °C

Procedure:
A solution of ethyl 2-diazo-3-(4-hydroxyphenyl)propanoate (c.f. N. Takamura and T. Mizoguchi, Tetrahedron Lett. 1971, 4495) (8.8 g) in benzene (40 mL) was added over 30 minutes to a stirred, refluxing mixture of rhodium (II) acetate dimer (10 mg), methanol 7.9 mL) and benzene (50 mL). The mixture was heated at reflux for a further 30 minutes, then allowed to cool to room temperature overnight and washed with water (2×200 mL). The benzene solution was dried (MgSO4) and evaporated and the residual oil chromatographed twice on silica gel, firstly with 20% ethyl acetate in hexane as eluent and subsequently with 4% ethyl acetate in dichloromethane as eluent to afford the title compound as an oil.