Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[K+].[OH:3][C:4]1([CH2:16][OH:17])[CH2:8][S:7][C:6](=[S:9])[N:5]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.Cl>O.C(#N)C>[N:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:5][C:6](=[S:9])[S:7][CH2:8][CH:4]([OH:3])[CH2:16][OH:17]
Reactant: OCC1(O)CSC(=S)N1c1ccccn1
Agent: Cl
Agent: [BH4-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: OCC(O)CSC(=S)Nc1ccccn1
Temperature: 2 °C
Reaction time: 0.5 h
Yield: 42.5 %

Procedure:
A solution of potassium borohydride (5.4 g) in distilled water (35 cc) is added, at a maximum of 20° C., to a suspension of 4-hydroxy-4-hydroxymethyl-3-(pyrid-2-yl)-thiazolidine-2-thione (23.8 g) in anhydrous acetonitrile (240 cc). The reaction is allowed to proceed for 30 minutes at 20° C. An 8.5 N aqueous solution of hydrochloric acid (12 cc) is added at a maximum of 20° C. The acetonitrile is evaporated off under reduced pressure (20 mm Hg) at 45° C. The aqueous phase is extracted 3 times with chloroform (500 cc in total). The organic solution is washed with distilled water (100 cc), dried over sodium sulphate and evaporated. The resulting product (21.2 g) is purified by crystallisation from a mixture of methylene chloride (100 cc) and isopropyl ether (50 cc). After drying in the atmosphere for 16 hours, yellow crystals (13 g), which melt at 96° C., are obtained and these are purified again by recrystallisation from a boiling mixture of acetonitrile (75 cc) and isopropyl ether (20 cc). After filtering the boiling solution and then cooling for 2 hours at 2° C., the crystals which have appeared are filtered off, washed with an ice-cooled mixture (25 cc in total) of acetonitrile (20 cc) and isopropyl ether (5 cc) and dried under reduced pressure (0.1 mm Hg) at 45° C. 2,3-Dihydroxy-propyl pyrid-2-yldithiocarbamate (10.2 g), which melts at 98° C., is thus obtained.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[C:12]([CH3:15])[CH:13]=[O:14])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]=[C:12]([CH3:15])[CH2:13][OH:14])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C=O)=Cc1ccc(C(C)(C)C)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(=Cc1ccc(C(C)(C)C)cc1)CO
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
404.5 g of 3-(p-tert.butyl-phenyl)-2-methyl-acrolein are dissolved in 2500 ml of methanol and treated portionwise with 38 g of sodium borohydride while cooling with ice. Subsequently, the mixture is stirred at room temperature for 2.5 hours, poured into 2500 ml of ice-cold 2-N hydrochloric acid and exhaustively extracted with hexane. The combined hexane extracts are washed neutral with water, dried over sodium sulphate and evaporated. Vacuum distillation yields pure 3-(p-tert.butyl-phenyl)-2-methyl-allyl alcohol of boiling point 119° C./0.005 Torr.
Reaction SMILES: [CH3:1][C:2]1(O)[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1.CCN(S(F)(F)[F:33])CC>ClCCl>[F:33][C:2]1([CH3:1])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(C)(O)CC3)c(F)c2)C(=O)O1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCC(C)(F)CC3)c(F)c2)C(=O)O1
Yield: 66 %

Procedure:
The title compound was prepared by stirring (S)-N-{3-[4-(4-methyl-4-hydroxypiperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.36 mmol) with DAST (1.64 mmol) in dichloromethane (10 ml) at a temperature 0° C. for half hour and by purifying the compound by silica gel column chromatography in 66% yield.
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:37])[CH2:16][C:17](=[O:36])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])=[C:22]([O:34][CH3:35])[CH:21]=2)=[CH:11][C:10]=1[O:38][CH3:39])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Na].[CH3:41]I>C(OCC)C>[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:37])[CH:16]([CH3:41])[C:17](=[O:36])[CH:18]=[CH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][Si:27]([C:30]([CH3:31])([CH3:32])[CH3:33])([CH3:28])[CH3:29])=[C:22]([O:34][CH3:35])[CH:21]=2)=[CH:11][C:10]=1[O:38][CH3:39])([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]
Reactant: CI
Reactant: COc1cc(/C=C/C(=O)CC(=O)c2ccc(O[Si](C)(C)C(C)(C)C)c(OC)c2)ccc1O[Si](C)(C)C(C)(C)C
Agent: [Na]
Solvent: CCOCC
Product: COc1cc(C=CC(=O)C(C)C(=O)c2ccc(O[Si](C)(C)C(C)(C)C)c(OC)c2)ccc1O[Si](C)(C)C(C)(C)C
Reaction time: 18 h
Yield: 66.7 %

Procedure:
To a solution of (E)-1,5-bis(4-tert-butyldimethylsilyloxy-3-methoxyphenyl)-pent-4-ene-1,3-dione (459 mg, 0.80 mmol) in anhydrous diethyl ether (8 ml) was added sodium (20 mg, 0.88 mmol). The mixture was stirred for 18 h, when all the sodium had been consumed, forming a yellow solid. The diethyl ether was removed under vacuum, and the yellow oily solid was dissolved in acetone (8 ml). Methyl iodide (45 μl, 0.72 mmol) was added to this mixture and stirred overnight at room temperature. The acetone was removed under vacuum, and the residue was taken up in ethyl acetate, washed with water, dried (MgSO4 (anh)), filtered and concentrated in vacuo. The residue was purified on silica gel column using dichloromethane/petroleum ether (1:1 to 1:0) to give 1,5-bis(4-tert-butyldimethylsilyloxy-3-methoxyphenyl)-2-methylpent-4-ene-1,3-dione (281 mg, 60%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 0.16 (6H, s, 2×CH3), 0.18 (6H, s, 2×CH3), 0.99 (18H, br s, 2×(CH3)3)), 1.54 (3H, d, J=7.0 Hz, CH3), 3.83 (3H, s, OCH3), 3.85 (3H, s, OCH3), 4.66 (1H, q, J=7.0 Hz, H-2), 6.69 (1H, d, J=16 Hz, H-4), 6.83 (1H, d, J=8.4 Hz, H-5′), 6.87 (1H, d, J=8.4 Hz, H-5′), 7.00 (1H, d, J=2.0 Hz, H-2′), 7.03 (1H, dd, J=8.4, 2.0 Hz, H-6′), 7.53-7.58 (2H, m, ArH), 7.60 (1H, d, J=16.0 Hz, H-5) ppm.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23.[F:22][C:23]1[C:31]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](O)=[O:26].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(Cl)Cl.CO.CN(C)C=O>[F:22][C:23]1[C:31]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:29]=[CH:28][C:24]=1[C:25]([NH:1][C:2]1[CH:3]=[C:4]2[C:20](=[O:21])[NH:19][N:18]=[CH:17][C:6]3=[C:7]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[NH:8][C:9]([CH:10]=1)=[C:5]23)=[O:26]
Reactant: O=C(O)c1cccc(C(F)(F)F)c1F
Reactant: Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O)c1cccc(C(F)(F)F)c1F
Yield: 87.6 %

Procedure:
Preparation of example 41 from the title compound of Example 7 (0.1 g, 0.36 mmol), 2-Fluoro-3-trifluoromethyl-benzoic acid (0.113 g, 0.54 mmol), triethylamine (0.2 mL, 1.45 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.207 g, 0.54 mmol) and N,N-dimethylformamide (0.1 M, 3.6 mL) was carried out analogously to Example 11. Silica gel chromatography (95:5 CH2Cl2/methanol) afforded the title compound (0.147 g) as a yellow powder in 87% yield.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[O:30][CH2:29][C:25]1([CH2:28][O:27][CH2:26]1)[C:5]12[CH2:9][O:8][C:7]([N:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[N:6]1.CC1(C)C(C)(C)OB([C:42]2[CH2:43][CH2:44][O:45][CH2:46][CH:47]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[O:45]1[CH2:44][CH:43]=[C:42]([C:2]2[CH:3]=[C:4]3[C:31](=[CH:32][CH:33]=2)[O:30][CH2:29][C:25]2([CH2:26][O:27][CH2:28]2)[C:5]23[CH2:9][O:8][C:7]([N:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])=[N:6]2)[CH2:47][CH2:46]1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC2(CO1)c1cc(Br)ccc1OCC21COC1
Reactant: CC1(C)OB(C2=CCOCC2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC2(CO1)c1cc(C3=CCOCC3)ccc1OCC21COC1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
A mixture of di-tert-butyl (6′-bromodispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl)imidodicarbonate (300 mg, 0.571 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (360 mg, 1.71 mmol), bis(triphenylphosphine)palladium(II) dichloride (40.1 mg, 0.057 mmol) and Na2CO3 (182 mg, 1.71 mmol) in dioxane (3.6 mL) and water (0.9 mL) was stirred for 1 hour at 100° C. The mixture was cooled down to ambient temperature and partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, diluted with hexane, and filtered through silica gel pad (eluted with 50% EtOAc in hexane). The filtrate was concentrated at reduced pressure to give crude di-tert-butyl [6′-(3,6-dihydro-2H-pyran-4-yl)dispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl]imidodicarbonate which was used for the next reaction without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=1.[O:16]=[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:26])N1C(OCC)=O.C(N(CC)CC)C.O>CN(C=O)C>[O:11]=[C:7]1[CH2:6][C:5]2[C:9](=[CH:10][C:2]([N:1]3[C:17](=[O:16])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:26])=[CH:3][C:4]=2[C:12]([F:15])([F:13])[F:14])[NH:8]1
Reactant: Nc1cc2c(c(C(F)(F)F)c1)CC(=O)N2
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: O=C1Cc2c(cc(N3C(=O)c4ccccc4C3=O)cc2C(F)(F)F)N1

Procedure:
In DMF, 6-amino-4-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one and ethyl 1,3-dioxo-1,3-dihydro-2H-isoindol-2-carboxylate were allowed to undergo the reaction at 60° C. for 18 hours in the presence of triethylamine. Water was added to the reaction liquid and the resulting precipitate was collected by filtration to obtain 2-[2-oxo-4-(trifluoromethyl)-2,3-dihydro-1H-indol-6-yl]-1H-isoindol-1,3-(2H)-dione.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1)([O-:3])=[O:2].[Cl:25][C:26]1[CH:31]=[C:30](Cl)[N:29]=[CH:28][N:27]=1.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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>[Cl:25][C:26]1[CH:31]=[C:30]([C:5]2[CH:6]=[C:7]([N:10]3[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]3)[CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])[N:29]=[CH:28][N:27]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CC1(C)OB(c2cc(N3CCCCC3)ccc2[N+](=O)[O-])OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(N2CCCCC2)cc1-c1cc(Cl)ncn1
Temperature: 75 °C
Reaction time: 8 h

Procedure:
Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-(4-nitro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (5 g, 15.06 mmol, 1.00 equiv) in 1,4-dioxane (150 mL), water (25 mL), 4,6-dichloropyrimidine (5.54 g, 37.69 mmol, 2.50 equiv), Pd(PPh3)2Cl2 (500 mg, 0.75 mmol, 0.05 equiv), triphenylarsine (460 mg, 1.50 mmol, 0.10 equiv), and K3PO4 (4.79 g, 22.59 mmol, 1.50 equiv). The resulting solution was stirred overnight at 75° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:10). This resulted in 2.5 g (47%) of 4-chloro-6-(2-nitro-5-(piperidin-1-yl)phenyl)pyrimidine as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7](S)[S:8][C:4]=2[C:3]=1[Cl:12].S(Cl)([Cl:15])=O>CN(C)C=O>[Cl:15][C:7]1[S:8][C:4]2[C:3]([Cl:12])=[C:2]([Cl:1])[CH:11]=[CH:10][C:5]=2[N:6]=1
Reactant: O=S(Cl)Cl
Reactant: Sc1nc2ccc(Cl)c(Cl)c2s1
Solvent: CN(C)C=O
Product: Clc1nc2ccc(Cl)c(Cl)c2s1
Temperature: 25 °C
Reaction time: 4 h
Yield: 41.9 %

Procedure:
To a suspension of 300 mg (1.270 mmol) 6,7-dichloro-benzothiazole-2-thiol in 1.4 mL (19.05 mmol) thionyl chloride was added dropwise 32.3 □L N,N-dimethylformamide dry at room temperature. The mixture was stirred at room temperature for 4 h. The solvent was removed in vacuo. The residue was purified with flash column chromatography on silica eluting with a gradient formed from n-heptane and ethyl acetate to provide 127 mg (41.9%) of the title compound as a yellow solid. MS(m/e): 239 (M+H+).
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[O:6][C:5](=[CH:7][C:8](Cl)=[O:9])[C:4](=[O:11])[O:3]1.[F:13][C:14]1[CH:26]=[CH:25][C:17]([CH2:18][NH:19][O:20][CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][CH:15]=1>>[CH3:1][C:2]1([CH3:12])[O:6][C:5](=[CH:7][C:8]([N:19]([CH2:18][C:17]2[CH:16]=[CH:15][C:14]([F:13])=[CH:26][CH:25]=2)[O:20][CH2:21][CH:22]([CH3:24])[CH3:23])=[O:9])[C:4](=[O:11])[O:3]1
Reactant: CC(C)CONCc1ccc(F)cc1
Reactant: CC1(C)OC(=O)C(=CC(=O)Cl)O1
Product: CC(C)CON(Cc1ccc(F)cc1)C(=O)C=C1OC(C)(C)OC1=O
Yield: 91 %

Procedure:
Reaction of (2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl chloride with N-(4-fluorobenzyl)-O-isobutyl-hydroxylamine as described in the preparation of Compound 44-C gave the title amide as white crystals (91% yield): mp 105–106° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 0.98 (3H, d, J=6.45 Hz, CH3), 1.77 (6H, s, CH3), 1.95 (1H, m, CH), 3.64 (2H, d, J=6.63 Hz, OCH2), 4.80 (2H, s, NCH2), 6.41 (1H, s, CH), 7.03 (2H, m, aromatics), 7.36 (2H, m, aromatics). Anal. calcd for C18H22FNO5: C, 61.53; H, 6.31; H, 3.98. Found: C, 61.47; H, 6.39; N, 3.97.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([NH2:15])=[O:14].[F:16][C:17]([F:22])([F:21])[C:18]([CH3:20])=O.CC1C=CC(S(O)(=O)=O)=CC=1.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:20][C:18]1([C:17]([F:22])([F:21])[F:16])[NH:1][C:2]2[CH:6]=[C:5]([C:7]3[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=3)[S:4][C:3]=2[C:13](=[O:14])[NH:15]1
Reactant: NC(=O)c1sc(-c2ccncc2)cc1N
Reactant: CC(=O)C(F)(F)F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: O=S(=O)([O-])[O-]
Solvent: CN(C)C=O
Product: CC1(C(F)(F)F)NC(=O)c2sc(-c3ccncc3)cc2N1
Reaction time: 3 h
Yield: 60 %

Procedure:
A mixture of 3-amino-5-(pyridin-4-yl)thiophene-2-carboxamide (110 mg, 0.502 mmol), 1,1,1-trifluoroacetone (1 mL, 11.2 mmol), PTSA (9.5 mg, 0.050 mmol), MgSO4 (60.4 mg, 0.50 mmol) and DMF (1 mL) was microwave-irradiated at 100° C. for 1 h then at 130° C. for 3 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL). Extraction with EtOAc (100 mL), washing with brine, drying over MgSO4, filtration and concentration under reduced pressure gave a yellow solid. This residue was purified by column chromatography (Purif, NH, hexane to EtOAc) to afford a yellow solid. This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (94.3 mg, 60%) as a yellow solid:
Reaction SMILES: CC1C=CC(S(O[CH:12]2[CH2:15][CH:14]([CH2:16][OH:17])[CH2:13]2)(=O)=O)=CC=1.[N:18]1[C:26]([NH2:27])=[C:25]2[C:21]([N:22]=[CH:23][NH:24]2)=[N:20][CH:19]=1.C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:27][C:26]1[N:18]=[CH:19][N:20]=[C:21]2[C:25]=1[N:24]=[CH:23][N:22]2[C@@H:12]1[CH2:13][C@H:14]([CH2:16][OH:17])[CH2:15]1
Reactant: Nc1ncnc2nc[nH]c12
Reactant: Cc1ccc(S(=O)(=O)OC2CC(CO)C2)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1ncnc2c1ncn2[C@H]1C[C@@H](CO)C1
Reaction time: 18 h

Procedure:
To a solution of 720 mg (2.0 mmol) of 3[[(4-methylphenyl)sulfonyl]oxy]cyclobutanemethanol, benzoate ester (95% trans isomer and 5% cis isomer) in 20 ml of dry dimethylformamide under nitrogen was added adenine (405 mg, 3 mmol), 18-crown-6 (528 mg, 2 mmol), and potassium carbonate (414 mg, 3 mmol). The mixture was stirred at 110° for 18 hours and then concentrated in vacuo to a residue. Water was added and the suspension was adjusted to pH 7.0 using 1N hydrochloric acid. Removal of solvent in vacuo gave a residue, which was chromatographed over 200 ml of LPS-1 silica gel using 4% methanol in dichloromethane to give 430 mg of desired product as a white solid.
Reaction SMILES: Br[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[O:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:19][O:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1>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>[CH3:19][O:20][C:21]1[CH:26]=[C:25]([CH:24]=[CH:23][CH:22]=1)[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[O:4][CH:3]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: O=c1c(Br)coc2ccccc12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1cccc(-c2coc3ccccc3c2=O)c1
Temperature: 80 °C
Reaction time: 4 h
Yield: 51 %

Procedure:
Prepared using a modified procedure of Hoshino et al. (Bulletin of the Chemical Society of Japan 1988, 61, (8), 3008-3010; herein incorporated by reference in its entirety). To a 10 mL round bottom flask was added 3-bromochromone (Gammill, R. B. Synthesis-Stuttgart 1979, (11), 901-903; herein incorporated by reference in its entirety) (225 mg, 1 mmol), K2CO3 (415 mg, 3 mmol), 3-methoxyphenylboronic acid (167 mg, 1.1 mmol), and PdCl2(PPh3)2(21 mg, 0.03 mmol). The flask was equipped with a reflux condenser and purged with N2, followed by addition of THF/H2O (2.5 mL/0.5 mL). The reaction was stirred at 80° C. for 4 hr. The reaction was then run through a plug of Celite and rinsed with EtOAc. The organic phase was washed with brine and dried over anhydrous Na2SO4. Purified by flash column chromatography (SiO2, 15% EtOAc/Hex) and recrystallized from CH2Cl2/Hex to afford 5 (128 mg, 51%) as an off-white solid. Analytical data for isoflavone 5: 1H NMR (500 MHz, CDCl3) δ 8.34 (d, J=9.5 Hz, 1H), 8.06 (s, 1H), 7.70 (app t, J=8.5 Hz, 1H), 7.50 (d, J=8.5 Hz, 1H), 7.45 (app t, J =7.5 Hz, 1H), 7.37 (app t, J =8 Hz, 1H), 7.19 (s, 1H), 7.15 (d, J=7 Hz, 1H), 6.96 (d, J=8.5 Hz, 1H), 3.87 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 176.4, 159.8, 156.4, 153.4, 133.9, 133.4, 129.8, 126.7, 125.5, 124.8, 121.5, 118.3, 114.7, 114.4, 55.6; LCMS: Mass calculated for C16H12O3, [M+H]+, 253. Found 253.
Reaction SMILES: C([C:6]1[N:11]2[C:12]3[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[C:13]=3[C:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[N:15][CH2:16][C:10]2=[N:9][C:8](=[O:30])[CH:7]=1)(OCC)=O.[I-].[Li+]>N1C=CC=CC=1>[CH3:29][C:24]1[C:13]2[C:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[N:15][CH2:16][C:10]3[N:11]([CH:6]=[CH:7][C:8](=[O:30])[N:9]=3)[C:12]=2[CH:27]=[C:26]([CH3:28])[CH:25]=1
Reactant: CCOC(=O)c1cc(=O)nc2n1-c1cc(C)cc(C)c1C(c1ccc(F)cc1)=NC2
Agent: [I-]
Agent: [Li+]
Solvent: c1ccncc1
Product: Cc1cc(C)c2c(c1)-n1ccc(=O)nc1CN=C2c1ccc(F)cc1

Procedure:
In the manner given in Example 32, 1-carboethoxy-8,10-dimethyl-7-(p-fluorophenyl)pyrimido[1,2-a][1,4]benzodiazepin-3(5H)-one was heated in pyridine with lithium iodide to give 8,10-dimethyl-7-(p-fluorophenyl)pyrimido[1,2-a][1,4]benzodiazepin-3(5H)-one.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])[C:3](O)=[O:4]>O1CCCC1>[NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])[CH2:3][OH:4]
Reactant: N[C@@H](Cc1ccccc1F)C(=O)O
Solvent: C1CCOC1
Product: N[C@H](CO)Cc1ccccc1F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of (2S)-2-amino-3-(2-fluorophenyl)propanoic acid (10.00 g, 54.59 mmol) in tetrahydrofuran (25 mL) with stirring was added 1.0 M borane-THF complex in THF (100.0 mL) (freshly opened) dropwise to keep the internal temperature around 0° C. After addition, the reaction mixture was stirred at room temperature for 3 hrs. Then the mixture was cooled with an ice-bath, quenched with AcOH:MeOH (1:5, 50 mL), and partitioned between saturated aqueous NaHCO3 solution and dichloromethane (DCM). The organic phases were dried over sodium sulfate, filtered, and evaporated under vacuum to give an oil residue which was purified on prep. HPLC to give the purified desired product. LC-MS found: 170.1 (M+H)+.
Reaction SMILES: [C:1](OC)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C>[CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCC(=O)OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\CCCCCCCCO
Temperature: 0 °C
Reaction time: 2 h
Yield: 97.8 %

Procedure:
A solution of 20.0 g of methyl linoleate in 20 ml of diethyl ether was added to a suspension of 1.8 g of lithium aluminum hydride in 150 ml of diethyl ether at approximately 0° C. under an argon atmosphere. The mixture was stirred for approximately 2 hours at 0° C. The reaction was quenched by the slow addition of 1.8 ml of water, followed by 1.8 ml of 15% sodium hydroxide and 5.4 ml of water. The mixture was filtered and the filtrate was evaporated to dryness. The resulting oil was dissolved in diethyl ether, washed with water, dried over magnesium sulfate, filtered, and evaporated to provide 17.7 g of linoleyl alcohol.
Reaction SMILES: [H-].[Na+].CN(C=O)C.[NH:8]1[CH:12]=[N:11][CH:10]=[N:9]1.Cl[C:14]1[C:19]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[C:18]([CH3:27])[N:17]=[N:16][C:15]=1[CH3:28]>C(OCC)(=O)C>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([C:19]2[C:14]([N:8]3[CH:12]=[N:11][CH:10]=[N:9]3)=[C:15]([CH3:28])[N:16]=[N:17][C:18]=2[CH3:27])=[CH:25][CH:24]=1
Reactant: c1nc[nH]n1
Reactant: Cc1nnc(C)c(-c2ccc(Cl)cc2)c1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1nnc(C)c(-n2cncn2)c1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 70.9 %

Procedure:
87 mg of sodium hydride (55% oil dispersion) was added to 5 ml of DMF. To this was added 0.14 g of 1,2,4-triazole, and the mixture was stirred for 0.5 hours at room temperature. To the resultant mixture was added 0.25 g of 4-chloro-5-(4-chlorophenyl)-3,6-dimethylpyridazine, and the mixture was stirred for 3 hours on an oil bath of 80° C. To the reaction mixture was added ethyl acetate, and the mixture was washed with brine four times. The organic layer was dried over anhydrous magnesium sulfate, then, concentrated under reduced pressure. 0.39 g of the resultant residue was subjected to silica gel column chromatography, to obtain 0.20 g of 5-(4-chlorophenyl)-3,6-dimethyl-4-(1,2,4-triazol-1-yl)pyridazine (hereinafter, described as compound (7) of the present invention.).