Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][C:9]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:10]=1[C:11]1[CH2:12][O:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([O:21]CC1C=CC=CC=1)[CH:15]=2)C1C=CC=CC=1.CC1C(C)=C(C)C(C)=C(C)C=1.B(Cl)(Cl)Cl>C(Cl)Cl>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:10]([C:11]2[CH2:12][O:13][C:14]3[CH:15]=[C:16]([OH:21])[CH:17]=[CH:18][C:19]=3[CH:20]=2)=[C:9]([OH:8])[CH:32]=1
Reactant: COc1ccc(C2=Cc3ccc(OCc4ccccc4)cc3OC2)c(OCc2ccccc2)c1
Agent: Cc1cc(C)c(C)c(C)c1C
Agent: ClB(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(C2=Cc3ccc(O)cc3OC2)c(O)c1
Temperature: -78 °C
Reaction time: 0.29 h
Yield: 610 %

Procedure:
To a solution of B4 (0.45 g, 0.1 mmol) and pentamethylbenzene (0.158 g, 1 mmol) in anhyd CH2Cl2 (30 mL) at −78° C., BCl3 (0.2 mmol) was dropwise added under N2. The reaction mixture was stirred at −78° C. and after 15-20 min the reaction was quenched with 20 mL of CHCl3/MeOH (10:1) mixture. The resulting mixture was warmed to rt. The organic solvents were evaporated under vacuum. The residues were purified by column chromatography [Silica gel 35 mm dia, 8 inch thick, EtOAc/hexanes (1:2)] to obtain B6 (0.17 g, 0.61 mmol, 61%) as brownish solid: mp 150-154° C.; TLC Rf=0.48 [EtOAc/hexanes (1:2)]; 1H NMR (CD3OD, 600 MHz) δ 7.14 (1H, d, J=8.4 Hz), 6.88 (1H, d, J=8.4 Hz), 6.53 (1H, s), 6.42 (1H, dd, J=2.4, 8.4 Hz), 6.37 (1H, d, J=2.4 Hz), 6.33 (1H, dd, J=2.4, 8.4 Hz), 6.24 (1H, d, J=1.8 Hz), 4.95 (2H, s), 3.75 (3H, s); 13C NMR (CD3OD, 150 MHz) δ 161.8, 159.1, 157.3, 155.9, 130.1, 130.0, 128.4, 121.4, 119.9, 117.6, 109.4, 106.1, 103.4, 102.4, 69.2, 55.6; Anal. (%) calcd for C16H14O4.0.1 H2O, C 70.63, H 5.26, found C 70.42, H 5.20.
Reaction SMILES: [O:1]1CCO[CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:16]3[NH:17][C:18]([C:20]([F:23])([F:22])[F:21])=[N:19][C:15]=3[CH:14]=2)=[CH:8][CH:7]=1.CC1C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[F:23][C:20]([F:21])([F:22])[C:18]1[NH:19][C:15]2[CH:14]=[C:13]([O:12][C:9]3[CH:10]=[CH:11][C:6]([CH:2]=[O:1])=[CH:7][CH:8]=3)[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:16]=2[N:17]=1
Reactant: FC(F)(F)c1nc2cc(Oc3ccc(C4OCCO4)cc3)cc(C(F)(F)F)c2[nH]1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)=O
Product: O=Cc1ccc(Oc2cc(C(F)(F)F)c3nc(C(F)(F)F)[nH]c3c2)cc1
Reaction time: 3 h

Procedure:
A mixture of 5-{[4-(1,3-dioxolan-2-yl)phenyl]oxy}-2,7-bis(trifluoromethyl)-1H-benzimidazole (0.260 g, 0.622 mmol) and MP-TSOH (Argonaut, macroporous polymer supported tosic acid, approximately 0.842 g, 1.24 mmol) in acetone (2 mL) was stirred for 3 h, then filtered and concentrated to give the desired 4-{[2,4-bis(trifluoromethyl)-1H-benzimidazol-6-yl]oxy}benzaldehyde which was used without further purification.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([O:11][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22](=[NH:24])[NH2:23])[CH:18]=3)[C:13]=2[CH2:25][C:26](=[O:28])[NH2:27])=[O:10])=[CH:7][CH:6]=1)([O-])=O>[C].[Pd].CN(C=O)C>[ClH:1].[ClH:1].[NH2:2][C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22](=[NH:23])[NH2:24])[CH:18]=3)[C:13]=2[CH2:25][C:26](=[O:28])[NH2:27])=[O:10])=[CH:29][CH:30]=1
Reactant: N=C(N)c1ccc2c(CC(N)=O)c(OC(=O)c3ccc([N+](=O)[O-])cc3)ccc2c1
Agent: [Pd]
Agent: Cl
Solvent: CN(C)C=O
Product: N=C(N)c1ccc2c(CC(N)=O)c(OC(=O)c3ccc(N)cc3)ccc2c1
Reaction time: 24 h
Yield: 188.1 %

Procedure:
To 600 mg of 6-amidino-1-carbamoylmethyl-2-naphthyl 4-nitrobenzoate.hydrochloride were added 10 ml of anhydrous DMF and 100 mg of 10% palladium carbon, and catalytic reduction was effected at room temperature for 24 hours. Then, insoluble matter was filtered off and the filtrate was concentrated under reduced pressure. To the residue was added 15 ml of methanol, and, furthermore, 350 μl of concentrated hydrochloric acid was added with stirring under cooling with ice. Then, the resulting solution was added dropwise to 200 ml of acetone, followed by stirring for 1 hour under cooling with ice. Then, the precipitate was collected by filtration to obtain 572.7 mg of the desired product.
Reaction SMILES: [C:1]1([CH2:7][CH:8]([NH2:11])[CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12](N1C=CN=C1)(N1C=CN=C1)=[S:13]>ClCCl.CCCCCC.C(OCC)(=O)C>[CH2:7]([CH:8]1[CH2:9][NH:10][C:12](=[S:13])[NH:11]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCC(N)Cc1ccccc1
Reactant: S=C(n1ccnc1)n1ccnc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: S=C1NCC(Cc2ccccc2)N1
Reaction time: 0.25 h
Yield: 90 %

Procedure:
A solution of 3 (9.75 g, 0.65 mol) in dichloromethane (75 mL) under argon was treated with a solution of 1,1′-thiocarbonyldiimidazole in dichloromethane (12.16 g, 0.068 mol) added over 45 min. The reaction was stirred for 15 min after the addition was complete and HPLC analysis indicated complete reaction. The reaction mixture was diluted with dichloromethane (200 mL) and washed with water (3×100 mL) and brine (100 mL). The organic solution was filtered through 1PS filter paper and evaporated under reduced pressure to give a yellow solid. The solid was suspended in 100 mL of 10% hexane-ethyl acetate and filtered. The filter cake was washed with 50 mL of 10% hexane-ethyl acetate and air dried to give 11.2 g (90% yield) of 4. HPLC analysis indicated 99% purity. NMR (CDCl3:d6-DMSO) δ 7.8 (S br, 2H), 7.4 (S, 5H), 4.0–4.7 (m, 1H), 3.3–3.9 (m, 2H), 2.7–3.2 (m, 2H).
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]3[C:19](=[O:20])[CH2:18][S:17][C:16]3=[O:21])[C:5]=12.[CH:22](=O)[CH2:23][CH2:24][CH3:25].N1CCCC1>C(O)C>[CH:22](=[C:18]1[S:17][C:16](=[O:21])[N:15]([CH2:14][CH2:13][CH2:12][CH2:11][O:10][C:6]2[C:5]3[N:4]([CH:3]=[CH:2][N:1]=3)[CH:9]=[CH:8][CH:7]=2)[C:19]1=[O:20])[CH2:23][CH2:24][CH3:25]
Reactant: CCCC=O
Reactant: O=C1CSC(=O)N1CCCCOc1cccn2ccnc12
Solvent: C1CCNC1
Solvent: CCO
Product: CCCC=C1SC(=O)N(CCCCOc2cccn3ccnc23)C1=O

Procedure:
To a solution of 1.25 g (4.32 mmol) of 3-[4-(imidazo[1,2-a]pyridin-8-yloxy)butyl]thiazolidine-2,4-dione and 0.39 ml (4.32 mmol) of 1-butanal in 20 ml of ethanol, 0.036 ml (0.43 mmol) of pyrrolidine was added at 60° C., followed by refluxing for 19 hours (1 and 2 hours later, 0.39 ml (4.32 mmol) was further added; 3 hours later, 0.39 ml (4.32 mmol) of 1-butanal and 0.036 ml (0.43 mmol) of pyrrolidine were further added). After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with purified water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=1/4), after which the solvent was distilled off, to yield 0.17 g (11.5%, yellow oily substance) of the desired product.
Reaction SMILES: [CH3:1][C:2]1([CH3:21])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-])=O)[CH2:4][CH2:3]1.[NH4+].[Cl-]>CO.[Zn]>[CH3:1][C:2]1([CH3:21])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH2:18])[CH2:4][CH2:3]1
Reactant: CC1(C)CCN(c2ccccc2[N+](=O)[O-])c2ccccc21
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Product: CC1(C)CCN(c2ccccc2N)c2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 72.9 %

Procedure:
The crude 1c (0.66 g) was stirred in MeOH (20 mL) at rt. Solid NH4Cl (0.62 g) was added, followed by addition of Zn dust (3.0 g) portionwise. The resulting mixture was stirred at rt for 2 h. It was filtered through Celite®, rinsed with CH2Cl2, and concentrated to dryness. The residue was purified by flash chromatography (hexanes/EtOAc) to give pure amine 1d (0.43 g, 73% for two steps). LC-MS ESI 253 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:22])=[C:6]([C:8]2[C:19](=[O:20])[N:18]([CH3:21])[C:11]3[N:12]=[C:13](SC)[N:14]=[CH:15][C:10]=3[CH:9]=2)[CH:7]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[CH3:34][NH2:35]>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:22])=[C:6]([C:8]2[C:19](=[O:20])[N:18]([CH3:21])[C:11]3[N:12]=[C:13]([NH:35][CH3:34])[N:14]=[CH:15][C:10]=3[CH:9]=2)[CH:7]=1
Reactant: CSc1ncc2cc(-c3cc(N)ccc3Cl)c(=O)n(C)c2n1
Reactant: CN
Agent: O=C(OO)c1cccc(Cl)c1
Product: CNc1ncc2cc(-c3cc(N)ccc3Cl)c(=O)n(C)c2n1
Yield: 79.8 %

Procedure:
6-(5-amino-2-chlorophenyl)-8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (0.500 g, 1.5 mmol), mCPBA (0.481 g, 1.953 mmol) and methylamine (0.76 mL. 2.0 M in THF, 1.52 mmol) were combined by analogy to Example A1 to provide 6-(5-amino-2-chlorophenyl)-8-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (0.378 g, 80% yield). MS (ESI) m/z: 316.0 (M+H+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[O:7][CH2:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[C:11](=[O:12])[C:5]=2[CH:4]=1.CO.[BH4-].[Na+]>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[O:7][CH2:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[CH:11]([OH:12])[C:5]=2[CH:4]=1
Reactant: COc1ccc2c(c1)C(=O)c1ccccc1CO2
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1ccc2c(c1)C(O)c1ccccc1CO2
Reaction time: 1 h
Yield: 89.3 %

Procedure:
A solution of 10 g of 2-methoxy-6,11-dihydrodibenz[b,e]oxepin-11-one [Monatsh. Chem., 93, 889 (1962)]in 100 ml of methanol is cooled to 0° C. Thereto 3 g of sodium borohydride is added and the mixture is stirred for 1 hour. After completion of the reaction, chloroform is added and the mixture is washed with a saturated saline solution. After drying over magnesium sulfate and the solvent is distilled off under reduced pressure, the residue is subjected to a silica-gel chromatography and eluted with toluene to give 9 g of the objective compound as an oily product. Mass spectrum m/z: 242(M+).
Reaction SMILES: [Br:1][C:2]1[C:11]([C@H:12]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:13]([OH:15])=[O:14])=[C:10]([CH3:21])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:22])=[N:7]2.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:30][CH3:31]>CN(C=O)C>[Br:1][C:2]1[C:11]([C@H:12]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[C:13]([O:15][CH2:30][CH3:31])=[O:14])=[C:10]([CH3:21])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:22])=[N:7]2
Reactant: CCI
Reactant: Cc1ccc2c(Br)c([C@H](OC(C)(C)C)C(=O)O)c(C)cc2n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(C)ccc2c1Br
Temperature: 25 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
To a stirred solution of (S)-2-(5-bromo-2,7-dimethylquinolin-6-yl)-2-tert-butoxyacetic acid (5G) (180 mg, 0.49 mmol) in DMF (15 mL) was added cesium carbonate (321 mg, 0.98 mmol) at 0° C. After being stirred for 10 min iodoethane (0.059 mL, 0.74 mmol) was added. The mixture was stirred at room temperature for 2 hours and quenched by the slow addition of a NaHCO3 solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated. The residue was purified by column chromatography to give the pure product 5H (168 mg, 87%). LCMS-ESI+ (m/z): 394.1, 396.1 (M+H)+.
Reaction SMILES: [Mg].[Br:2]C(Br)C.[Br:6][C:7]1[C:8]([O:27][CH2:28][CH:29]2[CH2:31][O:30]2)=[CH:9][CH:10]=[C:11]2[C:15]=1[N:14]([CH2:16][C@@H:17]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH3:18])[N:13]=[CH:12]2>C1COCC1>[Br:2][CH2:31][CH:29]([OH:30])[CH2:28][O:27][C:8]1[C:7]([Br:6])=[C:15]2[C:11]([CH:12]=[N:13][N:14]2[CH2:16][C@@H:17]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH3:18])=[CH:10][CH:9]=1
Reactant: CC(Br)Br
Reactant: C[C@@H](Cn1ncc2ccc(OCC3CO3)c(Br)c21)O[Si](C)(C)C(C)(C)C
Agent: [Mg]
Solvent: C1CCOC1
Product: C[C@@H](Cn1ncc2ccc(OCC(O)CBr)c(Br)c21)O[Si](C)(C)C(C)(C)C
Temperature: 50 °C
Reaction time: 1 h
Yield: 95.3 %

Procedure:
To a suspension of magnesium powder (0.73 g, 30.2 mmol) in anhydrous THF (50 mL) under nitrogen was added dibromoethane (2.13 g, 0.98 mL, 11.3 mmol) in portions over about 30 min. During this period the mixture was heated at about 50° C. until gas evolution was observed. The mixture was stirred for an additional 1 h, placed in an ice bath, and a solution of the product from Step D (3.33 g, 7.55 mmol) in THF (10 mL) was added. After stirring for 1 h at ambient temperature, the mixture was quenched with a saturated aqueous solution of ammonium chloride (100 mL) and extracted with EtOAc (3×100 mL). Evaporation of the extracts gave a crude oil (3.76 g, 95%): LC/MS (+APCI) m/z 441, 443 (M+H−HBr).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:28]([C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1)#[N:29]>ClCCl.N1C=CC=CC=1>[C:28]([C:30]1[CH:31]=[CH:32][C:33]([S:36]([N:18]2[CH2:17][CH2:16][N:15]([C:13]([CH:10]3[CH2:11][CH2:12][N:7]([C:4]4[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=4)[CH2:8][CH2:9]3)=[O:14])[CH2:20][CH2:19]2)(=[O:38])=[O:37])=[CH:34][CH:35]=1)#[N:29]
Reactant: N#Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=C(C1CCN(c2ccncc2)CC1)N1CCNCC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: N#Cc1ccc(S(=O)(=O)N2CCN(C(=O)C3CCN(c4ccncc4)CC3)CC2)cc1
Temperature: 0 °C

Procedure:
1-(1-(4-pyridyl)piperdin-4-ylcarbonyl)piperazine (0.411 g) was dissolved in dry dichloromethane (20 mL) and stirred under argon at 0° C. To the resulting solution was added triethylamine (0.56 mL) followed by the dropwise addition of a solution of 4-cyanobenzenesulphonyl chloride (0.33 g, 1.6 mmol) in dry pyridine (20 mL). The reaction was then stirred at 0° C. for 10 minutes and then allowed to warm to room temperature and stirred for a further 1 hour. The reaction was quenched by the removal of the dichloromethane and pyridine solvents by evaporation, taken up in water (60 mL) and then extracted with ethyl acetate (3×50 mL). The organic extracts were then washed with water, brine, dried (MgSO4) and evaporated to dryness. The product was then recrystallised to give 1-(4-cyanophenylsulphonyl)-4-(1-(4-pyridyl)piperidin-4-ylcarbonyl)piperazine as a white, hygroscopic solid m.p. 168-169° C.;
Reaction SMILES: [C:1]([C:4]1[C:8]2[C:9]([Cl:27])=[CH:10][C:11]([F:26])=[C:12]([N:13]3[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[N:15]([CH3:24])[C:14]3=[O:25])[C:7]=2[O:6][C:5]=1[CH3:28])(=O)[CH3:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:30]>C1(C)C=CC=CC=1>[Cl:27][C:9]1[C:8]2[C:4]([C:1](=[S:30])[CH3:2])=[C:5]([CH3:28])[O:6][C:7]=2[C:12]([N:13]2[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[N:15]([CH3:24])[C:14]2=[O:25])=[C:11]([F:26])[CH:10]=1
Reactant: CC(=O)c1c(C)oc2c(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c(F)cc(Cl)c12
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: Cc1ccccc1
Product: CC(=S)c1c(C)oc2c(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)c(F)cc(Cl)c12
Reaction time: 2 h
Yield: 9 %

Procedure:
100 ml of toluene was added to 0.50 g (1.2 mmol) of 3-(3-acetyl-4-chloro-6-fluoro-2-methylbenzofuran-7-yl)-1-methyl-6-trifluoromethyluracil and 1.5 g (6.7 mmol) of phosphorus pentasulfide, followed by stirring for 2 hours under heating and refluxing. After completion of the reaction, 100 ml of toluene was further added to the reaction solution. The organic layer was washed sequentially with water and a saturated sodium chloride aqueous solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. Then, the obtained residue was purified by silica gel column chromatography to obtain 47 mg (yield: 9%) of the desired product as an orange colored glassy substance. Refractive index: 1.5967 (20° C.).
Reaction SMILES: [H][H].[CH2:3]=[C:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:14]>C1(C)C=CC=CC=1.[Pd]>[CH3:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[OH:14]
Reactant: [H][H]
Reactant: C=C1CCc2ccccc2C1=O
Agent: [Pd]
Solvent: Cc1ccccc1
Product: Cc1ccc2ccccc2c1O
Temperature: 110 °C
Yield: 98.4 %

Procedure:
A 50-ml reaction vessel was charged with 20 ml of toluene and 100 mg of 5% Pd/C (dry type) and hydrogen gas was passed through the mixture at room temperature. After conducting activation for 1 hour, the atmosphere in the vessel was replaced with nitrogen and the vessel was heated to 110° C. To the mixture a solution of 1.25 g (7.9 mmoles) of 2-methylene-1-tetralone in 20 ml of toluene was added dropwise over 2 hours. After the addition, refluxing state was maintained for further 1 hour to permit the reaction to proceed until completion. GLC analysis revealed that there was formed 1.23 g of 2-methyl-1-naphthol (conversion: 98.5%; selectivity: 100%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[N:7][C:6]=2[CH:10]=1.C(N(CC)C(C)C)(C)C.N#N.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[C:64]1([SH:70])[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>CCOC(C)=O.[OH-].[Na+].O1CCOCC1>[C:64]1([S:70][C:2]2[CH:3]=[CH:4][C:5]3[O:9][CH:8]=[N:7][C:6]=3[CH:10]=2)[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1
Reactant: Brc1ccc2ocnc2c1
Reactant: Sc1ccccc1
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: N#N
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: c1ccc(Sc2ccc3ocnc3c2)cc1
Temperature: 100 °C

Procedure:
A 150 mL pressure bottle was charged with 5-bromobenzo[d]oxazole (2.43 g, 12.3 mmol), N,N-diisopropylethylamine (4.28 mL, 24.5 mmol), and 24 mL dioxane. N2 was bubbled through the solution for 3 min, at which point tris(dibenzylidineacetone)palladium(0) (0.281 g, 0.307 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.355 g, 0.614 mmol), and benzenethiol (1.26 mL, 12.3 mmol) were added. The dark brown solution was sealed and heated to 100° C. overnight. The mixture was diluted with EtOAc and NaOH, and the organic layer was extracted 2×1N NaOH. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to give an orange oil, which was purified by ISCO, 0-100% 10% EtOAc/hexanes in hexanes to give 5-(phenylthio)benzo[d]oxazole as an orange oil. MS (ESI) m/z: Calculated: 227.0; Observed: 228.0 (M++1).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]2[CH:15]=[CH:14][CH:13]=[CH:12]2)=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.CN(C)[CH2:19][CH2:20]CN=C=N.O.ON1C2C=CC=CC=2N=N1.C(O)C>CN(C)C=O.O>[N:11]1([C:8]2[CH:7]=[C:3]([C:4]([O:6][CH2:19][CH3:20])=[O:5])[C:2]([OH:1])=[CH:10][CH:9]=2)[CH:15]=[CH:14][CH:13]=[CH:12]1
Reactant: CN(C)CCCN=C=N
Reactant: O=C(O)c1cc(-n2cccc2)ccc1O
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1cc(-n2cccc2)ccc1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 36.8 %

Procedure:
2-Hydroxy-5-(pyrrol-1-yl)benzoic acid (406 mg), 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (420 mg), 1-hydroxybenzotriazole hydrate (337 mg), and ethanol (2 ml) were dissolved in N,N-dimethylformamide to prepare a solution which was then stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give ethyl 5-(pyrrol-1-yl)salicylate (170 mg, yield 20%).
Reaction SMILES: O[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11](=[O:20])[N:12]([CH3:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:6][CH:5]=1.[NH:21]1[CH:25]=[N:24][N:23]=[N:22]1>>[N:21]1([CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11](=[O:20])[N:12]([CH3:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:6][CH:5]=2)[CH:25]=[N:24][N:23]=[N:22]1
Reactant: c1nnn[nH]1
Reactant: CN(C(=O)Oc1ccc(CCO)cc1)c1ccccc1
Product: CN(C(=O)Oc1ccc(CCn2cnnn2)cc1)c1ccccc1
Yield: 10 %

Procedure:
The title compound was prepared in 10% yield as an oil using methyl-phenyl-carbamic acid 4-(2-hydroxy-ethyl)-phenyl ester and tetrazole. NMR (400 MHz; CDCl3): δ 3.19 (t, 2H), 3.40 (br s, 3H), 3.47 (s, 1H), 4.61 (t, 2H), 6.98-7.07 (m, 4H), 7.25-7.42 (m, 5H), 8.26 (s, 1H); HPLC-MS: m/z=324.1 (M+1); Rt=3.36 min.
Reaction SMILES: Cl.[N:2]1([CH:7]2[CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[CH:5][N:4]=[N:3]1.C1CCN2C(=NCCC2)CC1.[F:23][CH2:24][CH2:25][N:26]1[C:35]2[C:30](=[CH:31][C:32]([F:38])=[C:33](F)[C:34]=2[F:36])[C:29](=[O:39])[C:28]([C:40]([OH:42])=[O:41])=[CH:27]1>C(#N)C>[F:38][C:32]1[CH:31]=[C:30]2[C:35](=[C:34]([F:36])[C:33]=1[N:9]1[CH2:10][CH2:11][CH:7]([N:2]3[CH:6]=[CH:5][N:4]=[N:3]3)[CH2:8]1)[N:26]([CH2:25][CH2:24][F:23])[CH:27]=[C:28]([C:40]([OH:42])=[O:41])[C:29]2=[O:39]
Reactant: O=C(O)c1cn(CCF)c2c(F)c(F)c(F)cc2c1=O
Reactant: c1cn(C2CCNC2)nn1
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: O=C(O)c1cn(CCF)c2c(F)c(N3CCC(n4ccnn4)C3)c(F)cc2c1=O
Yield: 34.4 %

Procedure:
3-(1,2,3-triazol-1-yl)pyrrolidinehydrochloride (87 mg) and DBU (76 mg) were added to a suspension of 1-(2-fluoroethyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (72 mg, 0.25 mmol) in acetonitrile (5 ml). The reaction mixture was refluxed for 21 hrs, concentrated and the residue was diluted with water. The separated solid was filtered, washed with water and acetonitrile to give 35 mg of the title product. m.p. 240°-243° C. (dec). 1H NMR (TFA) δ: 9.76 (s, 1H), 9.08 (s, 1H), 8.73 (s, 1H), 8.12 (d, 13.7Hz, 1H), 5.8-5.6 (m, 1H), 5.4-4.1 (m, 9H), 3.0-2.65 (m, 2H). Anal. Calcd. for C18H16F3N5O3 . 1/2 H2O; C, 51.93; H, 4.12; N, 16.32.Found: C, 51.77; H, 3.84; N, 15.6.
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[N+]([O-])([O-])=O.[Ag+:29]>>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Ag+:29]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]

Procedure:
Silver Behenate was prepared using procedure 1 and using 10 g of behenic acid and 4.8 g of silver nitrate to give a white powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][CH:6]([N+:17]([O-])=O)[CH2:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1.C([O-])(=O)C.[NH4+]>CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.[Ni]>[CH3:1][O:2][C:3](=[O:20])[CH2:4][CH2:5][CH:6]([NH2:17])[CH2:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1
Reactant: COC(=O)CCC(Cc1c[nH]c2ncccc12)[N+](=O)[O-]
Agent: [Ni]
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: CC(=O)[O-]
Product: COC(=O)CCC(N)Cc1c[nH]c2ncccc12
Reaction time: 12 h
Yield: 57.8 %

Procedure:
To a solution of 165 mg (0.595 mM) of 4-Nitro-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-pentanoic acid methyl ester in 15 mL of acetic add was added 450 mg (0.595 mM) of ammonium acetate and approximately 100 mg of Raney nickel. The mixture was hydrogenated at 50 psi for 12 hours. The mixture was filtered and the solvent evaporated. The residue was treated with an equal volume of ethyl acetate and saturated sodium bicarbonate. The ethyl acetate layer was dried and evaporated to yield 85 mg of product which was used in the next synthetic step without further purification. TLC: (10:1 CHCl3 : CH3OH) Rf=0.1 Mass Spectrum: m/e=248 (P+1).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH:14][CH2:15][CH2:16][OH:17])[N:3]=1.[C:18]1([C:24]2([C:30]#[N:31])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(C(C)C)C(C)C)C>O1CCOCC1>[C:30]([C:24]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:25][CH2:26][N:27]([C:2]2[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH:14][CH2:15][CH2:16][OH:17])[N:3]=2)[CH2:28][CH2:29]1)#[N:31]
Reactant: N#Cc1c(Cl)nc(NCCO)nc1NCCO
Reactant: N#CC1(c2ccccc2)CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: N#Cc1c(NCCO)nc(NCCO)nc1N1CCC(C#N)(c2ccccc2)CC1

Procedure:
In analogy to the procedure described in example 20b, 4-chloro-2,6-bis-(2-hydroxy-ethylamino)-pyrimidine-5-carbonitrile was treated with 4-phenyl-piperidine-4-carbonitrile in dioxane in the presence of N-ethyl-diisopropylamine at 60° C. to yield 4-(4-cyano-4-phenyl-piperidin-1-yl)-2,6-bis-(2-hydroxy-ethylamino)-pyrimidine-5-carbonitrile as an amorphous, white solid; MS: [M+H]+=408.