Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:18]=4[O:19][CH2:20][C:21](=O)[CH3:22])=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:29].[CH3:30][NH:31][CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>C1COCC1.ClCCCl.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:18]=4[O:19][CH2:20][CH:21]([N:31]([CH3:32])[CH3:30])[CH3:22])=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:29]
Reactant: CNC
Reactant: CC(=O)COc1cc(F)ccc1C(=O)N1Cc2nn3c(C)c(Cl)c(C)nc3c2C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1nc2c3c(nn2c(C)c1Cl)CN(C(=O)c1ccc(F)cc1OCC(C)N(C)C)C3
Temperature: 70 °C
Reaction time: 3 h
Yield: 28 %

Procedure:
A mixture of Example 164 (90 mg; 0.22 mmol; 1 eq.), a 2M solution of dimethylamine in THF and sodium triacetoxyborohydride (59 mg; 0.28 mmol; 1.3 eq.) in DCE (2 mL) was stirred at 50° C. for 1 hour whereupon triacetoxyborohydride (59 mg; 0.28 mmol; 1.3 eq.) was added. The resulting mixture was stirred at 70° C. for 3 hours then diluted with ethyl acetate. The solution was washed with 0.1M NaOH, dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography (EA to 10 MeOH in EA) afforded the title compound (27 mg, 28%) as a white solid. 1H NMR (DMSO-d6) δ 7.42-7.26 (m, 1H), 7.09 (d, J=11.5 Hz, 1H), 6.86 (t, J=8.2 Hz, 1H), 4.78 (d, J=7.9 Hz, 2H), 4.59 (d, J=15.0 Hz, 2H), 4.13-3.89 (m, 2H), 2.92-2.74 (m, 4H), 2.61 (s, 1.4H), 2.56 (s, 1.6H), 2.06 (s, 6H), 0.95-0.78 (m, 3H). HPLC (max plot) 99.9%, Rt 2.77 min. UPLC/MS: (MS+) 446.3 ([M+H]+).
Reaction SMILES: C[O-].[Na+].[O:4]1[CH:8]=[N:7][N:6]=[C:5]1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]#[N:17])=[CH:11][CH:10]=1.[N:18]([C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=1[F:31])=[N+:19]=[N-:20]>CO>[F:31][C:22]1[CH:23]=[C:24]([C:27]([F:29])([F:30])[F:28])[CH:25]=[CH:26][C:21]=1[N:18]1[C:16]([NH2:17])=[C:15]([C:12]2[CH:13]=[CH:14][C:9]([C:5]3[O:4][CH:8]=[N:7][N:6]=3)=[CH:10][CH:11]=2)[N:20]=[N:19]1
Reactant: N#CCc1ccc(-c2nnco2)cc1
Reactant: [N-]=[N+]=Nc1ccc(C(F)(F)F)cc1F
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Nc1c(-c2ccc(-c3nnco3)cc2)nnn1-c1ccc(C(F)(F)F)cc1F
Reaction time: 1 h
Yield: 36.8 %

Procedure:
To a stirred and ice-cooled solution of sodium methoxide (0.158 g, 2.9252 mmol) in methanol (25 ml), commercial 2-[4-(1,3,4-oxadiazol-2-yl)phenyl]acetonitrile (0.430 g, 2.3401 mmol) and 1-azido-2-fluoro-4-trifluoromethyl-benzene (0.400 g, 1.9501 mmol) are added under a nitrogen atmosphere. The reaction mixture is kept at 0° C. for 1 h, and then allowed to attain spontaneously room temperature overnight. The reaction mixture is concentrated, added water (30 ml), and extracted with ethylacetate (3×100 ml). The combined organic layers are dried over MgSO4, filtered and evaporated, to afford a pink solid (0.74 g, 97% mass balance). The crude residue is purified by column chromatography over silica gel (230-400 mesh), eluting with 50% ethylacetate in petroleum ether, to obtain the title compound as a yellow solid (0.280 g, 37% yield). M.p. 184.6-186.1° C. LC-ESI-HRMS of [M+H]+ shows 391.0927 Da. Calc. 391.093046 Da, dev. −0.9 ppm.
Reaction SMILES: [OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[C:8]([C:9]([F:12])([F:11])[F:10])=[C:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:6][N:5]=1.[CH:20]([C:22]1[CH:31]=[C:30]2[C:25]([C:26](N3CCOCC3)=[CH:27][CH2:28][O:29]2)=[CH:24][CH:23]=1)=[CH2:21].C(N(CC)CC)C.C(O)(C(F)(F)F)=O>ClC(Cl)C.ClCCl>[C:13]1([C:7]2[O:6][N:5]=[C:4]([C:3]3[C:27]4[CH2:28][O:29][C:30]5[CH:31]=[C:22]([CH:20]=[CH2:21])[CH:23]=[CH:24][C:25]=5[C:26]=4[O:1][N:2]=3)[C:8]=2[C:9]([F:12])([F:11])[F:10])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C=Cc1ccc2c(c1)OCC=C2N1CCOCC1
Reactant: O/N=C(\Cl)c1noc(-c2ccccc2)c1C(F)(F)F
Solvent: CC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C=Cc1ccc2c(c1)OCc1c(-c3noc(-c4ccccc4)c3C(F)(F)F)noc1-2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 12.1 %

Procedure:
To a mixture of (Z)—N-hydroxy-5-phenyl-4-(trifluoromethyl)isoxazole-3-carbimidoyl chloride (Intermediate 13, 0.221 g, 0.646 mmol) and 4-(7-vinyl-2H-chromen-4-yl)morpholine (Preparation 53A, 0.535 M in dichloromethane, 1.21 mL, 0.646 mmol) at 0° C. was added triethylamine (0.108 mL, 0.776 mmol) dropwise over 3 min. The ice-bath was removed, and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with dichloromethane (30 mL), washed with water (15 mL), dried over anhydrous sodium sulfate, and concentrated to give a foamy solid. The product mixture was dissolved in dichloroethane (3 mL), TFA (0.075 mL, 0.970 mmol) was added, and the resulting solution was heated at 80° C. for ˜60 min. The reaction mixture was diluted with dichloromethane (30 mL), washed with a saturated aqueous solution of sodium bicarbonate (15 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate in hexane (5%-12%-20%) afforded 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4H-chromeno[3,4-d]isoxazole (0.033 g, 0.078 mmol, 12% yield) as a white solid. The product had an HPLC ret. time=3.93 min. (condition A); LC/MS M+1=411.0.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)(=[O:4])=[O:3].Br[C:15]1[N:16]=[C:17]([O:20][CH2:21][CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]2)[S:18][CH:19]=1>>[C:31]([O:30][C:28]([N:25]1[CH2:24][CH2:23][CH:22]([CH2:21][O:20][C:17]2[S:18][CH:19]=[C:15]([N:10]3[C:11]4[C:7](=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:13][CH:12]=4)[CH:8]=[CH:9]3)[N:16]=2)[CH2:27][CH2:26]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]
Reactant: CC(C)(C)OC(=O)N1CCC(COc2nc(Br)cs2)CC1
Reactant: CS(=O)(=O)c1ccc2[nH]ccc2c1
Product: CC(C)(C)OC(=O)N1CCC(COc2nc(-n3ccc4cc(S(C)(=O)=O)ccc43)cs2)CC1

Procedure:
The title compound was prepared by following the similar procedure as described in Example-1 by using 5-(methylsulfonyl)-1H-indole (intermediate-21) and tert-Butyl 4-(((4-bromothiazol-2-yl)oxy)methyl)piperidine-1-carboxylate (intermediate 47) (0.013 g, 10%).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([C:5]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[C:18]([O:23][CH3:24])[C:17]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)=[C:16]3[Cl:36])([C:7]2[N:11]([CH3:12])[N:10]=[N:9][CH:8]=2)[OH:6])[CH2:2]1.[C:37](OC(=O)C)(=[O:39])[CH3:38].C(Cl)(=O)C>CCN(CC)CC.ClCCl>[Cl:36][C:16]1[C:15]2[C:20](=[CH:21][CH:22]=[C:13]([C:5]([OH:6])([C:7]3[N:11]([CH3:12])[N:10]=[N:9][CH:8]=3)[CH:3]3[CH2:4][N:1]([C:37](=[O:39])[CH3:38])[CH2:2]3)[CH:14]=2)[N:19]=[C:18]([O:23][CH3:24])[C:17]=1[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]([F:33])([F:35])[F:34])=[CH:30][CH:31]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1nc2ccc(C(O)(c3cnnn3C)C3CNC3)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Solvent: CCN(CC)CC
Solvent: CC(=O)Cl
Solvent: ClCCl
Product: COc1nc2ccc(C(O)(c3cnnn3C)C3CN(C(C)=O)C3)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 58.2 %

Procedure:
To a flask containing azetidin-3-yl(4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (140 mg, 0.27 mmol, Intermediate 66: step d) was added dichloromethane (8 mL) which gave a suspension at room temperature. Et3N (0.13 mL, 0.9 mmol) was added, followed by acetic anhydride (0.3 mL, 0.32 mmol). After stirring at room temperature for 4 h, more Et3N (200 μL) was added along with more acetyl chloride (25 μL) and the suspension was heated to 35° C. for 18 h. The reaction was quenched with the addition of 1N NaOH (2 mL) and water (5 mL). The aqueous portion was extracted with dichloromethane (3×25 mL). The combined organics were dried over MgSO4, filtered and concentrated. The crude material was chromatographed on silica gel (5% MeOH-dichloromethane) to give the title compound (88 mg) as an off white solid. 1H NMR (500 MHz, CD3CN, racemate) δ 8.25 (dd, J=14.0, 1.9 Hz, 1H), 7.74 (dd, J=8.7, 2.6 Hz, 1H), 7.66 (d, J=4.4 Hz, 1H), 7.58-7.49 (m, 2H), 7.48-7.33 (m, 3H), 5.17 (s, 0.5H), 5.06 (s, 0.5H), 4.43-4.28 (m, 3H), 4.22-4.10 (m, 1H), 4.07-3.98 (m, 4H), 3.93 (dd, J=9.9, 6.0 Hz, 1H), 3.82 (dd, J=9.1, 5.6 Hz, 1H), 3.72 (t, J=8.6 Hz, 1H), 3.65-3.48 (m, 5H). MS (ESI) 560.1 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]3[O:28][N:27]=[C:26]([CH:29]([CH3:31])[CH3:30])[N:25]=3)[CH2:20][CH2:19]2)=[C:4]([C@H:10]([OH:17])[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8]>C(Cl)Cl>[Br:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]3[O:28][N:27]=[C:26]([CH:29]([CH3:31])[CH3:30])[N:25]=3)[CH2:20][CH2:19]2)=[C:4]([C@H:10]([O:17][C:4]([CH3:10])([CH3:5])[CH3:3])[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8]
Reactant: Cc1nc(C)c([C@H](O)C(=O)OC(C)C)c(N2CCC(c3nc(C(C)C)no3)CC2)c1Br
Solvent: ClCCl
Product: Cc1nc(C)c([C@H](OC(C)(C)C)C(=O)OC(C)C)c(N2CCC(c3nc(C(C)C)no3)CC2)c1Br
Temperature: 25 °C
Reaction time: 18 h
Yield: 154.6 %

Procedure:
The isobutylene gas was bubbled into a nitrogen purged, cooled (0° C.) solution of (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (540 g, 1.1 mmol) and 0.15 mL of 70% HClO4 in DCM (8 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 18 h in a pressure sealed vessel, diluted with DCM, washed with 1M Na2CO3 solution, and dried over Na2SO4. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-65% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 469 mg (78%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 6.15 (br. s, 1H), 4.94-4.89 (m, 1H), 3.94-3.90 (m, 1H), 3.21-3.13 (m, 1H), 3.11-3.01 (m, 2H), 2.93-2.78 (m, 1H), 2.53 (s, 3H), 2.43 (s, 3H), 2.17-2.02 (m, 3H), 1.90-1.82 (m, 2H), 1.26 (d, J=7.0 Hz, 6H), 1.16-1.14 (m, 12H), 1.07 (d, J=5.9 Hz, 3H). UPLC (M+H)=553.2.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9]([C:11]1[S:24][C:14]2[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:35])=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9]([C:11]1[S:24][C:14]2[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[S:35]
Reactant: CN(C(=O)c1cc2c(s1)-c1ccccc1OCC2)c1ccccc1Cl
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CN(C(=S)c1cc2c(s1)-c1ccccc1OCC2)c1ccccc1Cl
Temperature: 90 °C

Procedure:
To a suspension of N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide 157 (60 mg, 0.16 mmol) in dry toluene (2 mL) in a 20 mL scintillation vial was added Lawesson's reagent (4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide, 49 mg, 0.12 mmol, 0.75 equiv). The vial was sealed and heated at 90° C. for 36 hr. The mixture was cooled to room temperature, concentrated and purified by reverse phase HPLC to give 123 as a yellow solid. 1H NMR (CDCl3) δ 7.57 (m, 1H), 7.48 (m, 1H), 7.35-7.27 (m, 4H), 7.14 (m, 1H), 6.96 (m, 1H), 6.52 (s, 1H), 4.19 (m, 2H), 3.80 (s, 3H), 2.92 (m, 2H). MS: (ESI+) 386.1
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:9]2[CH:13]=NC=N2)=[N:4][C:5](=[O:8])[NH:6][CH:7]=1>CN>[CH3:13][NH:9][C:3]1[C:2]([CH3:1])=[CH:7][NH:6][C:5](=[O:8])[N:4]=1
Reactant: Cc1c[nH]c(=O)nc1-n1cncn1
Agent: CN
Product: CNc1nc(=O)[nH]cc1C
Temperature: 25 °C
Reaction time: 5 h
Yield: 80.2 %

Procedure:
1.06 g (6mmol) of 5-methyl-4-(1,2,4-triazol-1-yl)-pyrimidin-2(1H)-one are dissolved in 20 ml of 40% strength aqueous methylamine solution and the solution is stirred for 5 hours at room temperature. The solution is concentrated and chromatographed on silica gel using ethyl acetate/methanol 2/1. 0.67 g (80.3% of theory) of N4-methyl-5-methylcytosine is obtained as a colorless powder with melting point of 160°-165° C. (decomp.). 1H NMR, d6 -DMSO, δ[ppm]: 10.4 (s, 1H) 7.17 (s, 1H), 7.1 (s, broad, 1H), 2.8 (d, 3H), 1.82 (d, 3H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.Cl[C:16]1[N:21]=[C:20](N2CCCCC2)[C:19]([N+:28]([O-])=O)=[CH:18][N:17]=1>>[NH2:28][C:19]1[C:18]([N:1]2[CH2:6][CH2:5][CH2:4][C@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[N:17][CH:16]=[N:21][CH:20]=1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1N1CCCCC1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCNC1
Product: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ncncc2N)C1

Procedure:
Method 1 was followed using (S)-tert-butyl piperidin-3-ylcarbamate and 2-chloro-5-nitro-4-(piperidin-1-yl)pyrimidine. LCMS (m/z): 294.2 (MH+), Rt=0.56 min.
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][S:4]([C:6](SC)=[CH:7][N+:8]([O-:10])=[O:9])=O>CO>[CH3:3][S:4][C:6]([NH:2][CH3:1])=[CH:7][N+:8]([O-:10])=[O:9]
Reactant: CSC(=C[N+](=O)[O-])S(C)=O
Reactant: CN
Solvent: CO
Product: CNC(=C[N+](=O)[O-])SC
Yield: 54.7 %

Procedure:
A solution in methanol (100 ml) of methylamine (9.4 g) was added dropwise over 10 minutes to a stirred solution in methanol (500 ml) at 25°-30° of 1-methylsulphinyl-1-methylthio-2-nitroethylene (18.1 g). T.L.C. analysis indicated immediate complete disappearance of the sulphoxide. Evaporation of the reaction mixture yielded an oily solid which, on recrystallisation from isopropanol gave the title product (8.1 g) m.p. 113°-113.5°.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:10])[CH:5]=[CH:6][C:7](=O)[CH:8]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[SH:20].CN(C=O)C>CO>[CH3:1][O:2][C:3]1[C:4](=[O:10])[CH:5]=[C:6]2[C:7](=[N:11][C:12]3[C:13]([S:20]2)=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[CH:8]=1
Reactant: COc1ccc(N)c(S)c1
Reactant: COC1=CC(=O)C=CC1=O
Solvent: CN(C)C=O
Solvent: CO
Product: COc1ccc2nc3cc(OC)c(=O)cc-3sc2c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a suspension of 2-methoxy-p-benzoquinone (1.15 kg) (Step 1) in methanol (8 l) was added portionwise a suspension of 2-amino-5-methoxythiophenol (from Step 2) in methanol (6 l). The reacting mixture was stirred for 15 minutes, filtered and washed with methanol (8 l). The product isolated was swished with DMF (16 l) for 2 hours, filtered and air-dried. The crude material was dissolved in hot DMF (16 l) (130°-140° C.), filtered on Celite and the filtrate cooled to room temperature. The resulting crystals were filtered, washed with methanol (8 l) and air-dried to afford the title compound (70.3 g), m.p. 237°-238° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](B(O)O)[CH:6]=[CH:5]2.Br[C:16]1[CH:17]=[N:18][C:19]([C:22]([O:24]C)=[O:23])=[N:20][CH:21]=1>>[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:16]1[CH:17]=[N:18][C:19]([C:22]([OH:24])=[O:23])=[N:20][CH:21]=1)[CH:6]=[CH:5]2
Reactant: COC(=O)c1ncc(Br)cn1
Reactant: OB(O)c1ccc2cc(O)ccc2c1
Product: O=C(O)c1ncc(-c2ccc3cc(O)ccc3c2)cn1

Procedure:
Followed the two step procedure described for Example 7 starting from 6-hydroxynaphthalen-2-yl boronic acid and methyl 5-bromopyrimidine-2-carboxylate. 1H-NMR (DMSO-d6 500 MHz): 9.39 (s, 2H), 8.38 (s, 1H), 7.87-7.91 (t, J=8.5, 12.0 Hz, 3H), 7.17-7.20 (t, J=5.5, 10.5 Hz, 2H). MS (ESI): m/z=267.0 [M+1]+.
Reaction SMILES: FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:36]=[CH:35][C:34]([CH:37]2[CH2:41][CH2:40][O:39][CH2:38]2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]=[CH:23][C:15]=1[C:16]([O:18]C(C)(C)C)=[O:17])=[O:12]>C(Cl)Cl>[OH:8][C:9]1[CH:36]=[CH:35][C:34]([CH:37]2[CH2:41][CH2:40][O:39][CH2:38]2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:24]=[CH:23][C:15]=1[C:16]([OH:18])=[O:17])=[O:12]
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCOC2)ccc1O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1cc(C2CCOC2)ccc1O
Temperature: 25 °C
Reaction time: 3 h
Yield: 97 %

Procedure:
Trifluoroacetic acid (2 mL) was added to a methylene chloride (5 mL) solution of the obtained tert-butyl 2-(2-hydroxy-5-(tetrahydrofuran-3-yl)benzamido)-4-phenylbenzoate (0.027 g), followed by stirring at room temperature for 3 hours. The solvent was evaporated under reduced pressure, and diisopropyl ether was added to the obtained residue. The solid substance was collected by filtration to obtain 0.023 g of 2-(2-hydroxy-5-(tetrahydrofuran-3-yl)benzamido)-4-phenylbenzoic acid as a white solid.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]([CH2:12][CH3:13])[CH2:9][C:10]#[CH:11])(=O)=O.[F:14][C:15]([F:25])([F:24])[CH2:16][CH2:17][S:18]([CH2:21][C:22]#[N:23])(=[O:20])=[O:19].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[CH2:7]([CH:8]([CH2:9][C:10]#[CH:11])[CH2:12][CH2:13][CH:21]([S:18]([CH2:17][CH2:16][C:15]([F:14])([F:24])[F:25])(=[O:19])=[O:20])[C:22]#[N:23])[CH3:6]
Reactant: C#CCC(CC)CCOS(C)(=O)=O
Reactant: N#CCS(=O)(=O)CCC(F)(F)F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: C#CCC(CC)CCC(C#N)S(=O)(=O)CCC(F)(F)F
Temperature: 60 °C
Reaction time: 20 h
Yield: 37.7 %

Procedure:
To a solution of 0.7 g of 3-ethyl-5-hexynyl methanesulfonate and 0.7 g of (3,3,3-trifluoropropylsulfonyl)acetonitrile in 20 ml of dimethyl sulfoxide was added 0.5 g of potassium carbonate at room temperature. The reaction mixture was stirred at 60° C. for 20 hours. The reaction mixture was allowed to stand to cool to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to obtain 0.40 g of 5-ethyl-2-(3,3,3-trifluoropropylsulfonyl)-7-octynenitrile (hereinafter referred to as the present compound (29)).
Reaction SMILES: [CH3:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Br[CH2:17][CH2:18][CH2:19][CH2:20][C:21](OCC)([O:25]CC)[O:22][CH2:23][CH3:24].C(O)(=O)C>O1CCCC1>[CH2:23]([O:22][C:21]([CH2:20][CH2:19][CH2:18][CH2:17][CH2:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1)=[O:25])[CH3:24]
Reactant: CCOC(CCCCBr)(OCC)OCC
Reactant: Cc1cccc2cncn12
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCOC(=O)CCCCCc1cccc2cncn12
Reaction time: 0.29 h

Procedure:
5-Methylimidazo[1,5-a]pyridine [J. Org. Chem. 40, 1210 (1975), 424.7 g]is charged into a 12 liter flask equipped with mechanical stirrer, thermometer and nitrogen atmosphere. Dry tetrahydrofuran (THF, 3,000 ml) is charged into the flask and the resulting solution is cooled to -65° in a dry ice/acetone bath. n-Butyllithium (1.0 mole, 2.4 N in hexane) is poured into the flask all at once under a nitrogen atmosphere. The temperature rises to -32°. The mixture is recooled to -50° and a second mole of n-butyllithium is charged in the same manner. A second temperature rise occurs and after again cooling to -50°, a third mole of the n-butyl-lithium is charged into the reactor. The reaction mixture is then stirred for twenty minutes, the temperature drops to -65°. To this stirring solution a cold (-67°) solution of 5-bromo-1,1,1-triethoxypentane (606.9 g) in 500 ml of THF is added as rapidly as possible, raising the temperature to -25°. The reaction mixture is then warmed to -15° and stirred for 2 hours. Acetic acid (50 ml) is added and most of the solvent is removed under vacuum. The residue is taken up in 2,000 ml of ethyl ether; acetic acid (100 ml), and 12 N HCl (100 ml) are added while the reaction mixture is cooled to 0°. After 15 to 20 minutes, ice-cold 7.5 N ammonium hydroxide (1000 ml) is added. The organic phase is separated and the aqueous is washed again with ethyl ether (500 ml). The pH of the aqueous is adjusted to 9 with ammonium hydroxide and extracted again wth ethyl ether (500 ml). The combined ether extracts are washed with a dilute sodium chloride solution basified to pH 13-14 with potassium hydroxide. The ether extract is treated with charcoal and magnesium sulfate. The mixture is filtered and evaporated to give a dark oil which is dried at 2mm Hg. The oil is distilled under high vaccuum to give 5-(5-ethoxycarbonylpentyl)-imidazo[1,5-a]pyridine of Example 1, boiling at 220°/0.2 mm Hg.
Reaction SMILES: Br.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:19][C:18]([NH2:20])=[N:17][N:16]=3)=[CH:11][CH:10]=2)[CH:3]=1.[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>N1C=CC=CC=1.CO>[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[O:19][C:18]([NH:20][C:28](=[O:29])[C:27]4[CH:31]=[CH:32][C:24]([O:23][C:22]([F:21])([F:33])[F:34])=[CH:25][CH:26]=4)=[N:17][N:16]=3)=[CH:13][CH:14]=2)[CH:3]=1
Reactant: Nc1nnc(-c2ccc(Oc3cccnc3)cc2)o1
Reactant: O=C(Cl)c1ccc(OC(F)(F)F)cc1
Agent: Br
Solvent: CO
Solvent: c1ccncc1
Product: O=C(Nc1nnc(-c2ccc(Oc3cccnc3)cc2)o1)c1ccc(OC(F)(F)F)cc1
Reaction time: 6 h
Yield: 40.2 %

Procedure:
5-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt (167.5 mg, 0.5 mmol) was suspended in 2 mL of anhydrous pyridine. 4-Trifluoromethoxybenzoyl chloride (167.2 mg, 117 uL, 0.75 mmol) was added directly into the solution. The reaction mixture formed an orange-red solution with a small amount of precipitate. It was left to stir for 6 hours. Then it was diluted with ca. 1 mL of MeOH, filtered through 0.22 u syringe filter and purified by reverse phase preparative HPLC using acetonitrile/water mixture containing 0.01% of TFA. Fractions, containing the product, were combined and partitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3. The EtOAc layer was washed with brine, dried over anhydrous sodium sulfate and filtered. Solvent was removed in vacuo to give the title product as a yellow solid (89.0 mg). Yield 40.2%.
Reaction SMILES: [C:1]1(=[O:17])[N:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13](O)=[O:14])=[CH:8][CH:7]=2)[C:4](=[O:16])[CH:3]=[CH:2]1.C(Cl)(=O)C([Cl:21])=O>ClCCl>[C:1]1(=[O:17])[N:5]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13]([Cl:21])=[O:14])=[CH:8][CH:7]=2)[C:4](=[O:16])[CH:3]=[CH:2]1
Reactant: O=C(O)Cc1ccc(N2C(=O)C=CC2=O)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: O=C(Cl)Cc1ccc(N2C(=O)C=CC2=O)cc1
Temperature: 35 °C
Reaction time: 15 h
Yield: 59 %

Procedure:
1.0 g (4.33 mmol) of p-maleinimidophenylacetic acid were suspended in 25 ml of dichloromethane and diluted with a 2.5-fold excess of oxalic acid dichloride (1.37 g, 945 μl; 10.82 mmol). The reaction mixture was heated to 30-40° C. with the exclusion of moisture and stirred for 15 h. Then the solvent was removed under a vacuum and dried under a high vacuum. Crystallization from toluene yielded a yellow powder (yield: 59%); melting point: 154° C.; Rf-value: 0.29 (acetic ester/hexane 4/1)