Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:22][N:23]([CH3:28])[S:24](Cl)(=[O:26])=[O:25].C(OCC)(=O)C>ClCCl>[CH3:22][N:23]([CH3:28])[S:24]([N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:14])[CH2:5][CH2:6]1)(=[O:26])=[O:25]
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Reactant: CN(C)S(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CN(C)S(=O)(=O)N1CCC(NC(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 84.6 %

Procedure:
To a solution of 412 mg (2.06 mmol) of tert-butyl 4-piperidinyl-carbamate in 20 mL of dichloromethane were added 430 μL (3.09 mmol) of triethylamine and 265 μL (2.47 mmol) of dimethylsulfamoyl chloride and the mixture was stirred for 2 hours at room temperature. Then, the mixture was treated with ethyl acetate and the organic layer was washed with water and saturated saline solution, and then, dried over with anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent:dichloromethane/methanol=40/1) to give 536 mg (85%) of the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15](=O)[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])[CH3:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:29]>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15](=[S:29])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])[CH3:2]
Reactant: CCOC(=O)COc1cc(F)c(C)cc1C(=O)NCc1ccc(Br)cc1F
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCOC(=O)COc1cc(F)c(C)cc1C(=S)NCc1ccc(Br)cc1F
Temperature: 115 °C
Yield: 177.9 %

Procedure:
A stirring solution of [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (0.816 g, 1.83 mmol) in pyridine (3.7 mL, 0.5 M) was treated with phosphorus pentasulfide (0.41 g, 0.92 mmol) and heated to 115° C. for 3 h. The reaction was allowed to cool to room temperature, diluted with ethyl acetate and successively washed with 1 M HCl and saturated aq NaCl. The organic layer was dried over Na2SO41 filtered, and concentrated under reduced pressure. The resulting brown oil was dissolved in a minimal amount of methylene chloride and flushed through a plug of silica using 40% ethyl acetate in heptane as the eluant. The filtrate was concentrated to afford [2-(4-bromo-2-fluoro-benzylthiocarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (0.75 g, 89%) as a yellow solid: mp 98-100° C.; Rf 0.45 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 mHz) δ 10.15 (bs, 1H), 8.26 (d, J=8.4 Hz, 1H), 7.38 (t, J=8.4 Hz, 1H), 7.26-7.23 (m, 2H), 6.53 (d, J=10.8 Hz, 1H), 5.08 (d, J=5.4 Hz, 2H), 4.67 (s, 3H), 4.20 (q, J=7.2 Hz, 2H), 2.23 (s, 2H), 1.27 (dt, J1=6.8 Hz, J2=0.6 Hz, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:13][C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]3[CH:39]=[CH:38][C:28]([CH2:29][P:30](=[O:37])([O:34][CH2:35][CH3:36])[O:31][CH2:32][CH3:33])=[CH:27][C:26]=3[O:40][CH3:41])[N:15]=2)=[C:6]2[C:10]=1[CH2:9][N:8]([CH3:11])[C:7]2=[O:12].[CH3:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>>[CH2:32]([O:31][P:30]([CH2:29][C:28]1[CH:38]=[CH:39][C:25]([NH:24][C:16]2[N:15]=[C:14]([NH:13][C:5]3[CH:4]=[CH:3][C:2]([N:46]4[CH2:47][CH2:48][N:43]([CH3:42])[CH2:44][CH2:45]4)=[C:10]4[C:6]=3[C:7](=[O:12])[N:8]([CH3:11])[CH2:9]4)[C:19]([C:20]([F:22])([F:21])[F:23])=[CH:18][N:17]=2)=[C:26]([O:40][CH3:41])[CH:27]=1)(=[O:37])[O:34][CH2:35][CH3:36])[CH3:33]
Reactant: CN1CCNCC1
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(Br)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(N4CCN(C)CC4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC

Procedure:
The title compound was prepared according to the procedure for Example 199 using Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxybenzyl]phosphonate and N-methylpiperazine. MS (ES+): m/z 678.34 (100) [MH+]; HPLC: tR=0.71 min (UPLC, purity).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[S:15][C:14](Br)=[N:13][C:12]=2[CH3:17])=[O:10])[CH:2]=1.[NH:18]1[C:22](B(O)O)=[CH:21][CH:20]=[N:19]1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[S:15][C:14]([C:22]3[NH:18][N:19]=[CH:20][CH:21]=3)=[N:13][C:12]=2[CH3:17])=[O:10])[CH:2]=1
Reactant: Cc1nc(Br)sc1C(=O)NCc1cccnc1
Reactant: OB(O)c1ccn[nH]1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: Cc1nc(-c2ccn[nH]2)sc1C(=O)NCc1cccnc1
Temperature: 100 °C
Yield: 87.7 %

Procedure:
To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (pyridine-3-ylmethyl)-amide (5.0 g, 16.0 mmol) in toluene (30 mL), water (10 mL) and ethanol (10 mL) was added 1H-pyrazole-5-boronic acid (2.15 g, 19.2 mmol), Pd(PPh3)4 (1.85 g, 1.60 mmol), and potassium carbonate (6.64 g, 48.1 mmol). The resulting mixture was degassed three times and heated to 100° C. for 16 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and washed with brine (2×100 mL). The organic phase was dried (Na2SO4) and evaporated. The residue was recrystallized from ethyl acetate to provide 4-methyl-2-(2H-pyrazol-3-yl)-thiazole-5-carboxylic acid (pyridine-3-ylmethyl)amide as a white solid (4.20 g, 85% yield).
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][CH2:7][NH:8][C:9]1[N:13]([CH2:14][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:16])[C:12]2[CH:23]=[CH:24][CH:25]=[CH:26][C:11]=2[N:10]=1>C(Cl)(Cl)Cl>[ClH:3].[CH2:14]([N:13]1[C:12]2[CH:23]=[CH:24][CH:25]=[CH:26][C:11]=2[N:10]=[C:9]1[NH:8][CH2:7][CH2:6][Cl:3])[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:16]
Reactant: O=S(Cl)Cl
Reactant: O=C(Cn1c(NCCO)nc2ccccc21)c1ccccc1
Solvent: ClC(Cl)Cl
Product: Cl
Product: O=C(Cn1c(NCCCl)nc2ccccc21)c1ccccc1
Yield: 90 %

Procedure:
Add 0.7 ml (10 mmol) of freshly distilled thionyl chloride, with stirring, to a suspension of 1.5 g (5 mmol) of the base obtained above in 25 ml of anhydrous chloroform. Heat the resulting solution at reflux for 1 hour. After cooling, the 1-phenacyl-2-(2-chloroethylamino)benzimidazole hydrochloride precipitate is isolated by filtration, washed with petroleum ether and recrystallised from a mixture of ethanol/ether.
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:36])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:25]=2)=[CH:18][C:17]=1[NH:37][C:38](=[O:46])[C:39]1[CH:44]=[CH:43][C:42]([OH:45])=[CH:41][CH:40]=1.O[CH:48]1[CH2:52][CH2:51][O:50][CH2:49]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:36])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:25]=2)=[CH:18][C:17]=1[NH:37][C:38](=[O:46])[C:39]1[CH:40]=[CH:41][C:42]([O:45][CH:48]2[CH2:52][CH2:51][O:50][CH2:49]2)=[CH:43][CH:44]=1
Reactant: OC1CCOC1
Reactant: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)c2)cc1NC(=O)c1ccc(O)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)c2)cc1NC(=O)c1ccc(OC2CCOC2)cc1
Temperature: 5 °C
Yield: 298.2 %

Procedure:
Di-isopropyl azodicarboxylate (0.21 ml) was added to a stirred mixture of N-[2-methyl-5-(3-morpholinobenzamido)phenyl]4-hydroxybenzamide (0.15 g), 3-hydroxytetrahydrofuran (0.31 g), triphenyl phosphine (0.275 g) and methylene chloride (5 ml) which had been cooled to 5° C. The resultant mixture was stirred at ambient temperature for 18 hours. The mixture was poured onto a pre-wetted (methylene chloride) ion-exchange column (isolute SCX 5 g column from International Sorbent Technology Limited) and eluted in turn with methylene chloride (40 ml), with methylene chloride (40 ml) containing 20% methanol and with methylene chloride containing 20% methanol and 3% of a saturated aqueous ammonium hydroxide solution. The product so obtained was further purified by column chromatography on silica using a 4:1 mixture of ethyl acetate and methanol as eluent. There was thus obtained the title compound as a solid (0.52 g); Mass Spectrum: M+H+ 502.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7]#[C:8][C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])[N:6]=1.Cl.[Cl:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23]([CH2:25]Cl)[CH:24]=1>>[Cl:18][C:19]1[CH:24]=[C:23]([CH2:25][N:3]2[CH:4]=[C:5]([C:7]#[C:8][C:9]3[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=3)[C:12]#[N:13])[N:6]=[C:2]2[CH3:1])[CH:22]=[N:21][CH:20]=1
Reactant: ClCc1cncc(Cl)c1
Reactant: Cc1nc(C#Cc2cccc(C#N)c2)c[nH]1
Agent: Cl
Product: Cc1nc(C#Cc2cccc(C#N)c2)cn1Cc1cncc(Cl)c1

Procedure:
The title compound, MS: m/e=333.1 (M+H30), was prepared in accordance with the general method of example 1 from 3-(2-methyl-1H-imidazol-4-ylethynyl)-benzonitrile and 3-chloro-5-chloromethyl-pyridine hydrochloride.
Reaction SMILES: [C:1](OC(=O)C)(=O)[CH3:2].[Br:8][C:9]1[CH:10]=[C:11]([CH3:17])[C:12]([NH:15][NH2:16])=[N:13][CH:14]=1>C1COCC1.O1CCOCC1.C(O)(=O)C>[Br:8][C:9]1[CH:10]=[C:11]([CH3:17])[C:12]2[N:13]([C:1]([CH3:2])=[N:16][N:15]=2)[CH:14]=1
Reactant: Cc1cc(Br)cnc1NN
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: Cc1cc(Br)cn2c(C)nnc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 96.3 %

Procedure:
A solution of acetic anhydride (12.22 mL, 129 mmol) in THF (10 mL) was added over a 10 min period to a suspension of 5-bromo-2-hydrazinyl-3-methylpyridine (25 g, 118 mmol) (Step 130.5) in dioxane (125 mL) and acetic acid (25 mL), at rt. The reaction mixture was stirred for 10 min at rt, heated to 100° C., stirred for 7 h at this temperature, and concentrated. The solid residue was purified by trituration with TBME to provide the title compound (25.7 g) as a colorless solid. tR: 0.39 min (LC-MS 2); ESI-MS: 225.9 [M+H]+ (LC-MS 2).
Reaction SMILES: [CH3:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C:9]2[C:22]3[C:21](=[O:23])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14](=[O:24])[C:13]=3[CH:12]=[CH:11][C:10]=2[NH:25][C:26](=[O:29])[CH2:27]Cl)=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[N:41]1([CH2:47][CH2:48][OH:49])[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>O1CCCC1>[CH3:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C:9]2[C:22]3[C:21](=[O:23])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14](=[O:24])[C:13]=3[CH:12]=[CH:11][C:10]=2[NH:25][C:26](=[O:29])[CH2:27][N:44]2[CH2:45][CH2:46][N:41]([CH2:47][CH2:48][OH:49])[CH2:42][CH2:43]2)=[O:7])=[CH:4][CH:3]=1
Reactant: OCCN1CCNCC1
Reactant: Cc1ccc(C(=O)Nc2c(NC(=O)CCl)ccc3c2C(=O)c2ccccc2C3=O)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)Nc2c(NC(=O)CN3CCN(CCO)CC3)ccc3c2C(=O)c2ccccc2C3=O)cc1
Reaction time: 0.12 h
Yield: 48 %

Procedure:
Compound CC-12 (0.86 g, 2 mmole) was dissolved in anhydrous tetrahydrofuran (30 ml), and to the solution was added successively with DIPEA (1 ml, 6 mmole) and 2-(piperazin-1-yl)ethanol (0.97 ml, 8 mmole) under stirring for 5 to 10 minutes. This mixture was heated under reflux for 16 hours. After the completion of the reaction, the mixture was filtered, and the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator). The residue was extracted with ethyl acetate for several times. The extract was dried on magnesium sulfate, and concentrated under reduced pressure. The crude product was washed with ethyl acetate/hexane. Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-44. Mol. Wt.: 526.5830 (C30H30N4O5); Rf: 0.41 (ethyl acetate:n-hexane=1:2); Yield: 48%; Mp.: 210-211° C. (EtOH); HRMS (EI) m/z: calcd [M]+, 526.2216 (C30H30N4O5+). Found, 526.2219. 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 1.92 (t, J=6.0 Hz, 2H, —NCH2—), 2.03 (br, 4H, —CH2—), 2.39 (br, 4H, —CH2—), 2.43 (s, 3H, —CH3), 3.01 (s, 2H, —CH2N—), 3.26-3.30 (m, 2H, —CH2OH), 4.29 (t, J=5.4 Hz, 1H, —CH2OH), 7.43 (d, J=8.1 Hz, 2H, Ar—H), 7.87-7.91 (m, 2H, Ar—H), 8.07-8.19 (m, 4H, Ar—H), 8.27 (d, J=8.7 Hz, 1H, Ar—H), 8.79 (d, J=8.7 Hz, 1H, Ar—H), 10.00 (s, 1H, Ar—NH—), 10.50 (s, 1H, Ar—NH—); 13C-NMR (75 MHz, DMSO-d6) δ (ppm): 20.93, 52.32, 52.93, 58.21, 59.1, 61.69, 125.11, 126.37, 126.72, 126.98, 127.81, 128.04, 128.33, 129.24, 130.53, 130.53, 140.68, 142.70, 166.37 (NCO), 169.28 (NCO), 181.50 (CO), 183.67 (CO).
Reaction SMILES: [OH:1][C:2]1[C:3]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[CH:10][C:4]=2[S:5][C:6]=1[C:7]([NH2:9])=[O:8].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[CH:27]=O)=[CH:22][CH:21]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[OH:1][C:2]1[C:3]2[CH:13]=[C:12]([C:14]([F:17])([F:15])[F:16])[CH:11]=[CH:10][C:4]=2[S:5][C:6]=1[C:7]([NH:9][CH:27]=[C:26]([C:23]1[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=1)[C:29]1[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=1)=[O:8]
Reactant: COc1ccc(C(C=O)c2ccc(OC)cc2)cc1
Reactant: NC(=O)c1sc2ccc(C(F)(F)F)cc2c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(C(=CNC(=O)c2sc3ccc(C(F)(F)F)cc3c2O)c2ccc(OC)cc2)cc1
Yield: 78.9 %

Procedure:
To a solution of 3-hydroxy-5-trifluoromethylbenzo[b]thiophene-2-carboxamide (300 mg, 1.15 mmol) in hot toluene (30 ml) were added 2,2-di-(4-methoxyphenyl)acetaldehyde (380 mg, 1.48 mmol) and p-toluenesulfonic acid monohydrate (20 mg). The reaction mixture was stirred at reflux temperature for one hour with azeotropic removal of water, cooled, and evaporated. Trituration of the residue with diethyl ether gave a yellow solid that was filtered, washed with ether, and dried in vacuo; to yield 453 mg (79%) of 3-hydroxy-N-[2,2-di(4-methoxyphenyl)ethenyl]-5-trifluoromethylbenzo[b]-thiophene-2-carboxamide, m.p. 178°-183° C.
Reaction SMILES: [N:1]([C@@H:4]1[C@H:8]([OH:9])[C@@H:7]([CH2:10][OH:11])[O:6][C@H:5]1[N:12]1[CH:19]=[CH:18][C:16](=[O:17])[NH:15][C:13]1=[O:14])=[N+:2]=[N-:3].[I:20]Cl.CCOCC>CO>[I:20][C:18]1[C:16](=[O:17])[NH:15][C:13](=[O:14])[N:12]([CH:19]=1)[C@@H:5]1[O:6][C@H:7]([CH2:10][OH:11])[C@@H:8]([OH:9])[C@H:4]1[N:1]=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=N[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O
Reactant: ClI
Solvent: CO
Solvent: CCOCC
Product: [N-]=[N+]=N[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cc(I)c(=O)[nH]c1=O
Temperature: 50 °C
Reaction time: 0.25 h
Yield: 76.5 %

Procedure:
To a solution of 2′-azido,2′-deoxyuridine (2.5 g, 9.3 mmoles) in methanol (20 ml) is added ICl (3.3 g, 20.5 mmoles, 2.2 eq.). The mixture is heated at 50° C. for 30 min. After cooling to room temperature, an equal volume of ether is added and the white precipitate is filtered off. The precipitate is stirred in methanolic ammonia (20 ml) at room temperature for 15 min, and then evaporated to dryness to yield 2.81 g (76%) of 5-iodo,2′-azido,2′-deoxyuridine. 1H NMR (300 MHz, methanol -d4) δ 8.58 (s, 1H, H6), 5.88 (d, 1H, H1′, JH1′,H2′=3.5 Hz), 4.46 (t, 1H, H3′, J=5.8 Hz), 4.11 (dd, 1H, H2′, JH1′,H2′=3.9 Hz, J H2′,H3′=5.3 Hz), 4.01 (m, 1H, H4′), 3.91 (dd, 1H, H5′λJgem=12.3 Hz, JH5′,H4′=2.4 Hz) 3.76 (dd, 1H, H5′β, Jgem=12.3 Hz, JH5′,H4′=2.4 Hz). 13C NMR (75 MHz, methanol-d4) δ 163.03, 152.17, 146.50, 88.88, 86.18, 71.21, 67/67, 61.00, 48.15. FAB mass spectrum, (M+H) m/z 396.
Reaction SMILES: [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:9](OC(=O)C)(=[O:11])[CH3:10].S([O-])([O-])(=O)=O.[Mg+2]>[N+](C)([O-])=O.CCOCC.[Sc]>[CH3:8][O:7][C:1]1[CH:6]=[CH:5][C:4]([C:9](=[O:11])[CH3:10])=[CH:3][CH:2]=1
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccccc1
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Agent: [Sc]
Solvent: C[N+](=O)[O-]
Solvent: CCOCC
Product: COc1ccc(C(C)=O)cc1
Temperature: 21 °C
Reaction time: 0.17 h
Yield: 97.2 %

Procedure:
The catalytic effect of the scandium salt of 5-trifluoromethanesulfonyl-1,3-dibutyl-2-sulfonyl-barbituric acid, obtained in Example 25, towards a Friedel-Crafts reaction of acylation was evaluated in the following manner. In 40 ml of anhydrous nitromethane, there is added 887 mg (0.7 moles) of the scandium salt of 5-trifluoromethylsulfonyl-1,3-dibutyl-2-sulfonyl-barbituric acid, and 1.08 g (10 mmoles) of anisole and 2.04 g (20 mmoles) of acetic anhydride. After stirring during 10 min at 21° C., the reaction mixture was diluted with 50 ml of ether and the reaction was inhibited with 100 ml of a saturated solution of sodium bicarbonate NaHCO3. After filtration on Celite, the solution was extracted with three fractions of 50 ml ether, then the collected ether phase was washed with a saturated solution of potassium chloride. After drying the ether phase with magnesium sulfate and evaporation, 1.46 g of p-methoxyacetophenone (95% yield) were recovered with a purity characterized by a proton RMN higher than 99%.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>ClCCl>[CH3:21][S:22]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:24])=[O:23]
Reactant: OCCCCCCc1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCCCCc1ccccc1
Temperature: -4 °C
Reaction time: 0.5 h

Procedure:
To a chilled (-4° C.) solution of 19.4 g. of 6-phenylhexanol (prepared as described in Example 46) and 15.1 g. of triethylamine in 500 ml. of dichloromethane is added dropwise, over 5 minutes, 12.6 g. of methanesulfonyl chloride. The mixture is stirred at -10° C. for 30 minutes and the solution washed successively with 200 ml. of cold water, 200 ml. of cold 10% hydrochloric acid, 200 ml. of cold saturated sodium bicarbonate and 200 ml. of cold saturated sodium chloride solution. The organic layer is dried over magnesium sulfate and the solvent removed under reduced pressure to give 6-phenylhexanol O-methanesulfonate as an oil.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:18][C@@H:19]1[CH2:41][C@@H:40]2[C@:35]([CH3:49])([CH2:36][CH2:37][C@H:38]([O:42][CH:43]3[CH2:48][CH2:47][CH2:46][CH2:45][O:44]3)[CH2:39]2)[C@@H:34]2[C@@H:20]1[C@H:21]1[C@:31]([CH3:50])([CH2:32][CH2:33]2)[C@@H:24]([C@H:25]([CH3:30])[CH2:26][CH2:27][CH2:28][OH:29])[CH2:23][CH2:22]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:11]([O:18][C@@H:19]1[CH2:41][C@@H:40]2[C@:35]([CH3:49])([CH2:36][CH2:37][C@H:38]([O:42][CH:43]3[CH2:48][CH2:47][CH2:46][CH2:45][O:44]3)[CH2:39]2)[C@@H:34]2[C@@H:20]1[C@H:21]1[C@:31]([CH3:50])([CH2:32][CH2:33]2)[C@@H:24]([C@H:25]([CH3:30])[CH2:26][CH2:27][CH:28]=[O:29])[CH2:23][CH2:22]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: C[C@H](CCCO)[C@H]1CC[C@H]2[C@@H]3[C@H](OCc4ccccc4)C[C@H]4C[C@@H](OC5CCCCO5)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](CCC=O)[C@H]1CC[C@H]2[C@@H]3[C@H](OCc4ccccc4)C[C@H]4C[C@@H](OC5CCCCO5)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 97 %

Procedure:
DMSO (0.01 ml, 0.14 mmol) in CH2Cl2 (0.1 ml) was added dropwise to a stirred solution of oxalyl chloride (0.008 ml, 0.0917 mmol) in anhydrous CH2Cl2 (2 ml) at −78° C. under anhydrous conditions (drying tube). This solution was stirred at −78° C. for 15 minutes. Steroid 2008 (0.0234 g, 0.0423 mmol) in dry CH2Cl2 (0.5 ml) was then added dropwise and the solution stirred for 40 minutes at −78° C. Diisopropylethylamine (DIPEA) (0.08 ml, 0.458 mmol) was added and the solution allowed to warm to 0° C. with stirring over a 30-minute period. Aqueous saturated NaHCO3 solution (5 ml) was added and the solution extracted 3× with 5 ml CH2Cl2. The combined organic extracts were washed 2× with 5 ml of aqueous saturated NaCl solution, dried over anhydrous MgSO4, filtered, and the solvent removed in vacuo. Flash chromatography (SiO2, 10:1 hexanes:EtOAc) gave compound 2009 (0.0226 g, 97%) as a white solid foam. 1H NMR (500 MHz, CDCl3) δ: 9.76 (s, 1H, C-24 H), 7.35-7.34 (m, 5H, benzyl Ar—H), 4.71-4.69 (m, 1H, THP ether methine H), 4.59 (d, J=11.8 Hz, 1/2H, benzyl-CH2), 4.585 (d, J=11.8 Hz, 1/2H, benzyl-CH2), 4.30 (d, J=12.0 Hz, 1/2H, benzyl-CH2), 4.29 (d, J=12.0 Hz, 1/2H, benzyl-CH2), 3.95-3.89 (m, 1H, THP OCH2), 3.63-3.58 (m, 3H, C-24 H & THP OCH2) 3.50-3.47 (m, 1H, C-3 H), 3.45 (s, 1H, 7-H), 2.49-2.42 (m, 1H, C-23H), 2.37-2.31 (m, 1H, C-23 H), 0.958 (d, J=6.5 Hz, 3H, C-21 H), 0.81 (s, 3H, C-19 H), 0.63 (s, 3H, C-18 H) (Note: product is a mixture of diastereomers); IR (CHCl3) 2900, 1700 cm−1; MS (CI/isobutane) m/z 552 (M+1, 0.4%), 465 (M+1-THP, 3%), 449 (M+1-THPO, 14%), 375 (M+1-THP-Bn, 7%), 359 (M+1-THP-HOBn, 68%), 341 (M+1-THP-HOBn-H2O, 100%); m.p. 50-54° C.; Anal. calcd. for C36H54O4: C=78.50; H=9.88. Found: C=78.11; H=10.04.
Reaction SMILES: [C:1]([N:4]1[C:13]2[N:12]=[CH:11][C:10]([C:14]3[CH:15]=[C:16]([CH2:20][O:21][CH2:22][C:23]([OH:25])=O)[CH:17]=[N:18][CH:19]=3)=[CH:9][C:8]=2[CH2:7][CH2:6][CH2:5]1)(=[O:3])[NH2:2].CN(C(ON1N=N[C:36]2[CH:37]=[CH:38][CH:39]=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCCC1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:25]=[C:23]([N:40]1[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]1)[CH2:22][O:21][CH2:20][C:16]1[CH:15]=[C:14]([C:10]2[CH:9]=[C:8]3[C:13](=[N:12][CH:11]=2)[N:4]([C:1]([NH2:2])=[O:3])[CH2:5][CH2:6][CH2:7]3)[CH:19]=[N:18][CH:17]=1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: NC(=O)N1CCCc2cc(-c3cncc(COCC(=O)O)c3)cnc21
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: NC(=O)N1CCCc2cc(-c3cncc(COCC(=O)N4CCCCC4)c3)cnc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 30.8 %

Procedure:
To a stirred solution of [5-(8-carbamoyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-pyridin-3-ylmethoxy]-acetic acid (80 mg, 0.23 mmol) in DMF (3 mL) is added HATU (107 mg, 0.28 mmol) followed by piperidine (20 mg, 0.23 mmol) and DIEA (0.26 ml, 1.50 mmol). The resulting mixture is stirred at room temperature for 2 hrs. The reaction is concentrated and the remaining residue is purified via flash column chromatography to give the titled product (29 mg).
Reaction SMILES: Br[C:2]1[C:3](Br)=[C:4](Br)[C:5](Br)=[C:6]([CH3:9])[C:7]=1[CH3:8].[C:13](#[N:18])/[CH:14]=[CH:15]/[C:16]#[N:17].[I-].[Na+].S([O-])(O)=O.[Na+]>CN(C)C=O>[C:16]([C:15]1[C:14]([C:13]#[N:18])=[CH:8][C:7]2[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:9]=1)#[N:17]
Reactant: N#C/C=C/C#N
Reactant: Cc1c(C)c(Br)c(Br)c(Br)c1Br
Agent: O=S([O-])O
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1cc2ccccc2cc1C#N
Temperature: 0 °C
Reaction time: 7 h
Yield: 80 %

Procedure:
To 0.1 mole of tetrabromoxylene, 0.17 mole of fumaronitrile, 0.66 mole of sodium iodide and 400 ml of anhydrous dimethylformamide were added and heated with stirring at 70° to 80° C. for 7 hours. The reaction solution was added to 800 g of ice water. To the deposited precipitate, about 15 g of sodium hydrogen sulfite was added and allowed to stand overnight. After filtration by suction and drying, white 2,3-dicyano-naphthalene was obtained by recrystallization from chloroform/ethanol in yield of 80%.