Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:19]=[C:18]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1)([O-])=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClC1C=CC=CC=1Cl>[C:20]([C:18]1[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]2[N:1]=[C:4]3[C:5]([CH:6]=[CH:7][CH:8]=[CH:9]3)=[C:10]2[CH:19]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)c1cc(-c2ccccc2[N+](=O)[O-])nc2ccccc12
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Clc1ccccc1Cl
Product: CC(C)(C)c1cc2c3ccccc3nn2c2ccccc12

Procedure:
A solution of 15.3 g (50 mmol) of 2-(2-nitrophenyl)-4-tert-butylquinoline and 34.1 g (130 mmol) of triphenylphosphine in 150 ml of o-dichlorobenzene is heated under reflux for 12 h. After cooling, the solvent is removed in vacuo, the residue is recrystallised twice from ethyl acetate and then chromatographed on silica gel (DCM:heptane 3:1, v:v+0.2% of triethylamine). The solid obtained in this way is freed from readily volatile and non-volatile secondary components by fractional sublimation (p about 1×10−5 mbar, T about 180° C.). Yield: 8.8 g (32 mmol), 64%, purity: about 99.5% (NMR).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[C:15](SC)[N:14]=[C:13]([NH:19][C:20]3[CH:29]=[CH:28][C:23]4[O:24][CH2:25][CH2:26][O:27][C:22]=4[CH:21]=3)[CH:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1C=C(Cl)C=C([C:37](OO)=[O:38])C=1>C(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[C:15]([O:38][CH3:37])[N:14]=[C:13]([NH:19][C:20]3[CH:29]=[CH:28][C:23]4[O:24][CH2:25][CH2:26][O:27][C:22]=4[CH:21]=3)[CH:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CSc1nc(Nc2ccc3c(c2)OCCO3)cc(-c2ccc(C(C)(C)C)cc2)n1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1nc(Nc2ccc3c(c2)OCCO3)cc(-c2ccc(C(C)(C)C)cc2)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a 50-mL, round-bottomed flask containing a solution of 6-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-(methylthio)pyrimidin-4-amine from step (b) above (0.41 g, 1.0 mmol) in CH2Cl2 (10 mL) was added m-CPBA (0.38 g, 2.2 mmol, Aldrich). The reaction mixture was stirred at room temperature for 0.5 h, and the solvent was removed in vacuo. The residue was dried in vacuo to provide the title product. MS (ESI, pos. ion) m/z: 439 (M+1).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:7][C:5]=1[NH2:6])([O-])=O.[BH4-].[Na+]>CO.[Pd]>[C:11]1([C:9]2[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([NH2:1])[CH:10]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: Nc1ccc(-c2ccccc2)cc1[N+](=O)[O-]
Agent: [Pd]
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Nc1ccc(-c2ccccc2)cc1N

Procedure:
To a suspension of 2 g (9.3 mmol) of the product obtained in Example 22 in 20 ml of methanol were slowly added 0.2 g of palladium on carbon and 0.7 g of NaBH4. After the addition of NaBH4 had ended, the reaction was already complete. The reaction mixture was filtered through shell lime and washed with ethyl acetate, and the solvent was removed under reduced pressure. This gave 1.3 g (77%).
Reaction SMILES: C[Si](C)(C)N1C(=O)C2=CC=CC=C2C1=O.C[Si](C)(C)[O:18][C:19]([CH:21]([N:25]1[CH:28]([S:29][N:30]2[C:34](=[O:35])[C:33]3=[CH:36][CH:37]=[CH:38][CH:39]=[C:32]3[C:31]2=[O:40])[CH:27]([N:41]2[C:45](=[O:46])[C:44]3=[CH:47][CH:48]=[CH:49][CH:50]=[C:43]3[C:42]2=[O:51])[C:26]1=[O:52])[C:22]([CH3:24])=[CH2:23])=[O:20]>CC(N(C)C)=O>[C:19]([CH:21]([N:25]1[CH:28]([S:29][N:30]2[C:34](=[O:35])[C:33]3=[CH:36][CH:37]=[CH:38][CH:39]=[C:32]3[C:31]2=[O:40])[CH:27]([N:41]2[C:42](=[O:51])[C:43]3=[CH:50][CH:49]=[CH:48][CH:47]=[C:44]3[C:45]2=[O:46])[C:26]1=[O:52])[C:22]([CH3:24])=[CH2:23])([OH:20])=[O:18]
Reactant: C=C(C)C(C(=O)O[Si](C)(C)C)N1C(=O)C(N2C(=O)c3ccccc3C2=O)C1SN1C(=O)c2ccccc2C1=O
Agent: C[Si](C)(C)N1C(=O)c2ccccc2C1=O
Solvent: CC(=O)N(C)C
Product: C=C(C)C(C(=O)O)N1C(=O)C(N2C(=O)c3ccccc3C2=O)C1SN1C(=O)c2ccccc2C1=O

Procedure:
A solution of 1.1 g (3 mmoles) of 6-phthalimidopenicillanic acid-R-sulphoxide in 20 ml of dimethylacetamide was treated with 4 g (18 mmoles) of N-trimethylsilylphthalimide at 100° C. After 4 hours the mixture (containing 1-(1-trimethylsilyloxycarbonyl-2-methylprop-2-enyl)-3-phthalimido-4-phthalimidothio-azetidin-2-one) was concentrated, the residue was dissolved in 30 ml of dichloromethane and the solution was filtered. The filtrate was purified by chromatography on a silica gel column impregnated with 1% acetic acid, using a 4:1 (v/v) mixture of toluene and acetone containing 0.5% acetic acid as an eluent. There were obtained 100 mg of 7-phthalimido-Δ3 -desacetoxycephalosporanic acid and 210 mg of 1-(1-carboxy-2-methylprop-2-enyl)-3-phthalimido-4-phthalimidothio-azetidin-2-one contaminated with dimethylacetamide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]([CH3:38])[C:16]([N:18]3[CH2:23][CH2:22][CH:21]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[C:27]([C:34]([F:37])([F:36])[F:35])[CH:26]=4)[CH2:20][CH2:19]3)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:48])=CC=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]([CH3:38])[C:16]([N:18]3[CH2:23][CH2:22][CH:21]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[C:27]([C:34]([F:37])([F:36])[F:35])[CH:26]=4)[CH2:20][CH2:19]3)=[S:48])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC(CN1CCN(c2ccc(Cl)cc2)CC1)C(=O)N1CCC(Nc2ccc([N+](=O)[O-])c(C(F)(F)F)c2)CC1
Product: CC(CN1CCN(c2ccc(Cl)cc2)CC1)C(=S)N1CCC(Nc2ccc([N+](=O)[O-])c(C(F)(F)F)c2)CC1

Procedure:
3-[4-(4-Chloro-phenyl)-piperazin-1-yl]-2-methyl-1-[4-(4-nitro-3-trifluoromethyl-phenylamino)-piperidin-1-yl]-propan-1-one (6 mg; 0.011 mmol, prepared in accordance with Example 61) is reacted with Lawesson's reagent (2 mg; 0.005 mmol) according to the general conditions described in Example 109. The desired product is obtained following purification by preparative HPLC (2 mg; 0.004 mmol). The structure was confirmed using Protocol I-B. Calculated mass=570; observed mass=570; HPLC retention time=4.69 min
Reaction SMILES: Cl.[OH:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[N:8][C:9]([C:12]2[N:13]([CH3:20])[C:14]([N+:17]([O-:19])=[O:18])=[CH:15][N:16]=2)=[N:10][CH:11]=1.[C:21](OC(=O)C)(=[O:23])[CH3:22]>O>[C:21]([O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[N:10][C:9]([C:12]2[N:13]([CH3:20])[C:14]([N+:17]([O-:19])=[O:18])=[CH:15][N:16]=2)=[N:8][CH:7]=1)(=[O:23])[CH3:22]
Reactant: Cn1c([N+](=O)[O-])cnc1-c1ncc(OCCO)cn1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Solvent: O
Product: CC(=O)OCCOc1cnc(-c2ncc([N+](=O)[O-])n2C)nc1

Procedure:
0.29 g. (1 millimole) of 5-(2-hydroxyethoxy)-2-(5-nitro-1-methyl-2-imidazolyl)-pyrimidine hydrochloride is heated in 3 ml. of acetic anhydride to 100° C. for 1 hour. After cooling, the reaction mixture is introduced into water and the product is filtered off; m.p. 148°-150° C.
Reaction SMILES: N[C:2]1[C:3]([CH2:12][OH:13])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.N([O-])=O.[Na+].[I-:18].[K+].OS(O)(=O)=O.[O-]S([O-])=O.[Na+].[Na+]>O.CC(C)=O.Cl>[I:18][C:2]1[C:3]([CH2:12][OH:13])=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: [I-]
Reactant: Nc1cc2ccccc2cc1CO
Agent: Cl
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: OCc1cc2ccccc2cc1I
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of (3-amino-2-naphthyl)methanol (500 mg, 2.89 mmol) in water (3 mL), acetone (3 mL) and concentrated HCl (1.6 mL) was cooled to 0° C. and a solution of sodium nitrite (219 mg, 3.18 mmol) in water (0.7 mL) was added. The reaction was stirred for 2 h at 0° C. and a solution of potassium iodide (719 mg, 4.33 mmol) and concentrated H2SO4 (0.16 mL) in water (1.2 mL) was added. The reaction mixture was heated at 60° C. for 2-3 h. The reaction mixture was cooled to room temperature and 50% saturated Na2SO3 (30 mL) was added. The mixture was extracted with CH2Cl2 (3×20 mL) and the combined extracts were washed with brine (20 mL), dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-40% EtOAc in hexanes gradient) to afford (3-iodo-2-naphthyl)methanol. Rf=0.47 (20% EtOAc/hexanes). 1H NMR (600 MHz, CD3OD): δ 8.35 (s, 1H); 7.91 (s, 1H); 7.81 (d, J=8.0 Hz, 1H); 7.71 (d, J=8.0 Hz, 1H); 7.47-7.42 (m, 2H); 4.69 (s, 2H).
Reaction SMILES: [CH2:1]([P:3]([O-:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].[C:10](#[N:13])[CH:11]=[CH2:12]>C1(C)C=CC=CC=1>[CH2:1]([P:3]([CH2:12][CH2:11][C:10]#[N:13])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: C=CC#N
Reactant: CCCCOP([O-])CC
Solvent: Cc1ccccc1
Product: CCCCOP(=O)(CC)CCC#N
Yield: 84.1 %

Procedure:
150 g (1 mol) of butyl ethylphosphonite (produced as in Example 2) and 64 g (1.2 mol) of acrylonitrile in 217 g of toluene are heated to about 100° C. While stirring, 124 g of a 10% solution of Wako V65 in toluene are added by metered addition. The solvent is distilled off in vacuo to leave 171 g (84% of theory) of butyl ethyl(2-cyanoethyl)phosphinate.
Reaction SMILES: S(O)(C)(=O)=O.[Cl:6][C:7]1[CH:8]=[C:9]([O:23][CH3:24])[C:10]([F:22])=[C:11]([S:13][CH2:14][C:15](=O)[CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH:12]=1>>[CH3:20][O:19][C:17](=[O:18])[CH2:16][C:15]1[C:12]2[C:7]([Cl:6])=[CH:8][C:9]([O:23][CH3:24])=[C:10]([F:22])[C:11]=2[S:13][CH:14]=1
Reactant: COC(=O)CC(=O)CSc1cc(Cl)cc(OC)c1F
Agent: CS(=O)(=O)O
Product: COC(=O)Cc1csc2c(F)c(OC)cc(Cl)c12
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 89.8 %

Procedure:
MsOH (4.0 mL) was added to methyl 4-((5-chloro-2-fluoro-3-methoxyphenyl)sulfanyl)-3-oxobutanoate (400 mg) at 0° C. After stirring at 0° C. for 20 min, the mixture was warmed to room temperature and stirred for 2 h. The mixture was poured into ice water at 0° C. and extracted with EtOAc. The organic layer was separated, washed successively with saturated aqueous NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (338 mg).
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[C:10]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)=[N:9][CH2:8][CH2:7]2>C(O)C>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][CH2:16][CH:10]2[C:11]3[C:6](=[CH:5][C:4]([CH3:3])=[C:13]([O:14][CH3:15])[CH:12]=3)[CH2:7][CH2:8][NH:9]2)=[CH:23][CH:22]=1
Reactant: COc1cc2c(cc1C)CCN=C2CCc1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COc1cc2c(cc1C)CCNC2CCc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Add sodium borohydride (2.0 g) to a suspension of the dihydroisoquinoline from step B (4.75 g) in ethanol (175 mL) and stir the mixture for 2 h. Concentrate to a residue, treat with water and heat on a steam bath for 0.75 h. Cool the mixture to room temperature, extract with ether and concentrate the ethereal extract to a residue. Dissolve the residue in ethyl acetate, treat with 1.7 g of maleic acid and recrystallize the resulting salt from ethanol/ethyl acetate to give the title compound as the maleate salt (4.05 g). Elemental analysis: calc. for C19H22ClNO2, C=63.9%, H=6.03%, N=3.25%; found, C=63.91, H=5.99, N=3.22.
Reaction SMILES: [CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([OH:14])=O)[CH:8]=2)[CH2:3]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:46]1[CH2:50][CH2:49][C@@H:48]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:47]1>CN(C=O)C>[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([N:46]3[CH2:50][CH2:49][C@@H:48]([NH:51][C:52](=[O:58])[O:53][C:54]([CH3:56])([CH3:55])[CH3:57])[CH2:47]3)=[O:14])[CH:8]=2)[CH2:3]1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCNC1
Reactant: CN1CCc2cc(C(=O)O)ccc2C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CN1CCc2cc(C(=O)N3CC[C@@H](NC(=O)OC(C)(C)C)C3)ccc2C1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
1.1 g (4.8 mmol) 2-methyl-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (as hydrochloride) are dissolved in 12 ml DMF, mixed with 2.1 ml (19.3 mmol) NMM and 1.8 g (4.8 mmol) HATU and stirred for five minutes at RT. Then 0.9 g (4.8 mmol) tert. Butyl (R)-pyrrolidin-3-yl-carbamate are added and the mixture is stirred for 16 hours. Then the mixture is poured onto water and extracted with DCM. The organic phase is separated using a phase separation cartridge and evaporated to dryness i. vac. The residue is purified by flash chromatography on silica gel (eluant DCM/MeOH 9:1 to 8:2).
Reaction SMILES: [CH2:1]([N:5]([CH2:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31]CC)=[O:30])=[C:25]([CH3:38])[CH:24]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[N:7]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].Cl>CO.O1CCCC1>[CH2:1]([N:5]([CH2:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][C:28]([CH3:34])([CH3:35])[C:29]([OH:31])=[O:30])=[C:25]([CH3:38])[CH:24]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:16][CH:17]=2)[N:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(Cc1ccc(OC(C)(C)C(=O)OCC)c(C)c1)c1cccc(-c2ccc(C(F)(F)F)cc2)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCCCN(Cc1ccc(OC(C)(C)C(=O)O)c(C)c1)c1cccc(-c2ccc(C(F)(F)F)cc2)n1
Temperature: 70 °C
Reaction time: 18 h
Yield: 44.7 %

Procedure:
To a solution of ethyl 2-{4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}-2-methylpropanoate (45 mg, 0.085 mmol) in methanol (1.5 mL) and tetrahydrofuran (1.5 mL) was added 2M NaOH aq. (1 mL). The resulting mixture was heated to 70° C. for 1 h and then stirred at room temperature for 18 h, before heating to 70° C. for a further 4 h. The reaction mixture was allowed to attain room temperature and the solvents removed in vacuo. The residue was acidified with 2M HCl and extracted with EtOAc (2×10 mL). The organic solution was dried (MgSO4) and the solvents removed in vacuo. Purification by aminopropyl SPE (5 g) conditioning the cartridge, loading the compound and washing with methanol before eluting using 10% NH3 in methanol. Evaporation of the methanolic ammonia yielded a white solid, which was treated with 1 M HCl (5 mL) and then extracted into CH2Cl2 (20 mL). The organic extract was dried (Na2SO4) and the solvent removed in vacuo to afford the title compound as a colourless oil (19 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:13]([O:17][C:18](ON=C(C1C=CC=CC=1)C#N)=[O:19])([CH3:16])([CH3:15])[CH3:14]>O1CCCC1>[C:13]([O:17][C:18]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]
Reactant: NCCCNCc1ccccc1
Reactant: CC(C)(C)OC(=O)ON=C(C#N)c1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCCNCc1ccccc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 81.4 %

Procedure:
A solution of N-(3-aminopropyl)benzylamine (38 g, 231.71 mmoles) in dry tetrahydrofuran (300 mL) was cooled to 5° C. in an ice-alcohol bath. To this cold stirred solution 2-[[(tert-butyoxycarbonyl)oxy]imino]-2-phenylacetonitrile (BOC-ON) (56.58 g, 230 mmoles) in dry tetrahydrofuran (300 mL) was added slowly during a 6 hour period. After the addition of BOC-ON, the reaction mixture was stirred at room temperature under argon for an additional 6 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in ether (750 mL). The ether extract was washed with 5% sodium hydroxide solution (4×100 mL), dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was purified by flash column using a chromatograpay over a silica dichloromethane→methanol gradient. The pure fractions were pooled together and evaporated to give 49.5 g (81%) of product as oil: 1H nmr (deuteriochloroform): δ 1.42 (s, 9H, t-Boc), 1.65 (m, 2H, CH2CH2CH2), 2.70 (t, 2H, CH2NHCH2), 3.20 (m, 2H, BocNHCH2), 3.78 (s, 2H, ArCH2), 5.32 (br s, 1H, BocNH), 7.30 (m, 5H, ArH).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][CH2:12][CH2:13][OH:14].[N+:15]([CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([O-:17])=[O:16]>C(Cl)Cl.O.CCN(CC)CC>[F:11][CH2:12][CH:13]([OH:14])[CH:18]([N+:15]([O-:17])=[O:16])[CH2:19][C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21]
Reactant: CC(C)(C)OC(=O)CC[N+](=O)[O-]
Reactant: OCCF
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)CC(C(O)CF)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 24.4 %

Procedure:
A solution of oxalyl chloride (1.9 mL, 21.8 mmol) in dry CH2Cl2 (100 mL) was cooled to −78° C., a solution of DMSO (3.0 mL, 42.3 mmol) in dry CH2Cl2 (10 mL) was added with stirring in such a rate that the temperature was kept at −50 to −60° C. After 5 min stirring, a solution of 2-fluoroethanol (1.2 mL, 18.4 mmol) in dry CH2Cl2 (10 mL) was added, and stirring was continued for an additional 15 min, then dry Et3N (13.5 mL) was added. The reaction mixture was stirred for 15 min, then allowed to warm to rt. To the reaction mixture was added a solution of t-butyl 3-nitropropionate (2.87 g, 16.38 mmol) in CH2Cl2 (20 mL). The reaction mixture was stirred at rt for 3 h, then poured into water (100 mL). The organic layer was separated and the aqueous was extracted with CH2Cl2 (2×50 mL). The CH2Cl2 solution was washed with brine, dried and evaporated. The residue was purified by chromatography twice over silica gel (hexane-EtOAc, 7:3) to give 950 mg (24.5%) of the titled product as a colorless viscous oil. 1H NMR (CDCl3), 1.450 (s, 9H), 2.80-2.90 (m, 2H), 3.12-3.20 (m, 1H), 4.41-4.59 (m, 2H), 4.57-4.59 (m, 1H), 4.95-5.01 (m, 1H).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[CH:5][S:6][CH:7]=1.[CH2:8]([NH:15][C:16]([C:18]1[S:22][C:21]([N:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:24]2=[O:30])=[N:20][C:19]=1[CH3:31])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:8]([NH:15][C:16]([C:18]1[S:22][C:21]([N:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:2][C:3]3[N:4]=[CH:5][S:6][CH:7]=3)=[CH:25][C:24]2=[O:30])=[N:20][C:19]=1[CH3:31])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: ClCc1cscn1
Reactant: Cc1nc(-n2ccc(O)cc2=O)sc1C(=O)NCc1ccccc1
Product: Cc1nc(-n2ccc(OCc3cscn3)cc2=O)sc1C(=O)NCc1ccccc1
Yield: 29 %

Procedure:
Following the procedure as described in Example 21, making variation only as required to use 4-(chloromethyl)thiazole in place of 2-(chloromethyl)-5-phenyl-1,3,4-oxadiazole to react with N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide, the title compound was obtained as a colorless solid in 29% yield: 1H NMR (300 MHz, DMSO-d6) δ 9.12 (d, J=1.9 Hz, 1H), 8.79 (t, J=5.9 Hz, 1H), 8.61 (d, J=8.0 Hz, 1H), 7.89 (d, J=1.9 Hz, 1H), 7.33-7.27 (m, 4H), 7.25-7.17 (m, 1H), 6.38-6.32 (m, 2H), 5.27 (s, 2H), 4.38 (d, J=5.9 Hz, 2H), 2.54 (s, 3H); MS (ES+) m/z 439.1 (M+1).
Reaction SMILES: C1[O:3]C1.O[C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=CC=2)(C)C)=[CH:7][CH:6]=1.C1OC1C.C(O)(=O)C1C=CC(C(O)=O)=CC=1.C([Sn](=O)CCCC)CCC>>[CH:14]([CH:19]=[CH:18][C:17]([OH:20])=[O:3])=[CH:11][C:8]1[CH:7]=[CH:6][CH:5]=[CH:10][CH:9]=1
Reactant: C1CO1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: CC1CO1
Agent: CCCC[Sn](=O)CCCC
Agent: O=C(O)c1ccc(C(=O)O)cc1
Product: O=C(O)C=CC=Cc1ccccc1

Procedure:
In a reaction vessel equipped with a condenser, a stirrer and a nitrogen inlet tube, 682 parts of ethylene oxide 2 mol adduct of bisphenol A, 81 parts of propylene oxide 2 mol adduct of bisphenol A, 283 parts of terephthalic acid, 22 parts of trimellitic anhydride, and 2 parts of dibutyltin oxide were added. The mixture was subjected to a reaction for 8 hours at 230° C. under normal pressure, and subsequently reacted for 5 hours under a reduced pressure of from 10 mmHg to 15 mmHg. Thus [Intermediate Polyester 1] was obtained. The [Intermediate Polyester 1] was found to have a number average molecular weight of 2,100, a mass average molecular weight of 9,500, a glass transition temperature (Tg) of 55° C., an acid value of 0.5 mgKOH/g and a hydroxyl value of 51 mgKOH/g.
Reaction SMILES: [C@@H:1]1([N:9]2[C:18]3[N:17]=[CH:16][N:15]=[C:13](O)[C:12]=3[N:11]=[CH:10]2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.C(N(CC)C(C)C)(C)C.[I:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([NH2:37])[CH3:36])=[C:31]([N+:38]([O-:40])=[O:39])[CH:30]=1>CN(C=O)C>[I:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([NH:37][C:13]2[C:12]3[N:11]=[CH:10][N:9]([C:18]=3[N:17]=[CH:16][N:15]=2)[C@@H:1]2[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]2)[CH3:36])=[C:31]([N+:38]([O-:40])=[O:39])[CH:30]=1
Reactant: OC[C@H]1O[C@@H](n2cnc3c(O)ncnc32)C[C@@H]1O
Reactant: CC(N)c1ccc(I)cc1[N+](=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(Nc1ncnc2c1ncn2[C@H]1C[C@H](O)[C@@H](CO)O1)c1ccc(I)cc1[N+](=O)[O-]
Reaction time: 48 h

Procedure:
To a suspension of 2′-deoxyinosine (150 mg, 0.6 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphonate (BOP, 379 mg, 0.86 mmol) in anhydrous DMF (1.5 mL), N,N-diisopropylethylamine (186 μL, 1.1 mmol) was added followed by the addition of a solution of 1-(4-iodo-2-nitrophenyl)ethylamine (460 mg, 1.57 mmol) in anhydrous DMF (0.5 mL). The mixture was stirred under nitrogen atmosphere for 48 hours. DMF was removed in vacuo, and the crude product was purified by silica gel column chromatography to yield N6-[1-(4-iodo-2-nitrophenyl)ethyl]-2′-deoxyadenosine dA.20 (204 mg, 65%, 1:1 mixture of diastereomers) as a white foam.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]3[NH:23][C:24]4[C:29]([CH:30]=3)=[CH:28][CH:27]=[C:26]([C:31]#[N:32])[CH:25]=4)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].[Cl-].[NH4+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][C:22]3[N:23]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:24]4[C:29]([CH:30]=3)=[CH:28][CH:27]=[C:26]([C:31]#[N:32])[CH:25]=4)=[CH:18][CH:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CBr
Reactant: CC(C)(C)OC(=O)N1CC[C@H](Oc2ccc(CCc3cc4ccc(C#N)cc4[nH]3)cc2)C1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1c(CCc2ccc(O[C@H]3CCN(C(=O)OC(C)(C)C)C3)cc2)cc2ccc(C#N)cc21
Temperature: 25 °C

Procedure:
2.4 g of 2-[2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]ethyl]-6-indolecarbonitrile was dissolved in 50 ml of N,N-dimethylformamide. 300 mg of 60% sodium hydride was added to the thus prepared solution during stirring under ice cooling, and the resulting mixture was warmed up to room temperature and stirred at the same temperature for 20 minutes. 0.76 ml of ethyl bromoacetate was added to the above mixture during stirring under ice cooling, followed by stirring for 1 hour. The resulting reaction solution was mixed with an ammonium chloride aqueous solution and extracted with a toluene/ethyl acetate mixture, and the resulting organic layer was washed with water and dried. After distilling off the solvent, the resulting residue was purified by subjecting it to silica gel column chromatography using a dichloromethane/acetone mixture as an elution solvent. In this way, 2.3 g of the title compound was obtained in a viscous and oily form.