Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: ClCCC[SiH3].[CH2:6]([Si:9]([CH2:17][CH:18]=[CH2:19])([CH2:14][CH:15]=[CH2:16])[CH2:10][CH2:11][CH2:12]Cl)[CH:7]=[CH2:8].[SiH4].[I-:21].[Na+]>CC(C)=O>[CH2:6]([Si:9]([CH2:17][CH:18]=[CH2:19])([CH2:14][CH:15]=[CH2:16])[CH2:10][CH2:11][CH2:12][I:21])[CH:7]=[CH2:8]
Reactant: [I-]
Reactant: C=CC[Si](CC=C)(CC=C)CCCCl
Agent: [Na+]
Agent: [SiH3]CCCCl
Agent: [SiH4]
Solvent: CC(C)=O
Product: C=CC[Si](CC=C)(CC=C)CCCI
Reaction time: 18 h

Procedure:
Triallyl 3-iodopropyl silane was prepared by the Finkelstein transhalogenation reaction from chloropropyl silane prepared in Example 6. A 250 ml flask equipped with a stir bar and a reflux condenser was charged with 20 grams (90 millimoles) of triallyl (3-chloropropyl) silane (prepared as described in Example 6) and 100 ml of acetone (available commercially as Omnisolve Reagent grade from E. Merck, Gibbstown, N.J.). The silane solution was refluxed under positive nitrogen pressure with 40 grams (270 millimoles) of sodium iodide (available commercially from Aldrich Chemical Co. of Milwaukee, Wis.) for 18 hours. After cooling, the acetone solution was decanted from the insoluble iodide salts and was concentrated on a rotary evaporator to yield triallyl 3-iodopropyl silane, which was used without further purification.
Reaction SMILES: Cl.N[C@@H:3]([C:6]([CH3:9])([OH:8])[CH3:7])CO.C[N:11]([C:13]([O:17]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:32]([O:39][C:40](=[O:61])[C@H:41](NC(OC(C)(C)C)=O)[CH2:42][C:43]([NH:45][C@@H:46]([CH2:51][OH:52])[C:47]([OH:50])([CH3:49])[CH3:48])=[O:44])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[CH2:32]([O:39][C:40](=[O:61])[CH2:41][C@@H:42]([NH:11][C:13]([O:8][C:6]([CH3:3])([CH3:7])[CH3:9])=[O:17])[C:43]([NH:45][C@@H:46]([CH2:51][OH:52])[C:47]([OH:50])([CH3:48])[CH3:49])=[O:44])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: CC(C)(C)OC(=O)N[C@H](CC(=O)N[C@@H](CO)C(C)(C)O)C(=O)OCc1ccccc1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CC(C)(O)[C@H](N)CO
Agent: Cl
Agent: F[B-](F)(F)F
Product: CC(C)(C)OC(=O)N[C@H](CC(=O)OCc1ccccc1)C(=O)N[C@@H](CO)C(C)(C)O
Yield: 52 %

Procedure:
3-Benzyloxycarbonyl-2,2-dimethyl-4R-(1-hydroxy-1-methyl-ethyl)-oxazolidine was hydrogenolyzed in the presence of HCl according to conditions described in Example 1(a) to provide crude 2(R)-amino-3-methyl-butane-1,3-diol hydrochloride. According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butoxycarbonylamido-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, the crude amine salt was coupled to N-t-butoxycarbonyl-D-aspartic acid β-benzyl ester with TBTU. Purification via column chromatography with EtOAc/CH2Cl2 (1:1) to 10% MeOH/CH2Cl2 gradient elution led to isolation in 52% yield of 3 (R)-t-butoxycarbonylamino-N-[2-hydroxy-1(S)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl ester, which was used without further purification. 1H NMR (CD3CN): δ 7.51 (s, 5H), 6.99 (bs, 1H), 5.99 (bs, 1H), 5.25 (s, 2H), 4.57-4.50 (m, 1H), 3.83-3.76 (m, 3H), 3.00 (dd, 1H, J=5.7, 16.4 Hz), 2.87 (dd, 1H, J=7.2, 16.6 Hz), 1.55 (s, 9H), 1.34 (s, 3H), 1.22 (s, 3H). Anal. Calculated for C21H32N2O7.0.5 H2O.0.1 O═C[N-(CH3)2]2: C, 58.02; H, 7.74; N, 6.92. Found: C, 58.29; H, 7.75; N, 6.82.
Reaction SMILES: [Cl:1][C:2]1[C:15]([N:16]=[C:17]=S)=[C:14]([Cl:19])[CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6](=[O:11])[C:7]([CH3:10])([CH3:9])[CH3:8].[Cl:20][C:21]1[C:27]([N:28]2[CH2:33][CH2:32][CH:31]([C:34]([F:37])([F:36])[F:35])[CH2:30][CH2:29]2)=[CH:26][C:24]([NH2:25])=[C:23]([NH2:38])[CH:22]=1.CC(C)N=C=NC(C)C.C(Cl)Cl.CCO>CN(C=O)C>[Cl:1][C:2]1[C:15]([NH:16][C:17]2[NH:25][C:24]3[CH:26]=[C:27]([N:28]4[CH2:33][CH2:32][CH:31]([C:34]([F:37])([F:36])[F:35])[CH2:30][CH2:29]4)[C:21]([Cl:20])=[CH:22][C:23]=3[N:38]=2)=[C:14]([Cl:19])[CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6](=[O:11])[C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)C(=O)NCc1ccc(Cl)c(N=C=S)c1Cl
Reactant: Nc1cc(Cl)c(N2CCC(C(F)(F)F)CC2)cc1N
Agent: CC(C)N=C=NC(C)C
Solvent: CCO
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)C(=O)NCc1ccc(Cl)c(Nc2nc3cc(Cl)c(N4CCC(C(F)(F)F)CC4)cc3[nH]2)c1Cl

Procedure:
The title compound was prepared from N-(2,4-dichloro-3-isothiocyanato-benzyl)-2,2-dimethyl-propionamide (108 mg, 0.34 mmol), 4-chloro-2-amino-5-(4-trifluoromethyl-piperidin-1-yl)aniline (100 mg, 0.34 mmol), DIC (56 μL) in DMF (2 mL) in analogy to example 5, step (i). Rf(TLC): 0.35 (silica gel, DCM:EtOH 95:5). MS m/z: 576 [M+H]+. HPLC-method G: Rf=1.48 min.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([OH:24])([CH3:23])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[C:10]([O:21][CH3:22])[CH:9]=2)=[O:5])C.[OH-].[Na+]>C1COCC1.C(O)C>[OH:24][C:7]1([CH3:23])[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:21][CH3:22])[CH:9]=2)[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:6]1[C:4]([OH:5])=[O:3]
Reactant: CCOC(=O)C1=C(c2ccccc2)c2ccc(OC)cc2C1(C)O
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COc1ccc2c(c1)C(C)(O)C(C(=O)O)=C2c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 68.8 %

Procedure:
1-Hydroxy-6-methoxy-1-methyl-3-phenyl-1H-indene-2-carboxylic acid ethyl ester (100 mg, 0.309 mmol) prepared in Example 4 was dissolved in THF, and an excess amount of sodium hydroxide dissolved in aqueous ethanol was added thereto in such a way not to cause layer separation. The mixture was stirred for 24 hrs at RT, and the pH was adjusted to 3˜4 using 2N hydrochloric acid. The resulting mixture was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous MgSO4 and concentrated under a reduced pressure, to obtain 63 mg of the titled compound (yield: 69%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[CH:6][C:7]=1[OH:8].[Br:15]Br>C(Cl)(Cl)(Cl)Cl>[Br:15][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:3]=[C:2]([Cl:1])[C:7]=1[OH:8]
Reactant: BrBr
Reactant: CCOC(=O)Cc1ccc(O)c(Cl)c1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)Cc1cc(Cl)c(O)c(Br)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 81.5 %

Procedure:
To a stirred solution of compound ethyl 2-(3-chloro-4-hydroxyphenyl)acetate (11 g, 51 mmol) in 200 ml of CCl4, was slowly added bromine (8.22 g, 51 mmol) as a solution CCl4 (100 ml) at 0° C. over a period of 30 min. The reaction mixture was stirred for a further 30 min at 0° C. Upon which the reaction mixture was poured onto crushed ice and extracted with DCM (2×100 mL). The combined organic layers were washed with water followed by 10% sodium bisulfite solution, dried over Na2SO4 filtered and evaporated under reduced pressure to give ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (12.2 g) as a white solid in 80% yield. 1H NMR (CDCl3): 7.37 (s, 1H); 7.27 (s, 1H); 5.68 (bs, 1H); 4.16 (q, 2H); 3.48 (s, 2H); 1.29 (t, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@:9]23[CH2:14][C@H:13]2[CH2:12][C:11](=O)[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])(=O)C.[NH4+].C([BH3-])#[N:22].[Na+].C(OCC)(=O)C.CO.C(N(CC)CC)C>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]23[CH2:14][C@H:13]2[CH2:12][CH:11]([NH2:22])[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: [BH3-]C#N
Reactant: O=C1C[C@@H]2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CCN(CC)CC
Product: NC1C[C@@H]2C[C@]2(c2ccc(Cl)c(Cl)c2)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 99 %

Procedure:
To a solution of (1S,5S)-1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-3-one (0.7 g, 2.9 mmol) in methanol (87.5 mL) was added ammonium acetate (22.05 g, 290 mmol), stirred for 15 minutes at room temperature and sodium cyanoborohydride (1.45 g, 23 mmol) was added and the mixture was heated to 60° C. for 2 hours. The reaction was monitored by TLC (ethyl acetate/methanol/triethylamine (89:10:1)). The reaction mixture was concentrated under reduced pressure to remove methanol at 30° C., the crude mass was quenched with water (20 mL) and the aqueous layer was extracted with ethyl acetate (3×75 mL). The aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×75 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to yield 2.4 g of crude oil, which was purified by preparative HPLC to yield 430 mg (66%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD) 0.92-0.98 (2H,m), 1.28 (1H,m), 1.76-1.87 (3H,m), 2.08-2.14 (2H,m), 2.57-2.75 (3H,m), 3.98-4.04 (1H,m),7.10-7.15 (1H,m), 7.35-7.42 (2H,m). 13CNMR(CD3OD) δ: 145.91, 133.24, 131.51, 130.79, 129.78, 129.29, 127.58, 127.05, 54.33, 40.53, 37.67, 35.75, 34.36, 33.54, 31.10, 28.25, 26.08, 25.84, 18.53. Purity: 99.53% (a/a) by HPLC. MS, M+(241).
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[OH:27][CH2:28][CH2:29][N:30]([CH3:41])[S:31]([C:34]1[S:38][C:37]([NH2:39])=[N:36][C:35]=1[CH3:40])(=[O:33])=[O:32]>>[OH:27][CH2:28][CH2:29][N:30]([CH3:41])[S:31]([C:34]1[S:38][C:37]([NH:39][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([C:2]([F:26])([F:25])[F:1])=[CH:4][C:5]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=4)=[N:6][C:7]=23)=[O:13])=[N:36][C:35]=1[CH3:40])(=[O:32])=[O:33]
Reactant: Cc1nc(N)sc1S(=O)(=O)N(C)CCO
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Cc1nc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)sc1S(=O)(=O)N(C)CCO

Procedure:
The title compound was prepared from 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C. 1) and 2-amino-4-methyl-thiazole-5-sulfonic acid (2-hydroxy-ethyl)-methyl-amide (example B.20) according to general procedure II.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[S:9]1[CH:13]=[CH:12][N:11]=[C:10]1[C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH:16]=O.[CH3:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:24]=1[N+:30]#[C-:31].Cl(O)(=O)(=O)=O>C(O)C>[CH3:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:24]=1[NH:30][C:31]1[N:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]2=[N:1][C:16]=1[C:15]1[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=1[C:10]1[S:9][CH:13]=[CH:12][N:11]=1
Reactant: Nc1ccc(F)cn1
Reactant: O=Cc1ccccc1-c1nccs1
Reactant: [C-]#[N+]c1c(C)cccc1C
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: CCO
Product: Cc1cccc(C)c1Nc1c(-c2ccccc2-c2nccs2)nc2ccc(F)cn12
Temperature: 25 °C
Reaction time: 20 h
Yield: 42.7 %

Procedure:
118 mg (1.0 mmol) of 2-amino-5-fluoropyridine and 189 mg (1.0 mmol) of 2-thiazol-2-ylbenzaldehyde are dissolved successively in 5 ml of ethanol at RT under inert gas. 137 mg (1.0 mmol) of 2,6-dimethyiphenyl isocyanide are then added, 0.043 ml of 70% perchloric acid is added dropwise, and the mixture is stirred at RT for a further 20 h. 10 ml of petroleum ether are subsequently added, and the precipitated solid is filtered off with suction. This is triturated with a little ethyl acetate and filtered off with suction again, giving 177 mg (43%) of (2,6-dimethylphenyl)-[6-fluoro-2-(2-thiazol-2-yl-phenyl)imidazo[1,2-a]pyridin-3-yl]amine (“A1”) as solid; MS-FAB (M+H+)=415.7; Rf (polar method): 1.98 min;
Reaction SMILES: [CH2:1]([N:3]([CH2:14][CH3:15])[CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:16][S:17]([O:20]S(C)(=O)=O)(=[O:19])=[O:18]>C(#N)C>[CH3:16][S:17]([OH:20])(=[O:19])=[O:18].[CH2:14]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([NH:13][S:17]([CH3:16])(=[O:19])=[O:18])=[CH:11][CH:12]=1)[CH3:15]
Reactant: CCN(CC)CCOc1ccc(N)cc1
Reactant: CS(=O)(=O)OS(C)(=O)=O
Solvent: CC#N
Product: CCN(CC)CCOc1ccc(NS(C)(=O)=O)cc1
Product: CS(=O)(=O)O
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To a solution of 2.8 g (12.4 mmol) of 4-[2-(diethylamino)ethoxy]benzenamine dissolved in 30 mL of acetonitrile cooled to 0° C. add 2.6 g (15 mmol) of methanesulfonic anhydride. Stir the reaction mixture for 4 h at ambient temperature. Remove the solvent in vacuo and recrystallize the residue from acetonitrile/ethyl acetate to obtain the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]#[N:8].C[O-].[Na+].[NH:12]([C:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)=O)[NH2:13].C(O)(=O)C>CO>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[NH:13][N:12]=[C:14]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[N:8]=1
Reactant: N#Cc1cnccn1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)NN)CC1
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2n[nH]c(-c3cnccn3)n2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of pyrazinecarbonitrile (2.0 g, 19 mmol) in methanol (20 mL) was treated with sodium methoxide in methanol (25 wt %, 1.3 mL, 5.7 mmol) at room temperature. After 30 minutes, a solution of tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate (4.6 g, 19 mmol) in methanol (20 mL) was added and the reaction was heated to reflux for 19 hours. The reaction mixture was concentrated, dissolved in ethoxyethanol (50 mL) and heated to reflux for 22 hours. The reaction was cooled to room temperature, quenched with acetic acid (0.38 mL, 6.6 mmol) and concentrated. The residue was suspended in ether and filtered to give tert-butyl 4-(5-pyrazin-2-yl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate as a solid. HRMS (M+H+): observed=331.1876, calculated=331.1877; 1H NMR (400 MHz, CD3OD): δ 9.29 (d, J=1.6 Hz, 1H), 8.70 (dd, J=2.4, 1.6 Hz, 1H), 8.64 (d, J=2.4 Hz, 2H), 4.19-4.15 (m, 2H), 3.15-3.09 (m, 1H), 2.97 (m, 2H), 2.07-2.03 (m, 2H), 1.84-1.75 (m, 2H), 1.48 (s, 9H).
Reaction SMILES: [CH3:1][CH:2]([CH:4]=[O:5])[CH3:3].[CH:6]([C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[CH:12]=[C:11]([CH:18]([CH3:20])[CH3:19])[C:10]=1[S:21]Cl)([CH3:8])[CH3:7].O>C1COCC1>[CH3:1][C:2]([S:21][C:10]1[C:11]([CH:18]([CH3:19])[CH3:20])=[CH:12][C:13]([CH:15]([CH3:17])[CH3:16])=[CH:14][C:9]=1[CH:6]([CH3:8])[CH3:7])([CH3:3])[CH:4]=[O:5]
Reactant: CC(C)c1cc(C(C)C)c(SCl)c(C(C)C)c1
Reactant: CC(C)C=O
Solvent: O
Solvent: C1CCOC1
Product: CC(C)c1cc(C(C)C)c(SC(C)(C)C=O)c(C(C)C)c1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
To a suspension of KH (383 mg, 9.5 mmol, Aldrich; washed with hexanes to remove oil and dried in vacuum) in THF (10 mL) was added dropwise isobutyric aldehyde (0.79 mL, 8.7 mmol, Aldrich) in THF (3 mL). The suspension was stirred for 25 min at RT under Ar (evolution of H2). A solution of 2,4,6-triisopropylphenylsulfenyl chloride (2.35 g, 8.7 mmol) in THF (10 mL) was then added at once. The color immediately changed from red to yellow. The solution was stirred at RT for 10 min, water (20 mL) was added to the reaction mixture under Ar (caution —H2 evolution). The solution was extracted with ethyl ether (2×30 mL), the extracts were dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography on silica gel (13×4.3 cm) in toluene/hexane 1/5 followed by 1/4. Fractions containing the product were evaporated to give a light yellow oil that slowly crystallized, m=2.034 g (68.5%). Rf=0.33 (toluene/hexane 1/3). 1H NMR (CDCl3) 9.34 (s, 1H); 7.00 (s, 2H); 3.85 (septet, 2H; J=6.9 Hz); 2.86 (septet, 1H; J=6.9 Hz); 1.29 (s, 6H); 1.24 (d, 6H; J=6.9 Hz); 1.18 (unresolved broad d, 12H).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([N+:20]([O-:22])=[O:21])=[C:11]([N:14]4[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:23])[C:6]([C:24]([OH:26])=[O:25])=[CH:5]2)[CH2:3][CH2:2]1.[C:27]([O:31][CH3:32])(=[O:30])[CH:28]=[CH2:29].O.[CH3:34]OCCO>CS(C)=O>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([N+:20]([O-:22])=[O:21])=[C:11]([N:14]4[CH2:19][CH2:18][N:17]([CH2:29][CH2:28][C:27]([O:31][CH2:32][CH3:34])=[O:30])[CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:23])[C:6]([C:24]([OH:26])=[O:25])=[CH:5]2)[CH2:2][CH2:3]1
Reactant: COCCO
Reactant: C=CC(=O)OC
Reactant: O=C(O)c1cn(C2CC2)c2cc(N3CCNCC3)c([N+](=O)[O-])cc2c1=O
Solvent: O
Solvent: CS(C)=O
Product: CCOC(=O)CCN1CCN(c2cc3c(cc2[N+](=O)[O-])c(=O)c(C(=O)O)cn3C2CC2)CC1

Procedure:
537 mg (1.5 mmol) of 1-cyclopropyl-1,4-dihydro-6-nitro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid are heated under reflux in a mixture of 7.5 ml of glycol monomethyl ether and 3 ml of dimethylsulphoxide with 2 g of methyl acrylate for 8 hours. 10 ml of water are added to the solution and the precipitate is filtered off with suction, washed with methanol and dried. 0.5 g of 1-cyclopropyl-1,4-dihydro-7-[4-(2-ethoxycarbonylethyl)-1-piperazinyl]-6-nitro-4-oxo-3-quinolinecarboxylic acid of decomposition point 208° to 211° C. is obtained.
Reaction SMILES: [C:1]([O-:4])([O-])=O.[K+].[K+].Br[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[F:18].C[O:20][CH:21](O)[CH3:22]>O>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[CH2:8][O:20][CH2:21][CH2:22][O:4][CH3:1]
Reactant: COC(C)O
Reactant: O=C([O-])[O-]
Reactant: O=[N+]([O-])c1ccc(CBr)c(F)c1
Agent: [K+]
Solvent: O
Product: COCCOCc1ccc([N+](=O)[O-])cc1F
Temperature: 25 °C
Reaction time: 5 h
Yield: 40 %

Procedure:
To a suspension of K2CO3 (8.8 g, 64.0 mmol, 1.5 eq) in methoxyethanol (100 mL) was added 1-(bromomethyl)-2-fluoro-4-nitrobenzene (10.0 g, 42.0 mmol, 1 eq) and the mixture was stirred at RT for 5 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (30 mL×2). The ethyl acetate layers were collected and dried (Na2SO4) and evaporated under vacuum. The residue was purified by CC using PE/EtOAc (17:3) as eluant to get 2-fluoro-1-((2-methoxyethoxy)methyl)-4-nitrobenzene (4 g, 40%) as oil (TLC system: PE/EtOAc (7:3), Rf: 0.5).
Reaction SMILES: [OH-].[Na+].[CH3:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([S:25]([CH2:28][CH2:29][CH2:30][C:31]([O:33]C)=[O:32])(=[O:27])=[O:26])=[C:12]([CH2:14][C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:18]=[CH:17][CH:16]=3)[S:13][C:7]=2[N:6]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:5]1=[O:39].Cl>CO.O1CCCC1.O>[CH3:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([S:25]([CH2:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])(=[O:27])=[O:26])=[C:12]([CH2:14][C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:18]=[CH:17][CH:16]=3)[S:13][C:7]=2[N:6]([CH2:35][CH:36]([CH3:37])[CH3:38])[C:5]1=[O:39]
Reactant: COC(=O)CCCS(=O)(=O)c1c(Cc2cccc3ccccc23)sc2c1c(=O)n(C)c(=O)n2CC(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(S(=O)(=O)CCCC(=O)O)c(Cc3cccc4ccccc34)sc21
Reaction time: 4 h
Yield: 28.7 %

Procedure:
Sodium hydroxide solution (1M, 1 ml) was added to a stirred suspension of methyl 4-[(1,2,3,4-tetrahydro-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl)sulfonyl]butanoate (0.10 g) in methanol (3 ml) and tetrahydofuran (3 ml). After 4 hours, the reaction mixture was diluted with water (20 ml), acidified with hydrochloric acid (2M) and extracted with ethyl acetate (2×30 ml). The organic extracts were evaporated under reduced pressure. The residue was partitioned between ether (30 ml) and aqueous sodium hydroxide solution (0.1M, 30 ml). The aqueous phase was acidified with hydrochloric acid (2M) and extracted with ethyl acetate (2×30 ml). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was triturated with ethyl acetate/hexane to is give the title compound (0.028 g).
Reaction SMILES: [N+:1]([C:4]1[CH:29]=[CH:28][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=3)[CH:17]=2)[C:12]([O-:14])=[O:13])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:30](O)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]>>[CH2:45]([O:13][C:12](=[O:14])[C:11]1[CH:10]=[C:9]([O:8][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:29][CH:28]=2)[CH:17]=[C:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)[CH:15]=1)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH3:30]
Reactant: O=C([O-])c1cc(Oc2ccc([N+](=O)[O-])cc2)cc(Oc2ccc([N+](=O)[O-])cc2)c1
Reactant: CCCCCCCCCCCCCCCCO
Product: CCCCCCCCCCCCCCCCOC(=O)c1cc(Oc2ccc([N+](=O)[O-])cc2)cc(Oc2ccc([N+](=O)[O-])cc2)c1
Yield: 81 %

Procedure:
Using 3,5-bis(4-nitrophenoxy)benzoate (8) (25.6 g, 64.6 mmol) obtained in Example 4 and n-hexadecyl alcohol (17.3 g, 71.5 mmol), n-hexadecyl[3,5-bis(4-nitrophenoxy)]benzoate was obtained (32.4 g, yield: 81%) in the same manner as in Example 4.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:25]=[CH:24][C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[O:14])=[C:11]([O:26][CH3:27])[CH:10]=1.[Cl:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[Cl:37])[CH2:32]Cl.C(N(CC)CC)C.Cl>CN(C)C=O>[ClH:8].[ClH:28].[Cl:8][C:9]1[CH:25]=[CH:24][C:12]([C:13]([NH:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([CH2:32][C:31]3[CH:34]=[CH:35][C:36]([Cl:37])=[C:29]([Cl:28])[CH:30]=3)[CH2:20][CH2:19]2)=[O:14])=[C:11]([O:26][CH3:27])[CH:10]=1
Reactant: COc1cc(Cl)ccc1C(=O)NCCN1CCNCC1
Reactant: ClCc1ccc(Cl)c(Cl)c1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(Cl)ccc1C(=O)NCCN1CCN(Cc2ccc(Cl)c(Cl)c2)CC1

Procedure:
A solution of the product of step (a) (4.0 g), 3,4-dichlorobenzylchloride (1.9 ml) and triethylamine (9.0 ml) in N,N-dimethylformamide (20 ml) was stirred at room temperature. The solvent was removed and the residue purified by chromatography (dichloromethane:methanol, 1:0 to 4:1) to give an oil, which was treated with 1.0M ethereal hydrogen chloride to give the product as a solid (3.1 g), m.p. 240-41° C.
Reaction SMILES: C([N:3](CC)CC)C.CS(Cl)(=O)=O.[Si:13]([O:20][CH:21]([CH2:40][CH2:41]O)[CH:22]([C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[O:32])=[CH:26][C:25]=1[F:39])O)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.O>[Si:13]([O:20][CH:21]1[CH2:40][CH2:41][NH:3][CH:22]1[C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[O:32])=[CH:26][C:25]=1[F:39])([C:16]([CH3:18])([CH3:19])[CH3:17])([CH3:14])[CH3:15]
Reactant: CCN(CC)CC
Reactant: CC(C)(C)[Si](C)(C)OC(CCO)C(O)c1ccc(NC(=O)c2ccccn2)cc1F
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(C)(C)[Si](C)(C)OC1CCNC1c1ccc(NC(=O)c2ccccn2)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
155 mg of triethylamine and 130 mg of methanesulfonyl chloride were added in order to a chloroform (8 ml) solution of 165 mg of N-(4-(2-((t-butyl(dimethyl)silyl)oxy)-1,4-dihydroxybutyl)-3-fluorophenyl)pyridine-2-carboxamide, with cooling with ice, and the reaction liquid was stirred at room temperature for 30 minutes. The reaction liquid was diluted with chloroform, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 25 mg of sodium azide was added to a dimethylformamide (5 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled, water was added to it, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 50 mg of sodium borohydride and 5 mg of copper sulfate pentahydrate were added in order to a methanol (10 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled, aqueous saturated sodium bicarbonate was added to it, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=50/1) to obtain the entitled compound as a colorless oily substance.