Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:6]=1[C:7]1[C:8](=[O:18])[CH2:9][CH2:10][CH2:11][C:12]=1[NH:13]2)([O:3][CH3:4])=[O:2].[O:19]([C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[CH2:29]Cl)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C.C(OCC)(=O)C>[O:19]([C:26]1[CH:27]=[C:28]([CH2:29][N:13]2[C:12]3[CH2:11][CH2:10][CH2:9][C:8](=[O:18])[C:7]=3[C:6]3[C:14]2=[CH:15][CH:16]=[CH:17][C:5]=3[C:1]([O:3][CH3:4])=[O:2])[CH:31]=[CH:32][CH:33]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CCC3
Reactant: ClCc1cccc(Oc2ccccc2)c1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1cccc2c1c1c(n2Cc2cccc(Oc3ccccc3)c2)CCCC1=O
Reaction time: 0.08 h
Yield: 58.1 %

Procedure:
40% Methanolic Triton B (1.53 mL, 3.4 mM) was slowly added dropwise to a solution of 5-carbomethoxy-1,2-dihydro-9H-carbazol-4(3H)-one (554.6 mg, 2.28 mM) in 5 mL of DMF at 25° C. After 5 minutes, 3-phenoxybenzyl chloride (748.0 mg, 3.42 mM) was added and the resultant mixture stirred at room temperature for 24 hours. The mixture was diluted with ethyl acetate, washed three times with 1N HCl, three times with H2O, once with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient methylene chloride/ethyl acetate) to afford 563.6 mg (58%) of 9-[(3-phenoxyphenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one as a thick yellow oil. 1H NMR (DMSO-d6) δ7.7 (dd, 1H, J=1 and 8 Hz), 7.4-7.2 (m, 6H), 7.1 (t, 1H, J=8 Hz), 6.95 (m, 2H), 6.8-6.7 (m, 2H), 5.55 (s, 2H), 3.75 (s, 3H), 3.0 (t, 2H, J=6 Hz), 2.45 (t, 2H, J=6 Hz), and 2.1 (m, 2H). IR (CDCl3, cm−1) 3050, 2950, 1725, 1653, 1585, 1487, 1465, 1288, 1252, and 1119. MS (ES) m/e 426.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.I[C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([C:21]([O:23][CH3:24])=[O:22])[CH:20]=1)[C:15]([OH:17])=[O:16]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH3:24][O:23][C:21]([C:19]1[CH:18]=[C:14]([CH:13]=[C:12]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:20]=1)[C:15]([OH:17])=[O:16])=[O:22]
Reactant: COC(=O)c1cc(I)cc(C(=O)O)c1
Reactant: c1cocn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Product: COC(=O)c1cc(C(=O)O)cc(-c2ncco2)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a −70° C. stirred solution of oxazole (432 mg, 6.3 mmol) in tetrahydrofuran (10 mL) is added n-butyllithium (2.5 M in hexanes, 2.75 mL, 6.9 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 18.75 mL, 18.75 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of 3-iodo-5-(methoxycarbonyl)benzoic acid prepared by the method in Example SP-281, step 1 (1.8 g, 6 mmol) in anhydrous tetrahydrofuran (10 mL) followed by palladium(0)tetrakis(triphenylphosphine) (291 mg, 0.25 mmol). The reaction mixture is heated at reflux for 15 h. The reaction mixture is cooled, filtered through diatomaceous earth, diluted with ethyl acetate (50 mL), washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 5% methanol/methylene chloride) provides the title compound in pure form. ESI MS m/z 246.1 [M−H]−.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[N:10]=[C:11]=S.[NH:13]([C:15](=[O:37])[C:16]([NH:18][C:19]1[CH:36]=[CH:35][C:22]([O:23][C@H:24]2[CH2:29][CH2:28][C@H:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH2:25]2)=[CH:21][CH:20]=1)=[O:17])[NH2:14].CCN=C=NCCCN(C)C>CC(N(C)C)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11]1[O:37][C:15]([C:16]([NH:18][C:19]2[CH:36]=[CH:35][C:22]([O:23][C@H:24]3[CH2:25][CH2:26][C@H:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:28][CH2:29]3)=[CH:21][CH:20]=2)=[O:17])=[N:13][N:14]=1
Reactant: Fc1cc(F)c(N=C=S)cc1F
Reactant: CCOC(=O)[C@H]1CC[C@H](Oc2ccc(NC(=O)C(=O)NN)cc2)CC1
Agent: CCN=C=NCCCN(C)C
Solvent: CC(=O)N(C)C
Product: CCOC(=O)[C@H]1CC[C@H](Oc2ccc(NC(=O)c3nnc(Nc4cc(F)c(F)cc4F)o3)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2,4,5-trifluorophenyl isothiocyanate (70 mg, 0.37 mmol) in DMA (1 mL) was added in one portion to a stirred solution of ethyl trans-4-(4-{[hydrazino(oxo)acetyl]amino}-phenoxy)cyclohexanecarboxylate (Intermediate 80, 129 mg, 0.37 mmol) in DMA (3 mL) and the reaction mixture was stirred at room temperature for 1 h. EDCI (71 mg, 0.37 mmol) was added in one portion and the reaction mixture was heated to 85° C. for 20 minutes in a microwave. The mixture was cooled to room temperature and a further portion of EDCI (7.1 mg, 0.04 mmol) was added and the reaction mixture stirred at 85° C. for 10 minutes in a microwave. The reaction mixture was concentrated in vacuo to leave a solid, which was recrystallised (CH3CN) to give the title compound (125 mg, 69%) as a solid; 1H NMR δ1.33 (3H, t), 1.48-1.58 (2H, m), 1.68-1.72 (2H, m), 2.06-2.10 (2H, m), 2.18-2.22 (2H, m), 2.45-2.53 (1H, m), 4.21 (2H, q), 4.39-4.46 (1H, m), 7.07-7.11 (2H, d), 7.81-7.84 (2H, d), 7.80-7.91 (1H, m), 8.29-8.36 (1H, m), 11.12-11.25 (1H, m); MS m/e MH+ 505.
Reaction SMILES: COC1C=CC(C2SC3C=CC(OC)=CC=3C=2)=C(N)C=1.BrC1C=CC(OCCN2CCCCC2)=C(F)C=1.[F:38][C:39]1[CH:40]=[C:41]([NH:54][C:55]2[CH:60]=[C:59]([O:61]C)[CH:58]=[CH:57][C:56]=2[C:63]2[S:67][C:66]3[CH:68]=[CH:69][C:70]([O:72]C)=[CH:71][C:65]=3[CH:64]=2)[CH:42]=[CH:43][C:44]=1[O:45][CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1>>[F:38][C:39]1[CH:40]=[C:41]([NH:54][C:55]2[CH:60]=[C:59]([OH:61])[CH:58]=[CH:57][C:56]=2[C:63]2[S:67][C:66]3[CH:68]=[CH:69][C:70]([OH:72])=[CH:71][C:65]=3[CH:64]=2)[CH:42]=[CH:43][C:44]=1[O:45][CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]1
Reactant: COc1ccc(-c2cc3cc(OC)ccc3s2)c(Nc2ccc(OCCN3CCCCC3)c(F)c2)c1
Agent: COc1ccc(-c2cc3cc(OC)ccc3s2)c(N)c1
Agent: Fc1cc(Br)ccc1OCCN1CCCCC1
Product: Oc1ccc(-c2cc3cc(O)ccc3s2)c(Nc2ccc(OCCN3CCCCC3)c(F)c2)c1
Yield: 76.2 %

Procedure:
Synthesized from 5-methoxy-2-(5-methoxybenzo[b]thiophen-2-yl)phenylamine and 1-[2-(4-bromo-2-fluorophenoxy)ethyl]piperidine according to an analogous synthetic method to Example 116, [3-fluoro-4-(2-piperidin-1-ylethoxy)phenyl][5-methoxy-2-(5-methoxybenzo[b]thiophen-2-yl)phenyl]amine (300 mg) was used according to an analogous synthetic method to Example 111 to provide the title compound (216 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32]Cl)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[NH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>COCCO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1
Reactant: COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
Reactant: C1CNCCN1
Solvent: ClCCl
Solvent: COCCO
Product: COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCN4CCNCC4)c(OC)cc23)c2c1OCO2
Temperature: 110 °C
Yield: 69.3 %

Procedure:
N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.165 g) was dissolved in 2-methoxyethanol (5 ml) and piperazine (0.586 g) was then added and the mixture heated to 110° C. for 45 minutes. The reaction mixture was cooled to room temperature, diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and then evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol with methanolic ammonia as eluent. There was thus obtained the title compound (0.126 g) as a clear gum; NMR Spectrum: (CDCl3) 2.09 (quin, 2H), 2.46 (s(broad), 4H), 2.54 (t, 2H), 2.91 (t, 4H), 3.45 (s, 3H), 3.47 (s, 1H), 3.96 (s, 3H), 4.23 (t, 2H), 4.35 (s, 2H), 6.06 (s, 2H), 7.06 (s, 1H), 7.13 (s, 1H), 7.28 (s, 2H), 8.62 (s, 1H); Mass Spectrum: M+H+ 540/542.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([F:9])[C:6]([N+:10]([O-])=O)=[CH:5][C:4]=1[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])#[N:2]>CO.CCOC(C)=O.[Pd]>[NH2:10][C:6]1[C:7]([F:9])=[CH:8][C:3]([C:1]#[N:2])=[C:4]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:5]=1
Reactant: CCOC(=O)Cc1cc([N+](=O)[O-])c(F)cc1C#N
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)Cc1cc(N)c(F)cc1C#N
Temperature: 25 °C
Reaction time: 72 h
Yield: 81 %

Procedure:
To a solution of ethyl 2-(2-cyano-4-fluoro-5-nitrophenyl)acetate in methanol and EtOAc (1:1, 10 mL) was added 10% Pd/C. The solution was stirred under H2 (1 arm) at RT for 3 days. The solution was filtered and evaporated to obtain ethyl 2-(5-amino-2-cyano-4-fluorophenyl)acetate (0.21 g, 81% yield).
Reaction SMILES: [C:1]([CH:4]1[C:9](=O)[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1)(=O)[CH3:2].[NH2:18][NH2:19].O>CCO>[CH3:2][C:1]1[C:4]2[CH2:5][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:8][C:9]=2[NH:19][N:18]=1
Reactant: NN
Reactant: CC(=O)C1CN(C(=O)OC(C)(C)C)CCC1=O
Solvent: O
Solvent: CCO
Product: Cc1n[nH]c2c1CN(C(=O)OC(C)(C)C)CC2
Temperature: 90 °C
Yield: 76.3 %

Procedure:
To a solution of tert-butyl 3-acetyl-4-oxopiperidine-1-carboxylate (10.00 g, 41.44 mmol, 1.0 eq) in EtOH was added 98% H2NNH2—H2O (3.11 mL, 62.16 mmol, 1.5 eq). The reaction mixture was heated to 90° C. and refluxed for 2.0 h. The resulted mixture was concentrated in vacuo to give two tautomers as yellow oil (7.5 g, 76.5%), and which were used for the next step without further purification. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 238.31 (M+1);
Reaction SMILES: Cl.[F:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[OH-].[Na+].[C:21](Cl)([CH3:23])=[O:22]>C(Cl)Cl>[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:21](=[O:22])[CH3:23])=[CH:17][CH:18]=1
Reactant: Fc1ccc(CNCc2ccc(F)cc2)cc1
Reactant: CC(=O)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(=O)N(Cc1ccc(F)cc1)Cc1ccc(F)cc1
Reaction time: 0.5 h
Yield: 54.5 %

Procedure:
Bis-(4-fluoro-benzyl)-amine hydrochloride (43 grams, 0.16 mole) was suspended in 200 mL of CH2Cl2. To this was added 730 mL of 1N NaOH. The reaction mixture was stirred vigorously while AcCl (20 mL, 0.28 mole) was slowly added. The reaction was stirred for 0.5 h, then the organic layer separated, washed with 1N HCl, dried over Na2SO4, filtered and the solvent removed under vacuum to yield 24 grams (55% yield) of N,N-bis-(4-fluoro-benzyl)-acetamide as an oil. MS (M+H) calcd for C16H16F2NO: 276.1. found: 276.0. Anal. calcd for C16H15F2NO: C, 69.80; H, 5.49; N, 5.08. found: C, 69.53; H, 5.41; N, 5.06. 1H NMR (500 MHz, DMSO) δ: 2.10 (s, 3), 4.45 (s, 2), 4.50 (s, 2), 7.11–7.27 (overlapping m, 8). 13C NMR (125 MHz, DMSO) δ: 21.34, 50.04, 54.80, 114.90, 115.07, 115.27, 115.45, 128.51, 128.58, 129.57, 129.64, 133.32, 133.34, 133.86, 133.89, 160.25, 160.33, 162.27, 170.22.
Reaction SMILES: CS([O:5][CH2:6][C@@H:7]1[CH2:13][CH2:12][C:9]2([CH2:11][CH2:10]2)[N:8]1[CH3:14])(=O)=O.O[C:16]1[CH:25]=[C:24]2[C:19]([C:20]([O:26][C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]4[C:37](=[O:49])[N:38]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)[N:39]([CH3:42])[C:40]=4[CH3:41])=[O:35])=[CH:29][C:28]=3[F:50])=[CH:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[CH3:14][N:8]1[C@H:7]([CH2:6][O:5][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]5[C:37](=[O:49])[N:38]([C:43]6[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=6)[N:39]([CH3:42])[C:40]=5[CH3:41])=[O:35])=[CH:29][C:28]=4[F:50])=[CH:21][CH:22]=[N:23]3)=[CH:18][CH:17]=2)[CH2:13][CH2:12][C:9]21[CH2:11][CH2:10]2
Reactant: Cc1c(C(=O)Nc2ccc(Oc3ccnc4cc(O)ccc34)c(F)c2)c(=O)n(-c2ccccc2)n1C
Reactant: CN1[C@H](COS(C)(=O)=O)CCC12CC2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: Cc1c(C(=O)Nc2ccc(Oc3ccnc4cc(OC[C@@H]5CCC6(CC6)N5C)ccc34)c(F)c2)c(=O)n(-c2ccccc2)n1C
Temperature: 40 °C
Reaction time: 72 h
Yield: 6 %

Procedure:
To a mixture of ((5S)-4-methyl-4-azaspiro[2.4]heptane-5-yl)methyl methanesulfonate (150 mg, 0.685 mmol) and N-(4-(7-hydroxyquinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxamide (331.5 mg, 0.685 mmol) in 8 mL of N,N-dimethylacetamide was added cesium carbonate (893 mg, 2.74 mmol, Aladdin). After stirring at 40° C. for 3 days, the reaction mixture was concentrated in vacuo and the residue was chromatographed with a silica gel column (50:1 (v/v) CH2Cl2/CH3OH) to give the desired product as a pale yellow solid (25 mg, 6%).
Reaction SMILES: [Br:1][C:2]1[O:3][C:4]2[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:5]=2[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.BrC1OC2C=C(C)C=CC=2C=1C1C=CC=CC=1.Br[N:36]1C(=O)CC[C:37]1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.BrC1OC2C=CC=C(CBr)C=2C=1C1C=CC=CC=1.[C-]#N.[Na+]>CC(C)=O.C(O)C.C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[O:3][C:4]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][C:37]#[N:36])[C:5]=2[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc2oc(Br)c(-c3ccccc3)c12
Agent: BrCc1cccc2oc(Br)c(-c3ccccc3)c12
Agent: Cc1ccc2c(-c3ccccc3)c(Br)oc2c1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CC(C)=O
Solvent: CCO
Solvent: ClC(Cl)(Cl)Cl
Product: N#CCc1cccc2oc(Br)c(-c3ccccc3)c12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 2-bromo-4-methyl-3-phenylbenzofuran and 2-bromo-6-methyl-3-phenylbenzofuran (about 15 percent 6 isomer) (51.5 g., 0.179 mole), N-bromosuccinimide (37.7 g., 0.178 mole) and benzoyl peroxide (about 0.05 g.) in 400 ml. of carbon tetrachloride is heated at its reflux temperature while shining a sunlamp on the mixture until reaction is complete. The mixture is cooled, then filtered to remove succinimide, and the organic layer is evaporated to dryness and suspended in petroleum ether. The white solid product is separated by filtration. It is about 95 percent pure 2-bromo-4-bromomethyl-3-phenylbenzofuran. The 2-bromo-4-bromomethyl-3-phenylbenzofuran (44.5 g., 0.122 mole) dissolved in acetone (165 ml.), aqueous (30 ml.) sodium cyanide (6.0 g., 0.122 mole) and ethanol (112 ml.) are mixed and heated to reflux. After about five hours of heating the mixture is allowed to stir at about 25° C. for about 16 hours. The reaction mixture is evaporated under vacuum, the residue is dissolved in diethyl ether and water-washed, and the organic layer is again concentrated to provide an oily brown solid, 2-bromo-4-cyanomethyl-3-phenylbenzofuran.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH3:16][N:17]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:18](Cl)=[O:19]>C(OCC)(=O)C.CCCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:18](=[O:19])[N:17]([CH3:16])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: Oc1ccc(Oc2ccc(Cl)cn2)cc1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: CN(C(=O)Oc1ccc(Oc2ccc(Cl)cn2)cc1)c1ccccc1

Procedure:
The title product was prepared from 4-(5-chloro-pyridin-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to column chromatography (ethyl acetate/heptane (1:5) (85%, white solid). HPLC-MS: m/z=355.1 (M+1); Rt: 4.56 min.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)[NH:9][N:8]=2)=[CH:3][CH:2]=1.[H-].[Na+].CN(C)C=O.[CH2:25](I)[CH2:26][CH3:27]>O1CCCC1>[CH2:25]([N:8]1[C:7]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[N:11][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[N:9]1)[CH2:26][CH3:27]
Reactant: c1cc(-c2n[nH]c(-c3ccncc3)n2)ccn1
Reactant: CCCI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCCn1nc(-c2ccncc2)nc1-c1ccncc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To 3,5-bis(4-pyridyl)-1,2,4-triazole (4.4 g., 0.02 mole) in dry tetrahydrofuran (200 ml.) is added 57% sodium hydride in mineral oil (1 g. 0.024 mole) and the mixture is heated 45 minutes at reflux. The suspension is concentrated to a solid, N,N-dimethylformamide (70 ml.) and n-propyl iodide (0.022 mole) are added. The mixture is stirred 0.5 hour at ambient temperature followed by heating on the steam bath for 4 hours. The solution is concentrated to a gum, water is added and the material solidifies. Following recrystallization from methylcyclohexane there is obtained 1-n-propyl-3,5-bis(4-pyridyl)-1,2,4-triazole, m.p. 88°-89.5°C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([OH:20])[CH:16]=[C:17]([CH3:19])[CH:18]=1)(=[O:11])=[O:10].C(P(CCCC)CCCC)CCC.[CH2:34](O)[CH2:35][CH2:36][OH:37].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1.CCCCCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[O:20][CH2:34][CH2:35][CH2:36][OH:37])(=[O:10])=[O:11]
Reactant: Cc1cc(O)cc(OS(=O)(=O)c2cc(Cl)ccc2Cl)c1
Reactant: OCCCO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cc1cc(OCCCO)cc(OS(=O)(=O)c2cc(Cl)ccc2Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.5 %

Procedure:
To a solution of 3-(2,5-dichlorophenylsulfonyloxy)-5-methylphenol (642 mg, 2.0 mmol), as prepared in the preceding step, tri-n-butylphosphine (607 mg, 3.0 mmol) and 1,3-propanediol (760 mg, 10 mmol) in anhydrous tetrahydrofuran (20 mL) was added 1,1'-(azodicarbonyl) dipiperidine (757 mg, 3.0 mmol). The mixture was stirred at ambient temperature overnight. Hexane (30 mL) was added to the mixture, and the precipitates were removed by filtration. The filtrate was evaporated in vacuo, and the residue was purified by flash column chromatography (2:1 hexane/ethyl acetate) to give the title compound as a colorless oil (700 mg, 90%). 1H-NMR (300 MHz, CDCl3) δ 7.96 (s, 1H), 7.56 (s, 2H), 6.63 (s, 1H), 6.55 (s, 1H), 6.51 (s, 1H), 4.03 (t, J=6.0 Hz, 2H), 3.82 (m, 2H), 2.26 (s, 3H), 2.00 (m, 2H), 1.58 (s, 1H).
Reaction SMILES: [C:1]([O:4][CH:5]([C:10]1[CH:11]=[C:12]([CH3:16])[CH:13]=[CH:14][CH:15]=1)[CH2:6][CH2:7][CH2:8][CH3:9])(=[O:3])[CH3:2].[Br:17]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[C:1]([O:4][CH:5]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][Br:17])[CH:11]=1)[CH2:6][CH2:7][CH2:8][CH3:9])(=[O:3])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCCC(OC(C)=O)c1cccc(C)c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCC(OC(C)=O)c1cccc(CBr)c1
Temperature: 0 °C

Procedure:
11 g of 3-(1-acetoxy-pentyl)toluene are dissolved in 100 ml of absolute carbon tetrachloride. After addition of 8.9 g of N-bromosuccinimide and 200 mg of azobisisobutyronitrile, the mixture is warmed slowly to the reflux temperature. When the reaction has ended, the mixture is heated under reflux for a further hour and then cooled to 0° C. and the succinimide is filtered off.
Reaction SMILES: [H-].[Na+].[C:3]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:4][OH:5].[CH3:10][S:11][C:12]1[N:17]=[C:16](Cl)[C:15]([N+:19]([O-:21])=[O:20])=[C:14]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([N:31]([CH3:33])[CH3:32])=[O:30])[CH:24]=2)[N:13]=1>O1CCCC1>[CH3:10][S:11][C:12]1[N:17]=[C:16]([O:5][CH2:4][C:3]([O:7][CH2:8][CH3:9])=[O:6])[C:15]([N+:19]([O-:21])=[O:20])=[C:14]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([N:31]([CH3:32])[CH3:33])=[O:30])[CH:24]=2)[N:13]=1
Reactant: CCOC(=O)CO
Reactant: CSc1nc(Cl)c([N+](=O)[O-])c(Oc2cccc(C(=O)N(C)C)c2)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)COc1nc(SC)nc(Oc2cccc(C(=O)N(C)C)c2)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 48 %

Procedure:
To sodium hydride (0.63 g, 15.72 mmol) in 30 mL tetrahydrofuran at 0° C. was added ethyl glycolate (1.15 mL, 12.09 mmol) over 10 minutes. The resulting alkoxide was then added to 2-methylthio-4-chloro-5-nitro-6-(3-dimethylaminocarbonylphenoxy)pyrimidine, a compound of formula (C), (4.46 g., 12.09 mmol), dropwise at 0° C. over 5 minutes. After 1 hours, the reaction mixture was warmed to ambient temperature and stirred for an additional 2 hours. The volatiles were evaporated to yield 2.55 g (48% yield) of 2-methylthio-4-(ethoxycarbonyl)methoxy-5-nitro-6-(3-dimethylaminocarbonylphenoxy)pyrimidine, a compound of formula (Q), as a yellow oil.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][O:5][N:6]1[CH:14]=[N:13][C:12]2[C:11](=[O:15])[NH:10][C:9]([NH2:16])=[N:8][C:7]1=2.[C:17](OC(=O)C)(=[O:19])[CH3:18].CN(C)C=O>CN(C)C1C=CN=CC=1.C(O)C>[C:17]([O:1][CH2:2][CH2:3][CH2:4][O:5][N:6]1[CH:14]=[N:13][C:12]2[C:11](=[O:15])[NH:10][C:9]([NH2:16])=[N:8][C:7]1=2)(=[O:19])[CH3:18]
Reactant: Nc1nc2c(ncn2OCCCO)c(=O)[nH]1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CCO
Solvent: CN(C)C=O
Product: CC(=O)OCCCOn1cnc2c(=O)[nH]c(N)nc21
Temperature: 20 °C
Reaction time: 3 h
Yield: 67 %

Procedure:
A mixture of 9-(3-hydroxyprop-1-oxy)guanine (150 mg, 0.67 mmol), 4-dimethylaminopyridine (15.6 mg, 0.13 mmol), acetic anhydride (0.25 ml, 2.65 mmol) and N,N-dimethylformamide (5 ml) was stirred at 20° C. for 3 hours and then ethanol was added. After a further 15 minutes the solvent was evaporated under reduced pressure and the residue was chromatographed on silica gel (eluted with chloroform-ethanol, 4:1), yielding the title compound (120 mg, 67%). Recrystallisation from methanol-water gave 9-(3-acetoxy-prop-1-oxy)guanine (82 mg, 46%). IR: υmax (KBr) 3330, 3168, 1736, 1696, 1648, 1602, 1589, 1391 cm-1. 1H NMR: δH [(CD3)2SO] 1.98 (2H, quintet, J=6.3, 6.6 Hz, CH2CH2CH2), 2.02 (3H, s, ##STR14## 4.17 (2H, t, J=6.6 Hz, CH2ON), 4.32 (2H, t, J=6.3 Hz, ##STR15## 6.60 (2H, br.s, D2O exchangeable NH2), 7.94 (1H, s, H-8), 10.69 (1H, br.s, D2O exchangeable, H-1). Found: C, 44.99; H, 4.93; N, 26.20% M+ 267.0964 C10H13N5O4 requires C, 44.93; H, 4.91; N, 26.21% M+ 267.0968.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=O.[Si](Cl)(C(C)(C)C)(C)C.CCN(C(C)C)C(C)C.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:43])=CC=1.[F-].C([N+](C)(C)C)C1C=CC=CC=1>O1CCCC1>[OH:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[S:43]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: NC(=O)c1ccc(N2CCOCC2)cc1O
Agent: CC(C)(C)[Si](C)(C)Cl
Agent: C[N+](C)(C)Cc1ccccc1
Agent: [F-]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: NC(=S)c1ccc(N2CCOCC2)cc1O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a stirred solution of 2-hydroxy-4-morpholin-4-yl-benzamide (102 mg; 0.46 mmol) and t-butyldimethylsilyl chloride (73 mg; 0.48 mmol) in dry tetrahydrofuran (4 mL) was added Hunig's base (0.084 mL; 0.48 mmol) via syringe at room temperature under a nitrogen atmosphere. After stirring at room temperature for 4 hours, Lawesson's reagent was added (117 mg; 0.28 mmol) in one portion and the resulting solution was stirred for 16 hours. Benzyl trimethyl ammonium fluoride (1.84 mmol) then was added and stirring was continued for 2 hours longer. The reaction was concentrated at reduced pressure, and the residue re-dissolved in EtOAc (10 mL) and washed with water, 10% citric acid, 5% NaHCO3, and brine then dried (Na2SO4), filtered and concentrated in vacuo. The residue was then recrystallized from EtOAc/hexanes to provide the thioamide as a yellow solid (31 mg; 28%).