Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: ClC1C=C(C=CC=1F)[C:5]1[C:10]([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:21]4[N:25]([CH:26]5[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]5)[C:24]5[CH:32]=[CH:33][C:34]([C:36]([OH:38])=[O:37])=[CH:35][C:23]=5[N:22]=4)[CH:17]=3)[N:12]=2)=[CH:9][C:8]([O:39][CH3:40])=[CH:7][CH:6]=1.COC(C1C=CC2N(C3CCCCC3)C(C3C=C4C(=CC=3)N=C(C3C=C(OC)C=CC=3Br)C=C4)=NC=2C=1)=O.[CH3:83][O:84][C:85]1[N:90]=[C:89]([O:91][CH3:92])[C:88](B(O)O)=[CH:87][N:86]=1>>[CH:26]1([N:25]2[C:24]3[CH:32]=[CH:33][C:34]([C:36]([OH:38])=[O:37])=[CH:35][C:23]=3[N:22]=[C:21]2[C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([C:10]2[CH:9]=[C:8]([O:39][CH3:40])[CH:7]=[CH:6][C:5]=2[C:88]2[C:89]([O:91][CH3:92])=[N:90][C:85]([O:84][CH3:83])=[N:86][CH:87]=2)[CH:20]=[CH:19]3)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1
Reactant: COc1ncc(B(O)O)c(OC)n1
Reactant: COc1ccc(-c2ccc(F)c(Cl)c2)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1
Agent: COC(=O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(OC)ccc4Br)ccc3c1)n2C1CCCCC1
Product: COc1ccc(-c2cnc(OC)nc2OC)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1
Yield: 7 %

Procedure:
Following the full procedure and workup for Compound 366, Compound 365b (100 mg, 0.175 mmol) was reacted with 2,4-dimethoxypyrimidine-5-boronic acid (34 mg, 0.2625 mmol) to produce the title compound (8 mg, 7% yield).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[Cl:5][CH2:6][C:7]1[S:11][C:10]([NH2:12])=[N:9][N:8]=1>C(OCC)(=O)C>[Cl:5][CH2:6][C:7]1[S:11][C:10]([N:12]=[C:1]=[O:2])=[N:9][N:8]=1
Reactant: O=C(Cl)Cl
Reactant: Nc1nnc(CCl)s1
Solvent: CCOC(C)=O
Product: O=C=Nc1nnc(CCl)s1
Reaction time: 16 h

Procedure:
A saturated solution of phosgene in ethyl acetate (100 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer. A slurry of 5-chloromethyl-2-amino-1,3,4-thiadiazole (10 grams) in ethyl acetate (300 ml) is added to the reaction vessel, and the resulting mixture is stirred for a period of about 16 hours, resulting in the formation of a precipitate. The reaction mixture is then purged with nitrogen gas to remove unreacted phosgene. The purged mixture is then filtered to recover the desired product 5-chloromethyl-1,3,4-thiadiazol-2-yl isocyanate dimer as a solid.
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH:27]([F:31])[CH:26]([CH3:32])[CH2:25][CH:24]([O:33][CH3:34])[CH:23]2[O:35][C:19]([OH:39])([CH:20]([CH3:38])[CH2:21][CH:22]2[O:36][CH3:37])[C:18](=[O:40])[C:17](=[O:41])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:42])[O:9][CH:8]([C:43]([CH3:72])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][C:52]3[CH:61]=[CH:60][C:59]4[C:54](=[CH:55][CH:56]=[C:57]([O:62][Si](C(C)(C)C)(C)C)[CH:58]=4)[CH:53]=3)[CH:47]([O:70][CH3:71])[CH2:46]2)[CH:7]([CH3:73])[CH:6]([OH:74])[CH2:5][C:4]1=[O:75])[CH3:2].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.CO>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH:27]([F:31])[CH:26]([CH3:32])[CH2:25][CH:24]([O:33][CH3:34])[CH:23]2[O:35][C:19]([OH:39])([CH:20]([CH3:38])[CH2:21][CH:22]2[O:36][CH3:37])[C:18](=[O:40])[C:17](=[O:41])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:42])[O:9][CH:8]([C:43]([CH3:72])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][C:52]3[CH:61]=[CH:60][C:59]4[C:54](=[CH:55][CH:56]=[C:57]([OH:62])[CH:58]=4)[CH:53]=3)[CH:47]([O:70][CH3:71])[CH2:46]2)[CH:7]([CH3:73])[CH:6]([OH:74])[CH2:5][C:4]1=[O:75])[CH3:2]
Reactant: CCC1C=C(C)C(F)C(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(Oc4ccc5cc(O[Si](C)(C)C(C)(C)C)ccc5c4)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: ClCCl
Product: CCC1C=C(C)C(F)C(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(Oc4ccc5cc(O)ccc5c4)C(OC)C3)C(C)C(O)CC1=O)C(C)CC2OC
Reaction time: 4 h

Procedure:
To a stirred solution of 17-ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(6'"-tert-butyldimethylsilyloxynaphth-2-yloxy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (73 mg, 0.07 mmol) in CH2Cl2 (2 mL) was added a solution of p-toluenesulfonic acid in methanol (2 mL, 10% solution). The flask is capped and the mixture stirred 4 hours. The reaction is quenched with saturated aqueous NaHCO3 and extracted 4× with CH2Cl2. The organic extracts are combined and dried over anhydrous Na2SO4. The mixture is filtered and concentrated in vacuo. The product is isolated by preparative TLC on silica gel to afford the title compound.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[C:9]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)=[CH:8]2)=[O:4].[NH2:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34].C[O-].[Na+]>>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:29])[C:5]([C:3]([NH:30][CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:4])=[N:14][CH:13]=2)[CH:8]=[C:9]([C:23]2[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=2)[C:10]1=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)c1ncc2c(cc(-c3cccnc3)c(=O)n2Cc2ccccc2)c1O
Reactant: NCCC(=O)O
Agent: C[O-]
Agent: [Na+]
Product: O=C(O)CCNC(=O)c1ncc2c(cc(-c3cccnc3)c(=O)n2Cc2ccccc2)c1O
Temperature: 25 °C
Yield: 47.5 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-2-oxo-3-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (35 mg, 0.090 mmol), β-alanine (806 mg, 9.0 mmol) and NaOMe solution (13.6 mL, 6.78 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was dissolved in water and washed several times with ether. The aqueous layer was acidified to pH about 3-4 with 1 M HCl, and the resulting precipitate was isolated by filtration to give 19 mg of the title compound. MS: (+) m/z 445.33 (M+1).
Reaction SMILES: [C:1](=O)([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)OC.ClC[C:14]([O:16][CH2:17][CH3:18])=[O:15].CC1C(CN2CCC(N3CCC(N4C(=O)NC5C4=CC=CC=5)CC3)CC2)=CC=CC=1>>[O:4]([CH2:1][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: CCOC(=O)CCl
Reactant: COC(=O)Oc1ccccc1
Agent: Cc1ccccc1CN1CCC(N2CCC(n3c(=O)[nH]c4ccccc43)CC2)CC1
Product: CCOC(=O)COc1ccccc1
Temperature: 120 °C
Yield: 96 %

Procedure:
A mixture of 3.8 g of methyl phenyl carbonate, 3.06 g of ethyl chloroacetate, and 0.42 g of TBPB was heated at 120° C. for 2 hours. Distillation of the resulting reaction mixture provided a 96 percent yield of ethyl phenoxyacetate.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@@H:13]2[O:26][C:17]3[C:18]4[NH:22][C:21](=[O:23])[NH:20][C:19]=4[CH:24]=[CH:25][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[NH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:33]=[C:34]([NH:38][C:39](=[O:41])[CH3:40])[CH:35]=[CH:36][CH:37]=1>CS(C)=O.C(OCC)(=O)C>[O:23]=[C:21]1[NH:22][C:18]2=[C:17]3[C:16](=[CH:25][CH:24]=[C:19]2[NH:20]1)[O:15][CH2:14][CH:13]([CH2:12][NH:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:33]=[C:34]([NH:38][C:39](=[O:41])[CH3:40])[CH:35]=[CH:36][CH:37]=1)[O:26]3
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COc3ccc4[nH]c(=O)[nH]c4c3O2)cc1
Reactant: CC(=O)Nc1cccc(OCCCN)c1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1cccc(OCCCNCC2COc3ccc4[nH]c(=O)[nH]c4c3O2)c1
Temperature: 95 °C

Procedure:
A mixture of 0.60 g (1.6 mmole) of (8R)-1,3,7,8-tetrahydro-8-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-2H-[1,4]dioxino[2,3-e]benzimidazol-2-one and 1.6 g (8.0 mmole) of N-[3-(3-amino-propoxy)phenyl]-acetamide in 30 mL of DMSO was heated at 90-100° C. under nitrogen for 6 hours. The reaction was allowed to come to room temperature, diluted to 500 mL with ethyl acetate, washed with 500 mL portions of saturated aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 2% methanol in chloroform as eluant and the product fractions evaporated to give the free base of the title compound. This was recrystallized from ethanol with the addition of fumaric acid to give 0.19 g of the (S)-enantiomer of the title compound as a white solid fumarate, three-quarter hydrate, m.p. 125° C. (d).
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:11][N:12]1[C:17](=[O:18])[C:16]2[N:19]=[CH:20][N:21](C(OC(C)(C)C)=O)[C:15]=2[CH:14]=[N:13]1.[Cl:29]C(Cl)(Cl)C(Cl)(Cl)Cl.O.N>O1CCCC1>[Cl:29][C:20]1[NH:21][C:15]2[CH:14]=[N:13][N:12]([CH3:11])[C:17](=[O:18])[C:16]=2[N:19]=1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: Cn1ncc2c(ncn2C(=O)OC(C)(C)C)c1=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: N
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cn1ncc2[nH]c(Cl)nc2c1=O
Reaction time: 0.5 h
Yield: 83.1 %

Procedure:
8.4 ml of lithium hexamethyldisilazide (1.0 M tetrahydrofuran solution) was added dropwise over one hour to a 300-ml tetrahydrofuran solution containing 1.68 g of t-butyl 5-methyl-4-oxo-4,5-dihydroimidazo[4,5-d]pyridazine-1-carboxylate and 4.15 g of hexachloroethane under a nitrogen atmosphere at 0° C. The resulting mixture was stirred for 30 minutes. 2N ammonia water was added to the solution, and the mixture was stirred for three hours. Then, the reaction solution was concentrated to 50 ml, and washed with 20 ml of t-butyl methyl ether. The solution was acidified with concentrated hydrochloric acid. The resulting precipitate was collected by filtration, and washed successively with 10 ml of water and 10 ml of t-butyl methyl ether. Thus, 1.03 g of the title compound was obtained.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:16][CH:17](O)[CH3:18])[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P([N:67]=[N+:68]=[N-:69])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.ClCCl>[N:67]([CH:17]([CH3:18])[CH2:16][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][CH:13]=1)[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[N+:68]=[N-:69]
Reactant: CC(O)Cc1cccc(CO[Si](C)(C)C(C)(C)C)c1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(Cc1cccc(CO[Si](C)(C)C(C)(C)C)c1)N=[N+]=[N-]
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a stirring solution of 1-[3-(tert-butyldimethylsilyloxymethyl)-phenyl]-propan-2-ol (130 mg, 0.46 mmol) in THF (1.5 mL) under nitrogen at 0° C. was added diisopropyl azodicarboxylate (140 mg, 0.7 mmol), triphenylphosphine (180 mg, 0.7 mmol), and diphenylphosphoryl azide (190 mg, 0.7 mmol) and the mixture was stirred at 0° C. for 15 min. The mixture was diluted with dichloromethane, washed with water, brine, dried over magnesium sulfate, and purified by flash column chromatography (ethyl acetate/hexanes). 1H NMR (CDCl3) 7.27 (m, 1H), 7.2 (m, 1H), 7.16 (s, 1H), 7.08 (m, 1H), 4.74 (s, 2H), 3.65 (m, 1H), 2.82 (dd, 1H), 2.73 (dd, 1H), 1.25 (d, 3H), 0.94 (s, 9H), 0.10 (s, 6H).
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[O:3]1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1.O>CN(C=O)C>[Si:14]([O:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[O:3]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OC1CCC(c2ccc(F)cc2)O1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC1CCC(c2ccc(F)cc2)O1
Reaction time: 8 h
Yield: 93.3 %

Procedure:
2-Hydroxy-5-(4-fluorophenyl)-tetrahydrofuran (550 mg, 3.0 mmol), t-butyldimethylsilyl chloride (498 mg, 3.3 mmol) and imidazole (450 mg, 6.6 mmol) were dissolved in 2 mL of dry DMF. This solution was stirred under dry argon overnight, poured into 200 mL of water and extracted with a 2:1 mixture of ethyl acetate and hexane (3×100 mL). The combined organic extracts were washed with water (4×200 mL) and brine (100 mL), dried over sodium sulfate and evaporated to give 830 mg (93%) of 2-(t-butyldimethylsilyloxy)-5-(4-fluorophenyl) tetrahydrofuran (202, mixture of cis and trans isomers) as a colorless oil, which did not need any purification. 1H-NMR (CDCl3) δ 7.40-7.50(2H, m, minor isomer), 7.25-7.35 (2H, m, major isomer), 7.00-7.10(2H, m, both major and minor isomers), 5.71-5.75 (1H, m, major isomer), 5.59-5.62 (1H, m, minor isomer), 5.12-5.20 (1H, m, major isomer), 4.90-4.98 (1H, m, minor isomer), 2.40-2.55 (1H, m, both major and minor isomers), 2.05-2.17 (1H, m, both major and minor isomers), 1.87-2.00 (1H, m, both major and minor isomers), 1.67-1.70 (1H, m, both major and minor isomers), 0.92 (s, 9H, both major and minor isomers), 0.16 (s, 6H, both major and minor isomers).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]#N)=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15])(=[O:3])[CH3:2].[CH2:17](O)[CH2:18]C.[OH-].[K+].C(Br)CC>O>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:17][CH3:18])=[CH:7][C:6]=1[N+:14]([O-:16])=[O:15])(=[O:3])[CH3:2]
Reactant: CCCO
Reactant: CC(=O)Nc1ccc(SC#N)cc1[N+](=O)[O-]
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCCBr
Product: CCCSc1ccc(NC(C)=O)c([N+](=O)[O-])c1
Reaction time: 8 h

Procedure:
of 1-acetamido-2-nitro-4-thiocyanatobenzene in 70 ml. of n-propyl alcohol containing 4.8 g. potassium hydroxide is treated with 2.6 g. n-propylbromide. The mixture is stirred overnight at 15°-20° C., then poured into water, and extracted with chloroform. The dried extracts are stripped under vacuum and the residual red oil is dissolved in 25 ml. of acetic anhydride. A few drops of sulfuric acid are added and the mixture left at 20°-25° C for 1 hour. Sodium acetate is added and the solvent removed under vacuum. The residue is treated with water and the crude product filtered off. Recrystallization from methanol gives 1-acetamido-2-nitro-4-n-propylthiobenzene. (This intermediate may also be obtained directly by alkylation of 1-acetamido-2-nitro-4-thiocyanatobenzene with n-propylbromide in dimethylformamide in the presence of sodium borohydride.)
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]([NH:14][C:15](=[O:24])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:4]=1.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C:15]([NH:14][N:5]2[N:4]=[C:3]([CH2:2][NH:1][S:26]([CH3:25])(=[O:28])=[O:27])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:13])=[O:24])=[CH:22][CH:21]=1
Reactant: CS(=O)(=O)Cl
Reactant: NCc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12
Product: CS(=O)(=O)NCc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12

Procedure:
The product from Example 42 and methanesulfonyl chloride were processed using a method similar to that described in Example 4C to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.66-11.72 (m, 1H), 8.31-8.43 (m, 1H), 8.15 (d, J=8.0 Hz, 1H), 7.99-8.06 (m, 1H), 7.89-7.96 (m, 1H), 7.66-7.74 (bs, 1H), 7.36-7.45 (m, 4H), 4.46-4.49 (m, 2H), 3.68 (s, 2H), 2.94 (s, 3H); MS (ESI+) M/Z 421 (M+H)+.
Reaction SMILES: Cl.[N:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12](Cl)=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[C:15]12([NH2:25])[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]3)[CH2:16]1)[CH2:22]2.N1C=CC=CC=1>O>[C:15]12([NH:25][C:12]([C:8]3[CH:7]=[C:6]4[C:11](=[CH:10][CH:9]=3)[N:2]=[CH:3][CH:4]=[CH:5]4)=[O:13])[CH2:22][CH:21]3[CH2:20][CH:19]([CH2:18][CH:17]([CH2:23]3)[CH2:16]1)[CH2:24]2
Reactant: O=C(Cl)c1ccc2ncccc2c1
Reactant: NC12CC3CC(CC(C3)C1)C2
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C(NC12CC3CC(CC(C3)C1)C2)c1ccc2ncccc2c1
Yield: 10.8 %

Procedure:
Prepared from 6-quinolinecarbonyl chloride hydrochloride (1.51 g, 10 mmol), 1-adamantanamine (1.73 g, 10 mmol), pyridine (5 mL), and water (200 mL) yielding 330 mg (11%) of (42):
Reaction SMILES: [C:1]([C:3]1[C:4](=[O:20])[NH:5][C:6](=[O:19])[N:7]([C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[CH:12]=[CH:13][CH:14]=2)[N:8]=1)#[N:2].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>CC#N>[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][N:5]2[C:4](=[O:20])[C:3]([C:1]#[N:2])=[N:8][N:7]([C:9]3[CH:10]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[CH:12]=[CH:13][CH:14]=3)[C:6]2=[O:19])=[CH:24][CH:23]=1
Reactant: CC(=O)Nc1cccc(-n2nc(C#N)c(=O)[nH]c2=O)c1
Reactant: Clc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC(=O)Nc1cccc(-n2nc(C#N)c(=O)n(Cc3ccc(Cl)cc3)c2=O)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 64.6 %

Procedure:
According to Scheme 7 Step 3: A suspension of 11(B) (500 mg, 1.8 mmol), 4-chlorobenzyl bromide (455 mg, 2.2 mmol) and potassium carbonate (510 mg, 3.7 mmol) in CH3CN (10 mL) was stirred 12 h under reflux. The mixture was cooled at room temperature and 100 mL of water were added. The aqueous layer was extracted thrice with DCM (100 mL). The organic layers were mixed, dried over MgSO4, filtered and concentrated under reduced pressure to afford a brown solid. The crude solid was purified by flash chromatography with silica gel (AIT Flashmart prepacked column 50 g SiO2) using CH2Cl2/MeOH (98/2) as eluant to afford N-(3-(4-(4-chlorobenzyl)-6-cyano-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide 11(C) (460 mg, 63%) as a beige solid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1.[C:12]1([S:18](Cl)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[C:12]1([S:18]([N:1]2[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: CCOC(=O)C1CCCNC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)C1CCCN(S(=O)(=O)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.6 %

Procedure:
A mixture of ethyl piperidine-3-carboxylate (1.00 g, 6.36 mmol), benzenesulfonyl chloride (0.812 mL, 6.36 mmol), and triethylamine (2.66 mL, 19.1 mmol) in methylene chloride (10.0 mL) was stirred at r.t. for 2 hours. The mixture was quenched with water, then extracted with ethyl acetate. The extract was washed with 1N HCl solution, water, sat'd sodium bicarbonate solution, water, and brine, successively. Then, the extract was dried over sodium sulfate (anhydrous). After filtration, the filtrate was concentrated to yield 1.79 g (94%) of ethyl 1-(phenylsulfonyl)piperidine-3-carboxylate.
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11])[C:7]([OH:9])=O)(=[O:3])[CH3:2].[CH2:18]([O:25][C:26](=[O:30])[C@H:27]([CH3:29])[NH2:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([O:25][C:26](=[O:30])[C@H:27]([CH3:29])[NH:28][C:7](=[O:9])[CH:6]([CH2:5][S:4][C:1](=[O:3])[CH3:2])[CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: C[C@H](N)C(=O)OCc1ccccc1
Reactant: CC(=O)SCC(C(=O)O)C(C)c1ccccc1
Product: CC(=O)SCC(C(=O)N[C@@H](C)C(=O)OCc1ccccc1)C(C)c1ccccc1
Yield: 68 %

Procedure:
Using the procedure described in Example 60, starting with 2-acetylthiomethyl-3-phenylbutanoic acid and alanine benzyl ester, and after purification by chromatography, eluting with a cyclohexane/ethyl acetate (75:25 by volume) mixture, N-(2-acetylthiomethyl-1-oxo-3-phenylbutyl)alanine benzyl ester is obtained in a 68% yield, the characteristics of which are as follows: Rf =0.31 [hexane/ethyl acetate (75:25 by volume)].
Reaction SMILES: [C:1]([NH:12][NH2:13])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.NC1C=CC(C([NH:21][NH2:22])=O)=CC=1.C1C(N)=CC=C(N)C=1.NC1C=CC(C(Cl)=O)=CC=1.C(Cl)(=O)C1C=CC(C(Cl)=O)=CC=1>>[C:6]([NH:21][NH2:22])(=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([C:1]([NH:12][NH2:13])=[O:11])=[CH:3][CH:4]=1
Reactant: NNC(=O)c1ccc(N)cc1
Reactant: NNC(=O)c1ccc(C(=O)O)cc1
Agent: Nc1ccc(C(=O)Cl)cc1
Agent: Nc1ccc(N)cc1
Agent: O=C(Cl)c1ccc(C(=O)Cl)cc1
Product: NNC(=O)c1ccc(C(=O)NN)cc1

Procedure:
Terephthalic acid hydrazide, p-aminobenzoic acid hydrazide, p-phenylenediamine, p-aminobenzoyl chloride and terephthaloyl chloride are properly combined, and a 5 wt% solution of polyamide resin comprising 33 mol% of terephthalhydrazide, 33 mol% of p-benzamide, and 33 mol% of p-phenyleneterephthalamide is obtained by low temperature (about 10° to 35° C.) solution polymerization process. The solvent used for the solution polymerization is preferably dimethylacetamide and calcium chloride is contained in the polymerization solution as a neutralization product. This solution is cast on a metallic belt and dried until the polymer concentration becomes about 30 wt% by heating at about 100° C. for 5 minutes. The film is then dipped for about 2 minutes in water at normal temperatures (about 10° to 35° C.) to remove the solvent and calcium chloride. After further washing with water and drying at 230° C., the resulting film is rolled up. Orientation is conducted by stretching the dried film in the longitudinal direction in a 50° C. dimethylacetamide aqueous solution through the difference in rotating speeds of associated nip rolls, and subsequently stretching it in a lateral direction by guiding it to a tenter and expanding the rail distance. The draw ratio is generally kept from about 1.1 to 2.0 times in both longitudinal and lateral directions. Thus, a 3 μm thick aromatic polyamide film is obtained.
Reaction SMILES: [NH:1]([CH2:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:8]([C:9]([OH:11])=O)[C:7]=1[C:15]([OH:17])=O)[C:2]([NH2:4])=[O:3].Cl.[NH2:19][CH:20]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:21]1=[O:22]>N1C=CC=CC=1>[O:22]=[C:21]1[CH:20]([N:19]2[C:15](=[O:17])[C:7]3[C:8](=[CH:12][CH:13]=[CH:14][C:6]=3[CH2:5][NH:1][C:2]([NH2:4])=[O:3])[C:9]2=[O:11])[CH2:26][CH2:25][C:24](=[O:27])[NH:23]1
Reactant: NC(=O)NCc1cccc(C(=O)O)c1C(=O)O
Reactant: NC1CCC(=O)NC1=O
Agent: Cl
Solvent: c1ccncc1
Product: NC(=O)NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Yield: 34.7 %

Procedure:
A mixture of 3-ureidomethyl-phthalic acid (1.5 g, 6.1 mmol) and α-amino-glutarimide hydrochloride (1.0 g, 6.1 mmol) in pyridine (15 mL) was refluxed for 5 hours. The mixture was concentrated and the residue was stirred with water (20 mL). The solid was slurried with hot methanol to give [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.7 g, 36%): mp 292-294° C.; 1H NMR (DMSO-d6) δ 2.04-2.08 (m, 1H), 2.50-2.63 (m, 2H), 2.83-2.98 (m, 1H), 4.61 (d, J=6.1 Hz, 2H, CH2), 5.11-5.18 (m, dd, J=5.3 and 12.5 Hz, 1H, CH), 5.71 (s, 2H, NH2), 6.57 (t, J=6.0 Hz, 1H, NH), 7.70-7.87 (m, 3H, Ar), 11.15 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.98, 30.92, 38.66, 48.82, 121.63, 126.95, 131.50, 133.32, 134.61, 141.06, 158.65, 167.04, 167.57, 169.82, 172.76; Anal. calcd. for C15H14N4O5: C, 54.44; H, 4.27; N, 16.96. Found: C, 54.47; H, 4.17; N, 16.76.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](O)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:13][O:14][N:15](C)[C:16](C1SC=NC=1)=O>>[CH3:13][O:14][N:15]([CH3:16])[C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: CON(C)C(=O)c1cncs1
Product: CON(C)C(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
The title compound was prepared by substituting thiazole-5-carboxylic acid with 4-nitrobenzoic acid then following the procedure described for the preparation of N-methoxy-N-methylthiazole-5-carboxamide (Intermediate 11: step a).