Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](=[N:8][NH:9][C:10]1[CH:15]=[C:14]([S:16]([CH2:19][CH2:20]O)(=[O:18])=[O:17])[CH:13]=[CH:12][C:11]=1[S:22]([OH:25])(=[O:24])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:26](=O)(=[O:29])([OH:28])[OH:27]>>[CH:1](=[N:8][NH:9][C:10]1[CH:15]=[C:14]([S:16]([CH2:19][CH2:20][S:26]([OH:29])(=[O:28])=[O:27])(=[O:18])=[O:17])[CH:13]=[CH:12][C:11]=1[S:22]([OH:25])(=[O:24])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(=O)(O)c1ccc(S(=O)(=O)CCO)cc1NN=Cc1ccccc1
Reactant: O=S(=O)(O)O
Product: O=S(=O)(O)CCS(=O)(=O)c1ccc(S(=O)(=O)O)c(NN=Cc2ccccc2)c1

Procedure:
345 parts of the dry 2-(2-benzylidenehydrazino)-4-(2-hydroxyethylsulfonyl)-benzenesulfonic acid are added to 1000 parts of sulfuric acid (monohydrate); after quantitative esterification (after 10 h) the mixture is added to 2500 parts of ice. 2-(2-Benzylidenehydrazino)-4-(2-sulfoethylsulfonyl)-benzenesulfonic acid can then be isolated therefrom by precipitation with sodium chloride or be obtained as an aqueous neutral solution by bringing this acid solution to a pH of 5 with 900 parts of calcium carbonate and about 100 parts of sodium carbonate and at 60° C. filtering off the calcium sulfate with suction.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=[O:10])[CH:7]=1.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[CH3:19][O:18][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:7][C:6]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1)=[O:10]
Reactant: COc1ccc(N)cc1NC(=O)Nc1cnccn1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: COc1ccc(NS(C)(=O)=O)cc1NC(=O)Nc1cnccn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 60.8 %

Procedure:
A solution of 1-(5-amino-2-methoxyphenyl)-3-pyrazin-2-yl-urea (Compound 14, Example 4) (260 mg, 1 mmol) in dry pyridine (15 mL) was treated with methanesulfonyl chloride (0.08 mL, 1 mmol) and stirred 16 h at room temperature. The reaction mixture was concentrated in vacuo and the solid residue was triturated with ethanol, collected by filtration, and dried in vacuo to afford the product (205 mg, 61%). 1H NMR (300 Mhz, d6-DMSO) δ: 10.16 (s, 1H), 10.07 (s, 1H), 9.40 (s, 1H), 8.92 (s, 1H), 8.35 (s, 1H), 8.27 (s, 1H), 8.19 (d, J=2.2 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 6.91 (dd, J=8.7, 2.4 Hz, 1H), 3.91 (s, 3H), 2.91 (s, 3H).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:23]=[CH:24][CH:25]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([NH:18][NH:19][C:20]([NH2:22])=[O:21])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O>>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:23]=[CH:24][CH:25]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]2[O:21][C:20]([NH2:22])=[N:19][N:18]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NC(=O)NNC(=O)NCCCOc1cccc(CN2CCCCC2)c1
Solvent: O=P(Cl)(Cl)Cl
Product: Nc1nnc(NCCCOc2cccc(CN3CCCCC3)c2)o1

Procedure:
The compound is prepared by a method analogous to that of Example 40 from N-[3-[3-(1-piperidinylmethyl) phenoxy]propyl]-1,2-hydrazine dicarboxamide and phosphorus oxychloride.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:68]([O:75][CH2:76][C@@H:77]([C:79]([OH:81])=[O:80])[NH2:78])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[OH:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:78][C@H:77]([C:79]([OH:81])=[O:80])[CH2:76][O:75][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)=[O:35])=[O:31])=[CH:37][CH:38]=2)=[CH:6][CH:7]=1
Reactant: O=C(O)CNC(=O)COc1ccc([C@@H]2[C@@H](SCC(=O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1
Reactant: N[C@@H](COCc1ccccc1)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: O=C(COc1ccc([C@@H]2[C@@H](SCC(O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1)NCC(=O)N[C@@H](COCc1ccccc1)C(=O)O
Temperature: 30 °C
Reaction time: 1.5 h

Procedure:
To a stirred solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine, (20.3 mg, 0.038 mmol) in DMF (2 ml) was added N-methylmorpholine (15 μl, 0.14 mmol). TBTU (14.8 mg, 0.046 mmol) was added the mixture was stirred at 30° C. for 1.5 hours. O-benzyl-L-serine (8.8 mg, 0.045 mmol) was added and the mixture was stirred overnight. The formation of the ketone of the title compound was confirmed. M/z: 718.04 (M+1) and 716.02 (M−1). Methanol (3 ml) and sodium borohydride (10.3 mg, 0.27 mmol) were added and the mixture was stirred for 1.5 hours. Ammonium acetate (20 mg) was added and the methanol was removed under reduced pressure. The remaining DMF-solution was purified by preparative HPLC on a C8 column, UV 240/260 nm. A gradient from 20 to 45% MeCN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and the MeCN was removed under reduced pressure. The remaining water solution was acidified to pH 1 with HCl (1M) and extracted with DCM. The combined organic phases were concentrated and the residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained as a white solid (2.3 mg, 8.5%).
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[CH:4]=O.I.[NH2:12][NH:13][C:14]([NH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[NH:15].[OH-].[Na+]>C(O)C>[CH2:17]([NH:16][C:14]([NH:13][N:12]=[CH:4][C:3]1[C:2]([CH3:1])=[CH:9][CH:8]=[CH:7][C:6]=1[CH3:10])=[NH:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: N=C(NN)NCc1ccccc1
Reactant: Cc1cccc(C)c1C=O
Agent: I
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cccc(C)c1C=NNC(=N)NCc1ccccc1

Procedure:
A solution of 1.34 g. of 2,6-dimethylbenzaldehyde [G. Lock and K. Schmidt, J. Prakt. Chem., 140, 229 (1934) and 2.92 g. of 1-amino-3-benzylguanidine hydroiodide in 25 ml. of absolute ethanol is heated at reflux for 18 hours. The solution is evaporated under reduced pressure to give a syrup which is made alkaline with aqueous NaOH. The mixture is extracted with chloroform. The chloroform extract is evaporated under reduced pressure to give a yellow syrup. Trituration of this syrup with diethyl ether and n-hexane, followed by filtration, gives the desired product as light pink crystals, m.p. 125°-126° C.
Reaction SMILES: [CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:14]2[C:15]3[N:22]=[C:21]([NH2:23])[S:20][C:16]=3[N:17]=[CH:18][N:19]=2)=[CH:11][C:10]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])[CH:2]=[CH2:3].[C:32](Cl)(=[O:34])[CH3:33]>N1C=CC=CC=1>[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:13][C:12]([C:14]2[C:15]3[N:22]=[C:21]([NH:23][C:32](=[O:34])[CH3:33])[S:20][C:16]=3[N:17]=[CH:18][N:19]=2)=[CH:11][C:10]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])[CH:2]=[CH2:3]
Reactant: CC(=O)Cl
Reactant: C=CCn1ccnc1-c1sc(-c2ncnc3sc(N)nc23)cc1-c1ccc(Cl)cc1Cl
Solvent: c1ccncc1
Product: C=CCn1ccnc1-c1sc(-c2ncnc3sc(NC(C)=O)nc23)cc1-c1ccc(Cl)cc1Cl
Reaction time: 1 h
Yield: 94.3 %

Procedure:
To a mixture of 7-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl][1,3]thiazolo[5,4-d]pyrimidin-2-amine (200 mg, 0.41 mmol) and pyridine (20 mL), was added acetyl chloride (0.30 mL, 4.2 mmol) at rt. After being stirred for 1 hour, acetyl chloride (0.30 mL, 4.2 mmol) was added at rt. After being stirred for 2 hours, the mixture was concentrated in vacuo. To the residue, were added sat. NaHCO3 and EtOAc. After being stirred for 30 min, the organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was washed with ether to yield the title compound (204 mg, 90%) as a pale yellow solid. LCMS: (AA) ES+527, 529. 1H NMR (400 MHz, d6-DMSO) δ: 12.76 (s, 1H), 8.97 (s, 1H), 8.68 (s, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.44 (dd, J=8.3, 2.3 Hz, 1H), 7.26-7.23 (m, 2H), 7.04 (d, J=1.3 Hz, 1H), 5.70-5.62 (m, 1H), 5.09-5.06 (m, 1H), 4.85-4.80 (m, 1H), 4.38 (d, J=5.3 Hz, 2H), 2.25 (s, 3H).
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]#[N:18])[N:8]=1)=O.[CH:23]1[C:32]2[C:27](=[C:28]([NH:33]N)[CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][N:24]=1>>[CH:23]1[C:32]2[C:27](=[C:28]([N:33]3[C:5]([C:7]4[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]5[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=5)[C:17]#[N:18])[N:8]=4)=[CH:4][CH:3]=[N:2]3)[CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][N:24]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(C#N)c2)ccc1=O
Reactant: NNc1cccc2cnccc12
Product: N#Cc1cccc(-n2ccc(=O)c(-c3ccnn3-c3cccc4cnccc34)n2)c1

Procedure:
The product was obtained starting from 3-[3-((E)-3-Dimethylamino-acryloyl)-4-oxo-4H-pyridazin-1-yl]-benzonitrile (A-19) and isoquinolin-5-yl-hydrazine according to the method described for example 91. MS: M=391.2 (M+H)+
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5](I)=[CH:6][C:7]([O:10][CH3:11])=[N:8][CH:9]=1)[CH3:2].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:23]#[N:24])=[C:18](B(O)O)[CH:19]=1>>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:23]#[N:24])=[C:18]([C:5]2[C:4]([O:3][CH2:1][CH3:2])=[CH:9][N:8]=[C:7]([O:10][CH3:11])[CH:6]=2)[CH:19]=1
Reactant: N#Cc1ccc(Cl)cc1B(O)O
Reactant: CCOc1cnc(OC)cc1I
Product: CCOc1cnc(OC)cc1-c1cc(Cl)ccc1C#N

Procedure:
322 mg (purity 93%, 1.07 mmol) of 5-ethoxy-4-iodo-2-methoxypyridine and 234 mg (1.29 mmol, 1.2 eq.) of 5-chloro-2-cyanophenylboronic acid in the presence of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were reacted according to General Method 2A. The crude product was purified by flash chromatography (silica gel 50, cyclohexane/ethyl acetate gradient). Yield: 135 mg (41% of theory)
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([OH:11])[CH:3]=1.S(=O)(=O)(O)O.[CH2:17](O)[CH3:18]>>[CH2:17]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[CH:3][C:4]=1[OH:11])[CH3:18]
Reactant: CCO
Reactant: O=C(O)c1ccc(F)cc1O
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc(F)cc1O
Temperature: 120 °C
Yield: 85 %

Procedure:
To a solution of 4-fluoro-2-hydroxybenzoic acid compound 3 (20.0 g, 128.11 mmol) in ethanol (100 mL) was added conc. sulfuric acid (10 mL). The resulting mixture was heated in a 120° C. oil bath O/N. The solvent was removed under reduced pressure to give crude product, which was purified by column chromatography (silica gel, 10% EtOAc in hexane) to afford the title compound 4 (19.9 g, 85%) as a colorless solid. 1H NMR 400 MHz (CDCl3) δ: 11.15 (s, 1H), 7.83 (d, J=6.6 Hz, 1H), 7.81 (d, J=6.6 Hz, 1H), 6.62 (dd, J=10.1, 2.3 Hz, 1H), 6.61 (dd, J=7.0, 2.0 Hz, 1H), 4.41 (q, J=7.0 Hz, 2H), 1.42 (t, J=7.0 Hz, 3H); MS (ES) m/z: 185 (M+1)+.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[CH3:8][C:9]1([CH3:35])[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:19](O)=[O:20])[CH:16]=2)[NH:11][CH:10]1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)[CH:23]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[CH3:8][C:9]1([CH3:35])[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:19]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:20])[CH:16]=2)[NH:11][CH:10]1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([N:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)[CH:23]=1
Reactant: CN1CCN(c2cccc(C3Nc4ccc(C(=O)O)cc4CC3(C)C)c2)CC1
Reactant: CS(N)(=O)=O
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CCN(c2cccc(C3Nc4ccc(C(=O)NS(C)(=O)=O)cc4CC3(C)C)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.7 %

Procedure:
To a suspension of 60% sodium hydride (187 mg, 4.7 mmol) in N,N-dimethylformamide (1.5 mL) was added methanesulfonamide (451 mg, 4.8 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (180 mg, 0.47 mmol) and 1,1′-carbonyldiimidazole (155 mg, 1.0 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of methanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded N-{3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-methanesulfonamide (68 mg, 32%) as a white solid: LC/MS m/e calcd for C24H32N4O3S (M+H)+: 457.61, observed: 456.9.
Reaction SMILES: [CH:1]1([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:15]Br.C(=O)([O-])[O-].[Na+].[Na+].C(=O)=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[Br:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][CH:1]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:10][CH:11]=1
Reactant: BrBr
Reactant: c1ccc(NC2CCCCCC2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: O=C=O
Solvent: ClCCl
Product: Brc1ccc(NC2CCCCCC2)cc1
Temperature: 0 °C
Yield: 80.7 %

Procedure:
18.9 g N-cycloheptyl aniline (XXIV) (CA registration number [61142-86-7], see Synthesis, 1991, 11:1043-1045 for its preparation), 32.1 g tetrabutylammonium bromide [(C4H9)4N+Br−] and 100 ml methylene chloride (CH2Cl2) were placed into a three-necked flask and cooled down to 0° C. with iced saline. 15.8 g bromine (Br2) was dropped slowly with stirring and was stirred for 4 hours while maintaining at 0° C. The temperature was allowed to raise to room temperature and saturated sodium carbonate solution was dropped slowly till evolution of carbon dioxide ceased. Water layer was separated and extracted with methylene chloride for three times. The organic layers were combined and the solvent evaporated. The residue was recrystalized from 95% ethanol for two times to yield 21.4 g 4bromo-N-cycloheptyl aniline (XXV).
Reaction SMILES: [F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([OH:16])=O)[CH:13]=[C:8]2[C:7]([CH2:17][N:18]([CH3:20])[CH3:19])=[CH:6]1.Cl.[CH3:27][O:28][NH2:29]>>[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([NH:29][O:28][CH3:27])=[O:16])[CH:13]=[C:8]2[C:7]([CH2:17][N:18]([CH3:19])[CH3:20])=[CH:6]1
Reactant: CN(C)Cc1cn(Cc2ccc(F)cc2F)c2cnc(C(=O)O)cc12
Reactant: CON
Agent: Cl
Product: CONC(=O)c1cc2c(CN(C)C)cn(Cc3ccc(F)cc3F)c2cn1

Procedure:
The title compound was prepared by coupling of 1-(2,4-difluoro-benzyl)-3-dimethylaminomethyl-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid and O-methyl hydroxylamine hydrochloride in a manner similar to step (c) of example 1. 1H NMR (CD3OD) 6; 8.90 (s, 1H), 8.50 (s, 1H), 7.89 (s, 1H), 7.41 (m, 1H), 7.00-7.07 (m, 2H), 5.64 (s, 2H), 4.52 (s, 2H), 3.82 (s, 3H), 2.85 (s, 6H). LCMS (APCl, M+H+): 375.0. HRMS calcd for C19H21F2N4O2 (M+H) 375.1633, found 375.1644. HPLC: 100% purity.
Reaction SMILES: C(=O)([O-])[O-].[Sr+2:5].[C:6]([OH:18])(=[O:17])[CH2:7][NH:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10]>O>[C:6]([O-:18])(=[O:17])[CH2:7][NH:8][C:9]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:10].[Sr+2:5].[C:6]([O-:18])(=[O:17])[CH2:7][NH:8][C:9]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:10]
Reactant: O=C(O)CNC(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Sr+2]
Solvent: O
Product: O=C([O-])CNC(=O)c1ccccc1
Reaction time: 5 h

Procedure:
Strontium carbonate (0.5 g, 3.39 mmol) and hippuric acid (1.215 g, 6.77 mmol) in water (30 ml) were stirred at 70.degree. C. for 5 hours. The mixture was filtered and the filtrate was evaporated to dryness and dried in vacuo at ambient temperature. Yield 1.25 g (83%).
Reaction SMILES: [CH:1]([O:4][CH:5]1[CH2:10][CH2:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]([OH:18])=O)[C:12]=2[CH3:19])=[CH:7][CH2:6]1)([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:44][C:45]1[C:46](=[O:58])[N:47]([CH:52]2[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]2)[N:48]([CH3:51])[C:49]=1[CH3:50].C(N(CC)CC)C>CN1C(=O)CCC1>[CH:52]1([N:47]2[C:46](=[O:58])[C:45]([NH:44][C:16]([C:13]3[C:12]([CH3:19])=[C:11]([C:8]4[CH2:9][CH2:10][CH:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH2:6][CH:7]=4)[O:15][N:14]=3)=[O:18])=[C:49]([CH3:50])[N:48]2[CH3:51])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]1
Reactant: Cc1c(C(=O)O)noc1C1=CCC(OC(C)C)CC1
Reactant: Cc1c(N)c(=O)n(C2CCCCC2)n1C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: Cc1c(C(=O)Nc2c(C)n(C)n(C3CCCCC3)c2=O)noc1C1=CCC(OC(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 5-(4-isopropoxycyclohex-1-en-1-yl)-4-methylisoxazole-3-carboxylic acid (174 mg, 0.656 mmol) in dry NMP (3 mL), HATU (274 mg, 0.721 mmol) was added followed by 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (151 mg, 0.721 mmol) and triethylamine (0.201 mL, 1.443 mmol). The mixture was stirred at room temperature overnight. The resulting mixture was partitioned between EtOAc (20 mL) and 1M NaOH (aq) (20 mL) and the organic phase was washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in DMSO and purified using a UV-directed reverse phase chromatography with a gradient of 40-80% MeCN in water (0.1% formic acid) over 9.5 minutes. The product fraction was added to EtOAc (50 mL) and washed with a saturated aqueous NaHCO3 solution (50 mL). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound;
Reaction SMILES: [CH3:1][SiH:2]([CH3:7])[O:3][SiH:4]([CH3:6])[CH3:5].[CH2:8]([O:12][CH2:13][CH:14]=[CH2:15])[CH:9]1[O:11][CH2:10]1>C(OCCOCCOCC)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[O:11]1[CH2:10][CH:9]1[CH2:8][O:12][CH2:13][CH2:14][CH2:15][Si:2]([CH3:7])([CH3:1])[O:3][SiH:4]([CH3:6])[CH3:5]
Reactant: C[SiH](C)O[SiH](C)C
Reactant: C=CCOCC1CO1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CCOCCOCCOCC
Product: C[SiH](C)O[Si](C)(C)CCCOCC1CO1
Temperature: 120 °C
Reaction time: 2 h

Procedure:
An example of the synthesis of compound (5) is described in the following. 1,1,3,3-Tetramethyldisiloxane (17.5 g, 130 mmoles) is heated to the refluxing temperature and 1 mL of a 1 weight percent solution of hexachloroplatinic acid in diethylene glycol diethyl ether is added. Allyl glycidyl ether (11.4 g (100 mmoles) is added dropwise. At the same time, the temperature rises to 95° C. The reaction mixture is stirred for 2 hours at 120° C. and then fractionated with the help of a packed column. At 73° C. and 0.65 hPa, 1-(6,7-epoxy-4-oxaheptyl)-1,1,3,3-tetramethyldisiloxane (monoaddition compound) is obtained as a clear liquid.
Reaction SMILES: [C:1]1([C:7](=O)[S:8][C@@H:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:6]=[CH:5]C=CC=1>N.CO>[C:10]([C:9]1[S:8][C:6]([CH3:5])=[CH:1][C:7]=1[S:8][C@@H:9]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH2:10][NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])#[N:11]
Reactant: CC(C)(C)OC(=O)NC[C@@H](SC(=O)c1ccccc1)c1ccccc1
Agent: N
Solvent: CO
Product: Cc1cc(S[C@H](CNC(=O)OC(C)(C)C)c2ccccc2)c(C#N)s1
Reaction time: 2 h
Yield: 59.1 %

Procedure:
S-[(1S)-2-[[(1,1-Dimethylethoxy)carbonyl]amino]-1-phenylethyl] benzenecarbothioate (210 mg) was dissolved in 7M ammonia in methanol (10 ml) and stirred under nitrogen for 2 h. The solution was evaporated to dryness and the residue dissolved in dry DMF (10 ml). To this solution was added the product from step (a) (120 mg) followed by caesium carbonate (195 mg). The reaction mixture was stirred for 24 h, poured into water and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried (MgSO4). The solvent was evaporated off and the residue purified by chromatography (silica, 20% ethyl acetate/isohexane as eluent) to give the sub-title compound as an oil (65 mg).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]2[C:10]=1[CH2:11]O.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([SH:20])=[CH:16][CH:15]=1.[OH-].[Na+]>Cl>[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH2:11][C:10]2[N:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]3=[N:3][C:2]=2[CH3:1])=[CH:16][CH:15]=1
Reactant: Cc1nc2ccccn2c1CO
Reactant: Nc1ccc(S)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1nc2ccccn2c1CSc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 22.2 %

Procedure:
Under nitrogen atmosphere, to a suspension of aluminum lithium hydride (1.6 g) in THF (100 ml) was added dropwise a solution of ethyl 2-methylimidazo[1,2-a]pyridine-3-carboxylate (8.56 g) in THF (100 ml) at 0° C. under nitrogen atmosphere. The mixture was stirred for 1 hour at 0° C., water (1.6 ml), 15% aqueous solution of sodium hydroxide (1.6 ml) and water (4.8 ml) were sequentially and slowly added dropwise to the solution, and the mixture was stirred for 2 hours at room temperature. To the reaction solution was added magnesium sulfate, and the precipitates were removed by filtration. The mixture was concentrated under reduced pressure, to give 2-methylimidazo[1,2-a]pyridine-3-methanol (6.45 g) as pale yellow amorphous. A mixture of 2-methylimidazo[1,2-a]pyridine-3-methanol (1 g) and 4-aminothiophenol (0.65 g) in concentrated hydrochloric acid (10 ml) was stirred for 18 hours at room temperature. 8N aqueous solution of sodium hydroxide was added to adjust pH to 10 at 0° C. and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified by column chromatography (ethanol:ethyl acetate 1:4), to give 3-(4-aminophenylthiomethyl)-2-methylimidazo[1,2-a]pyridine (311 mg) as colorless crystals.
Reaction SMILES: [CH2:1]([Li])CCC.[C:6]1([C:12]2[CH2:13][C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CI>C1COCC1>[CH3:1][CH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:20]=[C:12]1[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: [Li]CCCC
Reactant: C1=C(c2ccccc2)Cc2ccccc21
Solvent: C1CCOC1
Solvent: CI
Product: CC1C(c2ccccc2)=Cc2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
Butyllithium (2.5 M in hexanes, 3.0 mL, 7.6 mmol was added dropwise to a suspension of 2-phenylindene (1.382 g, 7.2 mmol) in THF (50 mL) at -78 C. Upon addition of n-butyllithium the reaction mixture turned a dark orange color and 2-phenylindene dissolved. When the addition of the reagents was complete the solution was allowed to warm to room temperature and stirred for 30 minutes. CH3I (1.3 mL, 22 mmol) was added to this solution dropwise and the light brown reaction mixture was heated to 40° C. and stirred for 24 hours. After that the solvents were removed in vacuo and the light brown solid was recrystallized from EtOH (25 mL) at room temperature affording white needles (1.075 g, 75% yield). 1H NMR (CDCl3, 20° C., 300 MHz): δ 7.52-7.19 (overlapping signals from aromatic protons, 9H), 3.74 (s, 2H), 2.31 (s, 3H). 13C {1H} NMR (CDCl3, 20° C., 75 MHz): δ 147.49 (C), 142.42 (C), 140.31 (C), 137.56 (C), 134.70 (C), 128.37 (CH), 128.24 (CH), 126.63 (CH). 126.40 (CH), 124.74 (CH), 123.32 (CH), 119.11 (CH), 40.96 (CH2), 11.94 (CH3).