Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:18]2[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.[Li]C(C)(C)C.[C:36]1(=[O:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C1COCC1>[CH3:24][C:21]1([CH3:25])[CH2:22][CH2:23][C:18]([C:4]2[CH:3]=[C:2]([C:36]3([OH:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[CH:7]=[CH:6][C:5]=2[NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[CH:19][CH2:20]1
Reactant: CC1(C)CC=C(c2cc(Br)ccc2NC(=O)c2nc(C#N)c[nH]2)CC1
Reactant: O=C1CCCCC1
Agent: CC(C)[Mg]Cl
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: CC1(C)CC=C(c2cc(C3(O)CCCCC3)ccc2NC(=O)c2nc(C#N)c[nH]2)CC1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 45.1 %

Procedure:
A solution of 4-cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (159 mg, 0.397 mmol, as prepared in Example 1, step (g)) in THF (15 mL) was placed under Ar, cooled to −78° C., and treated with i-PrMgCl (199 μL, 0.397 mmol). The mixture was warmed to RT, allowed to stir at that temperature for 10 min, cooled to −78° C., treated with t-BuLi (701 μL, 1.19 mmol), stirred at that temperature for 10 min, and then treated with cyclohexanone (411 μL, 3.97 mmol). The mixture was warmed to RT, stirred 1.5 h, quenched with satd aq NH4Cl (20 mL), and extracted with EtOAc (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography of the residue with 25-50% EtOAc-hexane on a 20-g Isolute SPE column afforded 75.0 mg (45%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 12.11-11.91 (br s, 1H), 9.63 (s, 1H), 8.31 (d, 1H, J=8.4 Hz), 7.71 (s, 1H), 7.43 (dd, 1H, J=8.4, 2.0 Hz), 7.36 (d, 1H, J=2.0 Hz), 5.82-5.75 (m, 1H), 3.77-3.67 (m, 1H), 2.62-2.53 (m, 1H), 2.42-2.24 (m, 4H), 2.17-2.07 (m, 2H), 1.96-1.55 (m, 10H), 1.10 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H30NO2, 419.2 (M+H). found 419.1.
Reaction SMILES: COC[N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[CH2:9][C:10]1[NH:14][N:13]=[N:12][N:11]=1.O.Cl.[O-]CC.[Na+]>C(O)(=O)C>[NH:14]1[C:10]([CH2:9][C:5]2[NH:6][CH:7]=[CH:8][N:4]=2)=[N:11][N:12]=[N:13]1
Reactant: COCn1ccnc1Cc1nnn[nH]1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: c1c[nH]c(Cc2nnn[nH]2)n1

Procedure:
8.14 g (41.9 mmol) of 1-methoxymethyl-2-(5-tetrazolylmethyl)-imidazole are refluxed in a mixture of 85 ml glacial acetic acid, 8.5 ml of water and 8.5 ml of conc. hydrochloric acid for 24 hours. The mixture is then concentrated in vacuo and the residue rapidly dried to a far extent in a high vacuum over potassium hydroxide and conc. sulphuric acid. The acid addition salt obtained is decomposed with the stoichiometric quantity of sodium ethoxide in an ethanolic solution. After removal of the sodium chloride precipitated, the solvent is distilled off and the residue recrystallised from methanol at boiling heat with the addition of a little ether.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH:5]([S:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[CH3:6])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[CH2:1]([O:3][C:4](=[O:16])[C:5]([S:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=1)([CH3:6])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:2]
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)C(C)Sc1ccc(OC)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(Cc1ccccc1)Sc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a stirred solution of 2-(4-methoxy-phenylsulfanyl)-propionic acid ethyl ester (2.44 g, 10 mmol), in THF (100 ml) at −4° C., lithium bis(trimethylsilyl)amide (1 M solution, 15 ml, 15 mmol) was added slowly. The orange colored reaction mixture was stirred at room temperature for 15 minutes and then it was cooled to 0° C. at which time it was stirred for an additional hour. The temperature of the mixture was again brought to −40° C. and benzylbromide (1.72 gm, 10 mmol) was added dropwise in THF. The reaction was warmed to room temperature and stirred overnight before it was quenched with ice water, extracted with chloroform and washed with water. The organic layer was dried over MgSO4, filtered and concentrated and chromatographed on a silica-gel column with 10% ethyl acetate:hexane to afford 2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionic acid ethyl ester as a colorless oil. Yield: 860 mg, (26%); MS: 331 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]1[CH2:9][C@H:8]2[C@H:4]([CH2:5][NH:6][C@@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])[CH2:3]1.[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:27]([C:29](O)=[O:30])[N:28]=1>>[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[C:27]([C:29]([N:6]2[CH2:5][C@H:4]3[C@H:8]([CH2:9][CH:2]([CH3:1])[CH2:3]3)[C@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])=[O:30])[N:28]=1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2CC(C)C[C@@H]21
Reactant: Nc1nc(C(=O)O)c(-c2ccccc2)s1
Product: Cc1nc2sccn2c1C(=O)NC[C@@H]1[C@H]2CC(C)C[C@H]2CN1C(=O)c1nc(N)sc1-c1ccccc1

Procedure:
prepared by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid-[(1S,2S,5R)-7-methyl-3-aza-bicyclo[3.3.0]oct-2-ylmethyl]-amide with 2-amino-5-phenyl-thiazole-4-carboxylic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([OH:23])=O)[C:9]=2[CH3:24])=[CH:4][CH:3]=1.Cl.[F:26][C:27]1([F:34])[CH2:32][CH2:31][N:30]([NH2:33])[CH2:29][CH2:28]1>>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([NH:33][N:30]3[CH2:31][CH2:32][C:27]([F:34])([F:26])[CH2:28][CH2:29]3)=[O:23])[C:9]=2[CH3:24])=[CH:6][CH:7]=1
Reactant: NN1CCC(F)(F)CC1
Reactant: Cc1c(C(=O)O)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Agent: Cl
Product: Cc1c(C(=O)NN2CCC(F)(F)CC2)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1

Procedure:
Form the acid chloride from 3.6 mmol of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid and react it with 2.6 mmol of the product of Example 28 using the general procedure set forth in Example 39, to yield the title compound as a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([NH2:17])[CH3:16].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:17][CH2:15][CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCN
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCNC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 99 %

Procedure:
To a stirred solution of 1-tert-butoxycarbonyl-4-piperidone (3.99 g, 20 mmol) in THF (40 mL) were added ethylamine (20 mL of a 2.0 M solution in THF, 40 mmol), acetic acid (1.15 mL, 20 mmol) and sodium triacetoxyborohydride (8.48 g, 40 mmol) at 0° C., and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with 1 N aqueous sodium hydroxide (120 mL) at 0° C. and stirred at room temperature for 30 minutes. The organic solvent was evaporated under reduced pressure, and the remaining aqueous layer was extracted with ethyl acetate (40 mL, 2×20 mL). The combined organic layers were washed with brine (2×20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to afford the title compound (4.54 g, 19.9 mmol, 99%) as a pale yellow oil.
Reaction SMILES: [S:1]([O-])([O-])(=O)=[S:2].[Na+].[Na+].O.Br[CH2:10][CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH3:21])=[CH:13]1>C(O)C>[CH3:21][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:12]([CH2:11][CH2:10][S:1][S:2][CH2:10][CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([CH3:21])=[CH:13]2)[CH:13]=1
Reactant: O=S([O-])([O-])=S
Reactant: Cc1cn(CCBr)c2ccccc12
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: Cc1cn(CCSSCCn2cc(C)c3ccccc32)c2ccccc12

Procedure:
A solution of 10.4 g. of sodium thiosulfate in 60 ml. of water and 100 ml. of ethanol is poured onto 8.6 g. of 1-(2-bromoethyl)-3-methylindole. The reaction mixture is stirred and heated at reflux for 3.5 hr., allowed to cool, and evaporated to dryness. The solid residue is dissolved in boiling isopropanol, dried with a hydrated alkali-aluminum silicate ("Molecular Sieves"), and filtered. Chilling of the filtrate causes 6.4 g. of the sodium indolyethyl thiosulfate derivative to precipitate. This material is collected by filtration and washed with ether. The isolated intermediate is heated at reflux with a solution of sodium hydroxide (9 g. of NaOH, 60 ml. of water, 140 ml. of ethanol) for 3 hr. Ethanol is removed under reduced pressure, the aqueous residue diluted with water and extracted with three portions of ether. Combined ether extracts are washed with water, saturated brine solution, and dried over magnesium sulfate. The filtrate is evaporated, to yield bis-[2-(3-methylindole-1-yl)ethyl]disulfide.
Reaction SMILES: [CH3:1][S:2][CH2:3][N:4]1[C:9](=[O:10])[N:8]2[CH:11]=[N:12][C:13]([C:14]3[O:15][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:17][N:18]=3)=[C:7]2[N:6]=[N:5]1.S([O-])(O[O-])(=O)=[O:26].[K+].[K+].OOS([O-])=O.[K+]>CN(C=O)C.O>[CH3:1][S:2]([CH2:3][N:4]1[C:9](=[O:10])[N:8]2[CH:11]=[N:12][C:13]([C:14]3[O:15][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:17][N:18]=3)=[C:7]2[N:6]=[N:5]1)=[O:26]
Reactant: CSCn1nnc2c(-c3nnc(-c4ccccc4)o3)ncn2c1=O
Reactant: O=S(=O)([O-])O[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CS(=O)Cn1nnc2c(-c3nnc(-c4ccccc4)o3)ncn2c1=O
Temperature: 0 °C
Yield: 90 %

Procedure:
To a 0° C. solution of 3-(methylthiomethyl)-8-(5-phenyl-1,3,4-oxadiazol-2-yl)imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one (0.337 mmol, 115 mg, 1 eq.) in DMF (6 mL) was added potassium peroxymonosulfate (Oxone™) (0.37 mmol, 114 mg, 1.1 eq.) dissolved in water (1.2 mL) drop wise. The formed suspension was stirred at 0° C. and stepwise additions of Oxone™ in water were made until reaction completion. The reaction mixture was filtered and the obtained solid was washed with water, acetonitrile and ether, and dried under vacuum to give the title compound. Yield 90%. δH (DMSO-d6) 9.15 (1H, s), 8.13 (2H, dd, J: 7.96, 2.25), 7.70 (3H, m), 5.67 (1H, d, J: 13.06), 5.52 (1H, d, J: 13.06), 2.81 (3H, s).
Reaction SMILES: [F:1][C:2]1([CH2:18]OS(C)(=O)=O)[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1.[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C=O)C>[N:24]([CH2:18][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1)=[N+:25]=[N-:26]
Reactant: [N-]=[N+]=[N-]
Reactant: CS(=O)(=O)OCC1(F)CCN(C(=O)OCc2ccccc2)CC1
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCC1(F)CCN(C(=O)OCc2ccccc2)CC1
Temperature: 110 °C
Reaction time: 60 h

Procedure:
To a solution of benzyl 4-fluoro-4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.3 g, 3.7 mmol) in DMF (10 mL) at RT was added NaN3 (2.4 g, 37.0 mmol). The reaction mixture was heated to 110° C. and stirred for 60 h, cooled and partitioned between EtOAc and H2O. The organic layer was dried over Na2SO4, filtered, concentrated and purified on silica gel (10:1 to 1:2 hexanes:EtOAc) to give benzyl 4-(azidomethyl)-4-fluoropiperidine-1-carboxylate.
Reaction SMILES: C[O:2][P:3]([CH2:13][CH:14]([C:19](=[O:30])[NH:20][C@H:21]([C:26](=[O:29])[NH:27][CH3:28])[CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:15][CH:16]([CH3:18])[CH3:17])([CH2:5][N:6]1[C:10](=[O:11])[CH2:9][CH2:8][C:7]1=[O:12])=[O:4].Br[Si](C)(C)C>ClCCl>[CH3:17][CH:16]([CH3:18])[CH2:15][CH:14]([C:19](=[O:30])[NH:20][C@H:21]([C:26](=[O:29])[NH:27][CH3:28])[CH2:22][CH:23]([CH3:24])[CH3:25])[CH2:13][P:3]([CH2:5][N:6]1[C:10](=[O:11])[CH2:9][CH2:8][C:7]1=[O:12])(=[O:2])[OH:4]
Reactant: CNC(=O)[C@H](CC(C)C)NC(=O)C(CC(C)C)CP(=O)(CN1C(=O)CCC1=O)OC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: CNC(=O)[C@H](CC(C)C)NC(=O)C(CC(C)C)CP(=O)(O)CN1C(=O)CCC1=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 96.4 %

Procedure:
60 mg of [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl](succinimidomethyl)phosphinic acid methyl ester were dissolved in 5 ml of dichloromethane, 0.5 ml of bromotrimethylsilane was added and the mixture was stirred at room temperature for 1.5 hours. The solvent was removed by evaporation and the residue was then re-evaporated twice with 20 ml of acetone and 0.25 ml of water. After standing at room temperature for 15 minutes, the solvent was removed by evaporation and the residue was dissolved in 20 ml of acetone/dichloromethane (1:2). The solution was then evaporated to give 56 mg of [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl](succinimidomethyl)phosphinic acid in the form of a white foam.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:27][C:28]([CH3:40])([O:31][C:32]1[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][CH:33]=1)[C:29]#[CH:30]>C(NCC)C.[Pd](Cl)Cl.[Cu]I>[CH3:27][C:28]([CH3:40])([O:31][C:32]1[CH:33]=[CH:34][C:35]([C:36]#[N:37])=[CH:38][CH:39]=1)[C:29]#[C:30][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Ic1cccnc1
Reactant: C#CC(C)(C)Oc1ccc(C#N)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCNCC
Product: CC(C)(C#Cc1cccnc1)Oc1ccc(C#N)cc1
Reaction time: 72 h

Procedure:
10.25 g of 3-iodopyridine were added at to a solution of 44 mg of palladium(II) chloride, room temperature 131 mg of triphenylphosphine and 95 mg of copper(I) iodide in 200 mg of diethylamine 9.25 g of 4-(1,1-dimethyl-2-propynyloxy)benzonitrile were then added and the mixture was stirred for 3 days. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was dried over sodium sulphate and evaporated. The residue was chromatographed on silica gel using ethyl acetate/petroleum ether (11:9) for the elution to give 11.8 g of 4-[1,1-dimethyl-3-(3-pyridyl)-2-propynyloxy]benzonitrile in the form of an oil.
Reaction SMILES: Cl.[N:2]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])[CH:6]=[CH:5][N:4]=[CH:3]1.C(N(CC)CC)C.O[CH2:25][C:26]1[CH:30]=[C:29]2[C:31]([C:89]3[CH:94]=[CH:93][CH:92]=[CH:91][C:90]=3[NH:95][C:96](=[O:101])[C:97]([CH3:100])([CH3:99])[CH3:98])=[C:32]3[N:36]=[C:35]([C:37]([C:76]4[CH:81]=[CH:80][CH:79]=[CH:78][C:77]=4[NH:82][C:83](=[O:88])[C:84]([CH3:87])([CH3:86])[CH3:85])=[C:38]4[NH:42][C:41](=[C:43]([C:63]5[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=5[NH:69][C:70](=[O:75])[C:71]([CH3:74])([CH3:73])[CH3:72])[C:44]5[CH:45]=[CH:46][C:47](=[C:49]([C:50]6[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=6[NH:56][C:57](=[O:62])[C:58]([CH3:61])([CH3:60])[CH3:59])[C:27]=1[NH:28]2)[N:48]=5)[CH:40]=[CH:39]4)[CH:34]=[CH:33]3.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C>[N:2]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:25][C:26]2[CH:30]=[C:29]3[C:31]([C:89]4[CH:94]=[CH:93][CH:92]=[CH:91][C:90]=4[NH:95][C:96](=[O:101])[C:97]([CH3:100])([CH3:99])[CH3:98])=[C:32]4[N:36]=[C:35]([C:37]([C:76]5[CH:81]=[CH:80][CH:79]=[CH:78][C:77]=5[NH:82][C:83](=[O:88])[C:84]([CH3:87])([CH3:85])[CH3:86])=[C:38]5[NH:42][C:41](=[C:43]([C:63]6[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=6[NH:69][C:70](=[O:75])[C:71]([CH3:72])([CH3:73])[CH3:74])[C:44]6[CH:45]=[CH:46][C:47](=[C:49]([C:50]7[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=7[NH:56][C:57](=[O:62])[C:58]([CH3:59])([CH3:60])[CH3:61])[C:27]=2[NH:28]3)[N:48]=6)[CH:40]=[CH:39]5)[CH:34]=[CH:33]4)=[O:15])[CH:6]=[CH:5][N:4]=[CH:3]1
Reactant: O=C(O)CCCCCCCn1ccnc1
Reactant: CC(C)(C)C(=O)Nc1ccccc1-c1c2nc(c(-c3ccccc3NC(=O)C(C)(C)C)c3cc(CO)c([nH]3)c(-c3ccccc3NC(=O)C(C)(C)C)c3nc(c(-c4ccccc4NC(=O)C(C)(C)C)c4ccc1[nH]4)C=C3)C=C2
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)Nc1ccccc1-c1c2nc(c(-c3ccccc3NC(=O)C(C)(C)C)c3cc(COC(=O)CCCCCCCn4ccnc4)c([nH]3)c(-c3ccccc3NC(=O)C(C)(C)C)c3nc(c(-c4ccccc4NC(=O)C(C)(C)C)c4ccc1[nH]4)C=C3)C=C2
Reaction time: 0.17 h
Yield: 89 %

Procedure:
8-Imidazol-1-yloctanoic acid hydrochloride (90.1 mg, 0.37 mmol) and triethylamine (TEA, 0.1 ml, 0.74 mmol) were dissolved in dry DMF (4 ml) and stirred for 10 min. After removing TEA under reduced pressure, 2-hydroxymethyl-5,10,15,20-tetrakis(o-pivalamidophenyl)porphyrin, 76 mg, 73 μmol), 4-(N,N-dimethylamino)pyridine (DMAP, 4.5 mg, 37 μmol) and dicyclohexylcarbodiimide (DCC, 75.4 mg, 0.37 mmol) were added to the solution and stirred for 84 hours at room temperature in darkness. The mixture was chromatographed on a silica gel flash column using CHCl3 --MeOH (30/1 v/v) as the eluent. The residue was dried at room temperature in vacuo to give a purple product, 2-(8-imidazol-1-yloctanoyloxymethyl)-5,10,15,20-tetrakis(o-pivalamidophenyl)porphyrin (80 mg, 89%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.[CH:21]([O-])([O-])OCC.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:21]=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1
Reactant: CCOC([O-])[O-]
Reactant: NNC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NC1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Clc1ccc2c(c1)C(c1ccccc1)=NCc1nncn1-2

Procedure:
To a solution of 2.0 parts of 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine and 7.4 parts of ethyl orthoformate in 80 parts by volume of chloroform is added 2 parts of concentrated sulfuric acid with stirring. The mixture is stirred at room temperature for further 30 minutes, and neutralized with a saturated aqueous sodium bicarbonate solution. Chloroform layer is washed with water and dried over sodium sulfate, followed by distillation of the solvent. Recrystallization of the residue from acetone-n-hexane yields 8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepine as colorless flakes melting at 226°-227° C.
Reaction SMILES: N[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.S(=O)(=O)(O)[OH:11]>CN(C)C=O>[OH:11][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: Nc1ccc(C=O)cc1
Reactant: O=S(=O)(O)O
Solvent: CN(C)C=O
Product: O=Cc1ccc(O)cc1
Yield: 23 %

Procedure:
The procedure of Example 1 was repeated except that the N,N-dimethylformamide was not added and p-aminobenzaldehyde was reacted with sulphuric acid in 40% aqueous solution at 40° C. for one hour, to obtain p-hydroxybenzaldehyde in a yield of 23%, based on the weight of p-nitrotoluene used.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[C:14](=[O:15])[C:13]([CH3:17])([CH3:16])[NH:12]1)[CH2:8]2.[CH3:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br>>[CH3:16][C:13]1([CH3:17])[N:12]([CH2:18][C:19]2[CH:26]=[CH:25][CH:24]=[C:21]([CH3:22])[CH:20]=2)[N:11]([CH:2]2[CH:3]3[CH2:4][CH:5]4[CH2:6][CH:7]([CH2:8][CH:1]2[CH2:10]4)[CH2:9]3)[C:14]1=[O:15]
Reactant: CC1(C)NN(C2C3CC4CC(C3)CC2C4)C1=O
Reactant: Cc1cccc(CBr)c1
Product: Cc1cccc(CN2N(C3C4CC5CC(C4)CC3C5)C(=O)C2(C)C)c1

Procedure:
2-(Adamantan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one and 3-methylbenzyl bromide were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a white crystalline powder.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([NH2:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](=O)[CH2:33][C:34](OCC)=[O:35])=[CH:28][C:27]=1[O:40][CH3:41]>CCCCO>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[NH:13][C:11]3[N:10]([N:9]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[N:12]=3)[C:34](=[O:35])[CH:33]=2)=[CH:28][C:27]=1[O:40][CH3:41]
Reactant: CCOC(=O)CC(=O)c1ccc(Cl)c(OC)c1
Reactant: Nc1nc(-c2ccc(F)cc2)n[nH]1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCCO
Product: COc1cc(-c2cc(=O)n3nc(-c4ccc(F)cc4)nc3[nH]2)ccc1Cl
Temperature: 130 °C
Reaction time: 36 h
Yield: 16.1 %

Procedure:
To a solution of 3-(4-fluorophenyl)-1H-1,2,4-triazol-5-amine (100 mg, 0.56 mmol) in n-BuOH (3 ml) was added TsOH (5 mg, 0.03 mmol), and ethyl 3-(4-chloro-3-methoxyphenyl)-3-oxopropanoate (200 mg, 0.78 mmol), and the resulting mixture was stirred for 36 hours at 130° C. in an oil bath. The solids were collected by filtration to give a crude product, which was purified by Flash-Prep-HPLC to afford 5-(4-chloro-3-methoxyphenyl)-2-(4-fluorophenyl)-[1,2,4]triazolo[1,5-α]pyrimidin-7(4H)-one as a white solid (33.5 mg, 16%).
Reaction SMILES: [Li]CCCC.[Si:6]([C:13]1[O:14][CH:15]=[CH:16][C:17]=1[CH2:18][OH:19])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[Cl-].[Li+].CN(C)[CH:24]=[O:25]>CCCCCC.C(COC)OC>[Si:6]([C:13]1[O:14][CH:15]=[C:16]([CH:24]=[O:25])[C:17]=1[CH2:18][OH:19])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: CN(C)C=O
Reactant: CC(C)(C)[Si](C)(C)c1occc1CO
Agent: [Cl-]
Agent: [Li+]
Agent: [Li]CCCC
Solvent: COCCOC
Solvent: CCCCCC
Product: CC(C)(C)[Si](C)(C)c1occ(C=O)c1CO
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
n-BuLi (a 1.6M solution in hexane; 2.7 ml, 4.28 mmol) was added dropwise to a solution of 3-(2-tert-butyldimethylsilyl-furylmethanol (430 mg, 2.0 mmol) in dimethoxyethane (5 ml) at -78 degrees C. under argon. After stirring at 0 degrees C. for 15 minutes, lithium chloride (860 mg, 20.4 mmol), followed by N,N-dimethylformamide (0.35 ml, 4.48 mmol) was added. Stirring continued at 0 degrees C. for 16 hours and the mixture was quenched with ammonium chloride. Extraction with ethyl acetate and evaporation of the dried (magnesium sulfate) extracts gave a solid, which was recrystallized from hexane to give the titled aldehyde.
Reaction SMILES: [C:1]([C:9]1[CH:10]=[C:11]([CH:15]([CH3:19])[C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Br[CH:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:30](=[O:31])[O:29]1>C(Cl)(Cl)Cl>[C:1]([C:9]1[CH:10]=[C:11]([CH:15]([CH3:19])[C:16]([O:18][CH:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:30](=[O:31])[O:29]2)=[O:17])[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C(=O)O)c1cccc(C(=O)c2ccccc2)c1
Reactant: O=C1OC(Br)c2ccccc21
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(C(=O)OC1OC(=O)c2ccccc21)c1cccc(C(=O)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 25 h
Yield: 79 %

Procedure:
To a solution of 7.6 g of 2-(3-benzoylphenyl)propionic acid in 30 ml of chloroform and 3.4 g of triethylamine is added a solution of 6.2 g of 3-bromophthalide in 20 ml of chloroform. The solution thus obtained is stirred 25 hours at room temperature, the organic phase is washed with an aqueous solution of sodium bicarbonate, then with water and finally dried on anhydrous sodium sulfate and evaporated to dryness to give the phthalidyl 2-(3-benzoylphenyl)propionate; yield 79%.