Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[C:8]([CH3:9])=[C:7]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[S:6][C:5]=1[C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)(=[O:3])[CH3:2].CO.[BH4-].[Na+]>O>[N:19]1[CH:20]=[CH:21][C:16]([C:5]2[S:6][C:7]([C:10]3[CH:11]=[CH:12][N:13]=[CH:14][CH:15]=3)=[C:8]([CH3:9])[C:4]=2[CH:1]([OH:3])[CH3:2])=[CH:17][CH:18]=1
Reactant: CC(=O)c1c(-c2ccncc2)sc(-c2ccncc2)c1C
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cc1c(-c2ccncc2)sc(-c2ccncc2)c1C(C)O
Reaction time: 2 h

Procedure:
To a stirred solution of 3-acetyl-4-methyl-2,5-di(4-pyridyl)thiophene (200 mg, 0.68 mmol) in MeOH (5 mmol) was added sodium borohydride (30 mg, 0.79 mmol) at 0° C., and the mixture was stirred for 2 hours. Water (5 mL) was added to the mixture. The whole was extracted with ethyl acetate (50 mL), the organic layer washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was purified by flash chromatography eluting with CH2Cl2 -MeOH (20:1) to provide the title product as a solid. Recrystallized from ethyl acetate gave the title product (130 mg, 75% yield).
Reaction SMILES: [N+:1]([C:4]1[C:5]([NH2:14])=[CH:6][C:7]2[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=2[CH:13]=1)([O-])=[O:2].[N:15]#[C:16][NH2:17].[CH]Cl.[OH-].[Na+]>O>[N+:1]1([O-:2])[C:4]2[CH:13]=[C:12]3[C:7](=[CH:6][C:5]=2[N:14]=[C:16]([NH2:17])[N:15]=1)[CH2:8][CH2:9][CH2:10][CH2:11]3
Reactant: N#CN
Reactant: Nc1cc2c(cc1[N+](=O)[O-])CCCC2
Agent: [CH]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Nc1nc2cc3c(cc2[n+]([O-])n1)CCCC3
Temperature: 50 °C
Reaction time: 3 h
Yield: 34.7 %

Procedure:
A mixture of nitroaniline 174 (0.77 g, 4.0 mmol) and cyanamide (0.68 g, 16.0 mmol) were mixed together at 100° C., cooled to 50° C., cHCl (5 mL) added carefully and the mixture heated at 100° C. for 4 h. The mixture was cooled to 50° C., 7.5 M NaOH solution added until the mixture was strongly basic and the mixture stirred at 100° C. for 3 h. The mixture was cooled, diluted with water (100 mL) and filtered. The precipitate was washed with water (3×20 mL), washed with ether (10 mL) and dried. The residue was purified by chromatography, eluting with 5% MeOH/DCM, to give amine 175 (0.30 g, 35%) as a yellow powder: mp (MeOH/DCM) 270-274° C.; 1H NMR [(CD3)2SO] δ 7.83 (s, 1H, H-10), 7.23 (s, 1H, H-5), 7.11 (br s, 2H, NH2), 2.82-2.89 (m, 4H, H-6, H-9), 1.72-1.77 (m, 4H, H-7, H-8); 13C NMR [(CD3)2SO] δ 159.8, 146.9, 146.8, 136.2, 128.0, 124.0, 118.1, 29.1, 28.5, 22.0, 21.8. Anal. calcd for C11H12N4O.¼H2O: C, 59.9; H, 5.7; N, 25.4. Found: C, 60.4; H, 5.5; N, 25.5%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]([CH3:15])[NH:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1.[C:16]1([N:22]=[C:23]=[S:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C)C=O>[C:16]1([NH:22][C:23](=[S:24])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:9]([CH3:15])[NH:10][C:11](=[O:14])[NH:12][N:13]=3)=[CH:6][CH:7]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC1NC(=O)NN=C1c1ccc(N)cc1
Reactant: S=C=Nc1ccccc1
Solvent: CN(C)C=O
Product: CC1NC(=O)NN=C1c1ccc(NC(=S)Nc2ccccc2)cc1

Procedure:
A solution of 6-(4-aminophenyl)-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (3 g) and phenyl isothiocyanate (1.8 ml) in dimethylformamide (30 ml) was stirred at room temperature for 6 hours and then concentrated under reduced pressure. To the residue was added water and the thus-produced crystals were recovered by filtration, washed with water and dried to give 6-[4-(3-phenyl-thioureido)phenyl]-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (5.32 g).
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.[NH2:31][C:32]1([C:35]([NH:37][C@@H:38]([C:40]2[CH:45]=[CH:44][C:43]([C:46]3[C:47]([C:53]([OH:55])=[O:54])=[C:48]([F:52])[CH:49]=[CH:50][CH:51]=3)=[CH:42][CH:41]=2)[CH3:39])=[O:36])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:52][C:48]1[CH:49]=[CH:50][CH:51]=[C:46]([C:43]2[CH:42]=[CH:41][C:40]([C@H:38]([NH:37][C:35]([C:32]3([NH:31][C:4](=[O:5])[CH2:3][C:2]([F:8])([F:7])[F:1])[CH2:34][CH2:33]3)=[O:36])[CH3:39])=[CH:45][CH:44]=2)[C:47]=1[C:53]([OH:55])=[O:54]
Reactant: O=C(O)CC(F)(F)F
Reactant: C[C@@H](NC(=O)C1(N)CC1)c1ccc(-c2cccc(F)c2C(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H](NC(=O)C1(NC(=O)CC(F)(F)F)CC1)c1ccc(-c2cccc(F)c2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a solution of trifluoropropionic acid (128 mg, 1.0 mmol) in DCM (1 mL), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (229 mg, 1.2 mmol) and 1-hydroxy-7-azabenzotriazole (136 mg, 1.0 mmol) were added. The resulting solution was stirred at room temperature for 20 minutes, then 4′-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1′-biphenyl-2-carboxylic acid (171 mg, 0.5 mmol) in 1 mL DCM was added, followed by N,N-diisopropylethylamine until pH=10 was achieved. The reaction mixture was stirred at ambient temperature under N2 for 2 hours, concentrated under vacuum and then partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 40% MeOH in CHCl3. Collection and concentration of appropriate fractions provided 3-fluoro-4′-{(1R)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)amino]ethyl}-1,1′-biphenyl-2-carboxylic acid as a white powder.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[C:4]([CH3:9])=[CH:5][C:6]=1[CH:7]=O.[CH3:20][CH:21]([CH3:37])[C:22]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=1)=[O:23]>>[CH3:1][C:2]1[N:3]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:18])([F:17])[F:19])[CH:11]=2)[C:4]([CH3:9])=[CH:5][C:6]=1[CH2:7][N:34]1[CH2:35][CH2:36][CH:31]([C:27]2[CH:26]=[C:25]([NH:24][C:22](=[O:23])[CH:21]([CH3:37])[CH3:20])[CH:30]=[CH:29][CH:28]=2)[CH2:32][CH2:33]1
Reactant: Cc1cc(C=O)c(C)n1-c1cccc(C(F)(F)F)c1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Product: Cc1cc(CN2CCC(c3cccc(NC(=O)C(C)C)c3)CC2)c(C)n1-c1cccc(C(F)(F)F)c1

Procedure:
Prepared by Procedure F and Scheme R using 2,5-dimethyl-1-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 498.2 (M+H)+.
Reaction SMILES: Cl.[CH2:2]([N:5]1[C:13]2[N:12]=[C:11]([CH2:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=4)[CH:18]=[N:17][CH:16]=3)[NH:10][C:9]=2[C:8](=[O:29])[N:7]([CH3:30])[C:6]1=[O:31])[CH:3]=[CH2:4].C(N(C(C)C)CC)(C)C.[OH-:41].[Na+].OO>C1COCC1>[CH3:26][O:25][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][C:21]=1[O:27][CH3:28])[CH:18]=[N:17][CH:16]=[C:15]2[CH2:14][C:11]1[NH:10][C:9]2[C:8](=[O:29])[N:7]([CH3:30])[C:6](=[O:31])[N:5]([CH2:2][CH2:3][CH2:4][OH:41])[C:13]=2[N:12]=1
Reactant: C=CCn1c(=O)n(C)c(=O)c2[nH]c(Cc3cncc4cc(OC)c(OC)cc34)nc21
Reactant: [OH-]
Agent: Cl
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc2cncc(Cc3nc4c([nH]3)c(=O)n(C)c(=O)n4CCCO)c2cc1OC
Temperature: 50 °C

Procedure:
A suspension of the product of Example 13, 3-allyl-8-(6,7-dimethoxy-isoquinolin-4-ylmethyl)-1-methyl-3,7-dihydro-purine-2,6dione -hydrochloride salt (0.760 g, 1.87 mmol), 9-borabicyclo[2.2.0]nonane (0.5M THF solution, 18.7 ml, 9.35 mmol) and diisopropylethylamine (0.33 ml, 1.89 mmol) in THF (9 ml) is heated to reflux for 2.5 hours. Sodium hydroxide (4M aqueous solution, 6 ml) and hydrogen peroxide (27.5%, 3 ml) are added sequentially and the reaction heated at 50° C. for 1.5 hours. After evaporation, the crude product is purified by flash chromatography (19:1 CH2Cl2:methanol elution) and triturated with water to afford 8-(6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-(3-hydroxy-propyl)-1-methyl-3,7-dihydro-purine-2,6-dione, [MH]+ 426.
Reaction SMILES: [C:1]([N:20]1[CH:24]=[C:23](I)[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[Mg+].[Br-].[CH3:30][C:31]1[S:32][CH:33]=[CH:34][C:35]=1[CH:36]=[O:37]>C(Cl)Cl>[CH3:30][C:31]1[S:32][CH:33]=[CH:34][C:35]=1[CH:36]([C:23]1[N:22]=[CH:21][N:20]([C:1]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:24]=1)[OH:37]
Reactant: Ic1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: Cc1sccc1C=O
Agent: CC[Mg+]
Agent: [Br-]
Solvent: ClCCl
Product: Cc1sccc1C(O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reaction time: 3 h

Procedure:
To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH2Cl2 (75 mL) was added EtMgBr (10.0 mL, 3.0M in Et2O) and the solution was stirred for 3 hrs. Then a solution of 2-methylthiophene-3-carboxaldehyde (3.3 g, 27 mmol) in CH2Cl2 (20 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with NH4Cl (aq) and the mixture was transferred to a separatory funnel. The aqueous layer was extracted with a second portion of CH2Cl2. The extracts were combined and washed with a small portion of water, dried (Na2SO4), and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et2O to give a solid which was recrystallized with charcoal treatment from EtOAc to give (2-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, B1. 1H NMR (CDCl3) supported the assigned structure. ##STR36##
Reaction SMILES: C1(N=C=O)C=CC(N=C=O)=CC=1.C(N(CC)CC)C.COC1C=C[C:25]([C:28]#[C:29][C:30]([F:33])([F:32])[F:31])=CC=1.COC(=O)CCC[N+:40]([O-])=[O:41]>C1(C)C=CC=CC=1>[F:31][C:30]([C:29]1[CH:28]=[CH:25][O:41][N:40]=1)([F:33])[F:32]
Reactant: COc1ccc(C#CC(F)(F)F)cc1
Reactant: COC(=O)CCC[N+](=O)[O-]
Agent: O=C=Nc1ccc(N=C=O)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: FC(F)(F)c1ccon1
Temperature: 150 °C
Reaction time: 2 h
Yield: 56.5 %

Procedure:
1,4-Phenylene diisocyanate (597.1 mg, 3.73 mol) and triethylamine (780 μL, 5.60 mmol) were added to a solution of 1-methoxy-4-trifluoropropynylbenzene (373.2 mg, 1.86 mmol) and 4-nitrobutanoic acid methyl ester (441.5 mg, 2.80 mmol) in toluene (10 mL). Using a microwave reactor, the obtained mixture was stirred at 150° C. for 2 hours. The reaction solution was filtered with celite, and the solvent was then distilled away. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain a trifluoromethyl isoxazole compound (144.0 mg, yield: 25%).
Reaction SMILES: [Br:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:15](=O)[CH2:14][CH2:13][N:6]3[C:7]=2[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1.Br[CH2:18][C:19]([O:21][CH3:22])=[O:20].[NH4+].[Cl-].C[Si](Cl)(C)C.[Na+].[I-].C([O-])(O)=O.[Na+].S([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CC#N.CCOC(C)=O>[CH3:22][O:21][C:19](=[O:20])[CH2:18][CH:15]1[C:5]2=[CH:4][C:3]3[C:2]([Br:1])=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[N:6]2[CH2:13][CH2:14]1
Reactant: COc1cc(Br)c2cc3n(c2c1)CCC3=O
Reactant: COC(=O)CBr
Agent: C[Si](C)(C)Cl
Agent: O=C([O-])O
Agent: O=S([O-])[O-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CC#N
Product: COC(=O)CC1CCn2c1cc1c(Br)cc(OC)cc12
Reaction time: 0.75 h
Yield: 82.7 %

Procedure:
A mixture of the ketone from Step 4 (0.4 g, 1.43 mmol), methyl bromoacetate (0.7 mL, 7.1 mmol), and Zn/Cu couple (0.46 g, 7.1 mmol) in THF (6 mL) was suspended in an ultrasound bath for 45 minutes. Saturated NH4Cl solution and EtOAc were then added, and the suspension was filtered through abed of Celite. The organic phase was washed with H2O and brine, dried (MgSO4), filtered and evaporated. The crude material was purified by flash chromatography (1:1 EtOAc/hexane) and the resulting intermediate was dissolved in CH3CN (10 mL). This solution was then added to a stirring mixture of TMSCl (0.8 mL, 6.4 mmol) and NaI (0.95 g, 6.4 mmol) in CH3CN (4 mL) in a RT H2O bath. Saturated NaHCO3 solution and sodium sulfite were added, and the product was extracted with EtOAc. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and evaporated to give a pale yellow solid (0.40 g).
Reaction SMILES: Cl[C:2]1[C:3]([C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].CC(C)([O-])C.[K+].[OH:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1.O>CN(C)C=O>[NH2:7][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]([C:12]([F:15])([F:14])[F:13])=[C:2]([O:22][C:23]2[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=2)[CH:8]=1
Reactant: Nc1cc(Cl)c(C(F)(F)F)cc1[N+](=O)[O-]
Reactant: O=Cc1ccc(O)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1cc(Oc2ccc(C=O)cc2)c(C(F)(F)F)cc1[N+](=O)[O-]
Yield: 74.5 %

Procedure:
A solution of 5-chloro-2-nitro-4-(trifluoromethyl)aniline (0.240 g, 1.00 mmol), potassium t-butoxide (0.135 g, 1.2 mmol), and 4-hydroxybenzaldehyde (0.147 g, 1.2 mmol) in dimethylformamide (5 mL) was heated to 80 degrees Centigrade for 6 hours and then cooled. Water was added and the organics extracted using ethyl acetate (2×50 mL). The combined organics were then washed once in brine and then dried (Na2SO4), filtered and concentrated. Chromatography on silica gel using a gradient of 30%-40% ethyl acetate/hexanes eluted the product to give 0.243 g of 4-{[5-amino-4-nitro-2-(trifluoromethyl)phenyl]oxy}benzaldehyde as an yellowish solid.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:17]1([C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([S:32]([C:35]3[CH:43]=[CH:42][C:38]([C:39](O)=[O:40])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[CH:24]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>>[CH:17]1([C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([S:32]([C:35]3[CH:36]=[CH:37][C:38]([C:39]([NH:7][CH2:6][C:5]4[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=4)=[O:40])=[CH:42][CH:43]=3)(=[O:33])=[O:34])[CH:24]=2)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1
Reactant: NCc1ccc(F)cc1
Reactant: O=C(O)c1ccc(S(=O)(=O)n2cc(C3CCCCC3)c3ccccc32)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Product: O=C(NCc1ccc(F)cc1)c1ccc(S(=O)(=O)n2cc(C3CCCCC3)c3ccccc32)cc1
Yield: 90.8 %

Procedure:
Add 4-Fluoro-benzylamine (72 mg, 0.574 mmol, 1.1 eq) followed by triethylamine (343 mg, 0.472 ml, 3.39 mmol, 6.5 eq) to a CH2CL2 solution (8 ml) of 4-(3-Cyclohexyl-indole-1-sulfonyl)-benzoic acid (200 mg, 0.521 mmol, 1 eq). Add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (231 mg, 0.521 mmol, 1 eq) and stir at room temperature for 16 hours. Remove solvent on rotovap and purify crude by silica gel chromatography to give 4-(3-Cyclohexyl-indole-1-sulfonyl)-N-(4-fluoro-benzyl)-benzamide (232 mg, 99% yield). Mass Spectrum (m/e): 490.92 (MH+).
Reaction SMILES: C(O)(=O)CCCCC(O)=O.[CH2:11]=[CH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].O=O.[CH2:21]([CH:29]([CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])[C:30]([OH:32])=[O:31])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>C([O-])(=O)C.[Mn+2].C([O-])(=O)C.C([O-])(=O)C.[Co+2].C([O-])(=O)C.C(O)(=O)C>[CH2:21]([CH:29]([CH2:33][CH2:34][CH:35]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:36]([OH:38])=[O:37])[C:30]([OH:32])=[O:31])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: C=CCCCCCC
Reactant: CCCCCCCCC(CCCC(=O)O)C(=O)O
Agent: [Co+2]
Agent: [Mn+2]
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Product: CCCCCCCCC(CCC(CCCCCCCC)C(=O)O)C(=O)O

Procedure:
A mixture of 20 mmol of adipic acid, 2 mmol of 1-octene, 0.04 mmol of manganese(II) acetate, 0.002 mmol of cobalt (II) acetate and 2 ml of acetic acid was stirred at 90° C. in an atmosphere of a gaseous mixture of nitrogen and oxygen (9:1) (1 atm=0.101 MPa) for 3 hours. The resulting reaction mixture was analyzed to find that 2-octyladipic acid and 2, 5-dioctyladipic acid were produced in yields of 14% and 1%, respectively, with a conversion from 1-octene of 33%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[N:15]3)[NH:12][S:11](=[O:21])(=[O:20])[C:10]1[C:5]2=[CH:6][C:7](F)=[CH:8][CH:9]=1.[OH:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[N:15]3)[NH:12][S:11](=[O:21])(=[O:20])[C:10]1[C:5]2=[CH:6][C:7]([N:27]2[CH2:28][CH2:29][CH:24]([OH:23])[CH2:25][CH2:26]2)=[CH:8][CH:9]=1
Reactant: OC1CCNCC1
Reactant: O=S1(=O)Nc2c(cc(Cl)c3cccnc23)-c2cc(F)ccc21
Solvent: CN1CCCC1=O
Product: O=S1(=O)Nc2c(cc(Cl)c3cccnc23)-c2cc(N3CCC(O)CC3)ccc21
Yield: 48.1 %

Procedure:
12-Chloro-9-fluoro-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide 503 (100 mg, 0.3 mmol), 4-hydroxy piperidine (121 mg, 1.2 mmol) and NMP (2 ml) were heated in microwave at 180° C. for 4 h. After cooling, the mixture was poured into ice cold water and the resulting precipitate was collected by filtration and dried. The crude residue was purified by column chromatography with DCM/MeOH (99:1) as the eluent to give the title compound (60 mg, 48%).
Reaction SMILES: [Br:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:5](Br)=[N:4][CH:3]=1.[NH2:12][C:13]1[CH:14]=[CH:15][C:16]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[C:17]([CH:21]=1)[C:18]([NH2:20])=[O:19].C(N(CC)C(C)C)(C)C.CCOCC>C(O)(C)C>[Br:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[C:17]([CH:21]=2)[C:18]([NH2:20])=[O:19])=[N:4][CH:3]=1
Reactant: Brc1ncc(Br)n2ccnc12
Reactant: NC(=O)c1cc(N)ccc1N1CCOCC1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOCC
Product: NC(=O)c1cc(Nc2ncc(Br)n3ccnc23)ccc1N1CCOCC1
Yield: 64.8 %

Procedure:
In the same way as described in the general procedure for amine displacement using 5,8-dibromo-imidazo[1,2-a]pyrazine (0.131 g, 0.47 mmol), 5-amino-2-morpholin-4-yl benzamide (157 mg, 0.71 mmol), N,N-diisopropylethylamine (0.120 mL, 0.71 mmol) in iso-propanol (3.7 mL). Trituration with tPrOH and Et2O affords the title compound (127 mg, 67%).
Reaction SMILES: [C:1]1([C:7]2[N:16]=[C:15]([C:17]([O:19]CC)=O)[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29][OH:30])[CH2:24][CH2:23]1>O>[C:1]1([C:7]2[N:16]=[C:15]([C:17]([N:22]3[CH2:27][CH2:26][CH:25]([CH2:28][CH2:29][OH:30])[CH2:24][CH2:23]3)=[O:19])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1nc(-c2ccccc2)nc2ccccc12
Reactant: OCCC1CCNCC1
Solvent: O
Product: O=C(c1nc(-c2ccccc2)nc2ccccc12)N1CCC(CCO)CC1

Procedure:
Ethyl 2-phenylquinazoline-4-carboxylate (1.7 g) and piperidine-4-ethanol (8 g) are heated at 150° C. for 4 hours. After cooling, water is added and the mixture is extracted with ethyl acetate. The organic phase is dried over magnesium sulphate and evaporated to dryness under reduced pressure. The residue is chromatographed on silica gel with ethyl acetate as the eluant, and the product recovered is recrystallised from isopropyl ether. This gives 1-[(2-phenylquinazoline-4-yl)carbonyl]-piperidine-4-ethanol (0.5 g), melting at 146° C.
Reaction SMILES: [CH2:1]([NH:4][CH2:5][CH2:6][NH2:7])[CH:2]=[CH2:3].[C:8](=[S:10])=[S:9]>C(O)C>[CH2:1]([NH:4][CH2:5][CH2:6][NH:7][C:8](=[S:9])[SH:10])[CH:2]=[CH2:3]
Reactant: C=CCNCCN
Reactant: S=C=S
Solvent: CCO
Product: C=CCNCCNC(=S)S
Temperature: 5 °C
Reaction time: 0.25 h

Procedure:
To 10 g of N-allylethylendiamine (0.1 moles) dissolved in 50 cc of ethanol there were admixed, under stirring, 7.6 g of CS2 (0.1 moles) dissolved in 50 cc ethanol, the temperature being maintained at about 5° C. Once the addition is accomplished, stirring is continued for another 15 minutes, after which the resulting precipitate is filtered and, after washing with ethanol, consists of 15.6 g of white crystals having a m.p. of 125° C. (with decomposition) of N-(2'-allylaminoethyl)dithiocarbamic acid having the following structure of an internal salt: ##STR20##
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[C:3]=1[CH:21]([CH2:26][CH2:27][CH3:28])[C:22]([O:24]C)=[O:23].[OH-].[Na+]>CO.C(O)C>[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[C:3]=1[CH:21]([CH2:26][CH2:27][CH3:28])[C:22]([OH:24])=[O:23]
Reactant: CCCC(C(=O)OC)c1c(C)nc2sc3c(c2c1-c1ccc(Cl)cc1)CCC3
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CO
Product: CCCC(C(=O)O)c1c(C)nc2sc3c(c2c1-c1ccc(Cl)cc1)CCC3
Temperature: 25 °C
Yield: 61.5 %

Procedure:
To a solution of methyl [2-methyl-4-(4-chlorophenyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno [2,3-b]pyridin-3-yl]pentanoate (0.049 g; 0.118 mmol) in methanol (2.5 mL) and ethanol (2.6 mL) was added a 5% sodium hydroxide solution (3.3 mL; 4.125 mmol). The reaction mixture was heated under reflux for 4.5 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was suspended in water, acidified with 1N HCl (pH˜2) and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was crystallized from a mixture of ethyl acetate/heptane to afford 0.029 g (61%) of the title compound as a white powder.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH:20]([C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1)=[O:21]>CN(C)C1C=CN=CC=1>[C:7]([CH2:6][C:5]1[CH:9]=[CH:10][C:2]([NH:1][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([CH:20]=[O:21])=[CH:23][CH:24]=2)=[CH:3][CH:4]=1)#[N:8]
Reactant: N#CCc1ccc(N)cc1
Reactant: O=Cc1ccc(C(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Product: N#CCc1ccc(NC(=O)c2ccc(C=O)cc2)cc1
Yield: 66.7 %

Procedure:
In the same manner as that described in Example 2(1), a reaction was carried out using commercially available 4-aminobenzyl cyanide (329 mg, 2.5 mmol), N,N-diisopropylethylamine (0.91 ml, 5.2 mmol), 4-formylbenzoyl chloride (350 mg, 2.1 mmol) and 4-(dimethylamino)pyridine (a catalytic amount) and the reaction mixture was treated according to a similar procedure to that described in Example 2(1) to afford 4′-(cyanomethyl)-4-formylbenzanilide (370 mg, yield 67%) as a pale yellow solid which was recrystallized from a mixture of ethyl acetate and tetrahydrofuran to give pale yellow powdery crystals.