Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([OH:13])=O)[N:2]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:47][O:48][C:49]([C:51]1[C:59]2[N:58]=[C:57]([NH2:60])[NH:56][C:55]=2[C:54]([O:61][CH3:62])=[CH:53][CH:52]=1)=[O:50]>CN(C=O)C.[Cl-].[Na+].O>[CH3:47][O:48][C:49]([C:51]1[C:59]2[NH:58][C:57]([NH:60][C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)=[O:13])=[N:56][C:55]=2[C:54]([O:61][CH3:62])=[CH:53][CH:52]=1)=[O:50]
Reactant: O=C(O)c1cc2ccccc2cn1
Reactant: COC(=O)c1ccc(OC)c2[nH]c(N)nc12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Cl-]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(OC)c2nc(NC(=O)c3cc4ccccc4cn3)[nH]c12
Yield: 37.2 %

Procedure:
300 mg (1.5 mmol) of isoquinoline-3-carboxylic acid and 570 mg (1.50 mmol) of HBTU were dissolved in 1.0 mL of DMF and 0.8 mL of DIEA and reacted with 110 mg (0.5 mmol) of 2-amino-7-methoxy-1H-benzoimidazole-4-carboxylic acid methyl ester as described in general procedure A. Upon completion, the reaction was diluted with brine. The resulting solid was filtered, washed with water and EtOAc, and dried under vacuum to produce 70 mg (37%) of 2-[(isoquinoline-3-carbonyl)-amino]-7-methoxy-3H-benzoimidazole-4-carboxylic acid methyl ester. LCMS: 378 (M+1)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:29])=[C:14]([C:24](OCC)=[O:25])[C:15](=[O:23])[N:16]3[CH2:19][CH2:20][CH2:21][OH:22])=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[CH3:30][O:31][CH2:32][CH2:33][NH2:34]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:29])=[C:14]([C:24]([NH:34][CH2:33][CH2:32][O:31][CH3:30])=[O:25])[C:15](=[O:23])[N:16]3[CH2:19][CH2:20][CH2:21][OH:22])=[N:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCCO)c1=O
Reactant: COCCN
Product: COCCNC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCCO)c1=O
Yield: 33 %

Procedure:
In a similar manner to that described in example 196, from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-(3-hydroxypropyl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (60 mg, 0.15 mmol) and [2-(methyloxy)ethyl]amine (0.05 mL) was prepared 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-(3-hydroxypropyl)-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide (21 mg, 33% yield) as a yellow solid after purification by reverse phase HPLC. 1H NMR (CDCl3) δ 10.22 (br s, 1 H), 8.56 (s, 1 H), 7.46 (s, 1 H), 7.16-7.16 (m, 2 H), 7.03-6.99 (m, 2 H), 4.31 (m, 2 H), 4.12 (s, 2 H), 3.64 (m, 2 H), 3.57 (m, 2 H), 3.49 (m, 2 H), 3.39 (s, 3 H), 1.82 (m, 2 H); HRMS m/z calcd for C22H25N3O5F: 430.1778. Found: 430.1778.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16](=[O:32])[N:17]3[C:22](=[C:23]([C:25](O)=[O:26])[CH:24]=2)[C:21]2[N:28]=[CH:29][N:30]([CH3:31])[C:20]=2[CH:19]=[CH:18]3)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)Cl.CN(C=O)C.[CH:42]1([CH2:45][NH:46][CH2:47][CH2:48][O:49][CH3:50])[CH2:44][CH2:43]1>C1(C)C=CC=CC=1.ClCCl.C(N(CC)CC)C>[CH:42]1([CH2:45][N:46]([CH2:47][CH2:48][O:49][CH3:50])[C:25]([C:23]2[CH:24]=[C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:14][CH:13]=3)[C:16](=[O:32])[N:17]3[C:22]=2[C:21]2[N:28]=[CH:29][N:30]([CH3:31])[C:20]=2[CH:19]=[CH:18]3)=[O:26])[CH2:44][CH2:43]1
Reactant: Cn1cnc2c1ccn1c(=O)c(-c3ccc(OCc4ccccc4)cc3)cc(C(=O)O)c21
Reactant: COCCNCC1CC1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: COCCN(CC1CC1)C(=O)c1cc(-c2ccc(OCc3ccccc3)cc2)c(=O)n2ccc3c(ncn3C)c12

Procedure:
From 8-(4-benzyloxy-phenyl)-3-methyl-7-oxo-3,7-dihydro-imidazo[4,5-a]-quinolizine-10-carboxylic acid with SOCl2 and DMF in toluene and treatment with triethylamine and cyclopropylmethyl-(2-methoxy-ethyl)-amine in dichloromethane.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([NH:9][NH2:10])=[O:8])([O-:3])=[O:2].[CH2:14](OC(OCC)(OCC)C)[CH3:15]>>[CH3:14][C:15]1[O:8][C:7]([C:6]2[CH:11]=[CH:12][CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[N:9][N:10]=1
Reactant: CCOC(C)(OCC)OCC
Reactant: NNC(=O)c1cccc([N+](=O)[O-])c1
Product: Cc1nnc(-c2cccc([N+](=O)[O-])c2)o1

Procedure:
3-Nitrobenzoic acid, hydrazide, 24.5 g, (Chemical Abstracts, Vol. 102, 148507r (1983)) and 1,1,1-triethoxyethane are refluxed overnight. The mixture is cooled, filtered, and washed with hexane to give 21.9 g of 2-methyl-5-(3-nitrophenyl)-1,3,4-oxadiazole after recrystallization from 2-propanol; mp 154°-156° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](F)[N:3]=1.[S:9]([O-:12])([O-:11])=[O:10].[Na+:13].[Na+]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([S:9]([O-:12])(=[O:11])=[O:10])[N:3]=1.[Na+:13]
Reactant: Fc1cccc(F)n1
Reactant: O=S([O-])[O-]
Agent: [Na+]
Product: O=S(=O)([O-])c1cccc(F)n1
Yield: 10.5 %

Procedure:
In the same manner as in Example 1, 1.725 g (15 mmol) of 2,6-difluoropyridine and 2.27 g (18 mmol) of sodium sulfite were reacted at 170° C. for 5 hours. By conducting the same post-treatment as in Example 1, 0.315 g (10.5%) of sodium 2-fluoropyridine-6-sulfonate was obtained.
Reaction SMILES: [NH2:1][C:2](=[N:26][OH:27])[C:3]1[CH:25]=[CH:24][C:6]([O:7][CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:35](Cl)(=[O:37])[CH3:36]>CC(C)=O>[C:35]([O:27][NH:26][CH:2]([NH2:1])[C:3]1[CH:25]=[CH:24][C:6]([O:7][CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]2)=[CH:5][CH:4]=1)(=[O:37])[CH3:36]
Reactant: CC(C)(C)OC(=O)N1CCN(CCCOc2ccc(C(N)=NO)cc2)CC1
Reactant: CC(=O)Cl
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: CC(=O)ONC(N)c1ccc(OCCCN2CCN(C(=O)OC(C)(C)C)CC2)cc1
Reaction time: 1 h
Yield: 86.5 %

Procedure:
A solution of Example 2C (0.11 g, 0.29 mmol) and triethylamine (400 μL, 2.9 mmol) in acetone (10 mL) was treated with a solution of acetyl chloride (200 μL, 2.8 mmol) in acetone (1 mL) over 30 minutes, stirred for 1 hour, and concentrated. The concentrate was partitioned between water and dichloromethane. The layers were separated, and the aqueous layer was extracted with dichloromethane. The combined extracts were dried (Na2SO4), filtered and concentrated. The concentrate was purified by column chromatography on silica gel using 95:5 dichloromethane:methanol to afford 106 mg (87%) of the desired product.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[N:7]1.[C:15]1([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1.C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[N:6]1([CH2:5][CH2:4][CH2:3][CH2:2][N:28]2[CH2:29][CH2:30][CH:25]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:18]=[CH:17][CH:16]=3)[CH2:26][CH2:27]2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[N:7]1
Reactant: ClCCCCn1nnc2ccccc21
Reactant: c1ccc2c(C3CCNCC3)cccc2c1
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: c1ccc2c(C3CCN(CCCCn4nnc5ccccc54)CC3)cccc2c1
Temperature: 25 °C
Yield: 59.8 %

Procedure:
1-(4-chlorobutyl)-1H-benzotriazole (7.55 g, 0.036 mol) was dissolved into 100 ml of acetonitrile, 4-(1-naphthyl)piperidine (6.4 g, 0.03 mol), diisopropylethylamine (15.5 g, 0.12 mol) and potassium iodide (5.0 g, 0.03 mol) were respectively added. The mixture was stirred and mixed, then heated and refluxed to react for 20 hours. The mixture was cooled down to ambient temperature and filtered. The filtrate was concentrated to produce oily products, and treated by chromatography with neutral Al2O3 and purified, eluted with dichloromethane to produce 6.9 g compound (I-122) with a yield of 60.1%. ESI-MS [M+H]+: m/z 385.3.
Reaction SMILES: [C:1]([C:3]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20])([CH2:9][CH2:10][C:11]([OH:13])=O)[CH2:4][CH2:5][C:6]([OH:8])=[O:7])#[N:2].Cl[C:22]1C=CC(C(C#N)(CCC(O)=O)CCC(O)=O)=CC=1.O1CCCC1.CC(C)([O-])C.[K+]>C(O)(=O)C>[C:6]([CH:5]1[CH2:4][C:3]([C:1]#[N:2])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:9][CH2:10][C:11]1=[O:13])([O:8][CH3:22])=[O:7]
Reactant: N#CC(CCC(=O)O)(CCC(=O)O)c1ccc(Cl)cc1
Reactant: Cc1ccccc1C(C#N)(CCC(=O)O)CCC(=O)O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: COC(=O)C1CC(C#N)(c2ccccc2C)CCC1=O
Yield: 93 %

Procedure:
Following the procedure of Example 1, Part B, but substituting 21.76 gm. (0.0715 mole) of the dimethyl ester of 4-cyano-4-(o-tolyl)pimelic acid (prepared in Part A, above) for the 34.97 gm. of the dimethyl ester of 4-(p-chlorophenyl)-4-cyanopimelic acid and using 460 ml. of the tetrahydrofuran, 16.3 gm. (0.145 mole) of the potassium tert-butoxide, and 115 ml. of the 2.5 N aqueous acetic acid instead of the 700 ml., the 24.4 gm. and the 175 ml., respectively, there is prepared 18.0 gm. (93% yield) of 2-carbomethoxy-4-cyano-4-(o-tolyl)cyclohexanone as a crystalline solid having a melting range at 107° to 113° C.
Reaction SMILES: CO[CH:3](OC)[N:4]([CH3:6])[CH3:5].[I:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([CH3:19])=[CH:12][C:11]=1[F:20]>CN(C=O)C>[I:9][C:10]1[C:11]([F:20])=[CH:12][C:13]([CH:19]=[CH:3][N:4]([CH3:6])[CH3:5])=[C:14]([N+:16]([O-:18])=[O:17])[CH:15]=1
Reactant: COC(OC)N(C)C
Reactant: Cc1cc(F)c(I)cc1[N+](=O)[O-]
Solvent: CN(C)C=O
Product: CN(C)C=Cc1cc(F)c(I)cc1[N+](=O)[O-]
Temperature: 125 °C
Reaction time: 3 h
Yield: 0.1 %

Procedure:
A mixture of N,N-dimethylformamide dimethyl acetal (0.30 mL, 2.31 mmol) and 1-iodo-2-fluoro-4-methyl-5-nitro-benzene (0.50 g, 1.78 mmol) in dry DMF (3.0 mL) was stirred at 125° C. for 3 h. The resulting mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The residue was washed with hexane to give [2-(4-iodo-5-fluoro-2-nitro-phenyl)-vinyl]-dimethyl-amine as dark red solid (0.37 mg, 62%). 1H NMR (CDCl3, 400 MHz): 2.97 (s, 6H), 5.92 (d, J=13.3 Hz, 1H), 7.02 (d, J=13.3 Hz, 1H), 7.09 (d, J=10.2 Hz, 1H), 8.30 (d, J=6.2 Hz, 1H). 13C NMR (CDCl3, 100 MHz,): 40.8, 108.9, 109.1, 137.0, 139.3, 146.0.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].C([O-])([O-])=O.[K+].[K+].[I-].[Na+].Cl[CH:20]([CH3:25])[C:21]([O:23][CH3:24])=[O:22]>CC(C)=O>[CH3:24][O:23][C:21](=[O:22])[CH:20]([O:10][C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)[CH3:25]
Reactant: COC(=O)C(C)Cl
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)C(C)Oc1ccc([N+](=O)[O-])cc1
Yield: 30.9 %

Procedure:
To a mixture of 4-nitrophenol (200 grm, 1.439 mol), anhydrous K2CO3 (800 grm, 5.789 mol) and sodium iodide (10 g, 66.7 mmol) in anhydrous acetone (2.75 L) was, added methyl 2-chloropropionate (264 g, 2.154 mol) and refluxed for 20 hours. Acetone was distilled off and water (3 L) was added. Crude 14 was filtered, dried and recrystallised from a mixture of ethyl acetate:hexane (1:5) to give pure 14 (100 g, 31%) as a white fluffy powder with a m.p between 83-84° C.
Reaction SMILES: Cl([O-])(=O)(=O)=O.[Li+].[CH2:7]([O:10][CH2:11][CH2:12][CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[NH2:14])[CH:8]=[CH2:9].[O:23]1[CH2:25][C@@H:24]1[C@@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])(O)=O.[Na+]>CC#N.[Cl-].[Na+].O>[CH2:7]([O:10][CH2:11][CH2:12][CH:13]([NH:14][CH2:25][C@@H:24]([OH:23])[C@@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1)[CH:8]=[CH2:9]
Reactant: C=CCOCCC(N)c1cccc(OC)c1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@H]1CO1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Li+]
Solvent: CC#N
Solvent: O
Product: C=CCOCCC(NC[C@@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)c1cccc(OC)c1
Temperature: 50 °C
Yield: 82.1 %

Procedure:
Step R (4): Lithium perchlorate (936 mg, 8.80 mmol) was added to a mixture of 3-(allyloxy)-1-(3-methoxyphenyl)propan-1-amine (390 mg, 1.76 mmol) from Step R(3) and tert-butyl (S)-1-((S)-oxiran-2-yl)-2-phenylethylcarbamate (464 mg, 1.76 mmol) from Aldrich, dissolved in CH3CN (10 mL). The resulting mixture was heated at 50° C. for 16 h. The reaction mixture was poured into a mixture of brine and saturated aqueous NaHCO3 solution. Extracted with EtOAc, washed combined extracts with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography to give 700 mg (quantitative yield) of tert-butyl (2S,3R)-4-(3-(allyloxy)-1-(3-methoxyphenyl)propylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamate as a mixture of two diastereomers. LC-MS (M+H)+=485.57; 1H NMR (300 MHz, CDCl3) δ ppm 1.14-1.43 (m, 9H) 2.56-3.04 (m, 4H) 3.24-3.38 (m, 1H) 3.39-3.58 (m, 2H) 3.69-4.01 (m, 7H) 4.60 (t, J=9.88 Hz, 1H) 5.04-5.30 (m, 2H) 5.72-5.99 (m, 1H) 6.73-7.00 (m, 2H) 7.09-7.33 (m, 7H).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:31][C:20]3[C:21](=[O:30])[N:22]([CH3:29])[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=4[C:19]=3[N:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]2[N:31]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:20]3[C:21](=[O:30])[N:22]([CH3:29])[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=4[C:19]=3[N:18]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cn1c(=O)c2[nH]c(C3CCN(C(=O)OCc4ccccc4)CC3)nc2c2ccccc21
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Product: Cn1c(=O)c2c(nc(C3CCN(C(=O)OCc4ccccc4)CC3)n2Cc2ccccc2)c2ccccc21
Yield: 83.2 %

Procedure:
As described in example 3 step E, 4-(5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester (50 mg, 0.102 mmol), was alkylated by treating with NaH (5 mg, 0.12 mmol, 60% in mineral oil), and benzyl bromide (26 mg, 0.15 mmol) to give after work-up and chromatography, 4-(3-benzyl-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester (43 mg, 83% yield). 1H-NMR (CDCl3): δ 8.34 (dd, 1H, J=8.0, 1.6 Hz), 7.53 (m, 1H), 7.42 (m, 1H), 7.26–7.37 (m, 9H), 7.10 (m, 2H), 5.91 (m, 2H), 5.13 (s, 2H), 4.28 (m, 2H), 3.79 (s, 3H), 2.89 (m, 3H), 1.98 (m, 2H), 1.68 (m, 2H). MS: calculated for C24H24N4O3+H 507.2; found: 507.6.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[NH:13][CH:12]=2)=[O:10])=[N:6][C:7]=1[CH3:8].[H-].[Na+].Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[N:27]=1>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([C:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:34])([F:33])[F:35])[N:27]=3)[CH:12]=2)=[O:10])=[N:6][C:7]=1[CH3:8]
Reactant: Cc1ccc(C(=O)c2c[nH]c3ccccc3c2=O)nc1C
Reactant: FC(F)(F)c1cccc(CBr)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(C(=O)c2cn(Cc3cccc(C(F)(F)F)n3)c3ccccc3c2=O)nc1C

Procedure:
Experimental conditions analogous to those described for Step 3 of Example 1, from 63 mg (0.23 mmol) of 3-(5,6-dimethyl-pyridine-2-carbonyl)-1H-quinolin-4-one, 11 mg (0.27 mmol) of 60% sodium hydride, 65 mg (0.27 mmol) of 2-bromomethyl-6-trifluoromethyl-pyridine and 0.7 mL of N,N-dimethylformamide. Yield: 31 mg of a white solid: LC-MSD, m/z for C24H18F3N3O2 [M+H]+=438.1; HPLC retention time: 1.6 min.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[C:17]([O:18][CH3:19])=[CH:16][N:15]=[CH:14][C:13]=2Cl)[O:9][N:8]=1.B1([C:27]2[CH:32]=[CH:31][CH:30]=[N:29][CH:28]=2)OCCCO1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[C:13]([C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)=[CH:14][N:15]=[CH:16][C:17]=2[O:18][CH3:19])[O:9][N:8]=1
Reactant: c1cncc(B2OCCCO2)c1
Reactant: COc1cncc(Cl)c1-c1nc(-c2ccccn2)no1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: COCCOC
Product: COc1cncc(-c2cccnc2)c1-c1nc(-c2ccccn2)no1
Yield: 4.1 %

Procedure:
A mixture of 3-(2-pyridyl)-5-(3-chloro-5-methoxy-pyrid-4-yl)-1,2,4-oxadiazole (75 mg, 0.260 mmol), pyridine-3-boronic acid 1,3-propanediol cyclic ester (75 mg, 0.46 mmol), and tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4, 30 mg, 0.026 mmol), in a solution of ethylene glycol dimethyl ether (1 mL) and 2M sodium carbonate (1 mL) was heated in a sealed vial at 100° C. for 1 hour. The reaction was cooled, diluted with dichloromethane, washed with water and saturated brine, filtered, and concentrated. Silica gel chromatography using 40% ethyl acetate in hexane and 100% ethyl, acetate afforded 3.5 mg (4.1%) 3-(2-pyridyl)-5-[3-methoxy-5-(3-pyridyl)-pyrid-4-yl]-1,2,4-oxadiazole. 1H-NMR (CDCl3), δ (ppm): 9.39 (s, 1H), 8.91 (d, 1H), 8.72 (d, 1H), 8.42 (d, 1H), 8.25 (d, 1H), 8.20 (s, 1H), 7.92 (dt, 1H), 7.63 (dd, 1H), 7.50 (m, 2H), 4.12 (s, 3H).
Reaction SMILES: C([O:3][P:4]([C:9]1[C:13]([P:14]([O:19]CC)([O:16]CC)=[O:15])=[C:12]([C:22]2[S:23][C:24]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[CH:25][CH:26]=2)[S:11][C:10]=1[C:32]1[S:36][C:35]([C:37]2[S:38][CH:39]=[CH:40][CH:41]=2)=[CH:34][CH:33]=1)([O:6]CC)=[O:5])C.I[Si](C)(C)C>C(#N)C>[P:4]([C:9]1[C:13]([P:14]([OH:19])([OH:16])=[O:15])=[C:12]([C:22]2[S:23][C:24]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[CH:25][CH:26]=2)[S:11][C:10]=1[C:32]1[S:36][C:35]([C:37]2[S:38][CH:39]=[CH:40][CH:41]=2)=[CH:34][CH:33]=1)([OH:5])([OH:6])=[O:3]
Reactant: CCOP(=O)(OCC)c1c(-c2ccc(-c3cccs3)s2)sc(-c2ccc(-c3cccs3)s2)c1P(=O)(OCC)OCC
Agent: C[Si](C)(C)I
Solvent: CC#N
Product: O=P(O)(O)c1c(-c2ccc(-c3cccs3)s2)sc(-c2ccc(-c3cccs3)s2)c1P(=O)(O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 71 %

Procedure:
In 4.0 ml of acetonitrile, 0.2746 g (0.401 mmols) of 3″,4″-bis(diethoxyphosphoryl)-[2,2′;5′,2″;5″,2″′;5″′,2″″]-quinquethiophene was dissolved, to which 0.4012 g (2.005 mmols) of commercially available iodotrimethylsilane was added at room temperature. Thereafter, the mixture was stirred at room temperature for 12 hours. After the reaction, the solvent was removed by distilling off under reduced pressure, followed by addition of methanol and stirring at room temperature for further 12 hours. A sodium thiosulfate aqueous solution was added, followed by stirring, filtration of the precipitated crystals, washing with distilled water, methanol, chloroform and diethyl ether and drying to obtain the specified substance in the form of a yellow powder at a yield of 0.1630 g (yield: 71%).
Reaction SMILES: C(O[C:6]([NH:8][C@H:9]([C:20]([OH:22])=O)[C@@H:10]([CH3:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:7])(C)(C)C.Cl.[NH2:24][CH2:25][CH2:26][C:27]1[CH:34]=[CH:33][C:31]([OH:32])=[C:29]([OH:30])[CH:28]=1>>[OH:30][C:29]1[CH:28]=[C:27]([CH:34]=[CH:33][C:31]=1[OH:32])[C:6]([NH:8][C@H:9]([C:20]([NH:24][CH2:25][CH2:26][C:27]1[CH:34]=[CH:33][C:31]([OH:32])=[C:29]([OH:30])[CH:28]=1)=[O:22])[C@@H:10]([CH3:19])[O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:7]
Reactant: NCCc1ccc(O)c(O)c1
Reactant: C[C@@H](OCc1ccccc1)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: Cl
Product: C[C@@H](OCc1ccccc1)[C@H](NC(=O)c1ccc(O)c(O)c1)C(=O)NCCc1ccc(O)c(O)c1
Yield: 120.1 %

Procedure:
The title compound was prepared from Nα-(tert-butoxycarbonyl)-O-benzyl-L-threonine (2.0 g, 6.5 mmol) following the indications of general procedure F using dopamine hydrochloride (2.4 g, 9.7 mmol). The crude material was purified by flash chromatography eluting with 30% EtOAc/CHCl3 to give 2.8 g (98%) of the desired product as white crystals.
Reaction SMILES: [CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].[Br:20]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:20][C:15]1[C:16]([NH2:19])=[N:17][CH:18]=[C:13]([C:10]2[CH:11]=[CH:12][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:5])=[O:6])=[CH:8][CH:9]=2)[N:14]=1
Reactant: CC(C)S(=O)(=O)c1ccc(-c2cnc(N)cn2)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(Br)n2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.3 %

Procedure:
5-(4-(Isopropylsulfonyl)phenyl)pyrazin-2-amine (10 g, 36.06 mmol) was dissolved in dry DMF (70 mL) and N-bromosuccinimide (6.418 g, 36.06 mmol) was added portionwise. The mixture was stirred at ambient temperature for 2 hours. The reaction mixture was poured into water (200 mL) and stirred for 5 minutes. The solid was isolated by filtration and washed with water. The wet solid was dissolved in ethyl acetate and any insoluble material removed by filtration. The aqueous layer was separated and the organic phase washed with saturated aqueous Na2S2O3 (×1) and dried (MgSO4). The organic extracts were filtered through a plug of Florisil (200 mesh), eluting with ethyl acetate. The filtrate was concentrated to ca. 50 mL and resultant precipitate isolated by filtration and washed with Petroleum Ether. The solid was further dried under high vacuum to give the sub-title compound as a pale orange solid (8.0 g, 62% Yield).). 1H NMR (400.0 MHz, DMSO) δ 1.17 (d, 6H), 3.41-3.49 (m, 1H), 7.16 (br s, 2H), 7.89 (d, 2H), 8.17 (d, 2H) and 8.76 (s, 1H) ppm; MS (ES+) 356.1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[NH:8][C:7](=O)[CH2:6][CH2:5]2.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:23])=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[NH:8][C:7](=[S:23])[CH2:6][CH2:5]2
Reactant: O=C1CCc2cc(Br)cc(Cl)c2N1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: S=C1CCc2cc(Br)cc(Cl)c2N1
Temperature: 100 °C

Procedure:
To a stirred solution of 6-bromo-8-chloro-3,4-dihydroquinolin-2(1H)-one (80-1; 10 g, 0.038 mol) in toluene (130 mL) was added Lawesson's reagent (7.7 g, 0.019 mol). Reaction mass was refluxed at 100° C. for 3 h. The reaction mixture was concentrated and directly purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO-d6) δ: 11.25 (s, 1H), 7.61-7.60 (d, J=2.4 Hz, 1H), 7.48 (s, 1H), 2.96-2.93 (m, 2H), 2.85-2.81 (m, 2H). MS (M+2): 277.
Reaction SMILES: [N:1]1([CH:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]2=[N:12]O)[CH2:5][CH2:4][CH2:3][CH2:2]1>CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.O=[Pt]=O>[N:1]1([C@H:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]2[NH2:12])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: ON=C1CCCCC1N1CCCC1
Agent: O=[Pt]=O
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Product: N[C@@H]1CCCC[C@@H]1N1CCCC1
Reaction time: 96 h

Procedure:
2-(1-pyrrolidinyl)cyclohexanone oxime (c) (22.95 g, 0.105 mol) was dissolved in glacial acetic: acid (120 mL), PtO2 (1 g) was added and the mixture was hydrogenated at 45 psi for 96 hours. During this time, the catalyst was filtered and renewed every 24 hours. The reaction was followed by gas chromatography. The PtO2 was removed by filtration of the reaction mixture through celite and excess concentrated HCl was added. The solvent was removed in vacuo at 40°-50° C. and the resulting hydrochloride salt was dissolved in 100 mL of water. This aqueous solution was carefully basified to 30% w/v with pellets of NaOH and extracted with CHCl3 (5×50 mL). The organic layer was dried (Na2SO4), and the solvent was removed in vacuo. The crude amine was distilled under high vacuum to yield 13.7 g of (±)-(78%) as a colorless unstable oil. bp: 94° C./0.05 mmHg. Ir (film): 3380, 3300, 2940, 1590, 1440, 1125, 835 cm-1. (±)-d.HCl crystallized slowly from 2-propanol as small conglomerates: mp 263°-265° C. 1H-NMR (free base) (CDCl3): d 1.00-1.18 (m, 1H), 1.20-1.40 (m, 5H), 1.50-1.68 (m, 6H), 1.74 (t, J=3.5 Hz, 1H), 1.78 (t, J=3.5 Hz, 1H), 2.30-2.48 (m, 4H), 3.08 (br s, 2H). EIms (m/z, rel. int.): 168 (31, M+), 110 (100), 97 (42), 84 (92), 70 (33). Anal. Calcd. for C10 H22N2Cl2 : C 49.79, H 9.19, N 11.62; Found: C 49.82, H 9.19, N 11.67.