Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][NH:11][C:12]2[CH:16]=[CH:15][NH:14][C:13]=2[C:17]([O:19]CC)=O)=[CH:2]1.C([N:30]=[C:31]=[S:32])(=O)C1C=CC=CC=1>CO.C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][N:11]2[C:12]3[CH:16]=[CH:15][NH:14][C:13]=3[C:17](=[O:19])[NH:30][C:31]2=[S:32])=[CH:2]1
Reactant: CCOC(=O)c1[nH]ccc1NCc1c[nH]c2ccccc12
Reactant: O=C(N=C=S)c1ccccc1
Solvent: CO
Solvent: ClCCl
Product: O=c1[nH]c(=S)n(Cc2c[nH]c3ccccc23)c2cc[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 20.7 %

Procedure:
A crude mixture of ethyl 3-[(1H-indol-3-ylmethyl)amino]-1H-pyrrole-2-carboxylate (max 0.49 mmol) was added to CH2Cl2 (5 mL). A few drops of methanol were added to increase solubility. Benzoylisothiocyanate (0.072 g, 0.53 mmol) was added and the mixture was stirred at r.t. for 1 h. The mixture was concentrated in vacuo. Ammonia (7N in methanol, 3 mL) was added and the mixture was heated at 80° C. for 2 h. The mixture was concentrated and purified by preparative HPLC, obtaining the title compound (0.030 g, 21%) as a solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C:8](=[O:13])[CH2:7]2)([O-:3])=[O:2].[BH4-].[Na+].O>CCO.CC(O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([OH:13])[CH2:7]2)([O-:3])=[O:2]
Reactant: O=C1Cc2ccc([N+](=O)[O-])cc2C1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: CC(C)O
Product: O=[N+]([O-])c1ccc2c(c1)CC(O)C2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 83.2 %

Procedure:
5-nitro-2-indanone (5.3 g, 30 mmol) was dissolved in EtOH: i-PrOH (1:1, 150 mL). NaBH4 (1.7 g, 45 mmol) was added portion by portion at room temperature. The reaction mixture was stirred at r.t for additional 30 min and water was added at 0° C. (ice-water bath). The reaction mixture was extracted with EtOAc (100 mL×3) and the combined organic layers were washed with water and brine and dried over Na2SO4. Purification of the concentrated crude product by column chromatography (EtOAc:Hexane=4:6) afforded the title product as a pale yellow oil (4.47 g, 83%).
Reaction SMILES: Cl[CH2:2][C:3]1[O:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][CH2:14][CH2:13][C:12]=3[CH:16]=2)=[N:6][N:7]=1.[F:17][C:18]1[CH:19]=[C:20]([SH:24])[CH:21]=[CH:22][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[O:15]1[C:11]2[CH:10]=[CH:9][C:8]([C:5]3[O:4][C:3]([CH2:2][S:24][C:20]4[CH:21]=[CH:22][CH:23]=[C:18]([F:17])[CH:19]=4)=[N:7][N:6]=3)=[CH:16][C:12]=2[CH2:13][CH2:14]1
Reactant: ClCc1nnc(-c2ccc3c(c2)CCO3)o1
Reactant: Fc1cccc(S)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Fc1cccc(SCc2nnc(-c3ccc4c(c3)CCO4)o2)c1
Yield: 14.3 %

Procedure:
A solution of 2-(chloromethyl)-5-(2,3-dihydro-1-benzofuran-5-yl)-1,3,4-oxadiazole (0.16 g, 0.68 mmol), 3-fluorothiophenol (57 μL, 0.68 mmol) and potassium carbonate (0.10 g, 0.75 mmol) in N,N-dimethylformamide (5 mL) was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) and recrystallized from hexane/ethyl acetate to give the title compound (32 mg, yield 14%) as colorless crystals.
Reaction SMILES: [Br-:1].[Br-:2].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[C:22]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:32]=[C:33]3[C:38](=[CH:39][CH:40]=2)[N:37]=[C:36]([C:41](=[O:43])[CH3:42])[CH:35]=[CH:34]3)=[CH:27][CH:26]=1)(=[O:24])[CH3:23].Br>C(O)(=O)C>[Br:1][CH2:42][C:41]([C:36]1[CH:35]=[CH:34][C:33]2[C:38](=[CH:39][CH:40]=[C:31]([C:28]3[CH:27]=[CH:26][C:25]([C:22](=[O:24])[CH2:23][Br:2])=[CH:30][CH:29]=3)[CH:32]=2)[N:37]=1)=[O:43]
Reactant: [Br-]
Reactant: CC(=O)c1ccc(-c2ccc3nc(C(C)=O)ccc3c2)cc1
Agent: Br
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Product: O=C(CBr)c1ccc(-c2ccc3nc(C(=O)CBr)ccc3c2)cc1
Temperature: 70 °C
Reaction time: 6 h
Yield: 77.6 %

Procedure:
Pyridinium tribromide (221 mg, 0.691 mmol) was added to a suspension of 1-(6-(4-acetylphenyl)quinolin-2-yl)ethanone (100 mg, 0.346 mmol) and HBr (0.061 mL, 0.35 mmol) in acetic acid (3 mL) the reaction mixture was stirred at 70° C.) for 6 h. The reaction was concentrated under vacuum and the residue was partitioned between aq NaHCO3 (15 mL) and EtOAc (30 mL+10 mL+10 mL). The organic layers were combined, washed with brine, dried, filtered and concentrated to yield crude 2-bromo-1-(6-(4-(2-bromoacetyl)phenyl)quinolin-2-yl)ethanone (120 mg) as white solid. LC-MS retention time 4.138 min; m/z 448.01 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[N:15]=[C:16]([N:24]4[CH2:28][C@H:27]([OH:29])[CH2:26][C@H:25]4[C:30]([O:32]C)=[O:31])[C:17]4[S:22](=[O:23])[CH2:21][CH2:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:14]3[N:15]=[C:16]([N:24]4[CH2:28][C@H:27]([OH:29])[CH2:26][C@H:25]4[C:30]([OH:32])=[O:31])[C:17]4[S:22](=[O:23])[CH2:21][CH2:20][C:18]=4[N:19]=3)[CH2:12][CH2:13]2)=[CH:6][CH:7]=1
Reactant: COC(=O)[C@@H]1C[C@@H](O)CN1c1nc(N2CCN(c3ccc(Cl)cc3)CC2)nc2c1S(=O)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)[C@@H]1C[C@@H](O)CN1c1nc(N2CCN(c3ccc(Cl)cc3)CC2)nc2c1S(=O)CC2
Yield: 102.9 %

Procedure:
1.12 g methyl (2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylate as a mixture of diastereomers (cf Example 125) and 11.38 ml of 1 molar sodium hydroxide solution are placed in 10 ml of methanol, then refluxed for 4 hours with stirring. The resulting suspension is evaporated down, the residue is cooled and acidified with 2 molar hydrochloric acid and the suspension is evaporated down again. The product is purified by preparative HPLC (method A). 1.12 g of the product are obtained as a powder.
Reaction SMILES: Cl.[CH:2]([C:5]1[CH:6]=[C:7]([C@@H:11]([NH2:13])[CH3:12])[CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3].[CH3:14][O:15][C:16](=[O:41])[C@H:17]([O:19][C:20]1[CH:21]=[C:22]([CH:38]=[CH:39][CH:40]=1)[CH2:23][N:24]1[C:32]2[C:27](=[CH:28][C:29]([C:33](O)=[O:34])=[CH:30][CH:31]=2)[C:26]([CH3:36])=[C:25]1[CH3:37])[CH3:18]>>[CH:2]([C:5]1[CH:6]=[C:7]([C@@H:11]([NH:13][C:33]([C:29]2[CH:28]=[C:27]3[C:32](=[CH:31][CH:30]=2)[N:24]([CH2:23][C:22]2[CH:21]=[C:20]([CH:40]=[CH:39][CH:38]=2)[O:19][C@H:17]([CH3:18])[C:16]([O:15][CH3:14])=[O:41])[C:25]([CH3:37])=[C:26]3[CH3:36])=[O:34])[CH3:12])[CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3]
Reactant: COC(=O)[C@@H](C)Oc1cccc(Cn2c(C)c(C)c3cc(C(=O)O)ccc32)c1
Reactant: CC(C)c1cccc([C@H](C)N)c1
Agent: Cl
Product: COC(=O)[C@@H](C)Oc1cccc(Cn2c(C)c(C)c3cc(C(=O)N[C@@H](C)c4cccc(C(C)C)c4)ccc32)c1

Procedure:
The title compound was prepared following the same protocol as described in Step 5, Example 36, using the (S)-1-(3-isopropylphenyl)ethanamine hydrochloride instead of the (S)-1-(3-cyclopropylphenyl)ethanamine hydrochloride and the (R)-1-(3-((1-methoxy-1-oxopropan-2-yl)oxy)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid instead of the 1-(4-(2-methoxy-2-oxoethoxy)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([O:32][Si](C(C)(C)C)(C)C)[CH2:9][NH:10][C@H:11]([CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:12][O:13][C:14]2[CH:27]=[CH:26][C:17]([CH2:18][CH:19]3[S:23][C:22](=[O:24])[NH:21][C:20]3=[O:25])=[CH:16][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([OH:32])[CH2:9][NH:10][C@H:11]([CH2:28][CH:29]([CH3:30])[CH3:31])[CH2:12][O:13][C:14]2[CH:27]=[CH:26][C:17]([CH2:18][CH:19]3[S:23][C:22](=[O:24])[NH:21][C:20]3=[O:25])=[CH:16][CH:15]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)C[C@H](COc1ccc(CC2SC(=O)NC2=O)cc1)NC[C@H](O[Si](C)(C)C(C)(C)C)c1cccc(Cl)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)C[C@H](COc1ccc(CC2SC(=O)NC2=O)cc1)NC[C@H](O)c1cccc(Cl)c1

Procedure:
A procedure similar to that described in Preparation 4, above, was followed, but using 350 mg of 5-(4-{2(R)-[2(R)-(3-chlorophenyl)-2-t-butyldimethylsilyloxyethylamino]-4-methylpentyloxy}benzyl]thiazolidine-2,4 -dione [prepared as described in Preparation 18], 1,39 g of tetrabutyl ammonium fluoride and 10 ml of tetrahydrofuran to obtain the title compound in crude form. This crude product was then purified by column chromatography through silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as the eluent, to give 180 mg of the title compound, having an Rf=0.28 (thin layer chromatography on silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as the developing solvent).
Reaction SMILES: Cl.[O:2]1CCO[CH:3]1[C:7]1[CH:8]=[C:9]([NH:13][C:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][N:17]=2)=[O:15])[CH:10]=[CH:11][CH:12]=1>>[CH:3]([C:7]1[CH:8]=[C:9]([NH:13][C:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][N:17]=2)=[O:15])[CH:10]=[CH:11][CH:12]=1)=[O:2]
Reactant: O=C(Nc1cccc(C2OCCO2)c1)c1ccc(F)cn1
Agent: Cl
Product: O=Cc1cccc(NC(=O)c2ccc(F)cn2)c1

Procedure:
The title compound is prepared by treatment with HCl 10% of 5-fluoro-pyridine-2-carboxylic acid (3-[1,3]dioxolan-2-yl-phenyl)-amide: LC-MS A: tR=0.79 min; [M+H]+=245.05.
Reaction SMILES: [N+:1]([CH:4]1[N:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][NH:5]1)([O-])=O>CO.N.CO>[NH2:1][CH:4]1[N:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][NH:5]1
Reactant: O=[N+]([O-])C1NC=CN1c1ccncc1
Agent: N
Solvent: CO
Product: NC1NC=CN1c1ccncc1
Yield: 83.7 %

Procedure:
A stirred solution of 2-nitro-3-(4-pyridinyl)-1H-imidazole (1.19 g, 6.26 mmol) in 7N methanol/NH3 (25 ml) and methanol (25 ml) was hydrogenated at room temperature on Raney Nickel (1 g) for 4 h. The catalyst was removed by filtration and the solution evaporated. The crude product was purified by column chromatography on silica gel (dichloromethane/methanol/NH4OH 40:10:1) to yield 2-amino-3-(4-pyridinyl)-1H-imidazole (0.85 g, 85%) as a green solid. MS (ISP) 161.2 [(M+H)+]; mp 190° C.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:10]2[CH2:11][CH2:12][O:13][C:9]=2[C:8]([C:14]([NH2:16])=O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>C1COCC1>[C:14]([C:8]1[C:9]2[O:13][CH2:12][CH2:11][C:10]=2[C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=1)#[N:16]
Reactant: CC(=O)Nc1ccc(C(N)=O)c2c1CCO2
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CC(=O)Nc1ccc(C#N)c2c1CCO2
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 71.1 %

Procedure:
To a suspension of compound 4A (3.5 g, 16 mmol) in THF (64 mL) at 0° C. under Ar was added pyridine (6.5 mL, 80 mmol), followed by trifluoroacetic anhydride (5.6 mL, 40 mmol) dropwise. After addition, the reaction mixture was stirred at 0° C. for 5 min, then pored into H2O (50 mL), extracted with EtOAc (3×100 mL). The combined EtOAc extracts were washed with brine, dried (Na2SO4), and concentrated under reduced pressure to give a crude product, which was purified by crystallization from MeOH-EtOAc-Hexane to furnish the title compound (2.3 g) as a white solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][C:8]([CH3:28])([CH3:27])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([CH2:19]S(C(F)(F)F)(=O)=O)[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:30]([NH2:34])(=[O:33])[CH:31]=C>>[C:1]([O:5][C:6]([NH:7][C:8]([CH3:28])([CH3:27])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([CH:19]=[CH:31][C:30]([NH2:34])=[O:33])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)=[O:29])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CC(N)=O
Reactant: CC(C)(Cc1c[nH]c2c(CS(=O)(=O)C(F)(F)F)cccc12)NC(=O)OC(C)(C)C
Product: CC(C)(Cc1c[nH]c2c(C=CC(N)=O)cccc12)NC(=O)OC(C)(C)C

Procedure:
3-[3-(2-tert-Butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl]-acrylamide is prepared from [1,1-dimethyl-2-(7-trifluoromethanesulfonylmethyl-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester and acrylamide as described for the preparation of Amine 23 (98%). FDMS m/e 356.2 (M++1).
Reaction SMILES: [NH2:1][C:2](=[N:27][N+:28]([O-:30])=[O:29])[NH:3][CH2:4][CH2:5][CH2:6][C@H:7]([C:24](O)=[O:25])[NH:8][C:9](=[O:23])[CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:31][NH:32][S:33]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][NH2:44])=[CH:39][CH:38]=1)(=[O:35])=[O:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[NH2:1][C:2](=[N:27][N+:28]([O-:30])=[O:29])[NH:3][CH2:4][CH2:5][CH2:6][C@H:7]([C:24]([NH:44][CH2:43][C:40]1[CH:41]=[CH:42][C:37]([CH2:36][S:33]([NH:32][CH3:31])(=[O:35])=[O:34])=[CH:38][CH:39]=1)=[O:25])[NH:8][C:9](=[O:23])[CH:10]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: NC(=N[N+](=O)[O-])NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)O
Reactant: CNS(=O)(=O)Cc1ccc(CN)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Product: CNS(=O)(=O)Cc1ccc(CNC(=O)[C@@H](CCCNC(N)=N[N+](=O)[O-])NC(=O)C(c2ccccc2)c2ccccc2)cc1
Yield: 70 %

Procedure:
Prepared analogously to Example 6d) from (R)-N5 -[amino(nitroimino)methyl]-N2 -(diphenylacetyl)-ornithine, 4-(methylamino-sulphonylmethyl)benzenemethanamine and TBTU in a yield of 70% of theory. Colourless amorphous substance.
Reaction SMILES: C(O[C:6]([C:8]1[CH:18]=[C:17]([O:19][CH:20]([CH3:22])[CH3:21])[C:11]2[CH2:12][CH:13]([CH2:15][OH:16])[O:14][C:10]=2[CH:9]=1)=[O:7])(C)(C)C.[NH2:23][C:24]1[CH:28]=[CH:27][N:26]([CH3:29])[N:25]=1>>[CH3:29][N:26]1[CH:27]=[CH:28][C:24]([NH:23][C:6]([C:8]2[CH:18]=[C:17]([O:19][CH:20]([CH3:21])[CH3:22])[C:11]3[CH2:12][CH:13]([CH2:15][OH:16])[O:14][C:10]=3[CH:9]=2)=[O:7])=[N:25]1
Reactant: Cn1ccc(N)n1
Reactant: CC(C)Oc1cc(C(=O)OC(C)(C)C)cc2c1CC(CO)O2
Product: CC(C)Oc1cc(C(=O)Nc2ccn(C)n2)cc2c1CC(CO)O2

Procedure:
The title compound was prepared in a similar manner as described for Example 200, from 2-hydroxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester (215a) and 3-amino-1-methyl-pyrazole. 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1 H) 7.26-7.35 (m, 1 H) 6.95-7.05 (m, 1H) 6.76-6.86 (m, 2 H) 4.93-5.08 (m, 1 H) 4.59-4.71 (m, 1 H) 3.84-3.91 (m, 1 H) 3.83 (s, 3 H), 3.22 (dd, J=16.42, 9.60 Hz, 1 H) 2.89-3.02 (m, 1 H) 1.98 (t, J=6.44 Hz, 1 H) 1.35 (d, J=6.06 Hz, 6 H); LCMS for C17H21N3O4 m/z 332.20 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:27])/[CH:9]=[CH:10]/[C:11]2[CH:26]=[CH:25][C:14]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]3)=[O:16])=[CH:13][CH:12]=2)=[C:4]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:3]=1.C1COCC1.CC(C)=O>CCO.[Pt+3]=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:27])[CH2:9][CH2:10][C:11]2[CH:26]=[CH:25][C:14]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]3)=[O:16])=[CH:13][CH:12]=2)=[C:4]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:3]=1
Reactant: O=C(NC1CCC(O)CC1)c1ccc(/C=C/C(=O)c2ccc(Cl)cc2Nc2ccccc2)cc1
Agent: O=[Pt+3]
Solvent: CC(C)=O
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(NC1CCC(O)CC1)c1ccc(CCC(=O)c2ccc(Cl)cc2Nc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
A mixture of 4-[(E)-3-(4-chloro-2-phenylamino-phenyl)-3-oxo-propenyl]-N-(4-hydroxy-cyclohexyl)-benzamide (197 mg) and platinum (V) oxide (50 mg) in a mixture of EtOH, THF and acetone (100/50/100 mL) was stirred under H2 (balloon pressure) at RT for 1 h. The resulting mixture was filtered, and the filtrate concentrate under reduced pressure to yield 4-[3-(4-chloro-2-phenylamino-phenyl)-3-oxo-propyl]-N-(4-hydroxy-cyclohexyl)-benzamide (190 mg).
Reaction SMILES: CCCCC.C[Sn:7]([CH2:20][CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])([CH2:14][CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:8][CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11].[ClH:26].O>C1C=CC=CC=1>[CH3:11][C:10]([CH3:13])([CH3:12])[CH2:9][CH2:8][Sn:7]([Cl:26])([CH2:20][CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14][CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17]
Reactant: Cl
Reactant: CC(C)(C)CC[Sn](C)(CCC(C)(C)C)CCC(C)(C)C
Solvent: c1ccccc1
Solvent: O
Solvent: CCCCC
Product: CC(C)(C)CC[Sn](Cl)(CCC(C)(C)C)CCC(C)(C)C
Temperature: 25 °C
Yield: 90 %

Procedure:
Tris(3,3-dimethylbutyl)tin chloride was prepared by the gradual addition of stannic chloride (13.0 g., 0.05 mole) dissolved in 50 c.c. pentane to a solution containing 19.5 g. (0.05 mole) of methyl tris(3,3-dimethylbutyl)tin dissovled in 50 c.c. pentane. The addition required 20 minutes and was performed under a nitrogen atmosphere. External cooling was applied as necessary to maintain the temperature of the reaction mixture below 27° C. Following completion of the addition the resulant mixture was heated at the boiling point for 0.5 hour, then allowed to cool to ambient temperature. A solution containing 2 c.c. of 12 normal aqueous hydrochloric acid and 100 c.c. water was added to the reaction mixture over a three minute period, followed by 50 c.c. of benzene. The organic liquid phase was separated, combined with 102 c.c. of an aqueous hydrochloric acid solution as previously described, after which the organic solvent was separated, dried using a portion of anhydrous magnesium sulfate and the organic solvents removed under reduced pressure. A 10 g. portion of the resultant white solid residue, obtained in 90% yield, was recrystallized from 100 c.c. of hexane and exhibited the following analysis, by weight:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15](I)[CH:14]=2)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[N:20]1([C:15]2[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=2)[CH2:12][NH:11][C:9]2[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=[C:2]([Cl:1])[CH:10]=2)[CH:24]=[CH:23][N:22]=[CH:21]1
Reactant: NC(=O)c1cnc(Cl)cc1NCc1cccc(I)c1
Reactant: c1c[nH]cn1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CS(C)=O
Product: NC(=O)c1cnc(Cl)cc1NCc1cccc(-n2ccnc2)c1
Reaction time: 2 h
Yield: 51 %

Procedure:
A mixture of 6-chloro-4-(3-iodobenzylamino)nicotinamide (130 mg, 0.335 mmol), imidazole (30 mg, 0.441 mmol), 8-hydroxyquinoline (15 mg, 0.103 mmol), K2CO3 (60 mg, 0.434 mmol) and CuI (15 mg, 0.078 mmol) in DMSO (1 mL) was degassed with Ar, then was stirred at 130 C for 2 h. The mixture was purified by HPLC to give 4-(3-(1H-imidazol-1-yl)benzylamino)-6-chloronicotinamide (56 mg).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[OH-].[Na+].[I-].[K+].[CH:16](Cl)=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>CO>[CH:16]([C:3]1[C:2]([OH:1])=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1)=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCCCCCCC=CCl
Reactant: Oc1cccc2cccnc12
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CO
Product: CCCCCCCCCCC=Cc1ccc2cccnc2c1O
Temperature: 230 °C

Procedure:
One hundred forty five grams (1.0 mole) 8-hydroxyquinoline, 40 gm. sodium hydroxide, 500 ml. methanol and 5 gm. potassium iodide were combined in a two liter round bottom flask. To this was added 243 gm. dodecenyl chloride (as used in Example I) and the mixture stirred under reflux overnight. The product was filtered, taken up in ether and washed with 500 ml. Claisen's alkali (in five portions). The ether solution was washed several times with water until neutral, dried and the solvent stripped to yield 317.9 gm. of crude product. Of this amount, 310.9 gm. was distilled through a one foot Vigreaux after being heated in the pot to 230° C. and cooled to about 100° C. The fractions coming off at 197°-202° C., 0.7 mm. Hg. (51.1 gm.) and 202°-231° C., 0.8 mm. Hg. (96.8 gm.) consisted almost entirely of 7-dodecenyl-8-hydroxyquinoline.
Reaction SMILES: [OH:1][C:2]1[CH:38]=[CH:37][C:5]([C:6]([N:8]([CH:34]([CH3:36])[CH3:35])[C:9]2[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=2[CH:17]2[CH2:26][CH2:25][C:24]3[CH:23]=[C:22]([O:27]C(=O)C(C)(C)C)[CH:21]=[CH:20][C:19]=3[CH2:18]2)=O)=[CH:4][CH:3]=1.Cl[CH2:40][C:41]([N:43]1[CH2:48][CH2:47][CH:46]([CH3:49])[CH2:45][CH2:44]1)=O>>[CH:34]([N:8]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:40][CH2:41][N:43]2[CH2:48][CH2:47][CH:46]([CH3:49])[CH2:45][CH2:44]2)=[CH:38][CH:37]=1)[C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[CH:17]1[CH2:26][CH2:25][C:20]2[CH:21]=[C:22]([OH:27])[CH:23]=[CH:24][C:19]=2[CH2:18]1)([CH3:35])[CH3:36]
Reactant: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(N(C(=O)c2ccc(O)cc2)C(C)C)c1
Reactant: CC1CCN(C(=O)CCl)CC1
Product: COc1ccc(C2CCc3cc(O)ccc3C2)c(N(Cc2ccc(OCCN3CCC(C)CC3)cc2)C(C)C)c1
Yield: 66.5 %

Procedure:
Synthesized from pivalic acid 6-{2-[(4-hydroxybenzoyl)isopropylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (30 mg) and 2-chloro-1-(4-methylpiperidin-1-yl)ethanone (21 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (21 mg) was obtained.
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:36][CH2:37][CH:38]1[O:42][NH:41][C:40](=[O:43])[CH2:39]1>CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([NH:36][CH2:37][CH:38]2[O:42][NH:41][C:40](=[O:43])[CH2:39]2)=[O:21])=[CH:17][N:16]=1
Reactant: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)O)cn1
Reactant: NCC1CC(=O)NO1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)NCC2CC(=O)NO2)cn1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 5 %

Procedure:
To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.64 mmol) in DMF (2 mL) was added 1,1′-carbonyl-diimidazole (115 mg, 0.71 mmol) and the reaction mixture was stirred for 0.5 h at 80° C. After cooling to ambient temperature 5-aminomethyl-isoxazolidin-3-one (82 mg, 0.71 mmol) was added and stirring was continued for 1 h at this temperature and for 2 h at 80° C. It was diluted with ethyl acetate (10 mL) and washed with water (10 mL) and aqueous sodium chloride (saturated, 10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=40:60:0 to 0:90:10) afforded the title compound (13 mg, 5%) as a white solid. MS: m/e=409.3 [M+H]+.