Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH:6]=[C:7]([C:16]2[NH:24][C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[CH:17]=2)[C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1>[Pd].CO>[CH:1]1([CH2:6][CH:7]([C:16]2[NH:24][C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[CH:17]=2)[C:8]2[CH:9]=[C:10]([CH3:15])[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(C)cc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)c1
Agent: [Pd]
Solvent: CO
Product: Cc1cc(C)cc(C(CC2CCCC2)c2cc3cccnc3[nH]2)c1
Temperature: 50 °C
Yield: 25.8 %

Procedure:
A mixture of 2-[2-cyclopentyl-1-(3,5-dimethyl-phenyl)-vinyl]-1H-pyrrolo[2,3-b]pyridine (90 mg, 0.28 mmol) and 10% palladium on activated carbon (30 mg) in methanol (200 mL) was heated at 50° C. under hydrogen (50 psi) for 6 h. The mixture was cooled to room temperature, the catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[2-cyclopentyl-1-(3,5-dimethyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (23 mg, 25%): LC/MS m/e calcd for C22H26N [M+H]+ 319.47, observed 319.2; 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (br. s., 1H), 8.05 (d, J=7.8 Hz, 1H), 7.00-7.20 (m, 4H), 6.42 (s, 1H), 5.31 (s, 1H), 4.09 (t, J=7.8 Hz, 1H), 2.08-2.26 (m, 8H), 1.57-1.85 (m, 5H), 1.42-1.53 (m, 2H), 1.14-1.24 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[SH:15][C:16]1[S:17][CH:18]=[CH:19][CH:20]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Sc1cccs1
Product: CC(C)(C)OC(=O)N1CCC(Sc2cccs2)CC1

Procedure:
By a similar manner to Reference Example 35, 1-tert-butoxycarbonyl-4-hydroxypiperidine (1.01 g, 5.0 mmol) was reacted with 2-mercaptothiophene (0.70 g, 6.0 mmol) to give the titled compound as pale yellow oily substance (987 mg, 66%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]2[C:8]([CH3:22])([CH3:21])[N:9]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1.[O-:23][CH2:24][CH3:25].[Na+]>CN(C=O)C>[CH2:24]([O:23][C:2]1[N:7]=[C:6]2[C:8]([CH3:22])([CH3:21])[N:9]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1)[CH3:25]
Reactant: COc1ccc(CN2C(=O)c3ccc(Cl)nc3C2(C)C)cc1
Reactant: CC[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOc1ccc2c(n1)C(C)(C)N(Cc1ccc(OC)cc1)C2=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 88.9 %

Procedure:
To solution of 2-chloro-6-(4-methoxy-benzyl)-7,7-dimethyl-6,7-dihydro-pyrrolo[3,4-b]pyridin-5-one (intermediate A-16 [F], 3.15 g, 10 mmol) in DMF (30 mL) was added sodium ethoxide (1.02 g, 15 mmol) at room temperature. The reaction mixture was stirred at room temperature for 4 hours before it was quenched by water and extracted with EtOAc. The organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give title product (2.9 g, 89%) as a solid. MS: 327.2 (M+H+).
Reaction SMILES: CC(C)([O-])C.[K+].C(O[C:10]1[CH:24]=[CH:23][C:13]2[CH:14]3[CH2:20][CH2:19][CH:18](C=O)[CH2:17][CH:15]3[O:16][C:12]=2[C:11]=1F)C.O.Cl>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C1COCC1>[CH2:23]1[CH:13]2[CH:12]([O:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=32)[CH2:11][CH2:10][CH2:24]1
Reactant: CCOc1ccc2c(c1F)OC1CC(C=O)CCC21
Agent: CC(C)(C)[O-]
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: c1ccc2c(c1)OC1CCCCC21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
10.0 g (27.0 mmol) of ethyltriphenylphosphonium bromide are initially introduced in 100 ml of THF, and 2.98 g (26.0 mmol) of potassium tert-butoxide in 40 ml of THF are added at −5° C. After 1 h at this temperature, 6.50 g (24.6 mmol) of (±)-(3R*, 4aR*, 9bS*)-7-ethoxy-6-fluoro-1,2,3,4,4a,9b-hexahydrodibenzofuran-3-carbaldehyde as a solution in 60 ml of THF are added dropwise, and the batch is stirred at room temperature for 2 h. The reaction solution is hydrolysed using water and acidified using 2 N HCl. The mixture is extracted with MTBE, and the combined organic phases are dried using sodium sulfate. The crude product remaining after removal of the solvents is filtered adsorptively (SiO2, toluene), and the filtrate is concentrated to dryness. Recrystallisation of the residue from methanol gives (±)-(3R*, 4aR*, 9bS*)-7-ethoxy-6-fluoro-3-propenyl)-1,2,3,4,4a,9b-hexahydrodibenzofuran as E/Z isomer mixture.
Reaction SMILES: [C:1]1([C:7]2[N:11]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:10]=[C:9]([CH:25]=[O:26])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:27]N1C(=O)CCC1=O.O>CN(C)C=O>[Cl:27][C:10]1[N:11]([S:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=2)(=[O:13])=[O:14])[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][C:9]=1[CH:25]=[O:26]
Reactant: O=Cc1cc(-c2ccccc2)n(S(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
Reactant: O=C1CCC(=O)N1Cl
Solvent: O
Solvent: CN(C)C=O
Product: O=Cc1cc(-c2ccccc2)n(S(=O)(=O)c2ccc(C(F)(F)F)cc2)c1Cl
Reaction time: 24 h
Yield: 61.1 %

Procedure:
5-Phenyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}-1H-pyrrole-3-carbaldehyde (300 mg) was dissolved in N,N-dimethylformamide (6 mL), N-chlorosuccinimide (116 mg) was added at room temperature, and the mixture was stirred for 24 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 3% potassium hydrogensulfate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→4:1) to give the title compound as colorless crystals (yield 200 mg, 61%).
Reaction SMILES: [C@H:1]12[O:7][C@H:4]([CH:5]=[CH:6]1)[CH2:3][C@H:2]2[C:8]([OH:10])=[O:9]>C(O)C.[Pd]>[C@H:1]12[O:7][C@@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[C:8]([OH:10])=[O:9]
Reactant: O=C(O)[C@@H]1C[C@H]2C=C[C@@H]1O2
Agent: [Pd]
Solvent: CCO
Product: O=C(O)[C@@H]1C[C@@H]2CC[C@@H]1O2

Procedure:
A solution of 1 mmol of (1S,2R,4S)-7-oxabicyclo[2.2.1]-hept-5-ene-2-carboxylic acid [185840-15-7] in 30 ml of ethanol is hydrogenated in the presence of 0.150 g of Pd/C 10% at room temperature until conversion is complete. The reaction mixture is clarified by filtration, and the filtrate is evaporated. The title compound is obtained from the residue by flash chromatography (SiO2 60 F).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[CH:10]1([NH2:13])[CH2:12][CH2:11]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.[ClH:41].Cl.Cl.[Cl:44][C:45]1[C:46]([C:62]2[S:66][C:65]3[CH:67]=[C:68]([C:71](O)=[O:72])[CH:69]=[CH:70][C:64]=3[CH:63]=2)=[N:47][C:48]([NH:51][CH2:52][CH2:53][CH2:54][N:55]2[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]2)=[N:49][CH:50]=1.[Li+].[Cl-]>CN(C=O)C>[ClH:44].[ClH:41].[ClH:44].[CH:10]1([NH:13][C:71]([C:68]2[CH:69]=[CH:70][C:64]3[CH:63]=[C:62]([C:46]4[C:45]([Cl:44])=[CH:50][N:49]=[C:48]([NH:51][CH2:52][CH2:53][CH2:54][N:55]5[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]5)[N:47]=4)[S:66][C:65]=3[CH:67]=2)=[O:72])[CH2:12][CH2:11]1
Reactant: NC1CC1
Reactant: CN1CCN(CCCNc2ncc(Cl)c(-c3cc4ccc(C(=O)O)cc4s3)n2)CC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN1CCN(CCCNc2ncc(Cl)c(-c3cc4ccc(C(=O)NC5CC5)cc4s3)n2)CC1
Temperature: 25 °C

Procedure:
Diisopropylethylamine (0.210 mL, 1.20 mmol), cyclopropylamine (0.090 mL, 1.3 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (205 mg, 0.460 mmol) are added successively to a stirred suspension of 2-{5-chloro-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid tri-hydrochloride. (195 mg, 0.400 mmol) and LiCl (187 mg, 4.40 mmol) in DMF (4 mL) at ambient temperature under nitrogen, the resultant mixture is heated at 50° C. for 20 hours. After cooling to ambient temperature, the solvent is removed and the residue is subject to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, to give the free base of the title compound (97 mg). ES+(m/z) 485 (35Cl) and 487 (37Cl) [M+H]. Using the method of Preparation (E) in 2-{5-chloro-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid cyclopropylamide tri-hydrochloride, the free base is converted to the tri-hydrochloride salt as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[C:15]([S:24]([CH3:27])(=[O:26])=[O:25])=[N:16][N:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[NH2:43][C:44]1[CH:49]=[CH:48][C:47](Br)=[CH:46][N:45]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:43][C:44]1[N:45]=[CH:46][C:47]([C:31]2[CH:32]=[CH:33][C:28]([C:9]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[C:13](=[O:14])[C:12]4[C:15]([S:24]([CH3:27])(=[O:25])=[O:26])=[N:16][N:17]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[C:11]=4[N:10]=3)=[CH:29][CH:30]=2)=[CH:48][CH:49]=1
Reactant: Nc1ccc(Br)cn1
Reactant: CC1(C)OB(c2ccc(-c3nc4c(c(S(C)(=O)=O)nn4-c4ccccc4)c(=O)n3-c3ccc(Cl)cc3)cc2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Product: CS(=O)(=O)c1nn(-c2ccccc2)c2nc(-c3ccc(-c4ccc(N)nc4)cc3)n(-c3ccc(Cl)cc3)c(=O)c12
Temperature: 80 °C

Procedure:
A reaction tube charged with 5-(4-chloro-phenyl)-3-methanesulfonyl-1-phenyl-6-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (200.0 mg, 0.332 mmol), 2-amino-5-bromopyridine (114.8 mg, 0.664 mmol), Cs2CO3 (162.1 mg, 0.498 mmol), and Pd(dppf)2Cl2 (54.2 mg, 0.066 mmol) is purged with nitrogen. Anhydrous DMF (3.3 mL) is added via syringe. The reaction mixture is heated at 80° C. for 2 h, cooled down to room temperature, poured into water (30 mL) and EtOAc (30 mL). The insoluble solid is filtered off and the two layers of the filtrate are separated. The aqueous layer is extracted with EtOAc (2×30 mL). The combined organic phase is washed with brine, dried over MgSO4, concentrated, and purified by reverse phase HPLC to provide 6-[4-(6-amino-pyridin-3-yl)-phenyl]-5-(4-chloro-phenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one as a light yellow solid product; 1H NMR (CDCl3, 400 MHz) δ 8.21 (d, 1H), 8.11 (d, 2H), 7.71 (dd, 1H), 7.54 (t, 2H), 7.44 (t, 1H), 7.41 (m, 4H), 7.36 (d, 2H), 7.16 (d, 2H), 6.67 (d, 1H), 5.22 (br, 2H), 3.55 (s, 3H); HPLC-MS calculated for C29H21ClN6O3S (M+H+) 569.1, found 569.1.
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([OH:28])=O)=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:64][O:65][C@H:66]([CH2:69][N:70]1[CH2:75][CH2:74][N:73]([CH3:76])[CH2:72][CH2:71]1)[CH2:67][NH2:68].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:26]([NH:68][CH2:67][C@H:66]([O:65][CH3:64])[CH2:69][N:70]5[CH2:75][CH2:74][N:73]([CH3:76])[CH2:72][CH2:71]5)=[O:28])=[C:21]5[C:25]=4[O:24][CH2:23][CH2:22]5)[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8](=[O:30])[C@H:7]2[CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CO[C@@H](CN)CN1CCN(C)CC1
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)O)c4c3OCC4)nc2N1C1CCCC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=C([O-])[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)NC[C@@H](CN4CCN(C)CC4)OC)c4c3OCC4)nc2N1C1CCCC1
Reaction time: 2 h
Yield: 28.7 %

Procedure:
7-[[(7R)-8-Cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxylic acid 1q (100 mg, 0.23 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetra methyluronium tetrafluoroborate (74 mg, 0.23 mmol) were dissolved in 20 mL of anhydrous dichloromethane followed by the addition of diisopropylethylamine (0.1 mL, 0.50 mmol) and the crude compound (2S)-2-methoxy-3-(4-methylpiperazin-1-yl)propan-1-amine 38b (43 mg, 0.23 mmol) successively. The reaction solution was stirred for 2 hours, added with 30 mL saturated sodium carbonate solution and extracted with dichloromethane (20 mL×3). The combined organic phase was washed with saturated sodium chloride solution (20 mL), then dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 7-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-N-[(2S)-2-methoxy-3-(4-methylpiperazin-1-yl)propyl]-2,3-dihydrobenzofuran-4-carboxamide 38 (40 mg, yield: 30.0%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6]Cl.[C:15]1([CH:21]2[CH2:26][NH:25][CH2:24][C:23]3[S:27][CH:28]=[CH:29][C:22]2=3)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[C:15]1([CH:21]2[CH2:26][N:25]([CH2:6][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:10]([O:11][CH3:12])=[C:9]([O:13][CH3:14])[CH:8]=3)[CH2:24][C:23]3[S:27][CH:28]=[CH:29][C:22]2=3)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: c1ccc(C2CNCc3sccc32)cc1
Reactant: COc1cc(CCl)cc(OC)c1OC
Product: COc1cc(CN2Cc3sccc3C(c3ccccc3)C2)cc(OC)c1OC

Procedure:
3,4,5-Trimethoxy-benzyl chloride is condensed with 4-phenyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine (Example 3), according to the procedure of Example 8.
Reaction SMILES: [CH3:1][C:2]1([CH3:29])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]([CH2:16][O:17][C:18]3[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=3[CH3:28])[C:21]([O:23][CH3:24])=[O:22])=[O:15])[CH:5]=[CH:4][C:3]1=2.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:48]N1C(=O)CCC1=O.O>C(Cl)(Cl)(Cl)Cl.ClCCl>[CH3:1][C:2]1([CH3:29])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([C:14]([CH2:16][O:17][C:18]3[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=3[CH2:28][Br:48])[C:21]([O:23][CH3:24])=[O:22])=[O:15])[CH:5]=[CH:4][C:3]1=2
Reactant: COC(=O)c1ccc(C)c(OCC(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(CBr)c(OCC(=O)c2ccc3c(c2)C(C)(C)CCC3(C)C)c1

Procedure:
A solution of methyl 3-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoyl)methyloxy]-4-methylbenzoate (7.02 g, 16.7 mmol), benzoyl peroxide (0.02 g) and N-bromosuccinimide (4.28 g, 24 mmol) in carbon tetrachloride (370 ml) was heated at reflux and irradiated with a 1000 W lamp for forty five minutes. 350 ml of water and 250 ml of dichloromethane were added. After separation of the phases once settling had taken place, the organic phase was washed twice with 350 ml of water and dried over magnesium sulfate. After concentration on a rotary evaporator at 40° C. under vacuum, the three products obtained were purified by flash chromatography (CH2Cl2) and then by HPLC (70% CH2Cl2, 30% heptane). The properties of the monobromo benzyl compound were as follows:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=1.Br[C:22]1[CH:23]=[C:24]([CH:32]([CH3:34])[CH3:33])[CH:25]=[C:26]2[C:31]=1[N:30]=[CH:29][CH:28]=[CH:27]2.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.C(OCC)(=O)C.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>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:22]2[CH:23]=[C:24]([CH:32]([CH3:34])[CH3:33])[CH:25]=[C:26]3[C:31]=2[N:30]=[CH:29][CH:28]=[CH:27]3)[CH:6]=1
Reactant: COC(=O)Cc1cccc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: CC(C)c1cc(Br)c2ncccc2c1
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: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)Cc1cccc(-c2cc(C(C)C)cc3cccnc23)c1
Temperature: 21 °C

Procedure:
A solution of [3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid methyl ester from Step 2 (4 g, 14 mmol), 8-bromo-6-isopropylquinoline (3 g, 12 mmol), Na2CO3 (2M, 18 mL, 36 mmol) and Pd(PPh3)4 (692 mg, 0.6 mmol) in DMF (250 mL) was heated at 80° C. under N2 for 18 h. The resulting reaction mixture was cooled to 21° C. and diluted with water and ethyl acetate. The organic extracts were washed (H2O, brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (eluting with hexane/ethyl acetate, 80:20) provided the [3-(6-Isopropyl-quinolin-8-yl)-phenyl]-acetic acid methyl ester compound.
Reaction SMILES: NC1CCC2C(=CC=CC=2O[Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)C1.C1(C2N=C(CBr)OC=2C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[C:55]1([C:61]2[N:62]=[C:63]([CH2:72][NH:73][CH:74]3[CH2:83][CH2:82][C:81]4[C:76](=[CH:77][CH:78]=[CH:79][C:80]=4[O:84][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[CH2:75]3)[O:64][C:65]=2[C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C=O)C.C1COCC1>[C:55]1([C:61]2[N:62]=[C:63]([CH2:72][NH:73][CH:74]3[CH2:83][CH2:82][C:81]4[C:76](=[CH:77][CH:78]=[CH:79][C:80]=4[OH:84])[CH2:75]3)[O:64][C:65]=2[C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1
Reactant: CC(C)(C)[Si](Oc1cccc2c1CCC(NCc1nc(-c3ccccc3)c(-c3ccccc3)o1)C2)(c1ccccc1)c1ccccc1
Agent: BrCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Agent: CC(C)(C)[Si](Oc1cccc2c1CCC(N)C2)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Oc1cccc2c1CCC(NCc1nc(-c3ccccc3)c(-c3ccccc3)o1)C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2-amino-5-t-butyldiphenylsilyloxy-1,2,3,4-tetrahydronaphthalene (0.96 g), (4,5-diphenyloxazol-2-yl)methyl bromide (0.80 g) and potassium carbonate (0.41 g) in DMF (14 ml) was stirred for 3.5 hours at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine. The dried solvent was evaporated in vacuo to give crude 2-[(4,5-diphenyloxazol-2-yl)methylamino]-1,2,3,4-tetrahydro-5-t-butyldiphenylsilyloxynaphthalene. To a solution of crude 2-[(4,5-diphenyloxazol-2-yl)methylamino]-1,2,3,4-tetrahydro-5-t-butyldiphenylsilyloxynaphthalene in THF (5 ml) was added 1M THF (3 ml) solution of tetrabutylammonium fluoride. After being stirred for 1 hour at room temperature, the mixture was partitioned between ethyl acetate and sat. NaHCO3. The organic layer was washed with brine. The dried solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel to give 2-[(4,5-diphenyloxazol-2-yl)methylamino]-1,2,3,4-tetrahydro-5-hydroxynaphthalene (0.66 g). MS (m/z): 397 (M+ +1) NMR (CDCl3, δ): 1.54-1.84 (2H, m), 2.08-2.22 (1H, m), 2.48-3.20 (5H, m), 4.13 (2H, s), 6.58 (1H, d, J=7.8 Hz), 6.68 (1H, d, J=7.8 Hz), 6.99 (1H, dd, J=7.8, 7.8 Hz), 7.34-7.40 (6H, m), 7.55-7.66 (4H, m)
Reaction SMILES: [OH:1][CH:2]1[N:6]([C:7]2[N:8]=[N:9][C:10]([O:13][CH3:14])=[CH:11][CH:12]=2)[C:5](=[O:15])[C:4]2[S:16][CH2:17][CH2:18][S:19][C:3]1=2.[H-].[Na+].Cl[C:23]([N:25]1[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24].C(O)C>O1CCCC1>[CH3:14][O:13][C:10]1[N:9]=[N:8][C:7]([N:6]2[CH:2]([O:1][C:23]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)=[O:24])[C:3]3[S:19][CH2:18][CH2:17][S:16][C:4]=3[C:5]2=[O:15])=[CH:12][CH:11]=1
Reactant: COc1ccc(N2C(=O)C3=C(SCCS3)C2O)nn1
Reactant: CN1CCN(C(=O)Cl)CC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: COc1ccc(N2C(=O)C3=C(SCCS3)C2OC(=O)N2CCN(C)CC2)nn1
Temperature: 5 °C
Reaction time: 4 h
Yield: 60.7 %

Procedure:
A solution of 5-hydroxy-6-(6-methoxypyridazin-3-yl)-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (8.9 g.) in anhydrous tetrahydrofuran (90 cc.) is treated for 30 minutes at about 15°-20°C, with sodium hydride (0.87 g.), and a solution of 1-chlorocarbonyl-4-methylpiperazine (19.5 g.) in anhydrous tetrahydrofuran (120 cc.) is then added, at 5°C. The reaction mixture is stirred for 4 hours at 5°C. After evaporating the solvent under reduced pressure (20 mm.Hg), the residue is taken up in an ice-cold normal aqueous solution of methanesulphonic acid (150 cc.). The acid solution obtained is rapidly washed twice with diethyl ether (total 100 cc.) and then rendered alkaline by adding 10N sodium hydroxide solution (25 cc.). The oil which separates out is extracted three times with methylene chloride (total 300 cc.). The combined organic extracts are washed twice with distilled water (total 100 cc.), dried over anhydrous magnesium sulphate and evaporated. The crystals obtained (8.7 g.; m.p. 196°-198°C.) are dissolved in boiling ethanol (300 cc.). After filtering the boiling solution and then cooling it for three hours at 2°C, the crystals which have appeared are filtered off, washed three times with ice-cold ethanol (total 45 cc.) and dried under reduced pressure (20mm.Hg). 6-(6-Methoxypyridazin-3-yl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole (7.7 g.), melting at 200°C, is thus obtained.
Reaction SMILES: [Sb:1](=O)([O-])([O-])[O-].[Na+].[Na+].[Na+].[Sb].[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21])(=[O:13])[CH2:11][SH:12].Cl>>[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21])(=[O:13])[CH2:11][SH:12].[Sb+5:1]
Reactant: O=[Sb]([O-])([O-])[O-]
Agent: CC(C)CCCCCOC(=O)CS
Agent: Cl
Agent: [Na+]
Product: [Sb+5]
Temperature: 12 °C
Reaction time: 3.5 h

Procedure:
Sodium antimonate obtained from U.S. Antimony Corporation (19.2 g, 0.0476 mole) was placed in a reaction vessel and isooctyl thioglycolate from Evans Chemetics, Inc. (97.08 g, 0.4759 mole) added and stirred. Concentrated hydrochloric acid from Fisher Scientific Co. (9.5 ML, 0.0952 mole) was added dropwise and an immediate temperature increase of 12° C. was observed. The mixture was heated and the byproduct, water, was distilled over at 97° C. and collected. After 3.5 hours, a 93% yield of antimony (V) isooctyl thioglycolate was obtained. The resultant product was filtered to remove unreacted sodium antimonate and the additional byproduct of the reaction, sodium chloride. The product was then vacuum distilled at 3 mm Hg and a temperature range of 24°-100° C. to remove any unreacted isooctyl thioglycolate.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12](Cl)[C:11]([Cl:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:3])[CH3:2].[CH:20]([NH2:23])([CH3:22])[CH3:21]>CS(C)=O>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([NH:23][CH:20]([CH3:22])[CH3:21])[C:11]([Cl:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)c(Cl)cc1[N+](=O)[O-]
Reactant: CC(C)N
Solvent: CS(C)=O
Product: CC(C)Nc1cc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])cc1Cl

Procedure:
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and isopropylamine (7.0 ml, 81.4 mmol) in DMSO (35 mL) at 55° C. according to the general procedure C. Obtained as a brown solid (3.95 g, 73%).