Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1COC23OCCOC2([C@]2(CC[C@H]4[C@@H](CC(=C)[C@]5(O)[C@]4(C)CCCC5)[C@@H]2C3)C)[O:2]1.[CH2:30]=[C:31]1[CH:48]2[C@:43]([CH3:50])([CH2:44][CH2:45][C:46](=[O:49])[CH2:47]2)[C@@H:42]2[C@H:33]([C@H:34]3[C@@:38]([CH2:40][CH2:41]2)([CH3:39])[C:37](=[O:51])[CH2:36][CH2:35]3)[CH2:32]1>>[OH:2][C@:48]12[CH2:47][C:46](=[O:49])[CH2:45][CH2:44][C@:43]1([CH3:50])[C@@H:42]1[C@H:33]([C@H:34]3[C@@:38]([CH2:40][CH2:41]1)([CH3:39])[C:37](=[O:51])[CH2:36][CH2:35]3)[CH2:32][C:31]2=[CH2:30]
Reactant: C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)CC12
Reactant: C=C1C[C@H]2[C@@H]3CC45OCCOC4(OCCO5)[C@@]3(C)CC[C@@H]2[C@@]2(C)CCCC[C@]12O
Product: C=C1C[C@H]2[C@@H]3CCC(=O)[C@@]3(C)CC[C@@H]2[C@@]2(C)CCC(=O)C[C@]12O
Yield: 85 %

Procedure:
The title compound II-ap was prepared in 85% yield from 3,3:17,17-bis(ethylendioxy)-5α-hydroxy-6-methyleneandrostane by the procedure described above for the preparation of 6-methyleneandrostane-3,17-dione (II-ac, Prepn. 13). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography (SiO2, n-hexane/AcOEt 60/40). 1H-NMR (300 MHz, DMSO-d6, ppm from TMS): δ 4.91 (1H, s), 4.81 (1H, bs), 4.58 (1H, bs), 2.82 (1H, d), 2.42-1.10 (17H, m), 0.94 (3H, s), 0.77 (3H, s).
Reaction SMILES: [CH2:1]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-:13]#[N:14].[K+].[NH4+:16].[Cl-]>CO>[NH2:16][C:10]1([C:13]#[N:14])[CH2:11][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9]1
Reactant: [C-]#N
Reactant: [NH4+]
Reactant: O=C1CN(Cc2ccccc2)C1
Agent: [Cl-]
Agent: [K+]
Solvent: CO
Product: N#CC1(N)CN(Cc2ccccc2)C1
Temperature: -78 °C
Yield: 11.7 %

Procedure:
1-Benzyl-3-oxo-azetidine (1.6 g, 10 mmol, 1.0 equiv), prepared as described in the literature (Katritzky, A. R.; Cundy, D. J.; J. Heterocyclic Chem. 1994, 31 271-275), was dissolved in dry MeOH and the solution was cooled to −78° C. Gaseous ammonia was was bubbled through the solution for 30 mins at which time 3 angstrom molecular sieves were added and the mixture transferred to a pressure tube. The solution was heated for 30 min at 60° C. The mixture was cooled to −78° C., the tube opened and KCN (0.65 g, 10 mmol, 1.0 equiv) and NH4Cl (0.27 g, 5 mmol, 0.5 equiv) were added and the tube was resealed and heated at 60° C. for 4 h. The reaction mixture was filtered and the filtrate was evaporated. The crude residue was purified by flash chromatography using 2% MeOH in CH2Cl2 to give the desired product (0.11 g, 6%) as a brown oil; MS, m/z 188=M+1.
Reaction SMILES: C([C:8]1([C:25]2[CH:30]=[CH:29][C:28]3[O:31][CH2:32][O:33][C:27]=3[CH:26]=2)[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH3:20])=[CH:14][CH:15]=2)[C:10](=[O:21])[CH:9]1C([O-])=O)C1C=CC=CC=1.C1CC=CCC=1>C(O)(=O)C>[CH2:32]1[O:31][C:28]2[CH:29]=[CH:30][C:25]([CH:8]3[C:16]4[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][CH3:20])=[CH:14][CH:15]=4)[C:10](=[O:21])[CH2:9]3)=[CH:26][C:27]=2[O:33]1
Reactant: CCCOc1ccc2c(c1)C(=O)C(C(=O)[O-])C2(Cc1ccccc1)c1ccc2c(c1)OCO2
Solvent: C1=CCC=CC1
Solvent: CC(=O)O
Product: CCCOc1ccc2c(c1)C(=O)CC2c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
To a solution of benzyl-(1RS,2SR)-(3,4-methylenedioxyphenyl)-5-prop-1-yloxy-3-oxo-indane-2-carboxylate (8.2 g, 18.4 mmol) in warm acetic acid (130 ml), was added under argon 10% Pd/C (4.1 g) followed by 1,4-cyclohexadiene (17.4 ml, 185 mmol). The reaction was exothermic and gas evolution was observed. The reaction was allowed to stir under argon at room temperature for 2 h. The mixture was filtered through a pad of celite and concentrated in vacuo. Flash chromatography of the residue (silica gel, 3:7 ethyl acetate:hexane) afforded the title compound as a pinkish solid (5.08 g, 93%).
Reaction SMILES: [Cl:1][C:2]1[C:7](Cl)=[CH:6][C:5]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.[Cl:19][C:20]1[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[CH:22][C:21]=1[OH:28].[OH-].[Na+].CS(C)=O>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[C:4]([N+:16]([O-:18])=[O:17])[C:5]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:7]=1[O:28][C:21]1[CH:22]=[C:23]([Cl:27])[C:24]([Cl:26])=[CH:25][C:20]=1[Cl:19]
Reactant: O=[N+]([O-])c1cc(Cl)c(Cl)cc1Oc1ccccc1
Reactant: Oc1cc(Cl)c(Cl)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: O=[N+]([O-])c1cc(Cl)c(Oc2cc(Cl)c(Cl)cc2Cl)cc1Oc1ccccc1
Temperature: 150 °C
Reaction time: 6 h

Procedure:
A mixture of 28.4 gm of 4,5-dichloro-2-nitro-1-phenoxy-benzene, 21.6 gm of 2,4,5-trichloro-phenol, 10 ml of 10 N sodium hydroxide and 80 ml of dimethylsulfoxide was stirred for 6 hours at 150° C. and then allowed to stand overnight at room temperature. Thereafter, the reaction mixture was stirred into 600 ml of water, the aqueous mixture was made alkaline, and the precipitated reaction product was taken up in chloroform. The organic phase was washed with water, dried and evaporated, and the residue was recrystallized from 200 ml of ethanol, yielding 43 gm (97% of theory) of the light yellow crystalline title compound, m.p. 84° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:28])[CH2:5][N:6]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=2[C:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:9][CH2:8][C:7]1=O)[CH3:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:30].N1C=CC=CC=1>C(Cl)Cl.O>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][N:6]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=2[C:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:9][CH2:8][C:7]1=[S:30])[CH3:2]
Reactant: CCOC(=O)CN1C(=O)CN=C(c2ccccc2)c2cc(C(F)(F)F)ccc21
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: O
Product: CCOC(=O)CN1C(=S)CN=C(c2ccccc2)c2cc(C(F)(F)F)ccc21

Procedure:
A mixture of 0.01 mole of 7-trifluoromethyl-2,3dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-1-acetic acid ethyl ester and 0.0105 mole of phosphorus pentasulfide and 100 ml. of pyridine is heated under reflux for about 24 hours. The mixture is evaporated and the residue thus obtained is dissolved in methylene chloride-water. The organic layer is separated, washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate and evaporated to remove the solvent. The residue thus obtained is chromatographed on silica gel and eluted to give 2,3-dihydro-5-phenyl-2-thioxo-7-(trifluoromethyl)-1H-1,4-benzodiazepin-1-acetic acid ethyl ester.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH:13]([CH2:16][OH:17])[CH2:14][OH:15])=[CH:8][CH:7]=[CH:6]2.[C:18]1(C)C=CC(S(O)(=O)=O)=CC=1.COC(OC)[CH2:32][NH:33][C:34](=[O:36])[CH3:35]>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH:13]1[CH2:16][O:17][CH:32]([NH:33][C:34](=[O:36])[CH2:35][CH3:18])[O:15][CH2:14]1)=[CH:8][CH:7]=[CH:6]2
Reactant: COc1ccc2c(C(CO)CO)cccc2c1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: COC(CNC(C)=O)OC
Solvent: c1ccccc1
Product: CCC(=O)NC1OCC(c2cccc3cc(OC)ccc23)CO1

Procedure:
2.3 g (10 mmol) of 2-(6-methoxynaphthalen-1-yl)propane-1,3-diol, 0.45 g of paratoluenesulphonic acid and 1.6 g (11 mmol) of N-(2,2-dimethoxyethyl)acetamide are introduced into a flask containing 200 ml of benzene.
Reaction SMILES: C([N:8]1[CH2:13][CH:12]=[C:11]([CH2:14][C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.[Cl:20]C(OC(Cl)C)=O>ClCCl.O.CO>[ClH:20].[S:16]1[CH:17]=[CH:18][CH:19]=[C:15]1[CH2:14][C:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=1
Reactant: C1=C(Cc2cccs2)CCN(Cc2ccccc2)C1
Reactant: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CO
Product: C1=C(Cc2cccs2)CCNC1
Product: Cl
Temperature: 27.5 °C
Reaction time: 3 h
Yield: 94.5 %

Procedure:
To a stirred solution of 1-benzyl-4-(thiophen-2-ylmethyl)-1,2,3,6-tetra hydropyridine (1) (3.3 g, 12.26 mmol) in dichloromethane (30 mL) was added 1-chloroethyl chloroformate (12.27 g, 85.87 mmol) at 0° C. and the reaction mixture was allowed to stir at 20-35° C. for 3 h. Then the reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (50 mL). The organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was rotary evaporated to get residue; which was dissolved in methanol (20 mL) and heated at 70-80° C. for 1 h. The reaction mixture was rotary evaporated under vacuum to get residue which was triturated with diethyl ether to get the desired compound as a brown solid (2.5 g); 1H NMR (400 MHz, DMSO-d6) δ 9.04-8.92 (m, 2H), 7.38 (dd, J=1.5, 5.4 Hz, 1H), 6.97 (dd, J=3.4, 5.4 Hz, 1H), 6.90 (dd, J=1.0, 3.4 Hz, 1H), 5.54 (s, 1H), 3.56 (s, 2H), 3.54-3.52 (m, 2H), 3.14-3.11 (m, 2H), 2.24-2.16 (m, 2H).
Reaction SMILES: OS([O-])=O.[Na+].O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]([C:17](=[O:19])[CH3:18])[CH:11]=[CH:10]2.[CH3:20][NH:21][CH2:22][CH2:23][OH:24]>O.C(OCC)(=O)C>[OH:24][CH2:23][CH2:22][N:21]([CH3:20])[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]([C:17](=[O:19])[CH3:18])[CH:11]=[CH:10]2
Reactant: CNCCO
Reactant: CC(=O)c1ccc2cc(O)ccc2c1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)c1ccc2cc(N(C)CCO)ccc2c1
Yield: 73 %

Procedure:
A mixture of 4.15 g (55.5 mmol) NaHSO3, 8 mL of water, 0.78 g (4.19 mmol) of 1-(6-hydroxy-2-naphthyl)-1-ethanone (prepared as described in Example 1(b)), and 8 mL of 2-methylaminoethanol was heated and stirred in a steel bomb at 140° C. for 28 hours. After cooling, the mixture was distributed between ethyl acetate and water (500 mL and 200 mL, respectively). The organic layer was dried and evaporated to leave raw 1-(6-(2-hydroxyethyl-methylamino)-2-naphthyl)-1-ethanone (0.749 g, 73%) of which was further purified by radial chromatography (4 mm SiO2, CH2Cl2).
Reaction SMILES: [Cl:1][C:2]1[N:3]([CH2:10][C@:11]2([CH3:14])[CH2:13][O:12]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[F:15][C:16]([F:31])([F:30])[C:17]1[CH:29]=[CH:28][C:20]([O:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:19][CH:18]=1.O>CN(C=O)C>[Cl:1][C:2]1[N:3]([CH2:10][C@@:11]([CH3:14])([OH:12])[CH2:13][N:25]2[CH2:24][CH2:23][CH:22]([O:21][C:20]3[CH:19]=[CH:18][C:17]([C:16]([F:15])([F:30])[F:31])=[CH:29][CH:28]=3)[CH2:27][CH2:26]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1
Reactant: FC(F)(F)c1ccc(OC2CCNCC2)cc1
Reactant: C[C@@]1(Cn2cc([N+](=O)[O-])nc2Cl)CO1
Solvent: O
Solvent: CN(C)C=O
Product: C[C@](O)(CN1CCC(Oc2ccc(C(F)(F)F)cc2)CC1)Cn1cc([N+](=O)[O-])nc1Cl
Yield: 99.6 %

Procedure:
(R)-2-Chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 12 (500 mg, 2.30 mmol) and 4-(4-trifluoromethylphenoxy)piperidine (730 mg, 3.0 mmol) in DMF (10 ml) were stirred at 70-75° C. for 5 hours. The reaction mixture was allowed to return to room temperature, poured into water, and extracted with ethyl acetate. The extract was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) to afford (S)-1-(2-chloro-4-nitroimidazol-1-yl)-2-methyl-3-[4-(4-trifluoromethylphenoxy)piperidin-1-yl]propan-2-ol (1.06 g, yield 99%) as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[C:14]([F:16])=[CH:15][C:10]=3[N:9]=[C:8]2[CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:4][CH:3]=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>ClCCl>[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([N:17]4[CH2:22][CH2:21][N:20]([C:36]([CH:33]5[CH2:35][CH2:34]5)=[O:37])[CH2:19][CH2:18]4)[C:14]([F:16])=[CH:15][C:10]=3[N:9]=[C:8]2[CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)C1CC1
Reactant: Fc1cc2nc(COc3ccccc3)n(Cc3ccc(Cl)cc3)c2cc1N1CCNCC1
Solvent: ClCCl
Product: O=C(C1CC1)N1CCN(c2cc3c(cc2F)nc(COc2ccccc2)n3Cc2ccc(Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
72 mg of 1-(4-chloro-benzyl)-5-fluoro-2-phenoxymethyl-6-piperazin-1-yl-1H-benzoimidazole (0.16 mmol) and 0.033 ml TEA (0.24 mmol) were dissolved in 1.5 ml dichloromethane and treated with 0.0145 ml cyclopropanecarbonyl chloride (0.2 mmol). After 1.5 h of stirring at rt, the reaction mixture was diluted with dichloromethane, washed with water, saturated sodium bicarbonate and brine, dried with magnesium sulfate, filtered and concentrated in vacuo, leading to 82 mg white solid (98%). MS (ISP) 519.3 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])=[CH:6][CH:5]=[CH:4][N:3]=1.Cl[CH:18]([C:24]([CH3:26])=O)[C:19]([O:21][CH2:22][CH3:23])=[O:20].C(=O)(O)[O-].[Na+].C(COC)OC>CCCCCC>[CH2:22]([O:21][C:19]([C:18]1[N:3]2[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[F:16])[C:2]2=[N:1][C:24]=1[CH3:26])=[O:20])[CH3:23]
Reactant: Nc1ncccc1OCc1ccccc1F
Reactant: CCOC(=O)C(Cl)C(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: CCCCCC
Product: CCOC(=O)c1c(C)nc2c(OCc3ccccc3F)cccn12
Reaction time: 0.5 h

Procedure:
A mixture of 25.0 g of 2-amino-3-(2-fluorobenzyloxy)pyridine, 20.5 g ethyl 2-chloroacetoacetate, 10.0 g of sodium bicarbonate and 250 ml dimethoxyethane was heated under reflux for 48 hrs. An additional 5.0 g ethyl 2-chloroacetonacetate was added and refluxed for another 24 hrs., followed by another 5.0 g and refluxed for a further 66 hrs. The mixture was cooled and suctionfiltered. The solids collected were washed with tetrahydrofuran, and the combined filtrate and washings were evaporated invacuo to leave a dark-colored oil. Hexane (200 ml) was added to the oil with vigorous stirring, and the resulting precipitate filtered off. To this solid was added (with vigorous stirring) acetonitrile (50 ml) and diisopropyl ether (200 ml) and stirring was continued for 0.5 hr. The suspended solid was filtered and crystallized from acetonitrile to give the desired ester.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:14][CH3:15])=[CH:4][C:5]2[CH:9](O)[CH:8]([CH3:11])[S:7][C:6]=2[C:12]=1[Cl:13].B(F)(F)F.CCOCC.[OH-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[C:3]([O:14][CH3:15])=[CH:4][C:5]2[CH:9]=[C:8]([CH3:11])[S:7][C:6]=2[C:12]=1[Cl:13]
Reactant: COc1cc2c(c(Cl)c1Cl)SC(C)C2O
Agent: FB(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCOCC
Product: COc1cc2cc(C)sc2c(Cl)c1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 60.9 %

Procedure:
A solution of 3.7 g of 6,7-dichloro-2,3-dihydro-3-hydroxy-5-methoxy-2-methylbenzo[b]thiophene in 20 ml of glacial acetic acid containing 5 ml of boron trifluoride etherate is warmed on a steam bath for 5 min. to form a clear solution. After stirring at room temperature for 1 hour, the solution is poured into an ice-cold solution of 10% sodium hydroxide. The organic materials are extracted 3 times with ether, dried and concentrated under vacuum. The reddish brown residue is purified by dissolving it in ether and passing it through an alumina column packed with ether. Elution with ether gives 2.1 g of 6,7-dichloro-5-methoxy-2-methylbenzo[b]thiophene as off-white crystals, mp 113°-114°.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:21])[CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[H][H]>[Pd].C(OCC)(=O)C.O1CCCC1>[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][CH2:10][CH2:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[O:21])=[CH:13][CH:14]=1
Reactant: O=C(CCCc1ccc([N+](=O)[O-])cc1)c1ccc(F)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Nc1ccc(CCCC(=O)c2ccc(F)cc2)cc1
Yield: 77.7 %

Procedure:
A mixture of 1-(4-fluorophenyl)-4-(4-nitrophenyl)butan-1-one (0.5 g, 1.7 mmol) and 10% palladium on carbon (0.06 g) in ethyl acetate (15 mL) and tetrahydrofuran (5 mL) was hydrogenated at room temperature using the hydrogen balloon. The catalyst was removed by filtration, and the filtrate concentrated in vacuo. Purification by silica gel chromatography, eluting with 10% ethyl acetate/hexane gave the title compound as a white solid (0.34 g, 78%). The product was used in the next step.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)=[N:7][C:6]=12.[CH3:25][Si:26]([C:29]#[CH:30])([CH3:28])[CH3:27]>>[F:12][C:11]([F:14])([F:13])[C:10]1[N:5]2[N:4]=[CH:3][C:2]([C:30]#[C:29][Si:26]([CH3:28])([CH3:27])[CH3:25])=[C:6]2[N:7]=[C:8]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:9]=1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)n3ncc(I)c3n2)cc1
Reactant: C#C[Si](C)(C)C
Product: C[Si](C)(C)C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Yield: 101.3 %

Procedure:
Prepared from 3-iodo-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (87.5 g, 191 mmol) and trimethylsilylacetylene (54 mL, 390 mmol) as described in Example C.1, method 1, step 3a, to give the 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (82.71 g, 100%) as a yellow-orange solid.
Reaction SMILES: FC1C=C(OC)C=C(F)C=1[C:11]1=[C:12]([CH:42]=[CH:43][C:44]2[C:52]([CH3:54])([CH3:53])[C:51]3[C:46](=[CH:47][CH:48]=[C:49]([S:55]([O-:58])(=[O:57])=[O:56])[CH:50]=3)[N+:45]=2[CH2:59][CH2:60][CH2:61][CH2:62][S:63]([O-:66])(=[O:65])=[O:64])[CH2:13][CH2:14][CH2:15]/[C:16]/1=[CH:17]\[CH:18]=[C:19]1\[N:20]([CH2:34][CH2:35][CH2:36][CH2:37][S:38]([O-:41])(=[O:40])=[O:39])[C:21]2[C:26]([C:27]\1([CH3:29])[CH3:28])=[CH:25][C:24]([S:30]([O-:33])(=[O:32])=[O:31])=[CH:23][CH:22]=2.[Na+:67].[Na+].[Na+].B([C:73]1[C:74]([F:88])=[C:75]([CH2:81][CH2:82][CH2:83][CH2:84][C:85]([OH:87])=[O:86])[C:76]([F:80])=[CH:77][C:78]=1[F:79])(O)O>>[C:85]([CH2:84][CH2:83][CH2:82][CH2:81][C:75]1[C:74]([F:88])=[C:73]([C:11]2=[C:16]([CH:17]=[CH:18][C:19]3[C:27]([CH3:29])([CH3:28])[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([S:30]([O-:33])(=[O:31])=[O:32])[CH:25]=4)[N+:20]=3[CH2:34][CH2:35][CH2:36][CH2:37][S:38]([O-:41])(=[O:40])=[O:39])[CH2:15][CH2:14][CH2:13]/[C:12]/2=[CH:42]\[CH:43]=[C:44]2\[N:45]([CH2:59][CH2:60][CH2:61][CH2:62][S:63]([O-:66])(=[O:65])=[O:64])[C:46]3[C:51]([C:52]\2([CH3:54])[CH3:53])=[CH:50][C:49]([S:55]([O-:58])(=[O:56])=[O:57])=[CH:48][CH:47]=3)[C:78]([F:79])=[CH:77][C:76]=1[F:80])([OH:87])=[O:86].[Na+:67].[Na+:67].[Na+:67]
Reactant: COc1cc(F)c(C2=C(C=CC3=[N+](CCCCS(=O)(=O)[O-])c4ccc(S(=O)(=O)[O-])cc4C3(C)C)CCC/C2=C\C=C2\N(CCCCS(=O)(=O)[O-])c3ccc(S(=O)(=O)[O-])cc3C2(C)C)c(F)c1
Reactant: O=C(O)CCCCc1c(F)cc(F)c(B(O)O)c1F
Agent: CC1(C)C(/C=C/C2=C(c3c(F)cc(F)c(CCCCC(=O)O)c3F)/C(=C/C=C3/N(CCCCS(=O)(=O)[O-])c4ccc(S(=O)(=O)[O-])cc4C3(C)C)CCC2)=[N+](CCCCS(=O)(=O)[O-])c2ccc(S(=O)(=O)[O-])cc21
Agent: COc1cc(F)c(C2=C(/C=C/C3=[N+](CCCCS(=O)(=O)[O-])c4ccc(S(=O)(=O)[O-])cc4C3(C)C)CCC/C2=C\C=C2\N(CCCCS(=O)(=O)[O-])c3ccc(S(=O)(=O)[O-])cc3C2(C)C)c(F)c1
Agent: [Na+]
Product: CC1(C)C(C=CC2=C(c3c(F)cc(F)c(CCCCC(=O)O)c3F)/C(=C/C=C3/N(CCCCS(=O)(=O)[O-])c4ccc(S(=O)(=O)[O-])cc4C3(C)C)CCC2)=[N+](CCCCS(=O)(=O)[O-])c2ccc(S(=O)(=O)[O-])cc21

Procedure:
Compound 39 is prepared analogously to compound 17 (Example 17), except with 5-(3-borono-2,4,6-trifluorophenyl)pentanoic acid as a starting material.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].[C:9]1(=[O:19])[NH:13][C:12](=[O:14])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]12.[K].C(OCC)(=O)C.O>CN(C)C=O>[OH:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:13]1[C:12](=[O:14])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]2[C:9]1=[O:19]
Reactant: OCCCCCCBr
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCO
Reaction time: 72 h

Procedure:
6-Bromohexan-1-ol (8 g, 44 mmol) and potassium phthalimide (16.4 g, 88 mmol) were heated at 90° C. for two hours in dry N,N-dimethylformamide (50 ml). The mixture was cooled and partitioned between chloroform (150 ml) and water (150 ml). The organic layer washed with water (2×150 ml), dried over anhydrous magnesium sulphate, filtered, and the filtrate evaporated under reduced pressure to give a yellow liquid. The liquid was left at 4° C. for 72 hours before repartitioning between ethyl acetate (150 ml) and water (150 ml). The organic layer was washed with water (2×150 ml), dried over anhydrous magnesium sulphate, filtered, and the filtrate evaporated under reduced pressure. Diethyl ether was added and following cooling the solid was removed by filtration. The process was repeated and the liquors were evaporated to give N-(6-hydroxyhexyl)-phthalimide. 1H-NMR: (60 MHz) (CDCl3), δ 7.7 (4H,s), 3.6 (5H,m) and 1.4 (8H,m) ppm
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:29])=[C:10]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=4)=[O:21])[CH2:15][CH2:14]3)[CH:11]=2)[C:6](=[O:30])[C:5]([C:31]([OH:33])=[O:32])=[CH:4]1)[CH3:2].Cl.[NH2:35]O>>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:29])=[C:10]([N:13]3[CH2:14][CH2:15][N:16]([C:19](=[NH:35])[CH:20]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=4)[OH:21])[CH2:17][CH2:18]3)[CH:11]=2)[C:6](=[O:30])[C:5]([C:31]([OH:33])=[O:32])=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(CC(=O)c4ccc(Cl)cc4)CC3)cc21
Reactant: NO
Agent: Cl
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(N3CCN(C(=N)C(O)c4ccc(Cl)cc4)CC3)cc21

Procedure:
1-Ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-hydroxy-iminoethyl]-1-piperazinyl}-4-oxo-1,4-dihydro-3-quinoline-carboxylic acid was prepared from 1-ethyl-6-fluoro-7-{4-[2-(4-chlorophenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (0.24 g, 0.5 mmole) and hydroxylamine hydrochloride (0.07 g, 1 mmol) by a method similar to that described for Example 3 (73% yield). 1H NMR (DMSO-d6) δ 1.39 (t, 3H, J=7.0), 2.61 and 3.24 (two m, 8H), 3.44 and 3.73 (two s, 2H), 4.56 (q, 2H, J=7.0), 7.24 and 7.78 (two m, 5H), 7.89 (d, 1H, J=13.4), 8.93 (s, 1H), 11.03 and 11.49 (two s, 1 H), 15.35 (br s, 1H). Anal. Calcd. for C24H24FClN4O4•0.25 H2O: C, 58.66; H, 5.02; N, 11.40. Found: C, 58.48; H, 5.01; N, 11.29.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[OH2:10]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]([NH2:6])=[O:10]
Reactant: N#Cc1cccc(Br)c1
Reactant: O
Solvent: C1COCCO1
Product: NC(=O)c1cccc(Br)c1
Temperature: 80 °C
Yield: 80 %

Procedure:
To a solution of 3-bromobenzonitrile (0.91 g, 5 mmol) in dioxane (19 mL), NaBO3.4H2O (2.12 g, 13.78 mmol) and H2O (19 mL) were added. The mixture was stirred at 80° C. 16 hours (h), cooled, added of H2O and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and evaporated. Purification of the residue by column chromatography (hexane/EtOAc 2:8) and recrystallization gave the desired product as colorless tablets. Yield 80% (EtOH). Mp: 156–7° C. (lit. 156° C.) (Pearson, D. E. et al., J. Org. Chem., 28: 3147–3149, (1963)). MS (EI): m/z 199 (M+); 183 (100%).