Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:36][CH3:37])=[CH:5][C:6]2S[CH2:11][CH2:10][C:9]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:34])[C:22]4[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=4)[CH2:17][CH2:16]3)=[O:14])=[CH:8][C:7]=2[CH:35]=1.ClC1C=CC=C(C(OO)=O)C=1.[S:49]([O-:52])([O-])=[O:50].[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4]([O:36][CH3:37])=[CH:5][C:6]2[S:49](=[O:52])(=[O:50])[CH2:11][CH2:10][C:9]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:34])[C:22]4[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=4)[CH2:17][CH2:16]3)=[O:14])=[CH:8][C:7]=2[CH:35]=1
Reactant: O=S([O-])[O-]
Reactant: COc1cc2c(cc1OC)SCCC(C(=O)N1CCN(C(=O)c3cc(OC)c(OC)c(OC)c3)CC1)=C2
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1cc2c(cc1OC)S(=O)(=O)CCC(C(=O)N1CCN(C(=O)c3cc(OC)c(OC)c(OC)c3)CC1)=C2
Reaction time: 15 h

Procedure:
In methylene chloride (10 ml) is dissolved 1-(7,8-dimethoxy-2,3-dihydro-1-benzothiepin-4-carbonyl)-4-(3,4,5-trimethoxybenzoyl)piperazine (1.6 g) obtained in Working Example 24. To the solution is added, while stirring under ice-cooling, m-chloro-perbenzoic acid (1.71 g) in limited amounts. The mixture is stirred for one hour, and then left standing at -5° C. for 15 hours. To the reaction mixture is added an aqueous solution of acid sodium sulfite to decompose the excess peracid. The resultant is poured into an aqueous solution of sodium hydrogencarbonate; this is followed by extraction with methylene chloride. The organic layer is washed with an aqueous solution of sodium hydrogencarbonate, dried, and concentrated under reduced pressure. The residue is recrystallized from ethanol to give 1-(7,8-dimethoxy-1,1-dioxo-2,3-dihydro-1-benzothiepin4-carbonyl)-4-(3,4,5-trimethoxybenzoyl)piperazine as colorless prisms (1.4 g), m.p. 226°-229° C.
Reaction SMILES: [ClH:1].[CH3:2][C:3]1[CH:12]=[C:11]([O:13][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[N:29]=[N:30][N:31](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:32]=3)=[CH:18][CH:17]=2)[CH3:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1>C(O)C.CO>[ClH:1].[CH3:2][C:3]1[CH:12]=[C:11]([O:13][CH:14]([C:16]2[CH:17]=[CH:18][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[NH:32][N:31]=[N:30][N:29]=3)=[CH:20][CH:21]=2)[CH3:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: Cc1cc(OC(C)c2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c2ccccc2n1
Agent: Cl
Solvent: CO
Solvent: CCO
Product: Cc1cc(OC(C)c2ccc(-c3ccccc3-c3nnn[nH]3)cc2)c2ccccc2n1
Reaction time: 3 h

Procedure:
Concentrated hydrochloric acid (0.5 ml) was added to a solution of 2-methyl-4-[1-(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)-biphenyl-4-yl)ethoxy]quinoline (A) (320 mg) in a mixture of ethanol (2 ml) and methanol (1 ml). The solution was left to stand for 3 hours. The precipitated solid was collected by filtration and washed with ether to give 2-methyl-4-[1-(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)ethoxy]quinoline hydrochloride (120 mg), as a white solid, m.p. 168°-169° C.; NMR (d6 -DMSO): 1.8(d, 3H), 2.9(s, 3H), 6.2(q, 1H), 7.2(d, 2H), 7.45(s, 1H), 7.5-7.6(complex m, 4H), 7.65(d, 2H), 7.85(t, 1H), 8.1(t, 1H), 8.2(d, 1H), 8.45(d, 1H); mass spectrum (-ve FAB, DMSO/glycerol (GLY)): 406(M-H)-, 248,158,127; microanalysis, found: C, 66.5; H,5.1; N, 15.8; H2O 2.1%; C25H21N5O.HCl.0.5 H2O requires: C, 66.3; H, 5.1; N, 15.5; 2.0%.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[CH:21]=[CH:20][C:19]([S:22][CH3:23])=[CH:18][C:17]=4[CH3:24])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:38])C=1.C(=O)([O-])O.[Na+]>ClCCl>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[CH:21]=[CH:20][C:19]([S:22]([CH3:23])=[O:38])=[CH:18][C:17]=4[CH3:24])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1
Reactant: CCC(CC)c1ccc(Cl)c2nc3n(c12)CCCCN3c1ccc(SC)cc1C
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCC(CC)c1ccc(Cl)c2nc3n(c12)CCCCN3c1ccc(S(C)=O)cc1C
Temperature: 0 °C
Reaction time: 2 h
Yield: 29.2 %

Procedure:
To a solution of 10-chloro-7-(1-ethylpropyl)-1-[2-methyl-4-(methylthio)phenyl]-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (106 mg, 0.248 mmol) in dichloromethane (2.5 mL) was added m-chloroperbenzoic acid (47.0 mg, 0.272 mmol), and the mixture was stirred at 0° C. for 2 hr. The mixture was neutralized with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (32.1 mg, 0.0723 mmol, 29%).
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][C:13]([CH:25]=[O:26])=[C:14]2Cl)[CH2:6]1)(=[O:3])[CH3:2].[NH:27]1[CH:31]=[N:30][N:29]=[N:28]1>>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][C:13]([CH:25]=[O:26])=[C:14]2[N:28]2[N:29]=[N:30][CH:31]=[N:27]2)[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(Cl)=C(C=O)C[C@@H]32)C1
Reactant: c1nnn[nH]1
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(n4ncnn4)=C(C=O)C[C@@H]32)C1
Yield: 16.9 %

Procedure:
The method followed that described for Synthesis Example 7, but using 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene (Compound 3) (0.5 g, 1.329 mmol), 1H-tetrazole (187 mg, 1.59 mmol) and Li2CO3 (287 mg, 3.94 mmol) gave a crude product (520 mg). Flash column chromatography on elution with pet. ether/EtOAc, (5:1), gave firstly 3β-acetoxy-17-(2H-tetrazol-2-yl)-16-formylandrosta-5,16-diene (Compound 22) (92 mg, 28.2%), mp 170-172° C. (decomp.). 1H NMR (300 MHz, CDCl3): δ1.1 (3H, s, 18-Me), 1.29 (3H, s, 19-Me), 2.04 (3H, s, 3β-OAc), 4.62 (1H, m, 3α-H), 5.42 (1H, d, J=4.2 Hz, 6-H), 8.68 (1H, s, 5′-H) and 10.46 (1H, s, 16-CHO). Analysis calculated for C23H30O3N4: C, 67.28; H, 7.37; N, 13.65. Found: C, 67.15; H, 7.61; N, 13.45. Further elution with p. ether/EtOAc/Et3N (7:3:0.3) gave 3β-acetoxy-17-(1H-tetrazol-1-yl)-16-formylandrosta-5, 16-diene (Compound 23) (146 mg, 44.6%), mp 196-198° C. (decomp.). 1H NMR (300 MHz, CDCl3): δ1.09 (3H, s, 18-Me), 1.20 (3H, s, 19-Me), 2.04 (3H, s, 3β-OAc), 4.62 (1H, m, 3α-H), 5.43 (1H, d, J=4.8 Hz, 6-H), 8.93 (1H, s, 5′-H) and 9.92 (1H, s, 16-CHO). Analysis calculated for C23H30O3N4: C, 67.28; H, 7.37; N, 13.65. Found: C, 67.05; H, 7.65; N, 13.45.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:9]=[C:10]=[O:11])[CH3:8].[N+:12]([C:15]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[C:17]([C:24]([F:27])([F:26])[F:25])[C:16]=1[O:28][C:29]1[CH:33]=[C:32]([CH3:34])[NH:31][N:30]=1)([O-:14])=[O:13].Cl>C(OCC)(=O)C>[CH2:7]([NH:9][C:10]([N:31]1[C:32]([CH3:34])=[CH:33][C:29]([O:28][C:16]2[C:17]([C:24]([F:26])([F:27])[F:25])=[CH:18][C:19]([N+:21]([O-:23])=[O:22])=[CH:20][C:15]=2[N+:12]([O-:14])=[O:13])=[N:30]1)=[O:11])[CH3:8]
Reactant: Cc1cc(Oc2c([N+](=O)[O-])cc([N+](=O)[O-])cc2C(F)(F)F)n[nH]1
Reactant: CCN=C=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CCNC(=O)n1nc(Oc2c([N+](=O)[O-])cc([N+](=O)[O-])cc2C(F)(F)F)cc1C
Temperature: 25 °C
Reaction time: 12 h
Yield: 49.6 %

Procedure:
Potassium carbonate (0.15 g, 1.1 mmol) and ethyl isocyanate (0.07 g, 1.0 mmol) were added to a solution of 3-(2,4-dinitro-6-trifluoromethylphenyloxy)-5-methylpyrazole (0.33 g, 1.0 mmol) in ethyl acetate (10 ml), and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was poured into 2N hydrochloric acid and extracted with ethyl acetate (10 ml×3). An organic layer was washed with water, dried over anhydrous magnesium sulfate and filtered to remove a desiccant, and the solvent was distilled off from the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/10), to give a yellowish solid of N-ethyl-3-(2,4-dinitro-6-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide (0.20 g, yield: 49.6%). mp: 169-171° C.; 1H-NMR (CDCl3, TMS, ppm): δ 1.18 (t, J=7.2 Hz, 3H), 2.59 (d, J=0.4 Hz, 3H), 3.31 (dq, J=6.0 and 7.2 Hz, 2H), 5.95 (q, J=0.4 Hz, 1H), 6.25-6.50 (m, 1H), 8.85 (d, J=2.7 Hz, 1H), 9.02 (d, J=2.7 Hz, 1H).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[N:26]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])[CH:25]=[CH:24]5)[N:17]=3)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+:36]>CCOC(C)=O.O>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[N:26]([CH2:30][CH2:31][C:32]([O-:34])=[O:33])[CH:25]=[CH:24]5)[N:17]=3)[S:10][C:11]=2[C:12]([F:14])([F:15])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+:36]
Reactant: O=C(O)CCn1ccc2cc(-c3noc(-c4cc(-c5ccccc5)c(C(F)(F)F)s4)n3)ccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C([O-])CCn1ccc2cc(-c3noc(-c4cc(-c5ccccc5)c(C(F)(F)F)s4)n3)ccc21

Procedure:
E1 (30 mg) was dissolved in EtOAc (1 ml), treated with 2M aqueous NaOH (40 ul), diluted with H2O (1 ml) and extracted with EtOAc (3×5 ml), using a small volume of brine during the third extraction to aid phase separation. The combined organics were evaporated to give the title compound (37 mg) as a green solid. δH (methanol-d4, 400 MHz): 2.68 (2H, t), 4.48 (2H, t), 6.55 (1H, d), 7.49 (1H, d), 7.45-7.56 (5H, m), 7.62 (1H, d), 7.92 (1H, d), 8.03 (1H, s), 8.35 (1H, s). MS (ES+): C24H16F3N3O3S requires 483; found 484 (MH+).
Reaction SMILES: [OH-].[NH4+:2].[Cl:3][C:4]1[C:5]([F:17])=[C:6]([CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[C:12]=1F)[C:7]([OH:9])=[O:8].Cl>O>[NH2:2][C:12]1[C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([F:17])[C:4]=1[Cl:3]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(F)c(Cl)c1F
Reactant: [NH4+]
Agent: Cl
Agent: [OH-]
Solvent: O
Product: Nc1c([N+](=O)[O-])cc(C(=O)O)c(F)c1Cl
Temperature: 25 °C
Yield: 85.8 %

Procedure:
Ammonium hydroxide solution (6.88 g, ˜30% in water, 58.9 mmol) is added to a solution of 3-chloro-2,4-difluoro-5-nitro-benzoic acid 2a (3.5 g, 14.7 mmol) in water (16 mL) at 0° C. with stirring. Upon completion of the ammonium hydroxide addition the reaction mixture is warmed to room temperature. After 5 hours the reaction mixture is cooled to 0° C. and concentrated HCl is carefully added until the pH of the reaction mixture is near zero. The solid is collected by filtration and washed with water and diethyl ether. The solids are transferred to a round bottom flask as a solution in MeOH and EtOAc and concentrated under reduced pressure to give 2.96 g of a yellow solid. The filtrate is partitioned between diethyl ether and water and the organic layer is washed with brine. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure to give 0.65 g of product. Recovered a total of 3.61 g (104%) of pure desired product that is carried forward without further purification.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]([OH:9])=[O:8].[C:10]1([CH3:19])[CH:15]=[CH:14][CH:13]=[C:12](B(O)O)[CH:11]=1>>[C:10]1([CH3:19])[CH:15]=[CH:14][CH:13]=[C:12]([C:2]2[S:3][CH:4]=[CH:5][C:6]=2[C:7]([OH:9])=[O:8])[CH:11]=1
Reactant: Cc1cccc(B(O)O)c1
Reactant: O=C(O)c1ccsc1Br
Product: Cc1cccc(-c2sccc2C(=O)O)c1

Procedure:
prepared by reaction of 2-bromo-thiophene-3-carboxylic acid with m-tolylboronic acid. LC-MS (basic): tR=0.51 min; [M−H]−=217.3.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:11][CH:12]([CH3:14])[CH3:13])[CH:3]=1.C(N(CC)CC)C.[Cl-].[C:23]([O:29][CH2:30][CH3:31])(=[O:28])[CH2:24][C:25]([O-])=[O:26].Cl>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([N:11]([C:25](=[O:26])[CH2:24][C:23]([O:29][CH2:30][CH3:31])=[O:28])[CH:12]([CH3:14])[CH3:13])[CH:3]=1
Reactant: CCOC(=O)CC(=O)[O-]
Reactant: CC(C)Nc1cc(Br)ccc1C(=O)O
Agent: Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CC(=O)N(c1cc(Br)ccc1C(=O)O)C(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 72 %

Procedure:
To a solution of 4-bromo-2-(propan-2-ylamino)benzoic acid (6.8 g, 26.64 mmol) in 260 mL of DCM is added triethylamine (4 mL, 31.6 mmol), followed by dropwise addition of ethyl malonate chloride (4.0 mL, 31. mmol). The mixture is stirred for 2 hours at room temperature, and then poured into molar hydrochloric acid solution and extracted with EtOAc. The organic phase is washed with water and with saturated aqueous NaCl solution, dried over Na2SO4 and concentrated to dryness. 7.15 g of a pale yellow solid are obtained (yield: 72%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:26])([F:25])[F:24])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH2:21])=[C:16]([CH3:22])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:27](OC(=O)C)(=[O:29])[CH3:28].C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:23]([F:24])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH:21][C:27](=[O:29])[CH3:28])=[C:16]([CH3:22])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1CN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)NCc1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.6 %

Procedure:
To a solution of 1-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methylphenyl}methanamine (0.2 g) and acetic anhydride (0.1 g) in dichloromethane (50 mL), triethylamine (0.1 g) in dichloromethane (5 mL) was added dropwise under ice cooling, and the mixture was then stirred for one hour at room temperature. The reaction mixture was washed with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was then purified by silica gel chromatography to yield N-{4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methylbenzyl}acetamide (0.2 g).
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=O)[CH:3]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15].[C:16]([CH:23]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>O1CCCC1>[OH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH:3]1[CH:4]([CH:7]=[CH:23][C:16](=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:5][CH2:6][CH:2]1[OH:1]
Reactant: CCCCCC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=CC1CCC(O)C1CCCCCCO
Solvent: C1CCOC1
Product: CCCCCC(=O)C=CC1CCC(O)C1CCCCCCO
Yield: 64.2 %

Procedure:
A mixture of 3-hydroxy-2-(6-hydroxyhexyl)cyclopentanecarbaldehyde (8.6 g.) and hexanoylmethylene triphenylphosphorane (16 g., 0.043 mole) in dry tetrahydrofuran (100 ml.) was heated under reflux for 6 hours. The solvent was removed in vacuo and the residue was chromatographed on silica gel. Elution with a 3:2 mixture of petrol (b.p. 40°-60°C.) and ethyl acetate gave 2-(6-hydroxyhexyl)-3-(3-oxo-1-octenyl)cyclopentanol (8 g.), νmax 1660 cm-1, 1620 cm-1 (liquid film).
Reaction SMILES: [OH:1][CH:2]([C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=1)[CH:3]([NH:18][C:19]([C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[CH2:31][CH2:30][CH2:29][CH:28]=[CH:27][C:26]=12)=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:17])([F:16])[CH:13]([F:15])[F:14])[CH:6]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:46][C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=1>CN(C)C=O.O>[C:21]1([C:19]([NH:18][CH:3]([CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:16])([F:17])[CH:13]([F:15])[F:14])[CH:6]=2)[CH:2]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH2:46][C:47]3[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[CH:49][CH:48]=3)=[CH:34][CH:33]=2)[OH:1])=[O:20])[C:26]2[CH:27]=[CH:28][CH2:29][CH2:30][CH2:31][C:25]=2[CH:24]=[CH:23][CH:22]=1
Reactant: O=C(NC(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1ccc(O)cc1)c1cccc2c1C=CCCC2
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(COc2ccc(C(O)C(Cc3cccc(OC(F)(F)C(F)F)c3)NC(=O)c3cccc4c3C=CCCC4)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of N-{(1RS,2SR)-2-hydroxy-2-(4-hydroxyphenyl)-1-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]ethyl}-6,7-dihydro-5H-benzo[a][7]annulene-1-carboxamide (600 mg, 1.13 mmol) in N,N-dimethylformamide (20 ml) were added potassium carbonate (470 mg, 3.40 mmol) and methyl 4-(bromomethyl)-benzoate (780 mg, 3.40 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-2:1). Recrystallization from ethyl acetate-hexane gave the objective substance (361 mg, 47%).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([Br:11])=[CH:9][CH:10]=1)=O.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([NH2:20])=[O:19].C([O-])(O)=O.[Na+]>CCOC(C)=O>[Br:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:20]=[C:18]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=3)[O:19][CH:2]=2)=[CH:6][N:7]=1
Reactant: NC(=O)c1ccccn1
Reactant: O=C(CBr)c1ccc(Br)nc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: Brc1ccc(-c2coc(-c3ccccn3)n2)cn1
Yield: 10 %

Procedure:
A mixture of 2-bromo-1-(6-bromopyridin-3-yl)ethanone from Step A (2.3 g, 8.25 mmol) and pyridine-2-carboxamide (1 g, 8.25 mmol) was melted at 85°. Heating was continued until the mixture reached 140° at which point the product solidified. Ice, EtOAc and sat aq NaHCO3 were added. The aqueous layer was then back extracted with EtOAc/THF (3:1). Pooled organics were dried over MgSO4, filtered, concentrated, and purified on silica gel to afford 250 mg (10% yield) of 2-bromo-5-(2-pyridin-2-yl-1,3-oxazole-4-yl)pyridine. LC/MS: m/e 302.0 (M+H).
Reaction SMILES: [CH3:1][C@@:2]1([OH:18])[C@H:9]([CH3:10])[O:8][C@@H:5]([O:6]C)[CH2:4][C@@H:3]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14]>C(O)(=O)C.O>[CH3:1][C@@:2]1([OH:18])[C@H:9]([CH3:10])[O:8][C@@H:5]([OH:6])[CH2:4][C@@H:3]1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:14])[F:15]
Reactant: CO[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@](C)(O)[C@H](C)O1
Solvent: CC(=O)O
Solvent: O
Product: C[C@@H]1O[C@@H](O)C[C@H](NC(=O)C(F)(F)F)[C@]1(C)O
Yield: 99.8 %

Procedure:
A solution of 1 g (3.7 mmoles) of methyl 2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-α-L-lyxo-hexopyranoside (IV-A) in 20 ml of acetic acid and 80 ml of water was reacted at 100° C. for 2 hours. The solution was evaporated and 2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-α-L-lyxo-hexopyranose (V-A) (0.95 g; 95%) was obtained as a white solid; m.p. 181°-182° C. [α]D23° =-127° (c=1.0 in methanol). The PMR spectrum (CDCl3 +DMSO-d6) showed, inter alia, absorptions at: 1.05 (s, CH3 --C-4), 1.16 (d, CH3 -C-5), and 5.27δ(C-l-H). A solution of 0.75 g (2.9 mmoles) of compound V-A in a mixture of 10 ml of triethylamine and 20 ml of anhydrous methylene dichloride was treated under stirring with 2.20 g of p-nitrobenzoyl chloride and 0.220 g of 4-dimethylaminopyridine and then heated at 45° C. for 90 minutes. The solution was evaporated to form a residue which was dissolved in 100 ml of chloroform, washed with 10% sodium bicarbonate solution and then with water. The chloroform solution was then dried over sodium sulphate and concentrated to a residue which was chromatographed on a silica gel column. Elution with a 95:5 chloroform: acetone mixture gave 1,4-di-O-p-nitrobenzoyl-2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-L-lyxo-hexopyranose (VI-A, 1.55 g; 95%): m.p. 168°-170° C.; [α]D23° =-35° (c=1 in chloroform).
Reaction SMILES: Cl.C[O:3][C:4]1[CH:5]=[C:6]([C:10]2([CH3:18])[O:15][CH:14]([CH3:16])[CH2:13][N:12]([CH3:17])[CH2:11]2)[CH:7]=[CH:8][CH:9]=1>C1(C)C=CC=CC=1>[OH:3][C:4]1[CH:5]=[C:6]([C:10]2([CH3:18])[O:15][CH:14]([CH3:16])[CH2:13][N:12]([CH3:17])[CH2:11]2)[CH:7]=[CH:8][CH:9]=1
Reactant: COc1cccc(C2(C)CN(C)CC(C)O2)c1
Agent: Cl
Solvent: Cc1ccccc1
Product: CC1CN(C)CC(C)(c2cccc(O)c2)O1

Procedure:
2-(3-methoxyphenyl)-2,4,6-trimethylmorpholine hydrochloride (Isomer B) (2.49 g) was heated under reflux with redistilled constant boiling hydrobromic acid (20 ml) under nitrogen for 1 hour. After cooling and diluting with water to 40 ml the mixture was basified with conc. aqueous ammonia. The oil which precipitated was extracted with dichloromethane. After drying (MgSO4) the solvent was removed affording a colourless oil which gave 1.16 g of colourless rhombs mp 142°-143° C. from toluene. (Found: C, 70.6; H, 8.7; N, 6.05%. C13H19NO2 requires C, 70.55; H, 8.65; N, 6.3%. NMR data indicate that the product apparently has (2R*, 6S*)-configuration.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([O-])=[S:7])([O-:3])=[O:2].[NH2:13][C:14]([NH2:16])=[NH:15].C(O)C>O1CCCC1>[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([NH:15][C:14]([NH2:16])=[NH:13])=[S:7])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1C([O-])=S
Reactant: N=C(N)N
Solvent: CCO
Solvent: C1CCOC1
Product: N=C(N)NC(=S)c1ccccc1[N+](=O)[O-]

Procedure:
The reactions of Equation 57 above can be run by methods known in the art. Thus, in reaction 57a, a 2-nitrothiobenzoate of Formula (LXXV) is reacted with guanidine in a solvent such as ethanol or tetrahydrofuran at 0° to about 30° C. for 2 to 120 hours to form a 2-nitrothiobenzoylguanidine of Formula (LXXVI), according to the teachings of J. Goerdeler and A. Fincke, Chem. Ber., 89, 1033 (1956). In reaction 57b, LXXVI is cyclized by reaction with bromine in methanol at 0° to 60° C. for 0.5 to 3 hours to form a 3-amino-5-(2-nitrophenyl)-1,2,4-thiadiazole of Formula (LXXVII), according to the teachings of ibid. In reaction 57c, LXXVII is reacted with sodium nitrite in hydrochloric acid or hydrobromic acid, in the presence of copper powder, at -10° to 60° C. for 0.5 to 5 hours to form Xq' via Sandmeyer reaction, according to the teachings of F. Kurzer and S. Taylor, J. Chem. Soc., 3234 (1960). And in the last reaction, Xq' is reacted with sodium methoxide, sodium ethoxide or sodium methylmercaptide in a solvent such as methanol, ethanol or tetrahydrofuran at reflux for 0.5 to 5 hours to form Xq", according to the teachings of ibid.
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:26]=1[CH2:27][CH2:28][NH:29]2>>[N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15](=[O:17])[N:29]3[C:30]4[C:26](=[C:25]([C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][N:19]=5)[CH:33]=[CH:32][CH:31]=4)[CH2:27][CH2:28]3)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: c1ccc(-c2cccc3c2CCN3)nc1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: [Na+]
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)N1CCc2c(-c3ccccn3)cccc21
Yield: 62.8 %

Procedure:
The product is prepared by following the procedure described in example 10d using 26.7 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 1d, step 2d) and 25 mg of 4-pyridin-2-yl-2,3-dihydro-1H-indole in place of 4-pyridin-4-yl-2,3-dihydro-1H-indole. 26.8 mg of 6-(morpholin-4-yl)-2-{2-oxo-2-[4-(pyridin-2-yl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-one are obtained in the form of a purple solid, the characteristics of which are the following: