Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[F:14][C:15]([F:36])([F:35])[O:16][C:17]1[CH:34]=[CH:33][C:20]2[NH:21][C:22]([C:24]3[CH:32]=[CH:31][C:27]([C:28]([O-])=[O:29])=[CH:26][CH:25]=3)=[N:23][C:19]=2[CH:18]=1>>[F:36][C:15]([F:14])([F:35])[O:16][C:17]1[CH:34]=[CH:33][C:20]2[NH:21][C:22]([C:24]3[CH:32]=[CH:31][C:27]([C:28]([NH:11][C:10]4[CH:12]=[CH:13][C:7]([N:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)=[CH:8][CH:9]=4)=[O:29])=[CH:26][CH:25]=3)=[N:23][C:19]=2[CH:18]=1
Reactant: O=C([O-])c1ccc(-c2nc3cc(OC(F)(F)F)ccc3[nH]2)cc1
Reactant: Nc1ccc(N2CCOCC2)cc1
Product: O=C(Nc1ccc(N2CCOCC2)cc1)c1ccc(-c2nc3cc(OC(F)(F)F)ccc3[nH]2)cc1

Procedure:
Compound 481 was prepared from 4-morpholinoaniline and 4-(5-trifluoromethoxy-1H-benzimidazol-2-yl)benzoate by standard conditions. [M+H]+ calcd for C25H21F3N4O3: 483.17; found: 482.93.
Reaction SMILES: [H-].[Na+].[N:3]1([CH2:8][CH2:9][CH2:10][OH:11])[CH2:7][CH2:6][CH2:5][CH2:4]1.[Br:12][C:13]1[CH:14]=[CH:15][C:16](F)=[N:17][CH:18]=1>C1COCC1>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([O:11][CH2:10][CH2:9][CH2:8][N:3]2[CH2:7][CH2:6][CH2:5][CH2:4]2)=[N:17][CH:18]=1
Reactant: OCCCN1CCCC1
Reactant: Fc1ccc(Br)cn1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Brc1ccc(OCCCN2CCCC2)nc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.3 %

Procedure:
Sodium hydride (0.591 g, 14.77 mmol) was added portionwise to a solution, of 3-(pyrrolidin-1-yl)propan-1-ol (1.615 g, 12.50 mmol) in THF (20 mL) at to 0° C. then stirred at ambient temperature for 30 minutes, 5-Bromo-2-fluoropyridine (2 g, 11.36 mmol) was added and the resulting mixture stirred at ambient temperature for 2 h before being quenched by the addition of a sat. aqueous solution of ammonium chloride. The moisture was extracted with EtOAc (2×100 mL), the organic layer dried, over Na2SO4, filtered and evaporated to afford pale yellow solid. The crude product was purified by FCC, elution gradient 0 to 10% MeOH in DCM, to afford the desired material (2.70 g, 83%) as a yellow solid. Mass Spectrum: m/z (ES+)[M+H]+=285.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>C(OC(=O)C)(=O)C.O>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[C:17]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:18]([OH:20])=[O:19])=[CH:5][CH:4]=1
Reactant: COc1ccc(C=O)cc1
Reactant: O=C(O)Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)=O
Solvent: CCN(CC)CC
Solvent: O
Product: COc1ccc(C=C(C(=O)O)c2ccccc2)cc1
Temperature: 90 °C

Procedure:
A mixture of 4-methoxybenzaldehyde (30.0 g, 0.22 mol), phenylacetic acid (31.5 g, 0.23 mol), and triethylamine (31 ml) in acetic anhydride (75 ml) was heated at 90° C. for 5 hours. After cooling, 18 ml of water was dropped carefully during 15 min. Then, potassium carbonate (243 g) in water (1800 ml) was dropped and the solution was heated at 60° C. for 1 hour. After cooling, the solution was extracted with dichloro-methane. When the aqueous phase was acidified (pH 6-7), the product was precipitated. After stirring at 0° C., the product was filtered and dried.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]#[C:10]C1C=CC(OC)=CC=1C=O.Cl.NO.C([O-])(=O)C.[Na+].C(=O)([O-])[O-].[K+].[K+]>C(O)C.O>[C:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])#[CH:10]
Reactant: COc1ccc(C#Cc2ccccc2OC)c(C=O)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: NO
Solvent: O
Solvent: CCO
Product: C#Cc1ccccc1OC
Yield: 127.3 %

Procedure:
2-[2-(2-Methoxyphenyl)-ethynyl]-5-methoxybenzaldehyde (0.95 g), hydroxylamine hydrochloride (0.25 g) and sodium acetate (0.32 g) were reacted in ethanol (20 ml) at 60° C. for 2 hr. Potassium carbonate (0.6 g) and water (2 ml) were added to the reaction mixture, and the mixture was heated under reflux for 12 hr. The reaction solution was evaporated, and then the resulting residue was extracted with methylene chloride, washed with brine and dried. The solvent was removed, and the resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system), to give 0.60 g of the title compound as a yellowish brown amorphous. (232-4) 1-Chloro-7-methoxy-3-(2-methoxyphenyl)isoquinoline
Reaction SMILES: [CH2:1]([N:3]([CH2:20][CH3:21])[C:4]1[CH:9]=[CH:8][C:7]([S:10](CCCCC(O)=O)(=[O:12])=[O:11])=[CH:6][CH:5]=1)[CH3:2].[C:22]([O-:25])(=O)[CH3:23].[Na+]>C(OC(=O)C)(=O)C>[CH2:20]([N:3]([CH2:1][CH3:2])[C:4]1[CH:5]=[CH:6][C:7]([S:10]([N:3]2[CH2:4][CH2:5][CH2:6][CH2:23][C:22]2=[O:25])(=[O:11])=[O:12])=[CH:8][CH:9]=1)[CH3:21]
Reactant: CC(=O)[O-]
Reactant: CCN(CC)c1ccc(S(=O)(=O)CCCCC(=O)O)cc1
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(S(=O)(=O)N2CCCCC2=O)cc1
Temperature: 25 °C
Yield: 121.2 %

Procedure:
2 g of product obtained in Stage A are heated to reflux for 2 hours with 2 g of sodium acetate in 20 cm3 of acetic anhydride. The mixture is cooled to room temperature and evaporated to dryness, the residue is taken up in a mixture of chloroform and water, the organic phase is separated and dried and, after removal of the solvents, 1.8 g of expected crude product are obtained. M.p. 118°-120° C. After crystallization in isopropanol, 1.2 g of pure product are obtained. M.p. 122°-123° C.
Reaction SMILES: [F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[CH2:20])=[CH:15][C:14]=2[CH3:21])[C:8](=[O:22])[CH:7]=1.[Br:28]NC(=O)CCC(N)=O>C(#N)C>[Br:28][C:7]1[C:8](=[O:22])[N:9]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[CH2:20])=[CH:15][C:14]=2[CH3:21])[C:10]([CH3:12])=[CH:11][C:6]=1[O:5][CH2:4][C:3]1[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:2]=1[F:1]
Reactant: C=Cc1ccc(-n2c(C)cc(OCc3ccc(F)cc3F)cc2=O)c(C)c1
Reactant: NC(=O)CCC(=O)NBr
Solvent: CC#N
Product: C=Cc1ccc(-n2c(C)cc(OCc3ccc(F)cc3F)c(Br)c2=O)c(C)c1

Procedure:
The title compound was prepared by reacting 4-[(2,4-difluorobenzyl)oxy]-6-methyl-1-(2-methyl-4-vinylphenyl)pyridin-2(1H)-one (0.64 g, 1.74 mmol) with N-bromosuccinamide (0.325 g, 1.83 mmol) in acetonitrile (9 mL) at 0° C. using a similar procedure as described in step 3 of Example 465, to give 0.423 g (54.5% after recrystallization) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 7.67 (app q, J=7.59 Hz, 1H), 7.48 (s, 1H), 7.42 (dd, J=8.21, 1.98 Hz, 1H), 7.33 (dt, J=10.00, 2.27 Hz, 1H), 7.17 (dt, J=8.51, 2.44 Hz, 1H), 7.13 (d, J=7.88 Hz, 1H) 6.74 (dd, J=11.29, 6.34 Hz, 1H), 6.67 (s, 1H), 5.88 (d, J=17.85, 1H), 5.32-5.30 (m, 2H), 1.92 (s, 3H), 1.88 (s, 3H). ES-HRMS m/z 446.0579 (M+H calcd for C22H19BrF2NO2, requires 446.0568).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:25][O:26][CH3:27])[C:8]([NH:10][CH:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([O-:22])=[O:21])=[C:15]([CH:18]=[CH2:19])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+].Br[CH:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:32](=[O:33])[O:31]1.[I-].[Na+].C(OCC)(=O)C>CN(C)C=O.O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:25][O:26][CH3:27])[C:8]([NH:10][CH:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([O:22][CH:30]4[C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[C:32](=[O:33])[O:31]4)=[O:21])=[C:15]([CH:18]=[CH2:19])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: O=C1OC(Br)c2ccccc21
Reactant: C=CC1=C(C(=O)[O-])N2C(=O)C(NC(=O)C(=NOC)c3csc(N)n3)[C@H]2SC1
Agent: [I-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: C=CC1=C(C(=O)OC2OC(=O)c3ccccc32)N2C(=O)C(NC(=O)C(=NOC)c3csc(N)n3)[C@H]2SC1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 51.6 %

Procedure:
To a solution of sodium 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (2.16 g) in N,N-dimethylformamide (20 ml) were added 3-bromophthalide (1.3 g) and sodium iodide (1.35 g), and the mixture was stirred at ambient temperature for 40 minutes. Thereto were added ethyl acetate (100 ml) and water (50 ml), and the separated ethyl acetate layer was washed with a saturated aqueous solution of sodium bicarbonate and an aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate. After removal of the solvent, the residue (2.6 g) was chromatographed on silica gel (50 g) using a mixture of benzene and ethyl acetate as an eluent. The fractions containing the desired compound were collected and evaporated to give phthalid-3-yl 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (1.4 g).
Reaction SMILES: N1C=CC=CC=1.[CH2:7]1[CH2:25][O:24][C:9]2([CH2:15][O:14][C:13]([CH3:23])([CH2:16][CH2:17][CH2:18][CH:19]([CH3:22])[CH2:20][OH:21])[CH2:12][CH2:11][CH2:10]2)[O:8]1>C(Cl)Cl.[O-2].[O-2].[O-2].[Cr+6]>[CH2:25]1[CH2:7][O:8][C:9]2([CH2:15][O:14][C:13]([CH3:23])([CH2:16][CH2:17][CH2:18][CH:19]([CH3:22])[CH:20]=[O:21])[CH2:12][CH2:11][CH2:10]2)[O:24]1
Reactant: CC(CO)CCCC1(C)CCCC2(CO1)OCCO2
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C=O)CCCC1(C)CCCC2(CO1)OCCO2
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 68.6 %

Procedure:
A solution of pyridine (6.8 g, 0.086 mol) and chromium trioxide (4.3 g, 0.043 mol) in methylene chloride (450 ml) at 23° C. in a nitrogen atmosphere is stirred for 45 minutes. The mixture is cooled to -20° C. and celite (20 g) is added followed by 6,6-ethylenedioxy-2-methyl-2-(4'-methyl-5'-hydroxypentyl)-oxepane (1.95 g, 0.00717 mol) in methylene chloride (50 ml). The mixture is stirred for 1 hour at -20° C. and 30 minutes at 0° C. The mixture is then filtered and the celite cake is washed with methylene chloride (10×50 ml). The filtrate and washings are combined and washed with satd. NaHCO3 (2×150 ml). The methylene chloride phase is separated, dried (MgSO4) and the solvents are removed at reduced pressure. The crude product (1.9 g) is chromatographed on SilicAR CC-7 (50 g) in hexane. Elution with 15% ethyl acetate/hexane gives 6,6-ethylenedioxy-2-methyl-2-(4'-methyl-5'-oxopentyl)-oxepane (19) as a clear colorless oil (1.33 g, 68%): nmr (CDCl3) δ1.10 (d, J=6 Hz, 3H, CH3 --CH--CHO), 3.42 (s, 2H, O--CH2 --C), 3.97 (s, 4H, ketal), 9.53 (d, J=2H, 1H, CH--CHO).
Reaction SMILES: CO[CH:3]1[N:7]([C:8]([O:10][CH3:11])=[O:9])[C@H:6]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:4]1.C[Si]([C:20]#[C:21][CH3:22])(C)C.[Sn](Cl)(Cl)(Cl)Cl.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[C:20]([C@@H:3]1[N:7]([C:8]([O:10][CH3:11])=[O:9])[C@H:6]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:4]1)#[C:21][CH3:22]
Reactant: COC(=O)[C@@H]1CCC(OC)N1C(=O)OC
Reactant: CC#C[Si](C)(C)C
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC#C[C@H]1CC[C@@H](C(=O)OC)N1C(=O)OC
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a cold −45° C. solution of dimethyl (2S)-5-methoxypyrrolidine-1,2-dicarboxylate (10 g, 46.08 mmol, Example 1B) and trimethylsilylpropyne (14.24 mL, 92.16 mmol, 2.0 equiv) in methylene chloride (180 mL) was added a solution of tin (IV) chloride (1 M in methylene chloride, 60.0 mL, 60.0 mmol, 1.3 equiv) dropwise via an addition funnel over 30 minutes. To the dark yellow solution was added solid aluminum chloride (8.58 g, 64.52 mmol, 1.4 equiv) in one portion. The resulting mixture was allowed to warm to room temperature and stirred at room temperature for 48 hours. The reaction mixture was carefully quenched by saturated aqueous NH4OH (100 mL) with ice cooling. A white precipitate formed and was removed by filtration. The crude product was obtained after concentration. The residue was chromatographed on a Biotage flash 40 M eluting with 70% hexane/30% ethyl acetate to afford the titled compound. MS (DCI/NH3) m/e 226 (M+H)+.
Reaction SMILES: [C:1]([OH:14])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].P(=O)(O)(O)O.[CH-:20]1[CH:24]=[CH:23][CH:22]=[CH:21]1.[CH-:25]1[CH:29]=[CH:28][CH:27]=[CH:26]1.[Fe+2:30].[OH-].[K+]>O.C(Cl)Cl>[CH2:2]([C:1]([C-:20]1[CH:24]=[CH:23][CH:22]=[CH:21]1)=[O:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH-:25]1[CH:29]=[CH:28][CH:27]=[CH:26]1.[Fe+2:30]
Reactant: CCCCCCCCCCCC(=O)O
Agent: [Fe+2]
Agent: O=P(O)(O)O
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCCCCC(=O)[c-]1cccc1
Temperature: 180 °C
Yield: 86.9 %

Procedure:
8.01 g of lauric acid was added to 100 ml of 85% phosphoric acid and 100 g of polyphosphoric acid, and heated at 180° C. for three hours while the pressure was reduced (1 mmHg) with the use of vacuum pump. After the mixture was cooled, 1.86 g of ferrocene and 20 ml of methylene chloride were added, and the resulting mixture was heat-refluxed at 50° C. for 9 hours. Then, the mixture was poured into water, and made to be basic with potassium hydroxide, and subjected to extraction with methylene chloride, and dried. The unreacted ferrocene was removed by a column chromatography, to obtain 3.20 g of undecanylferrocenyl ketone represented by the formula (A) in a yield of 87.0%. The proton nuclear magnetic resonance (1H--NMR) spectrum of the product is shown in FIG. 1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([Br:31])[C:28]=1[O:29]C)[C:5]([N:7]1[CH2:12][CH2:11][O:10][C:9]2[N:13]=[CH:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23](=[O:25])[CH3:24])=[CH:19][CH:18]=3)=[CH:16][C:8]1=2)=[O:6].[Br-].[Li+].N1CCNCC1.Cl>CN(C)C=O.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[C:27]([Br:31])[C:28]=1[OH:29])[C:5]([N:7]1[CH2:12][CH2:11][O:10][C:9]2[N:13]=[CH:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23](=[O:25])[CH3:24])=[CH:19][CH:18]=3)=[CH:16][C:8]1=2)=[O:6]
Reactant: COc1c(Br)cc(C(=O)N2CCOc3ncc(-c4ccc(C(C)=O)cc4)cc32)cc1Br
Agent: C1CNCCN1
Agent: Cl
Agent: [Br-]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1ccc(-c2cnc3c(c2)N(C(=O)c2cc(Br)c(O)c(Br)c2)CCO3)cc1
Temperature: 100 °C
Reaction time: 2.5 h
Yield: 55.5 %

Procedure:
In a 10 ml flask, 1-{4-[1-(3,5-dibromo-4-methoxy-benzoyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl]-phenyl}-ethanone (119 mg, 0.22 mmol), lithium bromide (189 mg, 2.2 mmol) and piperazine (28 mg, 0.33 mmol) were dissolved in 3 ml of N,N-dimethyl formamide, and then stirred at 100° C. for 2.5 hours. After completion of the reaction by adding water dropwise, the mixture was adjusted to weak acidic condition (pH=6) with 1N hydrochloric acid. The formed solid was filtered and washed with distilled water. The resulting solid was recrystallized from methanol to obtain the target compound 67, i.e., 1-{4-[1-(3,5-dibromo-4-hydroxy-benzoyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl]-phenyl}-ethanone (65 mg, 56%).
Reaction SMILES: [OH:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:18]=[CH:19][C:20]=2[CH3:21])[C:12]([NH:14][CH:15]2[CH2:17][CH2:16]2)=[O:13])=[O:7])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[CH:49](O)[CH3:50].N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[CH:15]1([NH:14][C:12](=[O:13])[C:11]2[CH:18]=[CH:19][C:20]([CH3:21])=[C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:4]=[CH:3][C:2]([O:1][CH:49]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][N:43]=4)[CH3:50])=[CH:23][CH:22]=3)[CH:10]=2)[CH2:16][CH2:17]1
Reactant: CC(O)c1ccccn1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1NC(=O)c1ccc(O)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccc(C(=O)NC2CC2)cc1NC(=O)c1ccc(OC(C)c2ccccn2)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 14.6 %

Procedure:
To 3-{[4-(hydroxy)benzoyl]amino}-N-cyclopropyl-4-methylbenzamide (150 mg, 0.484 mmol) in DCM (20 mL) was added polymer supported triphenyl phosphine (937 mg, 1.45 mmol) and the 1-pyridin-2-ylethanol (45 mg, 0.363 mmol). Diethyl azodicarboxylate (126 mg, 0.726 mmol) was then added dropwise. The reaction was stirred for 17 h at room temperature and was then filtered and the filtrates were evaporated. The crude residue was purified by flash silica chromatography using ethyl acetate in iso-hexane (5-100%) as the eluent to give the title compound as a colourless oil (22 mg, 11%); NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.68 (m, 2H), 1.64 (d, 3H), 2.22 (s, 3H), 2.83 (m, 1H), 5.60 (q, 1H), 7.02 (d, 2H), 7.31 (d, 2H), 7.43 (d, 1H), 7.62 (d, 1H), 7.80 (m, 2H), 7.90 (d, 2H), 8.35 (d, 1H), 8.58 (d, 1H), 9.75 (s, 1H); Mass Spectrum: M+H+ 416.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]([NH:12][NH2:13])=[O:11])=[CH:4][CH:3]=1.[Br:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[F:23])[CH:18]=O>C(O)C>[Br:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[F:23])/[CH:18]=[N:13]/[NH:12][C:10](=[O:11])[CH2:9][NH:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1
Reactant: NNC(=O)CNc1ccc(Cl)cc1
Reactant: O=Cc1ccc(F)c(Br)c1
Solvent: CCO
Product: O=C(CNc1ccc(Cl)cc1)N/N=C/c1ccc(F)c(Br)c1
Temperature: 25 °C
Yield: 65.8 %

Procedure:
2-(4-Chlorophenylamino)acetohydrazide (B) (101 mg, 0.51 mmol) and 3-bromo-4-fluorobenzaldehyde (104 mg, 0.51 mmol) were refluxed in ethanol (3 mL) for 15 hours. After cooling to room temperature the precipitate was collected by filtration, washed with ethanol (20 mL) and water (20 mL). Drying in vacuo yielded the title compound (129 mg, 66%) as a colorless powder. 1H NMR δ (ppm) (DMSO-d6): 3.84 and 4.28 (2 H, two d), 6.01 and 6.25 (1 H, two br s), 6.62-6.69 (2 H, m), 7.12-7.17 (2H, m), 7.47-7.51 (1 H, m), 7.77-7.83 (1 H, m), 8.01 and 8.25 (1 H, two s), 8.05-8.12 (1H, m), 11.63 (1 H, two s). LCMS (10 cm_apci_formic) Rt 3.85 min; m/z 384/386/388 [M+H].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][C:7]#[N:8].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH2:7][NH2:8]
Reactant: COc1ccccc1OCC#N
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: COc1ccccc1OCCN
Temperature: 0 °C
Yield: 55 %

Procedure:
To a solution of 2-(2-methoxy-phenoxy)acetonitrile (5 g, 31 mmol) in anhydrous ethyl ether (100 ml) was added lithium aluminum hydride (1.6 g, 40 mmol) portionwise. The reaction mixture was heated to reflux for 3 hours and then cooled to 0° C. The reaction was quenched with 1N hydrochloric acid and diluted with water (PH=1, aqueous layer). The mixture was extracted with ethyl acetate (3×150 ml), neutralized with 50% sodium hydroxide to pH>10, and extracted again with more ethyl acetate (3×100 ml). The combined organic layers were washed with brine (3×150 ml), dried over anhydrous sodium sulfate and filtered. The solvent was removed under vacuum to afford 2.85 g (56%) of product as an oil; MS EI m/e 167 (M+).
Reaction SMILES: [F:1][C:2]1[C:3]([O:29][CH3:30])=[C:4]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[CH:19]=[N:20][N:21]([CH:23]5[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]5)[CH:22]=4)[CH:16]=3)[NH:11][CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(N(CC)CC)C.[CH2:38]([S:41](Cl)(=[O:43])=[O:42])[CH2:39][CH3:40]>C(Cl)Cl>[F:1][C:2]1[C:3]([O:29][CH3:30])=[C:4]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[CH:19]=[N:20][N:21]([CH:23]5[CH2:24][CH2:25][N:26]([S:41]([CH2:38][CH2:39][CH3:40])(=[O:43])=[O:42])[CH2:27][CH2:28]5)[CH:22]=4)[CH:16]=3)[NH:11][CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: CCCS(=O)(=O)Cl
Reactant: COc1c(F)cc(F)cc1-c1c[nH]c2ncc(-c3cnn(C4CCNCC4)c3)cc12
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCS(=O)(=O)N1CCC(n2cc(-c3cnc4[nH]cc(-c5cc(F)cc(F)c5OC)c4c3)cn2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 282 (100 mg, 0.244 mmol) in DCM was added triethylamine (49 mg, 0.4887 mmol). Propane sulfonyl chloride 339 (52 mg, 0.366 mmol) was added to the reaction and stirred for 2 h at rt. The reaction mixture was diluted with dichloromethane and washed with water twice. The organic layer was dried over sodium sulphate and concentrated to get the crude, which was purified by flash column using 100-200 mesh silica gel. The compound was eluted at 2% methanol in chloroform as off white coloured solid 3-(3,5-difluoro-2-methoxyphenyl)-5-(1-(1-(propylsulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine 340. 1H NMR (400 MHz, CDCl3) δ: 9.68 (s, 1H), 8.53 (d, 1H), 8.17 (d, 1H), 7.84 (s, 1H), 7.73 (m, 2H), 7.09 (m, 1H), 6.82 (m, 1H), 4.31 (m, 1H), 3.95 (m, 2H), 3.68 (d, 3H), 3.01 (m, 2H), 2.94 (m, 2H), 2.36 (m, 2H), 2.14 (m, 2H), 1.86 (m, 2H), 1.06 (m, 3H) and MS ES+516.1.
Reaction SMILES: C([O:4][CH2:5][C:6]1[C@@:23]2([CH3:24])[C:10]([CH2:11][CH2:12][C@@H:13]3[C@@H:22]2[CH2:21][CH2:20][C@@:18]2([CH3:19])[C@H:14]3[CH2:15][CH2:16][C:17]2=[O:25])=[CH:9][C:8](=[O:26])[CH:7]=1)(=O)C.CO.[OH-].[K+]>C(Cl)Cl>[OH:4][CH2:5][C:6]1[C@@:23]2([CH3:24])[C:10]([CH2:11][CH2:12][C@@H:13]3[C@@H:22]2[CH2:21][CH2:20][C@@:18]2([CH3:19])[C@H:14]3[CH2:15][CH2:16][C:17]2=[O:25])=[CH:9][C:8](=[O:26])[CH:7]=1
Reactant: CC(=O)OCC1=CC(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: C[C@]12C(CO)=CC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Yield: 87.6 %

Procedure:
2.2 g of 1-acetoxymethylandrosta-1,4-diene-3,17-dione is stirred under argon gas atmosphere in 20 ml of methylene chloride and 25 ml of methanol with 250 mg of potassium hydroxide at 0° to 5° C. for 5 hours. The mixture is then neutralized with acetic acid, concentration, and precipitated into water. The product is suctioned off, washed with water, and dried. Recrystallization from acetone/hexane yields 1.7 g of 1-hydroxymethylandrosta-1,4-diene-3,17-dione, mp 201°-202° C.
Reaction SMILES: C(NC1C=CC(C2C=C3C(=CC=2)C(=O)N([C@@H](C(C)C)C(O)=O)C3)=CC=1)(=O)C1C=CC=CC=1.[CH3:33][CH:34]([CH3:66])[C@H:35]([N:40]1[CH2:48][C:47]2[C:42](=[CH:43][CH:44]=[C:45]([C:49]3[CH:54]=[CH:53][C:52]([NH:55][C:56](=[O:64])[C:57]4[CH:62]=[CH:61][C:60]([CH3:63])=[CH:59][CH:58]=4)=[CH:51][CH:50]=3)[CH:46]=2)[C:41]1=[O:65])[C:36]([O:38]C)=[O:37]>>[CH3:33][CH:34]([CH3:66])[C@H:35]([N:40]1[CH2:48][C:47]2[C:42](=[CH:43][CH:44]=[C:45]([C:49]3[CH:54]=[CH:53][C:52]([NH:55][C:56](=[O:64])[C:57]4[CH:58]=[CH:59][C:60]([CH3:63])=[CH:61][CH:62]=4)=[CH:51][CH:50]=3)[CH:46]=2)[C:41]1=[O:65])[C:36]([OH:38])=[O:37]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2cc(-c3ccc(NC(=O)c4ccc(C)cc4)cc3)ccc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2cc(-c3ccc(NC(=O)c4ccccc4)cc3)ccc2C1=O
Product: Cc1ccc(C(=O)Nc2ccc(-c3ccc4c(c3)CN([C@H](C(=O)O)C(C)C)C4=O)cc2)cc1
Yield: 93 %

Procedure:
The compound of example 319 was prepared analogous to compound of example 305 by hydrolysis of compound of example 318.
Reaction SMILES: [CH2:1]([C:8](=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:9]=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(=O)C1C=CC=CC=1.[OH-].[Na+].C(=O)CCCCCCCC>>[CH2:11]([CH:8]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH2:9][OH:10])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CCCCCCCC(C=O)=Cc1ccccc1
Agent: CCCCCCCCC=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=Cc1ccccc1
Product: CCCCCCCC(CO)Cc1ccccc1

Procedure:
The acohol was prepared by hydrogenation of α-heptylcinnamaldehyde exactly as in Example 1.α-Heptylcinnamaldehyde was pepared as follows: To a mixture of 53.8g (0.50 mole) benzaldehyde 50ml ethanol and 25 ml 10% NaOH at reflux were added 56.8 g (0.40 mole) nonanal dropwise over 20 min. Halfway through the addition of nonanal an additional 25 ml 10% NaOH were added. After two hours at reflux the mixture was cooled, diluted with 100 ml 30°-60° petroleum ether, washed once with 50 ml 5% HCl, once with saturated NaCl brine, filtered through 4A molecular sieves, stripped and fractionally distilled, bp 135°-150°/0.15 mm, to give 56.6 g (61%) whose IR showed aromatic CH stretch from 3000-3100 cm -1, aldehyde CH at 2705 cm-1, and an aldehyde C=O at 1706 cm-1.