Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH:3]([O:17][CH3:18])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[C:6]([O:14][CH3:15])[C:5]=1Br.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[O:29][CH2:30][CH3:31])[CH:24]=[O:25]>>[CH3:1][O:2][CH:3]([O:17][CH3:18])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[C:6]([O:14][CH3:15])[C:5]=1[CH:24]([OH:25])[C:23]1[CH:26]=[CH:27][C:28]([O:29][CH2:30][CH3:31])=[C:21]([O:20][CH3:19])[CH:22]=1
Reactant: COc1cc(C(OC)OC)c(Br)c(OC)c1OC
Reactant: CCOc1ccc(C=O)cc1OC
Product: CCOc1ccc(C(O)c2c(C(OC)OC)cc(OC)c(OC)c2OC)cc1OC
Yield: 84 %

Procedure:
2-bromo-3,4,5-trimethoxybenzaldehyde dimethylacetal and 3-methoxy-4-ethoxybenzaldehyde are reacted in the same manner as described in Example 1-(1), whereby 2-(3-methoxy-4-ethoxy-α-hydroxybenzyl)-3,4,5-trimethoxybenzaldehyde dimethylacetal is obtained as colorless syrup. Yield: 84%
Reaction SMILES: [OH-].[Na+].[CH:3]1([C:6]2[CH:11]=[C:10]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[CH:24]=[CH:23][C:22]([C:25]([O:27]C)=[O:26])=[C:21]([CH2:29][CH3:30])[C:20]4=[O:31])[CH2:15][CH2:14]3)[C:9]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:8][C:7]=2[C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[CH2:5][CH2:4]1.Cl>CO>[CH:3]1([C:6]2[CH:11]=[C:10]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[C:21]([CH2:29][CH3:30])[C:20]4=[O:31])[CH2:15][CH2:14]3)[C:9]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:8][C:7]=2[C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[CH2:4][CH2:5]1
Reactant: CCc1c(C(=O)OC)ccn(C2CCN(Cc3cc(C4CC4)c(-c4ccc(F)cc4)cc3OC(C)C)CC2)c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCc1c(C(=O)O)ccn(C2CCN(Cc3cc(C4CC4)c(-c4ccc(F)cc4)cc3OC(C)C)CC2)c1=O
Reaction time: 1 h
Yield: 63.2 %

Procedure:
A 2 M aqueous sodium hydroxide solution (1 mL) was added at room temperature to a methanol (4 mL) solution of methyl 1-(1-((2-cyclopropyl-4′-fluoro-5-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-3-ethyl-2-oxo-1,2-dihydropyridine-4-carboxylate (390 mg), and the mixture was stirred at 60 C for 1 hour in a nitrogen atmosphere and then neutralized with 1 M hydrochloric acid. The reaction mixture was stirred at room temperature for 30 minutes, and then, the deposited crystal was collected by filtration and recrystallized (diisopropyl ether/ethanol) to obtain the title compound (240 mg).
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:6](=[O:7])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:4]([C:15]2[CH:20]=[CH:19][C:18](S(C)(=O)=O)=[CH:17][CH:16]=2)[O:3]1.FC1C=C(CC(C2C=C[C:39]([S:42](C)(=[O:44])=[O:43])=CC=2)=O)C=CC=1.[H-].[Na+].BrC(C)(C)C(C#N)=O>C1COCC1>[CH3:1][C:2]1([CH3:25])[C:6](=[O:7])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[C:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[S:42]([CH3:39])(=[O:44])=[O:43])[O:3]1
Reactant: CC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(c2cccc(F)c2)C1=O
Reactant: CS(=O)(=O)c1ccc(C(=O)Cc2cccc(F)c2)cc1
Agent: CC(C)(Br)C(=O)C#N
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(C)OC(c2ccccc2S(C)(=O)=O)=C(c2cccc(F)c2)C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Another variation to prepare 2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone was performed starting from 2-(3-fluorophenyl)-1-{4-(methylsulfonyl)phenyl}-ethanone as follows: To a stirred solution of 2-(3-fluorophenyl)-1-(4-methylsulfonylphenyl)-ethanone (1 g) in 10 ml of THF, was added 0.23 g of 95% sodium hydride at 0° C. The reaction solution was stirred for 1 hour at the same temperature. Then 0.64 g of a-bromo-isobutyric cyanide was added dropwise to the reaction mixture at 0° C. The reaction mixture was stirred for another 7 hours while being allowed to warm to room temperature. Then the reaction was quenched with 5 ml of water. The mixture was concentrated in vacuo, and was dissolved in 50 ml of water. The aqueous solution was extracted with ethylacetate (100 ml). The organic layer was washed with brine, concentrated in vacuo. Then the resulting residue was purified by column chromatography (hexane/ethylacetate) to afford 0.75 g of 2,2-dimethyl-4-(3-fluorophenyl)-5-{(methylsulfonyl)phenyl}-3(2H)-furanone.
Reaction SMILES: [CH2:1]([C:8]1([CH2:19][N:20]([CH3:22])[CH3:21])[CH2:13][CH2:12][C:11]([N:16]([CH3:18])[CH3:17])([C:14]#N)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]1([Mg]Cl)[CH:28]=[CH:27]C=[CH:25][CH:24]=1.[NH4+].[Cl-].O>C1COCC1>[CH2:1]([C:8]1([CH2:19][N:20]([CH3:21])[CH3:22])[CH2:13][CH2:12][C:11]([N:16]([CH3:17])[CH3:18])([C:14]2[CH:27]=[CH:28][CH:23]=[CH:24][CH:25]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN(C)CC1(Cc2ccccc2)CCC(C#N)(N(C)C)CC1
Reactant: Cl[Mg]c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Product: CN(C)CC1(Cc2ccccc2)CCC(c2ccccc2)(N(C)C)CC1
Reaction time: 8 h

Procedure:
The title compound of step 1 (0.88 g, 2.94 mmol) was dissolved in THF (35 mL) and mixed in drops with 2M phenylmagnesium chloride solution (5.1 mL, 10.2 mmol) with ice cooling. The reaction solution was heated to boiling for 8 h. For work up the solution was mixed with 20% NH4Cl solution (0.6 mL) and water (0.4 mL) with ice cooling, extracted with ether (3×25 mL), the ether solution was washed with water, dried (Na2SO4) and concentrated to low volume in a vacuum. The residue was purified by column chromatography with EtOH/EE (1:20). 2 fractions were obtained, wherein according to LCMS, inter alia, the more polar fraction (300 mg) contained the desired substance.
Reaction SMILES: Cl[CH2:2][CH:3]([OH:12])[CH2:4][CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[CH3:13][C:14]1[CH:19]=[C:18]([OH:20])[CH:17]=[C:16]([CH3:21])[C:15]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[OH-].[Na+]>C(O)C>[CH3:21][C:16]1[CH:17]=[C:18]([O:20][CH2:2][CH:3]([OH:12])[CH2:4][CH2:5][C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:19]=[C:14]([CH3:13])[C:15]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: OC(CCl)CCc1cccnc1
Reactant: Cc1cc(O)cc(C)c1-c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(OCC(O)CCc2cccnc2)cc(C)c1-c1ccccc1
Yield: 55 %

Procedure:
Prepared according to the method described in Example 24b) from (±)-α-(chloromethyl)-3-pyridinepropanol (0.70 g), 2,6-dimethylbiphenyl-4-ol (0.79 g), ethanol (15 ml) and aqueous sodium hydroxide (1.9 M, 2.5 ml). After work up the residue was purified by column chromatography over silica with ethyl acetate to give the title compound as a solid (0.72 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1.CN(C)CCN(C)C.[Li]CCCC.CN([CH:28]=[O:29])C.[NH4+].[Cl-]>C1COCC1.CCOCC>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[C:4]=1[CH:28]=[O:29]
Reactant: CN(C)C=O
Reactant: COc1ccc2c(c1)OCO2
Agent: CN(C)CCN(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: COc1ccc2c(c1C=O)OCO2
Temperature: -20 °C
Reaction time: 1 h

Procedure:
A cooled (−20° C.) mixture of 5-methoxybenzo[d][1,3]dioxole (4.560 g; 30.00 mmol), and N1,N1,N2,N2-tetramethylethane-1,2-diamine (5.36 ml; 36.00 mmol) in anh. THF (300 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (18.75 ml; 30.00 mmol). The resulting mixture was further stirred at −20° C. for 1 h. Anh. DMF (12.0 ml; 154.98 mmol) was then added, and the mixture was stirred at rt for 20 min. Aq. sat. NH4Cl and Et2O were successively added, and the aq. layer was further extracted with Et2O. The mixed organic layers were washed with water, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (heptane/AcOEt=1/1) afforded 5-methoxybenzo[d][1,3]dioxole-4-carbaldehyde as a yellow oil. LC-MS (conditions A): tR=0.55 min.; [M+H]+: 181.09 g/mol.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][C:9]1[CH:40]=[CH:39][C:12]2[N:13]([CH2:34][CH2:35][CH2:36][CH2:37][OH:38])[C:14]([CH2:16][N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20](=[O:27])[N:19]([CH2:28][C:29]([F:32])([F:31])[F:30])[C:18]3=[O:33])=[N:15][C:11]=2[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)(=O)C>ClCCl>[NH2:7][CH2:8][C:9]1[CH:40]=[CH:39][C:12]2[N:13]([CH2:34][CH2:35][CH2:36][CH2:37][OH:38])[C:14]([CH2:16][N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20](=[O:27])[N:19]([CH2:28][C:29]([F:32])([F:31])[F:30])[C:18]3=[O:33])=[N:15][C:11]=2[CH:10]=1
Reactant: CC(C)(C)OC(=O)NCc1ccc2c(c1)nc(Cn1c(=O)n(CC(F)(F)F)c(=O)c3ccccc31)n2CCCCO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CC(=O)Cl
Product: NCc1ccc2c(c1)nc(Cn1c(=O)n(CC(F)(F)F)c(=O)c3ccccc31)n2CCCCO
Reaction time: 6 h

Procedure:
To a suspension of [2-[2,4-dioxo-3-(2,2,2-trifluoro-ethyl)-3,4-dihydro-2H-quinazolin-1-ylmethyl]-1-(4-hydroxy-butyl)-1H-benzoimidazol-5-ylmethyl]-carbamic acid tert-butyl ester (80 mg, 0.14 mmol) in dichloromethane (3 mL) was added TFA (319 μL, 4.14 mmol). The solution was allowed to stir for 6 hrs. followed by the removal of the volatiles in vacuo. The resulting trifluoroacetate was dissolved in methanol (3 mL) followed by the addition of acetyl cloride (98 μL, 1.4 mmol) and concentrated after 10 min. This procedure was repeated once allowing the reaction to run for 3 hrs. The solution was concentrated in vacuo and the residue stripped with DCM (thrice). The product was triturated in diethyl ether and the ether decanted to yield 1-[5-Aminomethyl-1-(4-hydroxy-butyl)-1H-benzoimidazol-2-ylmethyl]-3-(2,2,2-trifluoro-ethyl)-1H-quinazoline-2,4-dione; HCl salt (79 mg, 100%) as a white solid:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][C:8]3=[CH:7][C:6]=2[C:5]=1[C:16]([O:18][CH3:19])=[O:17])([O-:3])=[O:2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>[N+:1]([C:4]1[CH:12]=[CH:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][CH:8]3[CH2:7][C:6]=2[C:5]=1[C:16]([O:18][CH3:19])=[O:17])([O-:3])=[O:2]
Reactant: COC(=O)c1c([N+](=O)[O-])ccc2c1cc1n2CCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: COC(=O)c1c([N+](=O)[O-])ccc2c1CC1CCCN21
Temperature: 25 °C
Yield: 164.7 %

Procedure:
Methyl 7-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 19, 1.00 g) was dissolved in TFA (100 ml) and sodium triacetoxyborohydride (8.11 g) was added. The reaction mixture was stirred at room temperature, then diluted with toluene and concentrated in vacuo. The residue was dissolved in aqueous potassium carbonate solution and extracted with ethyl acetate, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 0-2% to give methyl 7-nitro-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (1.66 g) as a yellow gum.
Reaction SMILES: [CH3:1][C:2]1[C:8]([Cl:9])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:10][C:11]1C2C(=CC=C(I)C=2)N=[CH:13][C:12]=1[C:22]([NH2:24])=[O:23]>>[Cl:10][C:11]1[C:5]2[C:3](=[C:2]([CH3:1])[C:8]([Cl:9])=[CH:7][CH:6]=2)[N:4]=[CH:13][C:12]=1[C:22]([NH2:24])=[O:23]
Reactant: Cc1c(N)cccc1Cl
Reactant: NC(=O)c1cnc2ccc(I)cc2c1Cl
Product: Cc1c(Cl)ccc2c(Cl)c(C(N)=O)cnc12

Procedure:
Intermediate 68 was prepared from 2-methyl-3-chloroaniline (Aldrich) in a similar manner to Intermediate 13.
Reaction SMILES: [CH2:1]([OH:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C([Li])CCC.[Br:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18]Br>O1CCCC1.C(N(C)C)=O.CCCCCC>[CH2:1]([O:9][CH2:18][C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[Br:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCO
Reactant: BrCc1ccccc1Br
Agent: [Li]CCCC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCCCCOCc1ccccc1Br

Procedure:
prepared from octanol and n-butyllithium, in a mixture of tetrahydrofuran/hexane dimethyl formamide was condensed with 2-bromobenzyl bromide to yield 2(octyloxy)methylbromobenzene. This material was treated with n-butyllithium in ether/hexane mixture and subsequently treated with paraformaldehyde to yield 2-(octyloxy)methylbenzyl alcohol. This material was then treated with triphenyl phosphonine bromide to yield [2-[(octyloxy)-methyl]phenyl]methyl]triphenyl phosphonium bromide. Condensation of this material with 7-formyl-3-methyl-2,4,6-octatrienoic acid ethyl ester, as in Example 3, followed by hydrolysis, as in Example 5, gave the (All-E)-3,7-Dimethyl-9-[2-[(octyloxy)-methyl]phenyl]-2,4,6,8-nonatetraenoic acid, mp 120-121 (from dichloro methane/hexane mixture).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[N:9]=[C:10]([C:20]([CH3:23])([CH3:22])[CH3:21])[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15](Cl)[N:14]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH:24][S:25]([C:28]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=1[F:35])(=[O:27])=[O:26].[NH3:36].C(O)(C)C>>[NH2:36][C:15]1[N:14]=[C:13]([C:12]2[S:11][C:10]([C:20]([CH3:22])([CH3:21])[CH3:23])=[N:9][C:8]=2[C:7]2[C:2]([Cl:1])=[C:3]([NH:24][S:25]([C:28]3[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=3[F:35])(=[O:26])=[O:27])[CH:4]=[CH:5][CH:6]=2)[CH:18]=[CH:17][N:16]=1
Reactant: N
Reactant: CC(C)(C)c1nc(-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2Cl)c(-c2ccnc(Cl)n2)s1
Solvent: CC(C)O
Product: CC(C)(C)c1nc(-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2Cl)c(-c2ccnc(N)n2)s1

Procedure:
Following a procedure analogous to the procedure described in Example 52, Step B using N-{2-chloro-3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide (156 mg, 0.281 mmol) and ammonia in isopropanol (15 mL, 30 mmol), the title compound was obtained as a white solid (56 mg, 35% yield). MS (ESI): 536 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:20][CH2:21][CH3:22])=[C:6]([C:8]2[NH:13][C:12](=[O:14])[C:11]([Br:15])=[C:10]([CH:16]([CH3:18])[CH3:17])[N:9]=2)[CH:7]=1.[O:23]=[CH:24][C@@H:25]([C@H:27]([C@@H:29]([C@@H:31]([CH2:33][OH:34])[OH:32])[OH:30])[OH:28])O>C(O)CCC.C(O)(=O)C>[Br:15][C:11]1[C:12](=[O:14])[NH:13][C:8]([C:6]2[CH:7]=[C:2]([NH:1][CH:33]3[CH:31]([OH:32])[CH:29]([OH:30])[CH:27]([OH:28])[CH:25]([CH2:24][OH:23])[O:34]3)[CH:3]=[CH:4][C:5]=2[O:19][CH2:20][CH2:21][CH3:22])=[N:9][C:10]=1[CH:16]([CH3:18])[CH3:17]
Reactant: CCCOc1ccc(N)cc1-c1nc(C(C)C)c(Br)c(=O)[nH]1
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CCCCO
Solvent: CC(=O)O
Product: CCCOc1ccc(NC2OC(CO)C(O)C(O)C2O)cc1-c1nc(C(C)C)c(Br)c(=O)[nH]1
Yield: 20.6 %

Procedure:
The compound of example 34 (200 mg, 0.55 mmol) was dissolved in n-butanol (10 ml), and added with glucose (200 mg, 1 mmol) and one drop of glacial acetic acid. The reaction mixture was heated under nitrogen protection to reflux for 12 h. The cooled reaction mixture was concentrated to dryness, and added with dichloromethane. The organic layer was washed with saturated saline (20 ml×3), dried with anhydrous Na2SO4, and concentrated under reduced pressure. The residue was passed through a silica gel column to give the title compound (60 mg, yield: 21%). 1H NMR (DMSO-d6) δ: 7.47 (1H, d), 7.21 (1H, dd), 7.09 (1H, d), 4.31 (1H, d), 4.01 (3H, t), 3.63 (1H, d), 3.46 (1H, d), 3.09-3.29 (4H, m), 2.57 (2H, q), 2.46 (2H, q), 1.72 (2H, m), 1.18 (6H, d), 0.95 (3H, t).
Reaction SMILES: N1C2C(=CC=CC=2)N=CC=1C=O.N1C=CC=C1C=O.N1C2C(=CC=CC=2)C(C=O)=C1.[CH:31]1([N:36]2[C:40]3=[N:41][C:42]([C:46]4C=N[C:53]5[C:48](=C[CH:50]=[CH:51][CH:52]=5)[N:47]=4)=[N:43][C:44](=[O:45])[C:39]3=[C:38]([CH2:56][CH3:57])[NH:37]2)[CH2:35][CH2:34][CH2:33][CH2:32]1.C1(N2C3=NC(C4NC=CC=4)=NC(=O)C3=C(CC)N2)CCCC1.C1(N2C3=NC(C4C5C(=CC=CC=5)NC=4)=NC(=O)C3=C(CC)N2)CCCC1>>[CH:31]1([N:36]2[C:40]3=[N:41][C:42]([C:46]4[C:51]([CH3:50])=[CH:52][CH:53]=[CH:48][N:47]=4)=[N:43][C:44](=[O:45])[C:39]3=[C:38]([CH2:56][CH3:57])[NH:37]2)[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: CCc1[nH]n(C2CCCC2)c2nc(-c3cnc4ccccc4n3)nc(=O)c1-2
Agent: CCc1[nH]n(C2CCCC2)c2nc(-c3c[nH]c4ccccc34)nc(=O)c1-2
Agent: CCc1[nH]n(C2CCCC2)c2nc(-c3ccc[nH]3)nc(=O)c1-2
Agent: O=Cc1c[nH]c2ccccc12
Product: CCc1[nH]n(C2CCCC2)c2nc(-c3ncccc3C)nc(=O)c1-2

Procedure:
It is contemplated that following the procedures of Example 2 but starting with 2-quinoxalinecarboxaldehyde, 2-pyrrolecarboxaldehyde, or 3-indolecarboxaldehyde in place of 6methyl-2-pyridinecarboxaldehyde there can be prepared 1-cyclopentyl-3-ethyl-6-(2-quinoxalyl)-pyrazolo [3,4-d]pyrimidin-4-one, 1-cyclopentyl-3-ethyl-6-(2-pyrrolyl)pyrazolo[3,4-d]-pyrimidin-4-one, and 1-cyclopentyl-3-ethyl-6-(3-indolyl) pyrazolo[3,4-d]pyrimidin-4-one.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[CH2:17][CH2:18][NH:19][C@@H:20]([CH3:30])[C@H:21]([OH:29])[C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[O:5][C:6]([CH3:13])([CH3:12])[C:7]([O:9]CC)=[O:8].[OH-].[Na+].Cl>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[CH2:17][CH2:18][NH:19][C@@H:20]([CH3:30])[C@H:21]([OH:29])[C:22]1[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=1)[O:5][C:6]([CH3:12])([CH3:13])[C:7]([OH:9])=[O:8]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CCN[C@@H](C)[C@H](O)c2ccc(O)cc2)c(Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: C[C@H](NCCc1ccc(OC(C)(C)C(=O)O)cc1Cl)[C@H](O)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 13 h
Yield: 90.3 %

Procedure:
To a solution of ethyl 2-[3-Chloro-4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-phenoxy]-2-methylpropionate (2.39 g) in ethanol (20 ml) was added 2N aqueous sodium hydroxide solution (8.2 ml ), and the mixture was stirred for 13 hours at room temperature. To the stirred reaction mixture was added 2N hydrochloric acid (8.2 ml) under ice-cooling. After the reaction mixture was concentrated under reduced pressure, azeotropic concentration with ethanol was undergone. The residue was washed with water (180 ml) and dried under reduced pressure to give 2-[3-chloro-4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]phenoxy]-2-methylpropionic acid (2.02 g).
Reaction SMILES: S([O-])([O-])(=O)=O.[Na+].[Na+].[SH:8][CH2:9][C@@H:10]([CH3:28])[C:11]([NH:13][C@@H:14]([CH2:18][S:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)[C:15]([OH:17])=[O:16])=[O:12].O.[C:30]1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[SH:8][CH2:9][C@@H:10]([CH3:28])[C:11]([NH:13][C@@H:14]([CH2:18][S:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)[C:15]([O:17][CH3:30])=[O:16])=[O:12]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: Cc1ccc(CSC[C@H](NC(=O)[C@H](C)CS)C(=O)O)cc1
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)[C@H](CSCc1ccc(C)cc1)NC(=O)[C@H](C)CS

Procedure:
Anhydrous sodium sulfate (3 g) is added to a solution of (2R)-2-[(2S)-3-mercapto-2-methylpropionylamino]-3-(4-methylbenzylthio)propionic acid (compound No. 1-1, 300 mg) and p-toluenesulfonic acid monohydrate (240 mg) in methanol (10 ml), and the mixture is refluxed for three hours and 30 minutes. Sodium sulfate is filtered out, and the filtrate is concentrated under reduced pressure. A 5% aqueous sodium hydrogencarbonate solution is added to the obtained residue, and the whole is extracted with ethyl acetate. The organic layer is washed with a 5% aqueous sodium hydrogencarbonate solution, a 5% aqueous citric acid solution and a saturated sodium chloride solution successively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the titled compound. The following compound is obtained by a method similar to Example 5.
Reaction SMILES: [Cl-].[Cl-].[Cl-].[Al+3].[CH3:5][C:6]1[N:16]2[C:17]3[C:12]([CH2:13][CH2:14][CH2:15]2)=[CH:11][CH:10]=[CH:9][C:8]=3[C:7]=1[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].[C:24](Cl)(=[O:28])[CH:25]([CH3:27])[CH3:26]>C(Cl)(Cl)Cl>[CH3:26][CH:25]([CH3:27])[C:24]([C:10]1[CH:11]=[C:12]2[C:17]3=[C:8]([C:7]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[C:6]([CH3:5])[N:16]3[CH2:15][CH2:14][CH2:13]2)[CH:9]=1)=[O:28]
Reactant: CCOC(=O)Cc1c(C)n2c3c(cccc13)CCC2
Reactant: CC(C)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Product: CCOC(=O)Cc1c(C)n2c3c(cc(C(=O)C(C)C)cc13)CCC2
Temperature: 10 °C
Reaction time: 12 h

Procedure:
63 g of aluminum trichloride were suspended in 150 ml of chloroform at a temperature of 10° C. A mixture of ethyl 5,6-dihydro-2-methyl-4H-pyrrolo[3,2,1-ij]quinoline-1-acetate and 26.3 g of isobutyryl chloride in 150 ml of chloroform was added to the suspension while the temperature was maintained at 10° C. The reaction mixture was stirred at room temperature for hour, then heated under reflux for 4 hours and kept at room temperature for a further 12 hours. A further 10 g of aluminum chloride were then added, and the mixture was heated under reflux for a further hour. The reaction mixture was worked up by pouring it onto ice and then extracting with dichloromethane. The organic phase was washed with dilute aqueous sodium hydroxide solution, then washed with water until neutral, dried and concentrated. 80 g of crude product were obtained, which was purified by chromatography on a silica gel column using dichloromethane as the eluent. 42.5 g of ethyl 5,6-dihydro-8-(2-methyl-1-oxopropyl)-2-methyl-4H-pyrrolo[3,2,1-ij]quinoline-1-acetate were obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]3[CH:16]=[C:17]([C:19]4[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=4)[O:18][C:11]=23)[CH:7]=[CH:8][CH:9]=1)([O-])=O>C1COCC1.[Pd]>[CH3:26][O:25][C:23]1[CH:24]=[C:19]([C:17]2[O:18][C:11]3[C:12](=[N:13][CH:14]=[CH:15][C:10]=3[C:6]3[CH:5]=[C:4]([NH2:1])[CH:9]=[CH:8][CH:7]=3)[CH:16]=2)[CH:20]=[C:21]([O:29][CH3:30])[C:22]=1[O:27][CH3:28]
Reactant: COc1cc(-c2cc3nccc(-c4cccc([N+](=O)[O-])c4)c3o2)cc(OC)c1OC
Agent: [Pd]
Solvent: C1CCOC1
Product: COc1cc(-c2cc3nccc(-c4cccc(N)c4)c3o2)cc(OC)c1OC
Reaction time: 16 h
Yield: 27 %

Procedure:
7-(3-Nitro-phenyl)-2-(3,4,5-trimethoxy-phenyl)-furo[3,2-b]pyridine (0.121 mmol) is dissolved in THF (10 ml) and Pd—C 5% (0.2 g) is added and the reaction is hydrogenated 16 h at RT. The mixture is filtered and the filtrate removed in vacuo. The precipitate is suspended in diethylether and filtrated. The product is obtained after reversed phase column chromatography as yellow solid in a yield of 27%. HPLC (method A): Rt 2.45 min (purity 99.2%); LCMS (ESI+) (method E): Rt 1.89 min, M+H+ 377.1 m/z; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 8.60 (d, J=5.3, 1H), 7.80 (s, 1H), 7.71-7.55 (m, 2H), 7.51-7.33 (m, 4H), 6.97 (d, J=6.9, 1H), 4.42 (s, br, 2H), 3.93 (s, 6H), 3.75 (s, 3H).
Reaction SMILES: O=[C:2]1[CH:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[CH:4][O:3]1.Cl.[C:19]([O:23][C:24](=[O:27])[CH2:25][NH2:26])([CH3:22])([CH3:21])[CH3:20]>CO>[C:19]([O:23][C:24](=[O:27])[CH2:25][N:26]1[C:2](=[O:3])[CH:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[CH:4]1)([CH3:22])([CH3:21])[CH3:20]
Reactant: O=C(OCc1ccccc1)c1ccc(=O)oc1
Reactant: CC(C)(C)OC(=O)CN
Agent: Cl
Solvent: CO
Product: CC(C)(C)OC(=O)Cn1cc(C(=O)OCc2ccccc2)ccc1=O
Temperature: 23 °C
Reaction time: 1 h

Procedure:
A solution of benzyl 2-oxo-2H-pyran-5-carboxylate (906 mg, 3.94 mmol) and glycine tert butyl ester hydrochloride (726 mg, 4.33 mmol) in MeOH (20 mL) was treated with TEA (1.642 mL, 11.81 mmol). The reaction was stirred at 23° C. under nitrogen. After 1 h, the solution was concentrated in vacuo and purified by silica gel chromatography (eluent: 10-50% EtOAc/hexane), affording the title compound as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.11 (d, J=2.35 Hz, 1H), 7.90 (dd, J=9.59, 2.54 Hz, 1H), 7.31-7.54 (m, 5H), 6.55 (d, J=9.59 Hz, 1H), 5.30 (s, 2H), 4.56 (s, 2H), 1.48 (s, 9H). MS (ESI, positive ion) m/z: 366.0 (M+H).