Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O-].[Na+].CO.C1(S([CH2:15][CH2:16][CH2:17][CH:18]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][C:19]2=O)(=O)=O)C=CC=CC=1.CC(C)([O-])C.[K+]>O.C1(C)C=CC=CC=1>[C:18]12[CH2:17][CH2:16][CH:15]=[C:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=2
Reactant: O=C1CCCCCCCCCCC1CCCS(=O)(=O)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: C[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CO
Product: C1=C2CCC=C2CCCCCCCCC1
Yield: 83.7 %

Procedure:
29.0 ml of a 30% solution of sodium methoxide in methyl alcohol (0.15 mole) were added dropwise to a mixture of 36.4 g (0.10 mole) of 2-(3-phenylsulfonyl-prop-1-yl)-cyclododecanone and 200 ml of toluene, kept at reflux in a reaction vessel fitted with a water separator (addition period: ca. 1 hour). After this first addition, 14.6 g (0.13 mole) of potassium tert-butoxide were added to the reaction mixture, which was then heated to reflux during 4 hours. After the usual treatments of extraction and distillation, there were isolated 17.1 g (84% yield) of the desired compound.
Reaction SMILES: OP([O-])([O-])=O.[K+].[K+].[Na+].[Cl-].[O-]S([O-])(=O)=O.[Mg+2].[O:16]=[CH:17][C@@H:18]([C@H:20]([C@@H:22]([C@@H:24]([CH2:26][OH:27])[OH:25])[OH:23])[OH:21])[OH:19].OC1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O>>[CH:26]1([OH:27])[CH:17]([OH:16])[CH:18]([OH:19])[CH:20]([OH:21])[CH:22]([OH:23])[CH:24]1[OH:25]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=P([O-])([O-])O
Agent: O=S(=O)([O-])[O-]
Agent: OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O
Product: OC1C(O)C(O)C(O)C(O)C1O

Procedure:
When the OD600 reached about 2 units, the culture was transferred to a fermentor at a 5% ratio. The fermentation medium consisted of: 2.0 g/L(NH4)2SO4; 8.0 g/L K2HPO4; 2.0 g/L NaCl; 1.0 g/L Na3Citrate.2H2O; 1.0 g/L MgSO4. 7H2O; 0.025 g/L CaCl2.2H2O; 0.05 g/L FeSO4.7H2O; 0.4 ml/L Neidhardt micronutrients and 2.0 g/L glucose. Two to three hours after inoculation, an exponential glucose feed was set up using a 60% glucose solution. The feed was supplied at the required rate to support microbial growth at an exponential rate of 0.15 h−1. When the OD600 reached a value of 30 (around 20 hours after inoculation, corresponding to a cell biomass of 15-16 g DCW/L), the temperature was reduced to 30° C., 30 μM ferric citrate was added and the feed was switched from glucose to a mixture of 50% glucose and 10% lactose. This exponential feed was maintained for 8 hours. At the end of the fermentation the cell concentration was 28 g DCW/L, with an enzyme expression level of about 25% of the total protein.
Reaction SMILES: CC(C)([O-])C.[K+].[F:7][C:8]1[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:9]=1[NH:10][C@@H:11]([CH3:14])[CH2:12][OH:13].C(O[CH:24]=[C:25]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])C>CN(C=O)C>[F:7][C:8]1[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:9]=1[N:10]([CH:24]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C@@H:11]([CH3:14])[CH2:12][OH:13]
Reactant: C[C@@H](CO)Nc1ccc(F)c(F)c1F
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(=CN(c1ccc(F)c(F)c1F)[C@@H](C)CO)C(=O)OCC
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 75 %

Procedure:
Potassium tertiary-butoxide (62 mg) was added to DMF (2 ml) and cooled to 0° C. Then a solution of the compound (100 mg) obtained in Example 51 in DMF (200 μl) was dropped thereinto. After stirring for 15 minutes, diethyl ethoxymethylenemalonate was dropped thereinto and the resultant mixture was stirred for 8 hours at room temperature. After treating in a conventional manner, it was subjected to silica gel column chromatography to thereby give 137 mg (75%) of the title compound as a colorless solid. The 1H-NMR and IR spectral data of this product was identical with those of the compound obtained in Example 63.
Reaction SMILES: [CH3:1][O:2][C:3]([C:13]#[N:14])=[CH:4][CH:5]1[CH:7]([C:8]([O-:10])=[O:9])[C:6]1([CH3:12])[CH3:11].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:13]#[N:14])=[CH:4][CH:5]1[CH:7]([C:8]([OH:10])=[O:9])[C:6]1([CH3:11])[CH3:12]
Reactant: COC(C#N)=CC1C(C(=O)[O-])C1(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COC(C#N)=CC1C(C(=O)O)C1(C)C

Procedure:
5 g of tert-butyl (1R,trans,ΔE) 3-(2-methoxy-2-cyanoethenyl)-2,2-dimethyl-cyclopropane carboxylate were dissolved in 50 ml of toluene and after 0.5 g of p-toluene sulfonic acid were added thereto, the reaction mixture was refluxed for 45 minutes, then cooled. The mixture was evaporated to dryness under reduced pressure and water and ether were added to the residue. After stirring, the decanted organic phase was evaporated to dryness under reduced pressure to obtain 3.8 g of (1R,trans,ΔE) 3-(2-methoxy-2-cyanoethenyl)-2,2-dimethyl-cyclopropane carboxylic acid melting at 125° C.
Reaction SMILES: [OH-].[Na+:2].[CH3:3][C:4]([C:7]1[CH:8]=[CH:9][C:10]([S:13]([NH:16][C:17]2[C:18]([O:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][C:39]=3[O:40][CH3:41])=[C:19]([O:29][CH2:30][CH2:31][OH:32])[N:20]=[C:21]([C:23]3[N:24]=[CH:25][CH:26]=[CH:27][N:28]=3)[N:22]=2)(=[O:15])=[O:14])=[CH:11][CH:12]=1)([CH3:6])[CH3:5]>CO.ClCCl.C(OCC)(=O)C>[CH3:6][C:4]([C:7]1[CH:12]=[CH:11][C:10]([S:13]([N-:16][C:17]2[C:18]([O:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][C:39]=3[O:40][CH3:41])=[C:19]([O:29][CH2:30][CH2:31][OH:32])[N:20]=[C:21]([C:23]3[N:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[N:22]=2)(=[O:14])=[O:15])=[CH:9][CH:8]=1)([CH3:3])[CH3:5].[Na+:2]
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCO
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: ClCCl
Product: COc1ccccc1Oc1c([N-]S(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCO
Reaction time: 3.5 h

Procedure:
Sodium hydroxide (0.44 g) was added to a mixture of bosentan (5 g) in methanol (10 mL), dichloromethane (2.5 mL) and ethyl acetate (40 mL). The reaction mixture was stirred for 3.5 hours at 20° C. to 25° C. and the solid was filtered to obtain the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=O.[O:11]1[C:15]2([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6][N:18]1[CH2:19][CH2:20][C:15]2([O:14][CH2:13][CH2:12][O:11]2)[CH2:16][CH2:17]1
Reactant: COc1cccc(C=O)c1
Reactant: C1CC2(CCN1)OCCO2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1cccc(CN2CCC3(CC2)OCCO3)c1
Reaction time: 19 h
Yield: 94.7 %

Procedure:
A mixture of 3-methoxybenzaldehyde (10.0 g, 73.4 mmol), 1,4-dioxa-8-azaspiro[4.5]decane (10.5 g, 73.4 mmol), sodium triacetoxyborohydride (20.2 g, 95.3 mmol), and acetic acid (4.2 mL), in methylene chloride (400 mL), was stirred at ambient temperature. After 19 h, a 2 N aqueous sodium carbonate solution (220 mL) was added portionwise. After stirring for 15 min, the aqueous layer was separated and extracted with methylene chloride (100 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo to provide 8-(3-methoxybenzyl)-1,4-dioxa-8-azaspiro[4.5]decane (18.3 g, 95%) as a yellow oil: 1H NMR (CDCl3, 500 MHz) δ 7.25-7.19 (m, 1H), 6.91-6.89 (m, 2H), 6.80-6.77 (m, 1H), 3.94 (s, 4H), 3.80 (s, 3H), 3.50 (s, 2H), 2.53-2.49 (m, 4H), 1.76-1.72 (m, 4H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].I[CH3:18]>CN(C)C=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([CH3:18])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1)#[N:2]
Reactant: CCOC(=O)Cc1ccc(C#N)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)c1ccc(C#N)cc1
Reaction time: 1 h

Procedure:
To a stirred solution of ethyl 2-(4-cyanophenyl)acetate (0.8 g, 4.101 mmol) in anhydrous dimethylformamide were added 60% sodium hydride (180 mg, 4.511 mol) and Iodo methane were added after 10 min with an ice bath. The reaction mixture was stirred for 1 h hours, quenched with water and extracted with ethylacetate which is washed with water and brine. The organic layer was dried over magnesium sulfate and filtered. The filterate was concentrated under reduced pressure. The residue was purified by column chromatography. Ethyl 2-(4-cyanophenyl)propanoate (453 mg) was obtained as 48%
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35](Cl)(=[O:37])=[O:36])[CH:34]=1.[Cl-].[NH4+]>CC1CCCO1.O>[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[N:10][N:11]=2)(=[O:37])=[O:36])[CH:34]=1
Reactant: COc1ccc(CNc2nncs2)c(OC)c1
Reactant: O=S(=O)(Cl)c1cc(Cl)c(F)cc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: O
Solvent: CC1CCCO1
Product: COc1ccc(CN(c2nncs2)S(=O)(=O)c2cc(Cl)c(F)cc2F)c(OC)c1
Temperature: 15 °C
Reaction time: 0.75 h
Yield: 58.5 %

Procedure:
N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 19, 203.4 g, 0.809 mol) was dissolved in 2-methyltetrahydrofuran (1.63 L) and the yellow suspension cooled to between −38° C. and −45° C. Lithium bis(trimethylsilyl)amide (890 mL of 1M solution in tetrahydrofuran, 0.890 mol) was added slowly over 15 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. This orange suspension was stirred at −38° C. to −45° C. for 45 minutes and then a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride, (200 g, 0.809 mol) in 2-methyltetrahydrofuran (407 mL) added slowly over 20 minutes keeping the temperature between −38° C. and −45° C. The mixture was warmed to 15° C. over 1 hour. The reaction was quenched with a solution of ammonium chloride (203.4 g, 3.80 mol) in water (1.02 L) and stirred vigorously for 5 minutes. The layers were separated and the organic layer washed with water (813.6 mL) and concentrated in vacuo to give an orange solid which was triturated with isopropyl acetate (1.22 L) to afford the title compound as a yellow-orange solid (218.6 g, 58%).
Reaction SMILES: [C:1]([CH2:4][C@@H:5]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])([OH:3])=O.[NH:20]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.Cl>C(Cl)Cl>[N:20]1([C:1]([CH2:4][C@@H:5]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[O:3])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: C1CCCNCCC1
Reactant: CC(C)C[C@H](CC(=O)O)C(=O)OCc1ccccc1
Agent: Cl
Solvent: ClCCl
Product: CC(C)C[C@H](CC(=O)N1CCCCCCC1)C(=O)OCc1ccccc1
Yield: 86.8 %

Procedure:
Benzyl (2R)-2-carboxymethyl-4-methylvalerate (320 mg), octahydroazocin (165 mg) and WSCD.HCl (280 mg) were reacted in methylene chloride (20 ml) in a similar manner to that of Preparation 18 to give benzyl (2R)-2-(octahydroazocin-1-ylcarbonylmethyl)-4-methylvalerate (378 mg).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[C:4]([Br:11])[N:3]=1.O.Cl>C(O)C.[Fe]>[NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([Br:11])[N:3]=1
Reactant: Nc1nc(Br)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Solvent: CCO
Solvent: O
Product: Nc1ccc(Br)nc1N
Yield: 47.9 %

Procedure:
To a suspension of 2-amino-6-bromo-3-nitropyridine (21.8 g) in ethanol (220 ml)—water (22 ml) was added iron powder (39.0 g) at room temperature. Conc. hydrochloric acid (0.8 ml) was added and the mixture was gradually heated with stirring to start the reaction. The mixture was refluxed under heating for 2 hr, and an insoluble matter was removed by filtration while hot. The solvent was evaporated under reduced pressure, and water (200 ml) and active charcoal were added to the resulting solid, which was followed by heating. The insoluble matter was removed by filtration while hot, and water was evaporated under reduced pressure from the filtrate to give 2,3-diamino-6-bromopyridine (9.00 g) as a green brown powder. To the resulting solid from the above reaction were added ethanol (100 ml)—water (100 ml) and the mixture was heated for dissolution. The insoluble matter was removed by filtration. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/3) to further give the objective compound (8.25 g) as a black-powder.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6].[Br:16]N1C(=O)CCC1=O>C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[Br:16][CH2:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc(C(=O)c2ccccc2)c1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(c1ccccc1)c1cccc(CBr)c1
Reaction time: 2 h
Yield: 114.4 %

Procedure:
A mixture of 32 g of 3-methyl-benzophenone (process of Ador et al, Berichte, Vol. 12, p. 2299), 96 ml of carbon tetrachloride, 26 g of N-bromosuccinimide and 100mg of benzoyl peroxide was refluxed for one hour and after the addition of another 100mg of benzoyl peroxide, the mixture was refluxed for 1 hour. Another 100 mg of benzoyl peroxide were added and reflux was maintained for 11/2 hours. Another 100 mg of benzoyl peroxide were added and reflux was maintained with stirring for 11/2 hours. The mixture was cooled, filtered and the filtrate was distilled to dryness under reduced pressure to obtain 46 g of 3-bromomethyl-benzophenone which was used as is for the next step.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:8]=1)([O-])=O>C(OCC)(=O)C.C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[N:6][N:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:8]=1
Reactant: O=[N+]([O-])c1cnn(CCc2ccccc2)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1cnn(CCc2ccccc2)c1
Reaction time: 8 h

Procedure:
To a solution of 4-nitro-1-phenethyl-1H-pyrazole (90 mg, 0.41 mmol) in ethyl acetate (2 mL) and ethanol (2 mL) was added 10% Pd—C (20 mg), and the resulting mixture was stirred under hydrogen atmosphere overnight. TLC showed the reaction was complete. The catalyst was removed by filtration through a pad of celite, and the filtrate was concentrated under reduced pressure to give the title compound as red oil. 1H NMR (CDCl3, 400 MHz): δ=2.36 (br s, 2H), 3.11 (t, J=7.5 Hz, 2H), 4.21 (t, J=7.5 Hz, 2H), 6.83 (d, J=0.8 Hz, 1H), 7.10-7.12 (m, 2H), 7.18 (d, J=0.8 Hz, 1H), 7.20-7.28 (m, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[C:16]1(=[O:26])[O:21][C:19](=[O:20])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.ClCCl.[Cl-].[Al+3].[Cl-].[Cl-]>O>[CH3:1][C:2]1([CH3:15])[C:3]2[CH:4]=[C:5]([C:16]([C:17]3[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=3[C:19]([OH:21])=[O:20])=[O:26])[CH:6]=[CH:7][C:8]=2[C:9]2[C:14]1=[CH:13][CH:12]=[CH:11][CH:10]=2
Reactant: O=C1OC(=O)c2ccccc21
Reactant: CC1(C)c2ccccc2-c2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Product: CC1(C)c2ccccc2-c2ccc(C(=O)c3ccccc3C(=O)O)cc21
Temperature: 25 °C
Yield: 80 %

Procedure:
9,9-dimethyl-9H-fluorene (40 g, 1 eq, 0.206 mol) and Phthalic anhydride (33.6 g, 1.1 eq, 0.227 mol) were placed in a reaction vessel, and added with Dichloromethane (1.5 l). At 0° C., aluminum chloride (40.8 g, 1.5 eq, 0.309 mol) was gradually added thereto, and the temperature was raised up to room temperature. Then, the resultant mixture was stirred for 12 hours. After the reaction was completed, the resultant product was gradually added with distilled water at 0° C. The resultant product was extracted with an excess of dichloromethane, and washed several times with distilled water. After solvent removal, the produced solid was placed in a Hexane 2 l-containing vessel, washed, filtered, and dried, 2-(9,9-dimethyl-9H-fluorene-2-carbonyl)benzoic acid (56.4 g, yield 82%) was obtained.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=[O:12].[BH4-].[Na+]>CO.C1COCC1>[N:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][OH:12]
Reactant: O=Cc1ccc2ncccc2n1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: OCc1ccc2ncccc2n1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 78 %

Procedure:
To a solution of 1,5-naphthyridine-2-carbaldehyde (8-3) (1.0 g, 6.32 mmol) in MeOH (15 mL) and THF (15 mL) was added NaBH4 (84 mg, 2.21 mmol). The reaction mixture was stirred at 0° C. for 0.5 h. The mixture was concentrated and purified by chromatography on silica gel to afford the title compound (790 mg).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1.N1C=CN=C1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCCc1ccc(Br)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCCc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a solution of 3-(4-bromophenyl)propan-1-ol (1 eq.) in DMF (0.25 M) was added imidazole (1.2 eq.) and tert-butyldimethylsilyl chloride (1.1 eq.). The resulting solution was stirred at RT for 13 h. The reaction mixture was quenched with sat. aq. NH4Cl and extracted with hexanes. The combined organic extracts were washed further with water and brine. Concentration of the organic extracts in vacuo afforded the title compound as a colorless oil.
Reaction SMILES: C(OC([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=O)C1C=CC=CC=1.C(Cl)(Cl)Cl.C(OC(N1C[C@H](O)C[C@H]1C(OC)=O)=O)C=C>C(OCC)(=O)C.C(O)C.[Pd]>[Si:19]([O:18][CH2:17][C@@H:12]1[CH2:13][C@@H:14]([OH:16])[CH2:15][NH:11]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1
Agent: [Pd]
Agent: C=CCOC(=O)N1C[C@H](O)C[C@H]1C(=O)OC
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](O)CN1

Procedure:
A slurry of 10% Pd/C (190 mg) in ethyl acetate (20 mL) was added to a solution of TBDMS ether (48) (1.90 g, 5.19 mmol) in ethanol (100 mL). The reaction mixture was hydrogenated (Parr apparatus) for 16 h. The catalyst was removed by vacuum filtration through Celite and excess solvent was evaporated under reduced pressure to give a yellow oil in quantitative yield (1.20 g, 100%). [α]22.2D=+35.6° (c 0.042, CHCl3). 1H NMR (CDCl3): δ −(0.07-0.08) (m, 6H, H1′, H2′), 0.82 (s, 9H, H3′, H4′, H5′), 1.68-1.73 (m, 2H, H1,), 2.99-3.11 (m, 2H, H11), 3.47-3.50 (m, 3H, H11a, H3), 4.09 (bs, 1H, NH or OH), 4.32 (bs, 1H, NH or OH). 13C NMR (CDCl): 5-5.4 (C3′, C5′, C6′), 18.1 (C4′), 25.8 (C1′, C2′), 37.4 (C1), 54.6 (C11), 58.1 (C2), 64.6 (C3), 72.2 (C11a). IR (thin film): ν=3330 (OH), 2928, 2857, 1557, 1421, 1331 (C—CH3), 1249 (CH3—Si), 1204 (t-Bu) 1191 (c-Bu), 1100 (Si—O), 1073, 993, 713 cm−1. MS (CI) m/e (relative intensity): 232 (M+., 100), 230 (13), 174 (5), 133 (6), 86 (6).
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13](Br)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].[F:19][C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1>C(Cl)(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([C:24]4[CH:25]=[CH:26][C:21]([C:20]([F:31])([F:30])[F:19])=[CH:22][CH:23]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(Br)cc3CC[C@@H]12
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CN1C(=O)CC[C@]2(C)c3ccc(-c4ccc(C(F)(F)F)cc4)cc3CC[C@@H]12
Yield: 56.4 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-bromo-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (200 mg, 0.65 mmol), tetrakis(triphenylphosphine) palladium (0) (23 mg, 0.02 mmol), 4-trifluoromethylphenylboronic acid (148 mg, 0.78 mmol), 0.65 mL of 2M sodium carbonate solution and 2 mL of THF, fitted with a reflux condenser, and the stirred mixture was heated at 80°, under nitrogen, for 16 h. The mixture was cooled, diluted with chloroform (50 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent), to give 137 mg (56%) of the title compound as a white solid. mp 86°-89°. FDMS: m/e=373 α[D]589 =+28.90 (c=1.04, chloroform).
Reaction SMILES: C(O[CH:5]([C:24]1(Br)[C:30](=[O:31])[N:29]2[C@@H:25]1[S:26][CH:27]=[C:28]2[C:32]([O:34]CC1C=CC([N+]([O-])=O)=CC=1)=[O:33])[C:6]1[N:23]=[C:9]2[N:10]=[CH:11][C:12]3[CH2:17][N:16]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:15][CH2:14][C:13]=3[N:8]2[N:7]=1)(=O)C.C(#N)C>C1COCC1.[Pd]>[CH2:21]([O:20][C:18]([N:16]1[CH2:15][CH2:14][C:13]2[N:8]3[N:7]=[C:6](/[CH:5]=[C:24]4\[C@@H:25]5[N:29]([C:30]\4=[O:31])[C:28]([C:32]([OH:34])=[O:33])=[CH:27][S:26]5)[N:23]=[C:9]3[N:10]=[CH:11][C:12]=2[CH2:17]1)=[O:19])[CH3:22]
Reactant: CCOC(=O)N1CCc2c(cnc3nc(C(OC(C)=O)C4(Br)C(=O)N5C(C(=O)OCc6ccc([N+](=O)[O-])cc6)=CS[C@@H]54)nn23)C1
Agent: [Pd]
Solvent: CC#N
Solvent: C1CCOC1
Product: CCOC(=O)N1CCc2c(cnc3nc(/C=C4/C(=O)N5C(C(=O)O)=CS[C@H]45)nn23)C1
Temperature: 3 °C

Procedure:
ethyl 2-[(acetyloxy)((5R)-6-bromo-2-{[(4-nitrobenzyl)oxy]carbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-en-6-yl)methyl]-8,9-dihydropyrido[3,4-e][1,2,4]triazolo[1,5-a]pyrimidine-7(6H)-carboxylate (220 mg, 0.28 mmol) was dissolved in THF (20 mL) and acetonitrile (20 mL) and phophate buffer (6.5 pH) (20 ml) and hydrogenated over Pd/C (10%) (200 mg) under 40 psi pressure. At the end, reaction mixture was filtered, cooled to 3° C., and 0.1 N NaOH was added to adjust the pH to 8.5. The filtrate was washed with ethyl acetate and the aqueous layer was separated. The aqueous layer was concentrated under high vacuum at 35° C. to give a yellow precipitate. The product was purified by HP21 resin reverse phase column chromatography. Initially the column was eluted with deionized water (2 L) and latter with 10% acetonitrile:water. The fractions containing the product were collected and concentrated under reduced pressure at room temperature. The yellow solid was washed with acetone, filtered and dried. Yield: 15 mg, 2%; Yellow crystals; mp>250° C. (Dec); (M+H+Na) 449. 1H NMR (DMSO-d6) δ 8.61 (s, 1H), 7.01 (s, 1H), 6.90(s, 1H), 6.44(s, 1H), 4.74(m, 2H, CH2), 4.13 (q, 2H, J=5.4 Hz), 3.84(s, m, 2H, CH2), 1.22(t, 3H, CH3, J=5.7 Hz).
Reaction SMILES: [C:1]([CH:6]1[CH2:10][CH2:9][CH2:8][C:7]1=[O:11])([O:3][CH2:4][CH3:5])=[O:2].[CH2:12](I)[CH3:13].[H-].[Na+]>>[C:1]([C:6]1([CH2:12][CH3:13])[CH2:10][CH2:9][CH2:8][C:7]1=[O:11])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)C1CCCC1=O
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)C1(CC)CCCC1=O

Procedure:
2-Carboethoxycyclopentanone is reacted with ethyl iodide in the presence of sodium hydride to produce 2-carboethoxy-2-ethyl-cyclopentanone.