Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13]O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1(=[O:25])[NH:19][C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:19]1[C:15](=[O:25])[C:16]2[C:17](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:18]1=[O:20])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC[C@H]1CN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 114.5 %

Procedure:
Commercially available (S)-(−)-1-tert-butoxycarbonyl-2-pyrrolidinemethanol (1.00 g, 4.97 mmol) was dissolved in toluene (10 mL), and the mixture was stirred at room temperature for 1.5 hours after adding phthalimide (877 mg, 5.96 mmol), triphenylphosphine (1.96 g, 7.46 mmol), and diethyl azodicarboxylate (40% toluene solution, 3.4 mL, 7.46 mmol). The mixture was further stirred at 60° C. for 4 hours. Thereafter, water and ethyl acetate were added to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give (S)-2-[(1,3-dioxoisoindolin-2-yl)methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.88 g, quantitative).
Reaction SMILES: C([O-])=O.[NH4+].C([N:12]1[CH:18]2[CH2:19][CH2:20][CH:13]1[CH2:14][N:15]([CH3:21])[CH2:16][CH2:17]2)C1C=CC=CC=1>[Pd].C(O)C>[CH3:21][N:15]1[CH2:16][CH2:17][CH:18]2[NH:12][CH:13]([CH2:20][CH2:19]2)[CH2:14]1
Reactant: CN1CCC2CCC(C1)N2Cc1ccccc1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CN1CCC2CCC(C1)N2

Procedure:
Neat ammonium formate (2 g, 31.7 mmol) was added to stirred suspension of 9-benzyl-3-methyl-3,9-diazabicyclo[4.2.1]nonane (250 mg, 1.085 mmol) and 10% Pd-C (150 mg, 0.141 mmol) in abs. ethanol (50 ml). The mixture was heated to reflux for 2-3 h. The suspension was filtered and to the filtrate TFA (0.5 ml) was added and evaporated to dryness to afford 3-methyl-3,9-diazabicyclo[4.2.1]nonane and isolated as the bis-TFA salt. LC/MS: m/e 141 (MH+).
Reaction SMILES: [Br-].[CH:2]([C:4]1C=CC=CC=1[P+](C)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:3].[C:24]([C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1)([O:26][CH3:27])=[O:25].C(OCC)(=O)C>C1(C)C=CC=CC=1>[C:24]([C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[CH:4][CH:2]=[O:3])=[CH:30][CH:29]=1)([O:26][CH3:27])=[O:25]
Reactant: COC(=O)c1ccc(C=O)cc1
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1C=O
Agent: [Br-]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C=CC=O)cc1

Procedure:
A solution of 27.3 g (0.09 mole) of formyl methyltriphenyl phosphonium bromide and 14.8 g (0.09 mole) of p-carbomethoxybenzaldehyde in 900 ml of dry toluene was refluxed under nitrogen for 24 hr. After evaporating toluene under reduced pressure, the residue was chromatographed over silica column with 5% ethyl acetate in petroleum ether as eluant. The second fraction obtained by using 10% ethyl acetate in petroleum ether gave 4-carbomethoxycinnamaldehyde. Recrystallization from benzene gave 12.5 g 4-carbomethoxycinnamaldehyde, yield 73% m.p. 99°-101° C. The infrared spectrum showed absorption at 1720 cm-1 ##STR8## 1680 cm-1 (CHO), and 1620 cm-1 (--CH=CH--). NMR (CDCl3) showed δ3.8 (s, --COOCH3, 3) 6.5-7.1 (m,=CH--CHO, l), 7.3-7.6 (m, aromatic, 4), 7.9-8.1 (d, --CH=, l), and 9.8 (d, --CHO, l). Analysis calculated for C11H10O3 : C, 69.42%, H, 5.2%. Found: C, 68.69%, H, 5.25%.
Reaction SMILES: [CH2:1](Cl)[CH2:2][CH2:3][CH2:4][CH3:5].[Mg].Cl[SiH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][C@H:17]2[CH2:22][CH2:21][C@H:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([F:36])[CH:30]=4)=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)[CH2:11][CH2:10]1>C1COCC1>[CH2:1]([Si@H:9]1[CH2:10][CH2:11][C@H:12]([CH2:15][CH2:16][C@H:17]2[CH2:18][CH2:19][C@H:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([F:36])[CH:30]=4)=[CH:25][CH:24]=3)[CH2:21][CH2:22]2)[CH2:13][CH2:14]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCCl
Reactant: Fc1cc(-c2ccc([C@H]3CC[C@H](CCC4CC[SiH](Cl)CC4)CC3)cc2)ccc1Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCCC[Si@H]1CC[C@H](CC[C@H]2CC[C@H](c3ccc(-c4ccc(Cl)c(F)c4)cc3)CC2)CC1

Procedure:
10.7 g (0.1 mol) of n-pentyl chloride was dripped into a mixture of 2.5 g (0.1 mol) of magnesium and 300 ml of THF to obtain a Grignard's reagent. This solution was then dripped into a 300 ml THF solution of 45 g (0.1 mol) of 4-(trans-4-(2-(4-chloro-4-silacyclohexyl)ethyl)cyclohexyl)-3'-fluoro-4'-chlorobiphenyl to obtain 4-(trans-4-(2-(trans-4-n-pentyl-4-silacyclohexyl)ethyl)cyclohexyl)-3'-fluoro-4'-chlorobiphenyl. The silacyclohexane rings of the product were a mixture of trans isomers and cis isomers. They were separated by means of chromatography to obtain 31.3 g (yield 69.9%) of the trans isomer.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH:19]=[C:20]([CH3:22])[CH3:21])[CH:18]=[C:13]3[C:12]([C:23]3[CH:24]=[N:25][N:26]([CH2:28][CH2:29][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[CH:27]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.[OH-].[OH-].[Pd+2]>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH2:19][CH:20]([CH3:21])[CH3:22])[CH:18]=[C:13]3[C:12]([C:23]3[CH:24]=[N:25][N:26]([CH2:28][CH2:29][N:30]4[CH2:31][CH2:32][O:33][CH2:34][CH2:35]4)[CH:27]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)=Cc1cnc2c(c1)c(-c1cnn(CCN3CCOCC3)c1)cn2S(=O)(=O)c1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(C)Cc1cnc2c(c1)c(-c1cnn(CCN3CCOCC3)c1)cn2S(=O)(=O)c1ccccc1
Reaction time: 24 h
Yield: 83.3 %

Procedure:
To a solution of 93 (80 mg, 0.18 mmol) in MeOH (4 mL) was added 20% Pd(OH)2 on C (30 mg, cat.), and the reaction mixture was stirred vigorously under H2 for 24 h. The mixture was then filtered through Celite, which was then washed with MeOH:CH2Cl2=1:1 (v/v; 50 mL). The solutions were combined and concentrated to afford 94 as a foam (66 mg, 0.15 mmol, 82%). 1H NMR (400 MHz, CDCl3) δ 0.84 (d, J=6.6 Hz, 2H), 1.40 (t, J=7.1 Hz, 3H), 1.80 (nonet, J=6.7 Hz, 1H), 2.50 (d, J=7.3 Hz, 2H), 2.49-2.60 (m, 4H), 2.84-3.06 (m, 2H), 3.63-3.76 (m, 4H), 4.29-4.46 (m, 2H), 7.42 (t, J=7.6 Hz, 2H), 7.50 (t, J=7.4 Hz, 1H), 7.66 (d, J=2.0 Hz, 1H), 7.68 (s, 1H), 7.71 (s, 1H), 7.76 (s, 1H), 8.03 (d, J=1.8 Hz, 1H), 8.14 (d, J=7.6 Hz, 1H), 8.20 (d, J=1.9 Hz, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=[CH2:26])[CH:20]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1.[OH2:27]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[CH:11][C:12]([S:15]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]3[CH2:26][O:27]3)[CH:20]=2)(=[O:16])=[O:17])=[CH:13][CH:14]=1
Reactant: C=Cc1cccc(NS(=O)(=O)c2ccc(-c3ccc(F)cc3F)cc2)c1
Reactant: O
Solvent: ClCCl
Product: O=S(=O)(Nc1cccc(C2CO2)c1)c1ccc(-c2ccc(F)cc2F)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Dry meta-chloroperoxybenzoic acid (˜85%, dried over KOH in a clean, dry, uncontaminated vacuum desiccator for at least 48 hours; 3.7 g, 21 mmol) was added to a solution of 2′,4′-difluoro-N-(3-vinylphenyl)biphenyl-4-sulfonamide (1.16 g, 4.3 mmol) in dry DCM (30 mL) at 0° C. The mixture was allowed to warm to room temperature and stirred for 5 hours. Water (30 mL) was added and the layers were separated. The DCM layer was washed with 10% Na2SO3 (30 mL), saturated NaHCO3 (30 mL), water (30 mL) and brine (30 mL) and dried over MgSO4. The solvent was evaporated and the title compound obtained as an orange oil (1.16 g) which was used without further purification.
Reaction SMILES: [C:1]1([C@H:7]([NH:9][C:10]([N:12]2[CH2:17][CH:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:15][CH:14]([C:24]([O:26]C)=[O:25])[CH2:13]2)=[O:11])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[OH-]>C1COCC1.CO>[C:1]1([C@H:7]([NH:9][C:10]([N:12]2[CH2:17][CH:16]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:15][CH:14]([C:24]([OH:26])=[O:25])[CH2:13]2)=[O:11])[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)C1CC(c2ccccc2)CN(C(=O)N[C@H](C)c2ccccc2)C1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C[C@@H](NC(=O)N1CC(C(=O)O)CC(c2ccccc2)C1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a 150 mL RBF was added the mixture from step 1 (150 mg), THF:MeOH (3:1, 15 mL), and LiOH, 1M (1.00 ml, 1.0 mmol) and the mixture was stirred at RT. After 2 hours, the reaction was neutralized and extracted with EtOAc (3×20 mL). The combined organic layers were concentrated in vacuo to give a white solid. The material was carried forward without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:11](C)([C:17](OCC)=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[Cl-].[Na+].CS(C)=O>O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: CCOC(=O)C(C)(C(=O)OCC)c1ccc([N+](=O)[O-])c(F)c1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)c1ccc([N+](=O)[O-])c(F)c1

Procedure:
A mixture of 100 millimoles of diethyl 2-(3-fluoro-4-nitrophenyl)-2-methylmalonate, 110 millimoles of sodium chloride and 50 milliliters of dimethyl sulfoxide is heated under nitrogen at about 130° to 180° C. for about 6 hours. On cooling the mixture is diluted with 100 milliliters of water and 100 milliliters of ethyl acetate. The layers are separated and the organic layer is washed two times with 25 milliliters of water. After drying over disodium sulfate the organic layer is concentrated in vacuo to give the desired ethyl 2-(3-fluoro-4-nitrophenyl)propionate.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)=O.[Cl-].[OH:21][NH3+:22].C([O-])(=O)C.[Na+]>C(O)C.O>[F:1][C:2]([F:19])([F:18])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)=[N:22][OH:21]
Reactant: [NH3+]O
Reactant: O=C(c1ccc(Oc2ccccc2)cc1)C(F)(F)F
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: ON=C(c1ccc(Oc2ccccc2)cc1)C(F)(F)F
Temperature: 80 °C
Yield: 84.3 %

Procedure:
122 g (0.46 mol) of 2,2,2-trifluoro-1-(4-phenoxyphenyl)-ethanone are dissolved in 370 ml of ethanol and heated at 80° C. To the solution are added 33.3 g (0.48 mol) of hydroxylammonium chloride and 63.7 g (0.78 mol) of sodium acetate dissolved in 190 ml of water. The reaction mixture is refluxed for 5.5 hours, and poured into water. A pale yellow solid is precipitated. The solid is isolated by filtration and rinsed with water, and added in hexane and heated at 60° C. for 20 min. After cooling, the solid is isolated and rinsed with hexane, yielding 109 g of 2,2,2-trifluoro-1-(4-phenoxyphenyl)-ethanone oxime as a white solid. The structure is confirmed by the 1H-NMR spectrum (CDCl3). δ [ppm]: 7.00-7.10 (m, 4H), 7.18 (t, 1H), 7.39 (t, 2H), 7.55 (d, 2H), 9.35 (br s, 1H).
Reaction SMILES: [C:1]([C:3]1[CH:18]=[CH:17][C:6]2[O:7][CH2:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[C:11](=[O:12])[C:5]=2[CH:4]=1)#[N:2].[N-:19]=[N+:20]=[N-:21].[Na+].[Cl-].[NH4+].Cl>O.CN(C)C=O>[NH:19]1[C:1]([C:3]2[CH:18]=[CH:17][C:6]3[O:7][CH2:8][C:9]4[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=4[C:11](=[O:12])[C:5]=3[CH:4]=2)=[N:2][N:21]=[N:20]1
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccc2c(c1)C(=O)c1ccccc1CO2
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2COc2ccc(-c3nnn[nH]3)cc21

Procedure:
Heat a mixture of 25 gm. (0.106 mole) of 2-cyano-6,11-dihydro-11-oxodibenz[b,e]oxepin, 8.28 gm. (0.127 mole of sodium azide and 7.37 gm. (0.138 mole of ammonium chloride in 250 ml. of N,N-dimethylformamide to 140° C. for 27 hours. Cool, dilute with 500 cc. of water and acidify with 20% aqueous hydrochloric acid. Separate the solids by filtration and crystallize from ethanol to obtain the title product (m.p. 248° C. dec.).
Reaction SMILES: [C:1]1([C:7]2[C:11]3[C:12](=O)[CH2:13][CH2:14][CH2:15][C:10]=3[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClCCl.[N-:20]=[N+]=[N-].[Na+].Cl>OS(O)(=O)=O>[N:8]1[O:9][C:10]2[CH2:15][CH2:14][CH2:13][C:12]3[C:11]=2[C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:20]=3
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1CCCc2onc(-c3ccccc3)c21
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClCCl
Product: c1ccc2c(c1)nc1c3c(onc32)CCC1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 31.3 %

Procedure:
3-Phenyl-4-oxo-4,5,6,7-tetrahydrobenz[1,2-d]isoxazole (6.0 g) was dissolved in 40 ml conc. H2SO4 and then dichloromethane (60 ml) was added. NaN3 (2.0 g) was added portionwise at such a rate that foaming could be controlled. After 90 minutes, the reaction mixture was poured into ice/water and conc. HCl was added until the precipitated amine sulfate dissolved. The dichloromethane layer was separated and the aqueous phase was washed with additional dichloromethane. The aqueous phase was made basic with 50% NaOH and ice (up to pH 1-4) and then with NaHCO3 (up to pH 8). The product was extracted into dichloromethane and then flushed over a short alumina column before concentration under reduced pressure. Recrystallization from EtOAc/hexane gave 1.85 g of product, m.p. 149°-150° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH2:19][F:20])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:21][N:22](COCC[Si](C)(C)C)[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)=[C:11]2[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O.N>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH2:19][F:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1
Reactant: C[Si](C)(C)CCOCn1nc2c(nc(-c3c(F)cccc3F)c3cc(CF)ccc32)c1NC1CCN(S(C)(=O)=O)CC1
Agent: N
Solvent: O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)N1CCC(Nc2n[nH]c3c2nc(-c2c(F)cccc2F)c2cc(CF)ccc23)CC1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 87 mg of [5-(2,6-difluorophenyl)-7-(fluoromethyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine in 7 ml of DCM. After cooling to 0° C. using an ice bath, 0.85 ml of TFA is added and the mixture is stirred at RT for 3 h. The mixture is concentrated under RP and the solid obtained is taken up in 24 ml of water and 1.1 ml of 0.75M aqueous ammonia solution. It is extracted with ethyl acetate, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a DCM/MeOH mixture (95/05 by vol.). This gives 27 mg of [5-(2,6-difluorophenyl)-7-(fluoromethyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-1H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid). 1H NMR; 1.67 (m, 2 H) 2.11 (m, 2 H) 2.87 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.80 (broad m, 1 H) 5.58 (d, J=47.2 Hz, 2 H) 6.05 (broad d, J=8.0 Hz, 1 H) 7.33 (t, J=77 Hz, 2 H) 7.57-7.73 (m, 2 H) 7.95 (broad d, J=8.3 Hz, 1 H) 8.45 (d, J=8.3 Hz, 1 H) 12.81 (s, 1 H).
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][C:14]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:30][C@H:29]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])[O:28][C:27]3=[O:36])=[CH:22][C:21]=2[F:37])([OH:17])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>CO.C(OCC)(=O)C.[Pd]>[F:37][C:21]1[CH:22]=[C:23]([N:26]2[CH2:30][C@H:29]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])[O:28][C:27]2=[O:36])[CH:24]=[CH:25][C:20]=1[O:19][CH2:18][C:14]1([OH:17])[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(OCC3(O)CCN(C(=O)OCc4ccccc4)CC3)c(F)c2)C(=O)O1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(=O)NC[C@H]1CN(c2ccc(OCC3(O)CCNCC3)c(F)c2)C(=O)O1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
A suspension of 31 g 4-{4-[(5S)-5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2-fluorophenoxymethyl}-4-hydroxy-piperidine-1-carboxylic acid benzylester (MW: 515.54 60.13 mmol) and 2.5 g of palladium 10% on activated carbon in 310 ml methanol and 150 ml ethyl acetate was stirred under hydrogen for 4 hrs. The reaction was monitored by TLC (ethyl acetate). The reaction slurry was diluted with 300 ml methanol, warmed to 40° C., and the catalyst filtered off using a glass fibre filter paper. The filtrate was concentrated to 150 ml, diluted with 300 ml ethyl acetate and concentrated again to 200 ml. 200 ml of diethyl ether were added, and the suspension was cooled to 0° C. under stirring. The solid was collected and dried. Yield: 21.6-g, 94.3%. MS: 382.6 (M+H)+, Method ESI+.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][CH2:7][C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][CH2:7][C:8]2[CH:20]=[CH:19][C:11]([O:12][C:13]([CH3:18])([CH3:17])[CH2:14][OH:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(Oc1ccc(COc2ccc(Cl)cc2)cc1)C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(CO)Oc1ccc(COc2ccc(Cl)cc2)cc1
Reaction time: 8 h

Procedure:
A solution of 3.2 g. of 2-[4-(4-chlorophenoxymethyl)-phenoxy]-2-methylpropionic acid in 20 ml. of absolute THF is added dropwise to a mixture of 0.57 g. of LiAlH4 in 20 ml. of absolute THF. The mixture is boiled for 8 hours, 2 ml. of water in 3 ml. of THF and 4 ml. of 25% sodium hydroxide solution are added, the liquid is decanted off and the residue is washed with ether. Drying, filtering and evaporating the combined organic phases gives 2-[4-(4-chlorophenoxymethyl)-phenoxy]-2-methyl-propanol, m.p. 67°-70° C.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]=1Cl)=[O:13])[CH2:8]2.[OH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:18]=1[N:30]1[CH2:31][CH2:32][CH:27]([OH:26])[CH2:28][CH2:29]1)=[O:13])[CH2:8]2
Reactant: OC1CCNCC1
Reactant: O=C(NC1C2CC3CC(C2)CC1C3)c1cnn(-c2ccccc2)c1Cl
Product: O=C(NC1C2CC3CC(C2)CC1C3)c1cnn(-c2ccccc2)c1N1CCC(O)CC1

Procedure:
5-(4-Hydroxy-piperidin-1-y1)-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide was prepared using Procedure A from 5-chloro-1-phenyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (Intermediate 3) and 4-hydroxypiperidine. Mass spectrum (ES) MH+=421.
Reaction SMILES: [CH3:1][C@:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[CH2:4][C:3]2=[O:13].C(N(CC)CC)C.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:24]=[C:25]([N:29]=[C:30]=[O:31])[CH:26]=[CH:27][CH:28]=1.Cl>CN(C)C1C=CN=CC=1.ClCCl>[F:21][C:22]([F:32])([F:33])[C:23]1[CH:24]=[C:25]([NH:29][C:30]([CH:4]2[C:5](=[O:12])[CH:6]3[C:9]([CH3:10])([CH3:11])[C@@:2]([CH3:1])([CH2:8][CH2:7]3)[C:3]2=[O:13])=[O:31])[CH:26]=[CH:27][CH:28]=1
Reactant: CC1(C)C2CC[C@@]1(C)C(=O)CC2=O
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(C)C2CC[C@@]1(C)C(=O)C(C(=O)Nc1cccc(C(F)(F)F)c1)C2=O
Temperature: 30 °C
Reaction time: 8 h
Yield: 51.7 %

Procedure:
To an ice-cooled solution of (1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.36 g, 2.0 mmole), triethylamine (0.20 g, 2.0 mmole) and 4-(dimethylamino)pyridine (0.24 g, 2.0 mmole) in dry dichloromethane (25 mL) was added a solution of 3-(trifluoromethyl)phenyl isocyanate (0.37 g, 2.0 mmole) in dry dichloromethane (5 mL). The resulting mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature, and then was heated at 30° C. for 7 hours. The reaction mixture was treated with 2N aqueous HCl and the layers separated. The acidic aqueous layer was extracted with two additional portions of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to give a yellow oil, which was purified by chromatography on silica gel (10% ethyl acetate/hexane) to yield a yellow oil, which was crystallized from 95% ethanol to yield the title compound as a beige solid (0.38 g, 51% yield), mp=66–68° C.; MS (−) ESI m/z=366 (M−H)−; [α]D25=+22.0° (c=1, EtOH).
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11](/[C:15](/[CH2:22][CH3:23])=[CH:16]/[C:17](OCC)=[O:18])[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[Si:1]([O:8][C:9]1[CH:10]=[C:11](/[C:15](/[CH2:22][CH3:23])=[CH:16]/[CH2:17][OH:18])[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]
Reactant: CCOC(=O)/C=C(\CC)c1cccc(O[Si](C)(C)C(C)(C)C)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: CC/C(=C\CO)c1cccc(O[Si](C)(C)C(C)(C)C)c1

Procedure:
In a manner analogous to example 1e, by reaction of 7.6 g (23 mmol) of ethyl (E)-3-[3-(tert-butyldimethylsilanyloxy)phenyl]pent-2-enoate with 1.05 g (25 mmol) of lithium aluminum hydride. A colorless oil is obtained (m=6.7 g; Y=100%).
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:19]=[CH:20][CH:21]=2)[CH2:10][NH:11]C(=O)OC(C)(C)C)[CH2:5][CH2:4][O:3]1.[ClH:22]>ClCCl>[ClH:22].[NH2:11][CH2:10][C:9]1[CH:8]=[C:7]([N:6]2[CH2:5][CH2:4][O:3][C:2]2=[O:1])[CH:21]=[CH:20][CH:19]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(N2CCOC2=O)c1
Agent: Cl
Solvent: ClCCl
Product: NCc1cccc(N2CCOC2=O)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
380 mg (1.30 mmol) tert-butyl [3-(2-oxo-oxazolidin-3-yl)-benzyl]-carbamate are placed in 2 ml dichloromethane, 4.00 ml (8 mmol) 2 molar ethereal hydrochloric acid are added. The mixture is stirred for 16 hours at ambient temperature, then evaporated down. The residue is lyophilised.
Reaction SMILES: [N:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3](N)[N:2]=1.N([O-])=[O:13].[Na+]>O.S(=O)(=O)(O)O>[N:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]([OH:13])[N:2]=1
Reactant: Nc1nnc2ccccc2n1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Oc1nnc2ccccc2n1
Yield: 53.4 %

Procedure:
To a solution of 2.0 g (14 mmol) 1,2,4-benzotriazine-3-amine in 30 ml water and 3 ml conc. sulphuric acid one adds dropwise at 10° C. a solution of 1 g sodium nitrite in 10 ml water. One stirs for 4 b at room temp., filters off the residue and dries. One obtains 1.1 g of title compound (55% of theory) of the m.p. 204-206° C.