Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@@H:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH3:25])[CH:18]=2)[N:9]=1.[CH3:32][C:33]([CH3:35])=O.CO>C(Cl)(Cl)Cl.C(Cl)Cl>[CH:33]([N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][N:2]2[C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@@H:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH3:25])[CH:18]=2)[N:9]=1)([CH3:35])[CH3:32]
Reactant: C[C@@H](Nc1cc(-c2cc3nccn3c(N3CC4CC3CN4)n2)ccn1)c1ccccc1
Reactant: CC(C)=O
Solvent: ClCCl
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CC(C)N1C[C@@H]2C[C@H]1CN2c1nc(-c2ccnc(N[C@H](C)c3ccccc3)c2)cc2nccn12
Temperature: 25 °C
Reaction time: 15 h

Procedure:
The mixture of 100 mg (0.24 mmol)(R)-{4-[5-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine in 5 mL chloroform was treated with 0.2 mL (2.4 mmol) acetone, 45 mg (0.72 mmol) NaBH3(CN) and 1 mL methanol. The mixture was stirred at rt for 15 h. MS showed all starting materials were converted. The mixture was diluted with 100 mL DCM, washed with 20 mL sat. NaHCO3, dried over anhydrous Na2SO4. After purification by chromatography, obtained the title compound as a yellow solid. MS (ES+): 454 (M+H)+.
Reaction SMILES: [C:1]1([C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([CH3:11])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH:25]([C:28]2[CH:29]=[C:30]([NH:34][C:35](=[O:39])[CH2:36][CH2:37][CH3:38])[CH:31]=[CH:32][CH:33]=2)[CH2:24][CH2:23]1>>[C:12]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([CH3:11])[C:8]([NH:18][CH2:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([C:28]3[CH:29]=[C:30]([NH:34][C:35](=[O:39])[CH2:36][CH2:37][CH3:38])[CH:31]=[CH:32][CH:33]=3)[CH2:24][CH2:23]2)=[O:10])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CCCC(=O)Nc1cccc(C2CCN(CCCN)CC2)c1
Reactant: CC(C(=O)O)(c1ccccc1)c1ccccc1
Product: CCCC(=O)Nc1cccc(C2CCN(CCCNC(=O)C(C)(c3ccccc3)c3ccccc3)CC2)c1

Procedure:
Example 98 was prepared from 2,2-diphenylpropanoic acid and N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}butanamide according to the procedures described in Scheme 10: 1H NMR (400 MHz, CDCl3) δ 7.43 (s, 1H), 7.37–7.22 (m, 13H), 6.91 (d, 1H, J=7.2 Hz), 6.24 (br s, 1H), 3.37 (dd, 2H, J=5.6, 11.6 Hz), 2.88 (d, 2H, J=11.6 Hz), 2.42 (m, 1H), 2.32 (m, 4H), 2.01 (s, 3H), 1.93 (t, 2H, J=11.6 Hz), 1.81–1.52 (m, 8H), 1.01 (t, 3H, J=6.8 Hz); ESMS m/e: 512.3 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C@@H:12]2[CH2:17][C@H:16]([N:18]([CH:20]([CH3:22])[CH3:21])[CH3:19])[CH2:15][CH2:14][C@@H:13]2[NH:23][C:24](=[O:39])[CH2:25][C:26]2[NH:30][C:29]3[CH:31]=[CH:32][CH:33]=[C:34]([C:35]([F:38])([F:37])[F:36])[C:28]=3[N:27]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Br-].[CH2:41]([Zn+])[CH2:42][CH3:43]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:20]([N:18]([CH3:19])[C@@H:16]1[CH2:15][CH2:14][C@H:13]([NH:23][C:24](=[O:39])[CH2:25][C:26]2[NH:30][C:29]3[CH:31]=[CH:32][CH:33]=[C:34]([C:35]([F:38])([F:37])[F:36])[C:28]=3[N:27]=2)[C@H:12]([CH2:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([CH2:41][CH2:42][CH3:43])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:17]1)([CH3:22])[CH3:21]
Reactant: CC(C)N(C)[C@@H]1CC[C@H](NC(=O)Cc2nc3c(C(F)(F)F)cccc3[nH]2)[C@H](CS(=O)(=O)c2ccc(Br)cc2)C1
Reactant: CCC[Zn+]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: C1CCOC1
Product: CCCc1ccc(S(=O)(=O)C[C@@H]2C[C@H](N(C)C(C)C)CC[C@@H]2NC(=O)Cc2nc3c(C(F)(F)F)cccc3[nH]2)cc1
Temperature: 150 °C
Reaction time: 0.08 h

Procedure:
(1S,2R,4R)—N-[2-(4-Bromo-benzenesulfonylmethyl)-4-(isopropyl-methyl-amino)-cyclohexyl]-2-(4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetamide, Example 3, was dissolved in THF (1 ml) prior to the addition of propyl zinc bromide (0.32 ml), Pd(PPh3)4 (3 mg). The mixture was stirred under microwave conditions (150° C.) for 5 min. After cooling, the crude reaction was filtered and the filtrate was concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue provided the two fractions, one of which contained the title compound (8 mg). MS found: (M+H)+=594.5
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH:6]=[CH2:7])=[O:3].[NH2:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[C:12]([O:26][CH3:27])=[CH:11][C:10]=1[C:28]([N:30]1[CH:34]=[C:33](/[CH:35]=[CH:36]/[CH3:37])[CH2:32][C@H:31]1[CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])=[O:29].N1C=CC=CC=1>C(Cl)Cl>[Si:40]([O:39][CH2:38][C@@H:31]1[CH2:32][C:33](/[CH:35]=[CH:36]/[CH3:37])=[CH:34][N:30]1[C:28]([C:10]1[CH:11]=[C:12]([O:26][CH3:27])[C:13]([O:15][Si:16]([CH:17]([CH3:19])[CH3:18])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:21])[CH3:22])=[CH:14][C:9]=1[NH:8][C:2](=[O:3])[O:4][CH2:5][CH:6]=[CH2:7])=[O:29])([C:43]([CH3:44])([CH3:46])[CH3:45])([CH3:41])[CH3:42]
Reactant: C=CCOC(=O)Cl
Reactant: C/C=C/C1=CN(C(=O)c2cc(OC)c(O[Si](C(C)C)(C(C)C)C(C)C)cc2N)[C@H](CO[Si](C)(C)C(C)(C)C)C1
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=CCOC(=O)Nc1cc(O[Si](C(C)C)(C(C)C)C(C)C)c(OC)cc1C(=O)N1C=C(/C=C/C)C[C@H]1CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 100 %

Procedure:
Allyl chloroformate (0.83 g, 6.88 mmol, 1.1 eq) was added to a solution of the amine 7 (3.6 g, 6.26 mmol, 1.0 eq) in dry DCM (80 mL) containing dry pyridine (1.09 g, 13.77 mmol, 2.2 eq) at −78° C. The dry ice was removed and the reaction mixture allowed to warm to room temperature. After stirring for a further 15 minutes, LC/MS indicated complete reaction. The organic phase was washed successively with 0.01N HCl (50 mL), saturated sodium bicarbonate (50 mL), brine (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure to leave a pale yellow oil which was used in the next step without further purification (4.12 g, assumed 100% yield). LC/MS (4.862 min (ES+)), m/z: 659.2 [M+H]+.
Reaction SMILES: C[Al]1[CH2:7][CH2:6][CH2:5][CH2:4]O1.[C:8]1(C)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH2:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][CH2:5]1
Reactant: C[Al]1CCCCO1
Reactant: Cc1ccccc1
Product: c1ccc2c(c1)CCCC2

Procedure:
Methylalumoxane (MAO) was received from Albemarle as a 30% wt/V toluene solution and used as such and the silica was received from INEOS (ES70Y, 100 microns).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([N+:10]([O-])=O)=[CH:4][C:3]=1[OH:13]>[Pd].C(O)C>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([NH2:10])=[CH:4][C:3]=1[OH:13]
Reactant: COc1cc(C)c(O)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: COc1cc(C)c(O)cc1N
Reaction time: 5 h
Yield: 78.5 %

Procedure:
320 mg of 10% palladium-on-carbon, 2.90 g (15.8 mmol) of 2-methyl-4-methoxy-5-nitrophenol and 75 ml of ethanol were fed into an autoclave (300 ml). The mixture was then hydrogenated at 50° C. under 50 kg/cm2 for 5 hours. After allowing to cool, the catalyst was filtered off and the solvent was distilled off under reduced pressure. Thus 19.0 g (12.4 mmol) of 2-methyl-4-methoxy-5-aminophenol was obtained in the form of brown crystals. The 1H-NMR spectra of this product showed no impurities. The yield was 78%.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:13])=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[N:14]1([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:13][C:5]1[CH:4]=[CH:3][C:2]([N:17]2[CH2:18][CH2:19][CH2:20][N:14]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15][CH2:16]2)=[CH:12][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CC(C)(C)OC(=O)N1CCCNCC1
Reactant: CCOC(=O)c1cc(Br)ccc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)c1cc(N2CCCN(C(=O)OC(C)(C)C)CC2)ccc1Cl
Temperature: 100 °C
Yield: 28.9 %

Procedure:
A mixture of 5-bromo-2-chloro-benzoic acid, ethyl ester (0.50 g), hexahydro-1H-1,4-diazepine-1-carboxylic acid, 1,1-dimethylethyl ester (0.46 g), cesium carbonate (0.86 g), palladium (II) acetate (8.5 mg) and (R)-BINAP (35 mg) in toluene (3 ml) was heated at 100° C. for 14 h in a pressure vessel flushed with nitrogen. The cooled reaction mixture was poured into water and extracted (3 times) with ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution and then dried over magnesium sulfate. Evaporation under reduced pressure gave an oil which was purified by chromatography over silica gel, eluting with 20% ethyl acetate in iso-hexane to yield the subtitle compound as an oil (0.21 g).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][CH:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.[CH3:28]I>CO>[CH3:28][N:12]([CH2:13][CH2:14][CH:15]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:11][CH2:10][CH2:9][S:8][C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1
Reactant: CI
Reactant: Oc1ccc(SCCCNCCC(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Product: CN(CCCSc1ccc(O)cc1)CCC(c1ccccc1)c1ccccc1

Procedure:
To a solution of 0.8 g (0.0021 moles) of N-(3'-p-hydroxyphenylthiopropyl)-3,3-diphenylpropylamine in 20 ml methanol containing 0.3 ml triethylamine are gradually added 0.13 ml (0.0021 moles) methyl iodide. After 36 hours at room temperature the solvent is evaporated under vacuum and the residue is dissolved in 20 ml benzene. The solution is washed three times with water, dried and evaporated.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](CCCOCc2ccccc2)C1
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCl
Product: c1ccc(COCCC[C@@H]2CCCNC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.9 %

Procedure:
To a solution of tert-butyl 3(S)-[3-(benzyloxy)propyl]piperidine-1-carboxylate (280 mg, 0.84 mmol) in CH2Cl2/H2O (6 mL/0.5 mL) was added CF3COOH (1.92 g, 16.8 mmol, 20 equiv.) at 0° C. under N2. The solution was stirred overnight at room temperature. After concentration under reduced pressure, water was added, and the solution was washed with hexane. The aqueous phase was basified with saturated NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed in vacuo to give 3(S)-[3-(benzyloxy)propyl]piperidine (190 mg, 97%) as a yellow oil. LC-MS (ESI) m/z 234 (M+H+).
Reaction SMILES: C([N:6]1[CH2:11][CH2:10][N:9]([CH:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[S:16][C:15]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:14]=3[CH2:13]2)[CH2:8][CH2:7]1)(OCC)=O.C(O)CO.[OH-].[K+]>O>[Cl:27][C:25]1[CH:24]=[CH:23][C:15]2[S:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH:12]([N:9]3[CH2:8][CH2:7][NH:6][CH2:11][CH2:10]3)[CH2:13][C:14]=2[CH:26]=1
Reactant: CCOC(=O)N1CCN(C2Cc3cc(Cl)ccc3Sc3ccccc32)CC1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: Clc1ccc2c(c1)CC(N1CCNCC1)c1ccccc1S2

Procedure:
110 g of 1-carbethoxy-4-(2-chloro-10,11-dihydro-dibenzo[b,f]thiepin-10-yl)-piperazine, 1.5 litres of ethylene glycol, 104 g of potassium hydroxide and 5.4 ml of water are heated to 160° C for 1 hour. The mixture is then poured on to water and extracted with chloroform. The organic phase is washed with water, dried over magnesium sulphate and evaporated. There is obtained 1-(2-chloro-10,11-dihydro-dibenzo[b,f]thiepin-10-yl)-piperazine as an oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:9][CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)Cl>CS(C)=O>[C:1]([O:5][C:6]([N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:9][CH:10]=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N(CCO)C(C)(C)C
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N(CC=O)C(C)(C)C
Yield: 94.8 %

Procedure:
To N-tert-butoxycarbonyl-N-tert-butylethanolamine (7.24 g), triethylamine (13.5 g) and methylene chloride (150 ml) in 500 ml round bottom flask, a solution dissolved sulfur trioxide-pyridine complex (15.9 g) into 150 ml of DMSO was added at a time under cooling with ice and stirring. After stirring for 10 minutes at room temperature, the reaction mixture was poured into 1 liter of saturated saline solution. After the methylene chloride layer was separated, the aqueous layer was extracted with ether and all of the organic layers were combined, which was dried over anhydrous sodium sulfate and then concentrated. The residue was purified by means of silica gel chromatography (chloroform: ethanol=20:1) to obtain 6.80 g of aimed product as a faintly yellow oily product. Yield: 94.8%
Reaction SMILES: [OH:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[NH:12][C:11]([CH:13]([C:21]3[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:10][CH:9]=2)=[N:5][CH:4]=1.Cl.C(N=C=NC[CH2:37][CH2:38][N:39]([CH3:41])C)C.ON1C2C=CC=CC=2N=N1.N1CCC1>CN(C)C=O.C(OCC)(=O)C>[N:39]1([C:25]([C:24]2[CH:28]=[CH:29][C:21]([CH:13]([C:11]3[NH:12][C:8]([C:6]4[S:7][C:3]([CH2:2][OH:1])=[CH:4][N:5]=4)=[CH:9][CH:10]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:22][CH:23]=2)=[O:27])[CH2:38][CH2:37][CH2:41]1
Reactant: O=C(O)c1ccc(C(CC2CCOCC2)c2ccc(-c3ncc(CO)s3)[nH]2)cc1
Reactant: CCN=C=NCCCN(C)C
Agent: C1CNC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(c1ccc(C(CC2CCOCC2)c2ccc(-c3ncc(CO)s3)[nH]2)cc1)N1CCC1
Reaction time: 0.5 h
Yield: 27.4 %

Procedure:
To a solution of 4-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl]benzoic acid (100 mg) in N,N-dimethylformamide (5 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (70.0 mg) and 1-hydroxybenzotriazole (50.0 mg), and the mixture was stirred for 30 min. To the reaction mixture was added azetidine (21.0 mg), and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (30.0 mg, yield 28%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). MS: 452 (MH+).
Reaction SMILES: [CH3:1][S:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][N:5]=1)=[O:3].C1C(=O)N([Br:18])C(=O)C1>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:18][CH2:10][C:7]1[CH:8]=[CH:9][C:4]([S:2]([CH3:1])=[O:3])=[N:5][CH:6]=1
Reactant: Cc1ccc(S(C)=O)nc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CS(=O)c1ccc(CBr)cn1
Temperature: 25 °C
Yield: 28.1 %

Procedure:
To a solution of 0.33 g of 2-methanesulfinyl-5-methyl-pyridine in 20 mL of carbon tetrachloride was added 0.40 g NBS and 6 mg benzoyl peroxide. This mixture was refluxed for 4 hours. The reaction mixture was cooled to room temperature, washed with aqueous sodium hydrogen carbonate solution, dried over sodium sulphate, and concentrated to dryness. Purification by flash chromatography (silica, heptane/ethyl acetate) provided 0.14 g of 5-bromomethyl-2-methanesulfinyl-pyridine.
Reaction SMILES: [C:1]([C:3]1([N:9]([CH3:11])[CH3:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].S(=O)(=O)(O)[OH:13]>O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>[CH3:10][N:9]([CH3:11])[C:3]1([C:1]([NH2:2])=[O:13])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: O=S(=O)(O)O
Reactant: CN(C)C1(C#N)CCCCC1
Agent: [Ba+2]
Agent: [OH-]
Solvent: O
Product: CN(C)C1(C(N)=O)CCCCC1
Reaction time: 0.25 h

Procedure:
1-Cyano-N,N-dimethyl cyclohexylamine (10 g.) was added portionwise to conc. sulphuric acid (20 ml.) and the solution left for 15 minutes. The cooled solution was diluted with ice-cold water and neutralised with barium hydroxide octahydrate. The mixture was filtered on hyflo and the filtrate evaporated to dryness when the residual oil (9.1 g., 81%) crystallised on standing. Recrystallisation from petrol (80/100) afforded 1-dimethylamino cyclohexane carboxamide m.p. 65°69°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH2:17][S:18][CH2:19][C:20]([N:22]3[C@@H:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:25][O:24][C:23]3=[O:33])=[O:21])[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2)=[CH:5][CH:4]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=[CH:42][C:43]2[CH:57]=[CH:56][C:46]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[CH:45][CH:44]=2)=[CH:37][CH:36]=1.C(N(C(C)C)C(C)C)C.C(O)(C)C>C(Cl)Cl.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].Cl[Ti](Cl)(Cl)Cl.O>[F:34][C:35]1[CH:36]=[CH:37][C:38]([NH:41][C@@H:42]([C:43]2[CH:44]=[CH:45][C:46]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])=[CH:56][CH:57]=2)[C@@H:19]([S:18][CH2:17][C:9]2([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2)[C:20](=[O:21])[N:22]2[C@@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[CH:39][CH:40]=1
Reactant: COc1ccc(C2(CSCC(=O)N3C(=O)OC[C@@H]3c3ccccc3)OCC(C)(C)CO2)cc1
Reactant: CC(C)(C)OC(=O)COc1ccc(C=Nc2ccc(F)cc2)cc1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CC(C)O
Product: COc1ccc(C2(CS[C@@H](C(=O)N3C(=O)OC[C@@H]3c3ccccc3)[C@@H](Nc3ccc(F)cc3)c3ccc(OCC(=O)OC(C)(C)C)cc3)OCC(C)(C)CO2)cc1
Temperature: -30 °C
Reaction time: 8 h
Yield: 58.9 %

Procedure:
Tetraisopropyl orthotitanate (0.31 ml, 1.06 mmol) was added to a solution of TiCl4 (1M in CH2Cl2, 3.18 ml, 3.18 mmol) in CH2Cl2 (50 ml) at 0° C. under inert atmosphere. The mixture was stirred for ten minutes. (4S)-3-[({[2-(4-Methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)acetyl]-4-phenyl-1,3-oxazolidin-2-one (2.00 g, 4.24 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 20 minutes. The mixture was stirred for ten minutes. tert-Butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate (2.79 g, 8.48 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 30 minutes. The mixture was cooled to −30° C. and stirred for 20 minutes. Ethyl diisopropyl amine (1.45 ml, 8.48 mmol) in 10 ml dry CH2Cl2 was added dropwise over ten minutes and the mixture was stirred at −30° C. for five hours. The mixture was cooled to −78° C. Isopropanol (60 ml) was added and the temperature was allowed to rise overnight. H2O (100 ml) was added and the mixture was stirred for 20 minutes and extracted twice with diethyl ether. The combined organic layers were washed with water, dried (MgSO4) and concentrated under reduced pressure. Purification by flash-chromatography (hexane:EtOAc 3:1) afforded 2.00 g (59%) of the title compound as a yellow solid. 1H-NMR (CDCl3, 200 MHz): δ 0.6 (s, 3H), 1.3 (s, 3H), 1.5 (s, 9H), 2.6-2.9 (m, 2H), 3.3-3.5 (m, 4H), 3.8 (s, 3H), 4.1-4.3 (m, 2H), 4.5 (s, 2H), 4.6-4.8 (m, 2H), 5.0-5.4 (s, broad, 1H), 5.4 (m, 1H), 5.7 (d, 1H), 6.4 (m, 2H), 6.6-6.8 (m, 4H), 6.8-7.0 (m, 4H), 7.1-7.4 (m, 7H).
Reaction SMILES: [OH:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1.[CH2:8](O)[CH2:9][CH2:10][CH2:11][CH3:12]>>[CH2:8]([O:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1)[CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCO
Reactant: O=C1CCC(O)N1
Product: CCCCCOC1CCC(=O)N1
Temperature: 25 °C

Procedure:
A mixture of 2.5 g of 5-hydroxy-pyrrolidin-2-one and 1.25 g of Amberlite IR 120 H is agitated at 65° C. for 3 hours in 55 cm3 of n-pentanol. After cooling to ambient temperature, filtering, and distilling under reduced pressure, the residue is chromatographed on silica (eluent: ethyl acetate), and 2.68 g of the expected product is obtained. m.p. 42°-43° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[O:17][CH:16]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:15][CH2:14]2)([O-])=O>C(O)(=O)C.[Zn]>[C:21]1([CH:16]2[CH2:15][CH2:14][C:13]3[C:18](=[CH:19][CH:20]=[C:11]([O:10][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[NH2:1])[CH:12]=3)[O:17]2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=[N+]([O-])c1ccccc1Oc1ccc2c(c1)CCC(c1ccccc1)O2
Agent: [Zn]
Solvent: CC(=O)O
Product: Nc1ccccc1Oc1ccc2c(c1)CCC(c1ccccc1)O2
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
2-Nitro-1-(2-phenylchroman-6-yloxy)-benzene (0.160 g) was mostly dissolved in 30 ml of glacial acetic acid. Zinc powder (1.190 g) was added in few portions and the mixture was stirred for 90 minutes at room temperature. The zinc was filtered and washed with glacial acetic acid and evaporated. The evaporation residue was taken up with toluene and evaporated again. The residue was dissolved in CH2Cl2 and washed with IM NaOH. NaOH solution was further washed with CH2Cl2. Both organic fractions were combined and dried over Na2SO4. The purification of the crude product was done by elution in CH2Cl2 through a small silica column. 1H-NMR (400 MHz; d6-DMSO): δ 7.45-7.28 (m, 5H), 6.89-6.83 (m, 1H), 6.80 (d, 1H, J=8.5 Hz), 6.77 (dd, 1H, J=8.0 Hz; J=1.7 Hz), 6.73-6.67 (m, 3H), 6.54-6.48 (m, 1H), 5.06 (dd, 1H, J=10.1 Hz; J=2.3 Hz), 4.85 (s, 2H), 2.99-2.87 (m, 1H), 2.73-2.61 (m, 1H), 2.19-2.09 (m, 1H), 2.03-1.90 (m, 1H).
Reaction SMILES: C1([Si](C2C=CC=CC=2)(C2C=CC=CC=2)[OH:8])C=CC=CC=1.[CH3:21][C:22]1[C:27](O)([C:28]#[CH:29])[C:26]([CH3:32])([CH3:31])[CH2:25][C:24](=[O:33])[CH:23]=1>C1(C)C(C)=CC=CC=1.[V].C(O)(=O)CCCCCCCCCCCCCCCCC>[CH3:21][C:22]1[C:27](=[CH:28][CH:29]=[O:8])[C:26]([CH3:32])([CH3:31])[CH2:25][C:24](=[O:33])[CH:23]=1
Reactant: C#CC1(O)C(C)=CC(=O)CC1(C)C
Reactant: O[Si](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [V]
Agent: CCCCCCCCCCCCCCCCCC(=O)O
Solvent: Cc1ccccc1C
Product: CC1=CC(=O)CC(C)(C)C1=CC=O
Yield: 365.2 %

Procedure:
Triphenylsilanol (22 g) and 80 g (0.45 mol) of 3,5,5-trimethyl-4-hydroxy-4-ethynylcyclohex-2-en-1-one and 1.6 g of stearic acid are dissolved in 800 ml of xylene, treated with 1.92 ml of vanadium isopropylate and heated to reflux temperature while stirring. After 31/2 hours the reaction mixture is cooled and washed with 5% sodium bicarbonate, whereby an emulsion results. The organic phase is then separated, the emulsion is also separated and extracted with ether. The organic phases are dried over magnesium sulphate and concentrated. The residue (117.9 g) is distilled (oil bath 130°-170°; 0.001 mm Hg). In this manner there are obtained 51.8 g (64.8%) of (2,6,6-trimethyl-4-oxo-2-cyclohexen-1-ylidene)acetaldehyde (Z:E=about 3:1).