Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[N:8]=[CH:7][C:6]([CH2:9]O)=[CH:5][CH:4]=1.O=P(Cl)(Cl)[Cl:15].O>CN(C=O)C>[Cl:15][CH2:9][C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:12])([F:11])[F:1])=[N:8][CH:7]=1
Reactant: OCc1ccc(C(F)(F)F)nc1
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: FC(F)(F)c1ccc(CCl)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.2 %

Procedure:
To a solution of Example 85B (2.8 g, 15.8 mmol) in 20 mL of anhydrous DMF was added POCl3 (5 mL) at 0° C. The resulting mixture was warmed to room temperature and stirred overnight. The solution was poured into 20 mL of icy water. The mixture was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel column (petroleum ether:ethyl acetate=20:1) to afford the title compound (2.1 g, 68.2%). LC-MS: m/z 300 (M+H). 1H NMR (400 MHz, CDCl3): δ 8.74 (s, 1H), 7.95 (d, J=8.0 Hz, 1H), 7.72 (s, J=8.0 Hz, 1H), 4.66 (s, 2H).
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl.CO.[OH-].[NH4+]>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(Nc3cccnc3)nc12
Agent: [NH4+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(Nc3cccnc3)nc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.4 %

Procedure:
To a solution of N-tert-butyl-2-(pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (44 mg, 99.9 mol) in dichloromethane (1.6 mL) was added trifluoroacetic acid (228 mg, 154 μL, 2.00 mmol) and the reaction mixture stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue obtained diluted with dichloromethane (1.6 mL), methanol (0.8 mL) and ammonium hydroxide (0.2 mL) and stirred at room temperature for 1 h. The mixture was concentrated and triturated with water. The solid was collected by filtration and washed with water and ether to give N-tert-butyl-2-(pyridin-3-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (24 mg, 77.3 mol, 77%) as a brown solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.26 (s, 1H), 9.54 (s, 1H), 8.77 (d, J=2.5, 1 H), 8.04 (d, J=4.6, 1 H), 7.98 (d, J=8.5, 1 H), 7.92 (d, J=3.3, 1 H), 7.91 (s, 1H), 7.57 (s, 1H), 7.19 (m, 1H), 1.31 (s, 9H); MS (EI/CI) m/z: 311.1 [M+H].
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([N:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[CH:6]=[CH:7][CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[CH3:26][O:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1>C(Cl)Cl>[CH3:18][N:15]1[CH2:16][CH2:17][N:12]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH2:3][C@H:2]([NH:1][C:32](=[O:33])[C:31]2[CH:35]=[CH:36][C:28]([O:27][CH3:26])=[CH:29][CH:30]=2)[CH2:11][CH2:10]3)[CH2:13][CH2:14]1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: CN1CCN(c2cccc3c2C[C@H](N)CC3)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)N[C@@H]2CCc3cccc(N4CCN(C)CC4)c3C2)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To an ice-cooled solution of (R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (130 mg, 0.53 mmol) and triethylamine (110 μL, 0.80 mmol) in methylene chloride (30 mL) was added dropwise 4-methoxybenzoyl chloride (95 mg, 0.56 mmol) in methylene chloride (5 mL). After the addition the reaction was allowed to stir at ambient temperature for 15 min and then washed with water. The phases were separated and the combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo to give a crude product which was purified on a silica gel column using chloroform/ethanol saturated with NH3 (100:3) as the eluent. Yield: 143 mg (71%) of the title compound as white crystals: mp 186-187° C.; [α]21D −52° (c 0.50, CHCL3); EIMS (70 eV) m/z (relative intensity) 379 (23, M+).
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][OH:3].[H-].[Na+].Cl[C:8]1[N:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][C:9]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1.O>CN(C=O)C>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C:9]2[C:8]([O:3][CH2:2][CH2:1][OH:4])=[N:13][CH:12]=[C:11]([CH:10]=2)[C:14]([OH:16])=[O:15])=[CH:22][CH:21]=1
Reactant: OCCO
Reactant: O=C(O)c1cnc(Cl)c(-c2ccc(Cl)cc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(O)c1cnc(OCCO)c(-c2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 41.8 %

Procedure:
To a solution of ethane-1,2-diol (301 mg, 270 μA, 4.84 mmol) in dried DMF (6 mL) was added sodium hydride (232 mg, 4.84 mmol) and the reaction mixture was stirred at room temperature for 15 minutes. The resulting solution was added slowly to a solution of 6-chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid (CAN 1012792-56-1; 0.590 g, 2.2 mmol) in dried DMF (6 mL) and stirred at 80° C. for 4 h. More sodium hydride (106 mg, 2.2 mmol) was added and at room temperature and stirring at 80° C. commenced for another 2 h. Water was added and DMF was evaporated. The residue was dissolved in water; acidified with 3M HCl to pH 3. The suspension was filtered; the filter cake was washed with water and dried under high vacuo. The crude material was purified by flash chromatography (ReproFlash Acidosil-S, 50 g, 50% to 100% ethylacetate in heptane) to give 0.27 g (41%) of the title compound as a white solid; MS (ESI): 292.1 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[S:23][C:22]([C:24](O)=[O:25])=[CH:21][CH:20]=4)[N:17]=3)[N:12]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:11]=2)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[OH:62][CH:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1>CN(C)C=O.C(OCC)(=O)C>[OH:62][CH:63]1[CH2:68][CH2:67][N:66]([C:24]([C:22]2[S:23][C:19]([C:16]3[N:17]=[C:18]4[C:10]([C:8]([C:2]5([CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]5)=[O:9])=[CH:11][N:12]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:13]4=[N:14][CH:15]=3)=[CH:20][CH:21]=2)=[O:25])[CH2:65][CH2:64]1
Reactant: OC1CCNCC1
Reactant: CC1(C(=O)c2cn(COCC[Si](C)(C)C)c3ncc(-c4ccc(C(=O)O)s4)nc23)CCCCC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC1(C(=O)c2cn(COCC[Si](C)(C)C)c3ncc(-c4ccc(C(=O)N5CCC(O)CC5)s4)nc23)CCCCC1
Yield: 34.3 %

Procedure:
A solution of 5-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acid (0.080 g, 0.16 mmol), BOP (0.071 g, 0.16 mmol) and 4-hydroxypiperidine (0.162 g, 1.6 mmol) in 2 mL of N,N-dimethylformamide was stirred overnight. The resulting black mixture was taken up in 30 mL of ethyl acetate and washed with three 20 mL portions of a sat. aq. NH4Cl solution, dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0->50% EtOAc/hexanes afforded 0.032 g (34%) of [2-[5-(4-hydroxy-piperidine-1-carbonyl)-thiophen-2-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanone as a tan oil.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[CH:7][S:8](=O)[C:4]=2[CH:3]=1.Cl.[CH3:13][N:14]([CH2:16][CH2:17]Cl)[CH3:15].C([O-])([O-])=[O:20].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]([CH2:17][CH2:16][N:14]([CH3:15])[CH3:13])[C:7](=[O:20])[S:8][C:4]=2[CH:3]=1
Reactant: CN(C)CCCl
Reactant: O=S1C=Nc2ccc(Cl)cc21
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [K+]
Solvent: CC(C)=O
Product: CN(C)CCn1c(=O)sc2cc(Cl)ccc21
Yield: 64.3 %

Procedure:
A solution of compound (VIII) (9.28 g, 50 mmol), N,N-dimethylaminoethylchloride hydrochloride (XIe) (7.92 g, 55 mmol), and K2CO3 (16.58 g, 120 mmol) in acetone (93 ml) was refluxed for 20 hours with stirring. After the reaction was complete, the reaction mixture was concentrated in vacuo. The residue was extracted with ethyl acetate. The layer of ethyl acetate was dried over MgSO4 and subjected to column chromatography on silica gel. From the eluate eluted with ethyl acetate, compound (XIIe) (3.3 g, yield=64.3%) was obtained as an oil.
Reaction SMILES: [C:1]([C:3]1[N:8]=[CH:7][C:6](C)=[C:5]([CH3:10])[CH:4]=1)#[N:2].[ClH:11].[H][H].[CH3:14]O>[Pd]>[NH2:2][CH2:1][C:3]1[C:4]([CH3:14])=[C:5]([CH3:10])[CH:6]=[CH:7][N:8]=1.[ClH:11]
Reactant: CO
Reactant: [H][H]
Reactant: Cc1cnc(C#N)cc1C
Agent: [Pd]
Agent: Cl
Product: Cc1ccnc(CN)c1C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
In an autoclave, 3.40 g of 6-cyano-3,4-dimethylpyridine (25.7 mmol), 0.15 g of Pd/C (water-content=50%), 200 mL methanol and 3.0 mL concentrated hydrochloric acid are placed, stirred at room temperature for 3 hours while pressurizing with hydrogen to 3 atm. The reaction solution was filtered through Celite and the filtrate was concentrated to dryness. This was washed with methanol to give 2.41 g of 2-aminomethyl-3,4-dimethylpyridine (3,4-Me2PICA) hydrochloride (93% yield). This 2-aminomethyl-3,4-dimethylpyridine hydrochloride was treated with an aqueous solution of potassium carbonate to give 2-aminomethyl-3,4-dimethylpyridine (3,4-Me2PICA) quantitatively.
Reaction SMILES: C([Li])CCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][O:25][CH3:26])[CH:18]=1.[C:27](=[O:29])=[O:28]>C1COCC1.O.C(OCC)C>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][O:25][CH3:26])[C:18]=1[C:27]([OH:29])=[O:28]
Reactant: O=C=O
Reactant: COCOc1cccc(Cl)c1
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCOCC
Product: COCOc1cccc(Cl)c1C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 3-chlorophenol (8 ml, 77 mmol, ABCR) in DCM (120 ml) was added dimethoxymethane (32 ml, 362 mmol, Aldrich) and then p-toluenesulphonic acid (0.164 g, 0.952 mmol, Alfa Aesar). The solution was heated to reflux under nitrogen using a Soxhlet apparatus containing 3A activated molecular sieves (approximately 20 g)* for 24 h. *The 3A molecular sieves were replaced after 6 h. Approximately a quarter of the reaction mixture was applied to a 70 g aminopropyl cartridge (prewashed with methanol). The cartridge was eluted with methanol (1-2 column volumes) and several fractions collected. Appropriate fractions were combined (TLC 50:50 DCM in cyclohexane) and the solvent removed in vacuo to give 1-chloro-3-{[(methyloxy)methyl]oxy}benzene as a colourless mobile oil (1.66 g). The remaining reaction mixture was applied evenly to 3×70 g aminopropyl cartridges (pre-washed with methanol). The cartridges were eluted with methanol (1-2 column volumes) and several fractions collected. Appropriate fractions were combined (TLC 50:50 DCM in cyclohexane) and the solvent removed in vacuo to leave a colourless mobile oil (first batch). The mixed fractions were combined and the solvent removed in vacuo to leave a colourless mobile oil. The residue from the mixed fractions was applied to a 70 g aminopropyl cartridge (pre-washed with methanol) and eluted with methanol. Appropriate fractions were combined (TLC 50:50 DCM in cyclohexane) and added to the first batch. The solvent was removed in vacuo to give another batch of 1-chloro-3-{[(methyloxy)methyl]oxy}benzene as a colourless mobile oil (5.27 g). To THF (20 ml) under nitrogen at 0° C. was added 1.6 M n-butyllithium in hexanes (18.1 ml, 29.0 mmol, Aldrich). To the solution at −60° C. was added a solution of 2,2,6,6-tetramethylpiperidine (4.90 ml, 29.0 mmol, Alfa Aesar) in THF (5 ml) and then a solution of 1-chloro-3-{[(methyloxy)methyl]oxy}benzene (5.01 g, 29.0 mmol) in THF (10 ml). The temperature was maintained below −50° C. during the addition. The solution was stirred at −60° C. to −70° C. for 1 h. To the solution was added a large excess of freshly ground solid carbon dioxide and the mixture allowed to warm to ambient temperature. The reaction mixture was diluted with water (100 ml) and diethyl ether (130 ml). The phases were separated and aqueous phase carefully acidified to pH1 using concentrated HCl. The suspension was extracted with dichloromethane (3×40 ml). The solvent was removed in vacuo to give the title compound as a white solid (4.36 g);
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][NH:25]4)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:15])[C:11]([F:14])([F:13])[F:12].B(C#N)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>CC(O)=O.O>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH2:23][CH2:24][NH:25]4)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:15])[C:11]([F:12])([F:13])[F:14]
Reactant: CC(Oc1ccc(-c2nc(-c3cccc4[nH]ccc34)no2)cc1C(F)(F)F)C(F)(F)F
Agent: N#CB([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: CC(Oc1ccc(-c2nc(-c3cccc4c3CCN4)no2)cc1C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.6 %

Procedure:
To a solution 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole (100 mg) in AcOH (3 ml) was added portionwise sodium cyanoboroate (29 mg). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water, alkalified with a 1M aqueous NaOH solution, and extracted with EtOAc. The organic layer was washed with saturated brine, dried over anhydrous MgSO4, and then filtered, the filtrate was concentrated, and the residue was purified by silica gel column chromatography (n-hexane:EtOAc=90:10 to 75:25), and washed with n-hexane to obtain 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}indoline (90 mg) as a pale yellow solid.
Reaction SMILES: [CH2:1]([N:4]1[C:8]2[C:9]([CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:18])[CH:2]=[CH2:3].[Cl:19]N1C(=O)CCC1=O>C1(C)C=CC=CC=1.[Cl-].[Zr+4].[Cl-].[Cl-].[Cl-]>[CH2:1]([N:4]1[C:8]2[C:9]([CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:10][CH:11]=[C:12]([Cl:19])[C:7]=2[NH:6][C:5]1=[O:18])[CH:2]=[CH2:3]
Reactant: C=CCn1c(=O)[nH]c2cccc(C(CC)CC)c21
Reactant: O=C1CCC(=O)N1Cl
Agent: [Zr+4]
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: C=CCn1c(=O)[nH]c2c(Cl)ccc(C(CC)CC)c21
Reaction time: 15 h
Yield: 38.3 %

Procedure:
To a mixture of 1-allyl-7-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazol-2-one (22.0 g, 89.8 mmol) and zirconium chloride (1.05 g, 4.49 mmol) in toluene (300 mL) was added N-chlorosuccinimide (12.4 g, 92.5 g) portionwise at 0° C. After stirring for 15 hr, the mixture was concentrated in vacuo to give a residue which was partitioned in aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate. Combined organic layer was washed with aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was dissolved in hot ethyl acetate. n-Hexane was then added and the solution was cooled down. Resulting precipitate was collected by filtration to afford the title compound (9.60 g, 34.4 mmol, 38%) as a colorless solid.
Reaction SMILES: [Br-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl.[CH3:24][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]2[C:34]=1[N:33]=[C:32]([C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)[CH:31]=[C:30]2[C:40]([OH:42])=O.[NH2:43][C:44]1[O:45][C:46]([C:49]2[O:50][CH:51]=[CH:52][CH:53]=2)=[N:47][N:48]=1>N1C=CC=CC=1>[O:50]1[CH:51]=[CH:52][CH:53]=[C:49]1[C:46]1[O:45][C:44]([NH:43][C:40]([C:30]2[C:29]3[C:34](=[C:25]([CH3:24])[CH:26]=[CH:27][CH:28]=3)[N:33]=[C:32]([C:35]3[S:36][CH:37]=[CH:38][CH:39]=3)[CH:31]=2)=[O:42])=[N:48][N:47]=1
Reactant: Cc1cccc2c(C(=O)O)cc(-c3cccs3)nc12
Reactant: Nc1nnc(-c2ccco2)o1
Agent: [Br-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1cccc2c(C(=O)Nc3nnc(-c4ccco4)o3)cc(-c3cccs3)nc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 12.5 %

Procedure:
Triphenylphosphine bromide (352 mg, 0.80 mmol) was added to a methylene chloride (1 mL) solution of commercially available 8-methyl-2-(2-thienyl)-4-quinolinecarboxylic acid (108 mg, 0.40 mmol), and the mixture was stirred at room temperature for 1 hour. The reaction solution was added to a pyridine (3 mL) solution of 2-amino-5-(2-furyl)-1,3,4-oxadiazole (90.7 mg, 0.60 mmol), and the mixture was stirred at room temperature for 2 hours and then heated with stirring overnight at 60° C. The reaction solution was concentrated. After that, to the residue, water was added, and the deposited solid was collected by filtration, washed with water, dried, and then purified by preparative HPLC to obtain the title compound (22 mg, 0.05 mmol).
Reaction SMILES: N1(CCCC(C2C=CC3OC4C(=CC(C(=O)CCCN5CCCCC5)=CC=4)CC=3C=2)=[O:11])CCCCC1.[N:37]1([CH2:43][CH2:44][CH2:45][CH2:46][C:47]([C:49]2[CH:62]=[CH:61][C:60]3[O:59][C:58]4[C:53](=[CH:54][C:55]([C:63](=[O:74])[CH2:64][CH2:65][CH2:66][CH2:67][N:68]5[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]5)=[CH:56][CH:57]=4)[CH2:52][C:51]=3[CH:50]=2)=[O:48])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+]>C(O)(=O)C>[N:37]1([CH2:43][CH2:44][CH2:45][CH2:46][C:47]([C:49]2[CH:62]=[CH:61][C:60]3[O:59][C:58]4[C:53](=[CH:54][C:55]([C:63](=[O:74])[CH2:64][CH2:65][CH2:66][CH2:67][N:68]5[CH2:69][CH2:70][CH2:71][CH2:72][CH2:73]5)=[CH:56][CH:57]=4)[C:52](=[O:11])[C:51]=3[CH:50]=2)=[O:48])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: O=C(CCCCN1CCCCC1)c1ccc2c(c1)Cc1cc(C(=O)CCCCN3CCCCC3)ccc1O2
Reactant: O=C(CCCN1CCCCC1)c1ccc2c(c1)Cc1cc(C(=O)CCCN3CCCCC3)ccc1O2
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(CCCCN1CCCCC1)c1ccc2oc3ccc(C(=O)CCCCN4CCCCC4)cc3c(=O)c2c1

Procedure:
Following the procedure of Example 42, only substituting for 2,7-bis(4-piperidinobutyryl)xanthene, 25.8 g (0.05 mole) 2,7-bis(5-piperidinovaleryl)xanthene and using 600 ml of glacial acetic acid and 19.7 g (0.066 mole) sodium dichromate, the solid obtained is recrystallized from a benzene-heptane mixture to give the title compound, M.P. 109°-110°C.
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[CH2:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.[CH3:17][C:18]1([CH3:34])[C:22]([CH3:24])([CH3:23])[O:21][B:20]([C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[O:19]1>>[CH3:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[CH2:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:29]([C:28]1[CH:27]=[CH:26][C:25]([B:20]2[O:21][C:22]([CH3:24])([CH3:23])[C:18]([CH3:34])([CH3:17])[O:19]2)=[CH:33][CH:32]=1)=[O:30]
Reactant: CC1(C)OB(c2ccc(C(=O)O)cc2)OC1(C)C
Reactant: C[C@@H]1CCCN1C[C@@H]1CCCN1
Solvent: O=S(Cl)Cl
Product: C[C@@H]1CCCN1C[C@@H]1CCCN1C(=O)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1

Procedure:
The title intermediate is prepared in a manner substantially analogous General Procedure PP, except thionyl chloride is used instead of oxalyl chloride, using 2-(R)-methyl-1-(2-(S)-pyrrolidinylmethyl)pyrrolidine and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (CAS 180516-87-4). MS (ES+) 399.5 (M+H)+
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]1[CH2:14][CH2:13][C:12]2[C:15]([O:25][CH3:26])=[C:16]([O:23][CH3:24])[C:17]([O:21][CH3:22])=[C:18]([O:19][CH3:20])[C:11]=2[CH2:10][CH2:9]1)(=O)=O.[I-:27].[Na+].CC(C)=O>O>[I:27][CH2:6][CH2:7][CH:8]1[CH2:14][CH2:13][C:12]2[C:15]([O:25][CH3:26])=[C:16]([O:23][CH3:24])[C:17]([O:21][CH3:22])=[C:18]([O:19][CH3:20])[C:11]=2[CH2:10][CH2:9]1
Reactant: [I-]
Reactant: COc1c2c(c(OC)c(OC)c1OC)CCC(CCOS(C)(=O)=O)CC2
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: COc1c2c(c(OC)c(OC)c1OC)CCC(CCI)CC2
Yield: 97.5 %

Procedure:
The mixture of 2-(1,2,3,4-tetramethoxy-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-7-yl)ethyl methanesulfonate (3.12 g), sodium iodide (3.61 g), and acetone (40 ml) was heated under reflux for 1 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium sulfite, water, and saturated aqueous sodium chloride, and dried. The solvent was removed in vacuo to yield the entitled compound (3.29 g) as crystals.
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH:5]([CH2:13][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])#[N:2].N.[H][H]>CO.[Ni]>[NH2:2][CH2:1][CH2:3][CH2:4][CH:5]([CH2:13][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10]
Reactant: [H][H]
Reactant: COC(=O)CCCC(CCC#N)CCc1cccnc1
Agent: [Ni]
Agent: N
Solvent: CO
Product: COC(=O)CCCC(CCCN)CCc1cccnc1

Procedure:
To a solution of 0.1 g (0.37 mmol) of methyl 7-cyano-5-[2-(3-pyridyl)ethyl]-heptanoate in 20 ml of methanol saturated with ammonia is added 0.15 ml Raney Nickel and the mixture is hydrogenated at 3 atmospheres (=3.04 bar) pressure of hydrogen and room temperature for 4 h. The catalyst is filtered off and washed with methanol (4×20 ml). The filtrate is evaporated to give methyl 8-amino-5-[2-(3-pyridyl)ethyl]-octanoate.
Reaction SMILES: ON1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=O.[C:13]([OH:16])(=[O:15])[CH3:14].[O:17]=O>CC1C=CC(C)=CC=1>[C:6]([OH:7])(=[O:17])[C:5]1[CH:4]=[CH:11][C:10]([C:13]([OH:16])=[O:15])=[CH:9][CH:8]=1.[CH3:3][C:4]1[CH:5]=[CH:6][C:14]([C:13]([OH:16])=[O:15])=[CH:10][CH:11]=1
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: O=O
Reactant: CC(=O)O
Solvent: Cc1ccc(C)cc1
Product: Cc1ccc(C(=O)O)cc1
Product: O=C(O)c1ccc(C(=O)O)cc1
Yield: 24 %
Yield: 71 %

Procedure:
A mixture of 1.06 grams (10 millimoles) of p-xylene, 0.32 gram (2 millimoles) of N-hydroxyphthalimide, 0.018 gram (0.05 millimole) of acetylacetonatocobalt(III) Co(AA)3 and 25 milliliters of acetic acid was stirred in an oxygen atmosphere at a temperature of 100° C. for 12 hours. As a result, p-xylene was transformed into terephthalic acid (yield 71%) and p-methylbenzoic acid (yield 24%) with a transformation rate of 99%.
Reaction SMILES: C[C:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(Br)[C:3]([OH:5])=[O:4].[CH2:13](N(CC)CC)C.[CH:20]1([NH2:23])[CH2:22][CH2:21]1.[Na+].[Cl-]>CC#N>[CH3:13][O:5][C:3](=[O:4])[CH:2]([NH:23][CH:20]1[CH2:22][CH2:21]1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCN(CC)CC
Reactant: CC(Br)(C(=O)O)c1ccccc1
Reactant: NC1CC1
Agent: [Cl-]
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)C(NC1CC1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In analogy to a procedure outlined in J. Chem. Soc. Perkin Trans. 1, 22, 1993, 2761-2772, methyl-α-bromophenylacetic acid (2.0 g) was dissolved in CH3CN and cooled to 0° C. by means of an ice bath. To this solution was added triethylamine (1.7 mL) dropwise and the mixture was stirred for 30 minutes. A solution of cyclopropylamine in CH3CN was then added dropwise at 0° C. over 5 minutes and stirring was continued for 2 hours. The mixture was poured into ice/water, saturated with NaCl and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography, eluting with a gradient of ethyl acetate in heptane (0 to 50% ethyl acetate). Fractions containing the product were combined and evaporated to give cyclopropylamino-phenyl-acetic acid methyl ester as a light yellow liquid (1.74 g). MS (ESI): 206.0 (MH+).