Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>CN(C)C=O>[CH2:28]([O:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]=[O:5])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH3:18]
Reactant: CCCCCCCCCCCBr
Reactant: COc1ccc(O)c(C=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCOc1ccc(OC)cc1C=O
Temperature: 100 °C
Reaction time: 1 h
Yield: 80.5 %

Procedure:
To a solution of 2-hydroxy-5-methoxybenzaldehyde (10 g, 65.7 mmoles) in 100 ml of sieve-dried dimethylformamide was added freshly-pulverized potassium carbonate (10 g, 72.3 mmoles) and undecyl bromide (15 ml, 67.3 mmoles). The reaction mixture was stirred at 100° C. for 1 hour, cooled to room temperature and then poured into ice-cold water/hexane. The layers were separated and the organic extract was washed with ice-cold 5% sodium hydroxide solution, water and saturated sodium chloride solution. The organic layer was dried with anhydrous magnesium sulfate, treated with charcoal and concentrated in vacuo. The resulting yellow solid was recrystallized from hexane, to give 16.2 g (80%) of the product as a white solid.
Reaction SMILES: [OH:1][C:2]1[C:9]([O:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.Cl[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:15][O:14][CH2:13][CH2:12][CH2:11][O:10][C:9]1[C:2]2[O:1][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:4][C:3]=2[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)CCl
Reactant: COCCCOc1cccc(C=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc2cccc(OCCCOC)c2o1

Procedure:
A suspension of 1.95 g of 2-hydroxy-3-(3-methoxypropoxy)benzaldehyde, 1.16 ml of ethyl chloroacetate and 2.51 g of potassium carbonate in 100 ml of N,N-dimethylformamide is stirred at reflux over 19 hours. The reaction mixture is cooled, poured onto water (at 0° C.), stirred and subsequently extracted with dichloromethane (2×). The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.50 (1:1 EtOAc-heptane); Rt=4.72.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.O>C1COCC1>[NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: c1cnc2cc[nH]c2c1
Solvent: O
Solvent: C1CCOC1
Product: c1cnc2c(c1)NCC2
Temperature: 25 °C
Yield: 14.1 %

Procedure:
To a solution of 1H-pyrrolo[3,2-b]pyridine (1.18 g, 10 mmol) in 100 mL of THF, was added borane tetrahydrofuran complex (60 mL of a 1 M solution, 6 eq) and the mixture was heated at reflux for 5 h. After allowing the reaction to cool down to room temperature, water was added slowly and the solution was extracted with ethyl acetate twice. The combined extracts were washed with a saturated solution of sodium bicarbonate, dried over sodium sulfate and evaporated. The residue was purified on silica gel (eluent: 15% methanol in DCM) to give 0.17 g of 2,3-dihydro-1H-pyrrolo[3,2-b]pyridine 1-1.
Reaction SMILES: Cl[C:2]1[C:3]([CH3:11])=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[OH:12][CH2:13][C:14]([CH3:22])([CH3:21])[CH2:15][CH2:16][S:17]([NH2:20])(=[O:19])=[O:18]>>[CH3:21][C:14]([CH3:22])([CH2:15][CH2:16][S:17](=[O:19])(=[O:18])[NH2:20])[CH2:13][O:12][C:2]1[C:3]([CH3:11])=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1
Reactant: Cc1cc2nccn2nc1Cl
Reactant: CC(C)(CO)CCS(N)(=O)=O
Product: Cc1cc2nccn2nc1OCC(C)(C)CCS(N)(=O)=O
Yield: 26.2 %

Procedure:
Using 0.84 g of 6-chloro-7-methylimidazo[1,2-b]pyridazine and 0.91 g of 4-hydroxy-3,3-dimethyl-1-butanesulfonamide, 0.41 g of title compound was obtained in the same manner as in Example 3.
Reaction SMILES: C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=[O:6].[Na+].[Na+].[C:23]1(/[CH:29]=[CH:30]/[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.OOS([O-])=O.[K+].C(=O)(O)[O-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C.O>[CH:26]1[CH:25]=[CH:24][C:23]([C@H:29]2[O:6][C@@H:30]2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[CH:28][CH:27]=1
Reactant: C(=C/c1ccccc1)\c1ccccc1
Reactant: O=C([O-])CN(CCN(CC(=O)[O-])CC(=O)O)CC(=O)O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: O=S(=O)([O-])O
Solvent: CC#N
Solvent: O
Product: c1ccc([C@H]2O[C@@H]2c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 73 %

Procedure:
Aqueous Na2EDTA (1×10−4 M, 10 mL) and a catalytic amount of tetrabutylammonium hydrogen sulfate were added to a solution of trans-stilbene (0.18 g, 1 mmol) in acetonitrile (15 mL) with vigorous stirring at 0° C. A mixture of Oxone® (3.07 g, 5 mmol) and sodium bicarbonate (1.3 g, 15.5 mmol) was pulverized and a small portion of this mixture was added to the reaction mixture to bring the pH to >7. After 5 min, ketone 1 (0.77 g, 3 mmol) was added portionwise over a period of 1 h. Simultaneously, the rest of Oxone® and sodium bicarbonate was added portion was added portionwise over 50 min. After the completion of the addition of ketone 1, the reaction mixture was stirred for another 1 h at 0° C., diluted with water (30 mL), and extracted with hexanes (4×40 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered, concentrated, and purified by flash chromatography [the silica gel was buffered with 1% triethylamine solution in hexane; hexane/ether (1/0 to 50/1, V/V) was used as the eluent] to afford trans-stilbene oxide as white crystals (0. 149 g, 73% yield, 95.2% ee).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:12][CH2:13]OS(C)(=O)=O)[C:8]2[C:4](=[CH:5][N:6]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:7]=2)[CH:3]=1.[Li+].[B-](CC)(CC)CC>C1COCC1.CCOCC.O>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:12][CH3:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:46])[CH3:47])[N:7]=2)[CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(COC(CCOS(C)(=O)=O)c2cc(Cl)cc3cn(COCC[Si](C)(C)C)nc23)(c2ccc(F)cc2)CC1
Agent: CC[B-](CC)CC
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: CCC(OCC1(c2ccc(F)cc2)CCN(C(=O)OC(C)(C)C)CC1)c1cc(Cl)cc2cn(COCC[Si](C)(C)C)nc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 61.5 %

Procedure:
Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-3-(methylsulfonyloxy)propoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (28.5 mg, 0.039 mmol) in THF (1 ml) at 0° C. was added Superhydride (0.059 ml, 0.059 mmol). It was stirred at R.T. over three hours, LC/MS showed no reaction. Another 1.5 eq of super hydride was added and it was stirred at R.T. overnight. LC/MS showed partial convertion to product, another 1.5eq of superhydride was added and it was stirred at R.T. overweekend. LC/MS showed the reaction was complete. The reaction was cooled to 0° C. and diluted with ether, water was added and layer separated, the organics were washed with brine and dried over magnesium sulfate, filtered and concentrated. It was purified by Biotage LC eluting with 25% EtOAc/Hex to afford title compound (15 mg, 0.024 mmol, 60.5% yield) as clear oil. 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.31 (m, 2H), 7.03 (t, J=8.9 Hz, 2H), 6.68 (s, 1H), 5.66 (AB, Δν=17.4 Hz, J=10.7 Hz, 2H), 4.77 (m, 1H), 3.72 (m, 2H), 3.59 (t, J=8.2 Hz, 2H), 3.34 (AB, Δν=23.5 Hz, J=8.8 Hz, 2H), 3.09 (m, 2H), 2.40 (m, 1H), 2.12 (m, 1H), 1.96 (m, 1H), 1.84 (m, 2H), 1.70 (m, 1H), 1.44 (s, 9H), 0.91 (m, 2H), 0.84 (t, J=7.3 Hz, 3H), −0.06 (s, 9H). LC/MS (HPLC method 4): tR=4.99 min, 632.2(MH)+.
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]1([OH:18])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].[F:25][C:26]([F:31])([F:30])[CH2:27][CH2:28]I>C(#N)C>[F:1][C:2]1[C:7]([C:8]([F:10])([F:11])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]1([OH:18])[CH2:17][CH2:16][N:15]([CH2:28][CH2:27][C:26]([F:31])([F:30])[F:25])[CH2:14][CH2:13]1
Reactant: OC1(c2cccc(C(F)(F)F)c2F)CCNCC1
Reactant: FC(F)(F)CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: OC1(c2cccc(C(F)(F)F)c2F)CCN(CCC(F)(F)F)CC1

Procedure:
Preparation according to Example 2: 4-[2-fluoro-3-(trifluoromethyl)phenyl]piperidin-4-ol (0.02 g, 0.076 mmol), acetonitrile (2 ml), potassium carbonate (0.02 g, 0.14 mmol), 1,1,1-trifluoro-3-iodopropane (0.010 ml, 0.082 mmol). MS m/z (relative intensity, 70 eV) 359 (M+, 20), 276 (bp), 258 (39), 191 (21), 152 (19).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:10]([O:17][C:18]1[CH:19]=[CH:20][C:21]2[O:27][CH2:26][CH2:25][CH:24](Br)[C:23](=[O:29])[C:22]=2[CH:30]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O1CCCC1>[CH2:10]([O:17][C:18]1[CH:19]=[CH:20][C:21]2[O:27][CH2:26][CH2:25][CH:24]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:23](=[O:29])[C:22]=2[CH:30]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Oc1ccccc1
Reactant: O=C1c2cc(OCc3ccccc3)ccc2OCCC1Br
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1c2cc(OCc3ccccc3)ccc2OCCC1Oc1ccccc1
Reaction time: 0.5 h
Yield: 42.8 %

Procedure:
To a solution of 1.4 g of phenol in 50 ml of tetrahydrofuran was added 720 mg of 50% sodium hydride. After stirring for 30 minutes, a solution of 4.5 g of crude 7-benzyloxy-4-bromo-3,4-dihydro-1-benzoxepin-5(2H)-one was added. The reaction was allowed to stir at room temperature for 5 hours. The tetrahydrofuran was evaporated in vacuo, and the residue dissolved in ethyl acetate and washed with water. The ethyl acetate layer was dried over sodium sulfate and evaporated in vacuo to give the crude product which was purified by recrystallization from methanol to give 2 g of title product, m.p. 112-114° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.C([Li])CCC.[C:27](=[O:29])=[O:28]>O1CCCC1>[C:16]1([C@H:14]([N:10]2[CH2:11][CH2:12][O:13][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([C:27]([OH:29])=[O:28])=[CH:3][CH:4]=3)[CH2:9]2)[CH3:15])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(Br)cc2)C1
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(C(=O)O)cc2)C1
Temperature: -78 °C
Yield: 98 %

Procedure:
To a suspension of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (3.46 g, 10.0 mmol) in tetrahydrofuran (80 ml) was added n-butyllithium (7.7 ml, 12.0 mmol, 1.56 M in hexane) at −78° C. After stirring for 10 minutes, excess of dry ice was added to the mixture and the reaction mixture was maintained at −78° C. for 1.5 hours and then partitioned between diethyl ether and 0.2 N aqueous sodium hydroxide. The aqueous layer was washed with diethyl ether and neutralized with 1N hydrochloric acid. The resulting aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. Filtration of the precipitate gave 4-[(2S)-4-((1R)-1-phenyl-ethyl)-morpholin-2-yl]-benzoic acid (3.05 g, 98%) as white crystals.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:10])=[C:4]([Br:9])[C:5]([F:8])=[CH:6][CH:7]=1.C([O:13][CH:14]=[C:15]([C:21](OCC)=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17])C.C1(OC2C=CC=CC=2)C=CC=CC=1.C1C2C3C=CC=CC=3OC=2C=CC=1>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[Br:9][C:4]1[C:3]([F:10])=[C:2]2[C:7]([C:14]([OH:13])=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:21]=[N:1]2)=[CH:6][C:5]=1[F:8]
Reactant: Nc1ccc(F)c(Br)c1F
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: c1ccc2c(c1)oc1ccccc12
Product: CCOC(=O)c1cnc2c(F)c(Br)c(F)cc2c1O
Temperature: 150 °C
Yield: 78 %

Procedure:
A stirred mixture of 26 g of 3-amino-2,6-difluorobromobenzene and 27 g of diethyl ethoxymethylenemalonate was heated at 150° C. for 1 hour. After cooling, 100 ml of Dowtherm "A" (commercially available high boiling inert solvent mixture of diphenylether and dibenzofuran) was added and the mixture was heated under nitrogen at 260° C. for 1.5 hour. The mixture was cooled to room temperature and 200 ml of hexanes was added. The resulting precipitate was collected by filtration, washed with hexanes and dried to give a cream solid, m.p. 285° C., yield 78% (32.32 g).
Reaction SMILES: [C:1]([C:3]1([OH:12])[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2C[CH2:4]1)#[CH:2].C(C1C=CC=CN=1)(=O)C>>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:6][C:7]=1[C:3]([OH:12])([C:1]#[CH:2])[CH3:4]
Reactant: C#CC1(O)CCc2cccnc21
Agent: CC(=O)c1ccccn1
Product: C#CC(C)(O)c1ccccn1

Procedure:
The title compound was prepared using the method described for the preparation of 7-ethynyl-5H,6H-cyclopenta[b]pyridin-7-ol, by replacing 5,6-dihydro-7H-cyclopenta[b]pyridin-7-one with 2-acetylpyridine; 1H NMR (500 MHz, CDCl3) delta 1.80 (3H, s), 2.55 (1H, s), 5.50 (1H, s), 7.20-7.32 (1H, m), 7.62 (1H, d, J=7.88 Hz), 7.78 (1 H, td, J=7.72, 1.58 Hz), 8.54 (1H, d, J=4.73 Hz); LC-MS: m/z=+147.9 (M+H)+.
Reaction SMILES: Br[C:2]1[C:6]2[N:7]=[CH:8][N:9]=[C:10]([S:11][CH3:12])[C:5]=2[S:4][CH:3]=1.C1(NC2CCCCC2)CCCCC1.[C:26]([Si:28]([CH3:31])([CH3:30])[CH3:29])#[CH:27].N#N>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:12][S:11][C:10]1[C:5]2[S:4][CH:3]=[C:2]([C:27]#[C:26][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:6]=2[N:7]=[CH:8][N:9]=1
Reactant: CSc1ncnc2c(Br)csc12
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: C1CCC(NC2CCCCC2)CC1
Solvent: CC#N
Product: CSc1ncnc2c(C#C[Si](C)(C)C)csc12
Temperature: 80 °C
Reaction time: 14 h
Yield: 65.6 %

Procedure:
7-Bromo-4-(methylthio)thieno[3,2-d]pyrimidine (3 g, 11.49 mmol) was dissolved in acetonitrile (30 mL) and then bis(triphenylphosphine)palladium(II) dichloride (204 mg, 0.29 mmol), CuI (76 mg, 0.40 mmol), dicyclohexylamine (2.5 mL, 12.64 mmol) and ethynyltrimethylsilane (3.2 mL, 22.98 mmol) were added thereto. The reaction mixture was treated with N2 gas for 15 minutes and stirred at 80° C. for 14 hours. The reaction mixture was cooled to room temperature, filtered using Celite and washed with ethyl acetate (50 mL). The filtrate was washed with brine and concentrated by drying with MgSO4. The resulting mixture was purified by silica gel chromatography (ethyl acetate/hexane=1:9˜2:8) to obtain the title compound (2.1 g, 65% yield) as a yellowish solid.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11](Cl)=[O:12].[CH3:14][NH:15][C@H:16]1[CH2:35][N:20]2[C:21]3[C:26]([C:27]([CH2:28][C:29]([O:31]CCC)=[O:30])=[C:19]2[CH2:18][CH2:17]1)=[CH:25][CH:24]=[CH:23][CH:22]=3>>[CH3:14][N:15]([C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[O:12])[C@H:16]1[CH2:35][N:20]2[C:21]3[C:26]([C:27]([CH2:28][C:29]([OH:31])=[O:30])=[C:19]2[CH2:18][CH2:17]1)=[CH:25][CH:24]=[CH:23][CH:22]=3
Reactant: O=C(Cl)c1ccc2ccccc2c1
Reactant: CCCOC(=O)Cc1c2n(c3ccccc13)C[C@H](NC)CC2
Product: CN(C(=O)c1ccc2ccccc2c1)[C@@H]1CCc2c(CC(=O)O)c3ccccc3n2C1

Procedure:
The title compound was prepared using analogous procedures described in Example 2 (Method B) from 2-naphthoyl chloride and propyl [(7R)-7-(methylamino)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate. MS (+ESI) m/z: 413.
Reaction SMILES: ClC1C=CC(C(O)=O)=CC=1S(=O)(=O)[N:12]([CH2:17][CH2:18][CH2:19][CH3:20])[CH2:13][CH2:14][CH2:15][CH3:16].CC1CCCCC1>>[CH2:13]([NH:12][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:14][CH2:15][CH3:16]
Reactant: CCCCN(CCCC)S(=O)(=O)c1cc(C(=O)O)ccc1Cl
Solvent: CC1CCCCC1
Product: CCCCNCCCC

Procedure:
4-chloro-3-di-n-butylsulfamoylbenzoic acid, melting point: 73°-75° C. (from methylcyclohexane)
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]=[CH:2]1.[NH:10]1[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]1.[OH-].[K+]>CO>[NH:10]1[CH2:11][CH:12]=[C:13]([C:3]2[C:4]3[C:9](=[N:8][CH:7]=[CH:6][CH:5]=3)[NH:1][CH:2]=2)[CH2:14][CH2:15]1
Reactant: O=C1CCNCC1
Reactant: c1cnc2[nH]ccc2c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: C1=C(c2c[nH]c3ncccc23)CCNC1
Yield: 83.8 %

Procedure:
7-Azaindole (10 g, 85 mmol), 4piperidone (34 g,0.22 mol) and potassium hydroxide (16.83 g, 0.3 mol) were heated to reflux in 150 ml methanol overnight. The reaction was cooled, filtered and concentrated to give an orange slurry. The slurry was then extracted with methylene chloride and washed with water. The organic layer was dried over anhydrous magnesium, filtered and concentrated to afford 14.2 g (84%) of product as a solid: mp 195-199° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]([O:19]C(C)(C)C)=[O:18])=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4]>Cl>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4]
Reactant: COC(=O)C1(c2ccc(OCCC(=O)OC(C)(C)C)cc2)CC1
Agent: Cl
Product: COC(=O)C1(c2ccc(OCCC(=O)O)cc2)CC1
Temperature: 25 °C
Yield: 94.6 %

Procedure:
A solution of 1-[4-(2-tert-butoxycarbonyl-ethoxy)-phenyl]-cyclopropanecarboxylic methyl ester (6.3 g, 20 mmol) in HCl (20%, 200 mL) was heated at 110° C. for 1 h. After cooling to room temperature, the resulting mixture was filtered. The solid was washed with water and dried under vacuum to give 1-[4-(2-carboxy-ethoxy)-phenyl]-cyclopropanecarboxylic methyl ester (5.0 g, 96%). 1H NMR (300 MHz, DMSO) δ 7.23-7.19 (m, 2 H), 6.85-6.81 (m, 2 H), 4.13 (t, J=6.0 Hz, 2 H), 3.51 (s, 3 H), 2.66 (t, J=6.0 Hz. 2 H), 1.43-1.39 (m, 2 H), 1.14-1.10 (m, 2H).
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:12][C:13]([C:17]([O:19]CC)=O)=[C:14]([CH3:16])[N:15]=2)=[CH:7][CH:6]=1>C(O)C>[CH3:16][C:14]1[N:15]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH3:3])=[CH:6][CH:7]=2)[S:12][C:13]=1[C:17]([NH:2][CH3:1])=[O:19]
Reactant: CN
Reactant: CCOC(=O)c1sc(-c2ccc(OC)cc2)nc1C
Solvent: CCO
Product: CNC(=O)c1sc(-c2ccc(OC)cc2)nc1C
Yield: 69 %

Procedure:
Into a mixed solvent of 80 ml of 40% methylamine and 600 ml of ethanol, 13.9 g of ethyl 2-(4-methoxyphenyl)-4-methylthiazole-5-carboxylate was dissolved. Then, in a similar manner as in Example 1, the object was obtained as colourless minute aciculate melting at 157.5° to 159° C. in an amount of 9.1 g corresponding to the yield of 69%.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=[N:7][OH:8])[CH2:3][CH2:2]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].[F:26][C:27]([F:35])([F:34])[C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30]>>[F:32][C:28]([F:33])([C:27]([F:35])([F:34])[F:26])[C:29]([O:31][C:4]1([N:7]=[O:8])[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[O:30]
Reactant: ON=C1CCOCC1
Reactant: O=C(O)C(F)(F)C(F)(F)F
Agent: CC(=O)[O-]
Agent: [Pb+4]
Product: O=NC1(OC(=O)C(F)(F)C(F)(F)F)CCOCC1

Procedure:
4-Nitrosotetrahydro-2H-pyran-4-yl 2,2,3,3,3-pentafluoropropanoate was prepared from tetrahydro-pyran-4-one oxime, lead tetraacetate and pentafluoropropionic acid using conditions of General Method 3. 1H NMR (250 MHz, chloroform-d) δ 4.11-4.30 (2H, m), 3.46-3.83 (2H, m), 2.45-2.73 (2H, m), 1.68-2.02 (2H, m).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5](=[O:24])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=[C:15]([CH3:23])[CH:14]=2)[CH:7]=1.[CH:25]1[CH:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.[BH4-].[Na+].[OH-].[Na+]>CCO.[Cl-].[Na+].O>[CH2:31]([NH:1][CH2:2][CH2:3][NH:4][C:5](=[O:24])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=[C:15]([CH3:23])[CH:14]=2)[CH:7]=1)[C:28]1[CH:29]=[CH:30][CH:25]=[CH:26][CH:27]=1
Reactant: O=Cc1ccccc1
Reactant: Cc1cc(Nc2cccc(C(=O)NCCN)c2)c2ccccc2n1
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: Cc1cc(Nc2cccc(C(=O)NCCNCc3ccccc3)c2)c2ccccc2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 456.7 %

Procedure:
A solution of amine 50 (0.22 g, 0.68 mmol) and benzyaldehyde (0.07 mL, 0.08 mmol) in EtOH (3.0 mL) was heated at reflux overnight before it was allowed to cool to room temperature. Sodium borohydride (0.04 g, 0.80 mmol) was added and the reaction was stirred at room temperature for 1 hour. The mixture was mixed with 2N NaOH (3.0 mL), brine (2.0 mL), and extracted with 7:3 CH2Cl2/MeOH (3×5.0 mL). The combined organic layers were dried (K2CO3) and concentrated under reduced pressure. The residue was purified by flash chromatrography (SiO2, gradient elution, 3:1 hexanes/EtOAc to 7:3 CH2Cl2/MeOH) to yield the desired product (0.15 g, 62%) as a pale yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].CC([O-])(C)C.[K+].CC(S([C:22]1[CH:27]=[CH:26][C:25]([S:28]([CH:31]([CH3:33])[CH3:32])(=[O:30])=[O:29])=[CH:24][N:23]=1)(=O)=O)C.O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[O:9][C:22]1[CH:27]=[CH:26][C:25]([S:28]([CH:31]([CH3:33])[CH3:32])(=[O:29])=[O:30])=[CH:24][N:23]=1
Reactant: Oc1ccc(Cl)c(Cl)c1
Reactant: CC(C)S(=O)(=O)c1ccc(S(=O)(=O)C(C)C)nc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)S(=O)(=O)c1ccc(Oc2ccc(Cl)c(Cl)c2)nc1
Yield: 42 %

Procedure:
To 4.89 g of 3,4-dichlorophenol dissolved in a 25 ml THF/25 ml DMSO mixture was added 3.2 g of t-BuOK and then 8.74 g of 2,5-bis((1-methylethyl)sulfonyl)pyridine, and the resulting mixture was heated at 58° C. for 11/2 hrs. The reaction mixture was allowed to cool overnight and then poured in approximately 3 to 4 volumes of water and stirred. The yellow-white precipitate which formed was removed by filtration. Recrystallization from CH2Cl2 /ethanol gave the product, 2-(3,4-dichlorophenoxy)-5-((1-methylethyl)sulfonyl)pyridine, (42% yield), as tiny white needles, m.p. 91°-92° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:12])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.[Cl:49][C:50]1[CH:62]=[CH:61][C:53]2[NH:54][C:55]([C:57]([NH2:60])([CH3:59])[CH3:58])=[N:56][C:52]=2[CH:51]=1.ClCl>O1CCCC1.C(OCC)(=O)C.C(O)C>[Cl:49][C:50]1[CH:62]=[CH:61][C:53]2[NH:54][C:55]([C:57]([NH:60][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][C:10]([C:11]([N:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)=[O:12])=[C:2]([CH3:1])[CH:3]=3)([CH3:59])[CH3:58])=[N:56][C:52]=2[CH:51]=1
Reactant: Cc1cc(C(=O)O)ccc1C(=O)N1CCCC1
Reactant: CC(C)(N)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: ClCl
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)NC(C)(C)c2nc3cc(Cl)ccc3[nH]2)ccc1C(=O)N1CCCC1
Yield: 71 %

Procedure:
Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine, and 1-(5-chloro-1H-benzimidazol-2-yl)-1-methylethylamine in tetrahydrofuran. Yield: 71%; Rf value: 0.37 (silica gel; ethyl acetate/ethanol=9:1); C23H25ClN4O2 (424.93); mass spectrum: (M+H)+=425/427 (chlorine isotope).