Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][CH2:9][C@H:10]1[C:15](=[CH2:16])[C@@H:14]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][CH3:32])=[CH:27][CH:26]=3)[CH:18]=2)[C@H:13]([O:33]CC2C=CC=CC=2)[C@@H:12]([O:41]CC2C=CC=CC=2)[C@@H:11]1[O:49]CC1C=CC=CC=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO>C(Cl)Cl>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C@@H:14]2[C:15](=[CH2:16])[C@H:10]([CH2:9][OH:8])[C@@H:11]([OH:49])[C@H:12]([OH:41])[C@H:13]2[OH:33])=[CH:18][C:19]=1[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][CH3:32])=[CH:29][CH:30]=1
Reactant: C=C1[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1c1ccc(Cl)c(Cc2ccc(CC)cc2)c1
Agent: ClB(Cl)Cl
Solvent: ClCCl
Solvent: CO
Product: C=C1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1c1ccc(Cl)c(Cc2ccc(CC)cc2)c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 0.1 %

Procedure:
To a solution of ((1S,2R,3R,4R,6S)-4-(benzyloxymethyl)-6-(4-chloro-3-(4-ethylbenzyl)phenyl)-5-methylenecyclohexane-1,2,3-triyl)tris(oxy)tris(methylene)tribenzene (34, 24 mg, 31.4 mmol) in anhydrous DCM (0.8 mL) in a vial at −78° C. under a nitrogen blanket was added BCl3 (1 M in DCM, 0.25 mL) drop-wise over 15 minutes. The resulting mixture was stirred at −78° C. for 30 minutes and gradually warmed to −20° C. The resulting mixture was stirred at −20° C. for another 30 minutes. At this time, LC-MS indicated that the reaction was complete. The solution was cooled to −78° C. and methanol (1 mL) was slowly added. The resulting solution was warmed to room temperature and concentrated under reduced pressure. The residue was dissolved in 0.5 mL of 1:1 DCM:MeOH and loaded on a preparative TLC plate, which was developed in 15:1 (DCM:MeOH) to obtain 9 mg (71%) of compound 35 as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.29-6.89 (m, 7H), 4.80 (s, 1H), 4.28 (s, 1H), 3.95 (m, 4H), 3.64 (m, 2H), 3.51(m, 3H), 3.22 (m, 1H), 2.58 (q, J=7.2 Hz, 2H), 2.25 (m, 1H), 1.18 (t, J=7.5 Hz, 3H). LC-ESI-MS m/z 425 (M+Na).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:11]2[C:12]([O:15][CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][C:24]4([OH:30])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[CH2:19][CH2:18]3)=[N:13][O:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3].O.[C:32]1([CH3:42])[CH:37]=[CH:36][C:35]([S:38]([OH:41])(=[O:40])=[O:39])=[CH:34][CH:33]=1>C(OCC)(=O)C>[C:32]1([CH3:42])[CH:33]=[CH:34][C:35]([S:38]([O-:41])(=[O:39])=[O:40])=[CH:36][CH:37]=1.[OH:30][C:24]1([CH2:23][NH+:20]2[CH2:19][CH2:18][CH:17]([CH2:16][O:15][C:12]3[C:11]4[C:6]([O:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:7][CH:8]=[CH:9][C:10]=4[O:14][N:13]=3)[CH2:22][CH2:21]2)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: CC(C)COc1cccc2onc(OCC3CCN(CC4(O)CCOCC4)CC3)c12
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)COc1cccc2onc(OCC3CC[NH+](CC4(O)CCOCC4)CC3)c12
Product: Cc1ccc(S(=O)(=O)[O-])cc1
Reaction time: 0.5 h
Yield: 93.8 %

Procedure:
4-[(4-{[(4-Isobutoxy-1,2-benzisoxazol-3-yl)oxy]methyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-ol (34.0 mg, 0.0812 mmol, EXAMPLE 8, step 5) was dissolved in ethyl acetate (approximately 0.3 mL). To this solution was added a solution of p-toluenesulfonic acid monohydrate (21.7 mg, 0.11 mmol) in ethyl acetate (2 mL) at room temperature. After being stirred for 30 min, resulting white precipitate was filtered and washed with ethyl acetate to afford 45 mg (93%) of the title compound as a white powdery solid.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH2:6].[Si:8](Cl)([CH3:11])([CH3:10])[CH3:9]>CCOCC>[Si:8]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])([CH3:11])([CH3:10])[CH3:9]
Reactant: CN(C)CCCN
Reactant: C[Si](C)(C)Cl
Solvent: CCOCC
Product: CN(C)CCCN[Si](C)(C)C
Temperature: 10 °C
Reaction time: 8 h
Yield: 85 %

Procedure:
Under argon, in a 500 ml Schlenk flask containing a magnetic stir bar, 49.38 g (0.480 mol) of 3-dimethylaminopropylamine (99%, Aldrich) was added to 120 ml of anhydrous hexanes (distilled from Na). This mixture was stirred and cooled with a constant temperature bath at 10° C. From a dropping funnel, 25 g of TMS—Cl (0.230 mol) were added dropwise to the mixture over a period of two hours. A white precipitate formed, and later redissolved forming a separate layer at the bottom of the flask. Once the TMS—Cl addition was complete, 200 ml of anhydrous ether (distilled from Na/K) was added to the flask. The mixture then was rapidly stirred overnight causing the two layers to merge into a homogeneous solution over a white precipitate. The solution was separated from the white solid by cannulation and distilled at ambient pressure to give TMS—NH—CH2CH2CH2NMe2 at 160° C. Yield: 85%. Characterization: 1H NMR: (400 MHz, positive δ downfield referenced to Si(CH3)4=0 ppm utilizing residual CDCl3=7.24 ppm in solvent CDCl3) 2.72 [m, 2H, —CH2NMe2], 2.24 [(m, 2H, TMS—NH—CH2—], 2.20 [s, 6H, —NCH3], 1.54 [m, 4H, TMS—NH—CH2CH2—], 0.02 [s, 18H, CH3Si—]. 13C{1H} NMR: (75 MHz, positive δ downfield referenced to Si(CH3)4=0 ppm utilizing residual C6D5H=128.0 ppm in solvent C6D6) 57.45 [—CH2NMe2], 45.40 [—NCH3], 40.00 [TMS—N—CH2—], 32.66 [TMS—N—CH2CH2—], −0.20 [(CH3)3Si—N—]. Mass Spectrum: (EI, 70 eV) 174 [TMS—NHCH2CH2CH2NMe2]+, 159 (M—Me), 129, 114, 100, 85, 72, 58.
Reaction SMILES: O[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27].[C:28]1([CH:34]2[NH:38][C:37](=[O:39])[NH:36][C:35]2=[O:40])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:24][O:23][C:18]1[CH:17]=[C:16]([O:25][CH3:26])[CH:15]=[C:14]2[C:19]=1[C:20](=[O:22])[NH:21][C:12]([C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([O:4][CH2:3][CH2:2][N:36]3[C:35](=[O:40])[CH:34]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[NH:38][C:37]3=[O:39])=[C:6]([CH3:27])[CH:7]=1)=[N:13]2
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCO)c(C)c3)nc2c1
Reactant: O=C1NC(=O)C(c2ccccc2)N1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCN4C(=O)NC(c5ccccc5)C4=O)c(C)c3)nc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a suspension of 2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.50 g, 1.35 mmol) in THF (20 mL), were added 5-phenyl-imidazolidine-2,4-dione (0.24 g, 1.35 mmol) and triphenyl phosphine (0.35 g, 1.35 mmol), then diethyl azodicarboxylate (0.43 mL, 2.70 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. Solvent was evaporated in vacuo and the residue was washed with dichloromethane and ether. The residue was dissolved in acetic acid and purified by preparative HPLC. The compound was further washed with dichloromethane and ether (1:1, 20 mL) to obtain the title compound as a white solid. Yield: 0.07 g (10%). MP 219.6-221.4° C. 1H NMR (400 MHz, DMSO-d6): δ 8.81 (s, 1H), 7.86 (s, 2H), 7.37 (m, 5H), 6.71 (s, 1H), 6.48 (s, 1H), 3.94 (m, 4H), 3.86 (s, 3H), 3.82 (s, 3H), 2.18 (s, 6H). MS (ES) m/z: 529.29 (M++1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[N+:11]([C:14]1[CH:15]=[N:16][NH:17][CH:18]=1)([O-:13])=[O:12].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:16]2[CH:15]=[C:14]([N+:11]([O-:13])=[O:12])[CH:18]=[N:17]2)=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: O=[N+]([O-])c1cn[nH]c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=[N+]([O-])c1cnn(-c2ccc(F)cc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 44.8 %

Procedure:
A mixture of 4-fluorobenzeneboronic acid (2.47 g, 17.7 mmol), 4-nitro-1H-pyrazole (1.00 g, 8.84 mmol), copper (II) acetate (2.41 g, 13.3 mmol) and pyridine (2.86 mL, 35.4 mmol) in CH2Cl2 (40 mL) was stirred at room temperature overnight. The reaction mixture was filtered and diluted with water (40 mL). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography (SiO2, 0-20% EtOAc/hexanes gradient elution) to give 1-(4-fluorophenyl)-4-nitropyrazole as a white solid (0.820 g, 22%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[F:9].[N:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.O.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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[CH:14]=[CH:15][N:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[F:9]
Reactant: Fc1cc(I)ccc1Br
Reactant: OB(O)c1ccncc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: Fc1cc(-c2ccncc2)ccc1Br
Temperature: 25 °C
Yield: 21.9 %

Procedure:
1-Bromo-2-fluoro-4-iodobenzene (300 mg, 0.997 mmol), 4-pyridineboronic acid (147 mg, 1.196 mmol), Na2CO3(211 mg, 1.994 mmol) and tetrakis(triphenylphosphine)palladium (230 mg, 0.199 mmol) in 3.3 mL of 1:1 Dioxane/water were heated to 100° C. for 20 h. The reaction was slowly warmed to room temperature, diluted with water and extracted with EtOAc. The organic phase was separated, dried (Na2SO4) and evaporated to dryness, giving an oil. This material was chromatographed on silica gel, eluting with 0-10% ethyl acetate in hexanes to give 4-(4-bromo-3-fluorophenyl)pyridine (55 mg) as an off-white solid.
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C:9]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:10]=1[C:11]([O:13][CH3:14])=[O:12].[Cl:20][C:21]1[CH:22]=[C:23]([CH2:27][C:28](Cl)=[O:29])[CH:24]=[CH:25][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[Br:19][C:16]1[CH:17]=[CH:18][C:9]([NH:8][C:28](=[O:29])[CH2:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([Cl:20])[CH:22]=2)=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12]
Reactant: COC(=O)c1cc(Br)ccc1N
Reactant: O=C(Cl)Cc1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1cc(Br)ccc1NC(=O)Cc1cccc(Cl)c1
Temperature: 0 °C

Procedure:
Triethylamine (18 mL, 130 mmol) was added to methyl 2-amino-5-bromobenzoate (25 g, 110 mmol) in DCM (150 mL). The mixture was cooled to 0° C. and 2-(3-chlorophenyl)acetyl chloride (24.3 g, 130 mmol) in DCM (100 mL) was added. The mixture was allowed to warm to room temperature overnight with stirring. Aqueous K2CO3 (10 wt. %) was added and the mixture was extracted with DCM. The organic phase was dried (MgSO4), filtered, and concentrated to yield the title compound.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:6](N)[C:5]([CH3:9])=[CH:4][CH:3]=1.N(OCCCCC)=O.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:9])=[C:6]([C:21]2[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=2)[CH:8]=1
Reactant: Cc1ccc(F)cc1N
Reactant: c1ccncc1
Agent: CCCCCON=O
Product: Cc1ccc(F)cc1-c1ccncc1

Procedure:
5-Fluorotoluidine (Example1,B), pyridine and pentyl nitrite are warmed until a vigorous reaction with evolution of gas sets in. This is allowed to proceed without heating until it has subsided (20 minutes) and the mixture is boiled under reflux for another 100 minutes. The excess pyridine is removed under reduced pressure to yield the title product.
Reaction SMILES: Cl.[CH:2]1([NH:6][CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:19]C)[C:13]=3[O:17]C)[C:8]2=[O:21])[CH2:5][CH2:4][CH2:3]1.[BrH:22].C(OC(=O)C)(=O)C>>[BrH:22].[CH:2]1([NH:6][CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([OH:19])[C:13]=3[OH:17])[C:8]2=[O:21])[CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc2c(c1OC)CCC(NC1CCC1)C2=O
Agent: Br
Agent: Cl
Solvent: CC(=O)OC(C)=O
Product: O=C1c2ccc(O)c(O)c2CCC1NC1CCC1

Procedure:
In a manner similar to that of Reference Example 4, 5.16 parts of 2-cyclobutylamino-5,6-dimethoxy-3,4-dihydro-1(2H)-naphthalenone hydrochloride is hydrolyzed in a mixture of 75 volume parts 48% hydrobromic acid and 15 volume parts acetic anhydride. The procedure yields 4 parts of 2-cyclobutylamino-5,6-dihydroxy-3,4-dihydro-1(2H)-naphthalenone hydrobromide. Melting point: 229°-240° C (decomposition).
Reaction SMILES: FC(F)(F)S(O[C:7]1[N:12]=[N:11][C:10]2[O:13][CH2:14][CH2:15][CH2:16][C:9]=2[CH:8]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].O.CO[CH2:28][CH2:29]OC>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:28]([C:7]1[N:12]=[N:11][C:10]2[O:13][CH2:14][CH2:15][CH2:16][C:9]=2[CH:8]=1)=[CH2:29]
Reactant: COCCOC
Reactant: O=S(=O)(Oc1cc2c(nn1)OCCC2)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: C=Cc1cc2c(nn1)OCCC2
Reaction time: 0.33 h
Yield: 77 %

Procedure:
Argon was bubbled for 15 minutes through a solution of 6,7-dihydro-5H-pyrano[2,3-c]pyridazin-3-yl trifluoromethanesulfonate (228 mg, 0.8 mmol) in 1,2-dimethoxyethane (6.5 ml). Tetrakis(triphenylphosphine)palladium(0) (50 mg, 0.0435 mmol) was added and the solution stirred for 20 minutes under argon. The mixture was then treated with potassium carbonate (111 mg, 0.8 mmol), water (1.9 ml) and triethenylboroxin pyridine complex (180 mg, 0.75 mmol). After stirring for 2 hours at 80° C., the mixture was cooled and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous fraction was extracted twice with 20% methanol/dichloromethane. The combined organic solution was dried, evaporated and the residue chromatographed on silica, eluting with ethyl acetate to give the product as a white solid (100 mg, 77%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]2[C:25]3[C:20](=[CH:21][C:22]([F:27])=[C:23](Br)[CH:24]=3)[CH2:19][CH2:18]2)=[O:16])[CH2:10][C@H:9]1[CH3:28])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]1([S:35]([O-:37])=[O:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[Na+].CNCCNC>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]2[C:25]3[C:20](=[CH:21][C:22]([F:27])=[C:23]([S:35]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)(=[O:37])=[O:36])[CH:24]=3)[CH2:19][CH2:18]2)=[O:16])[CH2:10][C@H:9]1[CH3:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=S([O-])c1ccccc1
Reactant: C[C@@H]1CN(CC(=O)N2CCc3cc(F)c(Br)cc32)CCN1C(=O)OC(C)(C)C
Agent: CNCCNC
Agent: [Na+]
Solvent: CS(C)=O
Product: C[C@@H]1CN(CC(=O)N2CCc3cc(F)c(S(=O)(=O)c4ccccc4)cc32)CCN1C(=O)OC(C)(C)C
Temperature: 150 °C
Reaction time: 18 h
Yield: 20 %

Procedure:
A mixture of (R)-4-[2-(6-bromo-5-fluoro-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.137 g, 0.30 mmol), sodium phenylsulfinate (0.064 g, 0.39 mmol), copper (1) trifluoromethylsulfonate-benzene complex (0.0045 g, 0.009 mmol), N,N′-dimethylethylenediamine (0.29 g, 0.33 mmol) and dimethyl sulfoxide (1.5 mL) was stirred at 150° C. under nitrogen for 18 h in a sealed vessel. The resulting mixture was partitioned between water (50 mL) and 1:1 Et2O− EtOAc (30 mL) and the organic phase was washed with water (2×20 mL), dried (Na2SO4) and evaporated in vacuo to give a brown oil. Chromatography (SiO2; gradient elution with 0-100% EtOAc in petrol) gave the title compound (0.031 g, ˜25%). MS: [M+H]+=518.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([O:7][C:8]2[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.[O:15]1[C:19]2[C:20]([CH:24]=O)=[CH:21][CH:22]=[CH:23][C:18]=2[CH2:17][CH2:16]1.[BH4-].[Na+].Cl>C1(C)C=CC=CC=1>[O:15]1[C:19]2[C:20]([CH2:24][NH:14][C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[O:7][C:4]3[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=3)=[CH:21][CH:22]=[CH:23][C:18]=2[CH2:17][CH2:16]1
Reactant: Nc1ccccc1Oc1ccccc1
Reactant: O=Cc1cccc2c1OCC2
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: c1ccc(Oc2ccccc2NCc2cccc3c2OCC3)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
2-Aminodiphenyl ether (1 g, 5.4 mmol) was treated with 2,3-Dihydro-benzofuran-7-carbaldehyde (1 g, 7.02 mmol) and toluene (10 ml) and heated at reflux for 4 h under an atmosphere of nitrogen with vigorous stirring. The solution became yellow and homogeneous. The reaction was then concentrated in vacuum to remove the toluene, cooled to 0° C., diluted with methanol (15 ml), and treated with sodium borohydride (612 mg 16 mmol) in portions over a period of 20 min. The reaction was then allowed to warm to room temperature and stirred for a further 30 min. 2N hydrochloric acid (5 ml) was added and the reaction stirred for a further 30 min. The reaction was then concentrated in vacuum to a gum and 10% aq potassium carbonate (50 ml) added. The product was then recovered by extraction into ethyl acetate (50 ml), the extract was dried over magnesium sulphate and concentrated in vacuum to a gum. The gum was chromatographed on a 120 g silica column in a gradient of 10-30% ethyl acetate in petrol. The main fast running fraction, N-(2,3-Dihydro-benzofuran-7-ylmethyl)-N-(2-phenoxyphenyl)-amine was collected as a gum (1.2824 g, 4.04 mmole, 74.9%) that crystallized on standing.
Reaction SMILES: CO.S(=O)(=O)(O)O.[CH3:8][NH:9][S:10]([C:13]1[CH:14]=[C:15]([C:23]([OH:25])=[O:24])[C:16]2[O:21][CH2:20][CH2:19][O:18][C:17]=2[CH:22]=1)(=[O:12])=[O:11].[C:26](=O)([O-])[O-].[Na+].[Na+]>O>[CH3:26][O:24][C:23]([C:15]1[C:16]2[O:21][CH2:20][CH2:19][O:18][C:17]=2[CH:22]=[C:13]([S:10](=[O:11])(=[O:12])[NH:9][CH3:8])[CH:14]=1)=[O:25]
Reactant: CNS(=O)(=O)c1cc2c(c(C(=O)O)c1)OCCO2
Reactant: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CNS(=O)(=O)c1cc2c(c(C(=O)OC)c1)OCCO2
Yield: 85 %

Procedure:
750 ml of methanol were introduced into a balloon flask provided with a condenser. Then, under cooling, 273 g of concentrated sulfuric acid and 160 g of 7-methylsulfamoyl-1,4-benzodioxane-5-carboxylic acid were added. The mixture was heated under reflux, cooled and poured into water and sodium carbonate. The precipitate was dried off, washed and dried. 143 g of methyl-7-methylsulfamoyl-1,4-benzodioxane-5-carboxylate were obtained (M.P.: 159°-160° C.: yield: 85%).
Reaction SMILES: [C:1]1([C:7]2[N:11]([CH2:12][C:13]([O:15]CC)=O)[N:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:18]([N:20]([CH2:25][CH3:26])[CH2:21][CH2:22][CH2:23][NH2:24])[CH3:19].[ClH:27]>CN(C=O)C.C(O)C.CCOCC>[ClH:27].[CH2:18]([N:20]([CH2:25][CH3:26])[CH2:21][CH2:22][CH2:23][NH:24][C:13](=[O:15])[CH2:12][N:11]1[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][CH:9]=[N:10]1)[CH3:19]
Reactant: CCN(CC)CCCN
Reactant: CCOC(=O)Cn1nccc1-c1ccccc1
Agent: Cl
Solvent: CCOCC
Solvent: CCO
Solvent: CN(C)C=O
Product: CCN(CC)CCCNC(=O)Cn1nccc1-c1ccccc1

Procedure:
By procedure analogous to that of example 4, but omitting the DMF solvent, the free base of N-[3-(diethylamino)propyl]-5-phenyl-1H-pyrazole-1-acetamide hydrochloride was prepared from 1.0g 4.3 mmol) of ethyl 5-phenyl-1H-pyrazole-1-acetate and 3-(diethylamino)propanamine. The hydrochloride salt was prepared by dissolving the free base (an oil) in ethanol, adding a solution of hydrogen chloride in anhydrous ether, and recrystallizing the resulting solid from ethanol-ether. Upon drying, the white, crystalline product collapsed to a brownish, amorphous solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:22])[C:16]#[C:17][C:18](O)([CH3:20])[CH3:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N(CC)CC.CC[OH:30]>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[O:22][C:18]([CH3:19])([CH3:20])[C:17](=[O:30])[CH:16]=2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(O)C#CC(=O)c1ccc(OCc2ccccc2)cc1
Reactant: CCO
Solvent: CCNCC
Product: CC1(C)OC(c2ccc(OCc3ccccc3)cc2)=CC1=O
Reaction time: 1 h
Yield: 98 %

Procedure:
To a RT solution of 1-(4-(benzyloxy)phenyl)-4-hydroxy-4-methylpent-2-yn-1-one (1.5 g, 0.005 mol) in EtOH (10 mL) was added a solution of Et2NH (0.86 mL) in EtOH (10 mL) under an inert atmosphere. The reaction mixture was stirred for 1 hr and then concentrated in vacuo to obtain the crude product. The crude material was partitioned between water and DCM and the organic layer was separated, washed with water, dried over Na2SO4 and then concentrated in vacuo to afford 5-(4-(benzyloxy)phenyl)-2,2-dimethylfuran-3(2H)-one (1.4 g, 98%) as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[CH2:7][CH:8]3[C:14](=O)[C:13]([CH3:16])([C:5]=2[CH:4]=1)[CH2:12][CH2:11][CH2:10][CH2:9]3.[OH-].[NH4+:20].[H][H]>[Ni].C(O)C>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[CH2:7][CH:8]3[CH:14]([NH2:20])[C:13]([CH3:16])([C:5]=2[CH:4]=1)[CH2:12][CH2:11][CH2:10][CH2:9]3
Reactant: COc1ccc2c(c1)C1(C)CCCCC(C2)C1=O
Reactant: [NH4+]
Reactant: [H][H]
Agent: [Ni]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc2c(c1)C1(C)CCCCC(C2)C1N

Procedure:
6,7,8,9,10,11-Hexahydro-3-methoxy-5-methyl-5,10-methano-5H-benzocyclononen-12-one, oxime (15 g. 0.058 m.) Raney nickel (3 tsps.) ethanol (100 ml.) and concentrated ammonium hydroxide (50 ml.) are shaken with hydrogen at 45 psi and 45° C. The catalyst is removed by filtration and the filtrate concentrated to remove solvent. The residue is distilled under reduced pressure to afford the title product (11 g.), b.p. 140°-142° C. (0.2 mm.) HCl salt, m.p. 298°-299° C.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=O.[CH2:13]([NH2:17])[CH:14]([CH3:16])[CH3:15].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:13]([N:17]1[C:8](=[O:9])[C:3]2=[C:2]([CH3:1])[CH:12]=[CH:11][CH:10]=[C:4]2[C:5]1=[O:7])[CH:14]([CH3:16])[CH3:15]
Reactant: CC(C)CN
Reactant: Cc1cccc2c1C(=O)OC2=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Cc1cccc2c1C(=O)N(CC(C)C)C2=O
Temperature: 140 °C
Reaction time: 16 h

Procedure:
N-Isobutyl-3-methylphthalimide is prepared as described in Example 2, starting with 5.0 g of 3-methylphthalic anhydride, 3.0 cm3 of isobutylamine and a catalytic amount of para-toluenesulfonic acid in 50 cm3 of toluene. The reaction mixture is heated at a temperature in the region of 140° C. for 2.5 hours and then stirred at a temperature in the region of 20° C. for 16 hours. The reaction mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The organic phase is separated out after settling has taken place, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 6.0 g of N-isobutyl-3-methylphthalimide are thus obtained in the form of a caramel-colored oil, Rf=0.76 (thin layer chromatography on silica gel, eluent: dichloromethane).
Reaction SMILES: [CH2:1]([Si:4]([Cl:7])([Cl:6])[Cl:5])[CH:2]=[CH2:3].[Cl-].[Na+].[C:10]1([CH3:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>[Cl-].[Al+3].[Cl-].[Cl-]>[CH3:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:2]([CH3:3])[CH2:1][Si:4]([Cl:7])([Cl:6])[Cl:5]
Reactant: C=CC[Si](Cl)(Cl)Cl
Reactant: Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Agent: [Na+]
Product: Cc1ccccc1C(C)C[Si](Cl)(Cl)Cl
Temperature: 50 °C
Yield: 71 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 9.7 g (105 mmol) of toluene and 0.2 g (1.5 mmol) of aluminum chloride were placed. The flask was then immersed in an ice water bath. To the reaction mixture was slowly added dropwise 3.0 g (15 mmol) of allyltrichlorosilane and the solution was stirred for an hour. After confirming that no toluene was left by gas chromatography, 0.48 g (8.0 mmol) of sodium chloride was added to reaction mixture, warmed up to 50° C. and stirred for two hours to deactivate the catalyst. Vacuum distillation of the reaction products gave 16.3 g (bp 74°-76° C./0.6 mmHg) of 3-(methylphenyl)-1,1,1-trichloro-1-silabutane in 71% yield.