Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH2:14].[CH3:15][C:16]([CH3:23])([CH3:22])/[CH:17]=[CH:18]/[C:19]([Cl:21])=O.N1C=CC=CC=1N1C2C=CC=CC=2N=C1/C=C/C1C=CC=CC=1.Cl>CO>[ClH:21].[CH3:15][C:16]([CH3:23])([CH3:22])/[CH:17]=[CH:18]/[C:19]1[N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]=1
Reactant: CC(C)(C)/C=C/C(=O)Cl
Reactant: Nc1ccccc1Nc1ccccn1
Agent: C(=C/c1nc2ccccc2n1-c1ccccn1)\c1ccccc1
Agent: Cl
Solvent: CO
Product: CC(C)(C)/C=C/c1nc2ccccc2n1-c1ccccn1

Procedure:
To a solution of (E)-4,4-dimethyl-2-pentenoic acid (Gream, G. E.; Serelis, A. K. Aust. J. Chem. 1978, 31, 863) (200 mg, 1.6 mmol) in benzene (10 ml) was added thionyl chloride (0.5 ml) and the mixture was heated to reflux for 60 min. Volatiles were removed by evaporation to give crude (E)-4,4-dimethyl-2-pentenoyl chloride. Free base of the titled compound was prepared from N-(2-pyridyl)-o-phenylenediamine (150 mg, 0.81 mmol) and (E)-4,4-dimethyl-2-pentenoyl chloride obtained as above according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A). The free base was dissolved with a 10% methanol solution of hydrogen chloride (5 ml). Concentration and recrystallization from ethyl acetate yielded the titled compound. MW: 313.83; mp: 171.0-172.3° C.; 1H-NMR (CDCl3) δ: 8.86-8.82 (1H, m), 8.27 (1H, d, J=16.3 Hz), 8.21-8.13 (2H, m), 7.72-7.65 (1H, m), 7.62-7.43 (4H, m), 6.31 (1H, d, J=16.3 Hz), 1.17 (9H, s).
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[CH:16][C:17]3[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][N:18]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl.O>[CH:12]1[C:8]2[CH2:9][CH2:10][C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6](=[CH:16][C:17]3[CH:22]=[C:21]([NH:23][S:32]([CH3:31])(=[O:34])=[O:33])[CH:20]=[CH:19][N:18]=3)[C:7]=2[CH:15]=[CH:14][CH:13]=1
Reactant: Nc1ccnc(C=C2c3ccccc3CCc3ccccc32)c1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CS(=O)(=O)Nc1ccnc(C=C2c3ccccc3CCc3ccccc32)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.5 %

Procedure:
Mix 2-(10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidenemethyl)-pyridin-4-ylamine (176 mg, 0.590 mmol), triethylamine (600 μL, 4.13 mmol), N,N-dimethylaminopyridine (7 mg, 0.059 mmol), and methanesulfonyl chloride (137 μL, 1.769 mmol) in CH2Cl2 (10 mL). Stir at room temperature for 3 h and dilute with H2O (15 mL). Extract into CH2Cl2, dry (MgSO4) and concentrate organics. Dissolve crude product in THF (10 mL), add 1.0M tetrabutylammonium fluoride (0.89 mL), and heat to reflux for 4 h. Cool to room temperature and dilute with H2O. Extract into ethyl acetate, dry (MgSO4) and concentrate organics. Chromatograph on silica gel (10 g), eluting with 80% →90% ethyl acetate/hexanes to afford 150 mg (68%) of the title compound as a yellow foam. MS (ES) 377 (M+H), 375 (M−H); BPLC shows 96% purity.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:6]=[C:7]([SH:15])[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])[CH3:3].[O-]CC.[Na+].[CH:20]12[O:26][CH:21]1[CH2:22][CH2:23][CH2:24][CH2:25]2.O>C(O)C>[CH3:4][C:2]([C:5]1[CH:6]=[C:7]([S:15][C@@H:20]2[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]2[OH:26])[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:1])[CH3:3]
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1
Reactant: C1CCC2OC2C1
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)c1cc(S[C@@H]2CCCC[C@H]2O)cc(C(C)(C)C)c1
Reaction time: 1 h

Procedure:
3,5-Bis(1,1-dimethylethyl)benzenethiol (Example 2) (5.0 g, 0.0225 moles) was added to freshly prepared sodium ethoxide (0.0230 moles) in absolute ethyl alcohol (50 ml). After stirring for 1 hour, cyclohexene oxide (2.2 g; 0.0225 moles) was added by syringe over 5 minutes, and the reaction mixture was stirred for 60 hours at room temperature. Water (100 ml) was added, and the reaction mixture was extracted twice with 75 ml of ethyl acetate. The combined ethyl acetate extracts were washed with brine (50 ml), dried over sodium sulfate, filtered and concentrated to give the title product as a yellow solid, which was recrystallized from cold pentane. The structure assignment was supported by NMR spectroscopy. The title compound was used in Example 4.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH:11][N:12]1C(=O)C2=CC=CC=C2C1=O.[N+]([O-])=[O:24].FC(C1C=CC=CC=1)(F)F.O=O>>[N+:12]([C:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2)([O-:11])=[O:24].[C:1]12([OH:11])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: C1C2CC3CC1CC(C2)C3
Reactant: O=[N+][O-]
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: O=O
Solvent: FC(F)(F)c1ccccc1
Product: O=[N+]([O-])C12CC3CC(CC(C3)C1)C2
Product: OC12CC3CC(CC(C3)C1)C2
Yield: 57 %
Yield: 6 %

Procedure:
Into a flask, 1 mmole of adamantane, 0.05 mmole of N-hydroxyphthalimide, 15 mmole of nitrogen dioxide (NO2) and 3 ml of trifluoromethylbenzene were added and stirred for 5 hours at 60° C. in an atmosphere of oxygen. The reaction products were analyzed by gas chromatography, and, as a result, the conversion of adamantane was 79%, and nitroadamantane (yield 57%), adamantanol (yield 6%) and adamantanone (yield 4%) were formed.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH2:4][OH:5].I[CH2:12][CH2:13][CH2:14][CH3:15].[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20].[CH2:24]([C@@H:26]1[CH2:31][NH:30][CH2:29][CH2:28][N:27]1[C:32](OCC1C=CC(OC(F)F)=CC=1)=[O:33])C>>[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20].[CH3:24][C@@H:26]1[CH2:31][NH:30][CH2:29][CH2:28][N:27]1[C:32]([O:5][CH2:4][C:3]1[CH:6]=[C:7]([O:10][CH2:12][CH2:13][CH2:14][CH3:15])[CH:8]=[CH:9][C:2]=1[F:1])=[O:33]
Reactant: OCc1cc(O)ccc1F
Reactant: CC[C@@H]1CNCCN1C(=O)OCc1ccc(OC(F)F)cc1
Reactant: CCCCI
Agent: O=C(O)/C=C/C(=O)O
Product: CCCCOc1ccc(F)c(COC(=O)N2CCNC[C@H]2C)c1

Procedure:
(R)-5-Butoxy-2-fluorobenzyl 2-methylpiperazine-1-carboxylate fumarate was prepared from 2-fluoro-5-hydroxybenzyl alcohol, 1-iodobutane and (R) 1-chlorocarbonyl-2-methyl-4-tert-butoxycarbonylpiperazine according to the methods described for Examples 54 and 96 to give the product as a white solid (18%); melting point 171.6–171.7° C.; NMR δH (400 MHz, DMSO-d6) 0.928(3H, t, J 7.0 Hz), 1.167(3H, d, J 7.0 Hz), 1.421(2H, m, J 7.5 Hz), 1.676(2H, m, J 7.5 Hz), 2.564(2H, bm), 2.787(2H, bs), 2.982(2H, bm), 3.717(1H, bdd), 3.931(2H, t, J 6.5 Hz), 4.122(1H, bm), 5.078(2H, q), 6.566(2H, s), 6.929(2H, m) and 7.123(1H, t, J 9.0 Hz).
Reaction SMILES: [NH2:1][C@@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].C(=O)([O-])[O-].[K+].[K+].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>C(#N)C>[CH2:14]([N:1]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@H:2]([CH2:3][OH:4])[C:5]([O:7][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: N[C@H](CO)C(=O)O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: O=C(OCc1ccccc1)[C@@H](CO)N(Cc1ccccc1)Cc1ccccc1
Yield: 88.9 %

Procedure:
D-serine (10.5 g, 0.1 mol) was stirred with potassium carbonate (69 g, 0.5 mol), benzyl bromide (64.8 g, 0.375 mol) and water (10 mL) in acetonitrile (250 mL) at 55° C. for 24 hours. The reaction mixture was filtered and washed with ethyl acetate. The filtrate was concentrated with silica gel. The product was purified by column chromatography, eluting with 5-20% ethyl acetate in hexanes to give benzyl (2R)-2-(dibenzylamino)-3-hydroxypropanoate (33.36 g, 88%) as a pale-yellow sticky oil. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.20-7.44 (m, 15H), 5.27 (q, 2H), 3.91 (d, 2H), 3.80 (m, 2H), 3.67 (d, 2H), 3.63 (m, 1H) and 2.52 (dd, 1H).
Reaction SMILES: [CH3:1][C:2](=O)[CH2:3][CH2:4][CH3:5].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:18])[CH2:15][C:16]#[N:17])=[CH:10][CH:9]=1.NCCC(O)=O.C(O)(=O)C>CCOC(C)=O.C1(C)C=CC=CC=1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([C:15](=[C:2]([CH3:1])[CH2:3][CH2:4][CH3:5])[C:16]#[N:17])=[O:18])=[CH:12][CH:13]=1
Reactant: N#CCC(=O)c1ccc(Cl)cc1
Reactant: CCCC(C)=O
Agent: NCCC(=O)O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCCC(C)=C(C#N)C(=O)c1ccc(Cl)cc1
Temperature: 25 °C

Procedure:
A mixture of pentan-2-one (20 mmol), 3-(4-chlorophenyl)-3-oxopropanenitrile (3.6 g, 20 mmol), β-alanine (180 mg, 2 mmol), acetic acid (2.6 mL) and toluene (60 mL) is heated to reflux in a Dean-Stark system for 18 h. The solution is cooled to RT, then diluted with EtOAc (50 mL), washed with 5% NaHCO3 (3×20 mL), water (20 mL), brine (20 mL), dried (Na2SO4) and finally concentrated in vacuo. A mixture of the two isomers is obtained as a colorless oil by chromatographic purification of the crude residue on silica gel using EtOAc:petroleum ether (0.5:9.5) as eluent.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=O.O1CCCC1.[N:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][CH2:24][CH2:25][CH2:26][NH2:27])[CH:18]=1>O>[ClH:1].[ClH:1].[NH2:11][C:4]1[CH:3]=[C:2]([Cl:1])[CH:10]=[CH:9][C:5]=1[C:6]([NH:27][CH2:26][CH2:25][CH2:24][CH2:23][C:19]1[CH:18]=[N:17][CH:22]=[CH:21][CH:20]=1)=[O:8]
Reactant: Nc1cc(Cl)ccc1C(=O)O
Reactant: NCCCCc1cccnc1
Solvent: O
Solvent: C1CCOC1
Product: Cl
Product: Nc1cc(Cl)ccc1C(=O)NCCCCc1cccnc1
Reaction time: 3 h

Procedure:
A mixture of 1.72 g of 4-chloroanthranilic acid, 1.62 g of N,N'-carbonyldiimidazole and 25 ml of tetrahydrofuran was stirred for 3 hours at 5°-25° C. and 1.50 g of 4-(3-pyridinyl)butylamine was added. The mixture was stirred overnight at room temperature, heated at reflux temperature for 1 hour and then with 10 ml of water for 30 minutes. The reaction mixture was concentrated and 100 ml of methylene chloride and 5 ml of 1N sodium hydroxide were added. The layers were separated and the organic layer was concentrated, washed with water, dried over magnesium sulfate and concentrated. The residue was treated with ethanolic hydrogen chloride. The mixture was again concentrated and triturated with acetone to obtain crystals of the desired product, mp 208°-210° C. after recrystallization from ethanol.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:11][C:12]1[C:26]([O:27][CH3:28])=[CH:25][C:15]([C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH:19]2[CH2:23][OH:24])=[O:17])=[C:14]([NH:29][C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31])[C:13]=1[O:38][CH3:39]>C(Cl)Cl.O>[CH3:11][C:12]1[C:26]([O:27][CH3:28])=[CH:25][C:15]2[C:16](=[O:17])[N:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[C@H:23]([OH:24])[N:29]([C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31])[C:14]=2[C:13]=1[O:38][CH3:39]
Reactant: COc1cc(C(=O)N2CCCC2CO)c(NC(=O)OCC(Cl)(Cl)Cl)c(OC)c1C
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: CS(C)=O
Solvent: ClCCl
Product: COc1cc2c(c(OC)c1C)N(C(=O)OCC(Cl)(Cl)Cl)[C@@H](O)[C@@H]1CCCN1C2=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 86.8 %

Procedure:
Anhydrous DMSO (1.006 g, 12.87 mmol) in dry DCM (10 mL) was added dropwise over 5 minutes to a stirred solution of oxalyl chloride (3.19 mL of a 2 N solution in DCM, 6.373 mmol) under a nitrogen atmosphere at −50° C. After stirring for 5 minutes, a solution of 192 (2.13 g, 4.53 mmol) in dry DCM (10 mL) was added dropwise over 45 minutes to the reaction mixture, which was then stirred for a further 45 minutes at −50° C. TEA (1.83 g; 18.13 mmol) was added dropwise to the mixture over 0.5 hours and stirred for a further 15 minutes. The reaction mixture was left to warm to room temperature, diluted with H2O (100 ml) and the phases allowed to separate. The organic phase was washed with 1 N HCl (2×50 mL), water (2×50 mL), brine (2×50 mL) and dried over MgSO4. The solvent was evaporated to afford the product (193) as an off-white glass (1.84 g, 3.93 mmol; 87%). 1H NMR (270 MHz, CDCl3) δ 7.05 (s, 1H) (minor rotamer 1:4, visible at d 7.06), 5.58 (dd, J=3.84 Hz, J=9.89, 1H) (minor rotamer 1:4, visible at d 5.68, J=4.21 Hz, J=9.53), 4.71 (d, J=11.72 Hz, 1H), 4.56 (d, J=11.73 Hz, 1H), 4.11 (d, J=3.85 Hz, 1H), 3.88 (s, 3H), 3.76 (s, 3H), 3.79-3.47 (m, 2H), 2.21-1.99 (m, 4H), 2.16 (s, 3H); 13C NMR (67.8 MHz, CDCl3) rotamers δ 166.82, 158.31, 157.92, 155.65, 155.43, 131.52, 124.17, 123.99, 121.62, 105.90, 105.64, 105.38, 94.53, 86.17, 85.93, 75.80, 75.23, 61.77, 61.65, 59.98, 59.58, 59.40, 55.88, 55.79, 46.56, 46.38, 28.70, 28.62, 22.94, 10.14, 9.75.
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Solvent: O
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 120 °C
Yield: 85 %

Procedure:
Into a 3/4 inch (about 20 mm) single screw extruder having a ratio of length to diameter of about 30:1 and three zones heated at 90° C., 120° C., and 180° C. were introduced 11.7 g per minute of 2,5-dianilinoterephthalic acid and 27.2 g per minute of polyphosphoric acid (117.7% phosphoric acid). The resultant mass was introduced into water. The resultant solid was collected by filtration and reslurried in water containing sodium hydroxide (pH greater than 10). The slurry was heated at 90 to 95° C. for one hour, then collected by filtration, washed until free of alkali, and dried to give an 85% yield of quinacridone (91.3% purity).
Reaction SMILES: [CH2:1]([O:3][CH:4]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17]CC2C=CC=CC=2)=[CH:13][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:2].[H][H]>[Pd].S1CCOCC1>[CH2:1]([O:3][CH:4]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:2]
Reactant: CCOC(=O)C(Cc1ccc(OCc2ccccc2)cc1)OCC
Reactant: [H][H]
Agent: [Pd]
Agent: C1CSCCO1
Product: CCOC(=O)C(Cc1ccc(O)cc1)OCC
Yield: 97 %

Procedure:
A mixture of racemic ethyl 2oxy-3-(4-benzyloxyphenyl)propionate of the formula (12a) (40 g) obtained according to the procedure described in step (iv) above, 5% Pd/C catalyst (8 g) and 1,4-thioxane (200 ml) was subjected to hydrogenation at room temperature and 50–60 psi of hydrogen pressure for a period of 8–12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the catalyst was filtered off and the solvent was removed under reduced pressure to afford the title compound of the formula (13a) (28–29 g, 97–98%).,
Reaction SMILES: [F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10](O)=[O:11].S(Cl)(Cl)=O.C[N:27](C=O)C>>[F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([NH2:27])=[O:11]
Reactant: CN(C)C=O
Reactant: O=C(O)c1cc(Oc2ccc(F)cc2F)ccc1[N+](=O)[O-]
Solvent: O=S(Cl)Cl
Product: NC(=O)c1cc(Oc2ccc(F)cc2F)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of compound (1B) (53 g, 0.18 mol), thionyl chloride (51.3 mL) and DMF (1 mL) was stirred at room temperature for 18 h, then concentrated in vacuo to dryness. This acid chloride (60.7 g) was dissolved in THF (400 mL), and NH4OH (235 mL) was added. The mixture was then stirred for 18 h and concentrated in vacuo. The residue was purified by flash chromatography eluting with hexane:EtOAc (4:1) to afford 27.7 g of 5-(2,4-difluoro-phenoxy)-2-nitro-benzamide (IC).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1.[OH-:13].[NH4+].OO>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:11]([NH2:12])=[O:13])[CH2:9][CH2:10]2)[CH:5]=[N:6][CH:7]=1
Reactant: N#CC1(c2cncc(Br)c2)CC1
Reactant: [OH-]
Agent: OO
Agent: [NH4+]
Solvent: C1CCOC1
Product: NC(=O)C1(c2cncc(Br)c2)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1-(5-Bromo-pyridin-3-yl)-cyclopropanecarbonitrile (150 mg, 0.672 mmol) is dissolved in THF (1.5 mL) in a reaction vial. Ammonium hydroxide (1 mL) is then added. Hydrogen peroxide (30% aq solution, 0.5 mL) is added slowly. The mixture is stirred at room temperature for 4 h. The volatiles is evaporated to afford 1-(5-bromo-pyridin-3-yl)-cyclopropanecarboxylic acid amide (157.5 mg, 97% crude yield).
Reaction SMILES: [C:1]([O-:9])([O-])([O:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH3:2].O[C:11]([CH2:15][CH2:16][CH:17]=[C:18]([CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH3:19])([CH:13]=[CH2:14])[CH3:12].C1(C=CC(O)=CC=1)O>C(O)CCC>[CH2:14]([CH2:2][C:1]([O:3][CH2:4][CH2:5][CH2:6][CH3:7])=[O:9])[CH:13]=[C:11]([CH2:15][CH2:16][CH:17]=[C:18]([CH2:20][CH2:21][CH:22]=[C:23]([CH3:24])[CH3:25])[CH3:19])[CH3:12]
Reactant: CCCCOC(C)([O-])[O-]
Reactant: C=CC(C)(O)CCC=C(C)CCC=C(C)C
Agent: Oc1ccc(O)cc1
Solvent: CCCCO
Product: CCCCOC(=O)CCC=C(C)CCC=C(C)CCC=C(C)C

Procedure:
Following the same procedures as in Example 26, a mixture of 1184 g. of n-butyl orthoacetate, 220 g. of nerolidol and 22 g. of hydroquinone was reacted with heating at 160° - 165° C., with removal of n-butanol produced from the reaction system. The reaction mixture was directly distilled in vacuo to give 598 g of n-butyl farnesylacetate, b.p. 134° - 142° C. (0.3 mmHg). Then, this product was fractionated through a rectifying column with 40 numbers of theoretical plates reflux ratio of 20 to give 147.5 g of n-butylΔ 4,8 -trans-farnesylacetate, b.p. 140° - 142° C. (0.3 mmHg). 64% of Δ4,8 -trans-isomer introduced was recovered on distillation.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[C:15]([F:18])([F:17])[F:16])[CH2:3][CH2:2]1.Cl.[NH2:20][C:21]([CH2:29][CH3:30])([CH2:27][CH3:28])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>>[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([NH:20][C:21]([CH2:27][CH3:28])([CH2:29][CH3:30])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:14])[CH:9]=[CH:8][C:7]=2[C:15]([F:18])([F:17])[F:16])[CH2:2][CH2:3]1
Reactant: CCOC(=O)C(N)(CC)CC
Reactant: O=C(O)c1ccc(C(F)(F)F)c(OCC2CC2)n1
Agent: Cl
Product: CCOC(=O)C(CC)(CC)NC(=O)c1ccc(C(F)(F)F)c(OCC2CC2)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (Example 113 d) and ethyl 2-amino-2-ethylbutanoate hydrochloride (CAN 1135219-29-2) as starting materials, MS (EI): m/e=403.4 [M+H]+.
Reaction SMILES: [OH:1][N:2]1[C:6]2[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[CH3:14][S:15](Cl)(=[O:17])=[O:16].C(OCC)(=O)C.O>[OH-].[Na+]>[CH3:14][S:15]([O:1][N:2]1[C:6]2[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1)(=[O:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc2nnn(O)c2c1
Reactant: CS(=O)(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: CS(=O)(=O)On1nnc2ccc([N+](=O)[O-])cc21
Yield: 70.7 %

Procedure:
1-Hydroxy-6-nitro-1,2,3-benzotriazole (7.2 g) is dissolved in 1 N aqueous sodium hydroxide (40 ml). To the solution is added dropwise methanesulfonyl chloride (5.6 g) with stirring under ice-cooling and thereto are added ethyl acetate (100 ml) and water (100 ml). The mixture is stirred at room temperature for 1 hour. To the reaction mixture is added ethyl acetate (50 ml) and the insoluble materials are filtered off. The ethyl acetate layer is dried over magnesium sulfate-charcoal. After drying, the layer is concentrated so as to be about 30 ml and thereto is added n-hexane (about 30 ml) and the mixture is allowed to stand. The precipitated crystals are separated by filtration and dried to give 1-methanesulfonyloxy-6-nitro-1,2,3-benzotriazole (7.3 g; 72%), melting point: 115°-116° c. The product is dissolved in ethyl acetate and treated with charcoal and thereto is added n-hexane to give faint yellow flakes melting point: 117°-118° C.
Reaction SMILES: [CH3:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:5](=[O:6])[CH2:4][C:3]1=[O:7].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:22][C:23]1[C:31]2[C:26](=[CH:27][C:28]([CH3:32])=[CH:29][CH:30]=2)[NH:25][CH:24]=1>>[CH3:22][C:23]1[C:31]2[C:26](=[CH:27][C:28]([CH3:32])=[CH:29][CH:30]=2)[NH:25][C:24]=1[CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:4]1[C:3](=[O:7])[C:2]([CH3:1])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:5]=1[OH:6]
Reactant: O=Cc1ccccc1
Reactant: Cc1ccc2c(C)c[nH]c2c1
Reactant: CC1(c2ccccc2)C(=O)CC1=O
Product: Cc1ccc2c(C)c(C(C3=C(O)C(C)(c4ccccc4)C3=O)c3ccccc3)[nH]c2c1

Procedure:
Using general procedure C, 2-methyl-2-phenyl-cyclobutane-1,3-dione (Lit. 1) was reacted with benzaldehyde and 3,6-dimethyl-1H-indole (Lit. 4) to give the title compound as a colorless solid. MS: 406.4 ([M−H]−).
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.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>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1
Reactant: COc1ccccc1B(O)O
Reactant: Brc1cncc2ccccc12
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
Solvent: CN(C)C=O
Product: COc1ccccc1-c1cncc2ccccc12
Temperature: 50 °C
Reaction time: 12 h

Procedure:
A solution of 4-bromoisoquinoline (2.06 g, 10 mmol), prepared as described in the Journal of Organic Chemistry 2003, 68, 9412-9415, 2-methoxyphenylboronic acid (2.79 g, 10 mmol), Pd(PPh3)4 (5% mol), K2CO3 (5 g) in DMF/water (3/1) is stirred at 50° C. for 12 hours. The reaction mixture is then pored on water (150 mL). The aqueous phase is extracted with ethyl acetate (3×100 mL). The combined organic layers are washed with water (3×200 mL). The organic phase is dried over magnesium sulfate and evaporated under vacuum to afford the title compound.
Reaction SMILES: Cl.CNC.[CH2:5]([N:7]([CH2:10]C)[CH2:8][CH3:9])C.C(O[BH-](O[C:22](=[O:24])[CH3:23])OC(=O)C)(=O)C.Cl.Cl[CH2:27][CH2:28]Cl>O>[CH3:10][N:7]([CH3:5])[CH:8]1[CH2:9][CH2:23][C:22](=[O:24])[CH2:28][CH2:27]1
Reactant: CCN(CC)CC
Reactant: ClCCCl
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: CNC
Agent: Cl
Solvent: O
Product: CN(C)C1CCC(=O)CC1
Reaction time: 0.17 h
Yield: 17 %

Procedure:
To a suspension of 1,4-cyclohexanedione monoethylene-ketal (3.82 g, 24.6 mmol) and dimethylamine hydrochloride (2.00 g, 24.6 mmol) in 1,2-dichloroethane (50 ml) were dropwise added triethylamine (4.2 ml, 29.6 mmol) and DBU (1,8-diazabicyclo-[5.4.0]-7-undecene) (4.4 ml), and the mixture was stirred for 10 minutes. To the mixture was added triacetoxyborohydride (7.68 g, 34.4 mmol), and the mixture was stirred for 4.5 hours. Precipitate was filtered off, and the filtrate was concentrated to give crude product (6.34 g), which was dissolved in water (10 ml). To the mixture was dropwise added concentrated hydrochloric acid (6 ml), and the mixture was stirred for 48 hours. The reaction mixture was diluted with water and washed twice with ether. The aqueous layer was made basic with sodium hydroxide and extracted with ether twice. The extract was washed with saturated sodium chloride solution, dried with potassium carbonate and purified by evaporation to give 4-dimethylaminocyclohexanone (0.59 g, 17%).