Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)([O-:3])=[O:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[C:31]=1[CH2:32][NH2:33]>ClCCl>[CH3:39][O:38][C:34]1[CH:35]=[CH:36][CH:37]=[C:30]([O:29][CH3:28])[C:31]=1[CH2:32][NH:33][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: O=C(O)c1ccccc1[N+](=O)[O-]
Reactant: COc1cccc(OC)c1CN
Agent: CC(C)COC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cccc(OC)c1CNC(=O)c1ccccc1[N+](=O)[O-]
Temperature: 5 °C
Reaction time: 1 h
Yield: 99.1 %

Procedure:
4 g 2-nitrobenzoic acid (23.93 mmol) and 2.42 g triethylamine were dissolved in 100 mL dichloromethane, mixed with one equivalent isobutyl chloroformate (3.27 g) at 5° C. and stirring was continued for 1 hour at room temperature. Then the mixture was cooled again to 5° C., 4.02 g 2,6-dimethoxybenzylamine was added and the mixture was stirred at room temperature until the reaction was complete. For workup, the mixture was diluted with dichloromethane, washed twice each with 10% citric acid, saturated NaHCO3 and saturated NaCl solution, dried with MgSO4, filtered and concentrated, yielding 7.5 g beige solids that were reacted further directly without any further workup.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22](Br)[S:21]4)[O:17][C:13]=2[CH:12]=[C:11]([Cl:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.[CH3:31][OH:32].C[O-].[Na+]>CCOC(C)=O>[CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22]([O:32][CH3:31])[S:21]4)[O:17][C:13]=2[CH:12]=[C:11]([Cl:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1cc(OCc2ccccc2)c2cc(-c3cn4nc(Br)sc4n3)oc2c1
Reactant: CO
Agent: C[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1nn2cc(-c3cc4c(OCc5ccccc5)cc(Cl)cc4o3)nc2s1
Yield: 81.5 %

Procedure:
To a stirred solution of 6-(4-(benzyloxy)-6-chlorobenzofuran-2-yl)-2-bromoimidazo[2,1-b][1,3,4]thiadiazole (Example 37G, 1.18 g, 2.56 mmol) in DCM (40 mL, 622 mmol) and methanol (10 mL, 247 mmol) was added sodium methoxide (1.164 mL, 5.12 mmol). The reaction mixture was stirred at r.t. for 1 h 15 min while monitoring by TLC (7:3 hexanes:EtOAc). The reaction mixture was quenched with 1N HCl and extracted with DCM. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was triturated with MeOH (sonication) and the solid material was filtered off, rinsed with MeOH and sucked dry to give the desired compound as a brown solid (859 mg, 2.086 mmol, 81% yield). LC (Method A): 2.478 min. LCMS (APCI) calcd for C20H15ClN3O3S [M+H]+ m/z 412.05, found 412.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 8.50 (s, 1H), 7.52 (m, 2H), 7.43 (m, 2H), 7.36 (m, 2H), 7.09 (d, J=0.8 Hz, 1H), 7.00 (d, J=1.6 Hz, 1H), 5.31 (s, 2H), 4.21 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH2:11])=[O:4].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:11][CH2:17][C:16]1[CH:19]=[CH:20][C:13]([F:12])=[CH:14][CH:15]=1)=[O:4]
Reactant: O=Cc1ccc(F)cc1
Reactant: COC(=O)[C@@H]1CCCC[C@@H]1N
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)[C@@H]1CCCC[C@@H]1NCc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 46.9 %

Procedure:
(1R,2S)-2-Amino-cyclohexanecarboxylic acid methyl ester (1 g, 6.4 mmol) was dissolved in methanol (70 mL). 4-Fluoro-benzaldehyde (0.794 g, 6.4 mmol) was added followed by acetic acid (1 mL). The solution was stirred at 25° C. for 10 min. Sodium cyanoborohydride (1 g, 16 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into 1/2 saturated aqueous sodium bicarbonate solution (150 mL). The aqueous layer was extracted with ethyl acetate (2×150 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product, (1R,2S)-2-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester (0.8 g, 3 mmol, 47%), as a light yellow oil. LC-MS (ESI) calcd for C15H20FNO2 265.15, found 266.2 [M+H+].
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[O:27][CH3:28])[CH:12]=[CH:13][C:14]=2[C:15](OCC)=[O:16])=[C:6]([CH3:29])[CH:5]=1)(=[O:3])[NH2:2].CC(C[AlH]CC(C)C)C.CCOC(C)=O.CO>C1(C)C=CC=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:11]2[CH:12]=[CH:13][C:14]([CH2:15][OH:16])=[C:10]2[C:7]2[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[CH:5][C:6]=2[CH3:29])=[C:21]([O:27][CH3:28])[CH:22]=1
Reactant: CCOC(=O)c1ccn(-c2ccc(Cl)cc2OC)c1-c1ccc(C(N)=O)cc1C
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1cc(Cl)ccc1-n1ccc(CO)c1-c1ccc(C(N)=O)cc1C
Reaction time: 2 h
Yield: 40 %

Procedure:
A solution of ethyl 2-(4-carbamoyl-2-methylphenyl)-1-(4-chloro-2-methoxyphenyl)-1H-pyrrole-3-carboxylate (1.2 g, 2.9 mmol) in anhydrous toluene (50 mL) was cooled to −78° C., DIBAL-H (1.0 mol/L, 14.5 mL) was added dropwise, and the reaction mixture was stirred at this temperature for two hours. TLC (EtOAc: MeOH=10:1) indicated that the starting material was consumed. Saturated aqueous NH4Cl solution was added to quench the reaction, and the mixture was filtered. The filtrate was extracted with EtOAc (20 mL×3), and the combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give the titled compound (430 mg, yield: 40.2%). 1H NMR (CD3OD 300 MHz TMS): δ 7.63 (s, 1H), 7.55 (m, 1H), 7.21 (d, J=7.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.95 (d, J=2.1 Hz, 1H), 6.82-6.87 (m, 2H), 6.43 (d, J=3.0 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 4.27 (d, J=11.7 Hz, 1H), 3.60 (s, 3H), 2.10 (s, 3H).
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:20][C:21]([NH:23][C@H:24]([C:40](O)=[O:41])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[NH2:58][C@H:59]([C:63]([OH:65])=[O:64])[C@@H:60]([CH3:62])[OH:61]>>[C:1]([O:18][CH:19]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:20][C:21]([NH:23][C@H:24]([C:40]([NH:58][C@H:59]([C:63]([OH:65])=[O:64])[C@@H:60]([CH3:62])[OH:61])=[O:41])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Reactant: C[C@@H](O)[C@H](N)C(=O)O
Product: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)O)[C@@H](C)O
Yield: 79.5 %

Procedure:
Starting from Nα -(3-hexadecanoyloxyoctadecanoyl)-Nε -benzyloxycarbonyl-L-lysine (2.68 g) prepared by the method of Example 20 (1), and L-threonine (0.95 g), N-[Nα -(3-hexadecanoyloxyoctadecanoyl)-Nε -benzyloxycarbonyl-L-lysyl]-L-threonine (2.4 g) was obtained as crystals according to a similar manner to that of Example 32.
Reaction SMILES: [CH:1]1([CH2:7][NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>[OH-].[Na+].C1C=CC=CC=1>[C:15]([O:14][C:12](=[O:13])[CH2:11][CH2:10][NH:8][CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)OC(=O)CCCl
Reactant: NCC1CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Product: CC(C)(C)OC(=O)CCNCC1CCCCC1
Reaction time: 1 h
Yield: 89.7 %

Procedure:
To 33.76 g of cyclohexylmethylamine was added with stirring 15.96 g of tert-butyl β -chloropropionate over a period of 30 minutes, while maintaining the temperature at 30°-70° C. The reaction mixture was held at 70° C. for an additional one hour. At the end of this period, the reaction mixture was taken up in 40 ml of 2N NaOH solution and 50 ml of benzene, transferred into a separatory funnel and well shaken. The benzene solution was separated, washed with water, dried over anhydrous sodium sulfate and filtered. After evaporation of benzene, the residue was distilled under reduced pressure to give 21.0 g (89 percent) of N-cyclohexylmethyl- β -alanine tert-butyl ester, B.P. 156° C./15 mmHg.
Reaction SMILES: [C:1]([O:10][CH3:11])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].C(=O)([O-])[O-].[Na+].[Na+].[I:18][CH2:19][CH2:20][CH2:21]I.C(OCC)(=O)C.CCCCCC>CC(C)=O>[I:18][CH2:19][CH2:20][CH2:21][O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH3:11])=[O:9]
Reactant: ICCCI
Reactant: COC(=O)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COC(=O)c1ccccc1OCCCI
Reaction time: 18 h

Procedure:
Combine methyl salicylate (5.09 g, 33.2 mmol), sodium carbonate (10.56 g, 99.67 mmol), and 1,3-diiodopropane (29.49 g, 99.67 mmol) in acetone (200 mL). Heat to reflux. After 18 hours, add sodium carbonate (10.56 g, 99.67 mmol) and continue to heat at reflux. After 18 hours, add 1,3-diiodopropane (29.49 g, 99.67 mmol) and continue to heat at reflux. After 18 hours. filter the reaction mixture and concentrate the filtrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 1/10 ethyl acetate/hexane to give the title compound: Rf=0.29 (silica gel, 1/10 ethyl acetate/hexane).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[O:30][C:29]([CH:31]=O)=[CH:28][CH:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:33]1[CH2:40][CH2:39][CH2:38][C@H:34]1[C:35]([NH2:37])=[O:36]>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[O:30][C:29]([CH2:31][N:33]5[CH2:40][CH2:39][CH2:38][C@H:34]5[C:35]([NH2:37])=[O:36])=[CH:28][CH:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC(=O)[C@@H]1CCCN1
Reactant: O=Cc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5ccccc5)cc4)c3c2)o1
Product: NC(=O)[C@@H]1CCCN1Cc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5ccccc5)cc4)c3c2)o1

Procedure:
5-(4-(4-Benzyloxy-phenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde and L-prolinamide were reacted in an analogous manner to Example 10 to give the title compound; δH [2H6]-DMSO 9.85 (1H, b), 8.72 (1H, s), 8.50 (1H, s), 8.14 (1H, d), 7.79 (1H, d), 7.71 (2H, d), 7.54-7.31 (5H, m), 7.24 (1H, s), 7.17 (1H, s), 7.09 (2H, d), 7.02 (1H, d), 6.53 (1H, d), 5.15 (2H, s), 3.82 (2H, s), 3.42 (1H, b), 3.12 (2H, b), 1.85-1.67 (4H, m); m/z 520 (M+1)+.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:25])[CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21]Cl)=[C:14]([O:23][CH3:24])[CH:13]=2)[CH2:4][CH2:3]1.[CH3:26][NH:27][CH3:28]>CC(CC(C)C)=O>[CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:25])[CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:27]([CH3:28])[CH3:26])=[C:14]([O:23][CH3:24])[CH:13]=2)[CH2:4][CH2:3]1
Reactant: COc1cc(C=CC(=O)N[C@H]2CC[C@H](C)CC2)ccc1OCCCCl
Reactant: CNC
Solvent: CC(=O)CC(C)C
Product: COc1cc(C=CC(=O)N[C@H]2CC[C@H](C)CC2)ccc1OCCCN(C)C

Procedure:
Using 5 g of N-(trans-4-methylcyclohexyl) -4-(3-chloropropoxy)-3-methoxycinnamamide (Example 134), 100 ml of methylisobutylketone, and 150 ml of a 50% aqueous dimethylamine solution, a reaction similar to that conducted in Example 107 was carried out. As a result, 4.61 g of N-(trans-4-methylcyclohexyl)-4-(3-dimethylaminopropoxy)-3-methoxycinnamamide (a compound of the present invention) was obtained as white crystal, which had the following physiochemical properties:
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[N:10][S:11][CH:12]=1)[C:5]([OH:7])=O.[NH2:13][CH:14]1[C:29](=[O:30])[N:16]2[C:17]([C:26]([OH:28])=[O:27])=[C:18]([CH2:21][O:22][C:23](=[O:25])[NH2:24])[CH2:19][S:20][C@H:15]12>>[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:9]=[N:10][S:11][CH:12]=1)[C:5]([NH:13][CH:14]1[C:29](=[O:30])[N:16]2[C:17]([C:26]([OH:28])=[O:27])=[C:18]([CH2:21][O:22][C:23](=[O:25])[NH2:24])[CH2:19][S:20][C@H:15]12)=[O:7]
Reactant: CON=C(C(=O)O)c1csnn1
Reactant: NC(=O)OCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(N)=O)CS[C@H]12)c1csnn1
Yield: 45.6 %

Procedure:
2-Methoxyimino-2-(1,2,3-thiadiazol-4-yl)acetic acid (syn isomer)(0.65 g) and 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (0.96 g) were reacted according to similar manners to those of Examples 12 and 15 to give 7-[2-methoxyimino-2-(1,2,3-thiadiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (syn isomer)(0.7 g).
Reaction SMILES: [CH3:1][N:2]1[CH2:8][C:6](=[O:7])[NH:5][C:3]1=[O:4].[NH2:9][CH2:10][C@@H:11]1[CH2:15][CH2:14]CN1CC.C(=O)C>>[NH2:9][CH2:10][CH2:11][CH2:15][CH2:14][N:5]1[C:6](=[O:7])[CH2:8][N:2]([CH3:1])[C:3]1=[O:4]
Reactant: CCN1CCC[C@H]1CN
Reactant: CN1CC(=O)NC1=O
Agent: CC=O
Product: CN1CC(=O)N(CCCCN)C1=O

Procedure:
By using 1-methylhydantoin (2.8 g) as a starting material, the title compound (1.38 g) was obtained in the same manners as those of Reference Example 63, (1) and Reference Example 9, (2).
Reaction SMILES: CC1C=CC(S([O:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:20][CH2:19][N:18](C(OCC3C=CC=CC=3)=O)[CH2:17][CH2:16]2)(=O)=O)=CC=1.[O:31]1[CH2:35][CH2:34][C@@H:33](O)[CH2:32]1>>[O:31]1[CH2:35][CH2:34][C@@H:33]([O:11][CH2:12][CH2:13][O:14][CH:15]2[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]2)[CH2:32]1
Reactant: O[C@@H]1CCOC1
Reactant: Cc1ccc(S(=O)(=O)OCCOC2CCN(C(=O)OCc3ccccc3)CC2)cc1
Product: C1CC(OCCO[C@@H]2CCOC2)CCN1
Yield: 78.5 %

Procedure:
Using benzyl 4-(2-{[(4-methylphenyl)sulfony]oxy}ethoxy)piperidine-1-carboxylate (4.00 g, 9.23 mmol) produced in Reference Example 1 (1c) and (3R)-tetrahydrofuran-3-ol (1.05 g, 12.0 mmol), the desired title compound (1.56 g, yield 79%) was obtained by the same method as in Reference Examples 1 (1d) and 1 (1e).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].Br[CH2:10][C@@H:11]([CH3:14])[CH2:12][Cl:13]>>[Cl:13][CH2:12][C@H:11]([CH3:14])[CH2:10][O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Br:1]
Reactant: Oc1ccccc1Br
Reactant: C[C@@H](CCl)CBr
Product: C[C@@H](CCl)COc1ccccc1Br

Procedure:
Prepared by Procedure U and Scheme AK using 2-bromophenol and (2S)-1-bromo-3-chloro-2-methylpropane.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[O:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:25](Cl)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CC(C)=O>[CH2:25]([O:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[O:9]2)=[CH:4][CH:3]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: ClCc1ccccc1
Reactant: CCOC(=O)C1CCc2ccc(O)cc2O1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C1CCc2ccc(OCc3ccccc3)cc2O1
Yield: 99.9 %

Procedure:
A mixture of ethyl 7-hydroxy-chroman-2-carboxylate (6.1 g, 27.5 mmol), potassium carbonate (7.6 g, 55 mmol), potassium iodide (1.8 g, 11 mmol) and benzyl chloride (3.4 mL, 30 mmol) in acetone is heated at reflux for 16 hr under nitrogen, cooled, concentrated, diluted with water and extracted with EtOAc. The combined extracts are dried over MgSO4 and concentrated to afford the title compound as a straw-colored oil 8.58 g (100% yield), identified by NMR and mass spectral analyses.
Reaction SMILES: [C:1]([N:5]([CH:15]([CH3:17])[CH3:16])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)(=[O:4])[CH:2]=[CH2:3].Cl.[CH3:19][NH:20][CH3:21]>>[CH3:19][N:20]([CH3:21])[CH2:3][CH2:2][C:1]([N:5]([CH:15]([CH3:17])[CH3:16])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)=[O:4]
Reactant: C=CC(=O)N(c1ccc([N+](=O)[O-])cc1)C(C)C
Reactant: CNC
Agent: Cl
Product: CC(C)N(C(=O)CCN(C)C)c1ccc([N+](=O)[O-])cc1

Procedure:
Prepared from N-acryloyl-N-isopropyl-4-nitro-aniline and dimethylamine hydrochloride
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10]([C:12]1[NH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[CH:16][CH:15]=2)=O)C.O.Cl>C1COCC1>[C:21]1([C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][CH:16]=2)[NH:13][C:12]([CH2:10][OH:9])=[CH:20]3)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CCOC(=O)c1cc2cc(-c3ccccc3)ccc2[nH]1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cc2cc(-c3ccccc3)ccc2[nH]1
Reaction time: 2 h
Yield: 90.5 %

Procedure:
1M Lithium aluminum hydride in THF was added to a cooled solution of 5-phenyl-1H-indole-2-carboxylic acid ethyl ester 44 (0.375 g, 1.41 mmole) in dry THF (5 ml). After 2 hrs at room temperature, the excess reagent was decomposed with water, acidified with 1M HCl, extracted, washed, dried, and evaporated to give about 0.285 g of (5-phenyl-indol-2-yl)-methanol 45, mp. 115-116° C.
Reaction SMILES: C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[S:52][C:51]([C:53]([OH:55])=[O:54])=[CH:50][CH:49]=1.[C:56]([C:60]#[CH:61])([CH3:59])([CH3:58])[CH3:57]>[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:57][C:56]([CH3:59])([CH3:58])[C:60]#[C:61][C:48]1[S:52][C:51]([C:53]([OH:55])=[O:54])=[CH:50][CH:49]=1
Reactant: O=C(O)c1ccc(Br)s1
Reactant: C#CC(C)(C)C
Agent: [Cu]I
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN(C)C=O
Product: CC(C)(C)C#Cc1ccc(C(=O)O)s1
Temperature: 70 °C
Reaction time: 48 h
Yield: 64.6 %

Procedure:
A 350 mL heavy wall round bottom flask was charged with TEA (33.7 mL, 24 mmol, 5.0 equiv), BINAP (3.0 g, 4.83 mmol, 0.1 equiv), 5-bromo-thiophene-2-carboxylic acid (48.3 mmol, 1.0 equiv), CuI (0.184 g, 0.97 mmol, 0.02 equiv), Pd2dba3 (2.2 g, 2.4 mmol, 0.05 equiv) and DMF (40.0 mL). The flask was flushed with N2 and to the mixture was added t-butyl acetylene (15.8 g, 193 mmol, 4.0 equiv). The mixture was sealed and stirred at 70° C. for 48 hours. After cooled at room temperature, the reaction mixture was filtered and the filtrate was concentrated under vacuum. The residue was acidified with 3.0 N HCl until pH=4. The aqueous layer was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silical gel, EtOAc/heptane 5% to EtOAc/heptane 30% with 2% of AcOH to give product 6.5 g (yield 65%).
Reaction SMILES: CO.C[O-].[Na+].[N+](C(C)C)([O-])=[O:7].Br[CH2:13][C:14]1[C:15]([Cl:25])=[C:16]([CH:21]=[CH:22][C:23]=1[Cl:24])[C:17]([O:19][CH3:20])=[O:18]>C(OCC)(=O)C>[Cl:25][C:15]1[C:14]([CH:13]=[O:7])=[C:23]([Cl:24])[CH:22]=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18]
Reactant: CC(C)[N+](=O)[O-]
Reactant: COC(=O)c1ccc(Cl)c(CBr)c1Cl
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(Cl)c(C=O)c1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To methanol in a volume of 100 ml, was added 28% methanol solution of sodium methylate in an amount of 26.61 g, and to the resulting solution, was fed dropwise 2-nitro propane in an amount of 12.29 g while cooling with ice to a temperature lower than 25° C. The mixture was then added with methyl 3-bromomethyl-2,4-dichlorobenzoate in an amount of 41.16 g and stirred for 30 minutes under heating reflux. After completing reaction, the reacted-mixture was cooled and condensed under reduced pressure. A residue obtained was then dissolved in ethyl acetate in a volume of 1,000 ml, and the resulting solution was then washed with 1% aqueous solution of sodium hydroxide while cooling with ice. An organic layer resulted was washed with water and then with saturated saline solution, and was dried over anhydrous magnesium sulfate. Crystals, which were obtained after condensation of the organic layer under reduce pressure, were washed with benzene and then with n-hexane to obtain an objective compound of methyl 2,4-dichloro-3-formylbenzoate in an amount of 22.0 g in crystalline state. The melting point of this compound is in a range of from 103° to 104° C.
Reaction SMILES: CN1CCOCC1.Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:10].Cl.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH:28]([NH:30][C:31](=[O:37])[C@H:32]([CH:34]([CH3:36])[CH3:35])[NH2:33])[CH3:29])=[N:24][CH:25]=1.O>C(Cl)Cl>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH:28]([NH:30][C:31](=[O:37])[C@H:32]([CH:34]([CH3:36])[CH3:35])[NH:33][C:9]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:10])[CH3:29])=[N:24][CH:25]=1
Reactant: CC(COc1ccc(Cl)cn1)NC(=O)[C@@H](N)C(C)C
Reactant: O=C(Cl)Oc1ccccc1
Agent: Cl
Solvent: O
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(COc1ccc(Cl)cn1)NC(=O)[C@@H](NC(=O)Oc1ccccc1)C(C)C
Temperature: 25 °C
Reaction time: 15 h
Yield: 34 %

Procedure:
0.8 g of N-methylmorpholine, and subsequently 0.7 g of phenyl chloroformate were added to a suspension containing 1.4 g of N1 -[2-(5-chloro-2-pyridyloxy)-1-methylethyl]-L-valinamide hydrochloride suspended in 50 ml of methylene chloride at -15° C. The mixture was allowed to sit and warm naturally to room temperature and stirred for 15 hours at room temperature. Water was subsequently added to the reaction mixture. After the methylene chloride layer was washed with water, the organic layer was dried over anhydrous magnesium sulfate and then the methylene chloride was removed under reduced pressure. The residue was purified by column chromatography on silica gel, thus obtaining 0.6 g of the desired product in the form of colorless grains (yield: 34%).
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].Cl[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH:3][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Clc1ccccc1
Reactant: C=CC(=O)OCC
Product: CCOC(=O)C=Cc1ccccc1

Procedure:
More specifically, we have found that chlorobenzene reacts with ethyl acrylate to form ethyl cinnamate in relatively high yield by reacting the chlorobenzene with iodide and/or bromide ion to form a mixture of chlorobenzene, iodobenzene and/or bromobenzene, then reacting the mixture with ethyl acrylate in the presence of a catalyst to form ethyl cinnamate.
Reaction SMILES: [CH3:1][CH:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][C:14](SC)=[N:13][C:12]=3[CH:18]=2)=[N:6][NH:5][C:4](=[O:19])[CH2:3]1.[NH2:20][CH2:21][CH2:22][CH2:23][CH2:24][NH2:25]>O>[CH3:1][CH:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][C:14]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])=[N:13][C:12]=3[CH:18]=2)=[N:6][NH:5][C:4](=[O:19])[CH2:3]1
Reactant: CSc1nc2cc(C3=NNC(=O)CC3C)ccc2o1
Reactant: NCCCCN
Solvent: O
Product: CC1CC(=O)NN=C1c1ccc2oc(NCCCCN)nc2c1
Reaction time: 0.5 h

Procedure:
4.1 g (15.0 mmol) of 5-methyl-6-(2-methylthiobenzoxazol-5-yl)-4,5-dihydro-3(2H)-pyridazinone and 15 ml of 1,4-diaminobutane are heated to 60° C. for 45 minutes, then stirred into 200 ml of water and left to crystallise at ambient temperature. After about 30 minutes the product is suction filtered, washed with about 50 ml of water and dried at 60° C. in a circulating air dryer.