Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:15])[CH:4]([C:6]1[CH:7]=[CH:8][C:9]2[O:13][CH:12]=[N:11][C:10]=2[CH:14]=1)[CH3:5].[Li+].[OH-].C(O)(=O)C>C1COCC1.O>[O:13]1[C:9]2[CH:8]=[CH:7][C:6]([CH:4]([CH3:5])[C:3]([OH:15])=[O:2])=[CH:14][C:10]=2[N:11]=[CH:12]1
Reactant: COC(=O)C(C)c1ccc2ocnc2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C(=O)O)c1ccc2ocnc2c1
Temperature: 25 °C
Reaction time: 40 h

Procedure:
methyl-2-(benzo[d]oxazol-5-yl)propanoate (2.07 mmol, 425 mg) was dissolved in THF (8 ml) and water (8 m). LiOH*H2O (2.21 mmol, 93 mg) was added at room temperature. The reaction mixture was stirred at room temperature for 40 h, water (25 ml) was added and the pH was set to 3 with acetic acid. The reaction mixture was extracted with dichloromethane and the combined organic phases were dried and filtered over magnesium sulphate. The solvent was removed in a vacuum and the residue was purified by column chromatography (SiO2, dichloromethane/MeOH=15:1). 1H-NMR (CD3OD) δ [ppm]: 8.46 (s, 1H, Ar), 7.70 (d, 1H, J=1.7 Hz, Ar), 7.61 (d, 1H, 8.0 Hz, Ar), 7.42 (dd, 1H, J=8.6, 1.8 Hz, Ar), 3.87 (q, 1H, J=7.1 Hz, CHCH3), 1.51 (d, 3H, J=7.1 Hz, CHCH3).
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:29][CH2:28][C:11]3([CH2:16][CH2:15][N:14]([C:17]([C:19]4[S:27][C:26]5[CH2:25][CH2:24][NH:23][CH2:22][C:21]=5[CH:20]=4)=[O:18])[CH2:13][CH2:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:37][C:38]1[CH:46]=[CH:45][CH:44]=[CH:43][C:39]=1[C:40](Cl)=[O:41]>ClCCl.CN(C)C=O>[Cl:37][C:38]1[CH:46]=[CH:45][CH:44]=[CH:43][C:39]=1[C:40]([N:23]1[CH2:24][CH2:25][C:26]2[S:27][C:19]([C:17]([N:14]3[CH2:15][CH2:16][C:11]4([CH2:28][CH2:29][N:8]([C:5]5[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=5)[CH2:9][CH2:10]4)[CH2:12][CH2:13]3)=[O:18])=[CH:20][C:21]=2[CH2:22]1)=[O:41]
Reactant: O=C(Cl)c1ccccc1Cl
Reactant: O=C(c1cc2c(s1)CCNC2)N1CCC2(CC1)CCN(c1ccncc1)CC2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(c1cc2c(s1)CCN(C(=O)c1ccccc1Cl)C2)N1CCC2(CC1)CCN(c1ccncc1)CC2
Temperature: 25 °C
Reaction time: 15 h

Procedure:
(9-(Pyridin-4-yl)-3,9-diazaspiro[5.5]undecan-3-yl)(4,5,6,7-tetrahydrothieno[3,2-c]-pyridin-2-yl)methanone hydrochloride (0.089 g, 0.208 mmol) was dissolved in dichloromethane (4 ml) and N,N-dimethylformamide (1 ml), and triethylamine (0.072 ml, 0.52 mmol) was added. The mixture was cooled with an ice bath, and 2-chlorobenzoyl chloride (0.036 g, 0.208 mmol), dissolved in dichloromethane (4 ml), was added slowly at 0° C. The cooling bath was removed and the reaction mixture was stirred for 15 h at RT. Saturated sodium hydrogen carbonate solution (15 ml) was then added and the phases were separated. The aqueous phase was extracted with dichloromethane (25 ml) and the combined organic phases were washed with saturated NaCl solution (10 ml) and saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.), 500:100:1). Yield: 80 mg (72%). MS, Rt=3.0 min; m/z=535.2 [MH]+
Reaction SMILES: [CH2:1]([CH:4]([CH2:9][CH2:10][CH3:11])[CH2:5][CH2:6][CH2:7]Br)[CH2:2][CH3:3].CC([O-])(C)C.[K+].O>C1C=CC=CC=1>[CH2:5]([CH:4]([CH2:9][CH2:10][CH3:11])[CH2:1][CH:2]=[CH2:3])[CH2:6][CH3:7]
Reactant: CCCC(CCC)CCCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: c1ccccc1
Solvent: O
Product: C=CCC(CCC)CCC
Reaction time: 2 h

Procedure:
To 100 g of 4-propylheptyl bromide in 400 ml of benzene was added 90 g of t-BuOK in 300 ml of DM$0. The temperature was kept below 50° C. during the addition. The mixture was stirred for 2 hrs and 600 ml of water was added. The organic phase was separated and the aqueous phase extracted with petroleumether (b.p. 40°-60°). The combined organic phases were washed with water and brine. After drying with Na2SO4 and evaporation the residue was distilled. Yield: 23.2 g (b.p. 56°-59° C./75 Torr). 1H-NMR(CDCl3): δ0.9(6H,CH3), 1.2(9H,CH2,CH), 2.0(2H,CH2C=C), 4.8-5.1(2H,CH2 =C), 5.5-6.0(1H,CH=C)
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:26])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([O:21]C(C)(C)C)=[O:20])=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OCC)(=O)C>C(O)=O>[CH2:1]([O:8][C:9](=[O:26])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CCc1ccc(CC(=O)OCc2ccccc2)cc1
Solvent: O=CO
Solvent: CCOC(C)=O
Product: O=C(O)CCc1ccc(CC(=O)OCc2ccccc2)cc1
Temperature: 0 °C
Yield: 87 %

Procedure:
1,1-dimethylethyl 3-[4-(2-benzyloxy-2-oxoethyl) phenyl]propanoate (3.0 g, 8.5 mmol) was stirred in formic acid (10 mL) for 8 hours. Removal of the solvent in vacuo provided a colorless oil that was shaken vigorously with a mixture of ethyl acetate and hexanes (1:3, 20 mL) until it solidified. The mixture was cooled in ice water and the product, collected by suction filtration to give 3-[4-(2-benzyloxy-2-oxoethyl)phenyl]propanoic acid, as a white solid (2.2 g, 7.4 mmol) in 87% yield, mp. 62°-64.5° C.
Reaction SMILES: [CH3:1][C@@H:2]([CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])[CH2:3][CH2:4][CH2:5]O.[CH3:13][S:14](Cl)(=[O:16])=[O:15].C(N(CC)CC)C.O>ClCCl>[CH3:13][S:14]([CH2:5][CH2:4][CH2:3][C@@H:2]([CH3:1])[CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)=CCC[C@H](C)CCCO
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)=CCC[C@H](C)CCCS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 4-(S)-methyl-8-methylnon-7-enyl alcohol (3.25 g, 19.1 mmol) in dichloromethane (50 ml) at 0° C. was added methanesulfonyl chloride (2.29 g, 20.0 mmol) followed by triethylamine (3.04 g, 30.0 mmol) After stirring for 10 min at 0° C., the reaction was allowed to warm to 25° C. and stirred for 3 hr. The reaction was poured into water (50 ml), separated and washed with dichloromethane (50 ml). The organic portions were combined, dried (magnesium sulfate), and evaporated to give the 1-methanesulfonyl-4-(S)-methyl-8-methylnon-7-ene as a yellow oil which was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH2:14].[C:16]([O:20][C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH:27]([NH:31][C:32]([O:34][CH2:35][CH:36]1[C:48]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[C:42]2[C:37]1=[CH:38][CH:39]=[CH:40][CH:41]=2)=[O:33])[C:28](O)=[O:29])=[O:22])([CH3:19])([CH3:18])[CH3:17].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH:14][C:28](=[O:29])[CH:27]([NH:31][C:32]([O:34][CH2:35][CH:36]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:42]=2[C:43]2[C:48]1=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:33])[CH2:26][CH2:25][CH2:24][NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22]
Reactant: CC(C)(C)OC(=O)NCCCC(NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Reactant: COC(=O)c1ccc(C(=O)OC)c(N)c1
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C(=O)OC)c(NC(=O)C(CCCNC(=O)OC(C)(C)C)NC(=O)OCC2c3ccccc3-c3ccccc32)c1
Temperature: -15 °C
Reaction time: 1 h
Yield: 73.9 %

Procedure:
In anhydrous pyridine (30 ml), 2-amino-terephthalic acid dimethyl ester (manufactured by Merck Ltd.) (1.46 g) and 5-t-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-valeric acid (manufactured by Watanabe Chemical Industries, Ltd.) (3.18 g) were dissolved. The whole was cooled to −15° C. and added with phosphorus oxychloride (0.718 ml), followed by stirring at room temperature for 1 hour. After completion of the reaction, the whole was poured in ice-cold water and subjected to extraction with ethyl acetate. The extract was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution and dried with magnesium sulfate. After the solvent was distilled off, the resultant was subjected to azeotropic distillation with toluene. The residue was purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (3.33 g) as a white crystal.
Reaction SMILES: C[O:2][C:3]([C@H:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]1[S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:30][C:29]=2[CH2:41][CH2:42][CH3:43])=[CH:19][CH:18]=1)(=[O:16])=[O:15])=[O:4].[OH-].[Na+].O1CCCC1>CO>[O:34]([C:31]1[CH:32]=[CH:33][C:28]([O:27][CH2:26][CH2:25][CH2:24][O:23][C:20]2[CH:21]=[CH:22][C:17]([S:14]([N:6]3[C:7]4[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH2:13][C@@H:5]3[C:3]([OH:4])=[O:2])(=[O:16])=[O:15])=[CH:18][CH:19]=2)=[C:29]([CH2:41][CH2:42][CH3:43])[CH:30]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: CCCc1cc(Oc2ccccc2)ccc1OCCCOc1ccc(S(=O)(=O)N2c3ccccc3C[C@@H]2C(=O)OC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CCCc1cc(Oc2ccccc2)ccc1OCCCOc1ccc(S(=O)(=O)N2c3ccccc3C[C@@H]2C(=O)O)cc1
Reaction time: 8 h
Yield: 71.1 %

Procedure:
To a mixture of the title D compound, (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid methyl ester (1.47 g, 2.44 mmol) in methanol (50 mL) under nitrogen at room temperature is added 1N aqueous sodium hydroxide (4.9 mL, 4.9 mmol) dropwise. Upon complete addition, the mixture is stirred at room temperature for 45 minutes, at which time 5 mL of tetrahydrofuran is added to facilitate the dissolution of the starting material. The mixture is stirred overnight. The reaction mixture is concentrated in vacuo, the residue is partitioned between water (50 mL) and ether (50 mL). The aqueous layer is separated and acidified with 1N aqueous hydrochloric acid. The product is extracted into dichloromethane. The extract is washed with brine, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give 1.02 g of (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid as a white foamy solid. The solid is treated with ethanol (1 mL) which results in dissolution of the solid and upon standing crystals start to form. The crystals are separated and dried at high vacuum at 40° C. to give 0.85 g of pure (R)-1-{4-[3-(4-phenoxy-2-propyl-phenoxy)-propoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid: [M+1]+=588.46, [M−1]−=586.41.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH2:7][S:6](=[O:9])(=[O:8])[CH2:5][C:4]([CH3:11])([CH3:10])[NH:3]1.[C-:13]#[N:14].[K+].[CH2:16]=O>Cl>[C:13]([CH2:16][N:3]1[C:2]([CH3:12])([CH3:1])[CH2:7][S:6](=[O:9])(=[O:8])[CH2:5][C:4]1([CH3:11])[CH3:10])#[N:14]
Reactant: CC1(C)CS(=O)(=O)CC(C)(C)N1
Reactant: [C-]#N
Reactant: C=O
Agent: Cl
Agent: [K+]
Product: CC1(C)CS(=O)(=O)CC(C)(C)N1CC#N
Temperature: 45 °C
Reaction time: 0.33 h

Procedure:
19.1 g (0.1 mole) of 2,2,6,6-tetramethyl-1-aza-4-thiacyclohexane-4,4-dioxide is added, with ice cooling, to 20 ml of 5N hydrochloric acid; 6.5 g of potassium cyanide is added and then in ca. 20 minutes, with good stirring, an addition made dropwise of 12.5 g of a 30% formaldehyde solution. The reaction mixture is subsequently stirred for 15 hours at 45° C. After cooling, the precipitate is filtered off under suction, washed with water, dried, and recrystallised from toluene/hexane to obtain 1-cyanomethyl-2,2,6,6-tetramethyl-1-aza-4-thiacyclohexane-4,4-dioxide (11), M.P. 188° C.
Reaction SMILES: CC(S(C(SC)C)=[O:6])SC.C([Li])CCC.[F:16][C:17]([F:34])([F:33])[C:18]1[CH:19]=[C:20]([CH:30]=[CH:31][CH:32]=1)[O:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=[O:26].[O:35]1[CH2:39]CCC1>CCCCCC>[OH:6][CH:39]([OH:35])[C:25]([C:24]1[CH:27]=[CH:28][CH:29]=[C:22]([O:21][C:20]2[CH:19]=[C:18]([C:17]([F:33])([F:34])[F:16])[CH:32]=[CH:31][CH:30]=2)[CH:23]=1)=[O:26]
Reactant: CSC(C)S(=O)C(C)SC
Reactant: O=Cc1cccc(Oc2cccc(C(F)(F)F)c2)c1
Reactant: C1CCOC1
Agent: [Li]CCCC
Solvent: CCCCCC
Product: O=C(c1cccc(Oc2cccc(C(F)(F)F)c2)c1)C(O)O
Temperature: 10 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of 3.10 g of methyl methyl thiomethylsulfoxide in 20 ml of tetrahydrofuran under argon in an ice bath was added 10.4 ml. of 2.4M n-butyllithium in hexane via a syringe during 15 minutes, maintaining the temperature at 10°-15° C. The mixture was stirred at 10° C. for 10 minutes, then recooled and a solution of 5.32 g of m-[m-(trifluoromethyl)phenoxy]benzaldehyde in 10 ml of tetrahydrofuran was added during 10 minutes, maintaining the temperature at <10° C. The resulting solution was stirred at 0°-5° C. for one hour, then the tetrahydrofuran was evaporated. The resulting yellow foam was added to dimethyl sulfoxide and cooled in an ice bath while aqueous hydrobromic acid was added. The reaction was then heated at 50° C. overnight, then poured into ice and extracted with ethyl acetate. The extract was washed with water, saturated sodium bicarbonate and brine, dried and evaporated, giving 2,2-dihydroxy-3'-(α,α,α-trifluoro-m-tolyloxy)acetophenone as a yellow oil.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18]([C:21]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[CH:44][CH:45]=2)=[N:8]1.[CH3:47][O:48][C:49]([C:51](Cl)=[O:52])=[O:50].C(N(CC)CC)C>O1CCCC1>[CH3:47][O:48][C:49]([C:51](=[O:52])[NH:46][C:42]1[CH:43]=[CH:44][CH:45]=[C:40]([C:9]2[C:10]3[C:15](=[CH:14][CH:13]=[C:12]([C:16]4[N:20]=[CH:19][N:18]([C:21]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=5)[N:17]=4)[CH:11]=3)[N:7]([CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[N:8]=2)[CH:41]=1)=[O:50]
Reactant: COC(=O)C(=O)Cl
Reactant: Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)C(=O)Nc1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenylamine (0.150 g, 0.248 mmol) in 2.5 mL of tetrahydrofuran was added methyl(chlorocarbonyl)formate (0.068 g, 0.496 mmol), followed by triethyl amine (0.173 mL, 1.24 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and water. The crude material that was obtained from evaporation of the extracts was not purified further. (Yield not calculated) ES-MS (m/z) 689 [M+H]+.
Reaction SMILES: [CH2:1]([NH:4][CH:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1)[CH2:2][CH3:3].[N+:18]([C:21]1[CH:31]=[CH:30][C:24]([CH2:25][O:26][C:27](Cl)=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19].[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>C(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([CH2:25][O:26][C:27]([N:4]([CH:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10]2)[CH2:1][CH2:2][CH3:3])=[O:28])=[CH:30][CH:31]=1)([O-:20])=[O:19]
Reactant: CCCNC1CCN(C(=O)OC(C)(C)C)CC1
Reactant: O=C(Cl)OCc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCN(C(=O)OCc1ccc([N+](=O)[O-])cc1)C1CCNCC1

Procedure:
The title compound was prepared by the reaction of 4-(N-(prop-1-yl)amino)-1-tert-butoxycarbonylpiperidine (from Example 17, Step A) with (4-nitrobenzyl)chloroformate, followed by treatment of the product with 50% TFA in CH2Cl2 to remove the tert-butoxycarbonyl group, affording the title compound. ESI-MS: 322.2 (M+H).
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1.[CH3:13][N:14]1[CH:18]=[CH:17][CH:16]=[CH:15]1.[OH2:19]>C(O)(=O)C.ClCCl>[CH3:13][N:14]1[C:18]([C:3]2[C:4](=[O:11])[C:5]3[C:10]([C:1](=[O:12])[CH:2]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)=[CH:17][CH:16]=[C:15]1[C:3]1[C:4](=[O:11])[C:5]2[C:10]([C:1](=[O:19])[CH:2]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: Cn1cccc1
Reactant: O
Reactant: O=C1C=CC(=O)c2ccccc21
Solvent: CC(=O)O
Solvent: ClCCl
Product: Cn1c(C2=CC(=O)c3ccccc3C2=O)ccc1C1=CC(=O)c2ccccc2C1=O
Yield: 90 %

Procedure:
The procedure described in the article Chemistry Express 1990, Vol. 5, No. 10, pages 749-752, the disclosure of which is specifically incorporated by reference herein, was followed, by stirring 10 millimol of 1,4-naphthoquinone with 2.5 millimol of N-methylpyrrole in 40 ml of acetic acid at 50° C. for 5 hours. The reaction mixture was diluted with 300 ml of dichloromethane and the resulting mixture was then poured into a large volume of water (300 ml). The organic phase was then separated out and washed four times with 100 ml of water and finally with saturated aqueous NaCl solution. The resulting organic phase was dried over Na2SO4 and then concentrated under vacuum. The 1-methyl-2,5-bis(1,4-naphthoquinon-2-yl)pyrrole was thus obtained in a yield of 90%.
Reaction SMILES: [CH2:1]([N:8]=[C:9]([C:11]1[C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=[CH:13][N:12]=1)[OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][I:21].O>[N+](C)([O-])=O>[I-:21].[CH2:1]([N:8]=[C:9]([C:11]1[C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=[CH:13][N+:12]=1[CH3:20])[OH:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CI
Reactant: O=C(O)c1cccnc1C(O)=NCc1ccccc1
Solvent: C[N+](=O)[O-]
Solvent: O
Product: C[n+]1cccc(C(=O)O)c1C(O)=NCc1ccccc1
Product: [I-]
Reaction time: 8 h

Procedure:
190.5 g (0.8 mol) of pyridine-2,3-dicarboxylic acid N-benzylimide are dissolved in 800 ml of nitromethane, while heating, and 136 g (0.96 mol) of methyl iodide are added dropwise. The mixture is then boiled for 8 hours while cooling under reflux (cooling water 0° C.). After cooling, the solid is filtered off with suction and washed with methylene chloride. 123 g of dark red crystals having a melting point of 162°-165° C. (decomposition) are obtained.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH:4]([NH:16][C:17](=[O:30])[CH:18]([NH:22]C(OC(C)(C)C)=O)[CH2:19][O:20][CH3:21])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[Cl:32]CCCl>Cl.O1CCOCC1>[ClH:32].[CH3:1][O:2][C:3](=[O:31])[CH:4]([NH:16][C:17](=[O:30])[CH:18]([NH2:22])[CH2:19][O:20][CH3:21])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1
Reactant: COCC(NC(=O)OC(C)(C)C)C(=O)NC(Cc1ccc2ccccc2c1)C(=O)OC
Reactant: ClCCCl
Agent: Cl
Solvent: C1COCCO1
Product: COCC(N)C(=O)NC(Cc1ccc2ccccc2c1)C(=O)OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-(2-tert-butoxycarbonylamino-3-methoxy-propionylamino)-3-naphthalen-2-yl-propionic acid methyl ester, 57, (5.2 g, 12.1 mmol) is dissolved in 4M hydrogen chloride in dioxane (40 mL) and stirred at room temperature for 1 hour. 1,2-Dichloroethane (40 mL) is added. The solution is concentrated in vacuo to afford 4.43 g (quantitative yield) of the desired product.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[OH-].[Na+:12].Cl[CH:14]([OH:16])[CH3:15]>C1(C)C(C)=CC=CC=1.O.C(OCCO)C>[C:1]([O-:10])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Na+:12].[C:1]([O:10][CH2:15][CH2:14][OH:16])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CC(O)Cl
Reactant: CCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Solvent: O
Solvent: CCOCCO
Product: CCCCCCCC(=O)OCCO
Product: CCCCCCCC(=O)[O-]
Yield: 66 %
Yield: 200 %

Procedure:
Sodium caprylate (2 mol) was prepared by neutralization of caprylic acid (2 mol; 288.4 g; 317.4 ml) in 750 ml xylene with sodium hydroxide (2 mol; 80 g) in water (160 ml). The reaction mixture was freed of water and then heated with chloroethanol (2.1 mol; 170 g; 204.4 ml) with addition of 2-ethoxyethanol (1000 ml) as a solvent under reflux for 28 hours. The precipitated NaCl was filtered off and washed with 2-ethoxyethanol. The filtrate was distilled and 66% of 2-hydroxyethyl caprylate was obtained; b.p. 141° C./266 Pa. Elemental analysis for C10H20O3 theory: 63.79% C, 10.71% H; found: 63.54% C, 10.93% H. The structure was confirmed by infrared and 13C--NMR spectroscopy. Further procedure was carried out according to example 1.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:4]([CH3:13])[CH2:3]1.[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:16]=1[C:17](Cl)=[O:18]>C1COCC1>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:26])[F:27])=[CH:20][C:16]=1[C:17]([NH:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:4]([CH3:13])[CH2:3]1)=[O:18]
Reactant: CCOC(=O)C1CCC(N)CC1C
Reactant: O=C(Cl)c1cc(C(F)(F)F)ccc1Cl
Solvent: C1CCOC1
Product: CCOC(=O)C1CCC(NC(=O)c2cc(C(F)(F)F)ccc2Cl)CC1C
Temperature: 0 °C
Reaction time: 3 h

Procedure:
Ethyl 4-amino-2-methylcyclohexanecarboxylate (780 mg, 4.21 mmol) in THF (10 ml) is treated with TEA (1.174 ml, 8.42 mmol) and the reaction mixture is cooled to 0° C. 2-Chloro-5-(trifluoromethyl)benzoyl chloride (921 mg, 3.79 mmol) is added dropwise and the reaction mixture is stirred and allowed to warm to RT. After 3 hours, the reaction is quenched with water and partitioned between EtOAc and sat. sodium bicarbonate. The organic portion is separated and dried over MgSO4 and concentrated in vacuo to afford the title compound which is used without further purification. [MH]+ 392.26.
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([O:17][CH3:18])[C:15]=1[CH3:16])[C:10]([OH:12])=O.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[OH:26].[CH:27](N(C(C)C)CC)(C)C>C1COCC1>[CH3:18][O:17][C:14]1[CH:13]=[C:9]([CH:8]=[C:7]([O:6][CH3:5])[C:15]=1[CH3:16])[C:10]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][CH3:27])=[O:12]
Reactant: Nc1ccccc1O
Reactant: COc1cc(C(=O)O)cc(OC)c1C
Reactant: CCN(C(C)C)C(C)C
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Product: COc1ccccc1NC(=O)c1cc(OC)c(C)c(OC)c1
Reaction time: 8 h

Procedure:
Thionyl chloride (10 mL) and 3,5-dimethoxy-4-methylbenzoic acid (1.0 g, 5.1 mmol) was refluxed under argon until no starting material was observed by TLC. After cooling reaction mixture to rt, concentrated mixture in vacuo. The resulting brown oil was added to a mixture of 2-aminophenol (580 mg, 5.3 mmol), diisopropylethyl amine (1.1 mL, 6.3 mmol) and THF (40 mL) at 0° C. and then brought to rt overnight. After concentrating mixture in vacuo, the resulting brown oil was purified by flash chromatography on silica gel, using a gradient elution from 1:9 EtOAc:hexanes to 1:1 EtOAc:hexanes. This afforded the desired intermediate, 3,5-dimethoxy-N-(2-methoxyphenyl)-4-methylbenzamide, as a colorless solid.
Reaction SMILES: ClCCl.C(N(CC)CC)C.[NH2:11][C:12]1[CH:23]=[CH:22][CH:21]=[CH:20][C:13]=1[CH2:14][C:15]1[NH:16][CH:17]=[CH:18][N:19]=1.[C:24](Cl)(Cl)=[S:25]>C(Cl)(Cl)(Cl)Cl>[N:19]1[CH:18]=[CH:17][N:16]2[C:15]=1[CH2:14][C:13]1[CH:20]=[CH:21][CH:22]=[CH:23][C:12]=1[NH:11][C:24]2=[S:25]
Reactant: Nc1ccccc1Cc1ncc[nH]1
Reactant: S=C(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: S=C1Nc2ccccc2Cc2nccn21

Procedure:
Dichloromethane (42,000 ml) and 5,120 g (50.65 moles) of triethylamine are charged into a 20 gallon flask. The solution is stirred under nitrogen atmosphere and 4,370 g (25.23 moles) of 2-(2-aminobenzyl)imidazole were added. The suspension is cooled to 0°-5° and 3,421 g (29.75 moles) of 85% thiophosgene in carbon tetrachloride are added over 3 hours, during which time the reaction temperature rises slowly to 15°. The suspension is then stirred at 10° for 4 hours and at ambient temperature overnight. The precipitated product is collected, washed with 2×3000 ml of dichloromethane and 5×4000 ml of water, and dried (5 mm Hg/60°) to give 11H-imidazo[1,2-c][1,3]benzodiazepine-5(6H)-thione, m.p. 182°-183°.