Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([CH3:7])([CH3:6])[C:3](O)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:39][C:40]1[C:45]([CH2:46][NH2:47])=[CH:44][CH:43]=[C:42]([Cl:48])[C:41]=1[NH:49][C:50]1[N:54]([CH3:55])[C:53]2[CH:56]=[C:57]([N:63]3[CH2:68][CH2:67][CH:66]([C:69]([F:72])([F:71])[F:70])[CH2:65][CH2:64]3)[C:58]([C:60]([OH:62])=[O:61])=[CH:59][C:52]=2[N:51]=1>CN(C=O)C>[Cl:39][C:40]1[C:45]([CH2:46][NH:47][C:3](=[O:4])[C:2]([F:1])([CH3:7])[CH3:6])=[CH:44][CH:43]=[C:42]([Cl:48])[C:41]=1[NH:49][C:50]1[N:54]([CH3:55])[C:53]2[CH:56]=[C:57]([N:63]3[CH2:68][CH2:67][CH:66]([C:69]([F:72])([F:71])[F:70])[CH2:65][CH2:64]3)[C:58]([C:60]([OH:62])=[O:61])=[CH:59][C:52]=2[N:51]=1
Reactant: Cn1c(Nc2c(Cl)ccc(CN)c2Cl)nc2cc(C(=O)O)c(N3CCC(C(F)(F)F)CC3)cc21
Reactant: CC(C)(F)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1c(Nc2c(Cl)ccc(CNC(=O)C(C)(C)F)c2Cl)nc2cc(C(=O)O)c(N3CCC(C(F)(F)F)CC3)cc21
Reaction time: 0.17 h

Procedure:
A mixture of 2-fluoroisobutyric acid (191 mg, 1.80 mmol), TBTU (578 mg, 1.80 mmol), DIPEA (1.00 mL, 5.7 mmol) and 10 mL DMF is stirred for 10 min and then the mixture is added to 2-{2,6-dichloro-3-[aminomethyl]-phenylamino}-6-[4-trifluoromethyl-piperidinyl]-1-methyl-1H-benzimidazole-5-carboxylic acid (929 mg, 1.80 mmol) in 10 mL DMF and it is stirred overnight. Then the mixture is concentrated and purified via prep HPLC.
Reaction SMILES: [C:1]([Si:5]([O:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[F:26])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)CCN(C)C.[Li]CCCC.[CH2:44]([O:46][C:47](=[O:50])[CH:48]=[O:49])[CH3:45].Cl>COCCOC.CCCCCC.C1(C)C=CC=CC=1>[CH2:44]([O:46][C:47](=[O:50])[CH:48]([C:21]1[C:22]([F:25])=[CH:23][CH:24]=[C:19]([O:18][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:20]=1[F:26])[OH:49])[CH3:45]
Reactant: CCOC(=O)C=O
Reactant: CC(C)(C)[Si](Oc1ccc(F)cc1F)(c1ccccc1)c1ccccc1
Agent: CN(C)CCN(C)CCN(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: COCCOC
Solvent: Cc1ccccc1
Product: CCOC(=O)C(O)c1c(F)ccc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1F
Temperature: -70 °C
Reaction time: 1 h
Yield: 54 %

Procedure:
A solution under Ar of tert-butyl-(2,4-difluoro-phenoxy)-diphenyl-silane (102 g) and 1,1,4,7,7-pentamethyldiethylenetriamine (50.6 g) in DME (800 ml) was cooled to −70° C. before addition of 1.6 N n-BuLi in hexane (182 ml) over a period of 1 h. The yellow solution was stirred 1 h at −70° C. 50% glyoxalic acid ethylester in toluene (113 g) was added over a period of 1 h. The reaction mixture was stirred 2 h more at −70° C. before heating up over 1 h to 0° C. Sat. NH4 sol. (300 ml) was added and the pH was lowered to pH=6 with 2 N HCl. The product was extracted with AcOEt (2×400 ml). The organic layers were washed with brine (500 ml) and dried (Na2SO4) and the solvent was evaporated. CC (Hept to Hept/AcOEt 9:1) afforded 70.8 g (54%) of (RS)-[3-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester. Yellowish oil. MS 488.5 ([M+H]+).
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[NH2:18].[Cl:19][CH2:20][C:21](Cl)=[O:22].C(OCC)(=O)C.CCCCCC>CN(C)C=O.CCO>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[NH:18][C:21](=[O:22])[CH2:20][Cl:19]
Reactant: Nc1ccc2c(c1N)C(=O)c1ccccc1C2=O
Reactant: O=C(Cl)CCl
Solvent: CCO
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Nc1c(NC(=O)CCl)ccc2c1C(=O)c1ccccc1C2=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 65 %

Procedure:
1,2-diaminoanthraquinone (1.19 g, 5 mmole) was dissolved in anhydrous N, N-dimethylformamide (30 ml). Nitrogen was insufflated in the reaction flask at room temperature. Chloroacetyl chloride (0.5 ml, 6 mmole) was added into the solution. The mixture was stirred at room temperature for 2 hours. After completion of reaction, the mixture was put in an ice-water bath (200 ml), and stood still for 10 to 20 minutes to allow precipitation. The precipitate was filtered and washed with hot ethanol to obtain a red compound CC-05. Mol. Wt.: 314.7231 (C16H11N2O3); Rf: 0.82 (ethyl acetate:n-hexane=1:4); Yield: 65%; Mp.: 193-194° C. (EtOH); HRMS (EI) m/z: calcd [M]+, 314.0458 (C16H11N2O3+); found, 314.0455; 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 4.38 (s, 2H, —CH2Cl), 7.48 (d, J=7.8 Hz, 1H, Ar—H), 7.74 (d, J=8.1 Hz, 1H, Ar—H), 7.84 (dd, J=8.1 Hz, J=1.8 Hz, 1H, Ar—H), 7.88 (t, J=1.5 Hz, 1H, Ar—H), 7.91 (dd, J=7.5 Hz, J=1.5 Hz, 1H, Ar—H), 7.96 (br, 2H, Ar—NH2), 8.14 (dd, J=7.2 Hz, J=1.8 Hz, 1H, Ar—H), 8.22 (dd, J=7.8 Hz, J=1.5 Hz, 1H, Ar—H), 9.80 (s, 1H, Ar—NH—); 13C-NMR (75 MHz, DMSO-d6) δ (ppm): 43.25, 112.98, 115.62, 126.69, 126.55, 129.88, 128.88, 128.92, 130.25, 131.01, 132.64, 133.65, 134.37, 165.72 (NCO), 182.28 (CO), 184.38 (CO).
Reaction SMILES: OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([NH:12][C:13](=[O:32])[CH2:14][NH:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH:25]([OH:30])[C:26]([F:29])([F:28])[F:27])[CH:23]=3)[N:18]([CH3:31])[N:17]=2)[CH2:9]1.[CH2:33]([C:35]1[S:36][C:37]([C:40]2([OH:47])[CH2:45][CH2:44][C:43](=O)[CH2:42][CH2:41]2)=[CH:38][N:39]=1)[CH3:34]>>[CH2:33]([C:35]1[S:36][C:37]([C:40]2([OH:47])[CH2:41][CH2:42][CH:43]([N:8]3[CH2:11][CH:10]([NH:12][C:13](=[O:32])[CH2:14][NH:15][C:16]4[C:24]5[C:19](=[CH:20][CH:21]=[C:22]([CH:25]([OH:30])[C:26]([F:29])([F:28])[F:27])[CH:23]=5)[N:18]([CH3:31])[N:17]=4)[CH2:9]3)[CH2:44][CH2:45]2)=[CH:38][N:39]=1)[CH3:34]
Reactant: CCc1ncc(C2(O)CCC(=O)CC2)s1
Reactant: Cn1nc(NCC(=O)NC2CNC2)c2cc(C(O)C(F)(F)F)ccc21
Solvent: O=C(O)C(F)(F)F
Product: CCc1ncc(C2(O)CCC(N3CC(NC(=O)CNc4nn(C)c5ccc(C(O)C(F)(F)F)cc45)C3)CC2)s1

Procedure:
The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-[1-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-indazol-3-ylamino]-acetamide TFA salt (as prepared in Example 60, Step B) and 4-(2-ethyl-thiazol-5-yl)-4-hydroxy-cyclohexanone using the procedure described in Step E of Example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[C:14]4[CH2:15][NH:16][CH2:17][CH2:18][C:13]=4[NH:12][C:7]=3[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH:19](O)=O>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[C:14]4[CH2:15][NH:16][CH2:17][CH:18]([CH3:19])[C:13]=4[NH:12][C:7]=3[CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=CO
Reactant: Clc1ccc2c(c1)ncc1[nH]c3c(c12)CNCC3
Product: CC1CNCc2c1[nH]c1cnc3cc(Cl)ccc3c21
Temperature: 90 °C

Procedure:
A mixture prepared from 3.7 g of 3-chloro-7,8,9,10-tetrahydro-11H-pyrido[3',4':4,5]pyrrolo[2,3-c]quinoline, 0.45 g of paraformaladehyde and 100 ml of formic acid was heated at 90° C. for one hour. The reaction was quenched with water and the solution was made alkaline (pH9) with a sodium hydroxide solution. The crystalline product was filtered, washed with water and purified by HPLC using dichloromethane/methanol=8:2 as an eluent. Clean fractions were combined and concentrated, and the crystalline residue was stirred in isopropanol and filtered. The yield was 2.1 g, mp=286°-287° C.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([N:11]([CH3:30])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[O:10].[C:31]1([CH3:41])[CH:36]=[CH:35][C:34]([S:37](Cl)(=[O:39])=[O:38])=[CH:33][CH:32]=1.[OH-].[Na+]>O1CCOCC1>[S:37]([O:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([N:11]([CH3:30])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[O:10])([C:34]1[CH:35]=[CH:36][C:31]([CH3:41])=[CH:32][CH:33]=1)(=[O:39])=[O:38]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCCCCCCCCCCCCCCCCCN(C)C(=O)c1ccccc1CO
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCCCCCCCCCCCCCCCCCN(C)C(=O)c1ccccc1COS(=O)(=O)c1ccc(C)cc1

Procedure:
A solution of [2-(hydroxymethyl)phenyl]-N-methyl-N-octadecylformamide and p-toluenesulfonyl chloride in 1,4-dioxane is added to sodium hydroxide solution and the reaction is effected at room temperature to obtain [2-(tosyloxymethyl)phenyl]-N-methyl-N-octadecylformamide.
Reaction SMILES: [Si]([O:8][C:9]1([C:12]2[CH:31]=[CH:30][C:15]([N:16]=C(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:14][C:13]=2[F:32])[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.Cl>C1COCC1>[NH2:16][C:15]1[CH:30]=[CH:31][C:12]([C:9]2([OH:8])[CH2:10][CH2:11]2)=[C:13]([F:32])[CH:14]=1
Reactant: CC(C)(C)[Si](C)(C)OC1(c2ccc(N=C(c3ccccc3)c3ccccc3)cc2F)CC1
Agent: Cl
Solvent: C1CCOC1
Product: Nc1ccc(C2(O)CC2)c(F)c1
Reaction time: 1 h
Yield: 41.4 %

Procedure:
To a stirred solution of 4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-N-(diphenylmethylene)-3-fluoroaniline (4.5 mg, 10.11 mmol, 1.0 eq) in THF (10 mL) was added 1N HCl (20 mL) and stirred vigorously for 1 h. The mixture was extracted with EtOAc (20 mL). The aqueous layer was basified with 1N aq. NaOH (30 mL) and extracted with EtOAc (50 mL). The combined organic layers were extracted with brine (20 mL) and dried over Na2SO4 and the solvent evaporated under vacuum; the resulting residue was purified by CC using EtOAc/PE (1:1) as eluent to get 1-(4-amino-2-fluorophenyl)cyclopropanol (0.7 g, 49%, yellow solid; TLC system: EtOAc/PE (1:1), Rf: 0.25).
Reaction SMILES: Cl.[CH2:2]([NH2:5])[CH2:3][CH3:4].[O:6]1[C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([CH2:16][CH2:17][CH2:18][C:19](O)=[O:20])[C:10]=2[O:9][CH:8]=[CH:7]1.C(Cl)CCl>CN(C)C=O>[CH2:2]([NH:5][C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C:15]1[C:10]2[O:9][CH:8]=[CH:7][O:6][C:11]=2[CH:12]=[CH:13][CH:14]=1)[CH2:3][CH3:4]
Reactant: O=C(O)CCCc1cccc2c1OC=CO2
Reactant: CCCN
Agent: Cl
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: CCCNC(=O)CCCc1cccc2c1OC=CO2
Temperature: 0 °C
Reaction time: 12 h

Procedure:
A suspension of 0.29 g (2.6 mmol) of n-propylamine hydrochloride in 7 ml of anhydrous N,N-dimethylformamide is cooled to 0° C. and then 0.33 g (3.54 mmol) of N,N-dimethylaminopyridine are added to the mixture. After the addition of 0.41 g (2.36 mmol) of the acid obtained in Step F of Example 40, 0.5 g (2.6 mmol) of EDC is added to the mixture. The solution is stirred for 12 hours under argon at room temperature and then the solvent is evaporated off in vacuo. The residue is taken up in a water/ethyl acetate (1/1) mixture and then the aqueous phase is extracted with ethyl acetate. The organic phase is dried over magnesium sulphate and then concentrated under reduced pressure. Chromatography over silica gel (eluant:AcOEt/PE:70/30) yields the title amide in the form of a clear syrup.
Reaction SMILES: [C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.COC1C(OC)=C(OC)C=C(/[CH:46]=[CH:47]/[C:48]([N:50]2[C:55](=[O:56])[CH:54]=[CH:53][CH2:52]C2)=[O:49])C=1.N(CCO)(CCO)CCO>C1(C)C=CC=CC=1.C1COCC1>[C:48]([NH:50][C:55](=[O:56])/[CH:54]=[CH:53]/[CH3:52])(=[O:49])[C:47]([CH3:46])=[CH2:1]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: COc1cc(/C=C/C(=O)N2CCC=CC2=O)cc(OC)c1OC
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Solvent: OCCN(CCO)CCO
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: C=C(C)C(=O)NC(=O)/C=C/C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 47 %

Procedure:
Experimental Procedure: Triphenylphosphine (79.0 mg, 0.30 mmol) and DIAD (61.0 mg, 0.30 mmol) were dissolved to a 1:1 mixture of THF and toluene (2 mL); then mono-demethylated piperlongumine (46.0 mg, 0.15 mmol) was added. After 10 min, triethanolamine (6.80 mg, 0.05 mmol) was added to the mixture. The reaction was stirred at room temperature for 3 h. At the end, the solvent was evaporated under vacuum. The crude product was purified by preparative TLC(CH2Cl2/MeOH=9/1) to afford the desired product in 47% yield.
Reaction SMILES: CS(O[CH2:6][CH2:7][N:8]1[C:16]2[N:15]=[C:14]([NH2:17])[N:13]3[N:18]=[C:19]([C:21]4[O:22][CH:23]=[CH:24][CH:25]=4)[N:20]=[C:12]3[C:11]=2[CH:10]=[CH:9]1)(=O)=O.Cl.[F:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=1[N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=1[N:35]1[CH2:36][CH2:37][N:38]([CH2:6][CH2:7][N:8]2[C:16]3[N:15]=[C:14]([NH2:17])[N:13]4[N:18]=[C:19]([C:21]5[O:22][CH:23]=[CH:24][CH:25]=5)[N:20]=[C:12]4[C:11]=3[CH:10]=[CH:9]2)[CH2:39][CH2:40]1
Reactant: CS(=O)(=O)OCCn1ccc2c1nc(N)n1nc(-c3ccco3)nc21
Reactant: Fc1ccc(F)c(N2CCNCC2)c1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1nc2c(ccn2CCN2CCN(c3cc(F)ccc3F)CC2)c2nc(-c3ccco3)nn12
Temperature: 100 °C
Reaction time: 5 h

Procedure:
To a solution of the title D compound, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), the title E compound, 1-(2,5-difluorophenyl)piperazine hydrochloride (0.33 mmol) and 0.06 mL of DIEA are added and the solution is stirred at 100° C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60° C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give 7-(2-(4-(2,5-difluorophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine: LC/MS (M+1=465.2). 1H NMR (DMSO-d6, 400 MHz) δ 2.64 (m, 4H), 2.76 (t, 2H, J=64 Hz), 3.01 (m, 4H), 4.28 (t, 2H, J=6.4 Hz), 6.60 (d, 1H, J=3.2 Hz), 6.72 (m, 1H), 6.75 (m, 1H), 6.80-6.85 (m, 1H), 7.12 (m, 1H), 7.18 (m, 2H), 7.51 (br s, 2H), 7.91 (s, 1H). Anal. calculated for (C23H22F2N8O): C, 59.48; H, 4.77; F, 8.18; N, 24.12; 0, 3.44. Found C, 59.45; H, 4.70; N, 24.19.
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]([F:22])=[C:18]([CH3:23])[NH:17][C:16]2=[O:24])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].S(OC)(O[CH3:29])(=O)=O>CN(C)C=O>[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]([F:22])=[C:18]([CH3:23])[N:17]([CH3:29])[C:16]2=[O:24])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]
Reactant: COS(=O)(=O)OC
Reactant: Cc1[nH]c(=O)n(-c2cc(C(=O)OC(C)C)c(Cl)cc2F)c(=O)c1F
Solvent: CN(C)C=O
Product: Cc1c(F)c(=O)n(-c2cc(C(=O)OC(C)C)c(Cl)cc2F)c(=O)n1C

Procedure:
using isopropyl 2-chloro-4-fluoro-5-[3,6-dihydro-5-fluoro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-benzoate and dimethyl sulphate in dimethylformamide there is obtained isopropyl 2-chloro-4-fluoro-5-[3,6-dihydro-3,4-dimethyl-5-fluoro-2,6-dioxo-1(2H)-pyrimidinyl]-benzoate, m.p. 112°-115° C.,
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[C:6]([NH:11][CH2:12][CH2:13][C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)(=[O:10])[CH2:7][CH2:8][CH3:9]>>[C:6]([NH:11][CH2:12][CH2:13][C:14]1[S:15][C:16]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:17][CH:18]=1)(=[O:10])[CH2:7][CH2:8][CH3:9]
Reactant: O=S(=O)(O)Cl
Reactant: CCCC(=O)NCCc1cccs1
Product: CCCC(=O)NCCc1ccc(S(=O)(=O)Cl)s1

Procedure:
6.6 ml (0.100 mol) of chlorosulphonic acid are cooled in an ice bath to 4°C whilst stirring, and 3.35 g (0.017 mol) of 2-(2-butyramido-ethyl)-thiophene are then added over the course of 15 minutes in such a way that the reaction temperature does not rise above 8°C. The ice bath is then removed and the reaction mixture is stirred for 30 minutes at 28°-30°C and then poured, whilst stirring, onto 100 g of ice under which there is a layer of 50 ml of methylene chloride. The methylene chloride phase is separated off and the aqueous phase is extracted with a further 50 ml of methylene chloride. The combined extracts are washed with 50 ml of concentrated sodium chloride solution, dried over sodium sulphate and evaporated at 40°C bath temperature with the aid of a rotary evaporator. The crude 5-(2-butyramido-ethyl)-2-thiophenesulphonyl chloride is obtained.
Reaction SMILES: C[CH:2]1[CH2:7][CH:6](O)C(C(C)C)[CH2:4][CH2:3]1.[N+](C1C=CC(C(Cl)=O)=CC=1)([O-])=O.[C:24]([O:27][CH2:28]C)(=[O:26])[CH3:25]>>[CH3:28][O:27][C:24]([C:25]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)=[O:26]
Reactant: CCOC(C)=O
Reactant: CC1CCC(C(C)C)C(O)C1
Agent: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Product: COC(=O)c1ccccc1

Procedure:
After stirring for an additional half hour and adding 50 ml of petroleum ether (40-60) the formed precipitate was sucked off, washed with petroleum ether and dried. The desired product was obtained in a yield of 2.0 g; melting-point 169°-170° C. The starting aniline was obtained from the corresponding nitro compound by reduction with hydrogen under the influence of Raney nickel as a catalyst, ethyl acetate being used as a solvent. 1-Nitro-4-dl-methyloxycarbonylbenzene was prepared by reaction of dl-menthol with 4-nitrobenzoylchloride.
Reaction SMILES: [CH:1](=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[OH-].[K+].Br[CH2:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)=[O:15]>CO>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([C:14]([C:13]2[O:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[CH:1]=2)=[O:15])=[CH:17][CH:18]=1
Reactant: O=Cc1ccccc1O
Reactant: COc1ccc(C(=O)CBr)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: COc1ccc(C(=O)c2cc3ccccc3o2)cc1

Procedure:
To 11.0 g. (0.09 mol.) of salicylaldehyde in 30 ml. of dry methanol was added 5.1 g. (0.09 mol.) of potassium hydroxide dissolved in 50 ml. of methanol. The solution was refluxed for 10 minutes and 20.5 g. (0.09 mol.) of α-bromo-p-methoxyacetophenone dissolved in 50 ml. of warm methanol was added dropwise but rapidly over a 10 minute interval. The resulting solution was refluxed for one hour, then filtered and concentrated. The residue was dissolved in ether and the ether solution was washed with water. The aqueous washings were extracted twice with ether and the ethereal extracts were combined, reduced in volume, refluxed with decolorizing carbon, filtered, dried (MgSO4) and concentrated to give 2-(4'-methoxybenzoyl)benzofuran which was recrystallized from isopropanol, m.p. 93°-94°.
Reaction SMILES: [OH:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:16])([CH3:15])[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]Br>C(O)C>[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][CH2:9][C:10]([CH3:15])([CH3:16])[C:11]([O:13][CH3:14])=[O:12])=[CH:17][CH:18]=1
Reactant: COC(=O)C(C)(C)CCCOc1ccc(O)cc1
Reactant: BrCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: COC(=O)C(C)(C)CCCOc1ccc(OCCCCCBr)cc1

Procedure:
To 2.52 g of methyl 5-(p-hydroxyphenoxy)-2,2-dimethylpentanoate and 1.38 g of anhydrous potassium carbonate was added 30 ml of ethanol and the mixture was heated under reflux for 30 minutes while stirring. After cooling, 2.53 g of 1,5-dibromopentane was added thereto and the mixture was reacted overnight with heating under reflux. After the solvent was removed by distillation under reduced pressure, water was added to the resulting residue followed by extracting with chloroform. After the chloroform layer was successively washed with an aqueous saturated hydrogen sodium carbonate solution and then an aqueous saturated sodium chloride solution, the chloroform layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the resulting residue was subjected to silica gel column chromatography. The product was eluted using an n-hexane-ethyl acetate mixture (8:1 in a volume ratio). The solvent was removed by distillation to give the desired product, methyl 5-[p-(5-bromopentyloxy)phenoxy]-2,2-dimethylpentanoate as an oily substance.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][N:7]1[CH:11]=[CH:10][C:9](/[CH:12]=[C:13]2\[CH2:14][N:15]([C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:16][CH2:17][C:18]\2=[O:19])=[CH:8]1)=[O:5])C.[BH4-].[Na+].[Cl-].[NH4+]>C(O)C>[CH3:1][O:3][C:4]([CH2:6][N:7]1[CH:11]=[CH:10][C:9](/[CH:12]=[C:13]2\[CH2:14][N:15]([C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:16][CH2:17][CH:18]\2[OH:19])=[CH:8]1)=[O:5]
Reactant: CCOC(=O)Cn1ccc(/C=C2\CN(C(c3ccccc3)(c3ccccc3)c3ccccc3)CCC2=O)c1
Agent: [BH4-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Product: COC(=O)Cn1ccc(/C=C2\CN(C(c3ccccc3)(c3ccccc3)c3ccccc3)CCC2O)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.9 %

Procedure:
To a solution of (E)-3-{[1-(ethoxycarbonylmethyl)pyrrol-3-yl]methylidene}-1-(triphenylmethyl)piperidin-4-one (19.4 g) in ethanol (100 ml) was added sodium borohydride (3.0 g) under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours. To the reaction mixture was added aqueous ammonium chloride solution, the resulting mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed in vacuo. To a solution of the residue in methanol (100 ml) was added potassium carbonate (10.6 g), and the resulting mixture was stirred at room temperature for 15 minutes. To the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to afford the title compound (12.1 g, yield: 64%) as a pale yellow amorphous solid.
Reaction SMILES: [F:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([F:11])[C:5]([F:12])=[C:4](F)[C:3]=1[F:14].[OH-:15].[K+]>CS(C)=O.O>[N+:8]([C:7]1[C:2]([F:1])=[C:3]([F:14])[C:4]([OH:15])=[C:5]([F:12])[C:6]=1[F:11])([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1c(F)c(F)c(F)c(F)c1F
Reactant: [OH-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1c(F)c(F)c(O)c(F)c1F
Reaction time: 24 h
Yield: 95 %

Procedure:
21.3 g of pentafluoronitrobenzene (0.1 mol) are dissolved in 400 ml of dimethyl sulfoxide; a solution of 11.2 g of potassium hydroxide (0.2 mol) in 100 ml of water is added drop wise to this solution with vigorous stirring. After 24 hours at room temperature, the crude product is washed by shaking with 200 ml of ethyl acetate and 400 ml of water. The organic phase is washed three times with water, dried over sodium sulfate and evaporated to half in a rotary evaporator. The reaction product is then recrystallized from a mixture of ethyl acetate and n-hexane (volume ratio 1:1) and then dried for 48 hours under nitrogen at 40° C./10 mbar in a vacuum drying cabinet (yield: 95%).
Reaction SMILES: [Na].[NH:2]1[CH:6]=[N:5][CH:4]=[N:3]1.[H-].[Na+].Br[CH2:10][CH2:11][CH2:12][Cl:13]>CN(C)C=O>[Cl:13][CH2:12][CH2:11][CH2:10][N:2]1[CH:6]=[N:5][CH:4]=[N:3]1
Reactant: c1nc[nH]n1
Reactant: ClCCCBr
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Product: ClCCCn1cncn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 34.6 %

Procedure:
A 1,2,4-triazole sodium salt (5 g, 54.91 mmol) was dissolved in dimethylformamide (50 mL) and the solution was cooled to 0° C. Then, sodium hydride (60%, 2.86 g, 71.38 mmol) was added thereto, followed by stirring for 30 minutes. 1-bromo-3-chloropropane (6.5 mL, 65.89 mmol) was added thereto, followed by stirring at room temperature for 12 hours, and the reaction was terminated with the addition of an ammonium chloride saturated solution. After extraction with ethyl acetate and water, the organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford the title compound (2.77 g, 35%).