Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.[CH2:18]([N:22]=[C:23]=[O:24])[CH2:19][CH2:20][CH3:21]>>[CH2:18]([NH:22][C:23]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)=[O:24])[CH2:19][CH2:20][CH3:21]
Reactant: CN1CCC(c2c[nH]c3ccc(N)cc23)CC1
Reactant: CCCCN=C=O
Product: CCCCNC(=O)Nc1ccc2[nH]cc(C3CCN(C)CC3)c2c1
Yield: 95.8 %

Procedure:
Beginning with 15.0 mg (0.0655 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole and 11.1 mg (0.131 mMol) n-butyl isocyanate, 20.6 mg (96%) of the title compound were recovered.
Reaction SMILES: [CH3:1][C:2]([O:10][CH3:11])([CH2:4][CH2:5][CH:6]=C(C)C)[CH3:3].[O:12]=[O+][O-].O=O.CSC>CO.C(Cl)Cl>[CH3:11][O:10][C:2]([CH3:3])([CH3:1])[CH2:4][CH2:5][CH:6]=[O:12]
Reactant: COC(C)(C)CCC=C(C)C
Reactant: O=[O+][O-]
Agent: O=O
Solvent: CSC
Solvent: ClCCl
Solvent: CO
Product: COC(C)(C)CCC=O
Reaction time: 16 h

Procedure:
A stirred, cooled (-65~C.) mixture of 2,6-dimethyl-2-methoxyhept-5-ene (125 g, 1.25 mol), methylene chloride (500 mL) and methanol (500 mL) was treated with a gas stream enriched with ozone. Upon the appearance of a blue color pure oxygen was passed through the mixture followed by nitrogen. Dimethyl sulfide (88 mL, 1.4 mol) was added and the mixture was allowed to stand 16 hours at 25~C. Upon workup 4-methoxy-4-methylpentanal was obtained, bp30 85-87~C. (64.4 g); NMR(CDCl3) 1.2(s,6H), 1.9(t,2H), 2.5(m,2H), 3.2(s,3H), 9.8(t,1H); IR(neat) 2975, 2825, 2725, 1730, 1470, 1370, 1090 cm-1 ;MS(m/e) 43, 73, 83, 115. ##STR37##
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C:12]([CH3:19])([C:15]([F:18])([F:17])[F:16])[O:11][C:10]2=[O:20])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH2:21]([NH2:24])[CH2:22][CH3:23]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([C:13](=[O:14])[C:12]([OH:11])([CH3:19])[C:15]([F:18])([F:17])[F:16])[C:10]([NH:24][CH2:21][CH2:22][CH3:23])=[O:20])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCCN
Reactant: CC1(C(F)(F)F)OC(=O)N(c2ccc(Cl)c(Cl)c2)C1=O
Solvent: ClCCl
Product: CCCNC(=O)N(C(=O)C(C)(O)C(F)(F)F)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 63 %

Procedure:
200 mg of 3-(3,4-dichlorophenyl)-5-methyl-5-(trifluoromethyl)oxazolidine-2,4-dione were dissolved in 10 ml of dichloromethane. 55 μl of propylamine were added. The reaction mixture was stirred for 24 hours at room temperature. After evaporation, the residue was purified by chromatography on a silica column (eluent: dichloromethane). 155 mg of 1-(3,4-dichlorophenyl)-3-propyl-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)urea were obtained, for a yield of 63%.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](OS(C2C=CC(C)=CC=2)(=O)=O)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:28]#[C:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>CCCCCCC.C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:28]#[C:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C#CCCCCC
Reactant: Cc1ccc(S(=O)(=O)Oc2nn(Cc3ccccc3)c3ccccc23)cc1
Solvent: CCCCCCC
Solvent: ClCCl
Product: CCCCCC#Cc1nn(Cc2ccccc2)c2ccccc12

Procedure:
This product was prepared from toluene-4-sulfonic acid 1-benzyl-1H-indazol-3-yl ester and 1-heptyne following the general procedure for the Sonogashira cross-coupling reaction described above. Chromatography eluent: heptane/DCM 1:1; yield (84 mg, 54%); 1H NMR δ (CDCl3): 7.9 (d, J=8.02 Hz, 1H), 7.4-7.19 (m, 8H), 5.5 (s, 2H), 2.48 (t, J=7.22 Hz, 2H), 1.65 (p, J=7.18 Hz, 2H), 1.5-1.32 (m, 4H), 0.94 (t, J=7.21 Hz, 3H); LCMS m/z: 302.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=[N:10]1.[N-:18]=[N+:19]=[N-:20].[Na+]>CN(C)C=O.C(OCC)(=O)C>[N:18]([CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=[N:10]1)=[N+:19]=[N-:20]
Reactant: COC(=O)c1ccnn1-c1ccccc1CBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccnn1-c1ccccc1CN=[N+]=[N-]
Temperature: 25 °C
Reaction time: 48 h
Yield: 70.7 %

Procedure:
To a solution of methyl 1-[2-(bromomethyl)phenyl]pyrazole-5-carboxylate (1.30 g, 4.40 mmol) in 10 mL of N,N-dimethylformamide was added sodium azide (2.86 g, 44.0 mmol). This mixture was stirred at ambient temperature for 48 h and then was diluted with ethyl acetate. The organics were washed with water and brine, dried (MgSO4) and concentrated to afford 0.80 g (71%) of the title compound which was used directly without purification. LRMS (ES+): 280.1 (M+Na)+.
Reaction SMILES: C([O:5][C:6](=[O:48])[CH:7]([NH:12][C:13](=[O:47])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[S:22][S:23][C:24]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:25]=1[C:32](=[O:46])[NH:33][CH:34](OC(C)(C)C)[C:35](=C=O)[CH:36]([CH3:38])[CH3:37])[CH2:8][CH:9]([CH3:11])[CH3:10])(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)[C:59]([OH:61])=[O:60].C1(C)C=CC=CC=1>ClCCl>[C:6]([CH:7]([NH:12][C:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[S:22][S:23][C:24]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:25]=1[C:32]([NH:33][CH:34]([CH2:35][CH:36]([CH3:37])[CH3:38])[C:59]([OH:61])=[O:60])=[O:46])=[O:47])[CH2:8][CH:9]([CH3:11])[CH3:10])([OH:5])=[O:48]
Reactant: O=C(O)C(F)(F)F
Reactant: COc1ccc(C(=O)NC(CC(C)C)C(=O)OC(C)(C)C)c(SSc2cc(OC)ccc2C(=O)NC(OC(C)(C)C)C(=C=O)C(C)C)c1
Solvent: COc1ccccc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1ccc(C(=O)NC(CC(C)C)C(=O)O)c(SSc2cc(OC)ccc2C(=O)NC(CC(C)C)C(=O)O)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of [S-(R*,R*)-2[2-[2-(1-tert-butoxy-carbonyl-3-methylbutylcarbamoyl)-5-methoxy-phenyldisulfanyl]-4-methoxybenzoylamino]-4-methyl-pentanoic acid tert-butyl ester (1.2 g, 1.7 mmol) and anisole (1 mL) in 10 mL dichloromethane, cooled to about 0° C., was treated dropwise with 10 mL of trifluoroacetic acid. The mixture was allowed to warm to ambient temperature. After 4 hours, 5 mL toluene was added, and the solvents were removed in vacuo. The crude product was recrystallized from methanol/water to yield 0.7 g of the title compound.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:19])[CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])=[CH:10][N:9]=1.[H-].[Na+]>>[CH3:1][NH:2][C:3](=[O:19])[CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]2[CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:10]=2[N:9]=1
Reactant: CNC(=O)CCCCc1ccc(CCCCN)cn1
Agent: [H-]
Agent: [Na+]
Product: CNC(=O)CCCCc1ccc2c(n1)NCCCC2

Procedure:
A mixture of 8-7 (24 g, 91.2 mmol) and NaH (10.9 g of a 60% weight dispersion in mineral oil, 273 mmol) in xylenes (500 mL) was purged with argon for 30 min, and then heated at reflux for 72 hours. The mixture was cooled, quenched with ethanol, diluted with 10% aqueous potassium carbonate and extracted with ethyl acetate. The organics were dried over MgSO4, and concentrated to an oil. The residue was chromatographed on silica gel (70:25:5 CHCl3/EtOAc/MeOH/H2O) to give 8-8 as a white solid.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[O-].[Na+].[Na].Cl[CH2:27][C:28]#[N:29]>C(OCC)C.C(O)C>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:27][C:28]#[N:29])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(NCCc1ccc(O)cc1)OCc1ccccc1
Reactant: N#CCCl
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Solvent: CCOCC
Product: N#CCOc1ccc(CCNC(=O)OCc2ccccc2)cc1
Reaction time: 5 h

Procedure:
48.82 g. (0.18 mol) of the above-prepared N-(benzyloxycarbonyl)-p-hydroxyphenethylamine are introduced into a sodium ethylate solution freshly prepared from 5.17 g. sodium and 270 ml. ethanol, 11.4 ml. (0.18 mol) chloroacetonitrile are slowly added dropwise thereto and the reaction mixture is heated to the boil. After 5 hours, the solvent is stripped off, the residue is taken up in diethyl ether, extracted twice with 2N aqueous sodium hydroxide solution, washed neutral, dried over anhydrous sodium sulphate and evaporated to dryness. The oily residue is recrystallised from ligroin/diethyl ether (8:2 v/v). There are obtained 44.74 g. (80% of theory) of the desired product in the form of colourless crystals; m.p. 110°-115° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][CH2:15][NH2:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]1[CH2:9][CH2:10][C@@H:11]([CH2:14][CH2:15][NH:16][C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](CCN)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@@H](CCNC(=O)OCc2ccccc2)CC1
Reaction time: 4 h

Procedure:
To a solution of cis-[4-(2-amino-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester (4.84 g, 20 mmol) in CH2Cl2 (50 mL) and triethylamine (3.06 mL, 22 mmol) was added benzyl chloroformate (3.13 mL, 22 mmol) and the mixture was stirred for 4 hr. The resulting mixture was washed with water, 1 M aqueous HCl, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel, CH2Cl2 to 10% MeOH in CH2Cl2) to give cis-[4-(2-benzyloxycarbonylamino-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester (5.46 g, 73%) as a colorless oil.
Reaction SMILES: FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.C(=O)([O-])[O-].[K+].[K+].Br[CH:31]([CH3:33])[CH3:32]>C(#N)C>[CH:31]([N:10]1[CH2:9][CH2:8][CH:7]([CH2:6][NH:5][C@@H:13]2[CH2:15][C@H:14]2[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)([CH3:33])[CH3:32]
Reactant: CC(C)Br
Reactant: O=C(N(CC1CCNCC1)[C@@H]1C[C@H]1c1ccccc1)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)N1CCC(CN[C@@H]2C[C@H]2c2ccccc2)CC1
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 40.1 %

Procedure:
To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (200 mg, 0.613 mmol) in acetonitrile (10 mL) was added potassium carbonate (254 mg, 1.838 mmol) followed by 2-bromopropane (98 mg, 0.797 mmol). The reaction mixture was heated in a sealed tube at 80° C. for 4 hours. The reaction mixture was filtered and evaporated. The resulting oil was purified by preparatory HPLC (5 to 40% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected. The solution was neutralized with 1 M NaOH, concentrated and extracted with ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and evaporated. The oil was dissolved in 6 ml of EtOH and 3 ml of 1 M NaOH. The reaction mixture was stirred for 20 min, and then it was concentrated. The concentrated solution was then partitioned between 2 ml of water and 5 mL of EtOAc. The organic layer was separated and evaporated. The resulting oil was dissolved in 3 mL of acetonitrile. 0.5 mL of 4 M HCl in dioxane was added. 3 mL of diethylether was added and the formed solid product was filtered. trans-N-((1-Isopropylpiperidin-4-yl)methyl)-2-phenylcyclopropanamine (80 mg, 0.246 mmol, 40.1% yield) was isolated as white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.29-7.40 (m, 2H), 7.13-7.28 (m, 3H), 3.43-3.63 (m, 3H), 3.21 (d, J=6.57 Hz, 2H), 3.11 (t, 2H), 3.04 (dt, J=3.98, 7.71 Hz, 1H), 2.49-2.69 (m, 1H), 2.17 (d, J=12.63 Hz, 3H), 1.56-1.86 (m, 3H), 1.34-1.48 (m, 7H); LC-MS Rt=0.42 min; MS (ESI): 273.3 [M+H]+.
Reaction SMILES: [C:1]([CH:5]1[CH2:10][C:9](=[O:11])[CH2:8][C:7](=[O:12])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[C:13]1([CH3:25])[CH:18]=[CH:17][C:16]([S:19]([N:22]=[C:23]=[O:24])(=[O:21])=[O:20])=[CH:15][CH:14]=1>C1C=CC=CC=1>[C:1]([CH:5]1[CH2:6][C:7](=[O:12])[CH:8]([C:23](=[O:24])[NH:22][S:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:25])=[CH:14][CH:15]=2)(=[O:20])=[O:21])[C:9](=[O:11])[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1ccc(S(=O)(=O)N=C=O)cc1
Reactant: CC(C)(C)C1CC(=O)CC(=O)C1
Solvent: c1ccccc1
Product: Cc1ccc(S(=O)(=O)NC(=O)C2C(=O)CC(C(C)(C)C)CC2=O)cc1

Procedure:
Reaction of 5-tert.-butyl-1,3-cyclohexanedione with p-toluenesulfonylisocyanate in benzene according to the procedure of Example 1 affords 5-tert.-BUTYL-2-(N-p-TOLUENESULFONYLCARBAMOYL)-1,3-CYCLOHEXANEDIONE, m.p. 161.5°-163° C. (corr.).
Reaction SMILES: C([Mg]Cl)(C)C.[Cl-].[Li+].[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[O:13]=[C:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1>C1COCC1>[OH:13][C:14]1([C:9]2[S:8][CH:12]=[CH:11][N:10]=2)[CH2:15][CH2:16][CH:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1
Reactant: CC(C)(C)OC(=O)C1CCC(=O)CC1
Reactant: c1cscn1
Agent: CC(C)[Mg]Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)C1CCC(O)(c2nccs2)CC1
Reaction time: 1 h
Yield: 80.5 %

Procedure:
To a flask containing THF (82 mL) was added isopropylmagnesium chloride/lithium chloride (1.2 M in THF, 37.7 mL, 45 mmol). A solution of thiazole (3.5 g, 41 mmol) in THF (20 mL) was added slowly. The reaction was stirred for one hour. A solution of tert-butyl 4-oxocyclohexanecarboxylate (12.23 g, 62 mmol) in THF (20 mL) was added and the reaction was stirred for 3 hours. The reaction was then quenched slowly with saturated ammonium chloride and diluted with ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield tert-butyl 4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexanecarboxylate (9.25 g, 33 mmol, 79% yield). MS ESI: [M+H]+ m/z 284.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]2)=[O:17])[CH:10]=1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][N:20]([S:32]([CH3:31])(=[O:34])=[O:33])[CH2:19]2)=[O:17])[CH:10]=1
Reactant: COc1ccccc1-c1cc(NC(=O)C2CCCNC2)ncn1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccccc1-c1cc(NC(=O)C2CCCN(S(C)(=O)=O)C2)ncn1
Temperature: 0 °C
Reaction time: 2 h
Yield: 65.5 %

Procedure:
Piperidine-3-carboxylic acid [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-amide (compound #16A) (110 mg, 0.352 mmol) was dissolved in 5 mL of anhydrous dichloromethane, cooled to 0° C. and triethyl amine (13.0 g, 15.5 mmol) and methane sulfonyl chloride (60 mg, 0.53 mmol) were added simultaneously. The mixture was stirred for two hours at room temperature, treated with crushed ice and partitioned with between water and dichloromethane. The organic layer was separated, dried over sodium sulfate and concentrated to provide 1-methanesulfonyl-piperidine-3-carboxylic acid [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-amide (compound #21A) (90 mg, 80.3%).
Reaction SMILES: [C:1]([C:3]1[CH:24]=[CH:23][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[NH:19][CH:20]=[CH:21][N:22]=3)=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].[OH:25]O.[OH-].[Na+].O>C(O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[NH:19][CH:20]=[CH:21][N:22]=3)=[CH:9]2)=[CH:23][CH:24]=1)(=[O:25])[NH2:2]
Reactant: N#Cc1ccc(Cn2cc(Cc3ncc[nH]3)c3ccccc32)cc1
Reactant: OO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: NC(=O)c1ccc(Cn2cc(Cc3ncc[nH]3)c3ccccc32)cc1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
1-(4-Cyanobenzyl)-3-(1-imidazolylmethyl)indole (1.0 g) was dissolved in ethanol (10 ml) and 30% hydrogen peroxide (5 ml) and 6 N sodium hydroxide (5 ml) were added. The resulting mixture was stirred for 2 hours at 50° C. and then poured into water. The solid product was filtered off, washed with water and crystallised from ethanol to give 1-(4-carbamoylbenzyl)-3-(1-imidazolylmethyl)indole (0.65 g), m.p. 173°-175° C. Found: C, 72.63; H, 5.54; N, 16.29. C20H18N4O4 requires: C, 72.71; H, 5.49; N, 16.96.
Reaction SMILES: O1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)/[C:4](=[N:11]/[OH:12])/[CH2:3][CH2:2]1.[CH3:13][O:14]C1C=C2C(=CC=1)C(=O)CC2>>[CH3:13][O:14][C:8]1[CH:7]=[C:6]2[C:5](=[CH:10][CH:9]=1)[C:4](=[N:11][OH:12])[CH2:3][CH2:2]2
Reactant: O/N=C1\CCOc2ccccc21
Reactant: COc1ccc2c(c1)CCC2=O
Product: COc1ccc2c(c1)CCC2=NO

Procedure:
Following the procedure for the preparation of (4E)-2,3-dihydro-4H-chromen-4-one oxime but substituting 5-methoxyindan-1-one and making non-critical variations provided the title compound as a oil: HRMS (EI) calcd for C10H11O2 177.0790, found 177.0783. Anal. Calcd for C10H11NO2: C, 67.78; H, 6.26; N, 7.90. Found: C, 67.73; H, 6.34; N, 7.77.
Reaction SMILES: COC(C)(C)C(C)CCC(C)CC=CC(C)=CC(O)=O.CC(C=CCC(C)CC(C)C(C)=C)=CC(O)=O.C([Li])C.[CH3:41][C:42]([CH:48]=[CH:49][CH2:50][CH:51]([CH3:58])[CH2:52][CH:53](C)[C:54]([CH3:56])=[CH2:55])=[CH:43][C:44](=[O:47])[CH2:45]C>>[CH3:41][C:42]([CH:48]=[CH:49][CH2:50][CH:51]([CH3:58])[CH2:52][CH:53]=[C:54]([CH3:56])[CH3:55])=[CH:43][C:44](=[O:47])[CH3:45]
Reactant: C=C(C)C(C)CC(C)CC=CC(C)=CC(=O)CC
Agent: C=C(C)C(C)CC(C)CC=CC(C)=CC(=O)O
Agent: COC(C)(C)C(C)CCC(C)CC=CC(C)=CC(=O)O
Agent: [Li]CC
Product: CC(=O)C=C(C)C=CCC(C)CC=C(C)C

Procedure:
Following the process of this example, each of 11-methoxy-3,7,10,11-tetramethyldodeca-2,4-dienoic acid and 3,7,9,10-tetramethylundeca-2,4,10-trienoic acid is reacted with ethyl lithium to prepare 13-methoxy-5,9,12,13-tetramethyltetradeca-3,6-dien-3-one and 5,9,11,12-tetramethyltrideca-4,6,12-trien-3-one, respectively.
Reaction SMILES: Cl.[NH:2]([C:6]1[CH:7]=[C:8]([CH:25]=[CH:26][CH:27]=1)[CH2:9][C:10]([NH:17]C(=O)C(CC)CC)(C([O-])=O)[C:11]([O-:13])=[O:12])[C:3]([NH2:5])=[NH:4]>O>[NH:2]([C:6]1[CH:7]=[C:8]([CH:25]=[CH:26][CH:27]=1)[CH2:9][CH:10]([C:11]([OH:13])=[O:12])[NH2:17])[C:3]([NH2:5])=[NH:4]
Reactant: CCC(CC)C(=O)NC(Cc1cccc(NC(=N)N)c1)(C(=O)[O-])C(=O)[O-]
Agent: Cl
Solvent: O
Product: N=C(N)Nc1cccc(CC(N)C(=O)O)c1
Yield: 43.2 %

Procedure:
A 50% solution of concentrated hydrochloric acid in water (40 mls) was added to 3-guanidino-benzyldiethylacetamidomalonate (910 mg, 2.5 mmol). The reaction mixture was stirred at reflux for 15 hours. The solvent was evaporated to a third of the volume and the crude product purified by ion exchange chromatography (Dowex AG 50W-X8, 100-200 mesh resin, 16 ml wet bed volume), eluting with 0.1M ammonia solution to give a tan glass/oil. Futher purified by flash column chromatography (10% 880 ammonia/methanol) gave 3-guanidino-DL-phenylalanine (240 mg, 43%) as a tan glass.
Reaction SMILES: [CH3:1][CH:2]([C:8](=[O:16])[CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(OC(CCC(Cl)=O)=O)C.C(N(CC)[CH2:30][CH2:31][C:32](=[O:44])[CH2:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([O:42][CH3:43])[CH:37]=1)C.[K]>C1C=CC=CC=1.C(O)C.CCOCC>[CH3:43][O:42][C:38]1[CH:37]=[C:36]([CH2:35][CH2:34][CH2:33][C:32](=[O:44])[CH2:31][CH2:30][C:2]([CH3:1])([C:8](=[O:16])[CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:41]=[CH:40][CH:39]=1
Reactant: CCOC(=O)CCC(=O)C(C)C(=O)OCC
Reactant: CCN(CC)CCC(=O)CCCc1cccc(OC)c1
Agent: CCOC(=O)CCC(=O)Cl
Agent: [K]
Solvent: c1ccccc1
Solvent: CCOCC
Solvent: CCO
Product: CCOC(=O)CCC(=O)C(C)(CCC(=O)CCCc1cccc(OC)c1)C(=O)OCC
Temperature: 160 °C

Procedure:
Stir a mixture of diethyl 2-methyl-3-oxoadipate (2.3 g, b.p. 111°-112° C/0.2 mm), prepared from 2- methylacetoacetic ester and ethoxycarbonylpropionyl chloride by the method of Cardwell, J. Chem. Soc., 1949, 715, and the methiodide of 1-diethylamino-6-m-methoxyphenylhexan-3-one (4.6 g) in benzene (20 cc) in an ice bath and add a solution of potassium (0.4 g) in ethanol (10 cc) dropwise over one hour. After stirring for a further 4 hours add ether (50 cc) and evaporate the washed and dried ether extracts. Heat the residue at 160°C and 0.2 mm pressure to remove unchanged starting materials. The residual gum is diethyl 2-(6-m-methoxyphenyl-3-oxohexyl)-2-methyl-3-oxoadipate (2.7 g); infrared absorption peaks at 5.78, 5.88, 6.25, 12.82, 14.49 μ.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]C(=O)C)=[CH:4][C:3]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.Cl>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CC(=O)Nc1ccc(Br)c(OCCN2CCCCC2)c1
Agent: Cl
Solvent: O
Product: Nc1ccc(Br)c(OCCN2CCCCC2)c1
Yield: 89 %

Procedure:
N-[4-Bromo-3-(2-{piperidin-1-yl}ethoxy)phenyl]acetamide (17.48 g), 35% hydrochloric acid (100 ml) and water (100 ml) were heated at 95° C. for 2 h, evaporated to near dryness, water (100 ml) added and the pH adjusted to 8 with sodium carbonate. Extraction with dichloromethane (3×200 ml), the combined organic phase washed with water, brine, dried (MgSO4) and evaporated to give the product as a solid (13.64 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:3]=1.[NH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>C(O)C>[N:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:4]1[N:3]=[C:2]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:5]=1
Reactant: C1CNCCN1
Reactant: Clc1cc(-c2ccccn2)nc(-c2ccccn2)n1
Solvent: CCO
Product: c1ccc(-c2cc(N3CCNCC3)nc(-c3ccccn3)n2)nc1

Procedure:
4-Chloro-2,6-bis(2-pyridinyl)pyrimidine [prepared by the method of J.A.C.S. 32, 1591 (1967), 4.2 g] piperazine (13.44 g) and ethanol (70 ml) are heated at reflux for 2 hr. The mixture is allowed to cool and the solvent is removed under reduced pressure. The residue is dissolved in chloroform (250 ml), washed with water (twice), dried over sodium sulfate and concentrated under reduced pressure to give an oil. The oil is crystallized from ether to give the title compound, m.p. 159°-161°; MS (m/e) 318 (M+)
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([F:14])=[C:5]([CH:9]=[C:10]([F:13])[C:11]=1[F:12])[C:6](O)=[O:7].S(Cl)([Cl:17])=O>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[C:4]([F:14])=[C:5]([CH:9]=[C:10]([F:13])[C:11]=1[F:12])[C:6]([Cl:17])=[O:7]
Reactant: COc1c(F)c(F)cc(C(=O)O)c1F
Reactant: O=S(Cl)Cl
Solvent: c1ccccc1
Product: COc1c(F)c(F)cc(C(=O)Cl)c1F

Procedure:
To a solution of 1.14 g (0.0055 mole) of 3-methoxy-2,4,5-trifluorobenzoic acid (XXVI) (prepared as described in Preparation 1 or 2) in 10 ml of dry benzene was added 5 ml of thionyl chloride and the mixture was heated under reflux for 1 hour. At the end of this time, benzene and the excess of thionyl chloride were removed completely to give 3-methoxy-2,4,5-trifluorobenzoyl chloride (XXVII) [Step (E7)].