Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:4][C@H:5]([CH2:10][C:11]1[CH:19]=[C:18]([CH3:20])[C:17]2[C:13](=[CH:14][N:15]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[N:16]=2)[CH:12]=1)[C:6]([O:8]C)=[O:7])(=O)C.O.[OH-].[Li+]>O1CCCC1.CO.O>[OH:4][C@H:5]([CH2:10][C:11]1[CH:19]=[C:18]([CH3:20])[C:17]2[C:13](=[CH:14][N:15]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[N:16]=2)[CH:12]=1)[C:6]([OH:8])=[O:7]
Reactant: COC(=O)[C@@H](Cc1cc(C)c2nn(COCC[Si](C)(C)C)cc2c1)OC(C)=O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1cc(C[C@@H](O)C(=O)O)cc2cn(COCC[Si](C)(C)C)nc12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of (R)-methyl 2-acetoxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)propanoate (700 mg, 1.72 mmol) in tetrahydrofuran (6 mL) and methanol (6 mL) at 0° C. was added a solution of lithium hydroxide monohydrate (289 mg, 6.89 mmol) in water (6 mL). The reaction was stirred at 0° C. for 1 h. The reaction was concentrated, dissolved in 5 mL of water, cooled to 0° C., and treated with 1M hydrochloric acid until mildly acidic. A non-solid ppt formed. The suspension was extracted with ethyl acetate (2×), which were washed with brine, dried over magnesium sulfate, and concentrated to give 620 mg (quant.) which was pure by LC/MS and was used without purification. Mass spec.: 351.13 (MH)+.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5]1(=[O:15])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1.[Br:16]Br.Cl>O.C(OCC)C>[Br:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[CH2:8][CH2:7][CH2:6][C:5]2=[O:15]
Reactant: BrBr
Reactant: O=C1CCCc2ccccc21
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOCC
Solvent: O
Product: O=C1CCCc2c(Br)cccc21
Temperature: 80 °C

Procedure:
2.21 g of AlCl3 are placed in a round-bottomed flask, to which 0.91 ml of 3,4-dihydro-2H-naphth-1-one is added over 10 min and 0.41 ml of Br2 is added over 5 min, and the mixture is heated at 80° C. for 10 min. It is allowed to return to ambient temperature and a solution comprising 20 g of ice and 2.7 ml of concentrated hydrochloric acid is added thereto. The mixture is then diluted with water and diethyl ether. The organic phase is subsequently separated, dried and concentrated under reduced pressure. The residue is purified by reverse phase preparative chromatography. 172 mg of compound are obtained.
Reaction SMILES: F[C:2](F)(F)[C:3]([OH:5])=[O:4].[C:8]1([C:14](Cl)=[O:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C(N(CC)CC)C>[O:5]([C:14]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:15])[C:3]([C:2]1[CH:12]=[CH:13][CH:8]=[CH:9][CH:10]=1)=[O:4]
Reactant: O=C(Cl)c1ccccc1
Reactant: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Product: O=C(OC(=O)c1ccccc1)c1ccccc1

Procedure:
For the preparation of compounds of formula I, (Q1 is R1CO or PhCO), an intermediate VIII (Q1 is t-butoxycarbonyl) is treated with trifluoroacetic acid (TFA) as in the conversion of VII to VIII. The resulting TFA salt of the corresponding amino compound is then treated with an acid chloride of the formula R1COCl or PhCOCl or an anhydride of the formula (R1CO)2O or (PhCO)2O in the presence of a tertiary amine such as triethylamine to give VIII (Q1 is R1CO or PhCO). This is subsequently transformed into IX (Q1 is R1CO or PhCO) by the same procedure as for the conversion of VIII (Q1 is t-butoxycarbonyl or benzyloxycarbonyl) to IX (Q1 is t-butoxycarbonyl or benzyloxycarbonyl).
Reaction SMILES: [NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:37])[CH:3]=1.[F:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46]([N:48]=[C:49]=[S:50])=[O:47])=[CH:41][CH:40]=1.C1(C)C=CC=CC=1.CCO>C1(C)C=CC=CC=1.CCO.CCOCC>[F:37][C:4]1[CH:3]=[C:2]([NH:1][C:49]([NH:48][C:46](=[O:47])[CH2:45][C:42]2[CH:43]=[CH:44][C:39]([F:38])=[CH:40][CH:41]=2)=[S:50])[CH:36]=[CH:35][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[N:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:18][CH:17]=3)[S:15][C:8]=12
Reactant: COCCN(Cc1ccc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)nc1)C(=O)OC(C)(C)C
Reactant: O=C(Cc1ccc(F)cc1)N=C=S
Solvent: CCOCC
Solvent: Cc1ccccc1
Solvent: CCO
Product: COCCN(Cc1ccc(-c2cc3nccc(Oc4ccc(NC(=S)NC(=O)Cc5ccc(F)cc5)cc4F)c3s2)nc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 61.6 %

Procedure:
To a suspension of intermediate 13 (5.53 g, 10.55 mmol) in toluene (80 mL) and EtOH (80 mL) was added 2-(4-fluorophenyl)acetyl isothiocyanate (2) (3.09 g, 15.83 mmol) in a minimum of toluene-EtOH mixture (1:1). The reaction mixture was stirred at r.t. for 45 min then concentrated. The residue was purified by flash column chromatography (eluent EtOAc), followed by two triturations: first one in a mixture Et2O-EtOAc-hexanes and second one in Et2O, to afford intermediate 14 (4.68 g, 62% yield) as a pink solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 12.49 (s, 1H), 11.84 (s, 1H), 8.55 (d, J=5.6 Hz, 1H), 8.51 (d, J=1.6 Hz, 1H), 8.34 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 8.04 (d, J=11.6 Hz, 1H), 7.79 (dd, J=8.2, 2.2 Hz, 1H), 7.55-7.54 (m, 2H), 7.38 (dd, J=8.6, 5.8 Hz, 2H), 7.18 (t, J=8.8 Hz, 2H), 6.69 (d, J=5.6 Hz, 1H), 4.48 (s, 2H), 3.84 (s, 2H), 3.43-3.34 (m, 4H), 3.23 (s, 3H), 1.44-1.34 (m, 9H). MS (m/z): 720.3 (M+H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-])=O)=[C:6]([OH:8])[CH:7]=1>[C].[Pd].CO>[NH2:9][C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][C:6]=1[OH:8]
Reactant: Cc1ccc([N+](=O)[O-])c(O)c1
Agent: [Pd]
Solvent: CO
Product: Cc1ccc(N)c(O)c1
Temperature: 50 °C
Reaction time: 3 h
Yield: 98.4 %

Procedure:
To an autoclave, there were fed 1.5 g of palladium carbon, 50.0 g (moisture content: 5.9%; 308 mmol) of 5-methyl-2-nitrophenol and 250 ml of methanol. The mixture was stirred under a hydrogen pressure of 20 kg/cm2 at 50° C. for 3 hours. After cooling, the catalyst was filtered and washed with 50 ml of warm methanol twice and the washing liquor was combined with the filtrate. After distilling off the solvent under reduced pressure, the residue was dried. Thus 37.3 g (303 mmol) of 6-amino-m-cresol was obtained as a brown solid. The yield was 98%. A 15.0 g portion of this brown solid product was recrystallized from 45 ml of isopropanol. Thus 11.9 of 6-amino-m-cresol was obtained as yellow crystals. The recovering yield was 79%.
Reaction SMILES: [CH2:1]([N:7]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].CN([CH:23]=[O:24])C.O=P(Cl)(Cl)Cl.CC([O-])=O.[Na+]>ClCCCl>[CH2:14]([N:7]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=1[CH:23]=[O:24])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CN(C)C=O
Reactant: CCCCCCN(CCCCCC)c1ccccc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: ClCCCl
Solvent: O=P(Cl)(Cl)Cl
Product: CCCCCCN(CCCCCC)c1ccccc1C=O
Reaction time: 8 h

Procedure:
To a solution of N,N-dihexylaniline (12.02 g, 4.60×10−2 mol) in anhydrous 1,2-dichloroethane (200 ml) at room temperature were successively added anhydrous DMF (3.60 ml, 4.65×10−2 mol) and POCl3 (5.20 ml, 5.58×10−2 mol), and the mixture was refluxed for 5.5 h. After cooling, 2M aqueous NaOAc solution (200 ml) was added and the reaction mixture was stirred overnight. The product was extracted three times with CHCl3 and the combined organic layers were dried over Na2SO4. The residue was chromatographed on silica gel with 1:1 hexane:CHCl3 as the eluent. Yield=10.793 g (81% based on 12.02 g of N,N-dihexylaniline). 1H NMR (250 MHz, CDCl3): δ 9.69 (s, 1H, —CHO), 7.70 (dd, 2H, J=8.9 Hz, Ph), 6.63 (d, 2H, J=9.0 Hz, Ph), 3.34 (t, 4H, J=7.8 Hz, —NCH2—), 1.48-1.70 (m, 4H, —NCH2CH2—), 1.19-1.41 (m, 12H, —CH2—), 0.91 (t, 6H, J=6.6 Hz, —CH3). CI MS m/z: 290.247 ((M+H)+) (calcd 290.248).
Reaction SMILES: O.O.O.O.O.O.[NH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.Cl.[O:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C:19](Cl)=[O:20].[OH-].[Na+]>O>[O:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C:19]([N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=[O:20]
Reactant: C1CNCCN1
Reactant: O=C(Cl)c1ccco1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(c1ccco1)N1CCNCC1
Reaction time: 1 h
Yield: 60 %

Procedure:
This compound and its preparation has been described in Great Britain Patents 1,390,014 and 1,390,015. Piperazine hexahydrate (194 g, 1 mole) was dissolved in 250 ml H2O. The solution was acidified to pH 4.5 with 6N HCl. Furoyl chloride (130.5 g, 1 mole, Aldrich) was added along with 10% NaOH solution at such a rate that the pH was maintained at 4.5. After 1 hour, the solution was made basic (pH=8.5) with NaOH solution. The reaction mixture was continuously extracted with chloroform for 36 hours. The CHCl3 extract was dried over MgSO4, and filtered. Distillation gave 108.2 g product (60%), b.p. 132°-138° C./0.6 mm Hg, m.p. 69°-70° C.
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:8][C:9]([CH2:11][N:12]2[CH2:15][CH:14]([NH2:16])[C:13]2=[O:17])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:24]([CH2:31][C:32](Cl)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>C1COCC1.O>[C:18]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][C:9]([CH2:11][N:12]2[CH2:15][CH:14]([NH:16][C:32](=[O:33])[CH2:31][O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:13]2=[O:17])=[O:10])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NC1CN(CC(=O)OC(c2ccccc2)c2ccccc2)C1=O
Reactant: O=C(Cl)COc1ccccc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1CCOC1
Product: O=C(COc1ccccc1)NC1CN(CC(=O)OC(c2ccccc2)c2ccccc2)C1=O

Procedure:
For example, N-(diphenylmethoxycarbonylmethyl)-3-amino- 2-azetidinone is reacted in THF-water with phenoxyacetyl chloride in the presence of triethylamine to provide N-(diphenylmethoxycarbonylmethyl)-3-phenoxyacetamido-2-azetidinone. Treatment of the product with trifluoroacetic acid in the presence of anisole removes the diphenylmethyl ester group to provide the N-(carboxymethyl)azetidinone.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH:6]([C:10]([OH:12])=[O:11])[C:7]([OH:9])=O)=[CH:2]1.[NH2:13][CH:14]1[C:27](=[O:28])[N:16]2[CH:17]([C:22]3[NH:26][N:25]=[N:24][N:23]=3)[C:18]([CH3:21])([CH3:20])[S:19][C@H:15]12>>[C:10]([CH:6]([C:3]1[CH:4]=[CH:5][S:1][CH:2]=1)[C:7]([NH:13][CH:14]1[C:27](=[O:28])[N:16]2[CH:17]([C:22]3[NH:23][N:24]=[N:25][N:26]=3)[C:18]([CH3:20])([CH3:21])[S:19][C@H:15]12)=[O:9])([OH:12])=[O:11]
Reactant: O=C(O)C(C(=O)O)c1ccsc1
Reactant: CC1(C)S[C@@H]2C(N)C(=O)N2C1c1nnn[nH]1
Product: CC1(C)S[C@@H]2C(NC(=O)C(C(=O)O)c3ccsc3)C(=O)N2C1c1nnn[nH]1
Yield: 67 %

Procedure:
(2.69 mmole) of 2-(3-thienyl)malonic acid (British Pat. No. 1,125,557) with 645 mg. (2.69 mmole) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam, according to the procedure of Example CXLVII, affords 810 mg. (67% yield) of 6-(2-carboxy-2-[3-thienyl]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam as its disodium salt. The infrared spectrum of the product KBr disc) shows absorptions at 1775 cm-1 (β-lactam), 1670 cm-1 (amide I), 1620 cm-1 (carboxylate) and 1525 cm-1 (amide II). The NMR spectrum (D2O) shows absorptions at 7.80-7.00 ppm (multiplet, thienyl hydrogens), 5.88 ppm (doublet, C-6 hydrogen), 5.65 ppm (doublet of doublets, C-5 hydrogen), 5.40 ppm (doublet, C-3 hydrogen), 1.60 ppm (doublet, C-2 methyl hydrogens) and 1.00 ppm (doublet, C-2 methyl hydrogens).
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH:14]=[CH:15][N:16]1C(=O)C2C(=CC=CC=2)C1=O)([CH3:4])([CH3:3])[CH3:2].O.NN>CCO>[C:1]([O:5][C:6](=[O:27])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH2:15][NH2:16])([CH3:2])([CH3:4])[CH3:3]
Reactant: CC(C)(C)OC(=O)Cc1ccccc1C=CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)Cc1ccccc1CCN
Yield: 66.9 %

Procedure:
A solution of {2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-vinyl]-phenyl}-acetic acid tert-butyl ester (1.97 g) and hydrazine hydrate (1.97 mL) in EtOH (75 mL) was heated at reflux for 90 minutes. The solids were removed by filtration and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc (50 mL) and the solution was washed with saturated NaHCO3 followed by brine. The organic solution was dried over MgSO4, filtered, and concentrated. Purification by flash chromatography (CHCl3:MeOH 97.5:2.5 to 95:5 to 9:1) provided the title amine (853 mg). MS 236 (M+1).
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:10]([NH:12][C@H:13]([C:20]([OH:22])=[O:21])[CH2:14][O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[ClH:33]>CO>[NH2:1][C@H:2]([C:10]([NH:12][C@H:13]([C:20]([OH:22])=[O:21])[CH2:14][O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[ClH:33]
Reactant: C[C@@H](OC(C)(C)C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](COC(C)(C)C)C(=O)O
Agent: Cl
Solvent: CO
Product: C[C@@H](OC(C)(C)C)[C@H](N)C(=O)N[C@@H](COC(C)(C)C)C(=O)O

Procedure:
25 g (55.24 mmols) of Z-Thr(But)-Ser(But)OH were dissolved in 200 ml of methanol and catalytically hydrogenated (pH 4.5) on an autotitrator with the addition of methanolic HCl. When hydrogenation was complete, the Pd/BaSO4 catalyst was removed by suction filtration, the filtrate was concentrated and dried in a high vacuum. Yield 21.1 g of an amorphous product (19.60 g 100%).
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([I:9])[C:6]([F:10])=[CH:5][C:3]=1[NH2:4].[CH3:11][S:12](Cl)(=[O:14])=[O:13].N1C=CC=CC=1>C(Cl)Cl>[F:1][C:2]1[CH:8]=[C:7]([I:9])[C:6]([F:10])=[CH:5][C:3]=1[NH:4][S:12]([CH3:11])(=[O:14])=[O:13]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cc(F)c(I)cc1F
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1cc(F)c(I)cc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 86.7 %

Procedure:
To a solution of 2,5-difluoro-4-iodoaniline (5.3 g, 19.4 mmol, Can. J. Chem., 2000(78), 1081-1088) in DCM (50 ml) was added methanesulfonyl chloride (1.65 ml, 21.3 mmol) and pyridine (4.7 ml, 58.2 mmol) at 0° C. The mixture was stirred for 24 hours at room temperature. The mixture was partitioned between EtOAc and 2 M HCl aqueous solution. The organic layer was separated and washed with 2 M aqueous HCl solution and brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with gradually from hexane/EtOAc (4:1) to hexane/EtOAc (3:1) to give the title compound (5.6 g, 87%) as purple solids.
Reaction SMILES: NC1N=CNN=1.C[O-].[Na+].BrCCCCC#N.[C:17]([CH2:19][CH2:20][CH2:21][CH2:22][N:23]1[CH:27]=[N:26][C:25]([NH2:28])=[N:24]1)#[N:18].[F:29][C:30]([F:36])([F:35])[CH2:31][N:32]=[C:33]=[S:34]>CO.C(#N)C>[F:29][C:30]([F:36])([F:35])[CH2:31][NH:32][C:33](=[S:34])[NH:28][C:25]1[N:26]=[CH:27][N:23]([CH2:22][CH2:21][CH2:20][CH2:19][C:17]#[N:18])[N:24]=1
Reactant: FC(F)(F)CN=C=S
Reactant: N#CCCCCn1cnc(N)n1
Agent: C[O-]
Agent: N#CCCCCBr
Agent: Nc1nc[nH]n1
Solvent: CC#N
Solvent: CO
Product: N#CCCCCn1cnc(NC(=S)NCC(F)(F)F)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 42.3 %

Procedure:
3-Amino-1,2,4-triazole (4.2 g.) was added to a solution of sodium methoxide in MeOH (1.2 g. sodium in 30 ml. MeOH) and the solution stirred for 0.5 hours at room temperature. 5-Bromovaleronitrile (8.1 g.) was added and the solution heated under reflux for 12 hours. The solution was evaporated and the residue partitioned between water and EtOAc. The extracts were washed with brine, dried over MgSO4 and evaporated to give a pale yellow oil (6.5 g.) which was purified by medium pressure liquid chromatography using EtOAc/MeOH 6:1 v/v as eluant. The colourless oil obtained was used without characterisation for the following reaction. The crude 1-(4-cyanobutyl)-3-amino-1,2,4-triazole (5.45 g.) in acetonitrile (80 ml.) was treated with 2,2,2-trifluoroethylisothiocyanate (4.4 g.) and the solution heated under reflux for 3.5 hours. Evaporation gave a white sticky solid which was triturated with ether/EtOH to give 5-(3-[3-(2,2,2-trifluoroethyl)thioureido]-1,2,4-triazol-1-yl)valeronitrile (4.04 g.) as a white solid, m.p. 136°-138°.
Reaction SMILES: [C:1]1([CH:17]=O)[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[C:19](#[N:23])[CH2:20][C:21]#[N:22].C(O)(=O)C.C([O-])(=O)C.[NH4+]>O1CCCC1.C(O)C.ClC1C=CC=CC=1.C1C=CC=CC=1>[C:21]([C:20]([C:19]#[N:23])=[CH:17][C:1]1[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1)#[N:22]
Reactant: O=Cc1ccc2ccc3cccc4ccc1c2c34
Reactant: N#CCC#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: Clc1ccccc1
Solvent: CCO
Product: N#CC(C#N)=Cc1ccc2ccc3cccc4ccc1c2c34
Reaction time: 0.5 h

Procedure:
About 100 grams (0.434 moles) pyrene-1-carboxaldehyde, about 28.7 grams (0.434 moles) malononitrile, about 10.4 milliliters acetic acid, about 3.48 grams ammonium acetate and about 400 milliliters benzene are heated to boiling under reflux conditions for 30 minutes. The entire contents of the flask crystallized, forming a deep orange red product which is soluble in tetrahydrofuran, moderately soluble in ethanol and very soluble in chlorobenzene. This product is recrystallized from a mixture of chlorobenzene and ethanol (30:70). Yield: 104.4 grams m. p 248°-250° C.
Reaction SMILES: [CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18]([OH:20])=O)[CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[N:43]1([CH2:49][CH2:50][CH2:51][NH2:52])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1>ClCCl.CC(=O)OCC.CO>[CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18]([NH:52][CH2:51][CH2:50][CH2:49][N:43]3[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)=[O:20])[CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc2c(c1)C(=O)N(Cc1ccccc1)C2
Reactant: NCCCN1CCCCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CO
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(NCCCN1CCCCC1)c1ccc2c(c1)C(=O)N(Cc1ccccc1)C2
Reaction time: 2 h

Procedure:
Under nitrogen atmosphere, 2-benzyl-3-oxoisoindoline-5-carboxylic acid (Chemical Formula 8) (100 mg, 0.374 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 0.144 g, 0.749 mmol), and 1-hydroxybenzotriazole (HOBT, 0.025 g, 0.187 mmol) were reacted at room temperature in distilled dichloromethane, with stirring, for 2 hours. After monitoring through TLC [CH2Cl2:MeOH=4:1], the temperature was decreased to −40° C. at which time 3-(piperidin-1-yl)propan-1-amine (80 μL, 0.562 mmol) was added before stirring for 3-4 hours. The reaction progress was monitored with TLC [Hex: EA=1:1]. When the reaction was completed, the reaction mixture was extracted with NaHCO3 and then with CH2Cl2. The organic layer thus obtained was dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in a vacuum and the concentrate was purified using column chromatography [CH2Cl2:MeOH=20:1] to afford 2-benzyl-3-oxo-N-(3-(piperidin-1-yl)propyl)isoindoline-5-carboxamide (Chemical Formula 1) in an amount of 96 mg (Yield 73%). This product was solidified with ethereal HCl to give a hydrochloride.
Reaction SMILES: [CH3:1][N:2]([Si](C)(C)C)[CH3:3].[CH3:8][O:9][S:10]([O-:13])(=[O:12])=[O:11].[CH3:14][N:15]([C+:17]([N:19]([CH3:21])[CH3:20])Cl)[CH3:16]>C(Cl)(Cl)Cl>[CH3:1][N:2]([CH3:3])[C:17](=[N+:15]([CH3:16])[CH3:14])[N:19]([CH3:21])[CH3:20].[CH3:8][O:9][S:10]([O-:13])(=[O:12])=[O:11]
Reactant: CN(C)[C+](Cl)N(C)C
Reactant: CN(C)[Si](C)(C)C
Agent: COS(=O)(=O)[O-]
Solvent: ClC(Cl)Cl
Product: CN(C)C(N(C)C)=[N+](C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.4 %

Procedure:
10 ml of dry chloroform and 1.29 g (11.00 mmol) of N,N-dimethyltrimethylsilylamine are added to 2.45 g (9.93 mmol) of bis(dimethylamino)chlorocarbenium methylsulfate. The reaction mixture is stirred for 1 hour at room temperature, and all volatile compounds are subsequently removed under reduced pressure. The residue is dried for a further 1 hour under reduced pressure at 7.0 Pa and an oil-bath temperature of 50° C., giving 2.42 g of hexamethylguanidinium methylsulfate, corresponding to a yield of 95.5%.
Reaction SMILES: O[N:2]([CH:9]=[O:10])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:11](OC=C)(=O)[CH3:12]>>[CH:9]([N:2]1[C:3]2[C:8](=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:12]=[CH:11]1)=[O:10]
Reactant: C=COC(C)=O
Reactant: O=CN(O)c1ccccc1
Product: O=Cn1ccc2ccccc21

Procedure:
In a manner analogous to that of Example 1, 3.1 g of N-hydroxy-N-formylaniline, 200 mg of Li2PdCl4 and 60 ml of vinyl acetate are reacted at 55° C. for 6 hours, and, after further processing, N-formylindole is obtained; IR spectrum (CHCl3): 1660 (CO): NMR spectrum (100 MHz, CDCl3): 6.54 (broad d, J=5 Hz, CH); 7.0-7.3 (m, 4H); 8.02 (broad d, J=6 Hz, CH); 8.68 (s, H--CO) ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17]([N:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]5[C:27]([O:32]C)=[N:28][CH:29]=[CH:30][CH:31]=5)[CH2:21][CH2:20]4)=O)([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.B(F)(F)F.CCOCC.O1CCCC1.B.C(OCC)C>O1CCCC1.Cl.CO>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([CH2:17][N:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]5[C:27]([OH:32])=[N:28][CH:29]=[CH:30][CH:31]=5)[CH2:21][CH2:20]4)([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1
Reactant: COc1ncccc1CC1CCN(C(=O)[C@@]23C[C@@H](c4ccccc42)c2ccc(Cl)cc23)CC1
Agent: B
Agent: Cl
Agent: FB(F)F
Solvent: CCOCC
Solvent: CO
Solvent: C1CCOC1
Product: Oc1ncccc1CC1CCN(C[C@@]23C[C@@H](c4ccccc42)c2ccc(Cl)cc23)CC1
Yield: 66.3 %

Procedure:
A solution of 1-((9S,10S)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-(2-methoxy-3-pyridylmethyl)piperidine (1.80 g. 3.92 mmol) in tetrahydrofuran (50 mL) was treated with boron trifluoride etherate (612 mg, 4.31 mmol) and borane- tetrahydrofuran (14.9 mL of a 1.0M solution, 14.9 mmol). The resulting solution was heated to reflux for 3 h. The mixture was then concentrated on a rotary evaporator to give a colorless residue. The residue was dissolved in concentrated hydrochloric acid (50 mL, 12N) and heated to reflux for 3 h. The solution was concentrated to dryness on a rotary evaporator to give a glassy residue. This residue was dissolved in methanol (100 mL) and concentrated to dryness on a rotary evaporator (3X) to give a white foam. This foam was dissolved in methanol (5 mL) and added to rapidly stirred diethyl ether (200 mL) to give a white precipitate which was collected and washed with diethyl ether to give the hydrochloride salt of the title compound (1.3 g, 2.60 mmol, 66%) as an off-white powder, mp 211°-215° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[N:11]3[N:17]=[CH:18][C:19]([C:20]([OH:22])=O)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.[OH:23][CH2:24][C:25]([NH:28][S:29]([C:32]1[S:36][C:35]([NH2:37])=[N:34][C:33]=1[CH3:38])(=[O:31])=[O:30])([CH3:27])[CH3:26]>>[OH:23][CH2:24][C:25]([NH:28][S:29]([C:32]1[S:36][C:35]([NH:37][C:20]([C:19]2[CH:18]=[N:17][N:11]3[C:12]([CH:14]4[CH2:16][CH2:15]4)=[CH:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[N:9][C:10]=23)=[O:22])=[N:34][C:33]=1[CH3:38])(=[O:31])=[O:30])([CH3:27])[CH3:26]
Reactant: Cc1nc(N)sc1S(=O)(=O)NC(C)(C)CO
Reactant: O=C(O)c1cnn2c(C3CC3)cc(-c3ccc(Cl)cc3)nc12
Product: Cc1nc(NC(=O)c2cnn3c(C4CC4)cc(-c4ccc(Cl)cc4)nc23)sc1S(=O)(=O)NC(C)(C)CO

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.19) and 2-amino-4-methyl-thiazole-5-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (example B.3) according to general procedure II. Pale-yellow solid. MS (ISN) 559.0 [(M−H)−]; mp 293-294° C.