Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]([CH3:16])([C:12]([F:15])([F:14])[F:13])[C:8]([O:10]C)=[O:9])=[CH:4][CH:3]=1.CO.[OH-].[K+]>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]([CH3:16])([C:12]([F:13])([F:14])[F:15])[C:8]([OH:10])=[O:9])=[CH:17][CH:18]=1
Reactant: COC(=O)C(C)(Oc1ccc(Cl)cc1)C(F)(F)F
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(Oc1ccc(Cl)cc1)(C(=O)O)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of (±)-methyl 2-(4-chlorophenoxy)-3,3,3-trifluoro-2 -methylpropionate (1.41 g.), methanol (4.0 ml.), and 4.5 N-aqueous potassium hydroxide (2.3 ml.) is stirred at ambient temperature for 10 minutes. The resulting solution is diluted with water, washed with ether, acidified with concentrated hydrochloric acid, and extracted with ether. The extract is washed with water, dried with sodium sulphate and evaporated to a residue which is crystallised from light petroleum (b.p. 60°-80° C.) to give (±)-2-(4-chlorophenoxy)-3,3,3-trifluoro-2-methylpropionic acid, m.p. 141°-142° C. (0.7 g.).
Reaction SMILES: [C:1]([C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11](SC)[C:12](=[O:18])[NH:13]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Ni].O1CCCC1>[C:1]([C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:18])[NH:13]2)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CSC1C(=O)Nc2cccc(C(=O)c3ccccc3)c21
Agent: [Ni]
Solvent: C1CCOC1
Product: O=C1Cc2c(cccc2C(=O)c2ccccc2)N1
Reaction time: 1.5 h

Procedure:
A stirred suspension of 7.0 g. (0.0248 mole) of 4-benzoyl-3-methylthioindolin-2-one in 400 ml. of tetrahydrofuran was treated portionwise under a nitrogen atmosphere with 35.0 g. of Raney nickel over a 2.5 hr. period. The reaction mixture was stirred for 1.5 hr. after addition as complete and the catalyst removed by filtration. The filter cake was washed well with tetrahydrofuran and methylene chloride and the filtrate evaporated under reduced pressure. The residue (5.6 g.) was recrystallized from methanol and gave 4.45 g. (76%) of product m.p. 210°-212° C.
Reaction SMILES: [OH:1][CH:2]([C:6]([O:19][CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4]>C(Cl)(Cl)Cl>[OH:1][C@@H:2]([C:6]([O:19][CH3:20])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]([OH:5])=[O:4]
Reactant: COC(c1ccccc1)(c1ccccc1)C(O)C(=O)O
Solvent: ClC(Cl)Cl
Product: COC(c1ccccc1)(c1ccccc1)[C@H](O)C(=O)O
Temperature: 27.5 °C
Reaction time: 0.5 h

Procedure:
R(+)-phenyl ethyl amine (11.12 grams) was added to a solution of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid (25 grams) and chloroform (25 ml) at 40° C. and stirred for 30 minutes. The reaction mixture was cooled, and the solid obtained was filtered and washed with chloroform. Ethyl acetate (50 ml) and water (50 ml) was added to the obtained solid and then the reaction mixture was acidified with concentrated hydrochloric acid. The layers were separated and the aqueous layer extracted with ethyl acetate. The solvent from combined organic layer was distilled off completely under reduced pressure at below 60° C. The obtained residue was dissolved in toluene (30 ml) at 60-70° C. and then cooled to 25-30° C. The solid was filtered, washed with toluene and then dried to get the title compound.
Reaction SMILES: OO.[CH:3]1[C:16]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]=2[CH:6]=[CH:5][CH:4]=1.C1C2C3=C4C(=CC=2)C=CC=C4C=CC3=CC=1.C(N=C=NC(C)C)(C)C.[C:42]([OH:45])(=O)[CH3:43].C1C=C2C3OC3C3C(C2=CC=1)=CC=CC=3>C(OCC)(=O)C>[CH:4]1[CH:5]=[C:6]2[CH:42]3[O:45][CH:43]3[C:9]3[C:8]4[C:7]2=[C:16]([CH:15]=[CH:14][C:13]=4[CH:12]=[CH:11][CH:10]=3)[CH:3]=1
Reactant: c1ccc2c(c1)ccc1ccccc12
Reactant: CC(=O)O
Agent: CC(C)N=C=NC(C)C
Agent: OO
Agent: c1cc2ccc3cccc4ccc(c1)c2c34
Solvent: CCOC(C)=O
Product: c1cc2c3c(c1)ccc1cccc(c13)C1OC21
Yield: 27 %

Procedure:
Anhydrous hydrogen peroxide (98%) and carbodiimides were used in acidic ethyl acetate, an aprotic solvent, to epoxidize two arenes, phenanthrene and pyrene, but only in about 3% yield, based on the initial amount of the arene (Hamilton et al., Tet. Lett, 1977, 16, 1369). For example, phenanthrene (4 mmol), diisopropylcarbodiimide (8 mmol), 98% hydrogen peroxide (16 mmol), and acetic acid (8 mmol) were reacted in ethyl acetate. The yield of phenanthrene 9, 10-oxide was 28% based on the amount of reacted phenanthrene and 2.9% based on the amount of phenanthrene initially present. A reaction of pyrene under similar conditions yielded pyrene 4,5-oxide in 27% yield, based on the amount of reacted pyrene; the yield based on the amount of pyrene initially present was not stated. These researchers state that, "Control experiments indicate that all four components (arene, carbodiimide, H2O2, and acid) are required for the reaction." They also state that approximately the same yield of oxide is formed from these arenes when 30% hydrogen peroxide, and a four-fold increase in the carbodiimide concentration, are used instead of 98% hydrogen peroxide. The authors also speculate that, "In addition to its use in arene oxide synthesis, the carbodiimide-H2O2 system may be useful for simple alkene epoxidations under mild conditions," and make reference to three earlier articles. Two of the references cited by the authors, however, refer to systems using reagents other than carbodiimides to effect epoxidation of olefins. One reference cited (Rebek, J., Jr. et al., J. Chem. Soc. Chem. Commun., 1974, 711) reports that substituted peroxycarbamic acids, generated in situ from anhydrous hydrogen peroxide and carbonyldiimidazole, can be used to epoxidize olefins. A second reference cited (Matsumura et al. Tet. Lett. 1970, 2029.) reports that reaction of an isocyanate and hydrogen peroxide, in the presence of an olefin, leads to epoxidation of olefins.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[CH2:7][C@@H:6]([F:8])[CH2:5][N:4]1[C:9]([NH:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]([C:21]([NH2:23])=[O:22])[CH:13]=1)=[O:10].[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C.O>C(Cl)Cl>[F:8][C@H:6]1[CH2:5][N:4]([C:9]([NH:11][C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([C:21]([NH2:23])=[O:22])[CH:13]=2)=[O:10])[C@H:3]([CH2:2][NH:1][S:31]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[F:24])(=[O:33])=[O:32])[CH2:7]1
Reactant: NC[C@@H]1C[C@@H](F)CN1C(=O)Nc1cn(C(N)=O)c2ccccc12
Reactant: O=S(=O)(Cl)c1ccccc1F
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: NC(=O)n1cc(NC(=O)N2C[C@H](F)C[C@H]2CNS(=O)(=O)c2ccccc2F)c2ccccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 3-[((2S,4R)-2-aminomethyl-4-fluoro-pyrrolidine-1-carbonyl)-amino]-indole-1-carboxylic acid amide (52 mg, 0.163 mmol) (prepared as described Scheme B11) and 2-fluorobenzenesulfonyl chloride (24 μL, 0.179 mmol) in CH2Cl2 (0.5 mL), was added triethylamine (25 μL, 0.179 mmol) and the resulting suspension was stirred at RT under nitrogen overnight. The mixture was poured into water and extracted twice with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude residue was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, eluent: 20% to 100% CH3CN in H2O in 15 min, CH3CN and H2O containing 0.1% HCOOH, flow: 20 mL/min) to give after lyophilization of the purified fractions the desired material. Rf, TLC (EtOAc)=0.55; MS (LC-MS): 478.1 [M+H]+, 500 [M+Na]+, 516 [M+K]+, 977.2 [2M+Na]+, 476 [M−H]−; tR (HPLC conditions f): 1.73 min.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[N:6]=[CH:7][N:8]([C:10]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:9]=1.[CH3:30][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI>C1COCC1>[CH3:1][O:2][C:3](=[O:29])[CH:4]([CH3:30])[C:5]1[N:6]=[CH:7][N:8]([C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:9]=1
Reactant: COC(=O)Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Product: COC(=O)C(C)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A solution of 1-(triphenylmethyl)-1H-imidazol-4-ylacetic acid methyl ester (1.01 g, 2.63 mmol) in THF (25 ml) was cooled to -78° C. Lithium hexamethyldisilazide (2.76 ml of a 1 M solution in THF, 2.76 mmol) was added dropwise and the reaction stirred 30 min at -78° C. Methyl iodide (0.164 ml, 2.76 mmol) was added and the reaction stirred a furthur 1 hr at -78° C. and then at -20° C. for 4 hrs. The reaction was quenched with water (10 ml) and saturated NaHCO3 solutuon (10 ml) and extracted with EtOAc. The organic extracts were dried (MgSO4) and the solvent evaporated in vacuo. Chromatography of the residue (SiO2, 2 to 3% MeOH in CH2Cl2, gradient elotion) afforded the product.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(O)(=O)C1C=CC=CC=1.C1(C)C=CC(S([N:42]2[CH:46]=[CH:45][CH:44]=[CH:43]2)(=O)=O)=CC=1.N1C=CC=C1.OP(O)(O)=O>CC#N.C(Cl)Cl>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:43]2[NH:42][CH:46]=[CH:45][CH:44]=2)=[O:8])=[CH:9][CH:10]=1
Reactant: O=C(O)c1ccc(O)cc1
Reactant: Cc1ccc(S(=O)(=O)n2cccc2)cc1
Agent: O=C(O)c1ccccc1
Agent: O=P(O)(O)O
Solvent: ClCCl
Solvent: CC#N
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: O=C(c1ccc(O)cc1)c1ccc[nH]1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
To a stirred suspension of 4-hydroxybenzoic acid (5.50 g, 40.0 mmol) in CH3CN cooled to 0° C. was added trifluoroacetic anhydride (TFAA, 10 mL, 72.0 mmol). After 15 minutes the benzoic acid dissolved. To this cooled solution at 0° C. was added 1-(p-tolylsulfonyl)pyrrole (8.85 g, 40.0 mmol) followed by enough CH2Cl2 to dissolve the pyrrole at this temperature. An additional volume of trifluoroacetic anhydride (10 mL, 72.0 mmol) was added to the reaction mixture followed by H3PO4 (2 mL, 37.0 mmol) with rapid stirring. After the reaction mixture was stirred at room temperature for 12 hours, additional trifluoroacetic anhydride (6 mL, 43.2 mmol) and 4-hydroxybenzoic acid (4.00 g, 29.0 mmol) were added and stirring was continued for 12 hours. After this, the solvents were removed to dryness and the residue was suspended in 5% NaOH (250 mL) and stirred overnight. The suspension was removed by filtration and the filter cake was washed with 5% NaOH (250 mL). To the filtrate was added a saturated solution of NaHCO3 (200 mL) and the pH of the solution was rendered neutral by adding concentrated HCl. A pink microcrystalline material formed and was collected by filtration, washed with water and dried. Yield (2-(4-Hydroxybenzoyl)-pyrrole) 3.30 g, 44%. 1H NMR (500 MHz, CD2Cl2, 25° C.) δ 6.35 (m, 1H), 6.90 (m, 1H), 6.94 (d, 2H), 7.14 (m, 1H), 7.87 (d, 2H), 9.70 (bs, 1H).
Reaction SMILES: [CH3:1][O:2][CH2:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([CH3:20])[CH:19]=1)[C:13]([O:15]C)=[O:14].O.[OH-].[Li+]>CO.O1CCCC1>[CH3:1][O:2][CH2:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([CH3:20])[CH:19]=1)[C:13]([OH:15])=[O:14]
Reactant: COC[C@H]1CCCN1Cc1cc(C)cc(C(=O)OC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COC[C@H]1CCCN1Cc1cc(C)cc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred solution of methyl 3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoate (120 mg, 0.43 mmol) in methanol (2 mL), tetrahydrofuran (1 mL), and water (1 mL) is added lithium hydroxide (180 mg, 4.3 mmol), and the reaction mixture stirred at room temperature for 2 h. The reaction mixture is concentrated under reduced pressure, dissolved in methylene chloride, filtered, and the filtrate concentrated under reduced pressure to provide the title compound. ESI MS m/z 264 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[C:3]([Cl:14])=[CH:4][C:5]([O:10][CH2:11][O:12][CH3:13])=[C:6]([CH:9]=1)[CH2:7]O.[CH2:15]([N:17](CC)CC)C.CS(Cl)(=O)=O.O>ClCCl>[Br:1][C:2]1[C:3]([Cl:14])=[CH:4][C:5]([O:10][CH2:11][O:12][CH3:13])=[C:6]([CH:9]=1)[CH2:7][C:15]#[N:17]
Reactant: COCOc1cc(Cl)c(Br)cc1CO
Reactant: CCN(CC)CC
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: O
Product: COCOc1cc(Cl)c(Br)cc1CC#N
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a solution of 5-bromo-4-chloro-2-methoxymethoxybenzyl alcohol (137.9 g) and triethylamine (105 ml) in dichloromethane (500 ml) was added at 0° C. methanesulfonyl chloride (45.5 ml) over a period of 30 minutes. The mixture was stirred overnight (13 hours), while warming up to room temperature. The reaction mixture was poured into water, to which was added dichloromethane for extraction. The extract solution was dried (anhydrous magnesium sulfate) and concentrated. To a suspension of the concentrate and sodium cyanide (51.4 g) in dichloromethane (40 ml) was added dropwise at 0° C. DMSO (300 ml). The mixture was then stirred for 3 hours at room temperature. The reaction mixture was poured into water, which was subjected to extraction with ethyl acetate. The extract solution was washed with water, dried (anhydrous magnesium sulfate) and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluted with ethyl acetate/hexane) to give 5-bromo-4-chloro-2-methoxymethoxybenzyl cyanide (86.4 g) (Compound B-35). The physical properties are shown in [Table 6].
Reaction SMILES: [CH2:1]1[CH2:23][O:22][C:3]2([C:9]3[CH:10]=[CH:11][C:12]([CH:14]([CH3:17])[CH2:15][OH:16])=[CH:13][C:8]=3[CH:7]=[CH:6][C:5]3[CH:18]=[CH:19][CH:20]=[CH:21][C:4]2=3)[O:2]1>C(=O)([O-])[O-].[Ag+2].C1C=CC=CC=1>[CH2:23]1[CH2:1][O:2][C:3]2([C:9]3[CH:10]=[CH:11][C:12]([CH:14]([CH3:17])[CH:15]=[O:16])=[CH:13][C:8]=3[CH:7]=[CH:6][C:5]3[CH:18]=[CH:19][CH:20]=[CH:21][C:4]2=3)[O:22]1
Reactant: CC(CO)c1ccc2c(c1)C=Cc1ccccc1C21OCCO1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: c1ccccc1
Product: CC(C=O)c1ccc2c(c1)C=Cc1ccccc1C21OCCO1
Yield: 70 %

Procedure:
0.5 Gm. of 2-(5,5-ethylenedioxy-5H-dibenzo[a,d]cyclohepten-2-yl)propan-1-ol in 50 ml. of benzene, is refluxed for 6 hours with 4.0 gm. of silver carbonate on celite, prepared as described in Compt. Rendus. (1968) C, 267, 900a. The mixture is cooled and filtered and the solution evaporated to afford a 70% yield of 2-(5,5-ethylenedioxy-5H-dibenzo-[a,d]cyclohepten-2-yl)propionaldehyde.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][N:13]([C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:37][O:38][C:39](=[O:72])[NH:40][CH:41]([C:45]([N:47]1[CH2:51][CH2:50][CH2:49][CH:48]1[C:52]1[NH:53][CH:54]=[C:55]([C:57]2[CH:62]=[CH:61][C:60](B3OC(C)(C)C(C)(C)O3)=[CH:59][CH:58]=2)[N:56]=1)=[O:46])[CH:42]([CH3:44])[CH3:43].C(=O)([O-])[O-].[K+].[K+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:60]4[CH:61]=[CH:62][C:57]([C:55]5[NH:56][C:52]([CH:48]6[CH2:49][CH2:50][CH2:51][N:47]6[C:45](=[O:46])[CH:41]([NH:40][C:39]([O:38][CH3:37])=[O:72])[CH:42]([CH3:44])[CH3:43])=[N:53][CH:54]=5)=[CH:58][CH:59]=4)=[CH:23][CH:22]=3)=[CH:18][N:17]=2)[CH2:14][N:13]([C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7]
Reactant: COC(=O)NC(C(=O)N1CCCC1c1nc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c[nH]1)C(C)C
Reactant: COC(=O)NC(C(=O)N1CN(C(=O)c2ccccc2)CC1c1nc(-c2ccc(Br)cc2)c[nH]1)C(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: COC(=O)NC(C(=O)N1CCCC1c1ncc(-c2ccc(-c3ccc(-c4cnc(C5CN(C(=O)c6ccccc6)CN5C(=O)C(NC(=O)OC)C(C)C)[nH]4)cc3)cc2)[nH]1)C(C)C
Temperature: 120 °C

Procedure:
{1-[1′-Benzoyl-4-(4-bromo-phenyl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (crude, <0.101 mmol) was combined with [2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (45.1 mg, 0.091 mmol) under an argon atmosphere. Potassium carbonate (27.8 mg, 0.202 mmol) and Pd(PPh3)4 (10 mg, 0.009 mmol) were added, followed by DME (2.0 mL) and water (0.4 mL). The mixture was heated under microwave conditions for 20 minutes at 120° C. All volatiles were removed in vacuo and the crude material was dissolved in DMF and purified via RP-HPLC (eluent: water/MeCN w 0.1% TFA) to yield the product {1-[1′-Benzoyl-5-(4′-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (20.7 mg): LCMS-ESI+: calc'd for C46H53N9O7: 843.9 (M+). Found: 844.3 (M+H+); 1H-NMR: 300 MHz, (MeOH-d4) δ: 7.90-7.84 (m, 10H), 7.66-7.52 (m, 5H), 5.68 (m, 1H), 5.59 (m, 1H), 5.49 (m, 1H), 5.26 (m, 1H), 4.24 (d, J=7.5 Hz, 1H), 4.11 (m, 2H), 3.86 (m, 2H), 3.66 (s, 3H), 3.65 (s, 3H), 3.46 (d, J=5.7 Hz, 1H), 2.57 (m, 1H), 2.29-2.09 (m, 5H), 1.01-0.85 (m, 12H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]3[C:12]4[N:26](C5CCCCO5)[N:25]=[CH:24][C:13]=4[C:14](=[O:23])[N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:16]=3[CH:17]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.ClC1C(C2C=CC3C4NN(C5CCCCO5)CC=4C(=O)N(CC(F)(F)F)C=3C=2)=CC=CN=1.Cl.O1CCOCC1>C(Cl)Cl>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]3[C:12]4[NH:26][N:25]=[CH:24][C:13]=4[C:14](=[O:23])[N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:16]=3[CH:17]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=c1c2cnn(C3CCCCO3)c2c2ccc(-c3cccnc3Cl)cc2n1CC(F)(F)F
Agent: Cl
Agent: O=c1c2c(c3ccc(-c4cccnc4Cl)cc3n1CC(F)(F)F)NN(C1CCCCO1)C2
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=c1c2cn[nH]c2c2ccc(-c3cccnc3Cl)cc2n1CC(F)(F)F
Temperature: 25 °C
Reaction time: 3 h
Yield: 15 %

Procedure:
To a solution of 7-(2-chloropyrid-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one and 7-(2-chloropyrid-3-yl)-2-(tetrahydro-2H-pyran-2-yl)-5-(2,2,2-trifluoroethyl)-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (1.6 g, 3.46 mmol) in 34 mL of DCM, is added a 4M solution of hydrogen chloride in dioxane (8.5 mL, 34.6 mmol). The mixture is stirred for 3 hours at room temperature and concentrated to dryness. After purification by flash chromatography on amine phase (DCM/EtOH: 100/0 to 90/10), 189 mg of a white solid are obtained (yield=15%).
Reaction SMILES: [CH2:1]([C:8]#[N:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[O-].[Na+].[C:14](OCC)(=[O:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16]>>[C:2]1([CH:1]([C:8]#[N:9])[C:14](=[O:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#CCc1ccccc1
Reactant: CCOC(=O)C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Product: CCOC(=O)C(=O)C(C#N)c1ccccc1
Yield: 90 %

Procedure:
Reaction of benzyl cyanide, sodium ethylate and diethyl oxalate according to the method described in Org. Synth. Coll. Vol. II (1943) 287 and Chem. Ber. 107 (1974) 2794-2795 in alcohol, acidification with conc. (37%) hydrochloric acid to pH 2 and subsequent recrystallization of the separated precipitate from ethanol yielded ethyl phenylcyanopyruvate in 90% yield as yellow crystals, melting point 127°-128°.
Reaction SMILES: [CH3:1][N:2]([CH3:14])[CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[C:8]([Br:13])[CH:7]=1.[C:15](Cl)(=[O:18])[CH2:16][CH3:17]>C(N(CC)CC)C>[CH3:1][N:2]([CH3:14])[CH2:3][CH2:4][N:5]([C:15](=[O:18])[CH2:16][CH3:17])[C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[C:8]([Br:13])[CH:7]=1
Reactant: CN(C)CCNc1ccc(Br)c(Br)c1
Reactant: CCC(=O)Cl
Solvent: CCN(CC)CC
Product: CCC(=O)N(CCN(C)C)c1ccc(Br)c(Br)c1

Procedure:
In the manner given in Example 2, to a solution of N,N-dimethyl-N'-(3,4-dibromophenyl)ethylenediamine and triethylamine is added propionyl chloride to give N-[2-(dimethylamino)ethyl]-3',4'-dibromopropionanilide.
Reaction SMILES: [C:1]1([C:7]2([C:15]([OH:17])=[O:16])[CH2:10][C:9](OC)([O:11]C)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CCCl)C(C)C)(C)C>CC(O)=O>[C:1]1([C:7]2([C:15]([OH:17])=[O:16])[CH2:8][C:9](=[O:11])[CH2:10]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC1(OC)CC(C(=O)O)(c2ccccc2)C1
Agent: CC(C)N(CCCl)C(C)C
Solvent: CC(=O)O
Product: O=C1CC(C(=O)O)(c2ccccc2)C1
Reaction time: 2 h

Procedure:
1-Phenyl-3-oxocyclobutanecarboxylic acid was prepared by refluxing 1-phenyl-3,3-dimethoxycyclobutanecarboxylic acid (8.5 mmol) with 90% HOAc, evaporating the reaction mixture, taking up the residue in 0.1 M HCl and Et2O, extracting the aqueous layer with Et2O and drying (Na2SO4) and evaporating the organic layer. The crude oxocarboxylic acid was dissolved in DMF (30 mL) and then added to NaH (60% dispersion in mineral oil, 20 mmol, washed twice with hexane) at ambient temperature. After 30 min N,N-diisopropyl-2-chloroethylamine (1.8 mmol) was added. After 2 h, the reaction mixture was partitioned between H2O and toluene. The crude product was chromatographed on silica gel using toluene-Et3N 98:2 as eluent. The afforded oil was dissolved in Et2O and HCl (g)/Et2O was added whereby the product crystallized to yield 0.25 g (10%); mp 133-135° C.; 1H NMR (CDCl3) δ 1.39 (d,12H), 3.10 (m, 2H), 3.54 (m, 4H), 4.05 (m, 2H), 4.72 (t, 2H), 7.38 (m, 5H), 11.8 (br, 1H). Anal. (C19H27NO3.HCl) C, H, N.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18]C2CCCCO2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:1]1([CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][OH:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C(=CCCc1ccccc1)CCCCCCCOC1CCCCO1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: OCCCCCCCC=CCCc1ccccc1

Procedure:
A solution of the product of step (b) (8.7 g) in tetrahydrofuran (150 ml) of 2M hydrochloric acid was stirred at room temperature for 4 hours. The mixture was neutralised with sodium bicarbonate solution and extracted with dichloromethane. Evaporation of the extract and chromatography of the residue on silica gel eluting with 1:1 ether:hexane to remove starting material, then with ether, gave the title product as a pale oil.