Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=1.I[C:18]1[CH:23]=[CH:22][N:21]([CH2:24][CH2:25][C@@:26]([CH3:41])([S:37]([CH3:40])(=[O:39])=[O:38])[C:27]([NH:29][O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)=[O:28])[C:20](=[O:42])[CH:19]=1.O>O1CCOCC1.[Pd]>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:18]2[CH:23]=[CH:22][N:21]([CH2:24][CH2:25][C@@:26]([CH3:41])([S:37]([CH3:40])(=[O:39])=[O:38])[C:27]([NH:29][O:30][CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][O:32]3)=[O:28])[C:20](=[O:42])[CH:19]=2)=[CH:10][CH:9]=1
Reactant: C[C@@](CCn1ccc(I)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Reactant: OB(O)c1ccc(F)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C[C@@](CCn1ccc(-c2ccc(F)cc2)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Temperature: 80 °C

Procedure:
Pd EnCat™ (200 mg, 0.06 mmol) was added to a mixture of potassium carbonate (250 mg, 1.81 mmol), (4-fluorophenyl)boronic acid (84 mg, 0.602 mmol), and (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide, which may be produced as in Preparation 2 B, (300 mg, 0.602 mmol) in dioxane:water (5.5 mL, 10:1 mixture) in a 25 mL round bottom flask. The flask was heated overnight at 80° C. The reaction was cooled to ambient temperature and filtered through celite and washed with ethyl acetate (20 mL). The crude material was concentrated, and purified by chromatography on silica gel (gradient: 100:0 dichloromethane:methanol to 95:5 dichloromethane:methanol) to provide title compound as a viscous, foamy oil. Yield: 257 mg, 91.5%. MS (APCI) m/z 467.6 (M+H) 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.54-1.65 (m, 3H) 1.68 (d, J=2.34 Hz, 3H) 1.71-1.99 (m, 3H) 2.32-2.44 (m, 1H) 2.44-2.57 (m, 1H) 3.18 (d, J=2.93 Hz, 3H) 3.54-3.66 (m, 1H) 3.97-4.10 (m, 1H) 4.11-4.25 (m, 1H) 4.25-4.38 (m, 1H) 5.16 (d, J=15.81 Hz, 1H) 6.48 (dd, J=6.93, 1.27 Hz, 1H) 6.76 (s, 1H) 7.12 (t, J=8.59 Hz, 2H) 7.39 (d, J=7.02 Hz, 1H) 7.47-7.57 (m, 2H) 12.15 (d, J=7.42 Hz, 1H)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([Cl:29])[C:11]=1[C:12]([C:14]1[C:22]2[C:17](=[C:18]([NH:23][C:24]([CH:26]3[CH2:28][CH2:27]3)=[O:25])[N:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)=[O:13])[C:5]([O:7]C)=[O:6].[OH-].[Na+].O.Cl>O1CCCC1>[Cl:29][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([Cl:1])[C:11]=1[C:12]([C:14]1[C:22]2[C:17](=[C:18]([NH:23][C:24]([CH:26]3[CH2:28][CH2:27]3)=[O:25])[N:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)=[O:13])[C:5]([OH:7])=[O:6]
Reactant: COC(=O)c1cc(Cl)c(C(=O)c2c[nH]c3c(NC(=O)C4CC4)nccc23)c(Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cc(Cl)c(C(=O)c2c[nH]c3c(NC(=O)C4CC4)nccc23)c(Cl)c1
Yield: 79.7 %

Procedure:
A mixture of methyl 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)benzoate, (30 mg, 0.06 mmol) and sodium hydroxide (27 mg, 0.06 mmol) were stirred in tetrahydrofuran and water (1:1, 6 mL) solution for about 2 hours, followed by slowly addition of aqueous hydrochloric acid till pH 4-5. The precipitated product was filtered and dried under vacuum to afford 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)benzoic acid (20 mg, 62.5%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([OH:7])=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[N:30]1[C:35](=[O:36])[CH:34]=[CH:33][C:32]([C:37](Cl)=[O:38])=[CH:31]1>C1COCC1>[Cl:11][C:10]1[CH:9]=[CH:8][C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[NH:1][C:37]([C:32]1[CH:33]=[CH:34][C:35](=[O:36])[N:30]([C:24]2[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:23]=2[F:22])[CH:31]=1)=[O:38]
Reactant: O=C(Cl)c1ccc(=O)n(-c2c(F)cccc2F)c1
Reactant: Nc1cc(C(=O)O)ccc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(O)c1ccc(Cl)c(NC(=O)c2ccc(=O)n(-c3c(F)cccc3F)c2)c1
Temperature: -5 °C
Reaction time: 0.5 h
Yield: 24 %

Procedure:
To a solution of 3-amino-4-chlorobenzoic acid (509 mg) in THF (8 mL) was added dropwise an 1 M THF solution of lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (6 mL) while keeping the internal temperature below −5° C. under a nitrogen atmosphere, and the mixture was stirred around −5° C. for 30 min. To the solution was added dropwise a solution of 1-(2,6-difluorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarbonyl chloride (800 mg) in THF (8 ml), and the resulting mixture was stirred around −5° C. for 1 hr. The reaction mixture was partitioned between EtOAc (16 mL) and 1 M HCl (16 mL). The aqueous layer was extracted with EtOAc (8 mL). The organic layers were combined, washed with brine two times, dried over MgSO4, filtered and evaporated in vacuo. The residue was triturated with CH2Cl2, and the precipitates produced were collected by filtration. The isolated product was triturated with MeOH and collected by filtration to give 4-chloro-3-({[1-(2,6-difluorophenyl)-6-oxo-1,6-dihydro-3-pyridinyl]carbonyl}amino)benzoic acid (288 mg).
Reaction SMILES: [O-]CC.[Na+].Cl.[C:6]([NH2:14])(=[NH:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:15][CH:16]([C:22]([CH3:24])=O)[C:17](OCC)=[O:18]>C(O)C>[CH3:15][C:16]1[C:17](=[O:18])[NH:13][C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:14][C:22]=1[CH3:24]
Reactant: CCOC(=O)C(C)C(C)=O
Reactant: N=C(N)c1ccccc1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: Cc1nc(-c2ccccc2)[nH]c(=O)c1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 51.5 %

Procedure:
To a mixture of sodium ethoxide (31.3 g) and anhydrous ethanol (200 ml) is added benzamidine hydrochloride (23.9 g) at 0-5° C. The mixture is stirred at 0° C. for 30 minutes, and thereto is added dropwise a solution of ethyl 2-methylacetoacetate (20 g) and anhydrous ethanol (50 ml) at the same temperature. After addition, the mixture is stirred at room temperature for 30 minutes, and refluxed for six hours. The reaction mixture is concentrated under reduced pressure, and the residue is dissolved in water. The pH value of the mixture is adjusted to pH 4 by addition of conc. hydrochloric acid while the mixture is stirred at 0-5° C. The precipitates are collected by filtration, washed with water, further washed with diethyl ether, and recrystallized from ethanol to give the desired compound (14.3 g), m.p. 205-207° C.
Reaction SMILES: [C:1]1([CH3:24])[CH:6]=[CH:5][C:4]([NH:7][C:8]2([C:21]([NH2:23])=[O:22])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[CH:25](OCC)(OCC)OCC>>[CH2:14]([N:11]1[CH2:12][CH2:13][C:8]2([N:7]([C:4]3[CH:3]=[CH:2][C:1]([CH3:24])=[CH:6][CH:5]=3)[CH:25]=[N:23][C:21]2=[O:22])[CH2:9][CH2:10]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: CCOC(OCC)OCC
Reactant: Cc1ccc(NC2(C(N)=O)CCN(Cc3ccccc3)CC2)cc1
Product: Cc1ccc(N2C=NC(=O)C23CCN(Cc2ccccc2)CC3)cc1
Temperature: 150 °C
Reaction time: 15 h

Procedure:
4-(p-tolyl-amino)-1-(phenylmethyl)-4-piperidine-carboxamide (1.62 g) was dissolved in 10 ml triethyl orthoformate and stirred at 150° C. for 15 hours. After cooling to room temperature, the reaction mixture was filtered and the light brown powder washed with ether to yield 8-benzyl-1-p-tolyl-1,3,8-triazaspiro[4,5]dec-2-en-4-one (0.99 g). M.p. 208-213° C.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].Br[CH2:6][C:7]1([CH3:11])[CH2:10][O:9][CH2:8]1>O>[N:1]([CH2:6][C:7]1([CH3:11])[CH2:10][O:9][CH2:8]1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC1(CBr)COC1
Agent: [Na+]
Solvent: O
Product: CC1(CN=[N+]=[N-])COC1
Temperature: 25 °C
Yield: 85 %

Procedure:
A 5 liter jacketed flask equipped with a mechanical stirrer was charged with 1062 grams of sodium azide, 1972 ml of water, and 2450 grams of 3-bromomethyl-3-methyloxetane (supplied by AmeriBrom, Inc. of New York). This mixture was brought to reflux with vigorous mixing. After 48 hours the mixture was cooled to room temperature. The organic layer was separated off and washed three times with 1000 ml of water before being dried over molecular sieves to yield pure 3-azidomethyl-3-methyloxetane at 85% yield.
Reaction SMILES: [CH3:1][N:2]([CH3:10])[CH:3]=[CH:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].C(N(CC)CC)C.[Br:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[C:21]([Cl:28])[CH:20]=1>C1(C)C=CC=CC=1>[Br:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([C:4](=[CH:3][N:2]([CH3:10])[CH3:1])[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[O:24])=[C:21]([Cl:28])[CH:20]=1
Reactant: O=C(Cl)c1ccc(Br)cc1Cl
Reactant: CCOC(=O)C=CN(C)C
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)C(=CN(C)C)C(=O)c1ccc(Br)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68 %

Procedure:
30.2 g of ethyl 3-dimethylaminoacrylate and 29.3 ml of triethylamine are dissolved in 180 ml of toluene and boiled at reflux. At this temperature a solution of 53 g of 4-bromo-2-chloro-benzoyl chloride (U.S. Pat. No. 4,959,363) in 50 ml of toluene is added dropwise over 30 min. and the mixture is subsequently heated at reflux for a further 1 hr. The mixture is left to cool to room temperature and is stirred in an ice bath for a further 30 min. The suspension is filtered and the precipitated triethylamine hydrochloride is washed with 40 ml of ice-cold toluene. The filtrate is concentrated to half of its volume and then, for crystallization, diluted with 100 ml of hexane and stirred in an ice bath for 1 hr. 51.2 g (67%) of ethyl 2-(4-bromo-2-chloro-benzoyl)-3-dimethylaminoacrylate are obtained as colourless crystals. M.p. 100°-101°.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1.[F:20][C:21]1[CH:22]=[C:23]([N:31]=[C:32]=[O:33])[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1>>[F:20][C:21]1[CH:22]=[C:23]([NH:31][C:32](=[O:33])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[C:16]4[C:11](=[CH:12][N:13]=[CH:14][CH:15]=4)[NH:10][C:9]=3[C:17]([NH2:19])=[O:18])=[CH:6][CH:7]=2)[CH:24]=[C:25]([C:27]([F:29])([F:30])[F:28])[CH:26]=1
Reactant: NC(=O)c1[nH]c2cnccc2c1-c1ccc(N)cc1
Reactant: O=C=Nc1cc(F)cc(C(F)(F)F)c1
Product: NC(=O)c1[nH]c2cnccc2c1-c1ccc(NC(=O)Nc2cc(F)cc(C(F)(F)F)c2)cc1

Procedure:
69 mg of pale yellow solid 3-{4-[3-(3-fluoro-5-trifluoromethylphenyl)ureido]-phenyl}-1H-pyrrolo[2,3-c]pyridine-2-carboxamide are prepared as described in Example 1 starting with 3-(4-aminophenyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide and 3-fluoro-5-trifluoromethylphenyl isocyanate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[NH:18][N:17]=[N:16][N:15]=2)[CH:9]=1.[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=1B(O)O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1.C(O)C>ClCCl.O.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>[CH2:19]([O:26][C:27]1[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][C:32]=1[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[NH:18][N:17]=[N:16][N:15]=3)[CH:9]=2)=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: Brc1ccccc1-c1cccc(-c2nnn[nH]2)c1
Reactant: OB(O)c1cc(Cl)ccc1OCc1ccccc1
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: ClCCl
Solvent: Cc1ccccc1
Solvent: O
Product: Clc1ccc(OCc2ccccc2)c(-c2ccccc2-c2cccc(-c3nnn[nH]3)c2)c1

Procedure:
A mixture of 5-(2′-bromo-biphenyl-3-yl)-1H-tetrazole (163 mg, 0.54 mmol), 2-benzyloxy-5-chlorobenzeneboronic acid (156 mg, 0.59 mmol), potassium carbonate (589 mg, 4.33 mmol), and tetrakis(triphenylphosphine)palladium(0) (63 mg, 0.05 mmol) in 1.1 toluene/ethanol (5 ml) was stirred and heated under nitrogen for 16 hours. After cooling the mixture was diluted with dichloromethane and water. The organic phase was dried and evaporated.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[O:9])=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.FC(F)(F)C(O)=O.[CH3:26][S:27]([N:30]1[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]1)(=[O:29])=[O:28]>>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[O:9])=[CH:6][CH:5]=[C:4]([NH:36][CH:33]2[CH2:34][CH2:35][N:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH2:31][CH2:32]2)[N:3]=1
Reactant: CS(=O)(=O)N1CCC(N)CC1
Reactant: COc1ccc(C(=O)c2ccc(Cl)nc2N)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(C(=O)c2ccc(NC3CCN(S(C)(=O)=O)CC3)nc2N)cc1

Procedure:
The title compound was prepared from (2-Amino-6-chloro-pyridin-3-yl)-(4-methoxy-phenyl)-methanone (Example 35) and 1-methanesulfonyl-piperidin-4-ylamine (Step A, Example 6) using the procedure described in Step B. Example 6. HRMS, observed: 405.1595, calcd for (M+H)+: 405.1591.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[C:6]3[CH:13]=[CH:12][N:11](COCC[Si](C)(C)C)[C:7]3=[N:8][CH:9]=2)[N:4]([C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[CH3:28])[C:3]1=[O:29].FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+].C(N)CN>O.O1CCCC1>[CH3:1][N:2]1[C:10]2[C:5](=[C:6]3[CH:13]=[CH:12][NH:11][C:7]3=[N:8][CH:9]=2)[N:4]([C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[CH3:28])[C:3]1=[O:29]
Reactant: C[C@@H]1CCCC[C@@H]1n1c(=O)n(C)c2cnc3c(ccn3COCC[Si](C)(C)C)c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: NCCN
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H]1CCCC[C@@H]1n1c(=O)n(C)c2cnc3[nH]ccc3c21
Temperature: 110 °C
Reaction time: 3 h
Yield: 91.1 %

Procedure:
To a solution of 3-methyl-1-[(1S,2R)-2-methylcyclohexyl]-6-{[2-(trimethylsilyl)ethoxy]methyl}-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one (40 mg) in water (2 mL) was added trifluoroacetic acid (2 mL) and the mixture was stirred 110° C. for 3 hours. The mixture was extracted with chloroform. The extract was washed with saturated aqueous sodium hydrogencarbonate and water, dried over MgSO4, filtrated and evaporated to give a white solid. The solid was dissolved with tetrahydrofuran (2 mL) and saturated potassium carbonate aqueous solution (2 mL) was added. The mixture was stirred for 1 hour. To the mixture was added 1,2-ethanediamine (0.5 mL) and the mixture was stirred for 1 hour. The mixture was extracted with chloroform. The extract was washed with water, dried over MgSO4, filtrated and evaporated. The residue was purified by column chromatography on silica gel with chloroform and methanol (100:0 to 95:5) to give 3-methyl-1-[(1S,2R)-2-methylcyclohexyl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one (25 mg) as a white powder.
Reaction SMILES: Cl[CH:2]([O:6][C:7]([NH:9][CH2:10][C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:8])[CH:3]([CH3:5])[CH3:4].N12CCCN=C1CCCCC2.[C:32]([OH:40])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[N:35][CH:34]=1>CC(C)=O>[C:32]([O:40][CH:2]([O:6][C:7]([NH:9][CH2:10][C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:8])[CH:3]([CH3:5])[CH3:4])(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[N:35][CH:34]=1
Reactant: CC(C)C(Cl)OC(=O)NCC1(CC(=O)O)CCCCC1
Reactant: O=C(O)c1cccnc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC(C)=O
Product: CC(C)C(OC(=O)NCC1(CC(=O)O)CCCCC1)OC(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 14.5 %

Procedure:
A mixture of (93) (268 mg, 0.88 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (158 μL, 1.01 mmol), and nicotinic acid (637 mg, 5.2 mmol) in acetone was stirred at room temperature for 48 h. After filtration, the filtrate was concentrated in vacuo and the resulting residue was purified by reverse phase preparative HPLC to afford 50 mg (14%) of the title compound. 1H NMR (CD3OD, 400 MHz): δ 1.07 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 1.32-1.58 (m, 10H), 2.19 (m, 1H), 2.26 (s, 2H), 3.23 (m, 2H), 6.78 (d, J=4.8 Hz, 1H), 7.58 (m, 1H), 8.39 (d, J=6.4 Hz, 1H), 8.76 (d, J=4.4 Hz, 1H), 9.10 (s, 1H). MS (ESI) m/z 393.42 (M+H+).
Reaction SMILES: C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[CH2:14][CH2:13]3)[CH2:9]2)C=CC=CC=1.C(O)(=O)C>CO.[OH-].[OH-].[Pd+2]>[NH:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[CH2:14][CH2:13]2)[CH2:9]1
Reactant: CN(C)C(=O)C1CCN(C2CN(C(c3ccccc3)c3ccccc3)C2)CC1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: CN(C)C(=O)C1CCN(C2CNC2)CC1
Temperature: 25 °C
Reaction time: 96 h
Yield: 98.2 %

Procedure:
Palladium hydroxide on carbon (0.10 g) was placed in a 5 mL vial intended for microwave synthesis. 1-[1-(Diphenylmethyl)azetidin-3-yl]-N,N-dimethylpiperidine-4-carboxamide (0.20 g, 0.53 mmol) dissolved in methanol (3 mL) and acetic acid (0.3 mL) was added. The mixture was stirred under hydrogen (1.6 bar) at RT for four days. The mixture was filtered through a plug of Celite®. The solvent was removed by evaporation and there was obtained 0.11 g (53%) of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)CC)C.C([N:25]1[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:28]([CH2:35]Br)[NH:27][C:26]1=[O:37])(=O)C.[ClH:38]>C(O)C>[ClH:38].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:35][C:28]2[NH:27][C:26](=[O:37])[NH:25][C:29]=2[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:11][CH2:10]1
Reactant: CCOC(=O)c1c(CBr)[nH]c(=O)n1C(C)=O
Reactant: COc1ccccc1N1CCNCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1[nH]c(=O)[nH]c1CN1CCN(c2ccccc2OC)CC1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To a cooled solution (0° C.) of 2 g of 1-(2-methoxyphenyl)piperazine and 2.1 g of triethylamine in 40 ml of ethanol is added 2.9 g of ethyl 3-acetyl-5-(bromomethyl)-2,3-dihydro-2-oxo-1H-imidazole-4-carboxylate. The resulting solution is stirred at 0° C. for 4 hours, 30 ml of ice-water is added and the mixture is filtered. One equivalent of hydrochloric acid is added to the filtrate and it is evaporated to dryness. The residue crystallizes from a mixture of ethanol and ethyl acetate (1:1) and is recrystallized from that solvent mixture to give ethyl 2,3-dihydro-5-[[4-(2-methoxyphenyl)-1-piperazinyl]methyl]-2-oxo-1H-imidazole-4-carboxylate hydrochloride melting at about 227° C. (dec.). The free base of this compound has the following structural formula: ##STR6##
Reaction SMILES: O1C=CC=C1C[NH:7][C:8]1[C:9](=[CH:13][C:14]([S:25](=[O:28])(=[O:27])[NH2:26])=[C:15]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)[CH:16]=1)[C:10]([OH:12])=[O:11].[CH2:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH2:29]([NH:36][NH:7][C:8]1[C:9](=[CH:13][C:14]([S:25](=[O:27])(=[O:28])[NH2:26])=[C:15]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)[CH:16]=1)[C:10]([OH:12])=[O:11])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: NS(=O)(=O)c1cc(C(=O)O)c(NCc2ccco2)cc1Oc1cccc(Cl)c1
Reactant: NCc1ccccc1
Product: NS(=O)(=O)c1cc(C(=O)O)c(NNCc2ccccc2)cc1Oc1cccc(Cl)c1

Procedure:
45.5 g of the carboxylic acid prepared in Example 9 (b) (0.1 mol) were reacted with 100 ml of benzylamine as in Example 9 (c), and the reaction product was purified by recrystallization from ethanol.
Reaction SMILES: C[CH:2]1[CH2:6][CH2:5][O:4][CH2:3]1.[CH2:7]1OC1C.[OH-].[K+]>O1CCCC1.C(O)=O>[CH2:5]1[O:4][CH:6]1[CH3:2].[CH3:7][CH:3]1[CH2:2][CH2:6][CH2:5][O:4]1
Reactant: CC1CCOC1
Agent: CC1CO1
Agent: [K+]
Agent: [OH-]
Solvent: O=CO
Solvent: C1CCOC1
Product: CC1CCCO1
Yield: 3 %

Procedure:
195 parts of the catalyst used in Example 2 were introduced into a thermostatically regulated reaction vessel equipped with a stirring means. Then the reaction vessel was charged with a mixture of 900 parts tetrahydrofuran, 50 parts 3-methyl tetrahydrofuran and 40 parts formic acid. To this mixture, which was stirred constantly, 10 parts of propylene oxide per hour were then added at a uniform rate over a period of five hours. In this way, the propylene oxide concentration in the reaction mixture was kept constant at 0.08 wt. %. The reaction temperature was 50 C. After all the propylene oxide had been added, the reaction mixture was stirred for another four hours at reaction temperature. The resulting copolymer solution was separated from the catalyst by filtering. The filtrate was free of propylene oxide and consisted of 43% copolymer, 53% unreacted tetrahydrofuran and 4% 3-methyl tetrahydrofuran, as was determined by boildown under standard pressure and under vacuum. The solvent-free copolymer had a saponification number of 37 mg KOH/g and a hydroxyl number of 13 mg KOH/g. The product contained less than 0.3% cyclic oligomeric ethers. The ester-containing polymer was then mixed with an equal volume of methanol and, after addition of 10 parts of calcium hydroxide, was transesterified to glycol under standard pressure at 32° C. by distillation on a column with 20 theoretical trays, the methyl formate ester being distilled off. When the transesterification to glycol was complete, the calcium hydroxide used as transesterification catalyst was filtered off and the methanolic solution of the copolymer was boiled down completely—first under standard pressure and later under vacuum—using a film evaporater. The polymer obtained was pure, ester-free glycol and had a hydroxyl number of 51 mg KOH/g, which corresponds to a molecular weight of 2210. The 13C NMR spectrum showed that the copolymer had been formed from approximately 10% propylene oxide, 87% tetrahydrofuran and 3% methyl tetrahydrofuran. The product's dispersity Mw/Mn was 1.25. Its color index was below 5 APHA and the acid number less than 0.01 mg KOH/g.
Reaction SMILES: [N:1]1[CH:6]=[C:5]([O:7][C:8]2[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=2)[CH:4]=[N:3][CH:2]=1.[CH3:16][NH2:17].[BH4-].[Na+].O>CCO>[CH3:16][NH:17][CH2:12][C:11]1[CH:14]=[CH:15][C:8]([O:7][C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)=[CH:9][CH:10]=1
Reactant: CN
Reactant: O=Cc1ccc(Oc2cncnc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CNCc1ccc(Oc2cncnc2)cc1
Reaction time: 1 h
Yield: 100 %

Procedure:
4-(Pyrimidin-5-yloxy)benzaldehyde (0.344 g, 1.7 mmol) was stirred with 33% methylamine in EtOH (30 mL) at reflux for 3 hours and then concentrated. The residue was dissolved in MeOH and treated with sodium borohydride (0.195 g, 5.2 mmol) over 1 hour and stirred for a further 1 hour. Water was added and the product was extracted three times with EtOAc. The organic phases were combined, washed with brine, dried and concentrated to give 0.267 g (100%) of product that was used without further purification.
Reaction SMILES: F[C:2]1[C:7]([CH:8]2[CH2:14][CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)=[O:25].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([C:26]1[CH:31]=[CH:30][C:29]([O:32][C:2]2[C:7]([CH:8]3[CH2:14][CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:28][CH:27]=1)=[O:25]
Reactant: O=C(c1ccc(O)cc1)c1nc2ccccc2[nH]1
Reactant: Fc1ncccc1C1CCCOCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=C(c1ccc(Oc2ncccc2C2CCCOCC2)cc1)c1nc2ccccc2[nH]1
Temperature: 140 °C
Reaction time: 96 h

Procedure:
2-Fluoro-3-(oxepan-4-yl)pyridine (0.10 g, 0.51 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.37 g, 1.54 mmol), and cesium carbonate (0.50 g, 1.54 mmol) were mixed in NMP (1.5 mL). The reaction mixture was placed under a nitrogen atmosphere and stirred at 140° C. for 96 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic layers were washed with 1 M aqueous sodium hydroxide, washed with sat. sodium chloride, dried over magnesium sulfate, and concentrated in vacuo. The resulting crude product was purified by silica gel chromatography (EtOAc/hexanes) to give (1H-benzo[d]imidazol-2-yl)(4-(3-(oxepan-4-yl)pyridin-2-yloxy)phenyl)methanone. MS (ESI, pos. ion) m/z: 414.1 (M+1). IC50 (uM) +++++.