Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:18][CH:17]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11](Br)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH:56]1([C:62]2[CH:67]=[CH:66][C:65](B(O)O)=[CH:64][CH:63]=2)[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]1.C([O-])(O)=O.[Na+]>CCO.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:18][CH:17]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:59]1[CH:58]=[CH:57][C:56]([CH:62]3[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]3)=[CH:61][CH:60]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc2cc(Br)ccc2n1-c1ccc(OC(C)C)cc1
Reactant: OB(O)c1ccc(C2CCCCC2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cc2cc(-c3ccc(C4CCCCC4)cc3)ccc2n1-c1ccc(OC(C)C)cc1
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 92.9 %

Procedure:
A mixture of 5-bromo-1-(4-isopropoxyphenyl)indole-2-carboxylic acid ethyl ester (154 mg, 0.38 mmol), K3PO4 (282 mg, 1.83 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), tri(o-tolyl)phosphine (12 mg, 0.04 mmol), and toluene (3.5 mL) was stirred under argon for 25 min at room temperature. 4-Cyclohexylphenylboronic acid (117 mg, 0.57 mmol) in EtOH (0.5 mL) was added and the mixture was heated at reflux for 1 h. The mixture was allowed to cool, poured into NaHCO3 (aq. sat.), and extracted wait EtOAc. The combined extracts were washed with brine, dried over Na2SO4, concentrated and purified by chromatography to give the sub-title compound (170 mg, 93%).
Reaction SMILES: CC([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([Hg]Cl)[CH:6]=1)(C)C.C([O-])([O-])=O.[K+].[K+].[CH2:20](Br)[CH:21]=[CH2:22]>[Na+].[Cl-]>[CH2:22]([O:11][C:8]1[CH:7]=[CH:6][CH:5]=[CH:10][CH:9]=1)[CH:21]=[CH2:20]
Reactant: CC(C)(C)c1ccc(O)c([Hg]Cl)c1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Product: C=CCOc1ccccc1
Yield: 92 %

Procedure:
More precisely, 9.3 g of mercurobutol are taken which are dissolved in 50 ml of hot denatured alcohol, in the presence of NaCl. 2 g of potash are carefully added. A thick white precipitate is formed. 4.4 ml of allyl bromide are added in 21 ml of denatured alcohol and the product is mixed with the precipitate which becomes more fluid. The product is heated for two hours at the boiling temperature of the alcohol, then filtered hot. 9.43 g of 2-chloromercuri 4-tertiobutyl phenol allyl-ether are obtained, with a yield of 92%. This product is pure, as may be checked by thin layer chromatography. Its melting temperature is 110° C. It is in the form of a white, water-insoluble powder.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Br)[N:3]=1.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.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>[N:3]1[C:2]([NH2:1])=[CH:7][CH:6]=[CH:5][C:4]=1[C:7]1[CH:2]=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1cccc(Br)n1
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: [Na+]
Solvent: CC#N
Product: Nc1cccc(-c2cccnc2)n1
Temperature: 25 °C
Yield: 153.7 %

Procedure:
To a stirred degassed suspension of a mixture of 2-amino-6-bromopyridine (5.38 g, 31.09 mmol), 2,4,6-(3-pyridinyl)-cyclotriboroxane (3.80 g, 12.07 mmol) and aqueous Na2CO3 (100 mL, 0.4M) in acetonitrile (100 mL) at room temperature Pd(PPh3)4 (1.70 g, 1.47 mmol) was added. The reaction mixture was heated at 95° for 1 to 2 days under nitrogen, cooled to the room temperature and filtered. The filtrate was concentrated purified by flash chromatography on silica gel (MeOH/CH2Cl2: 5/95→10/90 plus a few drops of NH4OH) and co-precipitated with a mixture of AcOEt/CH2Cl2/hexane to afford the title compound 11 (4.091 g, 23.90 mmol, 77% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.16 (dd, J=2.2, 0.8 Hz, 1H), 8.57 (dd, J=4.7, 1.6 Hz, 1H), 8.33-8.28 (m, 1H), 7.54-7.44 (m, 2H), 7.14 (dd, J=7.3, 0.5 Hz, 1H), 6.49 (dd, J=8.2, 0.4 Hz, 1H), 6.12 (bs, 2H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:47])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27](B4OC(C)(C)C(C)(C)O4)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:39][NH:40][C:41]([O:43][CH:44]([CH3:46])[CH3:45])=[O:42])([CH3:4])([CH3:3])[CH3:2].C(O)(=[O:50])C.OO.[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1.O>[C:1]([O:5][C:6](=[O:47])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:25]=[CH:26][C:27]([OH:50])=[CH:28][CH:29]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:39][NH:40][C:41]([O:43][CH:44]([CH3:45])[CH3:46])=[O:42])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)O
Reactant: Cc1oc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)nc1CCOc1ccc(CCC(=O)OC(C)(C)C)c(CNC(=O)OC(C)C)c1
Agent: O=S([O-])([O-])=S
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1oc(-c2ccc(O)cc2)nc1CCOc1ccc(CCC(=O)OC(C)(C)C)c(CNC(=O)OC(C)C)c1
Temperature: 25 °C
Yield: 94.5 %

Procedure:
According to the procedure in Organic Synthesis, vol. V, p. 918, a solution of 3-[2-(isopropoxycarbonylamino-methyl)-4-(2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazol-4-yl}-ethoxy)-phenyl]-propionic acid tert-butyl ester (1.4 g, 2.16 mmol, Example 368, Step A) in THF (8 mL) was treated with glacial acetic acid (194 mg, 3.24 mmol) at 0° C. A solution of 30% H2O2 in water (4.75 mL) was diluted with H2O (1 mL) and added to the reaction mixture. The mixture was warmed to room temperature and treated with 1M aqueous Na2S2O3 solution (50 mL). The THF was removed under vacuum and the aqueous phase was extracted with ethyl acetate. The organic layer was washed with 1M Na2S2O3 (2×50 mL), dried (MgSO4), filtered, and concentrated to an oil containing (1.21 g). Purification using silica gel chromatography (1:1 ηεξανεσ:ετηψλ acetate) yielded the title compound as a white solid (1.10 g, 95%). 1H NMR (300 MHz CDCl3) δ 1.15 (d, 6H), 1.19 (s, 9H), 2.26 (s, 3H), 2.39 (t, 2H), 2.75 (t, 2H), 2.85 (t, 2H), 4.10 (t, 2H), 4.28 (d, 2H), 4.85 (m, 1H), 5.01 (br d, 1H), 6.63 (dd, 1H), 6.74 (m, 3H), 6.96 (d, 1 h), 7.70 (d, 2H); MS [EI+] m/z 539 (M+H).
Reaction SMILES: [O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1.[C:18]([O-])([O-])=O.[Na+].[Na+].F[B-](F)(F)F.C[O+](C)C.O>C(Cl)Cl>[CH2:11]([O:10][C:8]([N:4]1[CH2:3][C:2]([O:1][CH3:18])=[N:7][CH2:6][CH2:5]1)=[O:9])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C([O-])[O-]
Reactant: O=C1CN(C(=O)OCc2ccccc2)CCN1
Agent: C[O+](C)C
Agent: F[B-](F)(F)F
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: COC1=NCCN(C(=O)OCc2ccccc2)C1
Temperature: 25 °C
Yield: 94.7 %

Procedure:
A solution of benzyl 3-oxopiperazine-1-carboxylate (20.50 g, 10.67 mmol) in CH2Cl2 (100 ml) was cooled to 0° C. and treated with Na2CO3 (23.0 g, 217 mmol) for 10 minutes. Neat trimethyloxonium tetrafluoroborate (5.50 g, 37.2 mmol) was added in one portion, then the reaction is allowed to warm to room temperature for 6 hours. The reaction was poured into water (100 ml), and the layers were separated. The aqueous layer was re-extracted aqueous with 50 ml CH2Cl2 and the combined organic layers were washed with brine (100 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to yield 5-methoxy-3,6-dihydro-2H-pyrazine-1-carboxylic acid benzyl ester (2.51 g, 95%) as an oil. LCMS (Table 1, Method a) Rt=3.00 min, m/z 249.24 (M+H)+−; 1H NMR (400 MHz, DMSO-d6) δ 7.36 (m, 5H), 5.16 (s, 2H), 3.96 (s, 2H), 3.68 (s, 3H), 3.54 (s, 2H), 3.47 (m, 2H)
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16]C)=[CH:5][CH:4]=1)[CH3:2].B(Br)(Br)Br.O>ClCCl>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[OH:16])=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(Cc2ccccc2OC)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: O
Product: CCc1ccc(Cc2ccccc2O)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
0.83 g of (4-ethylphenyl)(2-methoxyphenyl)methane 55 is dissolved in dichloromethane. 11.0 ml of boron tribromide (1 M in CH2Cl2) are added dropwise to the mixture. The mixture is stirred at room temperature for 5 hours and, after addition of water, the dichloromethane phase is separated off. The aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with water and NaCl solution, dried over sodium sulfate and concentrated. 0.77 g is obtained as crude product which can be purified by chromatography. C15H16O (212.29) MS (ESI): 235.20 (M+Na+)
Reaction SMILES: [F:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][CH2:7][CH2:8][CH2:9][C:10](=[O:11])[C:4]=2[CH:3]=1.[Br:14]Br>CCOCC>[Br:14][CH:9]1[CH2:8][CH2:7][O:6][C:5]2[CH:12]=[CH:13][C:2]([F:1])=[CH:3][C:4]=2[C:10]1=[O:11]
Reactant: BrBr
Reactant: O=C1CCCOc2ccc(F)cc21
Solvent: CCOCC
Product: O=C1c2cc(F)ccc2OCCC1Br
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Dissolved 7-fluoro-3,4-dihydrobenzo[b]oxepin-5(2H)-one (1.58 g, 8.77 mmol) in 80 mL ether and added bromine (0.497 mL, 9.65 mmol) and allowed the reaction mixture to stir at room temperature 20 hours. Reaction was complete by LCMS. Concentrated the reaction in vacuo and purified by flash chromatography (0 to 30% ethyl acetate/heptanes). Concentrated in vacuo and NMR indicated 4-bromo-7-fluoro-3,4-dihydrobenzo[b]oxepin-5(2H)-one.
Reaction SMILES: ClC1NC2C=C(Cl)C(Cl)=CC=2N=1.[Si](S(C(F)(F)F)(=O)=O)(C)(C)C.[Cl:24][C:25]1[N:29]([C@@H:30]2[O:42][C@H:41]([CH3:43])[C@@H:36]([O:37]C(=O)C)[C@H:31]2[O:32]C(=O)C)[C:28]2[CH:44]=[C:45]([Cl:49])[C:46]([Cl:48])=[CH:47][C:27]=2[N:26]=1.C([O-])([O-])=O.[Na+].[Na+].CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O>C(#N)C.CO.CCO.O.CO.C(Cl)(Cl)Cl>[Cl:24][C:25]1[N:29]([C@@H:30]2[O:42][C@H:41]([CH3:43])[C@@H:36]([OH:37])[C@H:31]2[OH:32])[C:28]2[CH:44]=[C:45]([Cl:49])[C:46]([Cl:48])=[CH:47][C:27]=2[N:26]=1
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1n1c(Cl)nc2cc(Cl)c(Cl)cc21
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: C[Si](C)(C)S(=O)(=O)C(F)(F)F
Agent: Clc1nc2cc(Cl)c(Cl)cc2[nH]1
Solvent: O
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: C[C@H]1O[C@@H](n2c(Cl)nc3cc(Cl)c(Cl)cc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
2,5,6-Trichlorobenzimidazole (500 mg, 2.26 mmol) was suspended in dry acetonitrile (90 mL) and treated with BSA (0.56 mL, 2.26 mmol). After 15 minutes, 1,2,3-tri-O-acetyl-5-deoxyribose (621 mg, 2.26 mmol) was added along with TMSTf (0.45 mL, 2.26 mmol). The mixture was allowed to stir at room temperature overnight. The mixture was concentrated under reduced pressure and applied to a silica gel column (3.5×9 cm) and eluted with dichloromethane, isolating 490 mg (64%) of the β anomer independent of the α anomer; the rest of the material isolated was an inseparable α, β mixture. For the β anomer (209): 1H NMR(CDCl3): δ 7.64 (s, 1H, C7 -H), 7.48 (s, 1H, C4 -H), 6.02 (d, 1H,1'-H, 6.66 Hz), 5.46 (dd, 1H, 2'-H), 5.12 (dd, 1H, 3' -H), 4.20 (m, 1H, 4'-H), 2.08 (s, 3H), 1.97 (s, 3H), 1.52 (d, 3H, 5'-H). 13C NMR (CDCl3): δ 169.42, 169.01, 141.32, 141.08, 131.98, 127.75, 127.75, 120.80, 112.37, 87.35, 78.63, 73.46, 71.40, 20.32, 20.02, 18.61. 2,5,6-Trichloro-1-(2,3-di-O-acetyl-5-deoxy-β-D-ribofuranosyl)benzimidazole (209), (460 mg., 0.001 moles) was dissolved in a MeOH/EtOH/H2O mixture (45 mL, 45 mL, 10 mL, respectively) and stirred for 2 hours at room temperature in the presence of Na2CO3 (112 mg, 0.001 moles). TLC analysis 2% of MeOH/CHCl3 indicated the disappearance of the protected nucleoside and complete formation of a more polar compound. The aqueous alcoholic solution was neutralized with the addition of glacial acetic and then concentrated under reduced pressure to about 10 mL. The yellow, oily residue was triturated with the addition of 10 mL H2O and the yellow precipitate that formed was collected by vacuum filtration. The isolated material was dissolved in EtOH, treated with charcoal, filtered, concentrated to dryness, and recrystallized from H2O/EtOH/dioxane. The compound was re-crystallized from H2O. mp: 85°-86° C. 1H NMR (DMSO-d6): δ 7.97 (s, 1H, C7 -H), 7.86 (s, 1H, C4 -H), 5.86 (d, 1H, 1'-H, 6.42 Hz), 5.53 (d, 1H, 2'-OH), 5.27 (d, 1H, 3'-OH), 4.48 (q, 1H, 2'-H), 4.00 (m, 1H, 3'-H), 3.88 (m, 1H, 4'-H), 1.40 (d, 3H, 5'-H). 13C NMR (DMSO-d6): δ 142.09, 141.03, 132.68, 126.14, 125.93, 120.40, 113.42, 90.02, 80.97, 73.80, 71.71, 18.88. MS (EI 70 EV with DCI probe): 336/338. Anal. Calcd for C12H11Cl3N2O3 : 42.69, 3.28, 8.30. Found 42.80, 3.49, 8.12.
Reaction SMILES: [C:1]([O:5][C:6](=[O:32])[CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[C:25]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([OH:30])([C:26]([F:29])([F:28])[F:27])[C:17]=3[CH:16]=[C:15]([F:31])[CH:14]=2)[CH:10]=[N:9]1)(C)(C)[CH3:2].[CH:33](OCC)=[O:34].[H-].[Na+].Cl>O.C(OCC)(=O)C.O1CCCC1>[F:31][C:15]1[CH:14]=[C:13]([C:11]2[CH:10]=[N:9][N:8]([CH:7]([CH:33]=[O:34])[C:6]([O:5][CH2:1][CH3:2])=[O:32])[CH:12]=2)[C:25]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([OH:30])([C:26]([F:29])([F:28])[F:27])[C:17]=2[CH:16]=1
Reactant: CCOC=O
Reactant: CC(C)(C)OC(=O)Cn1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C=O)n1cc(-c2cc(F)cc3c2-c2ccccc2C3(O)C(F)(F)F)cn1
Temperature: 0 °C

Procedure:
To a mixture of tetrahydrofuran (80 ml) and an optically active form (10.1 g) of t-butyl[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate was added ethyl formate (4.13 ml), and the mixture was stirred at 0° C. To this mixture was added sodium hydride (60 w/w % mineral oil dispersion, 2.57 g). The reaction mixture was warmed to room temperature and stirred for 3 hr. The reaction mixture was ice-cooled, 1N hydrochloric acid was added and the mixture was stirred. Ethyl acetate and water were added thereto, and the mixture was partitioned in a separatory funnel. The aqueous layer was further extracted with ethyl acetate, and the extract was combined with the organic layer obtained earlier. The organic layer was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (13.2 g). The obtained residue was directly used for the next reaction without further purification.
Reaction SMILES: Br[C:2]1[C:3]([O:29][CH3:30])=[C:4]([CH:18]=[C:19]([N:21]2[CH:26]=[CH:25][C:24](=[O:27])[NH:23][C:22]2=[O:28])[CH:20]=1)/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=1.[S:31]1[CH:35]=[CH:34][CH:33]=[C:32]1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[O:28]=[C:22]1[NH:23][C:24](=[O:27])[CH:25]=[CH:26][N:21]1[C:19]1[CH:20]=[C:2]([C:32]2[S:31][CH:35]=[CH:34][CH:33]=2)[C:3]([O:29][CH3:30])=[C:4]([CH:18]=1)/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=1
Reactant: COc1c(Br)cc(-n2ccc(=O)[nH]c2=O)cc1/C=C/c1ccc(NS(C)(=O)=O)cc1
Reactant: OB(O)c1cccs1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(C)(C)P([c-]1cccc1)C(C)(C)C
Solvent: O
Solvent: C1CCOC1
Product: COc1c(/C=C/c2ccc(NS(C)(=O)=O)cc2)cc(-n2ccc(=O)[nH]c2=O)cc1-c1cccs1
Temperature: 50 °C
Yield: 50 %

Procedure:
To a 5 ml microwave tube was added the product from Example 15, Part D (40 mg, 0.081 mmol), thiophen-2-ylboronic acid (10.40 mg, 0.081 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (2.65 mg, 4.06 μmol) and potassium phosphate (34.5 mg, 0.162 mmol) in THF (3.0 ml) and water (1.0 ml). The vessel was sealed and the mixture was sparged by nitrogen for 5 min and heated at 50° C. for 3 h. The mixture was partitioned with ethyl acetate and 1M HCl. The organic layer was washed with saturated sodium bicarbonate, brine, dried with sodium sulfate and filtered. The filtrate was treated with 3-mercaptopropyl functionalized silica gel, filtered through celite and evaporated. The residue was purified by reverse phase chromatography to give the title compound as a white solid (20 mg, 50%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.03 (s, 3 H) 3.70 (s, 3 H) 5.70 (dd, J=7.72, 2.21 Hz, 1 H) 7.18 (dd, J=5.43, 4.05 Hz, 1 H) 7.25 (d, J=8.82 Hz, 2 H) 7.35 (s, 2 H) 7.63 (d, J=8.82 Hz, 2 H) 7.68 (m, 2 H) 7.77 (m, 2 H) 7.83 (d, J=7.72 Hz, 1 H) 9.89 (s, 1 H) 11.49 (d, J=2.21 Hz, 1 H). MS (ESI+) m/z 496 (M+H)+.
Reaction SMILES: [CH:1]1([CH:7]([NH:18][C:19]2[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=2)[C:8]2[O:16][C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[C:9]=2[CH3:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH2:29]([O:31][C:32](=[O:36])[CH2:33][CH2:34][NH2:35])[CH3:30].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+]>CN(C)C=O.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([C:23]([NH:35][CH2:34][CH2:33][C:32]([O:31][CH2:29][CH3:30])=[O:36])=[O:24])=[CH:26][CH:27]=2)[C:8]2[O:16][C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[C:9]=2[CH3:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1c(C(Nc2ccc(C(=O)O)cc2)C2CCCCC2)oc2cccnc12
Reactant: CCOC(=O)CCN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCNC(=O)c1ccc(NC(c2oc3cccnc3c2C)C2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.2 %

Procedure:
To a mixture of 4-{[cyclohexyl(3-methylfuro[3,2-b]pyridin-2-yl)methyl]amino}benzoic acid (330 mg) synthesized above, β-alanine ethyl ester hydrochloride (209 mg), 1-hydroxybenzotriazole monohydrate (208 mg), triethylamine (379 μL) and N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (261 mg), and the mixture was stirred overnight at room temperature. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (70% ethyl acetate/hexane) to give the title object compound (383 mg, 91%) as a pale-brown oil
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([NH:15][C:16](=[O:30])[C:17]2[CH:22]=[C:21]([N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:20]=[C:19]([F:29])[CH:18]=2)=[CH:7][CH:6]=1.[O:31]1[C:35]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[O:34][CH2:33][CH2:32]1>>[O:31]1[C:35]2([CH2:40][CH2:39][N:38]([CH2:2][CH2:3][O:4][C:5]3[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:8]([NH:15][C:16](=[O:30])[C:17]4[CH:22]=[C:21]([N:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[CH:20]=[C:19]([F:29])[CH:18]=4)=[CH:7][CH:6]=3)[CH2:37][CH2:36]2)[O:34][CH2:33][CH2:32]1
Reactant: O=C(Nc1ccc(OCCCl)c2ccccc12)c1cc(F)cc(N2CCCCC2)c1
Reactant: C1CC2(CCN1)OCCO2
Product: O=C(Nc1ccc(OCCN2CCC3(CC2)OCCO3)c2ccccc12)c1cc(F)cc(N2CCCCC2)c1

Procedure:
Compound is prepared from N-[4-(2-chloroethoxy)-naphthalen-1-yl]-3-fluoro-5-piperidin-1-yl-benzamide and 1,4-dioxa-8-aza-spiro[4.5]decane according to conditions described in general procedure N. 1H NMR 300 MHz (CDCl3) 8.32(dd, 1H, J=1.8 and 8.7 Hz), 7.9(s, 1H), 7.83(d, 1H, J=7.8 Hz), 7.73(d, 1H, J=8.4 Hz), 7.53(m, 2H), 7.31(s, 1H), 6.99(d, 1H, J=8.4 Hz), 6.84(d, 1H, J=8.4 Hz), 6.76(d, 1H, J=11.7 Hz), 4.31(t, 2H, J=5.7 Hz), 3.97(s, 4H), 3.28(m, 4H), 3.02(t, 2H, J=6.9 Hz), 2.76(m, 4H), 1.8(t, 4H, J=5.7 Hz), 1.62-1.67(m, 6H).
Reaction SMILES: [C:1]([NH:9][NH2:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](C=O)[CH:12]=1>C(O)(=O)C.C(O)C>[C:1]([NH:9][N:10]=[C:15]1[CH:14]=[CH:13][CH:12]=[N:11][CH2:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: O=Cc1cccnc1
Reactant: NNC(=O)c1cccnc1
Solvent: CCO
Solvent: CC(=O)O
Product: O=C(NN=C1C=CC=NC1)c1cccnc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Five drops of glacial acetic acid are added at room temperature to a solution of 41.1 g of nicotinic acid hydrazide and 32.1 g of pyridine-3-carbaldehyde in 300 ml of ethanol. The reaction mixture, which exotherms slightly, is stirred for ca. 2 hours at room temperature. The precipitated product is isolated by filtration, washed with ca. 100 ml of ethanol and dried, affording the title compound of formula ##STR8## with a melting point of 213°-216° C.
Reaction SMILES: [N:1]#[C:2][NH2:3].[CH3:4][N:5]([C:12]1[S:13][C:14]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[N:15][N:16]=1)[C:6](=[O:11])[CH2:7][CH2:8]SC.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C1COCC1>[C:2]([NH:3][CH2:8][CH2:7][C:6]([N:5]([CH3:4])[C:12]1[S:13][C:14]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[N:15][N:16]=1)=[O:11])#[N:1]
Reactant: CSCCC(=O)N(C)c1nnc(-c2cccnc2)s1
Reactant: N#CN
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: Ic1ccccc1
Product: CN(C(=O)CCNC#N)c1nnc(-c2cccnc2)s1
Temperature: -10 °C
Reaction time: 4 h
Yield: 29.1 %

Procedure:
Cyanamide (42 mg, 1.0 mmol) and N-methyl-3-methylsulfanyl-N-[5-(3-pyridyl)-1,3,4-thiadiazol-2-yl]propanamide (294 mg, 1.0 mmol) were suspended in THF and cooled in a −10° C. bath. Iodobenzene diacetate (322 mg, 1.0 mmol) was added and the resulting suspension was stirred at for 4 h. The reaction mixture was concentrated under reduced pressure and purified by reversed phase silica chromatography eluting with an aqueous acetonitrile mobile phase to yield a white solid (84 mg, 29%): mp 155-159° C.; 1H NMR (300 MHz, CDCl3) δ 9.15 (m, 1H), 8.72 (m, 1H), 8.35 (m, 1H), 7.45 (m, 1H), 4.70 (bs, 1H), 3.90 (s, 3H), 3.55 (m, 2H), 3.05 (m, 2H); ESIMS m/z 289 ([M+H]+).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7]CC)=[O:6].[Br-].[CH:14]1([Zn+])[CH2:17][CH2:16][CH2:15]1.C1(C2C(C(O)=O)=CC=CC=2)CCCC1>>[CH:14]1([C:2]2[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=2)[C:5]([OH:7])=[O:6])[CH2:17][CH2:16][CH2:15]1
Reactant: CCOC(=O)c1cccc(Br)c1
Reactant: [Zn+]C1CCC1
Agent: O=C(O)c1ccccc1C1CCCC1
Agent: [Br-]
Product: O=C(O)c1cccc(C2CCC2)c1

Procedure:
This intermediate was prepared from ethyl 3-bromobenzoate and cyclobutylzinc bromide in two steps according to the preparation of 6-cyclopentyl-benzoic acid.