Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].C1(O)C=CC=CC=1.Br[CH2:23][C:24]([O:26][CH3:27])=[O:25]>>[CH3:27][O:26][C:24](=[O:25])[CH2:23][O:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: COC(=O)c1ccc(O)c([N+](=O)[O-])c1
Reactant: COC(=O)CBr
Solvent: Oc1ccccc1
Product: COC(=O)COc1ccc(C(=O)OC)cc1[N+](=O)[O-]

Procedure:
Using methyl 4-hydroxy-3-nitrobenzoate as the phenol and methyl 2-bromoacetate as the alkylating agent in the general procedure for alkylation of substituted-2-nitrophenols gives a light yellow solid: 1H NMR (DMSO-d6, 400 MHz): δ ppm 8.39 (d, J=2.0 Hz, 1H), 8.15 (dd, J=8.8, 2.3 Hz, 1H), 7.44 (d, J=8.8 Hz, 1H), 5.16 (s, 2H), 3.87 (s, 3H), 3.71 (s, 3H). ESI-MS: m/z 270.1 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:10]([C:15]2[NH:23][C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[CH:16]=2)=[CH:11][CH:12]([CH3:14])[CH3:13])[CH:7]=[CH:8][CH:9]=1)[CH3:2].[H][H]>CO.[Pd]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]([C:15]2[NH:23][C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:17]3[CH:16]=2)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH:7]=[CH:8][CH:9]=1)[CH3:2]
Reactant: [H][H]
Reactant: CCOc1cccc(C(=CC(C)C)c2cc3cccnc3[nH]2)c1
Agent: [Pd]
Solvent: CO
Product: CCOc1cccc(C(CC(C)C)c2cc3cccnc3[nH]2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 61.8 %

Procedure:
A solution of 2-(1-(3-ethoxy-phenyl)-3-methyl-but-1-enyl)-1H-pyrrolo[2,3-b]pyridine (1.3 g, 4.2 mmol) in methanol (30 mL) was treated with 10% palladium on carbon (130 mg). The reaction was stirred for 16 h at 25° C. under a balloon filled with hydrogen gas. The reaction mixture was filtered through a pad of celite and washed with methanol (2×20 mL). The filtrate was concentrated in vacuo. Silica gel column chromatography (30 g, ethyl acetate/petroleum ether: 1:10) afforded 2-(1-(3-ethoxy-phenyl)-3-methyl-butyl)-1H-pyrrolo[2,3-b]pyridine (800 mg, 62%) as a white solid: 1H NMR (300 MHz, CDCl3) δ ppm 9.37 (s, 1H), 8.15 (d, 1H, J=4.5 Hz), 7.83 (d, 1H, J=7.5 Hz), 7.20 (t, 1H, J=7.8 Hz), 7.01 (dd, 1H, J1=7.8 Hz, J2=4.8 Hz), 6.87-6.74 (m, 3H), 6.32 (s, 1H), 4.15 (t, 1H, J=8.1 Hz), 3.95 (q, 2H, J=6.9 Hz), 2.08-1.91 (m, 2H), 1.59-1.50 (m, 1H), 1.37 (t, 3H, J=6.9 Hz), 0.96 (s, 3H), 0.94 (s, 3H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:3][CH:2]=1.[H-].[Na+].[CH3:15]I>C1COCC1>[N:1]1[CH:6]=[CH:5][C:4]([CH:7]([CH3:15])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:3][CH:2]=1
Reactant: CCOC(=O)Cc1ccncc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C(C)c1ccncc1
Temperature: -10 °C
Reaction time: 1 h
Yield: 50.6 %

Procedure:
A solution of ethyl 2-(pyridin-4-yl)acetate (1.00 g, 6.06 mmol) in THF (10 ml) was added dropwise to a suspension of sodium hydride (0.24 g, 6.06 mmol, 60%) in THF (10 ml) at −50° C. under an atmosphere of nitrogen. The reaction mixture was stirred for 1 h. Methyl iodide (2.10 ml, 33.6 mmol) in THF (10 ml) was added slowly at −50° C. over a period of 15 min, then the reaction mixture was warmed up to −10° C. and continued to stir for another 4 h. The reaction mixture was quenched with aqueous ammonium chloride and extracted with ethyl acetate (2×50 ml). The combined organic extracts were washed with brine (50 ml), dried over anhydrous sodium sulfate, filtered and concentrated under vacuo. The crude was washed with diethyl ether (10 ml) to get 550 mg (50.7%) of ethyl 2-(pyridin-4-yl)propanoate as a colorless liquid.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH2:9]([NH2:13])[CH2:10][C:11]#[CH:12].[C:14](Cl)(=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16]>C(Cl)Cl>[CH2:9]([NH:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][C:11]#[CH:12]
Reactant: C#CCCN
Reactant: CC(C)(C)C(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C#CCCNC(=O)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 82.4 %

Procedure:
Add triethylamine (3 mL) to a suspension of but-3-ynylamine hydrochloride (200 mg, 2.1 mmol) in DCM (10 mL) and stir for 10 min at room temperature under nitrogen. Add then neat pivaloyl chloride (284.9 μL, 2.31 mmol) and stir at room temperature overnight under nitrogen. Concentrate in vacuo, take up the residue in methanol and filter through a SCX-2 cartridge eluting with methanol to obtain the title compound (265 mg, 65%).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].Br[CH:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH3:12]>>[CH2:1]([N:3]([CH:11]([CH3:12])[CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCCCCC(C)Br
Reactant: CCNc1ccccc1
Product: CCCCCC(C)N(CC)c1ccccc1

Procedure:
N-Ethyl-N-(1-methylhexyl)aniline was prepared from N-ethylaniline and 2-bromoheptane using the same method as in Example 3i).
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])=[CH:6][CH:5]=[C:4]([CH3:18])[N:3]=1.Cl.[C:20]1([CH2:26][C:27](=[NH:31])OCC)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O)C>[ClH:16].[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[CH2:9][O:8][C:7]1[C:2]([NH:1][C:27](=[NH:31])[CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:3][C:4]([CH3:18])=[CH:5][CH:6]=1
Reactant: Cc1ccc(OCc2c(Cl)cccc2Cl)c(N)n1
Reactant: CCOC(=N)Cc1ccccc1
Agent: Cl
Solvent: CCO
Product: Cc1ccc(OCc2c(Cl)cccc2Cl)c(NC(=N)Cc2ccccc2)n1
Yield: 30.7 %

Procedure:
A mixture of 2-amino-3-(2,6-dichlorobenzyloxy)-6-methyl-pyridine (5.66 g, 20 mmol) and ethyl phenylacetimidate hydrochloride (4.39 g, 22 mmol) in ethanol (80 ml) was heated under reflux for 2 hours. Evaporation of the solvent gave a residue which was purified by chromatography (silica, chloroform/methanol) and recrystallisation from ethanol/ether to obtain the product (1.34 g), m.p. 217°-218° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[C:4]([Cl:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[CH:21][C:22]([O:28][CH3:29])=[C:23](B(O)O)[CH:24]=1>>[Cl:17][C:4]1[CH:3]=[C:2]([C:21]2[CH:20]=[C:19]([F:18])[CH:24]=[CH:23][C:22]=2[O:28][CH3:29])[CH:7]=[CH:6][C:5]=1[S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:10])=[O:9]
Reactant: COc1ccc(F)cc1B(O)O
Reactant: O=S(=O)(c1ccccc1)c1ccc(Br)cc1Cl
Product: COc1ccc(F)cc1-c1ccc(S(=O)(=O)c2ccccc2)c(Cl)c1

Procedure:
The subtitle compound was prepared by the method of example 2 step (ii) using the product of step (i) and 5-fluoro-2-methoxybenzene boronic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15]([OH:17])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N1CCOCC1)C.FC(F)(F)C(O)=O.[Cl:61][C:62]([Cl:77])([Cl:76])[C:63]1[O:67][N:66]=[C:65]([N:68]2[CH2:73][CH2:72][CH:71]([CH2:74][NH2:75])[CH2:70][CH2:69]2)[N:64]=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15]([NH:75][CH2:74][CH:71]1[CH2:72][CH2:73][N:68]([C:65]2[N:64]=[C:63]([C:62]([Cl:77])([Cl:76])[Cl:61])[O:67][N:66]=2)[CH2:69][CH2:70]1)=[O:17]
Reactant: NCC1CCN(c2noc(C(Cl)(Cl)Cl)n2)CC1
Reactant: Cc1ccc(C(=O)O)cc1OCCc1ccc(Cl)cc1Cl
Agent: CCN1CCOCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: Cc1ccc(C(=O)NCC2CCN(c3noc(C(Cl)(Cl)Cl)n3)CC2)cc1OCCc1ccc(Cl)cc1Cl
Temperature: -15 °C
Reaction time: 0.5 h

Procedure:
3-[2-(2,4-Dichloro-phenyl)-ethoxy]-4-methyl-benzoic acid (200 mg, 0.615 mmol) was dissolved in 5 ml DMF. After cooling to −15° C. HATU (257.34 mg, 0.676 mmol) and N-ethylmorpholine (283.3 mg, 2.46 mmol) were added. The mixture was stirred at 0° C. for 15 min. and 30 min. at room temperature. C-[1-(5-trichloromethyl-[1,2,4]oxadiazol-3-yl)-piperidin-4-yl]-methylamine; compound with trifluoro-acetic acid (254.4 mg, 0.615 mmol) was added and the mixture stirred for 1 hour and evaporated under reduced pressure. The residue was dissolved in sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried with MgSO4 and evaporated. The crude material was used without further purification.
Reaction SMILES: C(Cl)(=O)C([Cl:4])=O.[Cl:7][CH2:8][CH2:9][CH:10]([C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([F:22])[CH:15]=1)[C:11](O)=[O:12]>CN(C=O)C.C(Cl)Cl>[Cl:7][CH2:8][CH2:9][CH:10]([C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([F:22])[CH:15]=1)[C:11]([Cl:4])=[O:12]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)C(CCCl)c1cc(F)c(F)c(F)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)C(CCCl)c1cc(F)c(F)c(F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
oxalyl chloride (0.63 mL) and DMF (1 drop) were added to a solution of 4-chloro-2-(3,4,5-trifluorophenyl)butyric acid (1.17 g) in methylene chloride (30 mL) at 0° C., and the reaction solution was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure to obtain 4-chloro-2-(3,4,5-trifluorophenyl)butyryl chloride. A solution of 4-chloro-2-(3,4,5-trifluorophenyl)butyryl chloride in THF (5 mL) was added to a solution of tert-butyl carbazate (600 mg) and triethylamine (3.1 mL) in THF (20 mL) at 0° C., and the reaction solution was stirred at room temperature for one hour. The reaction solution was added to a saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 1.35 g of the title compound. The property value of the compound is as follows.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([CH3:16])=[CH:15][C:10]=2[C:9](=[O:17])[NH:8][C:7]2[CH:18]=[CH:19][CH:20]=[N:21][C:6]1=2)=[O:4].[CH2:22]([N:24]([CH2:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][NH:29]1)[CH2:25][CH3:26])[CH3:23].C(OC(C)C)(C)C>C(#N)C>[CH2:22]([N:24]([CH2:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][N:29]1[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([CH3:16])=[CH:15][C:10]=2[C:9](=[O:17])[NH:8][C:7]2[CH:18]=[CH:19][CH:20]=[N:21][C:6]1=2)=[O:4])[CH2:25][CH3:26])[CH3:23]
Reactant: Cc1ccc2c(c1)C(=O)Nc1cccnc1N2C(=O)CCl
Reactant: CCN(CC)CC1CCCCN1
Solvent: CC#N
Solvent: CC(C)OC(C)C
Product: CCN(CC)CC1CCCCN1CC(=O)N1c2ccc(C)cc2C(=O)Nc2cccnc21
Yield: 54 %

Procedure:
Prepared in analogy to Example 2 from 11-(chloroacetyl)-5,11-dihydro-8-methyl-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one and 2-[(diethylamino)methyl]piperidine, but using acetonitrile as solvent, in a yield of 54% of theory. M.p. 173-174° C. (diisopropylether).
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[C:25]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[C:17](Cl)[C:16]=2[N:15]=[C:14]1[OH:27])(C(C)(C)C)(C)C.[NH3:28]>CO>[NH2:28][C:17]1[C:16]2[N:15]=[C:14]([OH:27])[N:13]([CH2:12][CH2:11][CH2:10][CH2:9][OH:8])[C:25]=2[C:24]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N:18]=1
Reactant: N
Reactant: CC(C)(C)[Si](C)(C)OCCCCn1c(O)nc2c(Cl)nc3ccccc3c21
Solvent: CO
Product: Nc1nc2ccccc2c2c1nc(O)n2CCCCO
Temperature: 150 °C

Procedure:
1-[4-(tert-Butyldimethylsilanyloxy)butyl]-4-chloro-1H-imidazo[4,5-c]quinolin-2-ol (5.0 g, 12 mmol) and ammonia (200 mL of a 7 N solution in methanol) were added to a high-pressure vessel, which was sealed and heated in an oven at 150° C. for five days, allowed to cool, and concentrated under reduced pressure. The crude product was triturated with hexane for 15 minutes, and the resulting solid was isolated by filtration, washed with hexane (500 mL), and dried under vacuum to provide 3.53 g of 4-amino-1-(4-hydroxybutyl)-1H-imidazo[4,5-c]quinolin-2-ol as a light gray solid.
Reaction SMILES: [Mg].[CH2:2]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([CH2:11][CH3:12])[C:5]=1Br)[CH3:3].[CH2:14]=[O:15].Cl>II.BrCCBr.O1CCCC1>[CH2:2]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([CH2:11][CH3:12])[C:5]=1[CH2:14][OH:15])[CH3:3]
Reactant: C=O
Reactant: CCc1cc(C)cc(CC)c1Br
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: BrCCBr
Product: CCc1cc(C)cc(CC)c1CO
Temperature: 60 °C

Procedure:
Under a nitrogen atmosphere, 11.24 g of magnesium, 200 g of tetrahydrofuran, 0.1 g of iodine and 1.0 g of 1,2-dibromoethane were mixed. This mixture was heated to 60° C. To this mixture, a small amount of 2,6-diethyl-4-methylbromobenzene was added. To this mixture, 0.1 g of iodine and 1.0 g of 1,2-dibromoethane were added. Then, 2,6-diethyl-4-methylbromobenzene (the total amount including the amount added first: 100.12 g) was added dropwise over 2.5 hours. After completion of addition, the resultant mixture was stirred at 50° C. for 1.5 hours. This mixture was cooled to 30° C. To this mixture, 14.84 g of paraformaldehyde was added portionwise in five additions over 30 minutes. The resultant mixture was stirred at 30° C. for 2 hours. To the reaction mixture, 143 g of 10% hydrochloric acid was added, followed by extraction with 300 g of tert-butyl methyl ether. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to obtain 77.56 g of 2,6-diethyl-4-methylbenzyl alcohol as a yellow crystal.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Br[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][OH:23].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O.O>[OH:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1
Reactant: OCCCCCCCCCCCBr
Reactant: N#CCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#CCc1ccc(OCCCCCCCCCCCO)cc1
Temperature: 80 °C
Reaction time: 48 h
Yield: 52.2 %

Procedure:
25.0 g (188 mmol) of (4-hydroxyphenyl)acetonitrile and 56.6 g (225 mmol) of 11-bromoundecan-1-ol are dissolved in 250 mL of N,N-dimethylformamide. 51.8 g (375 mmol) of potassium carbonate and 6.0 g (36 mmol) of potassium iodide are added and the suspension was heated to 80° C. After 48 h, the reaction mixture is cooled to room temperature and poured to icy water. The precipitate is filtered off, purified on column chromatography (AcOET/Tol: 2/8) and dried overnight at 40° C. 29.8 g of {4-[(11-hydroxyundecyl)oxy]phenyl}acetonitrile are obtained as a slightly yellow solid (52% yield). This material proves chromatographically homogenous and displays spectral characteristics consistent with its assigned structure.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[CH2:23][CH2:22][N:21]([CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH2:20][CH2:19]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N:18]1[CH2:19][CH2:20][N:21]([CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:8])[CH2:27][CH2:26]2)[CH2:22][CH2:23]1
Reactant: O=C(Cl)c1ccccc1
Reactant: COc1ccccc1N1CCN(CC2CCNCC2)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccccc1N1CCN(CC2CCN(C(=O)c3ccccc3)CC2)CC1
Temperature: 0 °C
Reaction time: 16 h
Yield: 66.1 %

Procedure:
Benzoyl chloride (0.49 g, 3.5 mmol) was added to a solution of 1-(2-methoxyphenyl)-4-piperidin-4-ylmethyl-piperazine (1.0 g, 3.5 mmol) from example 1 and triethylamine (2 equivalents, 1 mL) in CH2Cl2 (30 mL) and the solution stirred under N2 at 0° C. for 16 hours. The mixture was concentrated under vacuum, water (50 mL) added and the product extracted into ethyl acetate (3×25 mL). The combined organics were washed with water (25 mL), saturated sodium bicarbonate (20 mL) and brine (25 mL). After drying over sodium sulfate, filtration and concentration under vacuum afforded the titled product (0.91 g, 66% yield). An ethanolic solution of the product was treated with a hot ethanolic solution of fumaric acid (1.0 equivalents) and afforded the fumarate salt of the titled compound as a light yellow colored solid.
Reaction SMILES: [F:1][C:2]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[N:11][C:12]([C:14](O)=[O:15])=[CH:13][C:8]=2[N:7]=[CH:6]1.[CH3:22][O:23][NH2:24]>>[F:1][C:2]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[N:11][C:12]([C:14]([NH:24][O:23][CH3:22])=[O:15])=[CH:13][C:8]=2[N:7]=[CH:6]1
Reactant: CON
Reactant: O=C(O)c1cc2ncn(Cc3cccc(F)c3F)c2cn1
Product: CONC(=O)c1cc2ncn(Cc3cccc(F)c3F)c2cn1

Procedure:
The title compound can be prepared by coupling of 3-(2,3-difluorobenzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylic acid and N-methoxyamine under the same conditions as those in step (c) of example 1.
Reaction SMILES: [CH:1]1[C:6]([Cl:7])=[CH:5][C:4]2[NH:8][C:9]([O:11][C:3]=2[CH:2]=1)=[O:10].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]#[CH:20]>CC(C)=O>[CH2:20]([N:8]1[C:4]2[CH:5]=[C:6]([Cl:7])[CH:1]=[CH:2][C:3]=2[O:11][C:9]1=[O:10])[C:19]#[CH:18]
Reactant: C#CCBr
Reactant: O=c1[nH]c2cc(Cl)ccc2o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C#CCn1c(=O)oc2ccc(Cl)cc21
Temperature: 25 °C

Procedure:
In a 500-mL round bottom flask equipped with a magnetic stirrer, reflux condenser and a heating mantle were placed chlorzoxazone, or 5-chlorobenzoxazol-2-one, (10 g, 0.059 mole), potassium carbonate (9.8 g, 0.071 mole), propargyl bromide (10.5 g of 80% in toluene, 0.071 mole) and acetone (200 mL). The mixture was refluxed for 20 hours. The mixture was cooled down to room temperature and the solid was filtered off by suction-filtration. The filtrate was concentrated on a rotary evaporator to a solid residue. A pure, off-white product was obtained by crystallization from ethyl acetate hexane yielding 10.5 g (86%). m.p.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[C:16]([F:24])[CH:15]=3)[CH:11]=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:29]([NH:33][S:34]([C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1)(=[O:36])=[O:35])([CH3:32])([CH3:31])[CH3:30]>>[C:29]([NH:33][S:34]([C:37]1[CH:42]=[C:41]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:13]=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:22])[F:23])=[C:16]([F:24])[CH:15]=4)[CH:11]=[C:10]([C:25]([F:28])([F:26])[F:27])[N:9]=3)[CH:3]=2)[CH:40]=[CH:39][CH:38]=1)(=[O:36])=[O:35])([CH3:32])([CH3:30])[CH3:31]
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Reactant: Fc1cc(-c2cc(C(F)(F)F)nc(-c3cccc(Br)c3)n2)ccc1C(F)(F)F
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)c(F)c4)cc(C(F)(F)F)n3)c2)c1

Procedure:
3′-[4-(3-Fluoro-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidin-2-yl]-biphenyl-3-sulfonic acid tert-butylamide was prepared from 2-(3-bromo-phenyl)-4-(3-fluoro-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidine (example E.109) (0.465 g, 1.0 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.31 g, 1.2 mmol) according to the general procedure VI. Obtained as light yellow solid (0.47 g), which was subsequently deprotected.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[F:18][C:19]([F:26])([F:25])[C:20]1[CH:24]=[CH:23][NH:22][N:21]=1>>[F:18][C:19]([F:26])([F:25])[C:20]1[CH:24]=[CH:23][N:22]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[N:3]=2)[N:21]=1
Reactant: FC(F)(F)c1cc[nH]n1
Reactant: FC(F)(F)c1cc(Cl)nc(-c2cccnc2)n1
Product: FC(F)(F)c1cc(-n2ccc(C(F)(F)F)n2)nc(-c2cccnc2)n1

Procedure:
The title compound was prepared from 4-chloro-2-(3-pyridinyl)-6-trifluoromethyl-pyrimidine (74 mg, 0.285 mmol) and 3-trifluromethyl-pyrazol (48 mg, 0.353 mmol) similar to Example 166 and was isolated as a white solid (mp 139-140° C., 53 mg, 0.148 mmol, 52%). 1H NMR (CDCl3): 9.73 (s, 1H), 8.82 (m, 3H), 8.26 (s, 1H), 7.50 (m, 1H), 6.87 (d, J=2.7 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[N:6][C:5]([Cl:10])=[C:4](Cl)[N:3]=1.[CH2:12]([NH2:15])[CH2:13][CH3:14].O>C(O)(C)C>[NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[N:6][C:5]([Cl:10])=[C:4]([NH:15][CH2:12][CH2:13][CH3:14])[N:3]=1
Reactant: Nc1nc(Cl)c(Cl)nc1C=O
Reactant: CCCN
Solvent: O
Solvent: CC(C)O
Product: CCCNc1nc(N)c(C=O)nc1Cl
Temperature: 25 °C
Reaction time: 20.5 h

Procedure:
In 1.2 ml of isopropyl alcohol there was dissolved 2-amino-5,6-dichloro-3-formylpyrazine (0.095 g) 0.0005 M) prepared in Step B, after which n-propylamine (32 g; 0.042 ml; 0.00055 M) was added, and the reaction mixture was stirred at room temperature for 20.5 hours. When water was added to the reaction mixture, product precipitated, was filtered, and dried (23 mg). Additional product precipitated, was filtered, and dried (46 mg). The product was recrystallized from ethyl acetate/hexane. Elemental Analysis for C8H11N4OCl.
Reaction SMILES: [B-](F)(F)(F)F.[N:6]#[O+].[CH:8]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[C:21]3([CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[O:20][C:19]3[C:28]([CH3:34])=[C:29]([CH3:33])[CH:30]=[C:31]([CH3:32])[C:18]2=3)=[CH:13][CH:12]=1)([CH3:10])[CH3:9].[OH-].[Na+]>C(#N)C>[CH:8]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[C:21]3([CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)[O:20][C:19]3[C:28]([CH3:34])=[C:29]([CH3:33])[C:30]([NH2:6])=[C:31]([CH3:32])[C:18]2=3)=[CH:13][CH:12]=1)([CH3:10])[CH3:9]
Reactant: N#[O+]
Reactant: Cc1cc(C)c2c(c1C)OC1(CCN(C)CC1)C2c1ccc(C(C)C)cc1
Agent: F[B-](F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: Cc1c(C)c2c(c(C)c1N)C(c1ccc(C(C)C)cc1)C1(CCN(C)CC1)O2
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 80.5 %

Procedure:
A solution of nitrosyl tetrafluoroborate (470.7 mg, 4.03 mmol) in acetonitrile (40 ml) was cooled to 0° C. To the solution was added a solution of 3-(4-isopropylphenyl)-1′,4,6,7-tetramethylspiro[benzofuran-2(3H),4′-piperidine] (479.1 mg, 1.32 mmol) in acetonitrile (10 ml) and the mixture was stirred for 20 minutes. The reaction mixture was poured into ice water and basified with an 8 N aqueous solution of sodium hydroxide. The product was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was dissolved into ethanol (20 ml) and palladium-carbon (59.9 mg) was added into the solution, then the mixture was stirred at 60° C. for 18 hours under a hydrogen atmosphere. The reaction mixture was cooled down to room temperature, filtered to remove insoluble materials, and then concentrated under reduced pressure. The residue was subjected to column chromatography (on Chromatorex NHDM1020 (trade name, manufactured by Fuji Silysia Chemical Ltd.); hexane-ethyl acetate 3:1) to obtain 402.0 mg (83% yield) of the title compound. Melting point: 123-124° C. (Hexane).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([NH:9][C:10](=[S:18])OC2C=CC=CC=2)=[CH:7][C:6]([CH2:19][CH2:20][CH3:21])=[C:5]([CH3:22])[N:4]=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:28]=[C:29]([O:31][CH3:32])[CH:30]=1>>[CH3:1][O:2][C:3]1[C:8]([NH:9][C:10]([N:36]2[CH2:35][CH2:34][N:33]([C:27]3[CH:26]=[C:25]([O:24][CH3:23])[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=3)[CH2:38][CH2:37]2)=[S:18])=[CH:7][C:6]([CH2:19][CH2:20][CH3:21])=[C:5]([CH3:22])[N:4]=1
Reactant: CCCc1cc(NC(=S)Oc2ccccc2)c(OC)nc1C
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Product: CCCc1cc(NC(=S)N2CCN(c3cc(OC)cc(OC)c3)CC2)c(OC)nc1C
Yield: 55 %

Procedure:
Phenyl N-(2-methoxy-6-methyl-5-propylpyridin-3-yl)thiocarbamate and 1-(3,5-dimethoxyphenyl)piperazine were reacted by the same way with the example 22 to obtain the titled compound.