Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([Cl:13])=[CH:6][C:4]=1[NH2:5].[Cl:14][CH2:15][CH2:16][C:17](Cl)=[O:18]>C1C=CC=CC=1.N1C=CC=CC=1.O>[Cl:14][CH2:15][CH2:16][C:17]([NH:5][C:4]1[CH:6]=[C:7]([Cl:13])[C:8]([N+:10]([O-:12])=[O:11])=[CH:9][C:3]=1[O:2][CH3:1])=[O:18]
Reactant: COc1cc([N+](=O)[O-])c(Cl)cc1N
Reactant: O=C(Cl)CCCl
Solvent: c1ccncc1
Solvent: O
Solvent: c1ccccc1
Product: COc1cc([N+](=O)[O-])c(Cl)cc1NC(=O)CCCl
Temperature: 25 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
17.2 g of 2- methoxy 4- nitro 5- chloroaniline dissolved in 150 ml benzene are added with 11.1g of βchloropropionyl chloride dissolved in 40 ml benzene and 2 ml pyridine. The reaction mixture is kept under stirring at room temperature for two hours then diluted with 250 ml water. The benzenic phase is separated while the aqueous phase is extracted twice with benzene. The benzenic solutions are united, washed with 2N hydrochloric acid then with water dried on sodium sulphate, filtered and evaporated to dryness. The dry residue is recristallised from isopropyl ether and 21.1g of 1(βchloropropionylamino) 2- methoxy 4- nitro 5- chlorobenzene are recovered (yield 40-50%). It melts at 101°-110° (dec)
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH:10]1[CH2:14][CH2:13][CH:12]([O:15][C:16]([N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25]3[CH:30]=[C:29]([N:31]4[C:39]5[C:34](=[CH:35][C:36]([S:40]([CH3:43])(=[O:42])=[O:41])=[CH:37][CH:38]=5)[CH2:33][CH2:32]4)[N:28]=[CH:27][N:26]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:11]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:10]1[CH2:14][CH2:13][CH:12]([O:15][C:16]([N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25]3[CH:30]=[C:29]([N:31]4[C:39]5[C:34](=[CH:35][C:36]([S:40]([CH3:43])(=[O:42])=[O:41])=[CH:37][CH:38]=5)[CH2:33][CH2:32]4)[N:28]=[CH:27][N:26]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:11]1
Reactant: CS(=O)(=O)c1ccc2c(c1)CCN2c1cc(OC2CCN(C(=O)OC3CCNC3)CC2)ncn1
Reactant: O=Cc1ccccc1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Product: CS(=O)(=O)c1ccc2c(c1)CCN2c1cc(OC2CCN(C(=O)OC3CCN(Cc4ccccc4F)C3)CC2)ncn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Fluoro-benzaldehyde (11 μL, 0.1 mmol) was dissolved in 1 mL of DCE with 21b (49 mg, 0.1 mmol) and NaBH(OAc)3 (30 mg, 0.14 mmol). The mixture was stirred for 8 h at room temperature then was diluted with DCM and quenched with saturated NaHCO3. The organic layer was washed with saturated NaHCO3 followed by brine. The organic layer was dried, filtered and evaporated. The residue was purified by preparative HPLC to afford 21-1, LCMS 596.2 (MH+).
Reaction SMILES: [Mg].II.[CH3:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Cl)=[CH:7][CH:6]=1.[C:13](#N)[CH:14]([CH3:16])[CH3:15].Cl.C([O:21]CC)C>>[CH3:15][CH:14]([CH3:16])[C:13](=[O:21])[CH2:9][C:8]1[CH:11]=[CH:12][C:5]([CH3:4])=[CH:6][CH:7]=1
Reactant: Cc1ccc(CCl)cc1
Reactant: CCOCC
Reactant: CC(C)C#N
Agent: Cl
Agent: II
Agent: [Mg]
Product: Cc1ccc(CC(=O)C(C)C)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
While stirring magnesium (22.5 g, 925 mmol) and iodine (1 crumb) in diethyl ether (400 ml), a solution of 4-methylbenzyl chloride (65.0 g, 463 mmol) in diethyl ether (500 ml) was dropwise added slowly at room temperature. After completion of the dropwise addition, the mixture was stirred at room temperature for 0.5 hr. To the reaction solution was added dropwise a solution of isobutyronitrile (21.31 g, 308.3 mmol) in diethyl ether (100 ml) under ice-cooling, and the mixture was stirred overnight at room temperature. To the reaction solution was added dropwise 1N hydrochloric acid under ice-cooling, and the mixture was stirred at room temperature for 1 hr. The diethyl ether layer was separated from the mixture, and the aqueous layer was extracted with diethyl ether. The recovered organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=15/1−9/1) to give the objective substance.
Reaction SMILES: [F:1][CH:2]([F:40])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]1[N:15]2[CH:16]=[C:17]([C:21]3[CH:22]=[N:23][C:24]([C:27]4([OH:38])[CH2:30][N:29]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:28]4)=[N:25][CH:26]=3)[C:18]([F:20])=[CH:19][C:14]2=[N:13][C:12]=1[CH3:39].Cl>O1CCOCC1>[CH:31]([OH:33])=[O:32].[F:40][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]1[N:15]2[CH:16]=[C:17]([C:21]3[CH:22]=[N:23][C:24]([C:27]4([OH:38])[CH2:30][NH:29][CH2:28]4)=[N:25][CH:26]=3)[C:18]([F:20])=[CH:19][C:14]2=[N:13][C:12]=1[CH3:39]
Reactant: Cc1nc2cc(F)c(-c3cnc(C4(O)CN(C(=O)OC(C)(C)C)C4)nc3)cn2c1Cc1ccccc1OC(F)F
Agent: Cl
Solvent: C1COCCO1
Product: Cc1nc2cc(F)c(-c3cnc(C4(O)CNC4)nc3)cn2c1Cc1ccccc1OC(F)F
Product: O=CO
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 12.5 %

Procedure:
A solution of Example 320 (92%, 346 mg, 0.573 mmol) in 1,4-dioxane (3 mL) was treated with 4M hydrogen chloride in 1,4-dioxane (2.8 mL). The mixture was placed in a sonic bath for 15 minutes, then stirred at room temperature for 2 h to give a suspension. The reaction mixture was concentrated under vacuum, and purified by preparative HPLC (Method A), to afford the title compound (36 mg, 12.5%) as a colourless solid. δH (500 MHz, CD3OD) 9.05 (d, J 1.4 Hz, 2H), 8.38 (d, J 7.1 Hz, 1H), 8.23 (s, 1H), 7.41 (d, J 10.8 Hz, 1H), 7.33-7.27 (m, 1H), 7.18 (d, J 8.0 Hz, 1H), 7.16-7.12 (m, 1H), 7.11 (dd, J 7.7, 1.8 Hz, 1H), 6.91 (t, J 74.0 Hz, 1H), 4.64 (d, J 11.8 Hz, 2H), 4.42 (s, 2H), 4.33 (d, J 11.8 Hz, 2H), 2.42 (s, 3H). Method D HPLC-MS: MH+ m/z 456, RT 0.98 minutes.
Reaction SMILES: [C-:1]1(CC#N)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:9]1[CH:13]=[CH:12][CH:11]=[CH:10]1.[Fe+2:14].[OH-:15].[K+].[CH2:17]([OH:19])[CH3:18]>O>[C-:9]1([CH2:18][C:17]([OH:15])=[O:19])[CH:13]=[CH:12][CH:11]=[CH:10]1.[CH-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Fe+2:14]
Reactant: CCO
Reactant: [OH-]
Reactant: N#CC[c-]1cccc1
Agent: [Fe+2]
Agent: [K+]
Agent: c1cc[cH-]c1
Solvent: O
Product: O=C(O)C[c-]1cccc1

Procedure:
4.10 g (18.2 mmol) of ferrocenylacetonitrile are dissolved in 80 ml of ethanol. 10.08 g of KOH (180 mmol) are dissolved in 80 ml of water. The potassium hydroxide solution is poured into the first solution and the mixture is brought to reflux for 4 hours. The reaction mixture is concentrated in order to remove most of the ethanol. The product is extracted with 3 times 30 ml of ether. The aqueous phase is acidified with hydrochloric acid to a pH of 1 and is again extracted with 4 times 50 ml of ethyl ether. The organic phases are combined, dried over magnesium sulfate, filtered and then evaporated. 4.20 g of ferrocenylacetic acid are obtained in the form of a yellow solid.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:15])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[S:8][CH2:7][CH2:6][C:5]2=[O:14].[CH3:16][O:17][CH2:18]Cl.[H-].[Na+]>C1COCC1>[CH3:16][O:17][CH2:18][O:1][C:2]1[C:3]([CH3:15])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[S:8][CH2:7][CH2:6][C:5]2=[O:14]
Reactant: Cc1c(C)c2c(c(C)c1O)C(=O)CCS2
Reactant: COCCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCOc1c(C)c(C)c2c(c1C)C(=O)CCS2
Reaction time: 2 h

Procedure:
6-Hydroxy-5,7,8-trimethyl-2,3-dihydro-4H-thiochromen-4-one (2.24 g) was dissolved in anhydrous THF (100 mL) and treated with chloromethyl methyl ether (0.918 mL) and NaH (60% in mineral oil, 483 mg). The resulting reaction mixture was stirred for 2 h turning bright yellow as NaH was added and then gradually becoming pale yellow. The reaction mixture was quenched with a small amount of H2O followed by solvent evaporation and preloading the residue onto SiO2. Column chromatography (SiO2: hexane:EtOAc, 95:5 v/v) yielded 6-methoxymethoxy-5,7,8-trimethyl-2,3-dihydro-4H-thiochromen4-one as a white solid (2.37 g).
Reaction SMILES: [Cl:1][C:2]1[C:3](=[O:14])O[C:5](=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.Cl.[CH3:17][N:18]([CH3:27])[C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1.C(N(CC)CC)C>C(O)(=O)C>[Cl:1][C:2]1[C:3](=[O:14])[N:24]([CH2:23][C:22]2[CH:25]=[CH:26][C:19]([N:18]([CH3:27])[CH3:17])=[CH:20][CH:21]=2)[C:5](=[O:13])[C:6]=1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=C1OC(=O)C(c2ccccc2)=C1Cl
Reactant: CN(C)c1ccc(CN)cc1
Agent: Cl
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: CN(C)c1ccc(CN2C(=O)C(Cl)=C(c3ccccc3)C2=O)cc1
Temperature: 120 °C

Procedure:
To a solution of 3-chloro-4-phenylfuran-2,5-dione (0.20 mmol, 42 mg) and 4-dimethylaminobenzylamine dihydrochloride (0.20 mmol, 45 mg) in glacial acetic acid (1 mL) was added triethylamine (0.40 mmol). The mixture was heated in a microwave reactor at 120° C. for two min. After cooling, the solvent was evaporated at reduced pressure. The reaction mixture was purified by HPLC (95% 0.1M ammonium acetate buffer: 5% CH3CN→100% CH3CN).
Reaction SMILES: [H-].[Na+].C([Si](C)(C)OC[C:10]1[CH:15]=[CH:14][C:13]([CH:16]=[CH:17][C:18](=[O:20])[CH3:19])=[CH:12][C:11]=1[O:21][CH3:22])(C)(C)C.[C:25](OC)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CN(C)C=[O:38]>>[OH:38][C:12]1[C:11]([O:21][CH3:22])=[CH:10][CH:15]=[CH:14][C:13]=1[CH:16]=[CH:17][C:18](=[O:20])[CH2:19][C:25]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:32]
Reactant: COC(=O)c1ccccc1
Reactant: COc1cc(C=CC(C)=O)ccc1CO[Si](C)(C)C(C)(C)C
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Product: COc1cccc(C=CC(=O)CC(=O)c2ccccc2)c1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 30 %

Procedure:
To a slurry solution of sodium hydride (60%, 0.13 g, 3.28 mmol) in N,N-dimethylformamide were added 4-{4-[(tert-butyl-dimethyl-silanyloxy)-methyl}-3-methoxy-phenyl}-but-3-ene-2-one (0.50 g, 1.54 mmol) and methyl benzoate (0.26 g, 1.97 mmol) at 0° C. The reaction was stirred at 0° C. for 1 h. The reaction mixture was removed from ice-bath and heated for 1 h at 60° C. The reaction was cooled to room temperature and quenched with aqueous 1.0 N hydrochloric acid (2.0 mL) slowly. Excess tetrabutylammonium fluoride was added to the above solution to deprotect the silyl group. The reaction was diluted with ethyl acetate (200 mL), washed with water (3×60 mL) and saturated aqueous sodium chloride (50 mL). The organic layer dried over magnesium sulfate, filtered, and concentrated to give impure crude product. Purification on silica (9:1 to 7:3 hexanes/ethyl acetate) to afford 5-(hydroxy-3-methoxy-phenyl)-1-phenyl-pent-4-ene-1,3-dione (0.14 g, 30% yield) as a solid: MS (EI) for C18H16O4: 297 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:7]=[C:8]([NH:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:9]=[CH:10][CH:11]=1.[F:24][C:25]([F:32])([F:31])[CH2:26][S:27](Cl)(=[O:29])=[O:28].C(=O)([O-])[O-].[K+].[K+]>ClCCCl.N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:7]=[C:8]([N:12]([CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[S:27]([CH2:26][C:25]([F:32])([F:31])[F:24])(=[O:29])=[O:28])[CH:9]=[CH:10][CH:11]=1
Reactant: COc1ccccc1Oc1cccc(NCc2cccnc2)c1
Reactant: O=S(=O)(Cl)CC(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Solvent: ClCCCl
Product: COc1ccccc1Oc1cccc(N(Cc2cccnc2)S(=O)(=O)CC(F)(F)F)c1
Temperature: 5 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
The resultant N-(3-(2-methoxyphenoxy)phenyl)pyrid-3-ylmethylamine was dissolved in 2:1 1,2-dichloroethane/pyridine (6 mL) under nitrogen, cooled (5° C.), and treated with 2,2,2-trifluoroethylsulfonyl chloride (300 mg, 1.64 mmol). After one hour at 5° C., the mixture was allowed to warm to room temperature and stirred for 18 h. The product mixture was treated with anhydrous potassium carbonate (500 mg), stirred 30 min, filtered, and the filtrate concentrated in vacuo. The residue was chromatographed on silica gel (eluted with 2:1 dichloromethane/ethyl acetate) to afford the title compound (226 mg, 50%) as a viscous pale amber oil. The hydrochloride salt was obtained by treatment of this material in methanol with ethereal HCl. 1H NMR: 8.49 (d,1H,J=4 Hz), 8.29 (s,1H), 7.60-7.65 (m,1H), 7.20-7.25 (m,2H), 7.10-7.20 (m,1H), 6.97 (d,1H,J=8 Hz), 6.90 (m,2H), 6.80-6.85 (m,2H), 6.76 (m,1H), 4.82 (s,2H), 3.70-3.85 (m,2H), 3.75 (s,3H). MS calcd. 452.4; MS (M+1) 453.3
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]2[CH3:17])[N:3]=1.CI.[C:20]([O-])([O-])=O.[K+].[K+]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:20])=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][C@@H:12]2[CH3:17])[N:3]=1
Reactant: O=C([O-])[O-]
Reactant: C[C@H]1COCCN1c1nc(Cl)nc2[nH]cnc12
Agent: [K+]
Solvent: CI
Solvent: C1CCOC1
Product: C[C@H]1COCCN1c1nc(Cl)nc2c1ncn2C
Temperature: 25 °C
Reaction time: 18 h
Yield: 86.5 %

Procedure:
A mixture of 2-chloro-6-((S)-3-methylmorpholin-4-yl)-9H-purine (5.3 g, 20.89 mmol), methyl iodide (1.6 mL, 25.70 mmol) and K2CO3 (4.0 g, 28.94 mmol) in THF (100 mL) were stirred at r.t. for 18 h then concentrated in vacuo. The resulting residue was partitioned between EtOAc and H2O, the organic phase washed with brine, then dried (Na2SO4) and concentrated in vacuo affording the title compound (4.84 g, 87%). LCMS (method H): RT 2.74 min [M+H]+ 268.2
Reaction SMILES: [NH2:1][C:2]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:3]=1[CH:4]([OH:17])[C:5]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([O:13][CH3:14])=[CH:7][C:6]=1[O:15][CH3:16].[CH3:23][C:24]([CH3:28])([CH3:27])[CH:25]=O.C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[Cl:22][C:19]1[CH:20]=[CH:21][C:2]([NH:1][CH2:23][C:24]([CH3:28])([CH3:27])[CH3:25])=[C:3]([CH:18]=1)[CH:4]([OH:17])[C:5]1[C:6]([O:15][CH3:16])=[CH:7][C:8]([O:13][CH3:14])=[CH:9][C:10]=1[O:11][CH3:12]
Reactant: CC(C)(C)C=O
Reactant: COc1cc(OC)c(C(O)c2cc(Cl)ccc2N)c(OC)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: COc1cc(OC)c(C(O)c2cc(Cl)ccc2NCC(C)(C)C)c(OC)c1
Reaction time: 8 h

Procedure:
After a solution of 2.5 g of 2-amino-5-chloro-α-(2,4,6-trimethoxyphenyl)benzyl alcohol, 1.01 ml of trimethylacetaldehyde and 0.56 g of acetic acid in 30 ml of ethanol was stirred at room temperature for 1.5 hours, 0.81 g of sodium cyanoborohydride was added, followed by stirring overnight. After concentration and subsequent dilution with water, the solution was extracted with ethyl acetate. After solvent removal, the residue was subjected to silica gel column chromatography to yield 2.2 g of a crystal.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8](=[O:23])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[NH:10]2)=[CH:6][CH:5]=1.[CH3:24][Si:25]([CH2:28][CH2:29][O:30][CH2:31]Cl)([CH3:27])[CH3:26]>C1COCC1>[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8](=[O:23])[N:9]([C:13]3[CH:14]=[CH:15][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:17][CH:18]=3)[N:10]2[CH2:31][O:30][CH2:29][CH2:28][Si:25]([CH3:27])([CH3:26])[CH3:24])=[CH:6][CH:5]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: O=c1c2ccc(Br)cc2[nH]n1-c1ccc(C(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C[Si](C)(C)CCOCn1c2cc(Br)ccc2c(=O)n1-c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A suspension of NaH in mineral oil (60%, 0.17 g, 0.0041 mol) was added portionwise to a solution of the product of Step 4 (1.3 g, 0.0035 mol) in dry THF (50 mL) at room temperature under N2. After 20 min, SEM chloride (0.68 g, 0.0041 mol) in THF (15 mL) was added and the resulting slurry stirred at room temperature overnight. The mixture was quenched with brine (10 mL) and extracted into ether (3×20 mL). The organic phase was washed with 1N HCl (10 mL), 2N NaOH (10 mL), brine (10 mL), dried (MgSO4) and concentrated to give crude product as an oil.
Reaction SMILES: C[Si](C)(C)[C:3]1[Se:7][C:6]2=[C:8]([O:28][CH2:29][CH:30]([CH2:35][CH3:36])[CH2:31][CH2:32][CH2:33][CH3:34])[C:9]3[CH:13]=[C:12]([Si](C)(C)C)[Se:11][C:10]=3[C:18]([O:19][CH2:20][CH:21]([CH2:26][CH3:27])[CH2:22][CH2:23][CH2:24][CH3:25])=[C:5]2[CH:4]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[CH2:35]([CH:30]([CH2:31][CH2:32][CH2:33][CH3:34])[CH2:29][O:28][C:8]1[C:6]2[Se:7][CH:3]=[CH:4][C:5]=2[C:18]([O:19][CH2:20][CH:21]([CH2:26][CH3:27])[CH2:22][CH2:23][CH2:24][CH3:25])=[C:10]2[Se:11][CH:12]=[CH:13][C:9]=12)[CH3:36]
Reactant: CCCCC(CC)COc1c2cc([Si](C)(C)C)[se]c2c(OCC(CC)CCCC)c2cc([Si](C)(C)C)[se]c12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CCCCC(CC)COc1c2cc[se]c2c(OCC(CC)CCCC)c2cc[se]c12
Yield: 91.9 %

Procedure:
To a solution of 2,6-bis(trimethysilyl)-4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b′]diselenophene (11) (0.29 g, 0.423 mmol) in THF (10 mL) was added 1.3 mL of tetrabutylammonium fluoride (1 M solution in THF). The resulted solution was stirred for 3 hours at room temperature water was added (40 mL) then extracted with chloroform (2×40 mL). The extract was dried over MgSO4 (anhydrous), and concentrated in vacuo. The residue was purified by column chromatography on silica gel (hexane:CH2Cl2, 98:2) to give yellow oil (0.21 g, 92%). 1H-NMR(CDCl3): δ 7.90 (d, J=5.9 Hz, 2H), 7.73 (d, J=5.9 Hz, 2H), 4.12 (d, J=5.5 Hz, 4H), 1.80 (m, 2H), 1.35-1.70 (m, 12H), 1.03 (t, J=4.9 Hz, 6H), 0.94 (t, J=4.8 Hz, 6H). MS (EI) Calculated. 540.5 found [M+1]+ 541.5.
Reaction SMILES: [H-].[Na+].[CH2:3]1COCC1.[C:8]1([C:14]2[N:15]=[CH:16][NH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CI>ClCCl>[CH3:3][N:17]1[CH:18]=[C:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:15]=[CH:16]1.[CH3:3][N:15]1[C:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:18][N:17]=[CH:16]1
Reactant: c1ccc(-c2c[nH]cn2)cc1
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: ClCCl
Product: Cn1cnc(-c2ccccc2)c1
Product: Cn1cncc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a slurry of sodium hydride, 60% in mineral oil (1.2 g, 31 mmol) in 100 mL anhyd. THF at 0° C. was added 4-phenylimidazole (4.00 g, 28 mmol) in small portions under nitrogen. Upon complete addition, the reaction was homogeneous and orange. After 10 min, methyl iodide (2.1 ml, 33 mmol) was added and the reaction was allowed to warm to ambient temperature. After 2 h, the reaction was quenched with 10 mL water and concentrated in vacuo. The resulting liquid was partitioned between water/brine and DCM. The aqueous layer was extracted with DCM (4×). The combined organic extracts were dried over anhyd sodium sulfate, filtered, and concentrated in vacuo to give an orange solid. This was dissolved in dichloromethane and purified by silica gel chromatography, 120 g, 60 min, 0-50% 90/10 DCM/MeOH in DCM, to give 1-methyl-4-phenyl-1H-imidazole and 1-methyl-5-phenyl-1H-imidazole as off-white solids.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH:7]=[CH2:8])[CH2:3][C:4]([OH:6])=[O:5].[Br:10]C(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[C:33]([Cl:37])(Cl)([Cl:35])[Cl:34]>>[Br:10][CH:7]([CH2:8][C:33]([Cl:37])([Cl:35])[Cl:34])[C:2]([CH3:9])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: ClC(Cl)(Cl)Br
Reactant: ClC(Cl)(Cl)Cl
Reactant: C=CC(C)(C)CC(=O)O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: CC(C)(CC(=O)O)C(Br)CC(Cl)(Cl)Cl

Procedure:
A mixture of 3,3-dimethypent-4-enoic acid (18.2 g.), carbon tetrachloride (100 ml.), bromotrichloromethane (57.0 g.) and benzoyl peroxide (0.15 g.) was refluxed under a nitrogen atmosphere for 72 hours after which the volatile portion was removed by evaporation under reduced pressure. The residue was recrystallised from petroleum ether (boiling range 80° to 100° C.) to yield 4-bromo-3,3-dimethyl-6,6,6-trichlorohexanoic acid, m.p. 123°-124° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([NH2:12])=[O:11])=[CH:4][C:3]=1[C:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=1.[C:19]([C:21]1[N:22]=[C:23]([C:34]([O-])=[O:35])[N:24]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:25]=1)#[N:20].[K+].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:10]([CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:34]([C:23]2[N:24]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:25]=[C:21]([C:19]#[N:20])[N:22]=2)=[O:35])=[C:3]([C:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=2)[CH:4]=1)(=[O:11])[NH2:12]
Reactant: C[Si](C)(C)CCOCn1cc(C#N)nc1C(=O)[O-]
Reactant: NC(=O)CCc1ccc(N)c(C2=CCCCC2)c1
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Agent: [K+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1cc(C#N)nc1C(=O)Nc1ccc(CCC(N)=O)cc1C1=CCCCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 91 %

Procedure:
To a mixture of 3-(4-amino-3-cyclohex-1-enyl-phenyl)-propionamide (as prepared in the previous step, 85.0 mg, 0.378 mmol), potassium 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate (as prepared in Example 1, step (d), 117 mg, 0.383 mmol) and PyBroP (179 mg, 0.383 mmol) in 2.5 mL of DMF was added DIEA (182 μL, 1.04 mmol). After stirring at RT for 16 h, the mixture was treated with 30 mL of EtOAc and washed with H2O (2×10 mL), brine (10 mL) and dried (Na2SO4). The organic solvent was evaporated in vacuo and the residue was purified by flash chromatography on silica gel (0-2% MeOH/DCM) to give 156 mg (91%) of the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for C26H35N5O3Si, 494.3 (M+H). found 494.0.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][O:16][CH3:17])[N:9]=[CH:8][N:7]=[C:6]2[S:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].[CH:26]([C:29]1[O:33][N:32]=[C:31]([NH:34][C:35](=[O:43])OC2C=CC=CC=2)[CH:30]=1)([CH3:28])[CH3:27].[CH2:44](OCC)[CH3:45]>>[CH:26]1([C:29]2[O:33][N:32]=[C:31]([NH:34][C:35]([NH:22][C:21]3[CH:23]=[CH:24][CH:25]=[C:19]([S:18][C:6]4[C:5]5[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[C:3]([O:2][CH3:1])[CH:4]=5)[N:9]=[CH:8][N:7]=4)[CH:20]=3)=[O:43])[CH:30]=2)[CH2:27][CH2:45][CH2:44][CH2:28]1
Reactant: COCCOc1cc2ncnc(Sc3cccc(N)c3)c2cc1OC
Reactant: CC(C)c1cc(NC(=O)Oc2ccccc2)no1
Reactant: CCOCC
Product: COCCOc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C5CCCC5)on4)c3)c2cc1OC
Yield: 53 %

Procedure:
Using the procedure described in Example 113C compound 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)aniline described in Example 231A (114 mg, 0.32 mmol) was reacted with phenyl 5-isopropylisoxazol-3-ylcarbamate described in Example 135A (130 mg, 0.48 mmol). Upon addition of dietyl ether, the solid was filtered off and washed with diethyl ether to give 1-(5-cyclopentylisoxazol-3-yl)-3-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea (91.12 mg, 53%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.52 (s, 1H), 9.07 (s, 1H), 8.68 (s, 1H), 7.79 (s, 1H), 7.59-7.41 (m, 2H), 7.41-7.24 (m, 3H), 6.50 (s, 1H), 4.39-4.24 (m, 2H), 4.00 (s, 3H), 3.88-3.66 (m, 2H), 3.34 (s, 3H), 3.25-3.04 (m, 1H), 2.09-1.88 (m, 2H), 1.75-1.48 (m, 6H); LC-MS (ESI) m/z 536 (M+H)+.