Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:10]([CH2:13][C:14]#[N:15])(=[O:12])=[O:11])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][CH2:24]Br.Cl>CN(C)C=O.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:24][CH2:23][CH:13]([C:14]#[N:15])[S:10]2(=[O:12])=[O:11])=[CH:5][CH:4]=1
Reactant: BrCCBr
Reactant: COc1ccc(NS(=O)(=O)CC#N)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(N2CCC(C#N)S2(=O)=O)cc1
Temperature: 55 °C
Reaction time: 2 h
Yield: 47.1 %

Procedure:
To a solution of the compound obtained in Step A (0.59 g) in dimethylformamide (40 ml) was added potassium carbonate (1.1 g). Then, a solution of 1,2-dibromoethane (0.59 g) in dimethylformamide (25 ml) was added dropwise at 55° C. The reaction mixture was then stirred at 55° C. for 2 hours, cooled to room temperature, poured into 15 ml water, and aqueous 2N hydrochloric acid was added to acidic pH. The aqueous layer was then extracted with dichloromethane, the combined organic layers washed two times with 2% aqueous hydrochloric acid, dried over sodium sulfate and concentrated in vacuo. Column chromatography (ethyl acetate/cyclohexane 7:3) afforded the title product as a beige solid (310 mg). 1HNMR (CDCl3, 400 MHz): 7.30 (d, 2H), 6.90 (d, 2H), 4.25 (m, 1H), (m, 1H), 3.70-3.90 (m, 5H), 2.95 (m, 1H), 2.80 (m, 1H).
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O-].[Na+].CO.Br[CH:21]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=2)=[CH:28][CH:27]=1)[C:22]([O:24][CH3:25])=[O:23]>C1C=CC=CC=1>[CH3:25][O:24][C:22](=[O:23])[CH:21]([O:14][C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:12]=1)[C:26]1[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=2)=[CH:30][CH:31]=1
Reactant: Oc1ccc(Oc2ccccc2)cc1
Reactant: COC(=O)C(Br)c1ccc(OCCCOc2ccc(Cl)cc2)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)C(Oc1ccc(Oc2ccccc2)cc1)c1ccc(OCCCOc2ccc(Cl)cc2)cc1
Yield: 41.4 %

Procedure:
To a mixture of 4.66 g of p-phenoxyphenol, 1.19 g of sodium methoxide, 10 ml of benzene and 40 ml of methanol is added 8.27 g of methyl bromo{p-[3-(p-chlorophenoxy)propoxy]phenyl}acetate in 10 ml of benzene. The mixture is refluxed for 22 hours and the solvent removed under reduced pressure. The residue is chromatographed over silica gel with dichloromethane as eluent giving a viscous oil which is again chromatographed over silica gel with dichloromethane as eluent. There is obtained 4.3 g of viscous oil which is crystallized from methylcyclohexane-methanol to give 3.6 g of white crystals, mp 78°-80° C.
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:21])[NH:6][C:7]2[C:12]([C:13]=1C)=[C:11](OS(O)(=O)=O)[CH:10]=[CH:9][C:8]=2[F:20])(=[O:3])[CH3:2].[CH3:22][O:23][CH2:24][CH:25]([NH2:27])[CH3:26]>>[C:1]([C:4]1[C:5](=[O:21])[NH:6][C:7]2[C:12]([C:13]=1[NH:27][CH:25]([CH3:26])[CH2:24][O:23][CH3:22])=[CH:11][CH:10]=[CH:9][C:8]=2[F:20])(=[O:3])[CH3:2]
Reactant: CC(=O)c1c(C)c2c(OS(=O)(=O)O)ccc(F)c2[nH]c1=O
Reactant: COCC(C)N
Product: COCC(C)Nc1c(C(C)=O)c(=O)[nH]c2c(F)cccc12
Yield: 86.6 %

Procedure:
3-Acetyl-8-fluoro-4-methylsulfoxy-2-quinolinone (2.67g, 0.01 mol) and 1-methoxy-2-propylamine(0.88g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.53g, yield: 87%).
Reaction SMILES: Cl[S:2]([C:5]1[S:6][C:7]([CH2:10][O:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3].[NH2:20][C:21]1[O:25][N:24]=[C:23]([CH3:26])[C:22]=1[Br:27]>>[Br:27][C:22]1[C:23]([CH3:26])=[N:24][O:25][C:21]=1[NH:20][S:2]([C:5]1[S:6][C:7]([CH2:10][O:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)(=[O:4])=[O:3]
Reactant: Cc1noc(N)c1Br
Reactant: O=C(OCc1ccc(S(=O)(=O)Cl)s1)c1ccccc1
Product: Cc1noc(NS(=O)(=O)c2ccc(COC(=O)c3ccccc3)s2)c1Br
Yield: 30.3 %

Procedure:
N-(4-bromo-3-methyl-5-isoxazolyl)-5-(benzoyloxymethyl)thiophene-2-sulfonamide was prepared as described in Example 2 from 2-chlorosulfonyl-5-(benzoyloxymethyl)thiophene (520 mg, 1.72 mmol) and 5-amino-4-bromo-3-methyl isoxazole (319 mg, 1.8 mmol). Purification by column chromatography using 10% MeOH/CHCl3) gave 238 mg of pure N-(4-bromo-3-methyl-5-isoxazolyl)-5-(benzoyloxymethyl)thiophene-2-sulfonamide as brown semisolid (31% yield, m.p. 92° C.).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[CH2:12][CH2:11][NH:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:24][C:25](Br)=[O:26].[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][NH2:35])[CH:29]=1>>[C:1]1([CH2:7][CH2:8][CH:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[CH2:12][CH2:11][N:10]2[CH2:24][C:25]([NH:35][CH2:34][C:30]2[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=2)=[O:26])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NCc1cccnc1
Reactant: COc1cc2c(cc1OC)C(CCc1ccccc1)NCC2
Reactant: O=C(Br)CBr
Product: COc1cc2c(cc1OC)C(CCc1ccccc1)N(CC(=O)NCc1cccnc1)CC2

Procedure:
prepared by reaction of 1-(2-Phenyl-ethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 3-picolylamine
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:13][C:14]1[CH:18]=[C:17]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[NH:16][N:15]=1.C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[N:11]=[C:10]([NH:13][C:14]2[NH:15][N:16]=[C:17]([CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:18]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Nc1cc(C2CCCC2)[nH]n1
Reactant: Clc1nc(Cl)c2ccccc2n1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Clc1nc(Nc2cc(C3CCCC3)n[nH]2)c2ccccc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.1 %

Procedure:
2,4-Dichloroquinazoline (0.657 g, 3.3 mmol) in ethanol (9 ml) was treated with 3-amino-5-cyclopentyl pyrazole (0.5 g, 3.3 mmol) and triethylamine (0.46 ml, 3.3 mmol) and stirred overnight at room temperature. The mixture was filtered and the solid washed with ethanol to give (2-chloro-quinazolin-4-yl)-(5-cyclopentyl-2H-pyrazol-3-yl)-amine as colourless crystals (684 mg, 66%).
Reaction SMILES: [O:1]=[C:2]1[NH:6][C@H:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:8]=2)[C@@H:4]([C:21]#[N:22])[O:3]1.Cl.C(N(CC)CC)C.[N-:31]=[N+:32]=[N-:33].[Na+].O>C1(C)C=CC=CC=1>[C:15]1([C:14]#[C:13][C:9]2[CH:8]=[C:7]([C@@H:5]3[C@@H:4]([C:21]4[NH:33][N:32]=[N:31][N:22]=4)[O:3][C:2](=[O:1])[NH:6]3)[CH:12]=[CH:11][CH:10]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: [N-]=[N+]=[N-]
Reactant: N#C[C@H]1OC(=O)N[C@@H]1c1cccc(C#Cc2ccccc2)c1
Agent: Cl
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Product: O=C1N[C@H](c2cccc(C#Cc3ccccc3)c2)[C@@H](c2nnn[nH]2)O1
Reaction time: 48 h
Yield: 74.4 %

Procedure:
To a solution of (4R,5S)-2-oxo-4-(3-(phenylethynyl)phenyl)oxazolidine-5-carbonitrile (35 mg, 0.121 mmol) in Toluene (2 mL) was added triethylamine hydrochloride (50.6 mg, 0.364 mmol) and sodium azide (23.68 mg, 0.364 mmol) and the reaction was heated to reflux. After 2 days, the reaction was poured into water (1 ml) and extracted with ethylacetate (10 mL×2). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to an off white solid that was purified by Preparative HPLC method 4 providing (4R,5S)-4-(3-(phenylethynyl)phenyl)-5-(1H-tetrazol-5-yl)oxazolidin-2-one (30 mg, 0.090 mmol, 73.8% yield) 1H NMR (500 MHz, DMSO-d6) δ ppm 5.21-5.55 (m, 2H) 7.10 (br. s., 3H) 7.34 (d, J=7.93 Hz, 1H) 7.39-7.49 (m, 4H) 7.51 (d, J=7.32 Hz, 1H) 7.57 (dd, J=6.41, 3.05 Hz, 2H) 8.27 (s, 1H). Mass spec.: 331.99 (MH)+.
Reaction SMILES: [O:1]1CCO[CH:2]1[CH2:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[O:12][CH:11]=[CH:10]2.Cl>O1CCOCC1>[O:17]=[C:13]1[C:14]2[C:9](=[CH:8][C:7]([CH2:6][CH:2]=[O:1])=[CH:16][CH:15]=2)[CH:10]=[CH:11][O:12]1
Reactant: O=c1occc2cc(CC3OCCO3)ccc12
Agent: Cl
Solvent: C1COCCO1
Product: O=CCc1ccc2c(=O)occc2c1
Reaction time: 16 h

Procedure:
To a solution of 6-(1,3-dioxolan-2ylmethyl)-1H-isochromen-1-one (410 mg, 1.8 mmol) in dioxane (20 mL) was added HCl (20 ml, 3M), and then stirred for 16 hours. The reaction was extracted with ethyl acetate then separated. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to yield the title product. LC-MS (IE, m/z): 189 [M+1]+.
Reaction SMILES: [I-].[CH:2]1([CH2:7][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:37]([O:39][C:40](=[O:52])[C:41]([C:43]1[CH:48]=[CH:47][C:46]([S:49][CH2:50][CH3:51])=[CH:45][CH:44]=1)=O)[CH3:38]>O1CCCC1>[CH2:37]([O:39][C:40](=[O:52])[C:41]([C:43]1[CH:48]=[CH:47][C:46]([S:49][CH2:50][CH3:51])=[CH:45][CH:44]=1)=[CH:7][CH:2]1[CH2:6][CH2:5][CH2:4][CH2:3]1)[CH3:38]
Reactant: CCOC(=O)C(=O)c1ccc(SCC)cc1
Reactant: c1ccc([P+](CC2CCCC2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C(=CC1CCCC1)c1ccc(SCC)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 50.1 %

Procedure:
A suspension of cyclopentylmethyl triphenylphosphonium iodide (24.48 g, 51.82 mmol) in dry tetrahydrofuran (100 mL) was cooled to 0° C. and then treated dropwise with a 1.0M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (52 mL, 51.82 mmol). The bright orange reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then treated with (4-ethylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (9.50 g, 39.87 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 20 h. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran and then diluted with water (300 mL). The aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 19/1 hexanes/ethyl acetate) afforded the 3-cyclopentyl-2-(4-ethylsulfanyl-phenyl)-acrylic acid ethyl ester (6.08 g, 50%) as a yellow oil containing a 1.82:1 mixture of (E):(Z) isomers: FAB-LRMS m/e calcd for C18H24O2S (M+H)+ integer mass 304, found 305. The isomeric mixture was used without further separation in subsequent reactions.
Reaction SMILES: [C:1]1([CH2:7][C:8]([C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH:21]=O)[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32].Cl>CCO.O>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C:10]3[CH:14]=[CH:13][S:12][CH:11]=3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH3:16]
Reactant: O=C(Cc1ccccc1)c1ccsc1
Reactant: NC(N)=O
Reactant: CCOc1cc(C=O)cc([N+](=O)[O-])c1O
Agent: Cl
Solvent: CCO
Solvent: O
Product: CCOc1cc(C2NC(=O)NC(c3ccsc3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Yield: 22.9 %

Procedure:
A mixture of 2-phenyl-1-(thiophen-3-yl)ethanone (Intermediate 39) (100 mg, 0.49 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (95 mg, 0.45 mmol), urea (81 mg, 1.35 mmol), and concentrated HCl solution (0.04 mL, 0.45 mmol) in EtOH (5 mL) was refluxed overnight. The mixture was diluted with water, and extracted with EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layer was dried over Na2SO4, evaporated in vacuo, and purified by preparative HPLC to give Compound 79 (45 mg, yield 23%). 1H NMR (DMSO-d6 300 MHz): δ 10.19 (s, 1H), 8.50 (s, 1H), 7.43-7.40 (m, 2H), 7.30-7.24 (m, 2H), 7.04-7.00 (m, 4H), 6.83-6.80 (m, 2H), 6.52 (s, J=5.1 Hz, 1H), 5.07 (d, J=2.4 Hz, 1H), 3.97-3.88 (m, 2H), 1.22 (t, J=6.9 Hz, 3H); MS (ESI): m/z 438.0 [M+1]+.
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15](OB(O)O)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25](Cl)[N:24]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1(C)C=CC=CC=1.CCCCCC.O.CCCCCC>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([Cl:22])[N:24]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[C@H]1CC[C@H](c2ccc(OB(O)O)cc2)CC1
Reactant: Clc1cccc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCCCCC
Solvent: O
Product: CCCCC[C@H]1CC[C@H](c2ccc(-c3cccc(Cl)n3)cc2)CC1

Procedure:
A mixture of 0.23 mol of 4-(trans-4-pentylcyclohexyl)phenylboric acid, 0.23 mol of 2,6-dichloropyridine, 5 mmol of TPP, 230 ml of a 2 molar sodium carbonate solution and 400 ml of toluene are heated at the boil for 1 hour. The reaction mixture is cooled, and 200 ml of hexane and 200 ml of water are added. The organic phase is separated off, the solvent is removed by evaporation, and the pure product is obtained by chromatography on silica gel using toluene/hexane 3:1 as the eluent.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](C#N)[CH:15]=3)[N:10]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[O:25]([CH:32]([CH3:36])[C:33]([OH:35])=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl.[CH3:38][N:39](C)CCCN=C=NCC>ClCCl>[C:38]([CH:22]1[CH2:21][O:20][CH:19]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:8]([C:4]3[CH:3]=[C:2]([NH:1][C:33](=[O:35])[CH:32]([O:25][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH3:36])[CH:7]=[CH:6][CH:5]=3)=[N:9]2)[CH2:24][CH2:23]1)#[N:39]
Reactant: N#Cc1ccc2c(c1)c(-c1cccc(N)c1)nn2C1CCCCO1
Reactant: CC(Oc1ccccc1)C(=O)O
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: CC(Oc1ccccc1)C(=O)Nc1cccc(-c2nn(C3CCC(C#N)CO3)c3ccccc23)c1

Procedure:
To a solution of 3-(3-aminophenyl)-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile (0.300 g, 0.94 mmol) in dichloromethane (10 mL) was added 2-phenoxy propionic acid (0.172 g, 1.034 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.216 g, 1.13 mmol). After overnight reaction at room temperature, the reaction mixture was partitioned between dichloromethane and water. The organic phase was dried over sodium sulfate and evaporated to dryness. The title compound was purified by column chromatography (SiO2, 25% ethyl acetate in hexanes) (0.370 g, 84%): ES-MS (m/z) 489 [M+Na], 467 [M+H]+.
Reaction SMILES: [CH:1]([Si:4]([CH:13]([CH3:15])[CH3:14])([CH:10]([CH3:12])[CH3:11])[C:5]1[O:6][CH:7]=[CH:8][N:9]=1)([CH3:3])[CH3:2].C([Li])CCC.[BH:21]([OH:23])[OH:22].O[C:25]([CH3:31])([C:27](O)([CH3:29])[CH3:28])[CH3:26]>C1COCC1.C(OCC)C.C(O)(=O)C>[CH3:26][C:25]1([CH3:31])[C:27]([CH3:29])([CH3:28])[O:23][B:21]([C:7]2[O:6][C:5]([Si:4]([CH:1]([CH3:3])[CH3:2])([CH:10]([CH3:12])[CH3:11])[CH:13]([CH3:15])[CH3:14])=[N:9][CH:8]=2)[O:22]1
Reactant: CC(C)(O)C(C)(C)O
Reactant: CC(C)[Si](c1ncco1)(C(C)C)C(C)C
Reactant: OBO
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCOCC
Product: CC(C)[Si](c1ncc(B2OC(C)(C)C(C)(C)O2)o1)(C(C)C)C(C)C
Temperature: -78 °C
Reaction time: 2 h

Procedure:
2-Triisopropylsilanyl-oxazole (intermediate 16, 10 g, 44.365 mmol) is dissolved in 40 mL abs. diethylether under argon. The solution is cooled to −78° C. and n-butyllithium (1.6 M solution in hexane, 100 mL, 160 mmol) is added slowly at that temperature. After stirring for 1 h boronic acid triispropylester (12 mL, 52.193 mmol) 20 mL abs. THF is added slowly. The mixture is stirred for 2 h, and is warmed to r.t. The mixture is quenched with methanol. 2,3-Dihydroxy-2,3-dimethylbutane (pinacole, 5.243 g, 44.365 mmol) is dissolved in 10 mL THF and injected to the mixture at 18° C. within 3 min. The mixture is acidified to pH 5 with acetic acid and stirred for 12 h. After addition of 150 mL diethylether and filtration over silica gel, the solvent is evaporated in vacuo. Yield: 15.2 g; ESI mass spectrum: [M+H]+=352; retention time HPLC: 1.334 min (HPLC method Z001_002).
Reaction SMILES: [CH2:1]([C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20](O)=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:24]([O-:27])([O-])=O.[Cs+].[Cs+].CCO[CH2:33][CH3:34]>CN(C)C=O>[CH2:1]([C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([O:27][CH2:24][CH2:11][CH2:1][CH2:2][CH2:3][CH:33]=[CH2:34])=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:1]([C:11]1[CH:12]=[N:13][C:14]([C:17]2[CH:22]=[CH:21][C:20]([O:27][CH2:24][CH2:3][CH2:2][CH2:1][CH2:11][CH2:16][CH:33]=[CH2:34])=[CH:19][CH:18]=2)=[N:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: O=C([O-])[O-]
Reactant: CCCCCCCCCCc1cnc(-c2ccc(O)cc2)nc1
Reactant: CCOCC
Agent: [Cs+]
Solvent: CN(C)C=O
Product: C=CCCCCCCOc1ccc(-c2ncc(CCCCCCCCCC)cn2)cc1
Product: C=CCCCCCOc1ccc(-c2ncc(CCCCCCCCCC)cn2)cc1

Procedure:
Vinyl-terminated phenyl pyrimidines with different spacer lengths were synthesized from 4-(5-decylpyrimidin-2-yl)phenol for siloxane coupling to 1,2 polybutadiene. A general procedure for this synthesis is as follows: 4-(5-decylpyrimidin-2-yl)phenol (1.89 grams, 6.05 mmols), a bromoalkene (7-bromo hept-1-ene, 8-bromooct-1-ene or 10-bromododec-1-ene, 8 mmol) and Cs2CO3 (2.56 grams, 8 mmols) were stirred at room temperature in 40 mL of dimethyl formamide overnight, resulting in near-quantitative conversion to the ether (Scheme 3), monitored by thin layer chromatography. The reaction mixture was extracted three times with 50 mL of dichloromethane. The organic extracts were washed three times with water and dried with MgSO4. The crude product was recrystallized in hot 95% ethanol, resulting in analytically pure white crystals of 5-decyl-2-(4-(hept-6-enyloxy)phenyl)pyrimidine, 5-decyl-2-(4-(oct-7-enyloxy)phenyl)pyrimidine, -decyl-2-(4-(dec-9-enyloxy)phenyl)pyrimidine (1.20 g, 2.09 g, 1.69 g AND 48.0%, 83.6%, 66.02% overall yield, respectively).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH3:29])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([C:23]([F:26])([F:25])[F:24])[CH:12]=3)[O:8][C:7](=[O:27])[C:6]=2[CH:28]=1.C(N(CC)CC)C.Br.[S:38]1[CH2:41][CH:40]([NH2:42])[CH2:39]1.O>O1CCCC1>[Cl:1][C:2]1[CH:28]=[C:6]([C:7](=[O:27])[NH:42][CH:40]2[CH2:41][S:38][CH2:39]2)[C:5]([NH:10][C:9]([C:11]2[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=[C:13]([C:23]([F:24])([F:25])[F:26])[CH:12]=2)=[O:8])=[C:4]([CH3:29])[CH:3]=1
Reactant: NC1CSC1
Reactant: Cc1cc(Cl)cc2c(=O)oc(-c3cc(C(F)(F)F)nn3-c3ncccc3Cl)nc12
Agent: Br
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1cc(Cl)cc(C(=O)NC2CSC2)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Yield: 41 %

Procedure:
To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 250 mg (41%) of the title compound as a white solid.
Reaction SMILES: [H-].[Na+].[C:3]([C:7]1[CH:8]=[C:9]([OH:17])[CH:10]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:12]=1)([CH3:6])([CH3:5])[CH3:4].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1Br>[Cu].CC(N(C)C)=O>[C:13]([C:11]1[CH:10]=[C:9]([CH:8]=[C:7]([C:3]([CH3:6])([CH3:5])[CH3:4])[CH:12]=1)[O:17][C:22]1[CH:23]=[CH:24][C:19]([Br:18])=[CH:20][CH:21]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1
Reactant: Brc1ccccc1Br
Agent: [Cu]
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C)c1cc(Oc2ccc(Br)cc2)cc(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 8.8 g. of 50% sodium hydride (mineral oil dispersion) in 320 ml. of dry dimethylacetamide is added, in portions over 15 minutes with vigorous stirring, 32 g. of 3,5-di-tertiary butylphenol, during which the reaction mixture is cooled with an icebath to moderate the internal temperature. The reaction mixture is then stirred at room temperature for 1 hour, after which is added 75.2 g. of dibromobenzene and 800 mg. of copper powder. The resultant mixture is refluxed for 8 hours, after which time it is cooled and the dimethylacetamide is removed in vacuo. The resultant residue is extracted several times with methylene chloride and the insoluble copper filtered off. The combined methylene chloride extracts are washed two times with water, dried over sodium sulfate, filtered, evaporated in vacuo to dryness and the residue recrystallized from ethanol to obtain 1-(3,5-di-tertiary butylphenoxy)-4-bromobenzene, m.p. 98°-100° C.
Reaction SMILES: Cl.C[O:3][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][C:25]=1[O:26]C)[CH2:7][C@H:8]1[CH2:12][CH2:11][C@@H:10]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21]C)=[CH:17][CH:16]=2)[NH:9]1.B(Br)(Br)[Br:29]>C(Cl)Cl>[BrH:29].[OH:3][C:4]1[CH:5]=[C:6]([CH:23]=[CH:24][C:25]=1[OH:26])[CH2:7][C@H:8]1[CH2:12][CH2:11][C@@H:10]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[NH:9]1
Reactant: COc1ccc(CC[C@@H]2CC[C@H](Cc3ccc(OC)c(OC)c3)N2)cc1
Reactant: BrB(Br)Br
Agent: Cl
Solvent: ClCCl
Product: Br
Product: Oc1ccc(CC[C@@H]2CC[C@H](Cc3ccc(O)c(O)c3)N2)cc1
Temperature: 25 °C

Procedure:
To a cold solution of 3 g. (0.008 mole) of cis-2-(3,4-dimethoxybenzyl)-5-[2-(4-methoxyphenyl)ethyl]pyrrolidine hydrochloride in 50 ml. of methylene chloride was added dropwise 8 g. (0.032 mole) of boron tribromide at -60° C. After addition of boron tribromide was finished, the cold bath was removed, and the reaction mixture was gradually warmed up to room temperature over a period of about one and a half hours. The mixture was then cooled again in a Dry Ice-acetone bath and 25 ml. of methanol was carefully added. After methanol was completely removed, the residue was treated with ethyl acetate. Upon storing in a freezer, an off-white solid crystallized out, which was recrystallized from ethyl acetate and ethanol to give 3.11 g. of pure product, m.p. 195°-198° C.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[C:6]([C:8]1[C:9]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)=[N:10][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:12][C:13]=1O)#[N:7].CN(C)C1C=CC=CC=1>O1CCOCC1>[Cl:3][C:13]1[N:12]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]=[C:9]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:8]=1[C:6]#[N:7]
Reactant: N#Cc1c(O)nc(-c2ccccc2)nc1-c1cccc([N+](=O)[O-])c1
Reactant: O=P(Cl)(Cl)Cl
Solvent: C1COCCO1
Solvent: CN(C)c1ccccc1
Product: N#Cc1c(Cl)nc(-c2ccccc2)nc1-c1cccc([N+](=O)[O-])c1
Reaction time: 3 h

Procedure:
POCl3 (50 ml) was added to a stirred solution of 5-cyano-4-(3-nitrophenyl)-2-phenyl-6-hydroxy-pyrimidine (example 31(a), 15.0 g) and dimethylaniline (0.5 ml) in dry 1,4-dioxane p.a. (200 ml). After 3 h at 90° C., the warm mixture was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in 1,4-dioxane and ice water was added. The resulting precipitate was filtered off and washed with water. Residual water was removed by coevaporation with 1,4-dioxane.