Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[C:18]([CH2:20][S:21][C:22]3[C:27]([C:28]#[N:29])=[C:26]([N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)[C:25]([C:36]#[N:37])=[C:24]([OH:38])[N:23]=3)[N:19]=2)=[CH:11][CH:10]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Ag+2]>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[S:16][CH:17]=[C:18]([CH2:20][S:21][C:22]3[N:23]=[C:24]([O:38][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:25]([C:36]#[N:37])=[C:26]([N:30]4[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]4)[C:27]=3[C:28]#[N:29])[N:19]=2)=[CH:13][CH:14]=1
Reactant: CCOC(=O)CI
Reactant: N#Cc1c(O)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1N1CCCCC1
Agent: [Ag+2]
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCOC(=O)COc1nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c(N2CCCCC2)c1C#N
Reaction time: 24 h

Procedure:
43 mg ethyl iodoacetate are initially charged in 2.4 ml of dry toluene. 47 mg (0.10 mmol) of the compound from Example 10A and 14 mg (0.05 mmol) of silver carbonate are then added. The reaction mixture is stirred with exclusion of light for 24 h. The mixture is then diluted with 1 ml of ethyl acetate, and 1 ml of saturated aqueous sodium bicarbonate solution is added. After separation of the phases the organic phase is dried over magnesium sulfate. The solvent is removed on a rotary evaporator and the residue is purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]#[CH:10])[CH2:4][CH2:3]1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](/[C:35]2[CH:40]=[CH:39][C:38](I)=[CH:37][CH:36]=2)=[CH:19]/[CH2:20][O:21][C:22]2[CH:33]=[CH:32][C:25]([O:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[C:24]([CH3:34])[CH:23]=2)=[CH:14][CH:13]=1>O1CCCC1.C(N(CC)CC)C.C1C=CC=CC=1.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.[Cu]I>[Cl:11][C:12]1[CH:13]=[CH:14][C:15](/[C:18](/[C:35]2[CH:36]=[CH:37][C:38]([C:10]#[C:9][CH2:8][N:5]3[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]3)=[CH:39][CH:40]=2)=[CH:19]/[CH2:20][O:21][C:22]2[CH:33]=[CH:32][C:25]([O:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[C:24]([CH3:34])[CH:23]=2)=[CH:16][CH:17]=1
Reactant: COC(=O)COc1ccc(OC/C=C(/c2ccc(Cl)cc2)c2ccc(I)cc2)cc1C
Reactant: C#CCN1CCC(O)CC1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: COC(=O)COc1ccc(OC/C=C(/c2ccc(Cl)cc2)c2ccc(C#CCN3CCC(O)CC3)cc2)cc1C
Temperature: 0 °C
Reaction time: 72 h

Procedure:
4-Hydroxy-1-propargylpiperidine (280 mg, 2.01 mmol) was added under nitrogen atmosphere to a degassed solution of methyl (Z)-[4-[3-(4-chlorophenyl)-3-(4-iodophenyl)allyloxy]-2-methylphenoxy]acetate (450 mg, 0.82 mmol; prepared as described in example 7) in a mixture of tetrahydrofuran (10 mL) and triethylamine (8 mL) The solution was cooled to 0° C.; tetrakis(triphenylphosphine)palladium (85 mg, 0.073 mmol) and copper(I) iodide (22 mg, 0.115 mmol) were added. The reaction mixture was stirred at ambient temperature for 72 h, diluted with benzene (100 mL), decanted and evaporated in vacuo. The residue was purified by column chromatography (silica gel Fluka 60, benzene/methanol 10:0-4:6) yielding methyl (E)-[4-[3-(4-chlorophenyl)-3-[4-[3-(4-hydroxypiperidin-1-yl)propynyl]phenyl]allyloxy]-2-methylphenoxy]acetate.
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1[CH:15]=[CH:14][S:13][C:12]=1[NH:16][C:17](=O)[CH2:18][CH2:19][CH3:20])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)CO>[CH2:1]([N:8]1[C:9](=[O:10])[C:11]2[CH:15]=[CH:14][S:13][C:12]=2[N:16]=[C:17]1[CH2:18][CH2:19][CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC(=O)Nc1sccc1C(=O)NCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: OCCO
Product: CCCc1nc2sccc2c(=O)n1Cc1ccccc1
Temperature: 130 °C

Procedure:
A mixture of N-benzyl-2-(butyrylamino)thiophene-3-carboxamide (2-3, 230 mg, 0.76 mmol, 1 equiv) and sodium hydroxide (3 mg, 0.08 mmol, 0.1 equiv) in ethylene glycol (5 mL) was heated at 130° C. for 5 h. The reaction mixture was allowed to cool, then partitioned between a half-saturated aqueous sodium chloride solution and ethyl acetate (2×75 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column (hexanes initially, grading to 100% ethyl acetate) to provide 3-benzyl-2-propylthieno[2,3-d]pyrimidin-4(3H)-one (2-4) as a colorless oil which solidified upon standing. 1H NMR (300 MHz, CDCl3) δ 7.48 (d, 1H, J=5.8 Hz), 7.31 (m, 3H), 7.19 (d, 1H, J=5.8 Hz), 7.17 (d, 2H, J=7.9 Hz), 5.42 (s, 2H), 2.72 (t, 2H, J=7.6 Hz), 1.78 (sextet, 2H, J=7.6 Hz), 0.97 (t, 3H, J=7.3 Hz). 3-benzyl-5,6-dibromo-2-(1-bromopropyl)thieno[2,3-d]pyrimidin-4(3H)-one (2-5) and 3-benzyl-6-bromo-2-(1-bromoyropyl)thieno[2,3-d]pyrimidin-4(3H)-one (2-6)
Reaction SMILES: Br[CH2:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[C:11]([OH:18])[C:10]=2[Cl:19])=[CH:5][CH:4]=1.[OH:22][C:23]1[CH:27]=[C:26]([C:28]2[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=2)[O:25][N:24]=1.C([O-])([O-])=O.[Na+].[Na+].C(O)CC>O.C(COC)OC.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>[OH:22][C:23]1[CH:27]=[C:26]([C:28]2[CH:33]=[C:32]([CH:31]=[CH:30][CH:29]=2)[CH2:2][C:3]2[CH:21]=[CH:20][C:6]([CH2:7][O:8][C:9]3[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[C:11]([OH:18])[C:10]=3[Cl:19])=[CH:5][CH:4]=2)[O:25][N:24]=1
Reactant: OB(O)c1cccc(-c2cc(O)no2)c1
Reactant: CC(=O)c1ccc(OCc2ccc(CBr)cc2)c(Cl)c1O
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: CCCO
Solvent: O
Solvent: COCCOC
Product: CC(=O)c1ccc(OCc2ccc(Cc3cccc(-c4cc(O)no4)c3)cc2)c(Cl)c1O
Temperature: 70 °C
Yield: 5.5 %

Procedure:
Add 1-(4-(4-(bromomethyl)benzyloxy)-3-chloro-2-hydroxyphenyl)ethanone (180 mg, 0.487 mmol) and 3-(3-hydroxyisoxazol-5-yl)phenylboronic acid (218 mg, 1.06 mmol) to a 2.0 M solution of Na2CO3 in water (2.36 mL), dimethoxyethane (4.72 mL), and n-PrOH (4.72 mL). Degas the solution. Add tetrakis(triphenylphosphine)palladium (0) (123 mg, 0.106 mmol) and degas the mixture. Heat the mixture at 70° C. for 12 h. Quench the reaction with water. Extract with EtOAc. Dry, filter and concentrate. Purify the residue by flash chromatography on silica gel afforded the title compound (12 mg, 5%): 1H NMR (d6-DMSO) δ 2.61 (s, 3H), 4.02 (s, 2H), 5.31 (s, 2H), 6.51 (s, 1H), 6.89 (d, J=9.0 Hz, 1H), 7.31-7.36 (m, 3H), 7.39-7.44 (m, 3H), 7.62 (d, J=7.8 Hz, 1H), 7.70 (s, 1H), 7.93 (d, J=9.4 Hz, 1H), 11.34 (s, 1H), 13.13 (s, 1H); MS (APCI-neg mode) m/z (rel intensity): 448 (M−H, 100%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[CH:8][C:9]([OH:11])=O)[CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][NH2:33])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>ClCCl>[C:18]([O:22][C:23]([N:25]1[CH2:26][CH2:27][N:28]([CH2:31][CH2:32][NH:33][C:9](=[O:11])[CH:8]=[CH:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:29][CH2:30]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)OC(=O)N1CCN(CCN)CC1
Reactant: O=C(O)C=Cc1cccnc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(CCNC(=O)C=Cc2cccnc2)CC1

Procedure:
Batch size: 36.1 g (242 mmol) 3-(3-pyridyl)-acrylic acid, 23.1 ml (264 mmol) oxalyl chloride, 50 g (15.4 mmol) 2-[4-(tert-but-oxycarbonyl)-piperazin-1-yl]-ethylamine and 30.4 ml (220 mmol) TEA in 400 ml absolute dichloromethane.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:8]2[C:9](=[O:22])[C:10]3[NH:11][C:12]([Br:21])=[N:13][C:14]=3[N:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:7]2=[N:6][N:5]=1.[C:23]1([N:29]=[C:30]=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C.O.C(#N)C>[Br:21][C:12]1[NH:11][C:10]2[C:9](=[O:22])[N:8]3[C:4]([CH2:3][CH2:2][NH:1][C:30]([NH:29][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:31])=[N:5][N:6]=[C:7]3[N:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:14]=2[N:13]=1
Reactant: O=C=Nc1ccccc1
Reactant: CCCCCn1c2nc(Br)[nH]c2c(=O)n2c(CCN)nnc12
Solvent: O
Solvent: CN(C)C=O
Solvent: CC#N
Product: CCCCCn1c2nc(Br)[nH]c2c(=O)n2c(CCNC(=O)Nc3ccccc3)nnc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
A mixture of 3-(2-aminoethyl)-7-bromo-9-pentyl-6,9-dihydro-5H-[1,2,4]triazolo[4,3-a]purin-5-one (62 mg, 0.17 mmol) and phenyl isocyanate (0.018 mL, 0.16 mmol) in DMF (5 mL) was stirred at room temperature overnight. The reaction mixture was diluted with water and acetonitrile and then purified by preparative LCMS to give the desired product (about 80% conversion). LCMS calculated for C20H24BrN8O2 (M+H): 487.1; 489.1. Found: 487.0, 489.0.
Reaction SMILES: [Br-].C1([N+:8]2[NH:9][N:10]=[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]CCCCCCCC)[CH:12]=2)C=CC=CC=1.C(NNC=O)=O>O>[C:13]1([C:11]2[N:10]=[N:9][NH:8][CH:12]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CCCCCCCCCCCCCCc1c[n+](-c2ccccc2)[nH]n1
Agent: O=CNNC=O
Agent: [Br-]
Solvent: O
Product: c1ccc(-c2c[nH]nn2)cc1
Temperature: 180 °C
Reaction time: 3 h

Procedure:
2.6 ml (2.64 g, 0.028 mol) aniline 1 and 2.5 g (0.028 mol) diformyl hydrazine are combined in a Schlenk flask. The flask is covered with a plastic lid loosely and the reaction mixture is stirred for 3 h at 180° C. Toward the end of the reaction time the lid is removed to allow produced reaction water to evaporate. After cooling down, 20 ml chloroform is added. The remaining diformyl hydrazine is filtered off and washed with chloroform. The combined chloroform phases are dried over sodium sulfate. 100 ml diethylether is added and the solution allowed to rest 3 days in the fridge for crystallizing. The precipitated precipitate is filtered off, washed with diethylether, and dried in vacuum.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=3)=[CH:27][CH:26]=2)([CH3:24])[CH2:20][CH2:21][CH2:22][OH:23])=[CH:15][CH:14]=1.C1(N=C=NC2CCCCC2)CCCCC1.C(OCC)(=O)C>CS(C)=O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=3)=[CH:27][CH:26]=2)([CH3:24])[CH2:20][CH2:21][CH:22]=[O:23])=[CH:15][CH:14]=1
Reactant: CC(CCCO)(c1ccc(OCc2ccc3ccccc3n2)cc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(CCC=O)(c1ccc(OCc2ccc3ccccc3n2)cc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 68.5 %

Procedure:
To a solution in DMSO (20 mL) of 4,4-bis(4-(2-quinolylmethoxy)phenyl)pentan-1-ol (410 mg, 0.74 mmol), prepared as in Example 4, and 1,3-dicyclohexylcarbodiimide (515 mg, 2.5 mmol) was added aqueous 1M phosophoric acid (0.5 mL) and the resulting mixture was stirred at room temperature for 4 hours. Ethyl acetate (80 mL) was added and dicyclohexylurea was filtered off. The filtrate was washed with water and brine dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel (methylene chloride-ethyl acetate 9:1) to afford 280 mg of 4,4-bis(4-(2-quinolylmethoxy)phenyl)pentanal.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([CH3:19])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[CH2:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH:21]1[C:29](O)=[O:30]>>[CH3:19][N:12]1[C:13]2[N:14]=[CH:15][N:16]=[CH:17][C:18]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:29]([CH:21]3[CH2:22][C:23]4[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:20]3)=[O:30])[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1
Reactant: Cn1cc(C(=O)c2cncc(N)c2)c2cncnc21
Reactant: O=C(O)C1Cc2ccccc2C1
Product: Cn1cc(C(=O)c2cncc(NC(=O)C3Cc4ccccc4C3)c2)c2cncnc21

Procedure:
The title compound was prepared according to the method described for Library protocol 1 starting from (5-amino-pyridin-3-yl)-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanone (Preparation 110) and indane-2-carboxylic acid to afford the title compound. LCMS: Rt=2.58 min; m/z 398 [M+H].
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[C:5]([CH:10]=[O:11])=[CH:4][CH2:3]1.[CH2:12]([OH:16])[CH:13](O)[CH3:14].O>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:14][CH:13]1[CH2:12][O:16][CH:10]([C:5]2[C:6]([CH3:8])([CH3:9])[CH2:7][CH:2]([CH3:1])[CH2:3][CH:4]=2)[O:11]1
Reactant: CC(O)CO
Reactant: CC1CC=C(C=O)C(C)(C)C1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC1CC=C(C2OCC(C)O2)C(C)(C)C1
Yield: 65.1 %

Procedure:
4,6,6-Trimethyl-1-cyclohexen-1-carbaldehyde (2 g, 13 mmole), 1,2-propanediol (4 g, 53 mmole) and p-toluenesulfonic acid (50 mg) were refluxed in 20 ml of toluene, with water separation in a Dean-Stark apparatus, during 6 h. The resulting solution was washed with a NaHCO3 solution and the crude product distilled at a bath temperature of 80°/0.5 hPa, to obtain 1.78 g of the desired product in the form of a mixture of isomers.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28](O)=[O:29])=[N:9]1.CN(C=O)C.C(Cl)(=O)C([Cl:39])=O.O1CCOCC1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:25])=[O:26])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28]([Cl:39])=[O:29])=[N:9]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(=O)O)nn3-c3ccccc3Cl)s2)c1
Solvent: c1ccccc1
Solvent: CN(C)C=O
Solvent: C1COCCO1
Product: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(=O)Cl)nn3-c3ccccc3Cl)s2)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a suspension of 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1H-pyrazole-3-carboxylic acid (160 mg, 0.35 mmol) in PhH (1.0 mL) was added a small amount of DMF. Oxalyl chloride (60 μL, 0.69 mmol) was added to the suspension. After stirring for 15 minutes at ambient temperature, gas evolution had ceased and only part of the solids had dissolved. After 25 minutes dioxane (2.0 mL) was added. There was renewed gas evolution and most of the solids dissolved. After 30 minutes additional oxalyl chloride (50 μL, 0.57 mmol) was added. There was vigorous gas evolution and after a total of 90 minutes stirring the reaction mixture was concentrated under reduced pressure to afford 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1H-pyrazole-3-carbonyl chloride as a pale brown foam. This material was carried on to the subsequent acylation without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:15](=O)[O:14][C:12](=[O:13])[C:11]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:10]12.[CH2:21]([Zn]CC)C.O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:20]=[CH:19][CH:18]=[CH:17][C:11]=1[C:12]([O:14][CH2:15][CH3:21])=[O:13]
Reactant: COc1ccccc1-n1c(=O)oc(=O)c2ccccc21
Reactant: CC[Zn]CC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1ccccc1Nc1ccccc1OC
Temperature: 25 °C
Reaction time: 48 h

Procedure:
N-(2-Methoxyphenyl)isatoic anhydride (1 g, 0.00369 mole), 4 ml (0.00532 mole) of 1.33M diethylzinc in 4 ml of tetrahydrofuran, and 15 ml of tetrahydrofuran were combined at 0°-5° C. and then stirred at room temperature for two days. The reaction mixture was poured into water and extracted with ether. The ether extracts were washed with 20 ml of 1N potassium hydroxide, then dried over anhydrous magnesium sulfate and concentrated. The residue (1.12 g) was flash chromatographed on silica gel using 5% ethyl acetate/95% hexane as eluant to afford ethyl 2-(2-methoxyphenylamino)benzoate as a yellow viscous liquid, b.p. 284°-286° C. (760 mm).
Reaction SMILES: O.O.O.C([O-])(=O)C.[Pb+2:8].C([O-])(=O)C.[C:13]([OH:32])(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>C1(OC2C=CC=CC=2)C=CC=CC=1>[C:13]([O-:32])(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].[Pb+2:8].[C:13]([O-:32])(=[O:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: O
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]
Temperature: 150 °C

Procedure:
In one example, 0.76 g of lead acetate trihydrate and 2 ml of oleic acid were added to 10 ml of diphenyl ether solution and heated to about 150° C. for 30 min. under nitrogen condition to form lead oleate. After cooling to 60° C., the solution was mixed with 0.67 ml of 1M trioctylphosphine selenide solution in trioctylphosphine, resulting in a precursor stock solution for PbSe nanowires (“Solution A”). Reaction was carried out by injecting the stock solution containing the nanowire precursors lead oleate and trioctylphosphine selenide into another solution (“Solution B”) that was heated to about 250° C. Injecting Solution A into the pre-heated Solution B allows the precursor solution to be rapidly heated to a temperature necessary for nucleation to take place. In one embodiment, Solution B contains about 15 ml phenyl ether. Upon mixing Solution A with phenyl ether, nucleation was initiated and resulted in the formation of PbSe nanocrystals, and the temperature of the solution mixture also decreased to about 180° C.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1.[C:13]([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH3:13][O:9][C:8](=[O:10])[C:7]1[CH:11]=[CH:12][C:4]([CH2:3][CH2:2][Cl:1])=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccc(CCCl)cc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(CCCl)cc1
Reaction time: 18 h

Procedure:
A solution of 4-(2-Chloro-ethyl)-benzoic acid (20 g, 108 mmol) in DMF (200 mL) is treated with K2CO3 (59.7 g, 432 mmol) and Mel (16.8 mL, 270 mmol) and stirred at 23 C for 18 h. The reaction mixture is diluted with EtOAc (450 mL) and washed with H2O (2×150 mL), saturated aqueous NaHCO3 (1×200 mL), brine (1×200 mL), dried (MgSO4), and concentrated to afford the title compound as a yellow oil.
Reaction SMILES: [OH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:19]([CH:21]1[O:23][CH2:22]1)Cl>>[O:23]1[CH2:22][CH:21]1[CH2:19][O:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[O:4][N:3]=1
Reactant: Oc1cc(-c2ccccc2)on1
Reactant: ClCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: c1ccc(-c2cc(OCC3CO3)no2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 82 %

Procedure:
To a solution of 10.00 g of 3-hydroxy-5-phenylisoxazole dissolved in hexamethylphosphoroamide (50 ml) were added 10.28 g of anhydrous Potassium carbonate and 6.89 g of epichlorohydrin, and the mixture was stirred at room temperature for 24 hours. After insoluble materials in the reaction mixture were removed by filtration, the filtrate was diluted with ethyl acetate (200 ml) followed by washing with an aqueous 10% sodium chloride solution (200 ml ×2). After the organic layer was dried over anhydrous magnesium sulfate, the drying agent was filtered off and the filtrate was freed from the solvent by distillation under reduced Pressure. The residue was purified by column chromatography through silica gel (developing solvent: a 4:1 mixture of cyclohexane and ethyl acetate) to afford 11 00 g (82.0%) of the title compound with melting point 98° to 99° C. as colorless needles.
Reaction SMILES: I[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[NH2:8][C:5]1[N:4]=[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:2]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:7][N:6]=1
Reactant: OB(O)c1ccccc1
Reactant: Nc1ncc(I)c(-c2ccccc2)n1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: Nc1ncc(-c2ccccc2)c(-c2ccccc2)n1
Temperature: 25 °C
Yield: 50.5 %

Procedure:
To a stirred solution of 260 mg (0.88 mmol) 5-iodo-4-phenyl-pyrimidin-2-ylamine in 10 ml dioxane under argon at room temperature were added 112 mg (0.92 mmol) phenylboronic acid, 101 mg (0.09 mmol) tetrakis(triphenylphosphine)palladium(O) and 2.0 ml (4.0 mmol) 2M aqueous sodium carbonate solution. The reaction mixture was heated at reflux for 16 h, then cooled to room temperature, 1 g of kieselgel added, and the mixture concentrated in vacuo. Flash chromatography (1/1 ethyl acetate/hexane) followed by recrystallisation from ethyl acetate/pentane afforded 110 mg (51%) 2-amino-4,5-diphenylpyrimidine as a white crystalline solid. EI-MS m/e (%): 247 (M+, 90), 246 ([M—H]+, 100).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[OH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:14][C:13]1[O:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][C:9]=1[CH2:8][O:7][C:6]1[CH:21]=[CH:22][C:3]([CH2:2][O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:4][CH:5]=1
Reactant: CCOC(=O)Cc1ccccc1O
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1ccccc1OCc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Temperature: 90 °C
Reaction time: 2 h
Yield: 53.2 %

Procedure:
A mixture of 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.91 g), ethyl 2-(2-hydroxyphenyl)acetate (1.00 g), anhydrous potassium carbonate (0.76 g) and N,N-dimethylformamide (20 mL) was stirred at 90° C. for 2 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was subjected to silica gel column chromatography to give ethyl 2-[2-[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetate as an oil (1.35 g, 54%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v).