Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)[CH:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[OH:11].[C:31](O)(=[O:39])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37].C1(N=C=NC2CCCCC2)CCCCC1.N1(O)C2C=CC=CC=2N=N1>>[OH:11][CH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[CH:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:31]([CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:39])[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1
Reactant: Nc1ccccc1C(Nc1ccccn1)C(c1ccccn1)C(O)c1ccccc1
Reactant: O=C(O)CCCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: O=C(O)CCCCC(=O)Nc1ccccc1C(Nc1ccccn1)C(c1ccccn1)C(O)c1ccccc1

Procedure:
Prepared from 1.5 g of 3-(2-aminophenyl)-1-phenyl-2-pyridin-2-yl-3-(pyridin-2-ylamino)propan-1-ol, 3.4 g of hexanedioic acid, 1.04 g of dicyclohexylcarbodiimide and 640 mg of benzotriazol-1-ol, analogously to example II f) Product _of molecular weight 524.6 (C31H32N4O4); MS (ESI+): 525 (M+H+): (ESI−): 523 (M−H+)
Reaction SMILES: [C:1]([N:5]1[CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17](Br)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2].[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.C([O-])([O-])=O.[K+].[K+]>C(COC)OC.O.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>[C:1]([N:5]1[CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Br:23])=[C:10]3[C:19]4[CH:18]=[C:17]([C:30]5[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=5)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1cccnc1
Reactant: COc1cc2c(cc1Br)-c1c(Br)c3c(n1CC2)C(=O)N(C(C)(C)C)CCC3
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: [K+]
Solvent: COCCOC
Solvent: O
Product: COc1cc2c(cc1-c1cccnc1)-c1c(Br)c3c(n1CC2)C(=O)N(C(C)(C)C)CCC3
Temperature: 90 °C
Yield: 63.6 %

Procedure:
A mixture of 150 mg of 13c, 44 mg of pyridine-3-boronic acid, 80 mg of K2CO3 and 22 mg of Pd(PPh3)4 in 3 ml of degassed dimethoxyethane was heated at 90° C., for 16 hr. The reaction mixture was cooled and diluted with 20 ml of water and the product was extracted with ethyl acetate. The extract was washed once with 2N KOH and once with water, dried and concentrated. The crude material was chromatographed over silica gel, using a gradient of heptane/ethyl acetate as eluent. The product isolated was triturated with pentane, to provide 95 mg of 13d as white, crystalline material. Mp 184-186° C. Rf 0.25 (heptane/ethyl acetate 1/1). MS-ESI: [M+1] 494.11 and 496.11.
Reaction SMILES: [NH2:1]/[C:2](/[CH3:8])=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].[O:9]([C:16]([N:18]=[C:19]=[S:20])=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C=CC=CC=1>[NH:1]=[C:2]([CH3:8])[CH:3]([C:4]([O:6][CH3:7])=[O:5])[C:19]([NH:18][C:16]([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:17])=[S:20]
Reactant: COC(=O)/C=C(/C)N
Reactant: O=C(N=C=S)Oc1ccccc1
Solvent: Cc1ccccc1
Product: COC(=O)C(C(C)=N)C(=S)NC(=O)Oc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A warm solution of methyl 3-aminocrotonate (prepared according to the method of Conrad and Epstein, Chemische Berichte, 1887, 20, 3054, 10.4 g.) in toluene (20 ml.) was added with stirring to a solution of phenoxycarbonylisothiocyanate (16 g.) in toluene (50 ml.). The temperature of the mixture rose from 20° C. to 35° C. The mixture was then stirred for 11/2 hours at ambient temperature, filtered and the solid residue washed with light petroleum (b.p. 40°-60° C.) to give 3-imino-2-methoxycarbonyl-N-phenoxycarbonylthiobutyramide (8.6 g.) in the form of an orange solid, which was then dissolved in ethyl acetate (100 ml.). To this solution, a solution of bromine (1.67 ml.) in ethyl acetate (5 ml.) was added over 15 minutes at 2°-5° C. The mixture was stirred at ambient temperature for 11/2 hours and the solid product filtered off to give 4-methoxycarbonyl-3-methyl-5-phenoxycarbonylaminoisothiazole hydrobromide (9.6 g.) m.p. 170°- 173° C. A solution of methylamine in ethanol (30% w/v; 20 ml.) was added to 4-methoxycarbonyl-3-methyl-5-phenoxycarbonylaminoisothiazole hydrobromide (9.0 g.). The mixture was heated under reflux for 15 minutes, diluted with water (30 ml.), filtered and the solid residue dried at 100° C., to give 1-(4-methoxycarbonyl-3-methylisothiazol-5-yl)-3-methylurea (4.1 g.), m.p. 236°-237° C.
Reaction SMILES: [CH2:1]([N:8]1[CH2:15][CH:14]([CH3:16])[CH:13]2[CH:9]1[CH2:10][N:11](C(OCC)=O)[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>Cl>[CH2:1]([N:8]1[CH2:15][CH:14]([CH3:16])[CH:13]2[CH:9]1[CH2:10][NH:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)N1CC2C(C)CN(Cc3ccccc3)C2C1
Agent: Cl
Product: CC1CN(Cc2ccccc2)C2CNCC12

Procedure:
10 g (26.3 mmol) of ethyl 2-benzyl-4-methyl-2,7-diazabicyclo[3.3.0]octane-7-carboxylate are heated under reflux overnight with 100 ml of concentrated hydrochloric acid. The mixture is concentrated, the residue is taken up in 20 ml of water, the mixture is rendered alkaline with potassium carbonate and extracted five times using 50 ml of chloroform each time, the extracts are dried over potassium carbonate and concentrated, and the residue is distilled.
Reaction SMILES: [C:1]([O:9][CH:10]1[CH2:22][C:21]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][C:13]=2[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CN(C)C=O.[CH3:30][N:31]([CH2:33][CH2:34]Cl)[CH3:32]>C1C=CC=CC=1>[C:1]([O:9][CH:10]1[CH2:22][C:21]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([CH2:34][CH2:33][N:31]([CH3:32])[CH3:30])[C:13]=2[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OC1CCc2[nH]c3ccccc3c2C1)c1ccccc1
Reactant: CN(C)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: CN(C)CCn1c2c(c3ccccc31)CC(OC(=O)c1ccccc1)CC2

Procedure:
The 3-benzoyloxy-9-[2-(dimethylamino)ethyl]-1,2,3,4-tetrahydrocarbazole was prepared by following an alkylation procedure similar to that described in Example 11 and using 13.1 g. of 3-benzoyloxy-1,2,3,4-tetrahydrocarbazole and 1.93 g. of sodium hydride (50% in mineral oil) in 150 ml. of dimethylformamide, and 4.9 g. of (dimethylamino)ethyl chloride in 10 ml. of benzene. An ethereal solution of the crude product was filtered through alumina and the concentrated ethereal eluate was treated with ethereal hydrogen chloride to give after recrystallizaton from isopropyl alcohol - ether 5.6 g. of 3-benzoyloxy-9-[2-(dimethylaino)ethyl]-1,2,3,4-tetrahydrocarbazole hydrochloride, m.p. 222°-225°C.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[OH:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:12]=1[CH:13]=O.C(N(CC)CC)C>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]=[CH:13][C:12]2[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:11]=2[OH:10])=[C:4]([F:9])[CH:3]=1
Reactant: Cc1cccc(O)c1C=O
Reactant: Nc1ccc(Br)cc1F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: Cc1cccc(O)c1C=Nc1ccc(Br)cc1F
Temperature: 25 °C
Yield: 99.7 %

Procedure:
A solution of 4-bromo-2-fluoroaniline (19.6 g, 103.16 mmol), 2-hydroxy-6-methyl-benzaldehyde (14.03 g, 103.16 mmol) and p-toluenesulfonic acid (188 mg, 0.99 mmol) in toluene (300 mL) was heated to reflux in a Dean-Stark apparatus for 1 h and then allowed to cool to ambient temperature. After adding triethylamine (0.8 mL) the reaction mixture was concentrated to give the crude title compound (31.7 g, 99%) which was used without further purification. Data: 1H-NMR (400 MHz, CDCl3) δ 2.52 (s, 3H), 6.72 (d, J=7.6 Hz, 1H), 6.88 (d, J=8.6 Hz, 1H), 5.15 (t, J=7.8 Hz, 1H), 7.26-7.38 (m, 3H), 9.03 (s, 1H), 13.63 (s, 1H).
Reaction SMILES: C[O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12]Br)=[C:6]([Cl:14])[CH:5]=1.[C:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26](=[N:28][OH:29])[CH3:27])=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17]>>[C:16]([C:20]1[CH:25]=[CH:24][C:23](/[C:26](=[N:28]/[O:29][CH2:12][CH2:11][O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:15])=[CH:5][C:6]=2[Cl:14])/[CH3:27])=[CH:22][CH:21]=1)([CH3:19])([CH3:17])[CH3:18]
Reactant: CC(=NO)c1ccc(C(C)(C)C)cc1
Reactant: COC(=O)c1ccc(OCCBr)c(Cl)c1
Product: C/C(=N\OCCOc1ccc(C(=O)O)cc1Cl)c1ccc(C(C)(C)C)cc1

Procedure:
The title compound was prepared as white solid (0.334 g, 53%) from 4-(2-bromo-ethoxy)-3-chloro-benzoic acid methyl ester and 1-(4-tert-butyl-phenyl)-ethanone oxime using a procedure similar to that of step 1 of example 6. mp=167.1-168.8° C.; mass spectrum (+APCI, M+H) m/z 390. 1H NMR (400 MHz, DMSO-d6); δ 12.95 (bs, 1H), 7.89 (d, 1H), 7.84 (dd, 1H), 7.57 (d, 2H), 7.39 (d, 2H), 7.29 (d, 1H), 4.45 (m, 4H), 2.13 (s, 3H), 1.29 (s, 9H). Elemental analysis: Calcd. for C21H24ClNO4: C, 64.69; H, 6.20; N, 3.59, Found: C, 64.50; H, 6.28; N, 3.57.
Reaction SMILES: [CH2:1]([N:8]([CH2:11][CH2:12][CH2:13][CH:14]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[CH:17][C:16]2[CH:25]=[CH:26][CH:27]=[CH:28][C:15]1=2)CC)[C:2]1C=CC=CC=1>[Pd]>[CH2:1]([NH:8][CH2:11][CH2:12][CH2:13][CH:14]1[C:15]2[CH:28]=[CH:27][CH:26]=[CH:25][C:16]=2[CH:17]=[CH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]1=2)[CH3:2]
Reactant: CCN(CCCC1c2ccccc2C=Cc2ccccc21)Cc1ccccc1
Agent: [Pd]
Product: CCNCCCC1c2ccccc2C=Cc2ccccc21

Procedure:
5-[3-(N-Benzyl-N-ethylamino)-propyl]-5H-dibenzo[a,d]cycloheptene is dissolved in absolute alcohol and hydrogenated over palladium on alumina catalyst at 40°-60° C. The catalyst is separated and the product isolated by evaporating the solvent.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[CH2:6][N:7]1[C:12]([CH3:13])=[CH:11][C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2[F:23])=[C:9]([Br:24])[C:8]1=[O:25].N1C=CC=CC=1.Cl[C:36]([O:38][C:39]1[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=1)=[O:37]>ClCCl>[Br:24][C:9]1[C:8](=[O:25])[N:7]([CH2:6][C:5]2[CH:4]=[C:3]([CH:28]=[CH:27][CH:26]=2)[CH2:2][NH:1][C:36](=[O:37])[O:38][C:39]2[CH:40]=[CH:41][C:42]([N+:45]([O-:47])=[O:46])=[CH:43][CH:44]=2)[C:12]([CH3:13])=[CH:11][C:10]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23]
Reactant: Cc1cc(OCc2ccc(F)cc2F)c(Br)c(=O)n1Cc1cccc(CN)c1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1cc(OCc2ccc(F)cc2F)c(Br)c(=O)n1Cc1cccc(CNC(=O)Oc2ccc([N+](=O)[O-])cc2)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 66 %

Procedure:
1-[3-(aminomethyl)benzyl]-3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (EXAMPLE 161) (2.00 g, 4.45 mmol) was suspended in dichloromethane (15 mL). Pyridine was added (0.43 mL, 5.34 mmol). After stirring for 10 minutes at room temperature, a stock solution of 4-nitrophenyl chloroformate (10.0 mL, 0.50 M) in dichloromethane was added dropwise. After stirring for 4.5 hours at room temperature, a stock solution of 4-nitrophenyl chloroformate (2.5 mL, 0.50 M) in dichloromethane was again added dropwise and stirring continued at 40° C. overnight. The reaction mixture was concentrated and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) to afford a yellow solid (1.11 g, 66%). 1H NMR (400 MHz, DMSO d6) δ 8.56 (app t, J=6.10 Hz, 1H), 8.24-8.21 (m, 2H), 7.62 (app q, J=7.88 Hz, 1H), 7.40-7.27 (m, 7H), 6.98 (d, J=7.52 Hz, 1H), 6.54 (s, 1H), 5.30 (s, 2H), 5.24 (s, 2H), 4.25 (d, J=6.18 Hz, 2H), 2.30 (s, 3H). ES-HRMS m/z 614.0753 (M+H C28H22BrF2N3O6 requires 614.0733).
Reaction SMILES: C([O:4][CH2:5][CH2:6][N:7]([CH2:16][CH2:17][O:18]C(=O)C)[C:8]1[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=1)(=O)C.[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([CH2:31]C(O)=O)=[CH:27][CH:26]=1)([O-:24])=[O:23].N1CCCCC1>CN(C)C=O>[OH:18][CH2:17][CH2:16][N:7]([CH2:6][CH2:5][OH:4])[C:8]1[CH:9]=[CH:10][C:11]([CH:12]=[CH:31][C:28]2[CH:29]=[CH:30][C:25]([N+:22]([O-:24])=[O:23])=[CH:26][CH:27]=2)=[CH:14][CH:15]=1
Reactant: CC(=O)OCCN(CCOC(C)=O)c1ccc(C=O)cc1
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Solvent: CN(C)C=O
Solvent: C1CCNCC1
Product: O=[N+]([O-])c1ccc(C=Cc2ccc(N(CCO)CCO)cc2)cc1
Temperature: 0 °C

Procedure:
A mixture of the crude reaction product of the previous step, viz. 4-di(2-acetyloxyethyl)aminobenzaldehyde, 270 g of 4-nitrophenyl acetic acid, 2 l of dimethyl formamide, and 100 ml of piperdine was stirred for 4 days at 20°-25° C. Next, the reaction mixture was concentrated by evaporation at 70° C. to a thick red oil, which was titrated three times, each time with 1 l of n-hexane. The residue was dissolved in 2.5 l of dimethyl formamide. Then there was added a solution of 320 g of sodium hydroxide in 800 ml of water. The resulting reaction mixture was then heated for 16 hours to 100° C. and subsequently poured into 10 l of ice water. The precipitated product was filtered off and thoroughly after-washed three times, each time with 1 l of water. After drying the crude reaction product was crystallized from 250 ml of dimethyl formamide and 500 ml of dichloromethane. The resulting yield of 4-di(2-hydroxy-ethyl) amino-4'-nitrostilbene was 190 g with a melting point of 184°-185° C. Calculated on N,N-di(2-hydroxyethyl)aniline this is 58% of theory.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][CH:11]=[C:12]=[CH:13][CH2:14][CH2:15]Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[I-:17].[Na+].CC(C)=O>O>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH:12]=[C:13]=[CH:14][CH2:15][I:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCCC=C=CCCCl
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCCC=C=CCI

Procedure:
A mixture of 0.80 g of 7-chlorohepta-3,4-dien-1-ol t-butyldimethylsilyl ether, 1.0 g of sodium iodide and 5 ml of acetone were refluxed for 24 hours. The reaction mixture was cooled and diluted with 50 ml water. The product was extracted with 100 ml of ether and the ethereal solution washed with brine, dried over potassium carbonate and evaporated to give 7-iodohepta-4,5-dien-1-ol t-butyldimethylsilyl ether.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[C:11]1([S:17]([O-:19])=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Na+].O>CS(C)=O>[C:11]1([S:17]([C:8]2[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([Br:1])[CH:9]=2)(=[O:19])=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=Cc1ccc(F)cc1Br
Reactant: O=S([O-])c1ccccc1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=Cc1ccc(S(=O)(=O)c2ccccc2)cc1Br
Temperature: 125 °C
Yield: 32.4 %

Procedure:
A mixture of 2-bromo-4-fluorobenzaldehyde (10.2 g, 50 mmol) and sodium benzenesulfinate (8.21 g, 50 mmol) in DMSO (100 mL) was heated at 125° C. overnight. Upon cooling the mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified via flash chromatography (hexane/EtOAc, 4/1) to give 4-benzenesulfonyl-2-bromo-benzaldehyde (5.26 g, 32% yield) as white crystalline solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8].[OH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)=[CH:14][CH:13]=1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[C:24]([C:21]1[CH:20]=[CH:19][C:18]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH:6]([CH2:5][CH2:4][CH2:3][CH3:2])[C:7]([O:9][CH3:10])=[O:8])=[CH:13][CH:14]=2)=[CH:23][CH:22]=1)#[N:25]
Reactant: COC(=O)CCCCCBr
Reactant: N#Cc1ccc(-c2ccc(O)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCC(Oc1ccc(-c2ccc(C#N)cc2)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 84.7 %

Procedure:
8.80 g (42 mmole) of methyl 6-bromohexanoate, 8.20 g (42 mmole) of 4-hydroxy-4'-cyanobiphenyl, 20 ml dimethyl formamide and 5.8 g (42 mmole) potassium carbonate were placed in a 100 ml flask equipped with a calcium chloride drying tube, and stirred at room temperature for 24 hours, after which time the mixture was poured into water and the suspended solids filtered out and washed with water. The resultant product was dried in a vacuum desiccator for 48 hours to yield 11.50 g (85%) of the ester which was recrystallized from aqueous ethanol to yield a product with a melting point of 80° C.-81° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]([CH3:21])[CH3:20])[CH:14]=2)=[O:11])[CH:5]=[CH:6][CH:7]=1.Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([C:29]2[NH:30][CH2:31][CH2:32][N:33]=2)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[NH:30]1[CH2:31][CH2:32][N:33]=[C:29]1[C:25]1[CH:24]=[C:23]([O:1][C:2]2[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]([CH3:21])[CH3:20])[CH:14]=3)=[O:11])[CH:5]=[CH:6][CH:7]=2)[CH:28]=[CH:27][N:26]=1
Reactant: CC(C)c1cccc(NC(=O)/C=C/c2cccc(O)c2)c1
Reactant: Clc1ccnc(C2=NCCN2)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)c1cccc(NC(=O)/C=C/c2cccc(Oc3ccnc(C4=NCCN4)c3)c2)c1
Temperature: 100 °C

Procedure:
To a solution of (E)-3-(3-hydroxyphenyl)-N-(3-isopropylphenyl)acrylamide (3.20 mmol) in DMF (40 mL) was added 4-chloro-2-(4,5-dihydro-1H-imidazol-2-yl)pyridine (11.2 mmol) and cesium carbonate (16.0 mmol). The heterogeneous mixture was heated at 100° C. for 18 h and then cooled to rt. The mixture was diluted with water and extracted with EtOAc. The combined organic solutions were washed with water and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (90:10:1 DCM:MeOH:NH4OH) to give B-2. 1H NMR (300 MHz, d6-DMSO): δ 10.13 (s, 1H), 8.52 (d, J=5.6 Hz, 1H), 7.56-7.61 (m, 3H), 7.50-7.54 (m, 2H), 7.44-7.47 (m, 1H), 7.41 (d, J=2.8 Hz, 1H), 7.20-7.29 (m, 2H), 7.17 (dd, J=6.8, 2.8 Hz, 1H), 6.93-6.99 (m, 2H), 6.85 (d, J=15.6 Hz, 1H), 3.32 (s, 4H), 2.85 (sept, J=6.8 Hz, 1H), and 1.18 (d, J=7.2 Hz, 6H).
Reaction SMILES: B(F)(F)F.[CH:5]1([C:8]([OH:10])=O)[CH2:7][CH2:6]1.[CH3:11][C:12]([CH3:14])=[O:13]>CCOCC>[CH:5]1([C:8](=[O:10])[CH2:11][C:12](=[O:13])[CH3:14])[CH2:7][CH2:6]1
Reactant: CC(C)=O
Reactant: O=C(O)C1CC1
Agent: FB(F)F
Solvent: CCOCC
Product: CC(=O)CC(=O)C1CC1

Procedure:
Boron trifluoride gas is introduced for one hour at 40° C. into a mixture of 191 g of cyclopropanecarboxylic acid and 45 g of acetone. There is formed a black oily product, which is diluted with 800 ml of ether. The ether phase is then washed 4 times with 300 ml of water each time, and, with ice cooling, 30% sodium hydroxide solution is finally added until the pH value is ~9. The ether layer is separated, and the aqueous phase is extracted three times with 300 ml of ether each time. The ether phases are collected, dried over sodium sulfate, purified with active charcoal, filtered, and concentrated by evaporation. The oil which remains is purified by chromatography through a silica gel column with ether/hexane (1:3) as the eluant. The yield after removal of the solvent by evaporation is 22 g of the title compound as light-coloured oil; refractive index nD24 : 1.488.
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(N(CC)CC)C.Br[CH2:13][C:14]1[CH:15]=[C:16]([C:20](=[O:22])[CH3:21])[CH:17]=[CH:18][CH:19]=1>CO>[CH:1]1([NH:4][CH2:13][C:14]2[CH:15]=[C:16]([C:20](=[O:22])[CH3:21])[CH:17]=[CH:18][CH:19]=2)[CH2:3][CH2:2]1
Reactant: CC(=O)c1cccc(CBr)c1
Reactant: NC1CC1
Solvent: CCN(CC)CC
Solvent: CO
Product: CC(=O)c1cccc(CNC2CC2)c1
Yield: 34.9 %

Procedure:
Cyclopropylamine (5.71 g; 10.0 mmol) and triethylamine (1.01 g; 10.0 mmol) were dissolved in methanol (50 ml). While the mixture was stirred in an ice bath, 3′-bromomethylacetophenone (2.13 g; 10.0 mmol) in methanol (10 ml) was added dropwise. The mixture was removed from the ice bath, and stirred for 18 hours at room temperature. The solvent was evaporated under reduced pressure, and the residue was taken up in 2N hydrochloric acid (100 ml), followed by extraction with diethyl ether (100 ml). The aqueous layer was alkalinized with aqueous sodium hydroxide solution, and the mixture was extracted with chloroform (100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→0:1), to thereby yield 0.66 g of the target compound as yellow oily matter (yield: 34.9%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([P:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].OO.[O-:26]S([O-])=O.[Na+].[Na+].Cl>CO.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([P:11](=[O:26])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(P(c2ccccc2)c2ccccc2)cc1OC
Reactant: O=S([O-])[O-]
Agent: Cl
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc(P(=O)(c2ccccc2)c2ccccc2)cc1OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
da) 75 g of 3,4-dimethoxyphenyl-diphenylphosphine were taken up in 300 ml of methanol. 29.3 ml of 35% H2O2 solution were added dropwise to the suspension while cooling with an ice bath. The clear yellow solution was stirred at room temperature overnight, then treated with 100 ml of sat. Na2SO3 solution and 30 ml of 1N HCl and stirred for a further 1 hour. The resulting suspension was treated with 150 ml of water and the solution was evaporated on a rotary evaporator in order to remove the majority of the methanol. The precipitated yellow crystals were filtered off under suction, taken up in CH2Cl2, the solution was dried over MgSO4, filtered and evaporated. The residue was dissolved in 450 ml of hot ethyl acetate and the solution was treated with 450 ml of hexane. After standing overnight the crystallizate was filtered off under suction, washed with a small amount of hexane and dried at 0.1 mbar. There were obtained 54 g of (3,4-dimethoxyphenyl)diphenylphosphine oxide as a light beige powder. M.p. 154.5°-156° C.