Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:20][C:19](=[O:21])[N:18]([NH:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]4[CH:34]=[CH:33][N:32]=[C:31]([CH3:35])[CH:30]=4)[CH2:25][CH2:24]3)[CH:17]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH2:16]1)(=[O:14])=[O:13])[CH:6]=[CH:5]2.[OH-].[Na+].[CH2:43]=O>C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([N:15]1[CH2:20][C:19](=[O:21])[N:18]([N:22]([CH3:43])[CH:23]3[CH2:24][CH2:25][N:26]([C:29]4[CH:34]=[CH:33][N:32]=[C:31]([CH3:35])[CH:30]=4)[CH2:27][CH2:28]3)[CH:17]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH2:16]1)(=[O:13])=[O:14])[CH:6]=[CH:5]2
Reactant: COC(=O)CC1CN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)CC(=O)N1NC1CCN(c2ccnc(C)c2)CC1
Reactant: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=CO
Product: COC(=O)CC1CN(S(=O)(=O)c2ccc3cc(Cl)ccc3c2)CC(=O)N1N(C)C1CCN(c2ccnc(C)c2)CC1

Procedure:
Methyl 4-[(6-chloro-2-naphthyl)sulfonyl]-1-[[1-(2-methyl-4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazineacetate (0.30 g) obtained in Example 138 was dissolved in a 37% aqueous solution of formaldehyde (6.5 ml) and formic acid (3.0 ml) and refluxed for 15 hours. The reaction mixture was cooled, made alkaline by adding a 1N aqueous solution of sodium hydroxide, extracted with dichloromethane, dried and concentrated. The residue thus obtained was crystallized from ethanol to obtain the title compound (95 mg) as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:3]=1[C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19](O)=[O:20])[CH:13]=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5].[CH3:30][O:31][CH2:32][CH2:33][NH2:34].CCN=C=NCCCN(C)C.C(N(CC)C(C)C)(C)C>ClCCl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:3]=1[C:4]([C:6]1[O:7][C:8]2[CH:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19]([NH:34][CH2:33][CH2:32][O:31][CH3:30])=[O:20])[CH:13]=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5]
Reactant: Cc1c(C(=O)c2ccc(Cl)cc2Cl)oc2cc(-c3cccc(C(=O)O)c3)ccc12
Reactant: COCCN
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCCNC(=O)c1cccc(-c2ccc3c(C)c(C(=O)c4ccc(Cl)cc4Cl)oc3c2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 25.3 %

Procedure:
To a solution of 3-[2-(2,4dichloro-benzoyl)-3methyl-benzofuran-6-yl]-benzoic acid (40 mg, 0.09 mmol) in dichloromethane (2 mL) was added 2-methoxyethylamine (0.02 mL, 0.19 mmol), EDCI (20 mg, 0.1 mmol), DMAP (1 mg, 0.01 mmol), and N,N-diisopropylethylamine (0.02 mL, 0.1 mmol). The reaction mixture was stirred at rt overnight, then concentrated in vacuo and purified by prep-HPLC to afford the desired product (11 mg, 25%). 1H-NMR (CDCl3) δ 8.05 (t, J=1.8 Hz, 1H), 7.77-7.75 (m, 3H), 7.69 (m, 1H), 7.60 (dd, J=8.3, 1.0 Hz, 1H), 7.51 (m, 2H), 7.47 (m, 1H), 7.40 (ddd, J=8.2, 1.9, 0.5 Hz, 1H), 6.62 (t, J=4.5 Hz, 1H), 3.70 (m, 2H), 3.60 (m, 2H), 3.40 (s, 3H), 2.62 (s, 3H).
Reaction SMILES: [Cl:1][C:2]([S:7][CH:8]([CH3:10])[CH3:9])=[C:3]([Cl:6])[C:4]#[N:5].ClC1C=CC=C(C(OO)=[O:19])C=1>C(Cl)Cl>[Cl:1][C:2]([S:7]([CH:8]([CH3:10])[CH3:9])=[O:19])=[C:3]([Cl:6])[C:4]#[N:5]
Reactant: CC(C)SC(Cl)=C(Cl)C#N
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC(C)S(=O)C(Cl)=C(Cl)C#N
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Four grams of isopropyl 1,2-dichloro-2-cyanovinyl sulfide, prepared in Example 1, was dissolved in 50 milliliters methylene dichloride and the solution was cooled to 0° C. Four grams of solid 85% m-chloroperbenzoic acid was added in portions over one half hour. The reaction mixture was stirred for two hours while the temperature was maintained at 0° C. The reaction mixture was then filtered and washed with 5% potassium carbonate solution. The organic layer was dried over anhydrous magnesium sulfate and stripped of volatiles. A yield of 3 grams of isopropyl 1,2-dichloro-2-cyanovinyl sulfoxide having a refractive index--nD30 =1.5112 was obtained. The structure of the product was confirmed by IR and NMR.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:12](=[O:19])[C:13]3[S:17][CH:16]=[C:15]([Cl:18])[CH:14]=3)[C:7](=[O:11])[NH:8]2)=[N:4][CH:3]=1.[C:20](=[O:26])=[N:21]S(Cl)(=O)=O>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:12](=[O:19])[C:13]3[S:17][CH:16]=[C:15]([Cl:18])[CH:14]=3)[C:7](=[O:11])[N:8]2[C:20]([NH2:21])=[O:26])=[N:4][CH:3]=1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: O=C1Nc2cc(Cl)cnc2C1C(=O)c1cc(Cl)cs1
Solvent: CC#N
Product: NC(=O)N1C(=O)C(C(=O)c2cc(Cl)cs2)c2ncc(Cl)cc21

Procedure:
The title compound was prepared from 6-chloro-3-(4-chloro-2-thenoyl)-4-azaoxindole according to the procedure of Example 2C using 6-chloro-3-(4-chloro-2-thenoyl)-4-azaoxindole (850 mg, 2.7 mmol), N-chlorosulfonyl isocyanate (0.35 mL, 4.0 mmol) and acetonitrile (30 mL). The crude product was recrystallized from acetic acid. Yield: 280 mg (29%).
Reaction SMILES: [CH3:1][C:2](OC(OC(OC(C)(C)C)=O)=O)(C)C.[CH2:16]([C@H:23]1[CH2:27][O:26][C:25](=[O:28])[N:24]1[C:29](=[O:50])[CH2:30][C@@H:31]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:38][CH:37]=1)[CH2:32][N+:33]([O-])=[O:34])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C1C=CN=CC=1)C.C(Br)=C>[CH2:16]([C@H:23]1[CH2:27][O:26][C:25](=[O:28])[N:24]1[C:29](=[O:50])[CH2:30][C@@H:31]([C:36]1[CH:37]=[CH:38][C:39]([O:42][CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[CH:40][CH:41]=1)[C:32]1[CH:2]=[CH:1][O:34][N:33]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(C[C@H](C[N+](=O)[O-])c1ccc(OCc2ccccc2)cc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: C=CBr
Agent: CN(C)c1ccncc1
Product: O=C(C[C@@H](c1ccc(OCc2ccccc2)cc1)c1ccon1)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 60 h
Yield: 93.3 %

Procedure:
(Boc)2O (6.9 g, 31.65 mmol) was added at room temperature to a solution of 6.3 (10 g, 21.1 mmol), vinyl bromide (230 mL, 1.0 M solution in THF), DMAP (256 mg, 2.1 mmol), and TEA (3.5 mL, 25.3 mmol). The mixture was stirred at room temperature for 2.5 days. During the reaction, more (Boc)2O (2×2 g) was added. After HPLC indicated that all 6.3 was consumed, the reaction mixture was placed in EtOAc (500 mL), and saturated NaHCO3 (400 mL) was added. The organic layer was separated, washed with brine, dried, and concentrated under vacuum. The crude product was placed in hot MeOH (70 mL). The mixture was stirred vigorously at 75° C. for 5 hours. The mixture was then cooled to room temperature and allowed to stand for 3 hours. The solid product was collected by filtration and washed with MeOH to give 6.4 (9.5 g). MS ESI (pos.) m/e: 483 (M+H). 1H NMR (CDCl3) δ 8.30(d, 1H), 7.30 (m, 12H), 6.95 (d, 2H), 6.15 (d, 1H), 5.05 (s, 2H), 4.76 (dd, 1H), 4.64 (m, 1H), 4.15 (d, 2H), 4.05 (dd, 1H), 3.56 (dd, 1H), 3.23 (dd, 1H), 2.78 (dd, 1H).
Reaction SMILES: [H-].[Na+].C(S)C.[NH2:6][C:7]1[C:29]([Cl:30])=[CH:28][C:10]([C:11]([NH:13][CH2:14][CH:15]2[O:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:16]2)=[O:12])=[C:9]([O:31]C)[CH:8]=1>CN(C)C=O>[NH2:6][C:7]1[C:29]([Cl:30])=[CH:28][C:10]([C:11]([NH:13][CH2:14][CH:15]2[O:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:16]2)=[O:12])=[C:9]([OH:31])[CH:8]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)NCC1CN(Cc2ccccc2)CCO1
Agent: [H-]
Agent: [Na+]
Solvent: CCS
Solvent: CN(C)C=O
Product: Nc1cc(O)c(C(=O)NCC2CN(Cc3ccccc3)CCO2)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 70.2 %

Procedure:
To a stirred suspension of 60% sodium hydride (0.52 g) in dimethylformamide (20 ml) is added under ice-coolinga solution of ethanethiol (0.81 g) in dimethylformamide (5 ml). After the mixture is stirred at 25° C. for 0.5 hour, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-methoxybenzamide (3.4 g) is added, and the mixture is stirred at 100° C. for 1 hour. After cooling, the reaction mixture is evaporated under reduced pressure. The residue is diluted with water, washed with chloroform, and neutralized with 10% hydrochloric acid. The precipiate is collected, washed with water, and recrystallized from isopropyl alcohol to give the monohydrate of the title compound (2.3 g), mp 153°-155° C.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[N:3]=1.[N:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[C:29]([CH:30]=O)[C:24]=2[NH:23][CH:22]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[N:21]1[C:25]2[CH:26]=[CH:27][CH:28]=[C:29]([CH2:30][N:18]3[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][O:12][C:8]4[CH:7]=[CH:6][CH:5]=[C:4]5[C:9]=4[CH:10]=[CH:11][C:2]([CH3:1])=[N:3]5)[CH2:16][CH2:17]3)[C:24]=2[NH:23][CH:22]=1
Reactant: Cc1ccc2c(OCCN3CCNCC3)cccc2n1
Reactant: O=Cc1cccc2nc[nH]c12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: Cc1ccc2c(OCCN3CCN(Cc4cccc5nc[nH]c45)CC3)cccc2n1
Temperature: 20 °C
Reaction time: 24 h
Yield: 21.6 %

Procedure:
A mixture of 2-methyl-5-(2-piperazin-1-ylethoxy)quinoline (0.04 g, 0.15 mmol) and 3H-benzimidazole-4-carboxaldehyde (0.024 g, 0.15 mmol) in 1,2-dichloroethane (5 mL) was treated with sodium triacetoxyborohydride (47 mg, 0.22 mmol) and stirred at 20° C. under an atmosphere of argon for 24 h. The mixture was then treated with saturated aqueous NaHCO3 (20 mL) and the organic layer separated and purified directly by chromatography on silica (ethyl acetate to 10% methanol/ethyl acetate), to afford the title compound (0.013 g, 22%) as a solid.
Reaction SMILES: [N+:1]([C:4]1[C:5]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[N:6][CH:7]=[CH:8][CH:9]=1)([O-])=O.C1CCCCC=1>CO.[OH-].[OH-].[Pd+2]>[NH2:1][C:4]1[C:5]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[N:6][CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)(C)OC(=O)C1CNCCN1c1ncccc1[N+](=O)[O-]
Agent: [Pd+2]
Agent: [OH-]
Solvent: C1=CCCCC1
Solvent: CO
Product: CC(C)(C)OC(=O)C1CNCCN1c1ncccc1N
Temperature: 70 °C
Yield: 86.9 %

Procedure:
3-Nitro-2-(Boc-piperazine)pyridine 6 (1.765 g, 5.72 mmol) was dissolved in methanol (15 mL) at room temperature. Then Pd(OH)2 (1.234 g) and cyclohexene (2.0 mL, 19.52 mmol) were added. The resulting mixture was heated at 70° C. for 2 h. The mixture was concentrated to remove the solvent. DCM was added and then it was filtered through a pad of silica gel, washed with DCM and 10% MeOH/DCM. The collected solution was concentrated and dried under high vacuum to afford a slight pink solid as the product (1.384 g, 87% yield). 1H-NMR (CDCl3): 7.794 (dd, J=5.0 Hz and 1.5 Hz, 1 H, Ar—H), 6.956 (dd, J=7.5 Hz and 1.5 Hz, 1 H, Ar—H), 6.854 (dd, J=7.5 Hz and 5.0 Hz, 1 H, Ar—H), 3.783 (br, 2 H, NH2), 3.571 (t, J=4.5-5.0 Hz, 4 H, 2 CH2), 3.059 (t, J=4.5-5.0 Hz, 4 H, 2 CH2), 1.482 (s, 9 H, 3 CH3). LC-MS: 279.2 (MH+). (ref. Romero D. L. et al. J. Med. Chem. 37, 999-1014, 1994.)
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:24]=[CH:23][CH:22]=[C:21]([C:25]2[O:29][CH:28]=[N:27][C:26]=2[C:30](O)=[O:31])[CH:20]=1>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:30]([C:26]3[N:27]=[CH:28][O:29][C:25]=3[C:21]3[CH:20]=[C:19]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH:24]=[CH:23][CH:22]=3)=[O:31])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: O=C(O)c1ncoc1-c1cccc(-c2ccccc2)c1
Reactant: CC1(c2ccc(Cn3cc(N)cn3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2cc(NC(=O)c3ncoc3-c3cccc(-c4ccccc4)c3)cn2)o1

Procedure:
Following general procedure B followed by T, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-4-ylamine and 5-biphenyl-3-yl-oxazole-4-carboxylic acid. LC-MS-conditions 01b: tR=1.04 min; [M+H]+=453.15.
Reaction SMILES: C1O[C:4]2([CH2:9][CH2:8][C:7]([C:15]#N)([C:10]3[S:11][CH:12]=[CH:13][CH:14]=3)[CH2:6][CH2:5]2)[O:3]C1.[OH-:18].[Na+].C(O)C[OH:22].CCOCC>O>[C:15]([C:7]1([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][C:4](=[O:3])[CH2:9][CH2:8]1)([OH:22])=[O:18]
Reactant: N#CC1(c2cccs2)CCC2(CC1)OCCO2
Reactant: OCCO
Reactant: [OH-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Product: O=C1CCC(C(=O)O)(c2cccs2)CC1
Yield: 72 %

Procedure:
A mixture of 4.98 g. (0.02 mole) of 4-cyano-4-(2-thienyl)cyclohexanone ethylene ketal and 0.70 g. (0.02 mole) of sodium hydroxide in 40 ml. ethylene glycol is heated overnight at reflux. The mixture is allowed to cool and diluted with water. The solution is then cooled in ice, covered with ether and cautiously acidified. The organic layer is separated and the aqueous layer is washed twice more with ether. The extracts are combined, washed once with brine and taken to dryness. The residual solid is recrystallized from methylene chloride:Skellysolve B to afford 4.64 g. (72% yield) of 4-carboxy-4-(2-thienyl)cyclohexanone, ethylene ketal, m.p. 125°-127° C.
Reaction SMILES: O[CH2:2][C:3]([C:5]1[CH:6]=[C:7]([OH:12])[C:8](=[CH:10][CH:11]=1)[OH:9])=O.[CH3:13][O:14]C(C)(C)C>>[CH:11]1[C:5]([CH2:3][CH2:2][CH2:13][OH:14])=[CH:6][C:7]([OH:12])=[C:8]([OH:9])[CH:10]=1
Reactant: COC(C)(C)C
Reactant: O=C(CO)c1ccc(O)c(O)c1
Product: OCCCc1ccc(O)c(O)c1
Temperature: 40 °C

Procedure:
A special house made pressure reactor, a 50 ml 10 bar glass reactor with steel mantle and a magnetic stirring bar, was charged with catalyst, 4-hydroxyacetyl-catechol (produced according to Example 2) and t-butyl methyl ether. The reactor was evacuated and filled with hydrogen. Hydrogenation was started by stirring at 5 bar hydrogen pressure while heating to 40° C. By the end of the reaction the hydrogen was replaced by air, the slurry was filtered, the catalyst was washed with ethyl acetate. After evaporation of the solvents and drying at 1 mbar the product was analyzed quantitatively. The details of some reactions and the results are shown in Table 1.
Reaction SMILES: [C:1]([OH:7])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH:8](/[C@H:11]1[CH2:16][CH2:15][C@H:14]([C@H:17]2[CH2:22][CH2:21][C@H:20](/[CH:23]=[CH:24]/[CH2:25]O)[CH2:19][CH2:18]2)[CH2:13][CH2:12]1)=[CH:9]\[CH3:10]>CN(C)C1C=CN=CC=1.ClCCl>[C:1]([O:7][CH2:25]/[CH:24]=[CH:23]/[C@H:20]1[CH2:21][CH2:22][C@H:17]([C@H:14]2[CH2:13][CH2:12][C@H:11](/[CH:8]=[CH:9]/[CH3:10])[CH2:16][CH2:15]2)[CH2:18][CH2:19]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)C(=O)O
Reactant: C/C=C/[C@H]1CC[C@H]([C@H]2CC[C@H](/C=C/CO)CC2)CC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: C/C=C/[C@H]1CC[C@H]([C@H]2CC[C@H](/C=C/COC(=O)C(C)(C)C)CC2)CC1

Procedure:
0.4 g of pivalic acid, 1.0 g of 3E-[trans-4-(trans-4-[1E-propenyl]cyclohexyl)cyclohexyl]allyl alcohol and 0.1 g of 4-(dimethylamino)pyridine were dissolved in 50 ml of dichloromethane and the solution was treated portionwise within 10 minutes while stirring with 0.9 g of N,N'-dicyclohexylcarodiimide. The mixture was stirred at room temperature overnight and then filtered. The filtrate was diluted with dichloromethane, washed twice with 50 ml of saturated sodium carbonate solution each time and then with water, dried over magnesium sulphate, filtered and then concentrated. Chromatography of the residue on silica gel with toluene gave 1.3 g of 3E-[trans-4-(trans-4-[1E-propenyl]cyclohexyl)cyclohexyl]-allyl pivalate.
Reaction SMILES: CS(C)=[O:3].[CH3:5][C:6]1[C@@H:22]([O:23][C:24]([C@H:26]([OH:43])[C@@H:27]([NH:34][C:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:36])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:21][C@:17]2([OH:44])[C:18]([CH3:20])([CH3:19])[C:7]=1[C@@H:8]([O:62][C:63]([CH3:65])=[O:64])[CH2:9][C@@:10]1([CH3:61])[C@H:15]([C@@H:16]2[O:45][C:46]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:47])[C@:14]2([O:56][C:57]([CH3:59])=[O:58])[CH2:54][O:55][C@@H:13]2[CH2:12][C@@H:11]1[OH:60]>O1CCCC1>[CH3:5][C:6]1[C@@H:22]([O:23][C:24]([C@H:26]([OH:43])[C@@H:27]([NH:34][C:35]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:36])[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25])[CH2:21][C@:17]2([OH:44])[C:18]([CH3:19])([CH3:20])[C:7]=1[C@@H:8]([O:62][C:63]([CH3:65])=[O:64])[C:9]([C@@:10]1([CH3:61])[C@H:15]([C@@H:16]2[O:45][C:46]([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:47])[C@:14]2([O:56][C:57]([CH3:59])=[O:58])[CH2:54][O:55][C@@H:13]2[CH2:12][C@@H:11]1[OH:60])=[O:3]
Reactant: CC(=O)O[C@H]1C[C@]2(C)[C@@H](O)C[C@H]3OC[C@@]3(OC(C)=O)[C@H]2[C@H](OC(=O)c2ccccc2)[C@]2(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c3ccccc3)c3ccccc3)C(C)=C1C2(C)C
Reactant: CS(C)=O
Solvent: C1CCOC1
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reaction time: 0.07 h

Procedure:
A coated stent from Example 9 is dipped into a DESMODUR solution (50:50 mixture of dimethylsulfoxide and tetrahydrofuran). The device is then removed and the coating is then partially dried at room temperature for 3 to 5 minutes. The device is then immersed in a beaker of water (room temperature) for 3-5 minutes to cause the polymerization reaction to occur rapidly. An echogenic coating is formed. In addition to 9-deoxotaxol, the following are exemplary compounds that may be used to coat the device: 7-deoxy-9-deoxotaxol and 10-desacetoxy-7-deoxy-9-deoxotaxol.
Reaction SMILES: C(OC(=O)[CH2:5][NH:6][CH2:7][CH2:8][N:9]([C:22]([O:24]C(C)(C)C)=O)[CH2:10][CH2:11][C:12]1[CH:21]=[CH:20][C:15]2[C:16](=[O:19])[O:17][CH2:18][C:14]=2[CH:13]=1)C.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C>>[O:19]=[C:16]1[C:15]2[CH:20]=[CH:21][C:12]([CH2:11][CH2:10][N:9]3[CH2:8][CH2:7][NH:6][CH2:5][C:22]3=[O:24])=[CH:13][C:14]=2[CH2:18][O:17]1
Reactant: CCOC(=O)CNCCN(CCc1ccc2c(c1)COC2=O)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: O=C1OCc2cc(CCN3CCNCC3=O)ccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a flask charged with Ethyl[(2-{(tert-butoxycarbonyl)[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]amino}ethyl)amino]acetate (280 mg, 0.69 mmol) and a stir bar was added TFA (2 mL). The mixture was allowed to stir at RT for 1 hour. The solvent was removed under vacuum, and the residue was dissolved in EtOH (5 mL). To the solution was added Hunig's base (0.36 mL, 2.1 mmol), and the solution was heated to 150° C. in a microwave tube for 45 minutes. LC showed mostly product, which was purified by silica gel chromatography (MeOH-DCM). The adduct was treated with 4N HCl to remove the BOC group and provide the title compound. LC-MS (IE, m/z): 261 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]([OH:18])=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:19][O:20][CH2:21][CH2:22][N:23]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1)[CH3:24].ClCCl.CO.N>>[CH3:19][O:20][CH2:21][CH2:22][N:23]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]([NH:32][C:16](=[O:18])[C:15]#[C:14][C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[CH:13][CH:12]=2)=[CH:30][CH:31]=1)[CH3:24]
Reactant: O=C(O)C#Cc1ccc(-c2ccc(Cl)cc2)cc1
Reactant: COCCN(C)Cc1ccc(N)cc1
Agent: N
Solvent: CO
Solvent: ClCCl
Product: COCCN(C)Cc1ccc(NC(=O)C#Cc2ccc(-c3ccc(Cl)cc3)cc2)cc1

Procedure:
Prepared analogously to Example 3.8. from (4′-chlorobiphenyl-4-yl)propynoic acid and 4-{[(2-methoxyethyl)methylamino]methyl}phenylamine. Yield: 150 mg (35% of theory); melting point: 130° C.-133° C.; C26H25ClN2O2 (M=432.94); calc.: molecular ion peak (M+H)+: 433/435 (Cl); found: molecular ion peak (M+H)+: 433/435 (Cl); Rf value: 0.50 (silica gel, dichloromethane/methanol/ammonia (90:10:1)).
Reaction SMILES: [Cl:1][C:2]1[C:7]([B:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10]([CH3:16])([CH3:15])[O:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[OH:17].[C:18](=O)([O-])[O-].[K+].[K+].COS(OC)(=O)=O.Cl>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:17][CH3:18])=[CH:4][CH:5]=[CH:6][C:7]=1[B:8]1[O:12][C:11]([CH3:13])([CH3:14])[C:10]([CH3:16])([CH3:15])[O:9]1
Reactant: O=C([O-])[O-]
Reactant: CC1(C)OB(c2cccc(O)c2Cl)OC1(C)C
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: COS(=O)(=O)OC
Product: COc1cccc(B2OC(C)(C)C(C)(C)O2)c1Cl
Reaction time: 0.17 h
Yield: 85.3 %

Procedure:
To a stirred solution of 2-chloro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (830 g, 3.26 mol) in dry DMF (4.15 L) was added potassium carbonate (1126.4 g, 8.15 mol) under an inert atmosphere. Me2SO4 (402 mL, 4.24 mol) was added slowly to control the resulting exotherm (addition over 30 minutes gave a temperature rise from 28° C. to 55° C.) and after complete addition the reaction was stirred for 10 minutes. The reaction mixture was added to stirring HCl (5.98 L, 2 N, aq.) very slowly to control effervescence and the resulting precipitate stirred for 2 hours. The solids were filtered and washed with water (1 L) and dried in a vacuum oven over drying agent for 4 days to give 2-(2-chloro-3-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 7a as a white powder (746.7 g, 2.78 mol, 85%).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][Br:13])=[CH:6][CH:5]=1)[CH2:2][CH3:3].[C:14]1([P:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[Br-:13].[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][P+:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: CCCc1ccc(CCCBr)cc1
Solvent: Cc1ccccc1
Product: CCCc1ccc(CCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: [Br-]
Temperature: 25 °C
Yield: 102.6 %

Procedure:
3-(4-Propylphenyl)bromopropane (s4) (14.0 g), toluene (100 ml) and triphenylphosphine (31.5 g) were placed in a reaction vessel under an atmosphere of nitrogen, and the mixture was heated to reflux for 5 hours. After the reaction mixture had been cooled to 25° C., the deposits were filtered, and the unreacted material was removed by washing with toluene three times. The resulting colorless solids were dried to give 3-(4-propylphenyl)propyltriphenyl phosphonium bromide (s5) (30.0 g). The yield based on the compound (s4) was 99.1%.
Reaction SMILES: [F:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1[CH:4]=[CH:5][C:6]([OH:8])=[O:7].[C:14](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[F:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1/[CH:4]=[CH:5]/[C:6]([O:8][CH3:14])=[O:7]
Reactant: O=C(O)C=Cc1ccc(F)cc1F
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)/C=C/c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 7 h
Yield: 76.6 %

Procedure:
To a solution of 2,4-difluorocinnamic acid (20 g, 135 mmol) in N,N-dimethylformamide (500 mL) at room temperature under dry nitrogen was added potassium carbonate (90 g, 675 mmol) then iodomethane (21 mL, 337.5 mmol). The resulting mixture was stirred at room temperature under dry nitrogen for 7 hours before being quenched by the addition of water (1 L) and extracted with diethyl ether (3×200 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by an automated flash column chromatography system (CombiFlash® Separation System Sg 100c by Isco) using a pre-packed column (Redisep™ Disposable Columns for Flash Chromatography by Isco, 120 g column) eluting with 2% ethyl acetate in pentane increasing polarity in a linear gradient to 10% ethyl acetate in pentane over 1 hour to afford the title compound as a white solid (20.5 g, 77%). 1H NMR (400 MHz, CDCl3) δH 3.80 (3H, s), 6.50 (1H, d), 6.85 (1H, m), 7.50 (1H, m), 7.75 (1H, d); LRMS (APCI) 216 [MNH4+], 199 [MH+].