Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[C:13]3[Cl:20])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(#N)C>[ClH:20].[C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[C:13]3[N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(c1ccccc1)c1ccc2nccc(Cl)c2c1
Reactant: C1CNCCN1
Solvent: CC#N
Product: Cl
Product: O=S(=O)(c1ccccc1)c1ccc2nccc(N3CCNCC3)c2c1
Yield: 56 %

Procedure:
A solution of 6-benzenesulfonyl-4-chloro-quinoline (35 mg, 0.11 mmol) and piperazine (0.5 g, 2.5 mmol) in acetonitrile (2 mL) was heated at 80° C. over night. The mixture was extracted with toluene and water. The organic phase was purified by chromatography on silica gel eluted with CHCl3 saturated with NH3 (gas). The pure product was dissolved in ethyl acetate and HCl (gas) in diethyl ether was added. The resulting oily residue was dissolved in methanol and ethyl acetate and evaporated to yield a white solid (24 mg, 77%). MS m/z: 354 [M+H+]. 1H NMR (270 MHz, CH3OH-D4) δ ppm 3.52 (m, 4H) 4.13 (m, 4H) 7.36 (d, J=7.18 Hz, 1H) 7.57 (m, 3H) 8.01 (m, J=12.25, 8.54 Hz, 3H) 8.28 (d, J=8.91 Hz, 1H) 8.63 (d, J=6.68 Hz, 1H) 8.69 (s, 1H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9](Br)=[C:8]([F:13])[CH:7]=1)[CH2:2][CH2:3][CH3:4].FC(F)(O[C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[C:44]([F:46])[C:43]([C:47]([F:50])([F:49])[F:48])=[C:42]([F:51])[CH:41]=2)=[C:36]([F:52])[CH:35]=1)C1C(F)=CC(B2OC(C)(C)C(C)(C)O2)=CC=1F.[OH-:54].[NH3+]N>C1COCC1.O.CC(OC)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:49][C:47]([F:48])([C:43]1[C:42]([F:51])=[CH:41][C:40]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[CH:7][C:8]=2[F:13])=[CH:45][C:44]=1[F:46])[O:54][C:34]1[CH:35]=[C:36]([F:52])[C:37]([C:40]2[CH:41]=[C:42]([F:51])[C:43]([C:47]([F:50])([F:49])[F:48])=[C:44]([F:46])[CH:45]=2)=[CH:38][CH:39]=1
Reactant: CC1(C)OB(c2cc(F)c(C(F)(F)Oc3ccc(-c4cc(F)c(C(F)(F)F)c(F)c4)c(F)c3)c(F)c2)OC1(C)C
Reactant: [OH-]
Reactant: CCCCOc1ccc(Br)c(F)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: N[NH3+]
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Solvent: O
Product: CCCCOc1ccc(-c2cc(F)c(C(F)(F)Oc3ccc(-c4cc(F)c(C(F)(F)F)c(F)c4)c(F)c3)c(F)c2)c(F)c1

Procedure:
A mixture of 4.55 g (18.4 mmol) of 4-butoxy-2-fluorobromobenzene, 9.10 g (15.7 mmol) of 2-{4-[difluoro-(2,3′,5′-trifluoro-4′-trifluoromethylbiphenyl-4-yloxy)methyl]-3,5-difluorophenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 0.36 g (0.50 mmol) of bis(triphenylphosphine)palladium(II) chloride and 3.35 g (12.0 mmol) of sodium metaborate octahydrate is initially introduced in 60 ml of THF/water=4:1. 0.024 ml (0.5 mmol) of hydrazinium hydroxide is added, and the mixture is refluxed for 19 h. After cooling, the batch is diluted with MTBE, and the mixture is washed with water. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with water. The solution is dried using sodium sulfate and concentrated to dryness. The residue is purified by column chromatography (SiO2, n-heptane:toluene=9:1→3:1). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 4-[difluoro(3,5,2′-trifluoro-4′-butoxybiphenyl-4-yl)methoxy]-6,3′,5′-trifluoro-4′-trifluoromethylbiphenyl as a colourless solid.
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:24])([C:7]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]=O)[CH:17]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:25].[CH:26]([NH2:39])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:24])([C:7]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][NH:39][CH:26]([C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=5)[C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH:17]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:25]
Reactant: NC(c1ccccc1)c1ccccc1
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(-c4cccc(C=O)c4)cc3CC[C@@H]12
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CN1C(=O)CC[C@]2(C)c3ccc(-c4cccc(CNC(c5ccccc5)c5ccccc5)c4)cc3CC[C@@H]12
Temperature: 25 °C
Reaction time: 60 h
Yield: 79.9 %

Procedure:
To a suspension of (+)-(4aR)-(10bR)-4-methyl-8-(3-formylphenyl)-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (30 mg, 0.09 mmol), in 0.75 mL of methanol was added benzhydrylamine (0.09 mmol), sodium cyanoborohydride (0.09 mmol) and 2 drops of glacial acetic acid (mixture became homogeneous; pH=4). The reaction was stirred at room temperature for 60 h. The mixture was diluted with ethyl acetate, saturated aqueous sodium bicarbonate solution was added, and the resulting mixture was extracted repeatedly with ethyl acetate. The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent), followed by trituration of the resulting oil with ether/hexanes, to give 36 mg (80%) of the title compound as a white solid. mp 55°-57° FDMS: m/e =500. α[D]589 =+48.40 (c=0.64, methanol).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](=[N:12][C:13]#[N:14])[CH3:11])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:22][CH:23]=[C:24]([Cl:26])[Cl:25].[I-].[Cs+]>C(#N)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:22][CH:23]=[C:24]([Cl:26])[Cl:25])[C:10](=[N:12][C:13]#[N:14])[CH3:11])=[CH:4][CH:3]=1
Reactant: ClC(Cl)=CCBr
Reactant: CC(=NC#N)NCc1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Solvent: CC#N
Product: CC(=NC#N)N(CC=C(Cl)Cl)Cc1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81.6 %

Procedure:
174 mg (0.83 mmol) of N-[(6-chloropyridin-3-yl)methyl]-N′-cyanoethanimidamide are stirred into 5 ml of acetonitrile, and 543 mg (1.67 mmol) of cesium carbonate, 166 mg (0.88 mmol) of 3-bromo-1,1-dichloroprop-1-ene and 22 mg (0.08 mmol) of cesium iodide are added successively. The reaction mixture is then stirred at room temperature for 1 hour. The reaction mixture is concentrated under reduced pressure and then taken up in ethyl acetate, washed successively with 1 N aqueous hydrochloric acid, 1 N aqueous sodium hydroxide solution and saturated sodium chloride solution and dried over sodium sulphate. Concentration of the organic phase under reduced pressure and purification of the residue by column chromatography on silica gel using the mobile phase mixture ethyl acetate:cyclohexane (2:1) gives 215 mg (77% of theory) of N-[(6-chloropyridin-3-yl)methyl]-N′-cyano-N-(3,3-dichloroprop-2-en-1-yl)ethanimidamide
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[Na+].[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17]Cl)=[CH:15][CH:14]=1.O>CS(C)=O>[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[CH:15][CH:14]=1
Reactant: ClCc1ccc(Cl)cc1
Reactant: c1ccc2[nH]ccc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: Clc1ccc(Cn2ccc3ccccc32)cc1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A solution of 5.86 g (0.05 mol) of indole in 25 ml of DMSO is added to a mixture of 1.32 g of sodium hydroxide (0.055 mol, suspension in mineral oil) in 50 ml of dimethyl sulfoxide. The mixture is heated at 60° C. for 1.3 hours and then allowed to cool, and 17.7 g (0.11 mol) of 4-chlorobenzyl chloride are added dropwise. The solution is heated at 60° C., allowed to stand overnight and then poured with stirring into 200 ml of water. The mixture is extracted repeatedly with a total of 75 ml of CH2Cl2, the organic phase is dried with anhydrous sodium sulfate and filtered and the filtrate is concentrated under reduced pressure.
Reaction SMILES: C([O:5][C:6](=[O:43])[CH2:7][CH2:8][NH:9][C:10](=[O:42])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=3)=[CH:28][CH:27]=2)[CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:13][CH:12]=1)(C)(C)C.[Li+].[OH-].Cl>C1COCC1>[CH:20]1([CH2:19][CH:18]([C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:39])([F:40])[F:41])=[CH:34][CH:33]=3)=[CH:30][CH:31]=2)[O:17][C:14]2[CH:15]=[CH:16][C:11]([C:10]([NH:9][CH2:8][CH2:7][C:6]([OH:43])=[O:5])=[O:42])=[CH:12][CH:13]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: CC(C)(C)OC(=O)CCNC(=O)c1ccc(OC(CC2CCCCC2)c2ccc(-c3ccc(C(F)(F)F)cc3)cc2)cc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)CCNC(=O)c1ccc(OC(CC2CCCCC2)c2ccc(-c3ccc(C(F)(F)F)cc3)cc2)cc1
Temperature: 70 °C
Reaction time: 8 h
Yield: 88.4 %

Procedure:
To a mixture of (±)-3-{4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoylamino}-propionic acid tert-butyl ester (Isomer 1) (0.0999, 0.168 mmol) in THF (1.7 mL) is added LiOH (1 N aqueous, 1.7 mL) and stirred at 70° C. overnight. The reaction mixture is acidified with 1N HCl (2.0 mL) and extracted with EtOAc (3×10 mL). Combined organic extracts are dried over MgSO4, filtered, and conc. to provide 3-{4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoylamino}-propionic acid (Isomer 1) (0.0801 g, 88%) as a white solid. MS (ES): 540.0 [M+H]+.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.I[CH3:18].[H-].[Na+]>CN(C=O)C>[CH3:18][N:12]1[C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[N:9]=[C:8]1[C:5]1[CH:4]=[CH:3][C:2]([I:1])=[CH:7][CH:6]=1
Reactant: Ic1ccc(-c2nc3ccccc3[nH]2)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(-c2ccc(I)cc2)nc2ccccc21
Yield: 61.8 %

Procedure:
2-(4-Iodophenyl)benzimidazole (200 mg, 0.6 mmol) was methylated with iodomethane (180 mg, 1.2 mmol, 2.0 eq.) and NaH (45 mg, 1.8 mmol, 3 eq.) in DMF (3 mL) for 18 h. Dilution with diethyl ether, washing with water, drying over Na2SO4, and chromatography (10→25% EtOAc/hexanes) gave 1-methyl-2-(4-iodophenyl)benzimidazole (124 mg, 59%).
Reaction SMILES: FC(F)(F)S([C:6]1[C:14]2[S:13][C:12]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)(=O)=O.C(N(CC)CC)C.[CH3:30][Si:31]([C:34]#[CH:35])([CH3:33])[CH3:32]>CN(C=O)C.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:30][Si:31]([C:34]#[C:35][C:6]1[C:14]2[S:13][C:12]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)([CH3:33])[CH3:32]
Reactant: CCNC(=O)Nc1nc2cccc(S(=O)(=O)C(F)(F)F)c2s1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CO
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCNC(=O)Nc1nc2cccc(C#C[Si](C)(C)C)c2s1
Temperature: 100 °C
Reaction time: 18 h
Yield: 92.6 %

Procedure:
A mixture of 1-(7-trifluoromethylsulfonyl-2-benzothiazolyl)-3-ethylurea (0.080 g, 80% pure, 0.17 mmol), Pd(PPh3)2Cl2 (0.010 g, 0.014 mmol, 0.08 eq), and triethylamine (0.102 mL, 0.73 mmol, 4.3 eq) in 1 mL of anhydrous DMF was bubbled with nitrogen gas for 5 minutes, followed by the addition of trimethylsilyl acetylene (0.12 mL, 0.85 mmol, 5.0 eq). The mixture was heated at about 100° C. with stirring in a sealed tube for about 18 hours. The mixture was cooled down, taken up in 10 mL MeOH, and evaporated to dryness. Purification by flash chromatography on SiO2 with ethyl acetate and heptane (2/1) gave pure desired compound 0.050 g (93%). LC/MS 318 (M+1); LC retention time 9.25 min.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6](Cl)=[O:7])#[N:2].O[NH:17][C:18](=[NH:37])[C:19]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:20]=1[CH:21]=[N:22][N:23]2[CH2:28][C:29]([CH3:36])([CH3:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31].C(N(CC)CC)C>C(#N)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:7][N:17]=[C:18]([C:19]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:20]=3[CH:21]=[N:22][N:23]4[CH2:28][C:29]([CH3:35])([CH3:36])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:37]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]
Reactant: CC(C)Oc1ccc(C(=O)Cl)cc1C#N
Reactant: CCOC(=O)C(C)(C)Cn1ncc2c(C(=N)NO)cccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)C(C)(C)Cn1ncc2c(-c3noc(-c4ccc(OC(C)C)c(C#N)c4)n3)cccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 68.1 %

Procedure:
3-Cyano-4-[(1-methylethyl)oxy]benzoyl chloride (D106) (0.398 mmol) in acetonitrile (3.00 ml) at room temperature was treated with ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}-2,2-dimethylpropanoate (D103) (101 mg, 0.332 mmol) followed by triethylamine (0.069 ml, 0.498 mmol). The resulting yellow solution was stirred at room temperature for 1 hr, refluxed overnight, for a further 24 hours and again overnight then cooled to room temperature and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel [gradient ethyl acetate/cyclohexane] gave the title compound (107 mg, 68%) as a colourless solid. MS (ES) C26H27N5O4 requires 473, found 474 [M+H]+
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]#[N:14].[F:15][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH:18]=O.C([OH:26])C>>[Cl:1][C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[CH:5]=[C:4]2[C:3]=1[CH2:12][C:13](=[O:26])[NH:14][CH:18]2[C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[F:15]
Reactant: CCO
Reactant: O=Cc1ccccc1F
Reactant: N#CCc1ccc2ccccc2c1Cl
Product: O=C1Cc2c(cc3ccccc3c2Cl)C(c2ccccc2F)N1

Procedure:
From 1-chloro-2-naphthylacetonitrile and 2-fluorobenzaldehyde, m.p. 206°-9° (ethanol).
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]([OH:13])=[O:12].[CH3:14][C:15]1[CH:20]=[C:19]([B:21]2[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]2)[CH:18]=[C:17]([CH3:30])[C:16]=1O.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.CN(C)C1C=CN=CC=1.O>[CH3:30][C:17]1[CH:18]=[C:19]([B:21]2[O:25][C:24]([CH3:26])([CH3:27])[C:23]([CH3:29])([CH3:28])[O:22]2)[CH:20]=[C:15]([CH3:14])[C:16]=1[O:12][C:11]([C:3]1[O:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:2]=1[CH3:1])=[O:13]
Reactant: Cc1cc(B2OC(C)(C)C(C)(C)O2)cc(C)c1O
Reactant: Cc1c(C(=O)O)oc2ccccc12
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: O
Product: Cc1cc(B2OC(C)(C)C(C)(C)O2)cc(C)c1OC(=O)c1oc2ccccc2c1C
Temperature: 25 °C
Reaction time: 6 h
Yield: 28 %

Procedure:
To 3-methyl-benzofuran-2-carboxylic acid (500 mg, 2.84 mmol, 1 eq) in 5 mL of dichloromethane under argon was added 2,6-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (704 mg, 2.84 mmol, 1 eq.), 1,3-dicyclohexylcarbodiimide (1.17 g, 5.68 mmol, 2 eq.), and 4-(dimethylamino)pyridine (173 mg, 1.42 mmol, 0.5 eq.). The resulting mixture was stirred at room temperature for 6 h. The reaction was then diluted with water and extracted with ethyl acetate. The organics were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified using flash column chromatography on silica gel to provide 3-methyl-benzofuran-2-carboxylic acid 2,6-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl ester in 28% yield. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.3 (s, 12 H) 2.2 (s, 6 H) 2.7 (s, 3 H) 7.4 (m, 1 H) 7.5 (s, 2 H) 7.6 (m, 1 H) 7.8 (d, J=8.3 Hz, 1 H) 7.9 (m, 1 H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[C:14]([C:18]1[CH:22]=[C:21]([C:23](O)=[O:24])[O:20][N:19]=1)([CH3:17])([CH3:16])[CH3:15].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:23]([C:21]2[O:20][N:19]=[C:18]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:22]=2)=[O:24])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1
Reactant: Nc1nc(Br)ccc1[N+](=O)[O-]
Reactant: CC(C)(C)c1cc(C(=O)O)on1
Agent: O=C(Cl)C(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)c1cc(C(=O)Nc2nc(Br)ccc2[N+](=O)[O-])on1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 6-bromo-3-nitro-pyridin-2-ylamine (500 mg, 2.29 mmol) in THF (10 mL) was treated with NaH (275 mg, 6.88 mmol) at room temperature for 1 h. Simultaneously a solution of 3-tert-butyl-isoxazole-5-carboxylic acid (524 mg, 3.10 mmol, prepared as described in Example I) in DCM (10 mL) was treated with oxalyl chloride (270 μL, 3.10 mmol) and DMF (2 drops) at room temperature for 1 h. The acid chloride solution was concentrated to dryness in vacuo, taken up in THF (10 mL), and added to the sodium anilide solution. The resulting mixture was stirred at room temperature for 15 min, quenched with saturated aqueous NH4Cl (50 mL), and extracted twice with EtOAc (50 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system: Flow rate=25 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 1 min, then 1:99 to 3:17 v/v over 40 min) to yield 3-tert-butyl-isoxazole-5-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide as a solid. 1H-NMR (400 MHz, CDCl3) δ: 10.85 (br. s., 1H), 8.37 (d, J=8.6 Hz, 1H), 7.48 (d, J=8.6 Hz, 1H), 7.03 (s, 1H), 1.39 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C13H13BrN4O4: 369.0 (M+H). Measured: 369.0.
Reaction SMILES: CS(O[CH:6]1[CH2:9][N:8]([C:10]2[S:11][CH:12]=[C:13]([C:15](=[O:35])[NH:16][C@@H:17]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=4)=[O:23])[CH2:18]3)[N:14]=2)[CH2:7]1)(=O)=O.[C:36]([O-:39])(=[S:38])[CH3:37].[K+]>CN(C)C=O>[C:36]([S:38][CH:6]1[CH2:7][N:8]([C:10]2[S:11][CH:12]=[C:13]([C:15](=[O:35])[NH:16][C@@H:17]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=4)=[O:23])[CH2:18]3)[N:14]=2)[CH2:9]1)(=[O:39])[CH3:37]
Reactant: CC([O-])=S
Reactant: CS(=O)(=O)OC1CN(c2nc(C(=O)N[C@@H]3CCN(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)cs2)C1
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)SC1CN(c2nc(C(=O)N[C@@H]3CCN(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)cs2)C1
Temperature: 80 °C
Reaction time: 8 h
Yield: 69.3 %

Procedure:
To a solution of 3-methanesulfonyloxy-1-{4-[(3R)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (420 mg, 0.799 mmol) (obtained as described in Reference Example 53(8)) in dimethylformamide (21 ml) was added potassium thioacetate (548 mg, 4.79 mmol) at room temperature. The mixture was stirred in an oil bath (80° C.) overnight. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and 10% aqueous sodium chloride solution. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (1:2)→ethyl acetate:methanol (99:1) as the eluant to afford 3-acetylthio-1-{4-[(3R)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (280 mg, yield 69%) as a pale brown solid.
Reaction SMILES: [CH3:1][C:2]1([OH:12])[CH:9]2[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:11][CH:3]1[CH2:4]3)[CH2:8]2.[C:13](O)(=[O:16])[CH:14]=[CH2:15].[C:18]([OH:23])(=[O:22])[C:19]([CH3:21])=[CH2:20]>>[C:13]([O:12][C:2]1([CH3:1])[CH:3]2[CH2:11][CH:7]3[CH2:6][CH:5]([CH2:10][CH:9]1[CH2:8]3)[CH2:4]2)(=[O:16])[CH:14]=[CH2:15].[C:18]([O:23][C:2]1([CH3:1])[CH:3]2[CH2:11][CH:7]3[CH2:6][CH:5]([CH2:10][CH:9]1[CH2:8]3)[CH2:4]2)(=[O:22])[C:19]([CH3:21])=[CH2:20]
Reactant: C=CC(=O)O
Reactant: C=C(C)C(=O)O
Reactant: CC1(O)C2CC3CC(C2)CC1C3
Product: C=C(C)C(=O)OC1(C)C2CC3CC(C2)CC1C3
Product: C=CC(=O)OC1(C)C2CC3CC(C2)CC1C3

Procedure:
For example, by conducting a reaction using, as the 2-alkyl-2-adamantanol, 2-methyl-2-adamantanol and, as the carboxylic acid compound, acrylic acid or methacrylic acid, there is obtained 2-methyl-2-adamantyl acrylate or 2-methyl-2-adamantyl methacrylate.
Reaction SMILES: [CH2:1]1[CH:14]2[CH:5]([CH2:6][C:7]3[C:12]([CH:13]2[NH:15][CH:16]=[N:17][C:18]#[N:19])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:4][CH2:3][CH2:2]1.[C:20](=O)([O-])[O-].[K+].[K+].Br[CH:27](C)[C:28]([O-:30])=[O:29]>CN(C)C=O.C1OCCOCCOCCOCCOCCOC1>[CH2:1]1[CH:14]2[CH:5]([CH2:6][C:7]3[C:12]([CH:13]2[N:15]2[C:27]([C:28]([O:30][CH3:20])=[O:29])=[C:18]([NH2:19])[N:17]=[CH:16]2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:4][CH2:3][CH2:2]1
Reactant: N#CN=CNC1c2ccccc2CC2CCCCC21
Reactant: CC(Br)C(=O)[O-]
Reactant: O=C([O-])[O-]
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1c(N)ncn1C1c2ccccc2CC2CCCCC21
Yield: 43 %

Procedure:
20.8 Parts of N-(1,2,3,4,4a,9,9a,10-octahydroanthracen-9-yl)-N'-cyano-formamidine were dissolved in 140 ml of N,N-dimethylformamide together with 0.1 parts of 18-crown-6. 28.4 Parts of potassium carbonate were added. The mixture was heated to +80'C. and 13.8 Parts of α-bromo-methyl-acetate were added. After 15 hours at +80° C. to +100° C. the reactants were poured on ice and the mixture was extracted with ether. The etheral extracts were dried with Na2SO4, filtered and concentrated. 21 Parts of crude residue were chromatographed on a silica gel column and extracted with an ethyl acetate/hexane mixture (1:1). 11.6 Parts (43%) of methyl 1-(1,2,3,4,4a,9,9a,10-octahydroanthracen-9-yl)-4-amino-1H-imidazole-5-carboxylate (int. 15), mp. 155°-159° C. were isolated.
Reaction SMILES: [S:1]([O-])([O-])(=O)=[S:2].[Na+].[Na+].Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20].II.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.O>[C:19]([OH:21])(=[O:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][S:1][S:2][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20]
Reactant: O=C(O)CCCCCCCCCCBr
Reactant: O=S([O-])([O-])=S
Agent: II
Agent: O=S([O-])S(=O)(=O)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)CCCCCCCCCCSSCCCCCCCCCCC(=O)O
Temperature: 90 °C

Procedure:
Sodium thiosulfate (55.3 g, 350 mmol) is added to a suspension of 11-bromo-undecanoic acid (92.8 g, 350 mmol) in 50% aqueous 1,4-dioxane (1000 ml). The mixture is heated at reflux (90° C.) for 2 h until the reaction to the intermediate Bunte salt was complete (clear solution). The oxidation to the corresponding disulfide is carried out in situ by adding iodine in portions until the solution retained with a yellow to brown color. The surplus of iodine is retitrated with 15% sodium pyrosulfite in water. After removal of 1,4-dioxane by rotary evaporation the creamy suspension is filtered to yield product 11,11′-dithiobis(undecanoic acid). Recrystallization from ethyl acetate/THF provides a white solid (73.4 g, 96.5%): mp 94° C.; 1H NMR (400 MHz, CDCl3/CD3OD 95:5): δ2.69 (t, 2H, J=7.3 Hz), 2.29 (t, 2H, J=7.5 Hz), 1.76-1.57 (m, 4H), and 1.40-1.29 (m, 12H); FAB-MS (Cs+, 20 keV): m/z (relative intensity) 434 (100, M+). Anal. Calcd. for C22H42O4S2: C, 60.79; H, 9.74; S, 14.75. Found: C, 60.95; H, 9.82; S, 14.74. To a solution of 11,11′-dithiobis(undecanoic acid) (1.0 g, 2.3 mmol) in THF (50 ml) is added N-hydroxysuccinimide (0.575 g, 5 mmol) followed by DCC (1.03 g, 5 mmol) at 0° C. After the reaction mixture is allowed to warm to 23° C. and is stirred for 36 h at room temperature, the dicyclohexylurea (DCU) is filtered. Removal of the solvent under reduced pressure and recrystallization from acetone/hexane provides 11,11′-dithiobis(succinimidylundecanoate) as a white solid. Final purification is achieved by medium pressure liquid chromatography (9 bar) using silica gel and a 2:1 mixture of ethyl acetate and hexane. The organic phase is concentrated and dried in vacuum to afford 11,11′-dithiobis(succinimidylundecanoate) (1.12 g, 78%): mp 95° C.; 1H NMR (400 MHz, CDCl3): δ2.83 (s, 4H), 2.68 (t, 2H, J=7.3 Hz), 2.60 (t, 2H, J=7.5 Hz), 1.78-1.63 (m, 4H), and 1.43-1.29 (m, 12H); FAB-MS (Cs+, 20 keV): m/z (relative intensity) 514 (100), 628 (86, M+). Anal. Calcd. for C30H48N2O8S2: C, 57.30; H, 7.69; N, 4.45; S, 10.20. Found: C, 57.32; H, 7.60; N, 4.39; S, 10.25.