Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][CH:2]([F:34])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([N:20]([CH3:27])[CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[C:31]([O:32][CH3:33])[C:5]=2[N:4]=1.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>>[F:34][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]([CH3:27])[CH:21]3[CH2:26][CH2:25][N:24]([S:36]([CH3:35])(=[O:38])=[O:37])[CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[C:31]([O:32][CH3:33])[C:5]=2[N:4]=1
Reactant: COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N(C)C2CCNCC2)n1
Reactant: CS(=O)(=O)Cl
Product: COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N(C)C2CCN(S(C)(=O)=O)CC2)n1
Yield: 56 %

Procedure:
Reaction of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-methyl-6-(4-morpholinyl)-N-(4-piperidinyl)-1,3,5-triazin-2-amine from the previous step with methanesulphonyl chloride as in Example 4 gave 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-methyl-N-[1-(methylsulfonyl)-4-piperidinyl]-6-(4-morpholiny)-1,3,5-triazin-2-amine in 56% yield: mp (CH2Cl2/MeOH) 190-192° C.; 1H NMR (DMSO-d6) (rotamers) δ 7.97 and 7.89 (2d, J=8.3, 8.5 Hz, 1H), 7.69 and 7.74 (2t, JHF=52.9 Hz, 1H), 7.46-7.39 (m, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.69-4.61 (m, 1H), 3.98 (s, 3H), 3.80-3.69 (m, 10H), 3.09 and 2.95 (2s, 3H), 2.93-2.92 (2s, 3H), 2.92-2.78 (m, 2H), 1.93-1.67 (m, 4H); Anal. Calcd. for C23H30F2N8O4S: C, 50.0; H, 5.5; N, 20.3. Found: C, 49.5; H, 5.3; N, 20.0%.
Reaction SMILES: [CH3:1][C:2]([O:4][C@@H:5]1[C@@:9]2([CH3:30])[CH2:10][CH2:11][C@@H:12]3[C@@:17]4([CH3:29])[CH2:18][C@H:19]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[C@@H:20]([OH:22])[CH2:21][C@@H:16]4[CH2:15][CH2:14][C@H:13]3[C@@H:8]2[CH2:7][C@@H:6]1[N+:31]1([CH2:36][CH:37]=[CH2:38])[CH2:35][CH2:34][CH2:33][CH2:32]1)=[O:3].C([Br:42])C=C>C(Cl)Cl>[CH3:1][C:2]([O:4][C@@H:5]1[C@@:9]2([CH3:30])[CH2:10][CH2:11][C@@H:12]3[C@@:17]4([CH3:29])[CH2:18][C@H:19]([N:23]5[CH2:24][CH2:25][O:26][CH2:27][CH2:28]5)[C@@H:20]([OH:22])[CH2:21][C@@H:16]4[CH2:15][CH2:14][C@H:13]3[C@@H:8]2[CH2:7][C@@H:6]1[N+:31]1([CH2:36][CH:37]=[CH2:38])[CH2:32][CH2:33][CH2:34][CH2:35]1)=[O:3].[Br-:42]
Reactant: C=CCBr
Agent: C=CC[N+]1([C@H]2C[C@H]3[C@@H]4CC[C@H]5C[C@H](O)[C@@H](N6CCOCC6)C[C@]5(C)[C@H]4CC[C@]3(C)[C@H]2OC(C)=O)CCCC1
Solvent: ClCCl
Product: [Br-]

Procedure:
Rocuronium bromide was synthesised using conventional chemistry from the reaction of 1.7 kg of Rocuronium and 1.21 L of allyl bromide in 17 L of DCM.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[CH:11]=1.[Li]CCCC.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[C:9]([B:17]([OH:22])[OH:18])[S:8][C:7]=2[CH:11]=1
Reactant: COc1ccc2ccsc2c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1ccc2cc(B(O)O)sc2c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 71 %

Procedure:
To a solution of 6-methoxybenzo[b]thiophene (Graham, S. L., et al. J. Med. Chem. 1989, 32, 2548-2554)(18.13 g, 0.111 mol) in 150 mL of anhydrous THF at −60° C. was added n-BuLi (76.2 mL, 0.122 mol, 1.6 M solution in hexanes), dropwise via syringe. After stirring for 30 min, triisopropyl borate (28.2 mL, 0.122 mol) was introduced via syringe. The resulting mixture was allowed to gradually warm to 0° C. and then partitioned between 1.0 N HCl and EtOAc (300 mL each). The layers were separated, and the organic phase was dried over Na2SO4. Concentration in vacuo produced a white solid that was triturated from Et2O/hexanes. Filtration provided 16.4 g (71%) of 6-methoxybenzo[b]thiophene-2-boronic acid as a white solid.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([CH2:7][N:8]2[C:16]3[C:11](=[C:12]([C:19]([F:22])([F:21])[F:20])[C:13]([C:17]#[N:18])=[CH:14][CH:15]=3)[CH:10]=[C:9]2[CH3:23])[N:6]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1>>[CH3:23][C:9]1[N:8]([CH2:7][C:5]2[N:6]=[C:2]([C:30]3[CH:29]=[CH:28][CH:27]=[C:26]([C:25]([F:36])([F:35])[F:24])[CH:31]=3)[S:3][CH:4]=2)[C:16]2[C:11]([CH:10]=1)=[C:12]([C:19]([F:22])([F:21])[F:20])[C:13]([C:17]#[N:18])=[CH:14][CH:15]=2
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Reactant: Cc1cc2c(C(F)(F)F)c(C#N)ccc2n1Cc1csc(Br)n1
Product: Cc1cc2c(C(F)(F)F)c(C#N)ccc2n1Cc1csc(-c2cccc(C(F)(F)F)c2)n1

Procedure:
Synthesized as described in Example 310D using 1-[(2-bromo-1,3-thiazol-4-yl)methyl]-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 311B) and [3-(trifluoromethyl)phenyl]boronic acid: MS (ES) m/z 466 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([F:16])[C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH3:34][O:35][C:36](=[O:40])[C@H:37]([CH3:39])O>CS(C)=O>[CH3:34][O:35][C:36](=[O:40])[CH:37]([O:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][C:5]2[C:4]([F:16])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)=[CH:14][CH:13]=1)[CH3:39]
Reactant: Oc1ccc(Oc2ncc(Cl)cc2F)cc1
Reactant: COC(=O)[C@H](C)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)C(C)Oc1ccc(Oc2ncc(Cl)cc2F)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 24 g (0.1 mol) of 4-(5-chloro-3-fluoropyridin-2-yloxy)-phenol in 80 ml of dimethylsulfoxide is added dropwise to a stirred solution of 13.8 g (0.1 mol) of potassium carbonate in 50 ml of dimethylsulfoxide. When everything is added, the mixture is stirred for 2 hours at room temperature and then a solution of 25.8 g (0.1 mol) of (S)(-)-lactic acid-methylester tosylate is added dropwise over 30 minutes. The mixture is heated to 60° and stirred at that temperature for 20 hours, then poured onto ice/water and the organic material is extracted three times with ether. The ether-layer is washed with water and saturated salt solution, dried over magnesium sulfate, filtered and evaporated. The residue is passed for purification through a silicagel column with a hexane/ethyl acetate 3:1 solvent. After distillation of the solvent, 26 g of a clear oil of the above ester is obtained ([α]D20 =+38.8°±0.5°2% in acetone).
Reaction SMILES: [N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:15])=[C:9]([C:29]3C=C(OC4C=CC=C(C(F)(F)F)C=4)N=C[N:30]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1(C2C=CC(N)=C(C3C=C(O[C:66]4[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:74])[F:73])[CH:67]=4)N=CN=3)C=2)CCCCC1>>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:26]=[CH:27][CH:28]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:15])=[C:9]([C:29]3[CH:29]=[C:9]([CH2:10][NH:13][CH2:14][C:66]4[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:73])([F:74])[F:75])[CH:67]=4)[CH:8]=[CH:7][N:30]=3)[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Nc1ccc(N2CCCCC2)cc1-c1cc(Oc2cccc(C(F)(F)F)c2)ncn1
Reactant: O=C(O)CCSCc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(Oc3cccc(C(F)(F)F)c3)ncn2)c1
Product: O=C(O)CCSCc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2-c2cc(CNCc3cccc(C(F)(F)F)c3)ccn2)c1

Procedure:
This compound was prepared using the procedure described for the preparation of 3-((3-((4-(piperidin-1-yl)-2-(6-(3-(trifluoromethyl)phenoxy)pyrimidin-4-yl)phenyl)carbamoyl)benzyl)thio)propanoic acid 3.9 from 4-(piperidin-1-yl)-2-(6-(3-(trifluoromethyl)phenoxy)pyrimidin-4-yl)aniline 3.9b. MS (ES, m/z) 662.2 [M+H]+.
Reaction SMILES: [C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:25]([CH3:26])=[CH:24][C:18]2[N:19]([CH3:23])[C:20](=[O:22])[S:21][C:17]=2[C:16]=1[Br:27])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C(OC[C@H](C1C(C)=CC2N=C(O)SC=2C=1Br)OC(C)(C)C)(=O)C(C)(C)C.[CH3:54][Si:55]([CH3:62])([CH3:61])[CH2:56][CH2:57][O:58]CCl>>[C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:25]([CH3:26])=[CH:24][C:18]2[N:19]([CH2:23][O:58][CH2:57][CH2:56][Si:55]([CH3:62])([CH3:61])[CH3:54])[C:20](=[O:22])[S:21][C:17]=2[C:16]=1[Br:27])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:3])([CH3:5])[CH3:4]
Reactant: C[Si](C)(C)CCOCCl
Reactant: Cc1cc2c(sc(=O)n2C)c(Br)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Agent: Cc1cc2nc(O)sc2c(Br)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Product: Cc1cc2c(sc(=O)n2COCC[Si](C)(C)C)c(Br)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C

Procedure:
Prepared by the similar method to make (S)-2-(7-bromo-3,5-dimethyl-2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate (67C) in example 26 from 67B using 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) instead of methyl iodide.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:9]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[O:10])=[CH:4][CH:3]=1.Cl[CH2:25][C:26](=[O:28])[CH3:27]>>[O:28]=[C:26]([CH3:27])[CH2:25][S:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:9]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[O:10])=[CH:4][CH:3]=1
Reactant: CC(=O)CCl
Reactant: O=C(Nc1nccs1)C(CC1CCOCC1)c1ccc(S)cc1
Product: CC(=O)CSc1ccc(C(CC2CCOCC2)C(=O)Nc2nccs2)cc1

Procedure:
Reaction of 2-(4-mercaptophenyl)-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylpropionamide (see EXAMPLE 146, 363 mg, 1.04 mmol) with chloroacetone (90 μL, 1.10 mmol) employing a procedure similar to that described in EXAMPLE 146, furnished 2-[4-(2-oxopropylsulfanyl)phenyl]-3-(tetrahydropyran-4-yl)-N-thiazol-2-ylpropionamide: m/z (ES+)=405.3 [M+H]+. TBA-OX (2.46 g, 2.44 mmol) was added to a stirred solution of the abovementioned thioether (399 mg, 0.99 mmol) in CH2Cl2 (20 mL). After 19 h, the reaction mixture was treated with more TBA-OX (0.97 g, 0.96 mmol). An additional quantity of TBA-OX (1.09 g, 1.07 mmol) was added 20 h later, then the mixture was stirred further for 3 d. Solvent evaporation and flash chromatography (IH-EtOAc, 3:2 to 0:1) afforded the title compound: RTA=3.12 min; m/z (ES+)=437.2 [M+H]+.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:9][C:10](=[O:29])[C:11]([O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])([CH3:20])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[CH3:8].[CH3:30][O:31][C:32]1[CH:58]=[CH:57][C:35]([CH2:36][N:37]2[CH2:41][CH:40]([CH2:42][CH2:43]OS(C3C=CC(C)=CC=3)(=O)=O)[N:39]([CH3:55])[C:38]2=[O:56])=[CH:34][CH:33]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:7]([O:9][C:10](=[O:29])[C:11]([O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[F:28])([CH3:20])[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:43][CH2:42][CH:40]2[CH2:41][N:37]([CH2:36][C:35]3[CH:57]=[CH:58][C:32]([O:31][CH3:30])=[CH:33][CH:34]=3)[C:38](=[O:56])[N:39]2[CH3:55])=[CH:17][CH:18]=1)[CH3:8]
Reactant: COc1ccc(CN2CC(CCOS(=O)(=O)c3ccc(C)cc3)N(C)C2=O)cc1
Reactant: CCOC(=O)C(C)(Cc1ccc(O)cc1)Oc1ccccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)(Cc1ccc(OCCC2CN(Cc3ccc(OC)cc3)C(=O)N2C)cc1)Oc1ccccc1F
Yield: 92.4 %

Procedure:
Cesium carbonate (8.23 g, 25.3 nmol) is added to a solution of 2-(2-Fluoro-phenoxy)-3-(4-hydroxy-phenyl)-2-methyl-propionic acid ethyl ester (2.68 g, 8.43 mmol) and toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl ester (3.88 g, 9.27 mmol) in DMF (30 mL). The resultant mixture is stirred at 65° C. under an atmosphere of nitrogen for 18 h, then diluted with ethyl acetate. The organic layer is washed with 1N HCl, water, and brine. The organic layer is dried, concentrated in vacuo, and purified by flash chromatography (17% acetone in hexanes) to provide the title compound (4.4 g, 93%). 1H NMR 400 MHz, CDCl3): δ 7.19-7.15 (m, 4H), 7.06-7.01 (m, 1H), 6.97-6.87 (m, 3H), 6.83 (d, 2H, J=8.6 Hz), 6.74 (d, 2H, J=8.6 Hz), 4.31, 4.27 (ABq 2H, J=14.8 Hz), 4.21, 4.17 (ABq, 2H, J=7.2 Hz), 3.96-3.92 (m, 2H), 3.76 (s, 3H), 3.60-3.53 (m, 1H), 3.33 (t, 1H, J=8.6 Hz), 3.25, 3.13 (ABq 2H, J=13.8 Hz), 2.994-2.83 (m, 2H), 2.82 (s, 3H), 2.24-2.16 (m, 1H), 1.89-1.80 (m, 1H), 1.37 (s, 3H), 1.22 (t, 3H, J=7.2 Hz). MS [EI+] 565 (M+H)+. Rf=0.56 in 50% acetone in hexanes.
Reaction SMILES: C(O[C:4](=[O:17])[CH:5]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:6]([O:8]CC)=O)C.S(O)(O)(=O)=O.[NH2:23][C:24]1[NH:25][CH:26]=[CH:27][N:28]=1.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[C:11]1([C:5]2[C:4]([OH:17])=[N:23][C:24]3[N:25]([CH:26]=[CH:27][N:28]=3)[C:6]=2[OH:8])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)C(C(=O)OCC)c1ccccc1
Reactant: Nc1ncc[nH]1
Agent: O=S(=O)(O)O
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: Oc1nc2nccn2c(O)c1-c1ccccc1

Procedure:
18.3 g (0.0776 mol) diethylphenylmalonate and 20.5 g (0.0776 mol) 2-aminoimidazole sulfate were dissolved in 93 mL DMF and 35 mL DBU and the mixture was heated to 100° C. for 15 h. The solvent was removed, the residue dissolved in water and re-precipitated by adjusting the pH to 1 with 2 mol/l HCl. The precipitate was collected by filtration to obtain the desired product.
Reaction SMILES: [O:1]([C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](=O)CCCC)CCC.C[Si]([N:30]=[N+:31]=[N-:32])(C)C>C1(C)C=CC=CC=1>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([C:12]2[NH:32][N:31]=[N:30][N:13]=2)=[CH:14][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: N#Cc1ccc(Oc2ccccc2)cc1
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: c1ccc(Oc2ccc(-c3nnn[nH]3)cc2)cc1

Procedure:
A solution of 4-phenoxybenzonitrile (9.87 g), dibutyltin oxide (3.88 g), and trimethylsilyl azide (33.5 ml) in anhydrous toluene (200 ml) was heated to reflux for 6 hours. The reaction mixture was washed with 1.6M sodium hydroxide (2×250 ml). The combined aqueous layer was washed with diethyl ether (4×120 ml) then acidified to pH 6 with concentrated hydrochloric acid. The acidic solution was washed with ethyl acetate (3×200 ml) and the combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness to give 5-(4-phenoxyphenyl)-1H-tetrazole as a white powder.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Si:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH3:15])[CH2:9][N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[CH:4][CH:3]=1.C([Li])CCC.[I:28]I>C1COCC1.CCCCCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([Si:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([CH3:15])[CH2:9][N:10]2[C:14]([I:28])=[N:13][CH:12]=[N:11]2)=[CH:6][CH:7]=1
Reactant: II
Reactant: C[Si](Cn1cncn1)(c1ccc(F)cc1)c1ccc(F)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C[Si](Cn1ncnc1I)(c1ccc(F)cc1)c1ccc(F)cc1
Reaction time: 3 h
Yield: 18.8 %

Procedure:
A solution of 3.14 g (0.010 mol) of bis(4-fluorophenyl)methyl(1H-1,2,4-triazol-1-ylmethyl)silane in 15 ml of THF was lithiated as described in Example 1, using 7.1 ml (0.011 mol) of 1.55M n-butyllithium in hexane. To this solution was added 1.4 g (0.011 mol) of iodine. The reaction mixture was allowed to warm to 0°, stirred 3 hours, poured into 1:1 ether/hexanes, washed with 7% aqueous NaHCO3 and brine, dried over Na2SO4, filtered and evaporated. The crude product was flash chromatographed (5% ether/methylene chloride) to give 0.83 g of the title compound as a white solid: m.p. 102°-104°; nmr (CDCl3) δ 0.7 (3H, s), 4.2 (2H, s), 7.1 (4H, m), 7.5 (4H, m), 7.8 (1H, s).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]O)=[CH:4][C:3]=1[O:10][C:11]([F:14])([F:13])[F:12].[CH2:15]([O:17][C:18](=[O:34])[CH2:19][CH:20]([N:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[NH:26][C:25]1=[O:33])[CH2:21][CH2:22][CH3:23])[CH3:16].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[CH2:15]([O:17][C:18](=[O:34])[CH2:19][CH:20]([N:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([O:10][C:11]([F:14])([F:13])[F:12])[CH:4]=2)[C:25]1=[O:33])[CH2:21][CH2:22][CH3:23])[CH3:16]
Reactant: CCCC(CC(=O)OCC)n1c(=O)[nH]c2ccccc21
Reactant: Nc1ccc(CO)cc1OC(F)(F)F
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCC(CC(=O)OCC)n1c(=O)n(Cc2ccc(N)c(OC(F)(F)F)c2)c2ccccc21
Temperature: 25 °C
Yield: 8.3 %

Procedure:
(4-Amino-3-trifluoromethoxy-phenyl)-methanol (100 mg, 0.48 mmol) and 3-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-hexanoic acid ethyl ester (133 mg, 0.48 mmol) is taken up in 4 mL of tetrahydrofuran and then triphenyl phosphine is added (190 mg, 0.72 mmol). The reaction is stirred at room temperature and DIAD (141 μL, 0.72 mmol) is, added dropwise to the reaction. The reaction is stirred at room temperature for 1 hour and then the solvent evaporated in vacuo. Product is purified by preprative HPLC 30%-90% acetonitrile/water to give the title compound (20 mg, 0.04 mmol 9%). LCMS (ESMS): m/z 466.1 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6](O)=[O:7]>O1CCCC1>[Cl:1][C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][CH2:6][OH:7]
Reactant: O=C(O)COc1ccc(Cl)cc1Cl
Solvent: C1CCOC1
Product: OCCOc1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 22 h
Yield: 99.6 %

Procedure:
To a solution of 15.0 g of 2,4-dichlorophenoxyacetic acid in tetrahydrofuran (300 ml) was added dropwise 96 ml of 1.0 M borane-tetrahydrofuran complex/tetrahydrofuran solution under ice-cooling over 1.5 hours. The reaction solution was stirred at room temperature for 22 hours. After the reaction solution was concentrated, the residue was diluted with saturated aqueous ammonium chloride and ethyl acetate. The organic layer was washed with saturated ammonium chloride, saturated aqueous sodium hydrogen carbonate (×2) and saturated ammonium chloride, then dried over anhydrous sodium sulfate and concentrated, to give 14 g the title compound as a colorless oil.
Reaction SMILES: Br[C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=1[C:4]([N:6]([CH2:11][CH3:12])[CH2:7][C:8]([CH3:10])=[CH2:9])=[O:5].C([O-])=O.[Na+].C([O-])(=O)C.[Na+]>[Cl-].C([N+](CC)(CC)CC)C.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([N:6]1[CH2:7][C:8]([CH3:10])([CH3:9])[C:2]2[C:3](=[CH:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=2)[C:4]1=[O:5])[CH3:12]
Reactant: C=C(C)CN(CC)C(=O)c1cc([N+](=O)[O-])ccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC[N+](CC)(CC)CC
Solvent: CN(C)C=O
Product: CCN1CC(C)(C)c2ccc([N+](=O)[O-])cc2C1=O
Temperature: 70 °C
Reaction time: 15 h
Yield: 96.3 %

Procedure:
To a stirred de-gassed solution of 2-bromo-N-ethyl-N-(2-methyl-allyl)-5-nitro-benzamide (150 mg, 0.46 mmol), tetra-ethylammonium chloride (84 mg, 0.46 mmol), sodium formate (34 mg, 0.50 mmol) and sodium acetate (82 mg, 1.01 mmol) in anhydrous DMF (10 ml) was added palladium(II) acetate (10 mg, 0.046 mmol) and the reaction stirred at 70° C. for 15 hrs. The reaction was cooled to room temperature and filtered through a pad of celite. The solvent was evaporated in vacuo and the resulting residue purified by flash column chromatography (20% ethyl acetate in dichloromethane) to afford the title compound as a yellow solid (110 mg, 96%). HPLC retention time 4.21 min. Mass spectrum (ES+) m/z 249 (M+H).
Reaction SMILES: [CH3:1][C:2]1([CH3:21])[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[C:12]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8](B(O)O)=[CH:9]3)=[CH:4][C:3]1=2.[CH3:22][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=1I)[C:26]([O:28][CH3:29])=[O:27]>>[CH3:22][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][C:12]3[C:13]([CH3:17])([CH3:16])[CH2:14][CH2:15][C:2]([CH3:21])([CH3:1])[C:3]=3[CH:4]=2)[CH:9]=1)[C:26]([O:28][CH3:29])=[O:27]
Reactant: COC(=O)c1ccc(I)c(C)c1
Reactant: CC1(C)CCC(C)(C)c2cc3cc(B(O)O)ccc3cc21
Product: COC(=O)c1ccc(-c2ccc3cc4c(cc3c2)C(C)(C)CCC4(C)C)c(C)c1
Yield: 52.9 %

Procedure:
Following the basic procedure of Example 7(f), by reacting 2.8 g (10 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthrylboronic acid with 1.84 g (6.7 mmol) of methyl 3-methyl-4-iodobenzoate, 1.37 g (53%) of methyl 3-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthryl)benzoate was obtained in the form of a yellow oil.
Reaction SMILES: [CH3:1][S:2]([C:5]1[N:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:20]=2)[NH:17][C:16]([C:28]2[S:29][CH:30]([CH2:33][C:34](O)=[O:35])[CH2:31][N:32]=2)=[CH:15]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].O.O[N:39]1[C:43]2C=CC=C[C:42]=2[N:41]=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.NCC#N>CN(C)C=O.CCCCCC.C(OCC)(=O)C.CO.O.C(N(CC)CC)C>[C:43]([CH2:42][NH:41][C:34](=[O:35])[CH2:33][CH:30]1[S:29][C:28]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([O:11][C:8]2[CH:9]=[N:10][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][CH:7]=2)=[CH:20][C:19]=3[O:21][CH:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[N:32][CH2:31]1)#[N:39]
Reactant: CS(=O)(=O)c1ccc(Oc2cc(OC3CCOCC3)c3[nH]c(C4=NCC(CC(=O)O)S4)cc3c2)cn1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: N#CCN
Solvent: CN(C)C=O
Solvent: O
Solvent: CCCCCC
Product: CS(=O)(=O)c1ccc(Oc2cc(OC3CCOCC3)c3[nH]c(C4=NCC(CC(=O)NCC#N)S4)cc3c2)cn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 64.1 %

Procedure:
To a solution of {2-[5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (150 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole monohydrate (65 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (81 mg), aminoacetonitrile hydrochloride (52 mg), and triethylamine (120 μL), and the mixture was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (methanol:ethyl acetate:hexane=0:0:100 to 10:90:0, volume ratio), and crystallized from acetonitrile to give the title compound (103 mg, yield 64%) as white crystals.
Reaction SMILES: [CH3:1][O-:2].[Na+].[SH:4][CH2:5][CH2:6][CH2:7][Si:8]([O:13][CH3:14])([O:11][CH3:12])[O:9][CH3:10].II>CO>[CH3:12][O:11][Si:8]([O:13][CH3:14])([O:9][CH3:10])[CH2:7][CH2:6][CH2:5][S:4][S:4][CH2:5][CH2:6][CH2:7][Si:8]([O:11][CH3:12])([O:9][CH3:10])[O:2][CH3:1]
Reactant: CO[Si](CCCS)(OC)OC
Reactant: C[O-]
Agent: II
Agent: [Na+]
Solvent: CO
Product: CO[Si](CCCSSCCC[Si](OC)(OC)OC)(OC)OC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A 28% solution of sodium methylate in methanol (97.6 g. 0.51 mole) is diluted with methanol (100 ml), and thereto is added γ-mercaptopropyltrimethoxysilane (100 g, 0.51 mole). The temperature of the mixture raises in a certain degree owing to the mixing heat but return to room temperature after about 30 minutes. To the mixture is added in portions iodine (64.6 g. 0.51 mole) with stirring. In view of exothermic reaction, the reaction vessel is cooled with ice water. After completion of the addition of iodine, the brown mixture is allowed to stand at room temperature for 3 hours to give a clean liquid having pale yellow color. The reaction mixture is moved to a flask, and the methanol solvent is distilled off under reduced pressure with a rotary evaporator. The residue containing white crystals and pale yellow liquid is filtered to separate the oily liquid (86.4 g). This liquid is subjected to analyses of IR, H-NMR and UV spectra, and thereby, it is confirmed that the liquid product is bis[γ-(trimethoxysilyl)propyl ]disulfide of the formula:
Reaction SMILES: I[C:2]1C=C[C:5]([N:8]2C[C@H](CNC(=O)OC(C)(C)C)O[C:9]2=[O:22])=[CH:4][CH:3]=1.F[C:24]1[CH:25]=[C:26]([N:31]2[CH2:35][C@H:34]([CH2:36][NH:37][C:38](=[O:40])[CH3:39])[O:33][C:32]2=[O:41])[CH:27]=[CH:28][C:29]=1I>>[O:41]=[C:32]1[N:31]([C:26]2[CH:27]=[CH:28][C:29]([CH:4]3[CH2:3][CH2:2][C:9](=[O:22])[NH:8][CH2:5]3)=[CH:24][CH:25]=2)[CH2:35][C@H:34]([CH2:36][NH:37][C:38](=[O:40])[CH3:39])[O:33]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(I)c(F)c2)C(=O)O1
Reactant: CC(C)(C)OC(=O)NC[C@H]1CN(c2ccc(I)cc2)C(=O)O1
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCC(=O)NC3)cc2)C(=O)O1

Procedure:
N-({(5S)-2-oxo-3-[4-(6-oxopiperidin-3-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)acetamide is prepared by the route described in Example 1 substituting tert-butyl [(5S)-3-(4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methylcarbamate for N-{[(5S)-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide. 1H-NMR (DMSO) δ: 8.24, 7.51, 7.47, 7.33, 4.71, 4.10, 3.72, 3.40, 3.18, 3.14, 2.97, 2.28, 1.94, 1.83