Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH:2]([C:4]1[N:8]=[CH:7][N:6]([C:9]2[N:10]=[CH:11][C:12]([O:25][CH3:26])=[C:13]3[C:17]([C:18](=[O:24])[C:19]([O:21]CC)=[O:20])=[CH:16][NH:15][C:14]=23)[N:5]=1)[CH3:3].C([O-])([O-])=O.[K+].[K+].Cl>CO.O>[OH:1][CH:2]([C:4]1[N:8]=[CH:7][N:6]([C:9]2[N:10]=[CH:11][C:12]([O:25][CH3:26])=[C:13]3[C:17]([C:18](=[O:24])[C:19]([OH:21])=[O:20])=[CH:16][NH:15][C:14]=23)[N:5]=1)[CH3:3]
Reactant: CCOC(=O)C(=O)c1c[nH]c2c(-n3cnc(C(C)O)n3)ncc(OC)c12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: COc1cnc(-n2cnc(C(C)O)n2)c2[nH]cc(C(=O)C(=O)O)c12
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
Ethyl 2-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetate (100 mg, 0.278 mmol) and K2CO3 (77 mg, 0.557 mmol) were dissolved in MeOH (2 mL) and water (2 mL). The mixture was stirred at room temperature overnight, and neutralized with 1N HCl to pH 3. All solvents were removed and the residue was purified by prep. HPLC to give 2-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (46 mg, 0.139 mmol, 49.9% yield). LCMS: m/z 332.1 (M+H)+, 1.17 min (method 8).
Reaction SMILES: [N:1]([CH:4]([C:6]1[CH:7]=[C:8]([C:22]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[N:23]=2)[C:9]([NH:12][C:13]2[CH:14]=[N:15][C:16]([O:20][CH3:21])=[C:17]([F:19])[CH:18]=2)=[N:10][CH:11]=1)[CH3:5])=[N+]=[N-]>C1COCC1.[Pd]>[NH2:1][CH:4]([C:6]1[CH:7]=[C:8]([C:22]2[N:27]=[C:26]([CH3:28])[N:25]=[C:24]([N:29]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[N:23]=2)[C:9]([NH:12][C:13]2[CH:14]=[N:15][C:16]([O:20][CH3:21])=[C:17]([F:19])[CH:18]=2)=[N:10][CH:11]=1)[CH3:5]
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C(C)N=[N+]=[N-])cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc(C(C)N)cnc3Nc3cnc(OC)c(F)c3)n2)cc1
Reaction time: 16 h
Yield: 83.4 %

Procedure:
To a 50 mL round-bottomed flask was added 4-(5-(1-azidoethyl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1 g, 1.571 mmol) in THF (10 mL). Under nitrogen protection, 10% Pd—C (0.5 g) was mixed, the suspension was stirred under a hydrogen balloon for 16 h. The mixture was filtered through a Celite® (diatomaceous earth) pad, washed the pad with EtOAc, the filtrate was concentrated in vacuum to provide 4-(5-(1-aminoethyl)-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.8 g, 83% yield) as a black solid. m/z (ESI positive ion) m/z: 611 (M+H)+.
Reaction SMILES: [C:1]1([C:7]2[C:12]([N+:13]([O-])=O)=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.O>CCO.CC(O)=O.CCOC(C)=O.[Fe]>[C:1]1([C:7]2[C:12]([NH2:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: O=[N+]([O-])c1cccnc1C1=CCCCC1
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: Nc1cccnc1C1=CCCCC1
Temperature: 75 °C
Yield: 86.2 %

Procedure:
A solution of 497.0 mg (2.43 mmol) of 2-cyclohex-1-enyl-3-nitro-pyridine (as prepared in the previous step) in EtOH (10 mL) and water (5 mL) was treated with AcOH (6 drops) and 679 mg (12.2 mmol) of Fe powder, and heated to 75° C. for 19 h. The mixture was diluted with EtOAc (30 mL) and washed with water (1×20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to afford 365 mg (86%) of the title compound as a pale yellow solid: Mass spectrum (ESI, m/z): Calcd. for C11H14N2, 175.1 (M+H), found 175.2.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].F[C:12]1[C:17]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[N:19]=2)=[CH:16][C:15]([C@H:44]([N:46]2[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:47]2)[CH3:45])=[CH:14][N:13]=1.[Cl:56][C:57]1[N:62]=[CH:61][C:60]([NH2:63])=[CH:59][CH:58]=1>C1COCC1>[Cl:56][C:57]1[N:62]=[CH:61][C:60]([NH:63][C:12]2[C:17]([C:18]3[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]4[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=4)[CH2:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[N:19]=3)=[CH:16][C:15]([C@H:44]([N:46]3[CH2:47][CH2:48][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:50][CH2:51]3)[CH3:45])=[CH:14][N:13]=2)=[CH:59][CH:58]=1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(S(C)(=O)=O)CC4)cnc3F)n2)cc1
Reactant: Nc1ccc(Cl)nc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2nc(C)nc(-c3cc([C@@H](C)N4CCN(S(C)(=O)=O)CC4)cnc3Nc3ccc(Cl)nc3)n2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 75.7 %

Procedure:
Sodium bis(trimethylsilyl)amide (1.0M in THF) (Aldrich, St. Louis, Mo.; 0.777 mL, 0.777 mmol) was added to a mixture of (R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 146, Step 6) 141.2 mg, 0.222 mmol) and 6-chloropyridin-3-amine (Aldrich, St. Louis, Mo.; 57.1 mg, 0.444 mmol) in THF (2.5 mL) at 0° C., and the resulting dark brown solution was stirred at 0° C. for 30 min. Excess sodium bis(trimethylsilyl)amide was then quenched with saturated aqueous NH4Cl (2 mL), and the reaction mixture was partitioned between EtOAc (50 mL) and saturated aqueous NH4Cl (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic extracts were sequentially washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0 to 100% EtOAc/hexanes) furnished (R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (125.0 mg, 0.168 mmol, 76% yield) as a yellow-brown oil. 1H NMR (400 MHz, CDCl3) δ 12.12 (s, 1H), 8.74 (d, J=2.2 Hz, 1H), 8.50 (s, 1H), 8.28 (s, 1H), 8.18-8.24 (m, 1H), 7.21 (td, J=5.7, 2.4 Hz, 5H), 6.89 (s, 2H), 6.85 (d, J=8.6 Hz, 2H), 4.74-4.93 (m, 4H), 3.81 (s, 3H), 3.79 (s, 3H), 3.52-3.59 (m, 1H), 3.15 (br. s., 4H), 2.67 (s, 3H), 2.60 (s, 3H), 2.47-2.58 (m, 4H), 1.38 (d, J=6.7 Hz, 3H). m/z (ESI, +ve) 744.2 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:33])[C@H:4]([CH2:29][CH2:30][S:31][CH3:32])[NH:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:9][C:8]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.N>>[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH2:15][O:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([C:6]([NH:5][C@H:4]([C:3]([OH:33])=[O:2])[CH2:29][CH2:30][S:31][CH3:32])=[O:28])=[C:8]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:9]=2)[CH:17]=1
Reactant: COC(=O)[C@H](CCSC)NC(=O)c1ccc(COCc2cccnc2)cc1-c1ccccc1
Agent: N
Product: CSCC[C@H](NC(=O)c1ccc(COCc2cccnc2)cc1-c1ccccc1)C(=O)O

Procedure:
The desired compound was prepared by saponification of [4-(3-pyridylmethyloxymethyl)-2-phenylbenzoyl]methionine methyl ester, prepared as in Example 183C using the procedure of Example 183B; 1H NMR (CDCl3, 300 MHz) δ 1.66-2.17 (4H, m), 2.02 (3H, s), 4.62 (1H, m), 4.76 (2H, s), 4.78 (2H, s), 6.31 (1H, d, J=6.3 Hz), 7.23-7.44 (7H, m), 7.71 (1H, d, J=7.8 Hz), 7.86 (1H, m), 8.34 (1H, m), 8.65 (1H, m), 8.72 (1H, m); MS (DCI/NH3) m/e 451 (M+H)+. Anal calcd for C25H26N2O4S.1.45HCl: C, 59.65; H, 5.50; N, 5.56. Found: C, 59.80; H, 5.11; N, 5.26.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:13][CH2:12][NH:11][C:10]2=[O:14])=[CH:5][CH:4]=1.CC(C)([O-])C.[K+].Br[CH2:24][C:25]([O:27]CC)=[O:26].[OH-].[Li+]>O1CCCC1>[O:14]=[C:10]1[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=2)[CH2:13][CH2:12][N:11]1[CH2:24][C:25]([OH:27])=[O:26]
Reactant: O=C1NCCC1c1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)CBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(O)CN1CCC(c2ccc(C(F)(F)F)cc2)C1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of the product from Example 266C (3.1 g, 13.00 mmol) in tetrahydrofuran (40 mL) was added potassium tert-butoxide (1.0 Min tetrahydrofuran, 15.7 mL, 15.7 mmol) via syringe under nitrogen, and the resultant mixture was stirred for 15 minutes. Then ethyl 2-bromoacetate (1.59 mL, 14.4 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and then diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting residue was dissolved in ethanol/water (4:1, 60 mL) and treated with lithium hydroxide (1.254 g, 52.4 mmol). After stirring for 2 hours at reflux, the reaction was concentrated, diluted with ice/water (150 mL) and neutralized with 2 N HCl. The precipitate formed was filtered, washed with water (50 mL), and dried under vacuum to obtain the title compound. MS (DCI+) m/z 288.1 (M+H)+.
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:25]C)[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[C:8]([NH2:27])[N:7]=1)[CH2:2][CH2:3][CH3:4].I[CH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>>[NH2:27][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:25])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]1[CH2:20][CH2:21][N:22]([CH:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:23][CH2:24]1
Reactant: IC1CCCC1
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCCCC3CCNCC3)c2n1
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCCCC3CCN(C4CCCC4)CC3)c2n1

Procedure:
Prepared similarly to Example 80 from 2-(butyloxy)-8-(methyloxy)-9-[4-(4-piperidinyl)butyl]-9H-purin-6-amine and iodocyclopentane.
Reaction SMILES: [CH3:1][NH:2][CH3:3].C(O)C.[CH3:7][Si:8]([CH3:23])([CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH2:9][CH2:10][CH2:11][O:12][CH2:13][CH:14]1[CH2:16][O:15]1>O>[CH3:1][N:2]([CH3:3])[CH2:16][CH:14]([OH:15])[CH2:13][O:12][CH2:11][CH2:10][CH2:9][Si:8]([CH3:23])([CH3:7])[CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20]
Reactant: C[Si](C)(C)CC[Si](C)(C)CCCOCC1CO1
Reactant: CNC
Solvent: O
Solvent: CCO
Product: CN(C)CC(O)COCCC[Si](C)(C)CC[Si](C)(C)C
Temperature: 50 °C

Procedure:
Aqueous dimethylamine (25%; 10 g, dimethyl amine 55 mMol) and 40 mL of ethanol were charged to a 100 mL RB flask equipped with a magnetic stirrer. The mixture was stirred and heated to 50° C. 2-{3-[Dimethyl-(2-trimethylsilanyl-ethyl)-silanyl]-propoxymethyl}-oxirane 8 (2 g; 7.28 mMol) mixed with 10 g ethanol was placed in an addition funnel and added dropwise to the flask. The mixture was stirred and maintained at 50° C. for an additional 8 hours. Ethanol, water and excess dimethyl amine were stripped off on the rotovap. The mixture was distilled under vacuum to remove impurities.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH3:13])[CH3:12])=[CH:7][CH:6]=1)=[O:4].[CH3:14][C:15]1[CH:16]=[C:17]([OH:23])[CH:18]=[C:19]([CH3:22])[C:20]=1[CH3:21].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[CH3:14][C:15]1[CH:16]=[C:17]([CH:18]=[C:19]([CH3:22])[C:20]=1[CH3:21])[O:23][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH3:13])[CH3:12])=[CH:7][CH:6]=1)=[O:4]
Reactant: Cc1cc(O)cc(C)c1C
Reactant: CC(C)c1ccc(C(=O)CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: Cc1cc(OCC(=O)c2ccc(C(C)C)cc2)cc(C)c1C
Yield: 96 %

Procedure:
2-Bromo-1-(4-isopropylphenyl)ethanone obtained in Reference Example 164 (20 g, 82.9 mmol) and 3,4,5-trimethylphenol (10.3 g, 75.4 mmol) were added to a solution of potassium carbonate (12.5 g, 90.5 mmol) in acetonitrile solution (200 mL), and mixture was stirred with heating under reflux for 6 hours. The reaction solution was ice-cooled, was poured into cold water, which was extracted with ethyl acetate. The extract was washed with a saturated brine, and then was dried over sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:10). The obtained oily matter was crystallized from hexane-ethyl acetate to obtain 21.5 g (yield 96%) of the title compound. Melting point: 96-98° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:15][CH3:16])[CH:5]=[CH:6][C:7]=1[NH:8][C:9](=O)[C:10]([F:13])([F:12])[F:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N-:36]=[N+:37]=[N-:38].[Na+]>C(Cl)(Cl)(Cl)Cl.CN(C)C=O.O>[Br:1][C:2]1[CH:3]=[C:4]([O:15][CH3:16])[CH:5]=[CH:6][C:7]=1[N:8]1[C:9]([C:10]([F:13])([F:12])[F:11])=[N:38][N:37]=[N:36]1
Reactant: [N-]=[N+]=[N-]
Reactant: COc1ccc(NC(=O)C(F)(F)F)c(Br)c1
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Solvent: CN(C)C=O
Product: COc1ccc(-n2nnnc2C(F)(F)F)c(Br)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 54.2 %

Procedure:
3-Bromo-4-(trifluoroacetamido)anisole (4.7 g, 0.16 mol) was suspended in carbon tetrachloride (60 ml) and triphenylphosphine (6.2 g, 0.024 mol) was added. The reaction was heated at reflux for 12 hours. The reaction was allowed to cool to ambient temperature, and filtered. The solid was washed thoroughly with ethyl acetate:diethyl ether (1:1, 200 ml:200 ml). The filtrate was concentrated in vacuo to afford a red solid. This solid was dissolved in N,N-dimethylformamide (10 ml) and this solution was added to sodium azide (1.55 g, 0.024 mol). The reaction was stirred at ambient temperature for 12 hours, and diluted with water (100 ml). The product was extracted into ethyl acetate (3×50 ml) and the combined organics were washed with brine (100 ml), dried over magnesium sulphate and the solvent removed in vacuo. Chromatography on silica eluting with 10% ethyl acetate in hexane afforded the title compound as a pale orange solid (4.2 g, 66%), m/z (ES+) 323 (M+ +H, 100%). 1H NMR (250 MHz, CDCl3) δ 3.92 (3H, s), 7.03 (1H, dd J 2.7 Hz, J 8.8 Hz), 7.30 (1H, d, J 2.7 Hz), 7.34 (1H, d, J 8.8 Hz).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:40])[CH2:4][N:5]([S:29](=[O:39])(=[O:38])[NH:30]C(OC(C)(C)C)=O)[C:6]1[CH:11]=[CH:10][C:9]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:8][C:7]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:40])[CH2:4][N:5]([S:29](=[O:38])(=[O:39])[NH2:30])[C:6]1[CH:11]=[CH:10][C:9]([S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)(=[O:14])=[O:13])=[CH:8][C:7]=1[O:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: COC(=O)CN(c1ccc(S(=O)(=O)c2ccccc2)cc1OCc1ccccc1)S(=O)(=O)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)CN(c1ccc(S(=O)(=O)c2ccccc2)cc1OCc1ccccc1)S(N)(=O)=O

Procedure:
A solution of N-(t-butoxycarbonylsulfamoyl)-N-(4-benzenesulfonyl-2-benzyloxyphenyl)glycine methyl ester (620 mg, 1.05 mmol) in 10 mL TFA/CH2Cl2 (1:1) is stirred at RT for 30 min. The solvent is removed under reduced pressure and the residue is redissolved in CH2Cl2 and restripped (4×). The residual oil is chromatographed on a Biotage 40M column using CH2Cl2/EtOAc (90:10) as eluent to afford the title compound: 1H NMR (CDCl3) δ 7.87 (m, 2H), 7.72 (d, J=8.2 Hz, 1H), 7.60 (m, 2H), 7.50 (m, 3H), 7.41 (m, 5H), 5.18 (s, 2H), 4.92 (br s, 2H), 4.32 (s, 2H), 3.87 (s, 3H); MS (M−1)−=489.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[N:5]([O:10][CH3:11])[C:4]([CH3:13])([CH3:12])[CH2:3]1.[H-].[Na+].[N:16]1[C:23](Cl)=[N:22][C:20](Cl)=[N:19][C:17]=1Cl>O1CCOCC1>[CH3:11][O:10][N:5]1[C:6]([CH3:8])([CH3:9])[CH2:7][CH:2]([O:1][C:17]2[N:19]=[C:20]([O:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH3:11])[C:4]([CH3:13])([CH3:12])[CH2:3]3)[N:22]=[C:23]([O:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH3:11])[C:4]([CH3:13])([CH3:12])[CH2:3]3)[N:16]=2)[CH2:3][C:4]1([CH3:13])[CH3:12]
Reactant: CON1C(C)(C)CC(O)CC1(C)C
Reactant: Clc1nc(Cl)nc(Cl)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CON1C(C)(C)CC(Oc2nc(OC3CC(C)(C)N(OC)C(C)(C)C3)nc(OC3CC(C)(C)N(OC)C(C)(C)C3)n2)CC1(C)C

Procedure:
The title compound is prepared by the reaction of 4-hydroxy-1-methoxy-2,2,6,6-tetramethylpiperidine, sodium hydride, and cyanuric chloride in 1,4-dioxane solvent.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].Cl>C1(C)C=CC=CC=1.O>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][O:10][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:17]
Reactant: OCc1ccccc1
Reactant: CCOC(=O)CBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)COCc1ccccc1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a suspension of sodium hydride (44.2 g, 60 percent in oil, 1.1 mol) in dry toluene (800 mL) was added dropwise a solution of benzyl alcohol (108 mL, 1.0 mol, in 200 mL of toluene) at 0° C. under nitrogen over 30 min. The resulting mixture was stirred for 3.5 h at rt. The reaction was then cooled with ice water, to which a solution of ethyl bromoacetate (167.6 g, 1.0 mmol, in 200 mL of toluene) was added in 30 min and the resulting mixture was stirred for additional 25 min at 0° C. The reaction mixture was then poured into a mixed solution of 800 mL of cold water and 10 mL of cone HCl, followed by extraction with toluene. The organic layer was washed with saturated aq NaCl and dried over anhydrous MgSO4. Filtration, evaporation, and purification by flash chromatography provided ethyl(benzyloxy)acetate. (98 g, 50.5%). 1H-NMR δ (400 MHz, CDC3): 7.38-7.30 (m, 5H), 4.63 (s, 2H), 4.22 (q, J=7.2 Hz, 2H), 4.09 (s, 2H), 1.28 (t, J=7.2 Hz, 3H).
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].[NH2:6][C:7]1[CH:16]=[CH:15][C:14]([C:17]([C:19]2[N:27]3[C:22]([CH:23]=[CH:24][CH:25]=[CH:26]3)=[C:21]([NH:28][C:29](=[O:40])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH2:37][CH2:38][OH:39])[CH:31]=3)[C:20]=2[CH3:41])=[O:18])=[CH:13][C:8]=1[C:9]([O:11][CH3:12])=[O:10].O>N1C=CC=CC=1>[NH2:6][C:7]1[CH:16]=[CH:15][C:14]([C:17]([C:19]2[N:27]3[C:22]([CH:23]=[CH:24][CH:25]=[CH:26]3)=[C:21]([NH:28][C:29](=[O:40])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH2:37][CH2:38][O:39][S:1]([CH3:4])(=[O:3])=[O:2])[CH:31]=3)[C:20]=2[CH3:41])=[O:18])=[CH:13][C:8]=1[C:9]([O:11][CH3:12])=[O:10]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1cc(C(=O)c2c(C)c(NC(=O)c3cccc(OCCO)c3)c3ccccn23)ccc1N
Solvent: O
Solvent: c1ccncc1
Product: COC(=O)c1cc(C(=O)c2c(C)c(NC(=O)c3cccc(OCCOS(C)(=O)=O)c3)c3ccccn23)ccc1N
Temperature: -20 °C
Reaction time: 2 h
Yield: 68.7 %

Procedure:
59 μl (0.77 mmol) of mesyl chloride are added to the solution of 0.34 g (0.69 mmol) of methyl 2-amino-5-[(1-{[3-(2-hydroxyethoxy)benzoyl]amino}-2-methylindolizin-3-yl)carbonyl]benzoate in 9 ml of pyridine at −20° C. under nitrogen. The reaction mixture is stirred for 2 hours at −20° C. and is then run into 100 ml of water. The precipitate obtained is filtered, washed thoroughly with water and dried under vacuum, to give 268 mg (70%) of a yellow powder.
Reaction SMILES: Cl[CH2:2][Si:3]([CH3:10])([CH3:9])[C:4]1[O:5][CH:6]=[CH:7][CH:8]=1.[I-:11].[Na+]>CC(=O)CC>[I:11][CH2:2][Si:3]([CH3:10])([CH3:9])[C:4]1[O:5][CH:6]=[CH:7][CH:8]=1
Reactant: C[Si](C)(CCl)c1ccco1
Reactant: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: C[Si](C)(CI)c1ccco1
Temperature: 25 °C

Procedure:
Reflux the distilled chloromethyl(dimethyl)furylsilane (20 g, 114.5 mmol) in butanone (200 mL) containing sodium iodide (17.35 g, 116 mmol) for 4 h. GC/MS shows that the reaction is complete. Cool to room temperature and filter sodium chloride. Evaporate and redissolve in ethyl acetate. Wash with water (3×), then wash with saturated sodium chloride (3'). Dry and evaporate to obtain a yellow liquid. Distill the yellow liquid in a kugelrohr and collect iodomethyl(dimethyl)furylsilane between 90° C.--95° C. as a clear pink oil (26.8 g).
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]([CH3:17])[CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:5]=[N:4][C:3]=1[C:18]([NH2:20])=[O:19].[N:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28](OC)=O)=[CH:23][CH:22]=1>>[CH3:17][CH:7]([N:6]1[C:2]2[N:1]=[C:28]([CH2:27][C:24]3[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=3)[NH:20][C:18](=[O:19])[C:3]=2[N:4]=[N:5]1)[CH2:8][CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COC(=O)Cc1ccncc1
Reactant: CC(CCCc1ccccc1)n1nnc(C(N)=O)c1N
Product: CC(CCCc1ccccc1)n1nnc2c(=O)[nH]c(Cc3ccncc3)nc21

Procedure:
Analogously to the procedure of Example 1, the title compound is prepared from 1.0 g (3.8 mmol) of 5-amino-1-(1-methyl-4-phenyl-butyl)-1H-[1,2,3]triazole-4-carboxamide and 2.21 g (14.6 mmol) of methyl 4-pyridylacetate.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:14]2[NH:13][C:12]([CH3:15])=[N:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:5])[CH3:2].[Cl:16][C:17]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:18]=1[CH2:19]Cl.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>O.C(Cl)(Cl)Cl.CN(C)C=O>[Cl:16][C:17]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:18]=1[CH2:19][N:11]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:14]=2[N:13]=[C:12]1[CH3:15]
Reactant: ClCc1ccc(Cl)cc1Cl
Reactant: CCOC(=O)c1cccc2nc(C)[nH]c12
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1cccc2c1nc(C)n2Cc1ccc(Cl)cc1Cl
Temperature: 80 °C
Reaction time: 16 h
Yield: 25.5 %

Procedure:
A mixture of 4-ethoxycarbonyl-2-methylbenzimidazole (1.61 g), 2,4-dichlorobenzyl chloride (3.08 g), potassium iodide (1.51 g), potassium carbonate (1.05 g) and N,N-dimethylformamide (4 ml) is stirred for 16 hours at 80° C. Chloroform and water are added and extraction is performed. The chloroform layer is washed with water, dried, and concentrated. The residue is purified using silica gel column chromatography (eluate: hexane/ethyl acetate=2/8) and thus, 1-(2,4-dichlorobenzyl)-4-ethoxycarbonyl-2-methylbenzimidazole (0.730 g) is obtained. 1H-NMR (CDCl3, δ): 1.47 (3H, t, J=7.1 Hz), 2.63 (3H, s), 4.52 (2H, q, J=7.1 Hz), 5.39 (2H, s), 6.30 (1H, d, J=7.06 (1H, dd, J=2.1 and 8.4 Hz), 7.25 (1H, t, J=7.9 Hz), 7.32 (1H, dd, J=1.0 and 7.9 Hz), 7.48 (1H, d, J=2.0 Hz), 7.93 (1H, dd, J=1.0 and 7.7 Hz).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:15]=2[CH2:24][NH:25][CH2:26][CH3:27])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].Cl[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)=[O:31]>>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:21])[F:22])[CH:17]=[CH:16][C:15]=2[CH2:24][N:25]([CH2:26][CH3:27])[C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[O:31])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCNCc1ccc(C(F)(F)F)cc1-c1cc(CC(=O)OCC)ccc1OC
Reactant: O=C(Cl)OCc1ccc(F)cc1
Product: CCOC(=O)Cc1ccc(OC)c(-c2cc(C(F)(F)F)ccc2CN(CC)C(=O)OCc2ccc(F)cc2)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 6, using the following starting materials: (2′-ethylaminomethyl-6-methoxy-5′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester and 4-fluorobenzyl chloroformate.
Reaction SMILES: [F:1][C:2]1[C:3]([N+:15]([O-])=O)=[C:4]([CH:12]=[CH:13][CH:14]=1)[NH:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][CH3:11]>CO.[C].[Pd]>[F:1][C:2]1[C:3]([NH2:15])=[C:4]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][CH3:11])[CH:12]=[CH:13][CH:14]=1
Reactant: COCCCCNc1cccc(F)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: COCCCCNc1cccc(F)c1N
Reaction time: 3 h
Yield: 100 %

Procedure:
3-Fluoro-N-(4-methoxybutyl)-2-nitroaniline (2.90 g) was dissolved in methanol (50 ml), palladium-carbon (5%, 230 mg) was added, and the mixture was stirred for 3 hr under a hydrogen atmosphere. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure to give the object product (2.54 g).