Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]2)=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:37].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][CH:19]([C:16]2[CH:17]=[CH:18][C:13]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][C:2]=3[Cl:1])[NH:8][CH:7]=[C:6]4[C:11]([OH:37])=[O:12])=[CH:14][CH:15]=2)[CH2:20]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(-c3cc4c(C=O)c[nH]c4cc3Cl)cc2)C1
Reactant: [O-][Cl+][O-]
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Solvent: CC(C)(C)O
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(-c3cc4c(C(=O)O)c[nH]c4cc3Cl)cc2)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 36.3 %

Procedure:
To a solution of tert-butyl 3-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate (43 mg, 0.1 mmol) in acetonitrile (1.2 mL) and tert-butanol (1.2 mL) was added 2-methyl-2-butene (1.2 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (100 mg, 1.1 mmol) and sodium phosphate monobasic dihydrate (234 mg, 1.5 mmol) in water (0.6 mL). After the resulting mixture was stirred for 2 h at room temperature, additional sodium chlorite (134 mg, 1.47 mmol) and sodium phosphate monobasic dihydrate (312 mg, 2.0 mmol) in H2O (0.6 mL) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the aqueous residue was extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DMSO and purified via pre-HPLC to give 5-{4-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]phenyl}-6-chloro-1H-indole-3-carboxylic acid (16 mg, 36%) as a white solid. MS (ES+) 463.1 (M+Na)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:17]([C:19]1[N:23]([CH3:24])[N:22]=[CH:21][C:20]=1I)=[O:18].NC1C=CC(CC2C=CC(Cl)=CC=2)=CC=1C(C1N(C)N=CC=1I)=O>>[CH3:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]3[NH:1][C:20]4[CH:21]=[N:22][N:23]([CH3:24])[C:19]=4[C:17](=[O:18])[C:3]=3[CH:4]=2)=[CH:10][CH:11]=1
Reactant: COc1ccc(Cc2ccc(N)c(C(=O)c3c(I)cnn3C)c2)cc1
Agent: Cn1ncc(I)c1C(=O)c1cc(Cc2ccc(Cl)cc2)ccc1N
Product: COc1ccc(Cc2ccc3[nH]c4cnn(C)c4c(=O)c3c2)cc1

Procedure:
The title compound was prepared according to the procedure of step 6 in EXAMPLE 13 using [2-amino-5-(4-methoxybenzyl)phenyl](4-iodo-1-methyl-1H-pyrazol-5-yl)methanone (EXAMPLE 16, step 4), instead of [2-amino-5-(4-chlorobenzyl)phenyl](4-iodo-1-methyl-1H-pyrazol-5-yl)methanone.
Reaction SMILES: C(OC([N:8]1[C:16]2[CH:15]=[C:14]([N:17]3[CH2:21][CH2:20][CH2:19][C:18]3=[O:22])[N:13]=[CH:12][C:11]=2[C:10]([CH3:24])([CH3:23])[CH2:9]1)=O)(C)(C)C.[ClH:25]>>[ClH:25].[CH3:23][C:10]1([CH3:24])[C:11]2[CH:12]=[N:13][C:14]([N:17]3[CH2:21][CH2:20][CH2:19][C:18]3=[O:22])=[CH:15][C:16]=2[NH:8][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CC(C)(C)c2cnc(N3CCCC3=O)cc21
Agent: Cl
Product: CC1(C)CNc2cc(N3CCCC3=O)ncc21
Reaction time: 4 h

Procedure:
3,3-Dimethyl-6-(2-oxo-pyrrolidin-1-yl)-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (100 mg) was treated with HCl (saturated solution in EtOAc) and stirred for 4 h. The mixture was then evaporated to dryness in vacuo to give the title compound as a pale yellow solid. MS: [M+H]+=232.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[CH:13]=2)[CH:8]=[CH:7]1)[CH3:2].[F:17][C:18]([F:39])([F:38])[O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([CH2:36]O)=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:36][C:29]3[C:30]([C:32]([F:34])([F:33])[F:35])=[N:31][C:26]([C:23]4[CH:22]=[CH:21][C:20]([O:19][C:18]([F:39])([F:17])[F:38])=[CH:25][CH:24]=4)=[CH:27][CH:28]=3)[CH:13]=2)[CH:8]=[CH:7]1)[CH3:2]
Reactant: CCOC(=O)Cn1ccc2ccc(O)cc21
Reactant: OCc1ccc(-c2ccc(OC(F)(F)F)cc2)nc1C(F)(F)F
Agent: CCCCP(CCCC)CCCC
Agent: CN(C)C(=O)N=NC(=O)N(C)C
Solvent: C1CCOC1
Product: CCOC(=O)Cn1ccc2ccc(OCc3ccc(-c4ccc(OC(F)(F)F)cc4)nc3C(F)(F)F)cc21

Procedure:
In analogy to the procedure described in example 5 f], (6-hydroxy-indol-1-yl)-acetic acid ethyl ester (example 6 b]) was reacted with [6-(4-trifluoromethoxy-phenyl)-2-trifluoromethyl-pyridin-3-yl]-methanol in the presence of tributylphosphine and N,N,N′,N′-tetramethyl azodicarboxamide in tetrahydrofuran to yield the title compound as colorless crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5](OS(C(F)(F)F)(=O)=O)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.[NH2:19][C:20]1[CH:21]=[C:22]([SH:26])[CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:26][C:22]2[CH:21]=[C:20]([NH2:19])[CH:25]=[CH:24][CH:23]=2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1
Reactant: Nc1cccc(S)c1
Reactant: Cc1ccc(OS(=O)(=O)C(F)(F)F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(Sc2cccc(N)c2)c([N+](=O)[O-])c1
Temperature: 10 °C

Procedure:
The product from Example 4a (1.00 g, 3.51 mmol) and 3-Amino-benzenethiol (658 mg, 5.26 mmol) were dissolved in DMF to which was added K2CO3 (848 mg, 6.14 mmol). The reaction mixture was then heated to 10° C. for 16 hrs. Reaction mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate providing the title compound (650 mg, 71%).
Reaction SMILES: [CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]([O:24]C(C)(C)C)=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7]2[CH:29]=[C:30]([N:34]3[CH2:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:35]3=[O:43])[CH:31]=[C:32]([Cl:33])[C:6]=2[N:5]=1)[CH2:2][CH3:3].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7]2[CH:29]=[C:30]([N:34]3[CH2:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:35]3=[O:43])[CH:31]=[C:32]([Cl:33])[C:6]=2[N:5]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc2c(Cl)cc(N3Cc4ccccc4C3=O)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCc1nc2c(Cl)cc(N3Cc4ccccc4C3=O)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared analogously to Example 1 from tert.butyl 4'-[(2-n-propyl-4-chloro-6-(1-oxo-isoindolin-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH3:11][C:12]([CH3:43])([CH2:41]C)[CH2:13][C:14]1[N:15]=[C:16]([C:25](=[O:40])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][N:34]=3)=[CH:29][CH:28]=2)[N:17]([S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[CH:18]=1>O1CCCC1>[CH3:11][C:12]([CH3:43])([CH3:41])[CH2:13][C:14]1[N:15]=[C:16]([CH:25]([OH:40])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][N:34]=3)=[CH:29][CH:28]=2)[N:17]([S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[CH:18]=1
Reactant: CCC(C)(C)Cc1cn(S(=O)(=O)N(C)C)c(C(=O)Cc2ccc(-c3ccc(F)cn3)cc2)n1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: C1CCOC1
Product: CN(C)S(=O)(=O)n1cc(CC(C)(C)C)nc1C(O)Cc1ccc(-c2ccc(F)cn2)cc1
Temperature: 0 °C

Procedure:
Diisobutylaluminum hydride (1 M in methylene chloride) (0.91 mL, 0.91 mmol) was added to a −78° C. solution of 4-(2,2-dimethylbutyl)-2-{[4-(5-fluoropyridin-2-yl)phenyl]acetyl}-N,N-dimethyl-1H-imidazole-1-sulfonamide (for synthesis see example 15) (200 mg, 0.45 mmol) in tetrahydrofuran (5 mL). The reaction was allowed to warm to 0° C., quenched with saturated aqueous sodium potassium tartrate and stirred vigorously at ambient temperature until layers separated. The aqueous phase was extracted with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo to afford 4-(2,2-dimethylpropyl)-2-{2-[4-(5-fluoropyridin-2-yl)phenyl]-1-hydroxyethyl}-N,N-dimethyl-1H-imidazole-1-sulfonamide which was used in the subsequent step without further purification.
Reaction SMILES: [CH3:1][S:2][CH:3]([C:8]1[S:9][CH:10]=[CH:11][CH:12]=1)[C:4]([O:6][CH3:7])=[O:5].[H-].[Na+].[CH3:15]I.[Cl-].[NH4+]>CS(C)=O>[CH3:1][S:2][C:3]([C:8]1[S:9][CH:10]=[CH:11][CH:12]=1)([CH3:15])[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)C(SC)c1cccs1
Reactant: CI
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CS(C)=O
Product: COC(=O)C(C)(SC)c1cccs1
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 91 %

Procedure:
Methyl α-methylthio(2-thienyl)acetate (1.446 g) was dissolved in 8 ml of anhydrous dimethyl sulfoxide, and while cooling, at 20° C., 290 mg (65% content) of sodium hydride was added. When the mixture was stirred for 30 minutes, the reaction solution turned bluish violet. Methyl iodide (0.60 ml) was added to it over the course of 3 minutes, and the mixture was stirred at 20° C. for 1.5 hours, whereupon the bluish violet color gradually vanished. An aqueous solution of ammonium chloride (0.40 g/30 ml) was added, and the mixture was extracted three times with 20 ml of diethyl ether. The organic layer was washed three times with 10 ml of water, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was chromatographed on a silica gel column using benzene as an eluent to afford 1.410 g of methyl α-methylthio-α-(2-thienyl)propionate in a yield of 91% as a colorless liquid.
Reaction SMILES: [N:1]([CH:4]1[CH2:7][N:6]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)=[O:9])[CH2:5]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C(#N)C>[NH2:1][CH:4]1[CH2:7][N:6]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)=[O:9])[CH2:5]1
Reactant: [N-]=[N+]=NC1CN(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CC#N
Product: NC1CN(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Temperature: 70 °C
Reaction time: 2 h
Yield: 95.9 %

Procedure:
To a solution of 3-azido-1-(p-nitrobenzyloxycarbonyl)azetidine (2.15 g, 7.76 mmol) (obtained as described in Reference Example 54(3)) in acetonitrile (65 ml) was added triphenylphosphine (2.14 g, 8.14 mmol), and the mixture was stirred in an oil bath (70° C.) for 2 hours. After checking the disappearance of the raw materials, sodium sulfate decahydrate (2.62 g, 8.14 mmol) was added thereto and then the reaction mixture was stirred for 3 hours. After checking the completion of the reaction, the reaction mixture was filtered and partitioned between methylene chloride and 0.1M aqueous hydrogen chloride solution. To the obtained aqueous layer were added methylene chloride and sodium hydrogencarbonate, and the aqueous layer was extracted with methylene chloride. The obtained organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dried under reduced pressure to give 3-amino-1-(p-nitrobenzyloxycarbonyl)-azetidine (1.87 g, yield 96%) as pale yellow crystals.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15]Cl)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])[C:6]=2[CH:24]=1.[I-].[K+].[CH2:27]([NH2:30])[CH:28]=[CH2:29]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][NH:30][CH2:27][CH:28]=[CH2:29])=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])[C:6]=2[CH:24]=1
Reactant: Fc1ccc2c(c1)C(c1ccccc1Cl)=NCc1nnc(CCl)n1-2
Reactant: C=CCN
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=CCNCc1nnc2n1-c1ccc(F)cc1C(c1ccccc1Cl)=NC2

Procedure:
In the manner given in Example 31, 8-fluoro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine, potassium iodide and allylamine in tetrahydrofuran are reacted to give 8-fluoro-1-[(allyl-amino)methyl]-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:21]=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:7]=1)=[O:4].[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(O)C>[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:2][C:3]([NH:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]3[CH:21]=[N:20][C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]=3)[CH:7]=2)=[O:4])[CH2:25][CH2:24]1
Reactant: CN1CCNCC1
Reactant: O=C(CCl)Nc1cccc(-c2cnc3ccccc3n2)c1
Solvent: CCO
Product: CN1CCN(CC(=O)Nc2cccc(-c3cnc4ccccc4n3)c2)CC1
Yield: 34.6 %

Procedure:
A solution of 2-chloro-N-(3-quinoxalin-2-ylphenyl)acetamide (100 mg, 0.336 mmol) and N-methylpiperazine (79 μL, 0.706 mmol) in ethanol (5 mL) was heated at 100° C. for 18 hrs. The solvent was evaporated and the oily residue was submitted to preparative LCMS to afford 2-(4-methylpiperazin-1-yl)-N-[3-(quinoxalin-2-yl)phenyl]acetamide (42 mg, 34%). LCMS calculated for C21H23N5O (M+H): 362.19. found 362.16. 1H-NMR (DMSO-d6, 400 Mhz) δH: 9.90 (1H, br. s), 9.51 (1H, s), 8.54 (1H, m), 8.19-8.12 (2H, m), 8.08 (1H, d, J=7 Hz), 7.94-7.82 (3H, m), 7.55 (1H, m), 3.18 (2H, s), 2.60-2.53 (4H, br), 2.48-2.40 (4H, br), 2.20 (3H, s).
Reaction SMILES: [O:1]=[C:2]1[C:7]2[C:8]([C:11]([OH:13])=[O:12])=[CH:9][O:10][C:6]=2[CH2:5][CH2:4][N:3]1[CH2:14][CH3:15].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:29][CH3:30]>CN(C)C=O.C(OCC)(=O)C>[O:1]=[C:2]1[C:7]2[C:8]([C:11]([O:13][CH2:29][CH3:30])=[O:12])=[CH:9][O:10][C:6]=2[CH2:5][CH2:4][N:3]1[CH2:14][CH3:15]
Reactant: CCI
Reactant: CCN1CCc2occ(C(=O)O)c2C1=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1coc2c1C(=O)N(CC)CC2
Temperature: 85 °C
Yield: 80.4 %

Procedure:
To a stirred solution of potassium hydroxide (3.79 g, 67.6 mmol) in methyl alcohol (15 mL) under Nitrogen at 0° C. was added dropwise a solution of N-ethyl-2,4-piperidione (9.54 g, 67.6 mmol) in methyl alcohol (20 mL). The mixture was stirred at 0° C. for 1 hour, then a solution of ethyl bromopyruvate (8.9 mL, 71 mmol) in methyl alcohol(50 mL) was added dropwise. After allowing the mixture to stir at ambient temperature for 2.5 hours, a 50% aqueous sodium hydroxide solution (10 mL) was added dropwise and stirring continued an additional 17 hours. After cooling in an ice water bath, the solution was acididfied and the methanol removed in vacuo. Ice water was added and the precipitate filtered and dried in vacuo to afford 4-oxo-5-ethyl-4,5,6,7-tetrahydrofuro[3,2-c]pyridine-3-carboxylic acid (3.91 g). More acid (1.15 g) was obtained via extraction of the aqueous filtrate 2X wtih ethyl acetate, drying over magnesium sulfate, filtration, concentrating in vacuo, and purification on Silica gel (5% methyl alcohol/dichloromethane). A stirring mixture of 4-oxo-5-ethyl-4,5,6,7-tetrahydrofuro[3,2-c]pyridine-3-carboxylic acid (4.94 g, 23.6 mmol), potassium carbonate (9.79 g, 70.8 mmol), cesium carbonate (770 mg, 2.4 mmol), and iodoethane (9.4 mL, 118 mmol) in N,N-dimethylformamide was heated at 85° C. for 15.5 hours. The reaction mixture was cooled and concentrated in vacuo. Ethyl acetate was added, the mixture filtered, the filtrate washed with water, and the organic layer dried over magnesium sulfate, filtered, and concentrated in vacuo to give the title compound (4.5 g).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([C:8]1[CH:16]=[C:15]2[C:11]([C:12]([CH3:21])([CH3:20])[CH2:13][N:14]2[C:17](=[O:19])[CH3:18])=[CH:10][C:9]=1[F:22])(=[O:7])=[O:6].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH:4]1([S:5]([C:8]2[CH:16]=[C:15]3[C:11]([C:12]([CH3:21])([CH3:20])[CH2:13][N:14]3[C:17](=[O:19])[CH3:18])=[CH:10][C:9]=2[F:22])(=[O:7])=[O:6])[CH2:2][CH2:3]1
Reactant: CC(=O)N1CC(C)(C)c2cc(F)c(S(=O)(=O)CCCCl)cc21
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: CC(=O)N1CC(C)(C)c2cc(F)c(S(=O)(=O)C3CC3)cc21
Reaction time: 0.17 h
Yield: 69.1 %

Procedure:
To a solution of 1-[6-(3-chloro-propane-1-sulfonyl)-5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl]-ethanone (502 mg, 1.44 mmol) at −78° C. in THF (30 mL) under N2, KHMDS (0.5 M in toluene, 3 mL) was slowly added. The solution was stirred for 10 minutes at the same temperature and then 30 minutes at ambient temperature then quenched with 1 M hydrochloric acid and extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated. The crude material was purified by SiO2 chromatography (EtOAc:Petrol 1:1) to give the title compound (310 mg). MS: [M+H]+=312.
Reaction SMILES: [Cl-].[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[C:5]([N+](C)(C)C)[N:4]=1.[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[OH:25])([O-:18])=[O:17].C(N(CC)CC)C>CS(C)=O.C(OCC)(=O)C>[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[C:5]([O:25][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N+:16]([O-:18])=[O:17])[N:4]=1
Reactant: C[N+](C)(C)c1nc(N)nc2nc[nH]c12
Reactant: O=[N+]([O-])c1ccccc1O
Agent: [Cl-]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Nc1nc(Oc2ccccc2[N+](=O)[O-])c2[nH]cnc2n1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
(2-Aminopurin-6-yl)trimethylammonium chloride (see Example 1, Step 1; 2.08 g, 9.10 mmol) and o-nitrophenol (2.45 g, 17.63 mmol) were suspended in dry dimethylsulfoxide (25 ml) and triethylamine (5.5 ml) was added. This mixture was stirred at 75° under a refux condenser under N2 for 51/2 hours, then left at room temperature overnight. The reaction mixture was poured into ice-lN HCl (300 ml) and the mixture was extracted with ethyl ether (3×300 ml). The aqueous layer was neutralized by careful addition of solid NaHCO3 and then was extracted with ethyl acetate (3×300 ml). The organic phase was dried over MgSO4, l filtered and evaporated to dryness to give a yellow solid. This material was dissolved in hot ethyl acetate purified by chromatography on silica gel, using ethanol-ethyl acetate (1:9) followed by ethanol-ethyl acetate (15:85) as developing solvents. Chromatographically and spectroscopically pure material was obtained in essentially quantitative yield.
Reaction SMILES: C(OC1([CH2:23][C:24]2[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26](OC)[CH:25]=2)C2C(=CC=C(C)C=2)N(CC)C1=O)(=O)C1C=CC=CC=1.[C:36]([O:44][CH:45]1[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH2:56][CH:57]([CH3:59])[CH3:58])[C:46]1=[O:60])(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.BrCC1C=CC(OC)=C(OC)C=1>>[C:36]([O:44][C:45]1([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:32][CH3:33])=[C:28]([O:30][CH3:31])[CH:29]=2)[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH2:56][CH:57]([CH3:58])[CH3:59])[C:46]1=[O:60])(=[O:43])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: Cc1ccc2c(c1)C(OC(=O)c1ccccc1)C(=O)N2CCC(C)C
Reactant: CCN1C(=O)C(Cc2cc(OC)c(OC)c(OC)c2)(OC(=O)c2ccccc2)c2cc(C)ccc21
Agent: COc1ccc(CBr)cc1OC
Product: COc1ccc(CC2(OC(=O)c3ccccc3)C(=O)N(CCC(C)C)c3ccc(C)cc32)cc1OC

Procedure:
This compound was made in an analogous fashion to 1-ethyl-5-methyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl benzoate using 1-isopentyl-5-methyl-2-oxoindolin-3-yl benzoate and 4-(bromomethyl)-1,2-dimethoxybenzene. 1H-NMR δ 8.06 (d, 2H), 7.57 (t, 1H), 7.43 (t, 2H), 7.08 (d, 1H), 6.93 (s, 1H), 6.67 (d, 1H), 6.60 (t, 2H), 6.36 (s, 1H), 3.82 (s, 3H), 3.64 (m, 4H), 3.46 (m, 2H), 3.26 (d, 1H), 2.27 (s, 3H), 1.50 (m, 1H), 1.26 (m, 2H) 0.92 (dd, 6H).
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9](O)=[O:10])[CH:6]=[C:5]([CH3:12])[N:4]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)C(C)C)C.Cl.Cl.[CH2:38]([O:40][C:41]([O:55][CH2:56][CH3:57])([C:44]1[CH:49]=[C:48]([CH3:50])[N:47]=[C:46]([CH2:51][CH:52]([CH3:54])[CH3:53])[CH:45]=1)[CH2:42][NH2:43])[CH3:39]>CN(C=O)C.CC(=O)OCC>[CH2:56]([O:55][C:41]([O:40][CH2:38][CH3:39])([C:44]1[CH:49]=[C:48]([CH3:50])[N:47]=[C:46]([CH2:51][CH:52]([CH3:53])[CH3:54])[CH:45]=1)[CH2:42][NH:43][C:9](=[O:10])[C:7]1[CH:6]=[C:5]([CH3:12])[N:4]=[C:3]([CH3:2])[CH:8]=1)[CH3:57]
Reactant: CCOC(CN)(OCC)c1cc(C)nc(CC(C)C)c1
Reactant: Cc1cc(C(=O)O)cc(C)n1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(CNC(=O)c1cc(C)nc(C)c1)(OCC)c1cc(C)nc(CC(C)C)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 126.5 %

Procedure:
To a solution of 2,6-dimethyl-4-pyridine carboxylic acid hydrochloride (159 mg, 0.849 mmol) in DMF (6 mL), EDC (244 mg, 1.27 mmol) and HOBt (172 mg, 1.27 mmol) is added. The mixture is stirred at rt for 15 min before ethyl diisopropylamine (439 mg, 3.37 mmol) and a solution of 2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethylamine dihydrochloride (300 mg, 0.849 mmol) in DMF (0.5 mL) is added. The mixture is stirred at rt for 4 h, diluted with EA (30 mL), and washed with sat. aq. NaHCO3 (15 mL) and brine (15 mL). The org. extract is dried over Na2SO4, filtered and concentrated. The crude product is purified on prep. TLC plates with DCM containing 5% of methanol to give N-[2,2-diethoxy-2-(2-isobutyl-6-methyl-pyridin-4-yl)-ethyl]-2,6-dimethyl-isonicotinamide (444 mg) as a colourless resin; LC-MS: tR=0.89*, [M+1]+=414.11; 1H NMR (CDCl3): δ 0.91 (d, J=6.5 Hz, 6H), 1.26 (t, J=6.8 Hz, 6H), 2.01-2.13 (m, 1H), 2.55 (s, 6H), 2.59 (s, 3H), 2.67 (d, J=7.3 Hz, 2H), 3.40-3.49 (m, 2H), 3.52-3.61 (m, 2H), 3.86 (d, J=5.5 Hz, 2H), 5.80 (s br, 1H), 7.04 (s, 2H), 7.10 (s, 1H), 7.16 (s, 1H).
Reaction SMILES: [CH2:1]([O:19][C:20]1[CH:21]=[C:22]([CH2:26][C:27]([OH:29])=O)[CH:23]=[CH:24][CH:25]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[NH:30]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH2:31][C:32]([O:34][CH3:35])=[O:33].C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:40][O:39][C:37](=[O:38])[CH2:36][N:30]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:27](=[O:29])[CH2:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:21]=1
Reactant: COC(=O)CNCC(=O)OC
Reactant: CCCCCCCCCCCCCCCCCCOc1cccc(CC(=O)O)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCOc1cccc(CC(=O)N(CC(=O)OC)CC(=O)OC)c1
Reaction time: 17 h
Yield: 64.9 %

Procedure:
A solution of 1.9 g (4.78 mmol) of 3-(octadecyloxy)phenylacetic acid in 40 ml of thionyl chloride was refluxed for 1.5 hours. The excess thionyl chloride was removed at reduced pressure and the resultant acid chloride was dissolved in 40 ml of anhydrous methylene chloride. This solution was added dropwise to an ice bath cooled mixture of 1.0 g (6 mmol) of dimethyl iminodiacetate and 1.4 ml (10 mmol) of triethylamine in 25 ml of methylene chloride. The reaction mixture was kept at room temperature for 17 hours and then was washed with 1N HCl, dried and concentrated to a solid. Purification by chromatography on 150 g of silica gel using 40% ethyl acetate-hexane gave 1.7 g (65% yield, mp 52°-55°) of N-(2-methoxy-2-oxoethyl)-N-[3-(octadecyloxy)phenylacetyl]glycine methyl ester.