Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li].C1COCC1.C([O:14][CH2:15][C@@H:16]([CH3:33])[CH2:17]/[CH:18]=[CH:19]/[C@H:20]([CH3:32])[C@@H:21]([O:24][Si:25]([CH2:30][CH3:31])([CH2:28][CH3:29])[CH2:26][CH3:27])[CH2:22][CH3:23])C1C=CC=CC=1.[Cl-].[NH4+]>C(OCC)(=O)C>[CH3:33][C@@H:16]([CH2:17]/[CH:18]=[CH:19]/[C@H:20]([CH3:32])[C@@H:21]([O:24][Si:25]([CH2:28][CH3:29])([CH2:30][CH3:31])[CH2:26][CH3:27])[CH2:22][CH3:23])[CH2:15][OH:14]
Reactant: CC[C@H](O[Si](CC)(CC)CC)[C@@H](C)/C=C/C[C@H](C)COCc1ccccc1
Agent: [Cl-]
Agent: [Li]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC[C@H](O[Si](CC)(CC)CC)[C@@H](C)/C=C/C[C@H](C)CO
Temperature: 25 °C
Reaction time: 3 h
Yield: 76.9 %

Procedure:
Lithium (39.4 mg, 5.62 mmol) was added to a THF (25 ml) solution of di-tert-butyldiphenyl (1.87 g, 7.02 mmol) while ice cooling and the reaction solution was stirred at room temperature for three hours. The reaction solution turned dark green during stirring. This solution was added dropwise to THF (5 ml) solution of {[(1S,2S,3E,6S)-7-benzyloxy-1-ethyl-2,6-dimethylhept-3-en-1-yl]oxy}(triethyl)silane (500 mg, 1.28 mmol) slowly (at such a rate that green of the reaction solution was maintained) cooled to −78° C. under stirring. After the reaction solution was stirred at the same temperature for three hours, a saturated ammonium chloride aqueous solution was added thereto and the mixture was warmed to room temperature. After the reaction solution was diluted with ethyl acetate, it was washed with brine. After the organic layer was dried over anhydrous sodium sulfate and the drying agent was filtered off, the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Merck, commercial name Silica Gel 60, 230-400 mesh; hexane:ethyl acetate=15:1) to obtain the title compound (296 mg) as a colorless oil.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1(C)C=CC(S([CH2:20][N+:21]#[C-:22])(=O)=O)=CC=1.[C:24]([O:33][CH3:34])(=[O:32])[CH:25]=[CH:26][CH2:27][C:28]([O:30][CH3:31])=[O:29]>O1CCCC1>[CH3:34][O:33][C:24]([C:25]1[C:26]([CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:22][NH:21][CH:20]=1)=[O:32]
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: COC(=O)C=CCC(=O)OC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)Cc1c[nH]cc1C(=O)OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.7 %

Procedure:
To a lithium bis(trimethylsilyl)amide (1M; tetrahydrofuran solution) (21 ml), a tetrahydrofuran (100 ml) solution of p-toluenesulfonylmethylisocyanide (4.04 g) was added dropwise at −78° C., and the mixture was stirred for 30 minutes. Successively, a tetrahydrofuran (20 ml) solution of dimethyl glutaconate (3.78 g) was added dropwise thereto, followed by stirring while raising the temperature to room temperature for 2 hours. The reaction mixture was concentrated, and the residue was washed with water and 1N hydrochloric acid successively, followed by extraction with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:2) to give the title compound (2.11 g) having the following physical properties.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].C([Li])CCC.[C:16](OCC)(=[O:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18].[NH4+].[Cl-]>CCOCC.CCCCCC>[CH3:1][O:2][C:3]1[C:4]([O:9][CH3:10])=[CH:5][CH:6]=[CH:7][C:8]=1[C:16](=[O:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: CCOC(=O)C(=O)OCC
Reactant: COc1ccccc1OC
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Solvent: CCCCCC
Product: CCOC(=O)C(=O)c1cccc(OC)c1OC
Temperature: -40 °C
Reaction time: 24 h

Procedure:
A mixture of 27.6 g of 1,2-dimethoxybenzene in 160 ml of ether is cooled to −40° C., 250 ml of a 1.6 M solution of n-butyllithium in hexane are added dropwise and the mixture is then left stirring for 24 hours while allowing the temperature to return to RT. The reaction mixture is cooled to −20° C., 136 ml of diethyl oxalate are added rapidly and the mixture is left stirring while allowing the temperature to return to RT. After stirring for 30 minutes at RT, the reaction mixture is poured into saturated NH4Cl solution, the phases are separated after settling has taken place, the aqueous phase is extracted with ether, the combined organic phases are washed twice with water and dried over Na2SO4, and the solvents are evaporated off under vacuum. The excess diethyl oxalate is removed by distillation under vacuum (b.p.=90° C. at 2 400 Pa). The resulting crude product is chromatographed on silica gel, eluting with a heptane/iso ether mixture (90/10; v/v). 25 g of the expected product are obtained and are used without further purification in the following step.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8](=[O:29])[NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[S:22][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[N:20][CH:19]=3)[CH2:13][CH2:12]2)[N:5]=[C:4]([C:30]([O:32]C)=O)[C:3]=1[C:34]#[N:35].[NH3:36]>CO>[NH2:1][C:2]1[C:3]([C:34]#[N:35])=[C:4]([C:30]([NH2:36])=[O:32])[N:5]=[C:6]([C:8]([NH:9][CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([CH2:17][C:18]3[S:22][C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[N:20][CH:19]=3)[CH2:15][CH2:16]2)=[O:29])[CH:7]=1
Reactant: N
Reactant: COC(=O)c1nc(C(=O)NCC2CCN(Cc3cnc(-c4ccccn4)s3)CC2)cc(N)c1C#N
Solvent: CO
Product: N#Cc1c(N)cc(C(=O)NCC2CCN(Cc3cnc(-c4ccccn4)s3)CC2)nc1C(N)=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The compound prepared in Example 233 (0.057 g) was suspended in methanol (4 mL) and 7 M ammonia solution in methanol (4 mL) was added. After stirring overnight at room temperature, the reaction was concentrated to provide the title compound (0.053 g) with the following physical data.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[C:18]([F:21])([F:20])[F:19])[C:4]([CH3:10])=[CH:5][C:6]=1[C:7](Cl)=[O:8].[S:22]([NH2:32])(=[O:31])([C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1)=[O:23].C(N(C(C)C)CC)(C)C>C1COCC1>[S:22]([C:24]1[CH:25]=[CH:26][C:27]([NH:30][C:7]([C:6]2[CH:5]=[C:4]([CH3:10])[N:3]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[C:18]([F:21])([F:20])[F:19])[C:2]=2[CH3:1])=[O:8])=[CH:28][CH:29]=1)(=[O:23])(=[O:31])[NH2:32]
Reactant: Nc1ccc(S(N)(=O)=O)cc1
Reactant: Cc1cc(C(=O)Cl)c(C)n1-c1ccc(F)cc1C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1cc(C(=O)Nc2ccc(S(N)(=O)=O)cc2)c(C)n1-c1ccc(F)cc1C(F)(F)F
Temperature: 80 °C
Yield: 65.5 %

Procedure:
Into an oven-dried 1 dram vial was added 2,5-dimethyl-1-[4-fluoro-2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylic acid chloride (106 mg, 332 μmol), sulfanilamide (62.0 mg, 360 μmol), anhyd THF (2.0 mL) and diisopropylethylamine (50 μL). The vial was sealed and heated at 80° C. overnight. The resulting residue was purified by flash chromatography (SiO2), eluting with EtOAc/Hex (30:70 to 60:40) to afford the title compound as an off-white solid (99 mg, 66%); 1H NMR (CDCl3): δ 8.85 (s, 1H), 7.88 (d, J=7 Hz, 2H), 7.84 (d, J=7 Hz, 2H), 7.58 (dd, J=8, 3 Hz, 1H), 7.46 (m, 1H), 7.31 (dd, J=5, 8 Hz, 1H), 6.46 (s, 1H), 6.19 (s, 2H), 2.25 (s, 3H), 1.94 (s, 3H); MS (ESI) m/z 456 [M+H]+.
Reaction SMILES: [NH:1]1[C:10](=[O:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]=[C:2]1[NH2:3].C[Si](C)(C)N[Si](C)(C)C.C(O[CH2:25][O:26][CH2:27][CH2:28][O:29][C:30](=[O:32])[CH3:31])(=O)C.O>CC(C)=O.S([O-])([O-])(=O)=O.[NH4+].[NH4+]>[C:30]([O:29][CH2:28][CH2:27][O:26][CH2:25][N:6]1[CH:7]=[N:8][C:9]2[C:10](=[O:11])[NH:1][C:2]([NH2:3])=[N:4][C:5]1=2)(=[O:32])[CH3:31]
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Reactant: CC(=O)OCCOCOC(C)=O
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [NH4+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)OCCOCn1cnc2c(=O)[nH]c(N)nc21
Temperature: 130 °C
Yield: 57.3 %

Procedure:
A mixture of 10 gms (66 mmoles) of guanine, 50 ml of hexamethyldisilazane, and 0.4 gms (3 mmmol) of ammonium sulfate was heated to 115°-118° C. for 18 hours. The ammonia gas was removed as it was formed. After 18 hours of heating, a solution was formed indicating the completion of silylation. To this solution was added 15 gms (85 mmol) of 2-oxa-1,4-butanediol diacetate and 0.1 ml of trimethylsilyl triftriflate. The mixture was heated to 130° C. for a period of 4.5 hours. The solution was cooled to 50° C. and 10 ml of water dissolved in 100 ml of acetone was added. The mixture was heated to reflux and a precipitate was formed immediately. The mixture was cooled and the solid was collected by filtration to yield 10.1 g (58% yield) of 9-(2-acetoxyethoxy)methylguanine, with a 13:1 ratio of N-9 to N-7 isomer. Characteristic analytical data are as follows: 1H NMR (DMSO-d6) δ1.90 (3H, singlet, --OAc) , 3.58 (2H, multiplet, --OCH2 --) , 4.0 (2H, multiplet, --CH2OAc) , 5.25 (2H, singlet, --NCH2O--), 6.5 (2H, br singlet, --NH2), 7.75 (1H, singlet, --N=CH--N--).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13]C)=[O:12])=[CH:6][CH:5]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19]Br>O1CCCC1>[F:15][C:16]1[CH:17]=[C:18]([CH2:19][CH:10]([C:7]2[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=2)[C:11]([OH:13])=[O:12])[CH:21]=[CH:22][CH:23]=1
Reactant: COC(=O)Cc1ccc(F)cc1
Reactant: Fc1cccc(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(O)C(Cc1cccc(F)c1)c1ccc(F)cc1
Temperature: 25 °C
Yield: 62.9 %

Procedure:
To a solution of 10.8 g of 60% sodium hydride in 400 mL of tetrahydrofuran was added 44.7 g of methyl 4-fluorophenylacetate dropwise. Then, 50 g of 3-fluorobenzyl bromide was added dropwise. The mixture was then heated to reflux for approximately 18 hours. After this time, the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ether and 5% aqueous sodium bicarbonate, and the ether extracts were dried over magnesium sulfate and concentrated to 77.57 g of a yellow oil. The crude product was combined with 275 mL of methanol, 20 mL of 50% aqueous NaOH and 50 mL of H2O and the mixture was refluxed for about 18 hours. The reaction was then cooled to room temperature, concentrated and partitioned between water and ether. The aqueous extracts were made acidic with concentrated HCl and extracted with ether. The ether extracts were dried over MgSO4, filtered, concentrated and the crude product was triturated with hexane to afford 43.62 g of a white solid; mp 92-94° C. 1H NMR (CDCl3) δ: 3.00 (dd, 1H), 3.38 (dd, 1H), 3.83 (t, 1H), 6.8-7.4 (m, 6H).
Reaction SMILES: [C:1]([OH:7])(=O)[CH2:2][CH2:3][C:4]#[CH:5].CCN(CC)CC.ClC(OCC)=O.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>C(Cl)Cl>[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([C:1](=[O:7])[CH2:2][CH2:3][C:4]#[CH:5])[CH2:24][CH2:23]1
Reactant: C#CCCC(=O)O
Reactant: CN1CCNCC1
Agent: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C#CCCC(=O)N1CCN(C)CC1
Reaction time: 0.75 h

Procedure:
A solution of 4-pentynoic acid (519 mg, 5.29 mmol) and Et3N (737 μL, 5.29 mmol) in DCM (10 mL) was treated with ethyl chloroformate (504 μL, 5.29 mmol) at rt for 15 min. Then N-methyl-piperazine (588 μL, 5.29 mmol) was added, and stirring was prolonged for 45 min. Work-up (sat. aq. NaHCO3) and concentration gave the title compound as a colorless oil. 1H NMR (CDCl3) δ 3.63 (t, 2H), 3.48 (t, 2H), 2.55 (m, 4H), 2.38 (quint., 4H), 2.30 (s, 3H).
Reaction SMILES: C(O[C:4]([CH:6]1[CH2:11][NH:10][CH2:9][CH2:8][NH:7]1)=O)C.[CH:12](Br)([CH3:14])[CH3:13]>>[CH:12]([N:7]1[CH2:8][CH2:9][N:10]([CH:6]([CH3:11])[CH3:4])[CH2:11][CH:6]1[C:4]1[NH:7][CH2:8][CH2:9][N:10]=1)([CH3:14])[CH3:13]
Reactant: CC(C)Br
Reactant: CCOC(=O)C1CNCCN1
Product: CC(C)N1CCN(C(C)C)C(C2=NCCN2)C1
Yield: 35 %

Procedure:
Reacting 2-ethoxycarbonylpiperazine with 2,2 aquivalents of isopropyl bromide in the same conditions as for example 21, and treating the obtained product in the same conditions as for example 1, step d, the desired product is obtained.
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][C@H:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1C=CC=CC=1>[CH3:3][C@H:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:5][NH:2][CH3:1]
Reactant: CN
Reactant: C[C@@H](C=O)NC(=O)OC(C)(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Product: CNC[C@H](C)NC(=O)OC(C)(C)C
Temperature: 25 °C

Procedure:
6.00 ml methylamine solution (2 M in tetrahydrofuran) are added to 1.73 g tert.butyl ((S)-1-methyl-2-oxoethyl)-carbamate in 20 ml benzene with stirring at ambient temperature. Then 2.50 g anhydrous sodium sulphate are added and the reaction mixture is stirred overnight at ambient temperature. The sodium sulphate is suction filtered and washed again with benzene. The filtrate is evaporated down, taken up in 20 ml of methanol and combined with 397 mg sodium cyanoborohydride with stirring at ambient temperature. After 2.5 hours the reaction mixture is acidified by dropwise addition of approx. 20 ml 2 N citric acid and extracted with tert.-butylmethylether. The aqueous phase is made alkaline with 10 M sodium hydroxide solution and extracted with a methylene chloride/methanol mixture. The combined organic phases are dried over magnesium sulphate and evaporated down.
Reaction SMILES: [CH3:1][O:2][CH2:3][O: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][CH2:18][CH2:19][CH2:20][N:21]1C(=O)C2=CC=CC=C2C1=O.O.NN>C(O)C>[CH3:1][O:2][CH2:3][O: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][CH2:18][CH2:19][CH2:20][NH2:21]
Reactant: COCOCCCCCCCCCCCCCCCCN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: O
Solvent: CCO
Product: COCOCCCCCCCCCCCCCCCCN

Procedure:
To a suspension of 0.97 g of N-(16-methoxymethoxyhexadecyl)phthalimide in 50 ml of ethanol was added 0.4 ml of hydrazine monohydrate and the mixture was heated under reflux for 2 hours. The reaction solution was distilled under reduced pressure. The residue was diluted with chloroform, washed with a 1N aqueous solution of sodium hydroxide, dried over anhydrous sodium sulfate and then distilled under reduced pressure. The residue was chromatographed over a silica gel column to afford the title compound as a colorless oily substance.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)#[CH:10].C(N(CC)CC)C>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:10]#[C:9][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:4][N:3]=1
Reactant: Clc1ncc(I)cn1
Reactant: C#Cc1ccc(F)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Fc1ccc(C#Cc2cnc(Cl)nc2)cc1
Temperature: 25 °C
Yield: 86.8 %

Procedure:
A solution of 2-chloro-5-iodopyrimidine (600 mg, 2.5 mmol), 1-ethynyl-4-fluorobenzene (330 mg, 2.75 mmol), triethylamine (556 mg, 761 μl, 5.49 mmol), and bis(triphenyl-phosphine)palladium (II) chloride (175 mg, 250 μmol) in 7 ml of THF was purged with argon. Then copper (I) iodide (23.8 mg, 125 μmol) was added and the reaction was heated for 2 h at room temperature. The dark solution was filtered and the solids were washed with THF. The residue was taken up in ethyl acetate, adsorbed onto 3 g of silicagel which was loaded onto a 50 g prepacked flash chromatography column. After elution with a 0% to 20% ethyl acetate in heptane gradient, the fractions containing the desired product were collected to yield 505 mg (87%) of the title compound as an crystalline light yellow solid, MS: m/e=233.1, 235.1 (M+H+).
Reaction SMILES: [CH:1]1([Si:7]([CH3:10])([CH3:9])Cl)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CN=C1.[CH2:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][C:17]1=[O:25].O>CN(C=O)C>[CH:1]1([Si:7]([CH3:10])([CH3:9])[O:25][C:17]2[CH2:18][C:19]3[C:24]([CH:16]=2)=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1Cc2ccccc2C1
Reactant: C[Si](C)(Cl)C1CCCCC1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: C[Si](C)(OC1=Cc2ccccc2C1)C1CCCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.8 %

Procedure:
A solution of cyclohexyldimethylchlorosilane (84.62 g, 478.7 mmol) and imidazole (32.59 g, 478.7 mmol) in DMF (300 mL) was reacted with 2-indanone (57.62 g, 436.0 mmol). The reaction mixture was stirred overnight at room temperature, treated with water (300 mL) and extracted with Et2O (3×200 mL). The combined organic phases were washed with water (3×300 mL) and dried over sodium sulfate. The solvents were removed to leave an orange oil. Distillation under reduced pressure gave 81.67 g (68.8%) of the title compound as a yellow oil (bp. 140-142° C./0.2 mbar). 1H NMR (CDCl3, δ): 7.25-7.11 (m, 3H); 7.01 (td, 3J=7.3 Hz, 4J=1.4 Hz, 1H); 5.76 (d, 4J=0.7 Hz, 1H); 3.29 (s, 2H) 1.77-1.74 (m, 5H); 1.27-1.13 (m, 5H); 0.90 (m, 1H); 0.24 (s, 6H). 13C NMR (CDCl3, δ): 162.44; 145.24; 136.60; 126.47; 123.07; 122.37; 118.91; 106.32; 39.52; 27.69; 26.77; 26.46; 26.33; −3.55.
Reaction SMILES: [NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([NH2:7])=[O:6])[CH2:3][CH2:2]1.Br[CH2:11][C:12](=[O:15])[CH2:13][CH3:14]>>[O:15]=[C:12]([CH2:13][CH3:14])[CH2:11][N:1]1[CH2:9][CH2:8][CH:4]([C:5]([NH2:7])=[O:6])[CH2:3][CH2:2]1
Reactant: NC(=O)C1CCNCC1
Reactant: CCC(=O)CBr
Product: CCC(=O)CN1CCC(C(N)=O)CC1

Procedure:
The title compound was prepared according to the procedure described in the step 5 of Example 4 from isonipecotamide and 1-bromobutan-2-one.
Reaction SMILES: [C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([S:21](Cl)(=[O:23])=[O:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:25]([NH:27][CH2:28][CH3:29])[CH3:26]>CN(C1C=CN=CC=1)C.CC#N.CCOC(C)=O>[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([S:21]([N:27]([CH2:28][CH3:29])[CH2:25][CH3:26])(=[O:23])=[O:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc2cc(S(=O)(=O)Cl)ccc2n1CC1CCOCC1
Reactant: CCNCC
Agent: CN(C)c1ccncc1
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCN(CC)S(=O)(=O)c1ccc2c(c1)nc(C(C)(C)C)n2CC1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.5 %

Procedure:
2-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (61.2 mg, 0.165 mmol) (see following Steps B, C, D, E, F, G and H for preparation), was added to a solution of diethylamine (0.2 mL, 1.93 mmol) and DMAP (50 mg, 0.41 mmol) in MeCN (5 mL). The reaction mixture was stirred overnight at room temperature, diluted with EtOAc (60 mL), washed with NH4Cl (2×5 mL), NaCl (2×5 mL) and dried over Na2SO4. The crude product was purified by MPLC using Hex/EtOAc (1:1) on silica gel to give 20.5 mg (30%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.13 (t, J=7.13 Hz, 6 H), 1.46-1.63 (m, 4 H), 1.66 (s, 9 H), 2.25-2.48 (m, 1 H), 3.22-3.29 (m, 4 H), 3.31-3.41 (m, 2 H), 3.94 (m, 2 H), 4.50 (d, J=7.42 Hz, 2 H), 7.89 (dd, J=8.79, 1.76 Hz, 1 H), 7.96-8.04 (m, 1 H), 8.14 (d, J=1.17 Hz, 1 H); MS (ESI) (M+H)+=408.0; Anal. Calcd for C21H33N3O3S+1.00 TFA+0.1H2O+0.30 EtOAc (549.84): C, 52.86; H, 6.71; N, 7.64. Found: C, 52.91; H, 6.52; N, 7.61.
Reaction SMILES: Cl[Si:2]([CH3:23])([CH3:22])[CH:3]1[C:14]2[C:6](=[CH:7][C:8]3[CH2:9][CH2:10][CH2:11][C:12]=3[CH:13]=2)[C:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:4]1[CH3:21].CCN(CC)CC.[CH:31]1([NH2:37])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>CCCCCC>[CH:31]1([NH:37][Si:2]([CH3:23])([CH3:22])[CH:3]2[C:14]3[C:6](=[CH:7][C:8]4[CH2:9][CH2:10][CH2:11][C:12]=4[CH:13]=3)[C:5]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:4]2[CH3:21])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: CC1=C(c2ccccc2)c2cc3c(cc2C1[Si](C)(C)Cl)CCC3
Reactant: NC1CCCCC1
Solvent: CCN(CC)CC
Solvent: CCCCCC
Product: CC1=C(c2ccccc2)c2cc3c(cc2C1[Si](C)(C)NC1CCCCC1)CCC3
Reaction time: 24 h
Yield: 89.9 %

Procedure:
Chlorodimethyl(1,5,6,7-tetrahydro-2-methyl-3-phenyl-s-indacen-1-yl) silane (9c)) (5.5340 g, 0.01633 moles) was stirred in hexane (100 mL) as NEt3 (2.9673 g, 0.02932 moles) and cyclohexylamine (1.6373 g, 0.01651 moles) were added. This mixture was allowed to stir for 24 hours. After the reaction period the mixture was filtered and the volatiles removed resulting in the isolation of the desired product as a yellow oil (5.8969 g, 89.9 percent).
Reaction SMILES: N#N.[CH3:3][O:4][C:5]([C:8]1[O:9][CH:10]=[C:11]([CH2:13][OH:14])[N:12]=1)([CH3:7])[CH3:6].CCN(CC)CC.[S:22](Cl)([CH3:25])(=[O:24])=[O:23]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:25][S:22]([O:14][CH2:13][C:11]1[N:12]=[C:8]([C:5]([O:4][CH3:3])([CH3:7])[CH3:6])[O:9][CH:10]=1)(=[O:24])=[O:23]
Reactant: CS(=O)(=O)Cl
Reactant: COC(C)(C)c1nc(CO)co1
Agent: CN(C)c1ccncc1
Agent: N#N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(C)(C)c1nc(COS(C)(=O)=O)co1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 98.1 %

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of (2-(2-methoxypropan-2-yl)oxazol-4-yl)methanol (31 mg, 0.18 mmol) in dry CH2Cl2 (1.4 mL) was treated at 0° C. with Et3N (0.03 mL, 0.23 mmol) followed by DMAP (2.2 mg, 0.02 mmol) and Ms-Cl (0.02 mL, 0.23 mmol). After stirring at 0° C. for 30 min, the reaction was quenched with water (10 mL). The org. layer was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to give 44 mg of crude (2-(2-methoxypropan-2-yl)oxazol-4-yl)methyl methanesulfonate as a yellow oil. LC-MS-conditions 07: tR=0.62 min, [M+H]+=250.00. A solution of this crude material (44 mg) in DMF (0.4 mL) was added to a solution of 4-nitro-2H-[1,2,3]triazole (T. E. Eagles et al. Organic preparations and procedures 2 (2), 117-119, 1970; P. N. Neuman J. Heterocycl. Chem. 8, 51-56, 1971) (203 mg of a 9.6% solution in DMF, 0.17 mmol) in DMF (0.4 mL) pre-treated for 30 min with DIPEA (0.06 mL, 0.34 mmol) and the reaction mixture was stirred for 24 h at 50° C. Water (5 mL), followed by EA (5 mL) was added. The aq. layer was extracted with EA (10 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (1:1 hept-EA) gave the title compound as a yellow oil: TLC: rf (1:1 hept-EA)=0.43. LC-MS-conditions 07: tR=0.72 min, [M]+=267.96.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]=[CH:2]1.[Br:10]N1C(=O)CCC1=O>C1COCC1.S(=O)(=O)(O)O.[Cl-].[NH4+].C(OCC)(=O)C>[Br:10][C:3]1[C:4]2[C:9](=[N:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: c1cnc2[nH]ccc2c1
Agent: O=S(=O)(O)O
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Brc1c[nH]c2ncccc12
Yield: 74.6 %

Procedure:
To a solution of 7-azaindole (5 g, 42.2 mmol) in THF (400 mL) were added first the solid N-bromosuccinimide (8 g, 45.0 mmol) then 20 drops of conc. sulfuric acid at room temperature. While stirring some suspension was formed during 2 days. The mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (4×150 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude yellow solid. This solid was dissolved in ethyl acetate (˜100 mL) at hot condition and then stored in the refrigerator overnight. The solids were collected by filtration and washed with ethyl acetate. After drying in air, 6.2 g (75% yield) of 3-bromo-1H-pyrrolo[2,3-b]pyridine was isolated as an yellow solid: EI-HRMS m/e calcd for C7H5BrN2 (M+) 195.9636. found 195.9636.