Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][C@@:3]([S:31]([CH3:34])(=[O:33])=[O:32])([CH2:14][CH2:15][N:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:18][C:17]1=[O:30])[C:4]([NH:6][O:7]C1CCCCO1)=[O:5]>ClCCl.CO>[OH:7][NH:6][C:4](=[O:5])[C@:3]([CH3:2])([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:14][CH2:15][N:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[CH:18][C:17]1=[O:30]
Reactant: C[C@@](CCn1ccc(CCc2ccccc2)cc1=O)(C(=O)NOC1CCCCO1)S(C)(=O)=O
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: C[C@@](CCn1ccc(CCc2ccccc2)cc1=O)(C(=O)NO)S(C)(=O)=O
Reaction time: 2 h
Yield: 70.3 %

Procedure:
A solution of hydrochloric acid (1.0 mL, 4.0 M in 1,4-dioxane) was added to a solution of (2R)-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2-phenylethyl)pyridin-1(2H)-yl]-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (14 mg, 0.029 mmol) in 5:1 dichloromethane-methanol (1.2 mL) at 0° C. After 2 h, the reaction was concentrated under reduced pressure. The resulting residue was triturated with 1:1 pentane-dichloromethane, filtered, washed with pentane, and dried under reduced pressure to provide a light pink solid (8 mg, 70%). MS (APCI) m/z 393.3 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51 (s, 3 H) 2.00-2.14 (m, 1 H) 2.24-2.36 (m, 1 H) 2.63-2.74 (m, 2 H) 2.78-2.88 (m, 2 H) 3.06 (s, 3 H) 3.58-3.73 (m, 1 H) 3.94-4.08 (m, 1 H) 6.16-6.26 (m, 2 H) 7.11-7.32 (m, 5 H) 7.55 (d, J=7.41 Hz, 1 H) 11.14 (br s, 1 H).
Reaction SMILES: N1C=CC=CC=1NC1C=CC=CC=1N.CC(C)C=CC([Cl:21])=O.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1/[CH:38]=[CH:39]/[C:40]1[CH:45]=CC=C[CH:41]=1.Cl>CO>[ClH:21].[CH3:41][CH:40]([CH3:45])/[CH:39]=[CH:38]/[C:30]1[N:29]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=1
Reactant: CC(C)C=CC(=O)Cl
Reactant: C(=C/c1nc2ccccc2n1-c1ccccn1)\c1ccccc1
Agent: Cl
Agent: Nc1ccccc1Nc1ccccn1
Solvent: CO
Product: CC(C)/C=C/c1nc2ccccc2n1-c1ccccn1

Procedure:
Free base of the titled compound was prepared from N-(2-pyridyl)-o-phenylenediamine and 4-methyl-2-pentenoyl chloride (Yamada, T.; Takashima, K.; Miyazawa, T.; Kuwata, S.; Watanabe, H. Bull. Chem. Soc. Jpn. 1978, 51, 878) according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A). The free base was treated with a 10% methanol solution of hydrogen chloride and concentrated to dryness. The residue was recrystallized from ethyl acetate-hexane to give the titled compound. MW: 299.81; mp: 140.0-141.0° C.; 1H-NMR (DMSO) δ: 8.81-8.79 (1H, m), 8.25 (1H, td, J=8.1, 1.8 Hz), 7.85-7.79 (2H, m), 7.77-7.71 (1H, m), 7.56-7.45 (3H, m), 7.31 (1H, dd, J=16.1, 7.0 Hz), 6.47-6.40 (1H, m), 2.75-2.55 (1H, m), 1.05 (6H, d, J=7.0 Hz).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[CH3:12][C:13]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[C:14]=1[CH2:15]Cl.O>CS(C)=O>[CH3:12][C:13]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[C:14]=1[CH2:15][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: Cc1cc(C)c(CCl)c(C)c1
Reactant: c1ccc2[nH]ccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1cc(C)c(Cn2ccc3ccccc32)c(C)c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 87.2 %

Procedure:
A solution of indole (1.185 g) in dry DMSO (3 ml) is dropped into a suspension of sodium hydride (60% mineral oil suspension; 0.44 g) in dry DMSO (10 ml). After two hours, the resulting solution is added with a solution of 2,4,6-trimethylbenzyl chloride (1.9 g) in dry DMSO (2 ml) heating at 60° C. for 6 h. The reaction mixture is kept at room temperature overnight, then poured into water (250 ml) extracted with ethyl acetate and dried (Na2SO4). The drying agent is filtered off, the solvent is evaporated off under reduced pressure and the resulting residue is purified by column chromatography (silica gel; eluent n-hexane/AcOEt 9/1) to obtain 2.2 g of 1-(2,4,6-trimethylbenzyl)indole.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][N:19]4[C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=5[NH:21][C:20]4=[O:28])[CH2:12][CH2:11]3)[C:7](=[S:9])[NH:8][C:4]=2[CH:3]=1.I[CH3:32].C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][N:19]4[C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=5[NH:21][C:20]4=[O:28])[CH2:12][CH2:11]3)[C:7]([S:9][CH3:32])=[N:8][C:4]=2[CH:3]=1
Reactant: O=c1[nH]c2ccccc2n1CCCN1CCC(n2c(=S)[nH]c3cc(Cl)ccc32)CC1
Reactant: CI
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CSc1nc2cc(Cl)ccc2n1C1CCN(CCCn2c(=O)[nH]c3ccccc32)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 2.21 parts of 1-{3-[4-(5-chloro-2,3-dihydro-2-thioxo-1H-benzimidazol-1-yl)-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one, 0.71 parts of iodomethane, 0.28 parts of sodium methanolate and 40 parts of methanol is stirred overnight at room temperature. The reaction mixture is evaporated. The residue is stirred with water and the product is extracted with trichloromethane. The extract is dried, filtered and evaporated. The residue is crystallized from 4-methyl-2-pentanone. The product is filtered off and dried, yielding 1.1 parts of 1-[3-{4-[5-chloro-2-(methylthio)-1H-benzimidazol-1-yl]-1-piperidinyl}propyl]-1,3-dihydro-2H-benzimidazol-2-one; mp. 196.1° C.
Reaction SMILES: [C:1]1(=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.C(O)(=O)C.C(=O)([O-])O.[Na+]>CO>[CH:1]1([NH:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[CH:12]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCCCC1
Reactant: Nc1ccc2[nH]ncc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: c1cc2[nH]ncc2cc1NC1CCCCC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 86.8 %

Procedure:
Cyclohexanone (59 mg), 5-aminoindazole (67 mg), and acetic acid (0.02 ml) were dissolved in methanol (1 ml), and a borane-pyridine complex (0.06 ml) was added dropwise to the solution at room temperature. The reaction mixture was stirred at room temperature for 18 hr. A saturated aqueous sodium hydrogencarbonate solution (1 ml) was then added thereto, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by HPLC [chloroform/methanol] to give the title compound (94 mg, yield 87%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:16]3[CH:15]=[CH:14][NH:13][C:12](=[O:17])[C:11]=3[C:10]([C:18]3[CH:19]=[C:20]([C:23]([OH:25])=[O:24])[S:21][CH:22]=3)=[N:9]2)=[CH:5][CH:4]=1.[CH3:28]CN=C=NCCCN(C)C.Cl>CC(N(C)C)=O.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16]3[CH:15]=[CH:14][NH:13][C:12](=[O:17])[C:11]=3[C:10]([C:18]3[CH:19]=[C:20]([C:23]([O:25][CH3:28])=[O:24])[S:21][CH:22]=3)=[N:9]2)=[CH:26][CH:27]=1
Reactant: CCN=C=NCCCN(C)C
Reactant: COc1ccc(Cn2nc(-c3csc(C(=O)O)c3)c3c(=O)[nH]ccc32)cc1
Agent: Cl
Solvent: CC(=O)N(C)C
Solvent: O
Product: COC(=O)c1cc(-c2nn(Cc3ccc(OC)cc3)c3cc[nH]c(=O)c23)cs1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.1 %

Procedure:
To a solution of 4-(1-(4-methoxybenzyl)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl)thiophene-2-carboxylic acid (38.8 mg) in DMA (3 mL) were added EDCI hydrochloride (23.4 mg) and HOBt ammonium salt (18.6 mg) at room temperature, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (basic silica gel, ethyl acetate/methanol) to give the title compound (31.4 mg).
Reaction SMILES: Br[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:36][Si:37]([C:40]#[CH:41])([CH3:39])[CH3:38]>C(NC(C)C)(C)C>[CH3:36][Si:37]([C:40]#[C:41][C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[CH:3]=1)([CH3:39])[CH3:38]
Reactant: BrC1=Cc2ccccc2Cc2ccccc21
Reactant: C#C[Si](C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)NC(C)C
Product: C[Si](C)(C)C#CC1=Cc2ccccc2Cc2ccccc21
Yield: 53.6 %

Procedure:
To a stirred mixture of 10-bromo-5H-dibenzo[a,d]cycloheptene (9.70 g, 0.036 mol) (J. Med. Chem. 1995 38(4), 708-714), palladium(II)chloride bistriphenylphosphine (1.25 g, 0.018 mol), triphenyl phosphine (0.942 g, 0.0036 mol), copper(ll)acetate hydrate (0.327 g, 0.002 mol) in 20 ml of diisopropyl amine was added (trimethylsilyl)acetylene (3.88 g, 0.040 mol) and refluxed for an hour. The resulting mixture was concentrated, diluted with hexane (25 ml) and filtered through a pad of silica gel. The filtrate was concentrated to yield 5.57 g of 10-(trimethylsilyl)ethynyl-5H-dibenzo[a,d]cycloheptene.
Reaction SMILES: N1(S(N[C:9](=O)[C:10]2[CH:15]=C(Cl)C(OCC3(C(F)(F)F)CCCC3)=CC=2F)(=O)=O)CCC1.[N:30]1([S:34]([NH:37][C:38](=[O:57])[C:39]2[CH:44]=[C:43](Cl)[C:42]([O:46][CH2:47][CH:48]3[C:50]4([CH2:55][CH2:54][CH2:53][CH2:52][CH2:51]4)[CH2:49]3)=[CH:41][C:40]=2[F:56])(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31]1>>[N:30]1([S:34]([NH:37][C:38](=[O:57])[C:39]2[CH:44]=[C:43]([CH:15]3[CH2:10][CH2:9]3)[C:42]([O:46][CH2:47][CH:48]3[C:50]4([CH2:55][CH2:54][CH2:53][CH2:52][CH2:51]4)[CH2:49]3)=[CH:41][C:40]=2[F:56])(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31]1
Reactant: O=C(NS(=O)(=O)N1CCC1)c1cc(Cl)c(OCC2(C(F)(F)F)CCCC2)cc1F
Reactant: O=C(NS(=O)(=O)N1CCC1)c1cc(Cl)c(OCC2CC23CCCCC3)cc1F
Product: O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC2CC23CCCCC3)cc1F

Procedure:
Following the procedure as described in Example 165 and making variations as required to replace N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzamide with N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[2.5]octan 1-ylmethoxy)benzamide, the title compound was obtained (0.03 g, 7%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.67 (br s, 1H), 7.58 (d, J=9.1 Hz, 1H), 6.58 (d, J=14.4 Hz, 1H), 4.24 (t, J=7.7 Hz, 5H), 3.86 (t, J=9.6 Hz, 1H), 2.26 (q, J=7.7 Hz, 2H), 2.15-2.05 (m, 1H), 1.79-1.18 (m, 10H), 1.14-1.04 (m, 1H), 0.96-0.92 (m, 2H), 0.77-0.58 (m, 3H), 0.28 (t, J=5.0 Hz, 1H); MS (ES−) m/z 435.2 (M−1).
Reaction SMILES: [S:1]([CH2:5][C:6]([OH:8])=[O:7])([OH:4])(=[O:3])=[O:2].[CH2:9](O)[CH3:10]>>[S:1]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])([OH:4])(=[O:3])=[O:2]
Reactant: CCO
Reactant: O=C(O)CS(=O)(=O)O
Product: CCOC(=O)CS(=O)(=O)O
Temperature: 80 °C

Procedure:
2.21 g (15.8 mmol) of sulfoacetic acid was suspended in 30 ml of ethanol, and the suspension was heated at 80° C. under reflux for 5 hours. The solvent was distilled off to obtain the title compound.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:22][N:5]2[C:6](=[O:21])[N:7]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:11][CH:10]=3)[CH2:8][C@H:4]2[CH2:3]1.[H-].[Na+].Br[CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29]>C1COCC1>[CH3:29][CH:28]([CH3:30])[CH2:27][CH2:26][O:1][C@@H:2]1[CH2:22][N:5]2[C:6](=[O:21])[N:7]([C:9]3[CH:10]=[CH:11][C:12]([O:15][CH2:16][C:17]([F:20])([F:18])[F:19])=[CH:13][CH:14]=3)[CH2:8][C@H:4]2[CH2:3]1
Reactant: CC(C)CCBr
Reactant: O=C1N(c2ccc(OCC(F)(F)F)cc2)C[C@H]2C[C@H](O)CN12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)CCO[C@H]1C[C@@H]2CN(c3ccc(OCC(F)(F)F)cc3)C(=O)N2C1
Reaction time: 0.5 h
Yield: 49.1 %

Procedure:
To a solution of (6S,7aR)-6-Hydroxy-2-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-hexahydro-pyrrolo[1,2-c]imidazol-3-one (100 mg, 0.316 mmol) in THF (3 mL) was added NaH (60% dispersion, 18.96 mg, 0.474 mmol) at room temperature and stirred for 30 min and then added 1-Bromo-3-methyl-butane (57.3 mg, 0.379 mmol) and left stirring for 12 h. The reaction mixture was quenched with NH4Cl aq., DCM was added. The organic layer was separated, washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified through column chromatography (elution with ethyl acetate in hexane) to afford 60 mg (49%) of the title compound. LC-MS: 386 [M+1]+.
Reaction SMILES: Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]=[C:4]2[CH:12]=[N:13][NH:14][C:3]=12.[CH2:15]([NH2:19])[CH:16]([CH3:18])[CH3:17]>C1(C)C(C)=CC=CC=1>[CH2:15]([NH:19][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[N:5]=[C:4]2[CH:12]=[N:13][NH:14][C:3]=12)[CH:16]([CH3:18])[CH3:17]
Reactant: Clc1c2c(nc3cn[nH]c13)CCCC2
Reactant: CC(C)CN
Solvent: Cc1ccccc1C
Product: CC(C)CNc1c2c(nc3cn[nH]c13)CCCC2
Yield: 14.5 %

Procedure:
9-Chloro-5,6,7,8-tetrahydro-1H-pyrazolo[4,3-b]quinoline (4.90 g, 0.024 mole) and isobutylamine (11.7 ml, 0.118 mole) were heated under reflux under nitrogen in dry xylene (50 ml) for 6 days. The solution was concentrated to dryness, the residue dissolved in water/methanol and the solution adjusted to pH 9-10 by addition of 10% sodium carbonate solution. The precipitate was filtered of, washed with water, dried and recrystallised from ethyl acetate to give the title compound as a beige solid (0.85 g, 15%), m.p. 124°-127° C. Found: C, 68.45; H, 8.55; N, 22.80%. C14H20N4 requires C, 68.80; H, 8.25; N, 22.95%.
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].[NH2:17][C:18]1[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=1)[C:21]([O:23][CH2:24][CH3:25])=[O:22].CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C)C1C=CN=CC=1>[C:1]([S:4][CH2:5][CH:6]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:7]([NH:17][C:18]1[CH:19]=[C:20]([CH:26]=[CH:27][CH:28]=1)[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:9])(=[O:3])[CH3:2]
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)O
Reactant: CCOC(=O)c1cccc(N)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CCOC(=O)c1cccc(NC(=O)C(CSC(C)=O)Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.5 %

Procedure:
2-Acetylthiomethyl-3-phenylpropionic acid (11.9 g) and ethyl 3-aminobenzoate (8.26 g) are dissolved in dichloromethane (150 ml), and thereto are added 4-dimethylaminopyridine (0.61 g) and EDC.HCl (10.54 g), and the mixture is stirred at room temperature overnight. The reaction mixture is washed with saturated aqueous citric acid solution, saturated aqueous sodium chloride solution and saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution in this order, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue is washed with diethyl ether to give the title compound (13 g).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]=[CH:12][CH3:13])[CH:6]=1.C([O-])(O)=O.[Na+].[H][H]>[Pd].CCOC(C)=O.CCO>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH2:12][CH3:13])[CH:6]=1
Reactant: CC=Cc1cccc(OCOC)c1
Reactant: [H][H]
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCCc1cccc(OCOC)c1
Yield: 100.3 %

Procedure:
To a solution of 3-hydroxybenzaldehyde (11.0 g, 90.1 mmol) in DMF (110 mL) at 0° C. was added methoxymethyl chloride (7.5 mL, 99.1 mmol) followed by NaH (99.1 mmol, 3.96 g, 60% dispersion in oil) in three portions (violent deprotonationl). The mixture was stirred at 0° C. for 15 min and then at room temperature for 15 h. The reaction was quenched with water and more water was added until all the precipitate dissolved. The solution was extracted in ether (2×150 mL) with water (50 mL), then with saturated Na2CO3 (100 mL), and finally with water (100 mL). The crude product was used in the next reaction. To a suspension of (ethyl)triphenylphosphonium bromide (36.8 g, 99.1 mmol, dried at 90° C. under high vacuum overnight) in THF (250 mL) at 0° C. was added n-BuLi (39.6 mL, 99.1 mmol, 2.5 M in hexanes) over five min. The resulting pretty dark burgundy mixture was stirred at 0° C. for 10 min and then at room temperature for 30 min. It was re-cooled to 0° C. and a solution of the above crude 3-methoxymethoxybenzaldehyde in THF (15 mL) was added slowly. The resulting medium brown mixture was stirred at 0° C. for 2 h and then at room temperature for 2 h. The mixture was quenched by exposing it to air for several min. Because filtering the mixture for this particular Wittig reaction would result in a sticky precipitate clogging the sintered-glass filter, the THF was removed in vacuo and the crude material was dissolved in DMF (100 mL). Extraction in hexanes (4×100 mL) with 50% saturated brine (100 mL) eliminated triphenylphosphonium oxide into the aqueous layer. Flash chromatography with silica gel (gradient to 6% ether/hexanes) produced 1-(methoxymethoxy)-3-(1-propenyl)benzene [(E)/(Z)˜1:1] as a colorless liquid (13.2 g, 82% yield for two steps). A suspension of 3 produced 1-(methoxymethoxy)-3-(1-propenyl)benzene (13.2 g, 74.1 mmol), NaHCO3 (1.24 g, 14.8 mmol), and 10% palladium on carbon (3.3 g) in EtOAc (75 mL) and EtOH (19 mL) was stirred at room temperature for 20 h with a hydrogen balloon attached. The round-bottom flask was purged with nitrogen, the mixture was filtered through Celite, and the Celite was washed well with EtOAc to furnish 1-(methoxymethoxy)-3-propylbenzene as a colorless liquid (13.4 g, 100% yield): 1H NMR (300 MHz, CDCl3) δ 0.94 (t, 3H, J=7.4 Hz), 1.64 (m, 2H), 2.56 (t, 2H, J=7.7 Hz), 3.48 (s, 3H), 5.17 (s, 2H), 6.80-6.90 (three overlapping peaks, 3H), 7.19 (m, 1H).
Reaction SMILES: [CH3:1][C:2]([CH3:21])([Si:4]([CH3:20])([CH3:19])[O:5][CH2:6][CH:7]([OH:18])[CH2:8][CH2:9][O:10][Si:11]([CH3:17])([CH3:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[CH3:3].C(N(CC)CC)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>ClCCl>[CH3:29][S:30]([O:18][CH:7]([CH2:8][CH2:9][O:10][Si:11]([CH3:17])([CH3:16])[C:12]([CH3:13])([CH3:14])[CH3:15])[CH2:6][O:5][Si:4]([CH3:20])([CH3:19])[C:2]([CH3:21])([CH3:1])[CH3:3])(=[O:32])=[O:31]
Reactant: CC(C)(C)[Si](C)(C)OCCC(O)CO[Si](C)(C)C(C)(C)C
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCC(CO[Si](C)(C)C(C)(C)C)OS(C)(=O)=O
Reaction time: 0.5 h

Procedure:
To a solution of 2,2,3,3,10,10,11,11-octamethyl-4,9-dioxa-3,10-disiladodecan-6-ol (i.e. the product of Step A) (36.31 g, 0.109 mol) in dichloromethane (300 mL) cooled to about 0° C. under nitrogen, was added triethylamine (22.8 mL, 0.163 mol), followed by dropwise addition of a solution of methanesulfonyl chloride (10.14 mL, 0.13 mol) in dichloromethane (100 mL), maintaining the reaction mixture below 10° C. The reaction mixture was stirred for another 30 minutes, and then washed with citric acid (about 200 mL, 10%), water (about 200 mL) and sodium bicarbonate (about 200 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide the title compound as a yellow oil (42.16 g) which was used without further purification.
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[C:3](Cl)=[O:4].[OH:7][C:8]1[C:9]([CH3:22])=[C:10]([CH3:21])[C:11]2[O:15][C:14]([CH3:17])([CH3:16])[C:13](=[O:18])[C:12]=2[C:19]=1[CH3:20].N1C=CC=CC=1>ClCCl>[CH3:1][CH:2]([CH3:6])[C:3]([O:7][C:8]1[C:9]([CH3:22])=[C:10]([CH3:21])[C:11]2[O:15][C:14]([CH3:16])([CH3:17])[C:13](=[O:18])[C:12]=2[C:19]=1[CH3:20])=[O:4]
Reactant: CC(C)C(=O)Cl
Reactant: Cc1c(C)c2c(c(C)c1O)C(=O)C(C)(C)O2
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1c(C)c2c(c(C)c1OC(=O)C(C)C)C(=O)C(C)(C)O2
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.8 %

Procedure:
A solution of 2-methylpropionylchloride (isobutyryl-chloride, 8.05 g, 75.55 mmol) in dichloromethane (10 mL) is added dropwise at 0° C. and under nitrogen to a solution of 5-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-one (12.8 g, 58.11 mmol) and pyridine (5.97 g, 61 mmol) in dichloromethane (58 mL). The ice bath is removed and the mixture is stirred for 2 hrs at room temperature. Water (10 mL) is added and the organic phase is washed with 2N hydrochloric acid (100 mL), water (100 mL), 10% sodium bicarbonate (100 mL) and brine. The solution is dried (magnesium sulfate) and evaporated to dryness to give 17 g (100%) of 5-(2-methylpropionoxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-one as an oil which is used without purification for the next step. Rf=0.5 (heptane/ethyl acetate 90:10)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([F:21])[CH:14]=2)[CH:5]=[C:6]2[C:11]=1[CH:10]=[C:9]([OH:12])[CH:8]=[CH:7]2.C1C(=O)N([Cl:29])C(=O)C1>>[Cl:29][C:10]1[C:11]2[C:6](=[CH:5][C:4]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([F:21])[CH:14]=3)=[CH:3][C:2]=2[F:1])[CH:7]=[CH:8][C:9]=1[OH:12]
Reactant: COc1ccc(-c2cc(F)c3cc(O)ccc3c2)cc1F
Reactant: O=C1CCC(=O)N1Cl
Product: COc1ccc(-c2cc(F)c3c(Cl)c(O)ccc3c2)cc1F

Procedure:
The title compound was prepared by reacting 8-fluoro-6-(3-fluoro-4-methoxyphenyl)-2-naphthol (0.30 g, 1.05 mmol) and NCS (0.17 g, 1.26 mmol) according to method C to yield 0.21 g (62%) of a light orange solid: mp 126-128° C.; 1H NMR (DMSO-d6): δ 3.90 (3H, s), 7.25-7.31 (1H, m), 7.35 (1H, d, J=8.91 Hz), 7.64-7.67 (1H, m), 7.70-7.78 (2H, m), 7.87 (1H, dd, J=1.58 Hz, J=9.04 Hz), 10.68 (1H, s); MS (ESI) m/z3191321 (M−H)−.
Reaction SMILES: [CH2:1]([NH:4][CH:5]1[CH2:13][CH2:12][C:8]2[N:9]=[CH:10][S:11][C:7]=2[CH2:6]1)[CH2:2][CH3:3].[C:14]12([NH:24][C:25](=[O:31])[CH2:26][CH2:27][CH2:28][CH:29]=O)[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH2:17]3)[CH2:15]1)[CH2:21]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:14]12([NH:24][C:25](=[O:31])[CH2:26][CH2:27][CH2:28][CH2:29][N:4]([CH2:1][CH2:2][CH3:3])[CH:5]3[CH2:13][CH2:12][C:8]4[N:9]=[CH:10][S:11][C:7]=4[CH2:6]3)[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH2:17]3)[CH2:15]1)[CH2:21]2
Reactant: CCCNC1CCc2ncsc2C1
Reactant: O=CCCCC(=O)NC12CC3CC(CC(C3)C1)C2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CCCN(CCCCC(=O)NC12CC3CC(CC(C3)C1)C2)C1CCc2ncsc2C1
Reaction time: 8 h
Yield: 60 %

Procedure:
A solution of 395 mg (2 mmol) propyl-(4,5,6,7-tetrahydro-benzothiazol-6-yl)-amine and 748 mg (3 mmol) N-adamantyl-5-oxopentanamide in 1,2-dichloroethane (20 mL) is stirred for about 30 minutes. Then 0.75 g (3 mmol) of sodium triacetoxyborohydride is added and the mixture is stirred overnight. After hydrolysation with 30 mL of 1N aqueous NaOH solution the organic phase is separated, dried over sodium sulfate and concentrated in vacuum. The crude product obtained is purified via column chromatography on silica gel.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[C:5](#N)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O.O.C([O-])(=O)C.[Cd+2].C([O-])(=O)C>[C:6]1([C:5]2[O:2][CH2:1][CH2:3][N:4]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: N#Cc1ccccc1
Reactant: NCCO
Agent: CC(=O)[O-]
Agent: [Cd+2]
Solvent: O
Product: c1ccc(C2=NCCO2)cc1
Reaction time: 16 h

Procedure:
Linear polyethyleneimine with a number average molecular weight of about 30,000 as determined by gel permeation chromatography was prepared as follows. Ethanolamine (304 grams) was added over a period of 90 minutes to a stirred suspension of 16.5 grams of cadmium acetate dihydrate in 512 grams of benzonitrile at 130° C. After 16 hours, distillation of the mixture yielded a clear fraction of 2-phenyl-2-oxazoline boiling at 82° C. and at a pressure of 1.5 millimeters of mercury. Subsequently, 2-phenyl-2-oxazolium perchlorate was prepared by adding 19.5 grams of perchloric acid to 20 grams of 2-phenyl-2-oxazoline in 20 milliliters of water and 20 milliliters of ethanol. The resultant solution was cooled to -20° C. to form white crystals of 2-phenyl-2-oxazolium perchlorate, which were isolated by filtration and dried in vacuo at 30° C. Polymerization of 2-phenyl-2-oxazoline was then effected by heating a mixture of 0.52 gram of 2-phenyl-2-oxazolium perchlorate and 100 grams of 2-phenyl-2-oxazoline to 150° C. in an oil bath with stirring under argon. The mixture became too thick to stir within 1 hour. The resulting light yellow solid is poly(2-phenyl-2-oxazoline).