Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:6])[C:4]#[CH:5].Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].CO>C(OCC)C>[CH2:3]([O:6][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]#[CH:5]
Reactant: C#CCO
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CO
Product: C#CCOCC(=O)OCC
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 70.4 %

Procedure:
To an anhydrous solution containing 5.1 g of 55% oily sodium hydride in 120 ml of diethyl ether were added 24 ml of an anhydrous diethyl ether solution containing 5.6 g of propargyl alcohol. The mixture was stirred at room temperature for 1.5 hours, after which 20.9 g of ethyl bromoacetate were added dropwise. The mixture was allowed to stand overnight, after which the excess sodium hydride was decomposed with methanol. After separating off the precipitate produced, the filtrate was distilled to give 10 g of ethyl α-propargyloxyacetate, boiling at 52°-60° C./4-7 mmHg.
Reaction SMILES: [C:1]([C:5]1[CH:22]=[CH:21][C:8]([CH2:9][NH:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(S(F)(F)[F:29])CC.C(=O)(O)[O-].[Na+].C(=O)=O>C(Cl)Cl>[C:1]([C:5]1[CH:22]=[CH:21][C:8]([CH2:9][NH:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[F:29])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCN(CC)S(F)(F)F
Reactant: CC(C)(C)c1ccc(CNCC(O)c2ccc(Cl)cc2)cc1
Agent: O=C([O-])O
Agent: O=C=O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)c1ccc(CNCC(F)c2ccc(Cl)cc2)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
159 mg of [rac]-(4-tert-butyl-benzyl)-[2-(4-chloro-phenyl)-2-hydroxy-ethyl]-amine (0.5 mmol, described in example S43) in 5 ml DCM was cooled to 2° C. and treated with 0.2 ml of DAST (1.5 mmol) for 2 min. After 2 h stirring at 0° C. followed by 1 h at rt, the reaction mixture was again cooled down to 0° C. and treated with 5 ml saturated aqueous sodium bicarbonate. The reaction mixture was stirred until CO2 evolution stopped, then the organic phase was separated, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was Purified by silicagel chromatography (40 g silica gel; heptane/EtOAc 2:1) leading to 27 mg of a light yellow semi-solid (17%). M(ISP) 320.3 (M+H)+.
Reaction SMILES: Cl[C:2]1[O:3][C:4]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH3:25])=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)[N:6]=1.[NH:26]1[CH:30]=[CH:29][N:28]=[C:27]1[C:31]([O:33][CH2:34][CH3:35])=[O:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[N:6]=[C:2]([N:26]3[CH:30]=[CH:29][N:28]=[C:27]3[C:31]([O:33][CH2:34][CH3:35])=[O:32])[O:3][C:4]=2[CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][CH3:25])=[CH:8][CH:9]=1
Reactant: CCOC(=O)c1ncc[nH]1
Reactant: COc1ccccc1OCCCc1oc(Cl)nc1-c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1nccn1-c1nc(-c2ccc(Cl)cc2)c(CCCOc2ccccc2OC)o1
Temperature: 125 °C
Reaction time: 1 h
Yield: 22.8 %

Procedure:
A mixture of 2-chloro-4-(4-chlorophenyl)-5-[3-(2-methoxyphenoxy)propyl]oxazole (1.00 g), ethyl 2-imidazolecarboxylate (990 mg), potassium carbonate (1.38 g) and N,N-dimethylformamide (10 ml) was stirred at 120-130° C. for 1 hour. The reaction mixture was poured into water (100 ml), and the resulting solid precipitate was filtered, air-dried and recrystallized from acetone-isopropyl ether to give ethyl 1-[4-(4-chlorophenyl)-5-[3-(2-methoxyphenoxy)propyl]-2-oxazolyl]imidazole-2-carboxylate as pale yellow prisms (290 mg, 23%). Melting point 90-91° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][N:6]1[C:12](=[O:13])[C:11]2[CH:14]=[C:15]([CH:18]([CH3:20])[CH3:19])[CH:16]=[CH:17][C:10]=2[NH:9][C:8](=O)[CH2:7]1.CN(C)C1C=CC(C)=CC=1.P(Cl)(Cl)([Cl:40])=O>C1(C)C=CC=CC=1>[Cl:40][C:8]1[CH2:7][N:6]([CH2:5][C:4]2[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:3]=2[O:2][CH3:1])[C:12](=[O:13])[C:11]2[CH:14]=[C:15]([CH:18]([CH3:20])[CH3:19])[CH:16]=[CH:17][C:10]=2[N:9]=1
Reactant: COc1ccc(CN2CC(=O)Nc3ccc(C(C)C)cc3C2=O)c(OC)c1
Reactant: O=P(Cl)(Cl)Cl
Solvent: Cc1ccc(N(C)C)cc1
Solvent: Cc1ccccc1
Product: COc1ccc(CN2CC(Cl)=Nc3ccc(C(C)C)cc3C2=O)c(OC)c1
Temperature: 100 °C
Reaction time: 2.5 h

Procedure:
4-(2,4-Dimethoxy-benzyl)-7-isopropyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (1.5 g, 4.1 mmol) and N,N-dimethyl-p-toluidine (1.76 mL, 12.2 mmol) were mixed in toluene (8 mL) and heated to 100° C. Then phosphorus oxychloride (559 μL, 6.1 mmol) was added dropwise and heating at 100° C. was continued for 2.5 h. After cooling, the mixture was evaporated and dissolved in THF (10 mL) and was used directly in the subsequent step.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][C:15]=1[N:16]=[N:17][C:18]1[C:23]([CH3:24])=[CH:22][C:21]([Br:25])=[CH:20][C:19]=1Br)[N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])(=[O:3])[CH3:2].[CH2:27]=[N:28]O.[N+](C1C=CC=CC=1)([O-])=O>[Cu]I.C(N(CC)CC)C>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][C:15]=1[N:16]=[N:17][C:18]1[C:23]([CH3:24])=[CH:22][C:21]([Br:25])=[CH:20][C:19]=1[C:27]#[N:28])[N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])(=[O:3])[CH3:2]
Reactant: C=NO
Reactant: CCN(CC)c1ccc(N=Nc2c(C)cc(Br)cc2Br)c(NC(C)=O)c1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: O=[N+]([O-])c1ccccc1
Product: CCN(CC)c1ccc(N=Nc2c(C)cc(Br)cc2C#N)c(NC(C)=O)c1
Temperature: 90 °C

Procedure:
A stirred mixture of 3-acetylamino-4-(2', 4'-dibromo-6'-methylphenylazo)-N,N-diethylaniline (4.8 parts), copper (I) iodide (2.0 parts), formaldoxime trimer (1.8 parts), triethylamine (1.5 parts), and nitrobenzene (100 parts) was heated to 90° C. for 11/2 hours when thin layer chromatography showed reaction to be complete. Isolation by the method of Example 3 gave 3-acetylamino-4-(2'-cyano-4'-bromo-6'-methylphenylazo)-N,N-diethylaniline, infra red spectrum identical with that of authentic material.
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[CH:5]1([NH2:11])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>ClC1C=CC=CC=1.CS(C)(=O)=O>[CH:5]1([N:11]=[C:1]=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: O=C(Cl)Cl
Reactant: NC1CCCCC1
Agent: CS(C)(=O)=O
Solvent: Clc1ccccc1
Product: O=C=NC1CCCCC1
Yield: 228.8 %

Procedure:
500 g of chlorobenzene and 2.4 g of dimethyl sulfone (0.025 mol) were placed in the glass vessel and 30 g of gaseous phosgene was introduced at room temperature. The reaction mixture was subsequently heated to 78° C., with vigorous phosgene reflux being established. While stirring vigorously at 78–80° C., a total of 99.2 g of cyclohexylamine (1 mol) dissolved in 200 g of chlorobenzene and at the same time a further 105 g of phosgene were introduced over a period of 3 hours. After addition was complete, the system was maintained at 78–80° C. for a further one hour without introduction of phosgene to allow further reaction to occur and the residual unreacted phosgene was subsequently stripped out at 50° C. by means of nitrogen. The reaction mixture obtained was a suspension from which the solid obtained was separated by filtration. 7.8 g of solid were able to be isolated in this way. The filtered crude product was worked up by distillation. Removal of the solvent and fractional distillation gave 86.8 g of cyclohexyl isocyanate (0.694 mol). This corresponds to 69.4% of the theoretical yield.
Reaction SMILES: Cl.[C:2]([O:8][CH2:9][O:10][C:11]([C:13]1[N:18]2[C:19](=[O:41])[C@@H:20]([NH:21][C:22](=[O:40])/[C:23](/[C:27]3[N:28]=[C:29]([NH:32]C(OC(C)(C)C)=O)[S:30][CH:31]=3)=[CH:24]\[CH2:25][CH3:26])[C@H:17]2[S:16][CH2:15][CH:14]=1)=[O:12])(=[O:7])[C:3]([CH3:6])([CH3:5])[CH3:4]>C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>[C:2]([O:8][CH2:9][O:10][C:11]([C:13]1[N:18]2[C:19](=[O:41])[C@@H:20]([NH:21][C:22](=[O:40])/[C:23](/[C:27]3[N:28]=[C:29]([NH2:32])[S:30][CH:31]=3)=[CH:24]\[CH2:25][CH3:26])[C@H:17]2[S:16][CH2:15][CH:14]=1)=[O:12])(=[O:7])[C:3]([CH3:6])([CH3:4])[CH3:5]
Reactant: CC/C=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)OCOC(=O)C(C)(C)C)=CCS[C@H]12)c1csc(NC(=O)OC(C)(C)C)n1
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CC/C=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)OCOC(=O)C(C)(C)C)=CCS[C@H]12)c1csc(N)n1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 83.5 %

Procedure:
[Hydrochloride] A solution of 7beta-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-pentenoyl]amino-3-cephem-4-carboxylic acid pivaloyloxymethyl ester (360 mg) in a mixture of anisole (2 ml) and trifluoroacetic acid (2 ml) is stirred at room temperature for 150 minutes and concentrated. The residue is dissolved in aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract is purified by silica gel column chromatography to give 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoyl]amino-3-cephem-4-carboxylic acid pivaloyloxymethyl ester (250 mg). This is dissolved in dichloromethane, mixed with a solution of hydrochloric acid in ethyl acetate, and concentrated. The crystalline residue is washed with ether to give the hydrochloride of above ester.
Reaction SMILES: Br[C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].[OH-].[K+].C1C=CC2C(C3C=CC(O)=CC=3)(C3C=CC(O)=CC=3)OC(=O)C=2C=1.[F:35][C:36]([F:45])([F:44])[C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1>CO>[F:35][C:36]([F:44])([F:45])[C:37]1[CH:38]=[CH:39][C:40]([NH:41][C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4])=[CH:42][CH:43]=1
Reactant: CC(C)[C@@H](Br)C(=O)O
Reactant: Nc1ccc(C(F)(F)F)cc1
Agent: O=C1OC(c2ccc(O)cc2)(c2ccc(O)cc2)c2ccccc21
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CC(C)[C@@H](Nc1ccc(C(F)(F)F)cc1)C(=O)O
Reaction time: 1 h

Procedure:
A solution of 10.01 g (55.3 mmol) of (R)-2-bromo-3-methylbutanoic acid in methanol is titrated with 1 M potassium hydroxide (~53 ml) in methanol to the phenolphthalein endpoint. The methanol is then removed under high vacuum at 35°, and the solid is kept at 35° under high vacuum for one hour. 4-Trifluoromethylaniline (23.89 g, 148.3 mmol) is added to the salt, and the mixture is heated in a pre-heated oil bath (90°) under nitrogen for 30 minutes. The mixture is then cooled and worked up immediately by partitioning between pentane/5% sodium hydroxide. The layers are separated and the pentane phase is extracted with 5% sodium hydroxide (2×). The combined aqueous phases are extracted with pentane (2×) and acidified with cold conc. hydrochloric acid. The aqueous phase is then extracted with ether (3×), and the combined ether phases are washed with brine and dried over magnesium sulfate. Filtration and evaporation yield (R)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid.
Reaction SMILES: Cl[C:2]([N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]1=2)=[O:3].[CH2:20]([N:22]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][N:27]1[CH2:32][CH2:33][CH2:34][NH2:35])[CH2:23][CH3:24])[CH3:21].C(OC(C)C)(C)C>O>[CH2:20]([N:22]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][N:27]1[CH2:32][CH2:33][CH2:34][NH:35][C:2]([N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]1=2)=[O:3])[CH2:23][CH3:24])[CH3:21]
Reactant: O=C1Nc2ccccc2N(C(=O)Cl)c2ccccc21
Reactant: CCN(CC)CC1CCCCN1CCCN
Solvent: CC(C)OC(C)C
Solvent: O
Product: CCN(CC)CC1CCCCN1CCCNC(=O)N1c2ccccc2NC(=O)c2ccccc21
Yield: 54 %

Procedure:
Prepared analogously to Example 2 from 5-chlorocarbonyl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one and 3-[2-[(diethylamino)methyl]-piperidin-1-yl]propanamine in a yield of 54% of theory, m.p. 148.0°-149.5° C. (diisopropylether). Soluble in water.
Reaction SMILES: [C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@@H:19]([C:38](O)=[O:39])[NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].Cl.[NH2:57][CH2:58][CH2:59][CH2:60][C:61]([P:64](=[O:71])([O:68][CH2:69][CH3:70])[O:65][CH2:66][CH3:67])([F:63])[F:62].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH:35]1[C:36]2[CH:24]([CH2:23][O:22][C:21]([NH:20][C@@H:19]([CH2:18][S:17][CH2:16][C@H:15]([O:14][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[C:38]([NH:57][CH2:58][CH2:59][CH2:60][C:61]([P:64](=[O:71])([O:68][CH2:69][CH3:70])[O:65][CH2:66][CH3:67])([F:62])[F:63])=[O:39])=[O:37])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]=2[CH:32]=[CH:33][CH:34]=1
Reactant: CCCCCCCCCCCC(=O)OC[C@H](CSC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)OC(=O)CCCCCCCCCCC
Reactant: CCOP(=O)(OCC)C(F)(F)CCCN
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCCCCCC(=O)OC[C@H](CSC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)NCCCC(F)(F)P(=O)(OCC)OCC)OC(=O)CCCCCCCCCCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acid (6, 1 eq) in DCM (0.1 M) was added diethyl 4-amino-1,1-difluorobutylphosphonate hydrochloride (1.1 eq), DIEA (3.5 eq) and HBTU (1.1 eq). The reaction mixture was then stirred at room temperature for 2 hours. The mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 30-70% EtOAc/Hex to give the product.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[H-].[Na+].Cl[C:23]1[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][N:26]=[C:25]2[N:34]([CH3:38])[N:35]=[C:36]([CH3:37])[C:24]=12.O>CN1CCCC1=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([S:9]([N:12]([CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[C:23]2[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][N:26]=[C:25]3[N:34]([CH3:38])[N:35]=[C:36]([CH3:37])[C:24]=23)(=[O:10])=[O:11])=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1cnc2c(c(C)nn2C)c1Cl
Reactant: COc1ccc(S(=O)(=O)NCc2cccnc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: CCOC(=O)c1cnc2c(c(C)nn2C)c1N(Cc1cccnc1)S(=O)(=O)c1ccc(OC)cc1
Temperature: 25 °C
Yield: 57.8 %

Procedure:
To a solution of 1.39 g (5 mmol) of (4-methoxybenzenesulfonyl)(3-pyridinylmethyl) amine in 4 ml of anhydrous 1-methyl-2-pyrrolidinone was added 0.2 g (5 mmol) of sodium hydride (60% in oil) and the mixture stirred at room temperature until gas evolution ceased. To this mixture was added 1.15 g (4.54 mmol) of ethyl 4-chloro-1,3-dimethylpyrazolo[3,4-b]pyridine-5-carboxylate and 2 ml of anhydrous 1-methyl-2-pyrrolidinone. The mixture was stirred in a sealed tube under nitrogen in an oil bath at 90° C. for 3 days. The mixture was cooled, poured into water and extracted with ethyl acetate. The extract was washed with H2O, brine and dried (Na2SO4). The solution was filtered through a thin pad of hydrous magnesuim silicate and the filter pad washed with ethyl acetate. The filtrate was concentrated to dryness under vacuum to give 1.3 g of solid. Chromatography on silica gel with ethyl acetate as solvent gave 0.35 g of product as a solid, mp 152-154° C.
Reaction SMILES: [C:1]([O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]=[O:14])=[CH:9][CH:8]=1)(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH2:15](O)[CH2:16][OH:17].C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[C:1]([O:6][C:7]1[CH:8]=[CH:9][C:10]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)=[CH:11][CH:12]=1)(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: OCCO
Reactant: C=C(C)C(=O)Oc1ccc(C=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: C=C(C)C(=O)Oc1ccc(C2OCCO2)cc1
Temperature: 25 °C

Procedure:
A 500 mL round bottom flask fitted with reflux condenser, Dean Stark trap and nitrogen line was charged with 30.0 g of 4-formylphenyl methacrylate, 19.0 g of ethylene glycol, 250 mL of toluene and a catalytic amount of p-toluenesulfonic acid monohydrate. The solution was heated at reflux for 1 day, during which time the water formed in the reaction was removed periodically from the Dean Stark trap. Toluene was added to make up for losses from the Dean Stark trap, and the solution was heated at reflux for an additional 15 hours. Thereafter the solution was cooled to room temperature, was washed with three 75 mL portions of saturated sodium bicarbonate solution, and the toluene extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude acetal was chromatographed on silica gel (20:1 silica gel to compound weight ratio) with hexane/ethylacetate (4:1 volume ratio) to give purified acetal (18.8 g). 1H NMR (CDCL3) 7,5 (d, 2H), 7,1 (d, 2H), 6.3 (s, 1H), 5.78 (s, 1H), 5.7 (s, 1H), 4.15-3.85 (m, 4H), 2.02 (s, 3H); 13C NMR (CDC13) 165, 151, 135, 128, 127, 121, 103, 65, 18; IR (neat) 1735 cm-1 ester carbonyl. The spectral data are consistent with the postulated structure. The chromatographed acetal was used directly in the free radical polymerizations.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:19]#[C:20]Br>>[CH2:1]([N:8]1[CH2:9][CH2:10][N:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:20]1=[NH:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(CNCCNCc2ccccc2)cc1
Reactant: N#CBr
Product: N=C1N(Cc2ccccc2)CCN1Cc1ccccc1

Procedure:
The title compound was prepared in one step from N,N′-dibenzylethylenediamine and cyanogen bromide as described in Procedure A. The precipitated solid was filtered off the reaction mixture, washed with acetonitrile and recrystallized from MeOH to give the title compound as a hydrogen bromide salt. 1NMR (DMSO-d6) δ 3.48 (s, 4H), 4.61 (s, 4H), 7.32-7.46 (m, 10H), 8.51 (s, 2H). MS (ES+) m/z 266 ([M+1]+, 100).
Reaction SMILES: [NH2:1][C@@H:2]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:3][C@H:4]([OH:41])[C@@H:5]([NH:19][C:20](=[O:40])[C@@H:21]([N:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=2)[C:27]1=[O:39])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:49][O:50][C:51]([NH:53][C@@H:54]([C:58]([CH3:61])([CH3:60])[CH3:59])[C:55](O)=[O:56])=[O:52].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:42]([C@H:2]([NH:1][C:55]([C@@H:54]([NH:53][C:51](=[O:52])[O:50][CH3:49])[C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:3][C@H:4]([OH:41])[C@@H:5]([NH:19][C:20](=[O:40])[C@@H:21]([N:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[N:33]=2)[C:27]1=[O:39])[C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:11][CH:12]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1
Reactant: Cc1cccc(CN2CCN([C@H](C(=O)N[C@@H](Cc3ccc(-c4ccccn4)cc3)[C@@H](O)C[C@@H](N)Cc3ccccc3)C(C)(C)C)C2=O)n1
Reactant: COC(=O)N[C@H](C(=O)O)C(C)(C)C
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccc(-c2ccccn2)cc1)NC(=O)[C@@H](N1CCN(Cc2cccc(C)n2)C1=O)C(C)(C)C)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 10.6 %

Procedure:
A solution containing the product from Example 132B (0.023 mmol) in THF (0.25 mL) were added the product from Example 1F (0.005 g, 0.026 mmol), DEPBT (0.010 g, 0.033 mmol), and N,N-diisopropylethylamine (0.020 mL, 0.115 mmol), stirred at 25° C. for 16 hours, and partitioned between chloroform and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and then brine, dried over MgSO4, filtered and concentrated. The product was purified by chromatography on silica gel eluting with 0-100% ethyl acetate/dichloromethane, followed by 0-5% methanol in ethyl acetate to give the product. The product was re-purified by preparative TLC eluting with 5% methanol in ethyl acetate to give the title compound (0.002 g, 11% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.82 (s, 9 H), 0.91 (s, 9 H), 1.25 (m, 1 H), 1.52 (m, 2 H), 2.41 (m, 1 H), 2.43 (s, 3 H), 2.74 (m, 3H), 2.97 (q, J=9.2 Hz, 1 H), 3.24 (m, 1 H), 3.54 (s, 3 H), 3.66 (m, 1 H), 3.82 (d, J=9.9 Hz, 2 H), 4.09 (s, 1 H), 4.17 (m, 1 H), 4.25 (d, J=16 Hz, 1 H), 4.35 (d, J=16 Hz, 1 H), 4.53 (d, J=7.4 Hz, 1 H), 6.63 (d, J=9.9 Hz, 1 H), 7.11 (m, 8 H), 7.21 (d, J=8.09 Hz, 2 H), 7.51 (d, J=8.56 Hz, 1 H), 7.62 (t, J=7.7 Hz, 1 H), 7.75 (m, 2H), 7.83 (d, J=8.09 Hz, 1 H), 8.60 (d, J=4.1 Hz, 1 H).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[CH2:18][C:17]([CH3:20])=[CH:16]3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.C([Cu])#N.[C:29]([C:33]1[CH:41]=[C:40]2[C:36]([CH:37]=[C:38]([CH3:46])[CH:39]2[Si:42](Cl)([CH3:44])[CH3:43])=[C:35]([C:47]2[CH:52]=[C:51]([C:53]([CH3:56])([CH3:55])[CH3:54])[CH:50]=[C:49]([C:57]([CH3:60])([CH3:59])[CH3:58])[CH:48]=2)[C:34]=1[O:61][CH3:62])([CH3:32])([CH3:31])[CH3:30]>CCOCC.O>[C:29]([C:33]1[CH:41]=[C:40]2[C:36]([CH:37]=[C:38]([CH3:46])[CH:39]2[Si:42]([CH:16]2[C:15]3[C:19](=[C:11]([C:8]4[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][CH:7]=4)[CH:12]=[CH:13][CH:14]=3)[CH:18]=[C:17]2[CH3:20])([CH3:44])[CH3:43])=[C:35]([C:47]2[CH:48]=[C:49]([C:57]([CH3:60])([CH3:59])[CH3:58])[CH:50]=[C:51]([C:53]([CH3:56])([CH3:55])[CH3:54])[CH:52]=2)[C:34]=1[O:61][CH3:62])([CH3:31])([CH3:30])[CH3:32]
Reactant: CC1=Cc2cccc(-c3ccc(C(C)(C)C)cc3)c2C1
Reactant: COc1c(C(C)(C)C)cc2c(c1-c1cc(C(C)(C)C)cc(C(C)(C)C)c1)C=C(C)C2[Si](C)(C)Cl
Agent: N#C[Cu]
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: COc1c(C(C)(C)C)cc2c(c1-c1cc(C(C)(C)C)cc(C(C)(C)C)c1)C=C(C)C2[Si](C)(C)C1C(C)=Cc2c(-c3ccc(C(C)(C)C)cc3)cccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
To a solution of 5.54 g (21.1 mmol) of 7-(4-tert-butylphenyl)-2-methyl-1H-indene in 150 ml of ether 8.50 ml (21.3 mmol) of 2.5 M nBuLi in hexanes was added in one portion at −40° C. This mixture was stirred overnight at room temperature, then cooled to −40° C., and 190 mg of CuCN was added. The resulting mixture was stirred for 1 h at −20° C., then cooled to −40° C., and a solution of 10.5 g (21.1 mmol) of [6-tert-butyl-4-(3,5-di-tert-butylphenyl)-5-methoxy-2-methyl-1H-inden-1-yl](chloro)dimethyl-silane in 150 ml of ether was added in one portion. Further on, this mixture was stirred overnight at ambient temperature, then 0.5 ml of water was added. This solution was filtered through a pad of silica gel 60 (40-63 um) which was additionally washed by 2×75 ml of dichloromethane. The combined elute was evaporated to dryness, and the residue was triturated with 70 ml of n-hexane. The obtained suspension was filtered on glass frit, the precipitate was washed with 30 ml of n-hexane and dried in vacuum to give a white powder. Additionally, the mother liquor was evaporated to small volume. The formed suspension was filtered through glass frit (G3), and the precipitate was washed with 2×15 ml of n-hexane and then dried in vacuum. Again, the mother liquor was evaporated to give a yellowish oil which was re-crystallized at −30° C. for two months. Crystals precipitated from this solution were collected and dried in vacuum. Thus, 12.2 g (80%) of the title product was isolated. Assignment in NMR spectra was made using the following abbreviations: L1 for 4-(4-tert-butylphenyl)-2-methyl-1H-inden-1-yl and L2 for 6-tert-butyl-4-(3,5-di-tert-butylphenyl)-5-methoxy-2-methyl-1H-inden-1-yl.