Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([Mg]Br)[CH:2]([CH3:4])[CH3:3].[C:7]1([C:13]2[CH:25]=[CH:24][C:16]([C:17]([C:19]([O:21]CC)=O)=[O:18])=[CH:15][CH:14]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[OH:26][C:27]1[C:28](=O)[O:29][C:30](C)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)C=1O.C(Cl)(Cl)Cl>C1COCC1>[C:13]1([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:14]=[CH:15][C:16]([C:17]2([CH2:1][CH:2]([CH3:4])[CH3:3])[O:18][C:27](=[O:26])[C:28]([O:29][CH2:30][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[C:19]2[OH:21])=[CH:24][CH:25]=1
Reactant: CCOC(=O)C(=O)c1ccc(-c2ccccc2)cc1
Reactant: CC1(c2ccccc2)OC(=O)C(O)=C1O
Reactant: CC(C)C[Mg]Br
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: CC(C)CC1(c2ccc(-c3ccccc3)cc2)OC(=O)C(OCc2ccccc2)=C1O
Yield: 8 %

Procedure:
A total of 5.2 mL (10.4 mmol) of 2.0M isobutylmagnesium bromide was added to a solution of 2.4 g (10 mmol) of ethyl 4-phenylbenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 0.35 g (8% yield) of 5-[(1,1'-biphenyl)-4-yl]-4-hydroxy-3-phenylmethoxy-5-(2-methylpropyl)-2(5H)-furanone as an off white solid after crystallization from CHCl3 and hexanes.
Reaction SMILES: [H-].[Na+].[C:3]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:8]=[CH:7][C:6]([CH2:9][C@H:10]2[NH:14][C:13](=[O:15])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1.CC(O)=O>CN(C)C=O>[C:3]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:4]=[CH:5][C:6]([CH2:9][C@H:10]2[N:14]([CH2:28][C:27]3[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=3)[C:13](=[O:15])[CH2:12][CH2:11]2)=[CH:7][CH:8]=1
Reactant: COc1ccc(CCl)cc1
Reactant: O=C1CC[C@@H](Cc2ccc(-c3ccccc3)cc2)N1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: COc1ccc(CN2C(=O)CC[C@H]2Cc2ccc(-c3ccccc3)cc2)cc1
Temperature: 55 °C
Reaction time: 3 h

Procedure:
Under N2, sodium hydride (55%, 6.9 g, 158 mmol) is added to the mixture of (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (3a, R1=H) (36 g, 143 mmol) in 400 mL dry dimethylformamide at r.t., then 4-methoxybenzyl chloride (24.7 g, 158 mmol) is added. The reaction mixture is heated to 55° C. and stirred for 3 h. Cooled to r.t., 5 mL AcOH is added, and stirred for another 15 min, then dimethylformamide is removed, the residue is redissolved in 400 mL ethyl acetate, washed with water, dried with sodium sulfate. The solvent is removed, the residue is redissolved in 100 mL tert-butylmethylether, cooled to 0° C. and stirred for 5 h, filtered, and dried to afford (S)-5-biphenyl-4-ylmethyl-1-(4-methoxy-benzyl)-pyrrolidin-2-one (3a, R1=p-methoxybenzyl). 1HNMR (400 MHz, CDCl3): 1.78 (m, 1H, 3-CHH), 1.90 (m, 1H, 3-CHH), 2.28 (m, 2H, 2-CH2), 2.59 (dd, 1H, 5-CHH), 3.05 (dd, 1H, 5-CHH), 3.80 (s, 3H, OCH3), 3.98 (d, 1H, CHH), 5.05 (d, 1H, CHH), 6.80˜7.40 (13H, m, aromatic).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[N:29]1([CH2:34][CH2:35][NH2:36])[CH2:33][CH2:32][CH2:31][CH2:30]1>C(Cl)Cl>[N:29]1([CH2:34][CH2:35][NH:36][C:8]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)=[O:10])[CH2:33][CH2:32][CH2:31][CH2:30]1
Reactant: O=C(O)c1ccc(Br)cn1
Reactant: NCCN1CCCC1
Agent: COc1nc(Cl)nc(OC)n1
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: O=C(NCCN1CCCC1)c1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5-Bromo-pyridine-2-carboxylic acid (0.81 g, 4 mmol) was combined with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (0.85 g, 4.8 mmol) and diluted with DCM (20 mL). This was immediately treated with 4-methyl morpholine (0.81 g, 8 mmol) and allowed to stir at ambient temperature for 1 h. 2-Pyrrolidin-1-yl-ethylamine (0.46 g, 4 mmol) was then added in one portion. Stirring was continued overnight. Reaction solvents were removed and residue was taken up in ethyl acetate and washed once with water. Aqueous phase was back extracted once with fresh ethyl acetate. Organic phases were combined, washed once with brine and dried over sodium sulfate. Filtration followed by rotary evaporation provided product as yellow oil which solidified upon standing. Yellowish solids (0.5 g, 42%)
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=2)[CH:2]=1.[C@@H:15]1([NH2:25])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][CH2:16]1>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:14]=[CH:13][C:10]([CH2:11][NH:25][C@@H:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)[CH:2]=1
Reactant: O=Cc1ccc(-c2cccnc2)cc1
Reactant: N[C@H]1CCCc2ccccc21
Product: c1cncc(-c2ccc(CN[C@H]3CCCc4ccccc43)cc2)c1

Procedure:
4-(3-Pyridinyl)benzaldehyde and (1S)-1,2,3,4-tetrahydro-1-naphthalenylamine were processed as described in Example 1A to provide the title compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:14]=[CH:13][C:10]=1[CH:11]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([CH2:27][C:28]([O:30][CH3:31])=[O:29])#[N:26].N1CCCCC1>C(O)C>[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:14]=[CH:13][C:10]=1/[CH:11]=[C:27](\[C:25]#[N:26])/[C:28]([O:30][CH3:31])=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(OCc2ccccc2)cc1OCc1ccccc1
Reactant: COC(=O)CC#N
Solvent: C1CCNCC1
Solvent: CCO
Product: COC(=O)/C(C#N)=C/c1ccc(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A mixture of 2,4-dibenzyloxybenzaldehyde (1 g), methyl cyanoacetate (0.27 mL), piperidine (0.1 mL) and ethanol (30 mL) is stirred at ambient temperature for 20 minutes and the solvent is removed under reduced pressure. The residue is recrystallized from ethanol to give methyl (E)-3-(2,4-dibenzyloxyphenyl)-2-cyanoacrylate as a yellow solid (400 mg).
Reaction SMILES: S(Cl)([Cl:3])=O.[Br:5][C:6]([F:17])([F:16])[C:7]([F:15])([F:14])[CH2:8][CH2:9][CH2:10][C:11](O)=[O:12]>>[Br:5][C:6]([F:17])([F:16])[C:7]([F:15])([F:14])[CH2:8][CH2:9][CH2:10][C:11]([Cl:3])=[O:12]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)CCCC(F)(F)C(F)(F)Br
Product: O=C(Cl)CCCC(F)(F)C(F)(F)Br
Temperature: 50 °C
Reaction time: 4 h
Yield: 88 %

Procedure:
In nitrogen atmosphere, 780 g (6.33 mol) of thionyl chloride was added to 1300 g (4.87 mol) of the 6-bromo-5,5,6,6-tetrafluorohexanoic acid obtained as discussed above, followed by stirring at 50° C. for 4 hours. Then distillation was conducted under reduced pressure thereby obtaining 1223 g of the objective 6-bromo-5,5,6,6-tetrafluorohexanoyl chloride in the form of a light yellow liquid (88% yield, 91% GC purity).
Reaction SMILES: [CH2:1]([Si:3]([CH2:12]C)([CH2:10]C)[C:4]#[C:5][CH2:6][CH2:7][CH2:8][I:9])C.[C:14]1([P:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OCC)C>C(O)C>[I-:9].[C:27]1([P+:20]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][CH2:7][CH2:6][C:5]#[C:4][Si:3]([CH3:1])([CH3:10])[CH3:12])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CC[Si](C#CCCCI)(CC)CC
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCO
Solvent: CCOCC
Product: C[Si](C)(C)C#CCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [I-]
Temperature: 50 °C
Reaction time: 24 h

Procedure:
A solution of triethyl-(5-iodpent-1-inyl)silane (5.02 g, 16.3 mmol) and triphenylphosphine (3.94 g, 15 mmol) in absolute ethanol (100 mL) was stirred 4 h with reflux and overnight at 50° C. and then heated once again with reflux for 7 h. The reaction solution was then concentrated to low volume in a vacuum, the yellowish crystals formed were mixed with diethyl ether (50 mL) and stirred. The diethyl ether was itself concentrated to low volume in a vacuum and the crystals mixed with ethyl acetate (50 mL). After standing in the refrigerator for 24 h the crystals were aspirated, washed with cold ethyl acetate (50 mL) and dried in an exsiccator over phosphorus pentoxide.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:16][C:17]([F:41])([F:40])[C:18]([F:39])([F:38])[C:19]([F:37])([F:36])[O:20][C:21]([F:35])([C:26]([F:34])([F:33])[O:27][C:28]([F:32])=[C:29]([F:31])[F:30])[C:22]([F:25])([F:24])[F:23].C(C1C=CC=C(OC(F)(F)C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F)C=1)#C>O1CCCC1>[F:31][C:29]([F:30])([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[CH:28]([F:32])[O:27][C:26]([F:33])([F:34])[C:21]([F:35])([O:20][C:19]([F:36])([F:37])[C:18]([F:38])([F:39])[C:17]([F:16])([F:40])[F:41])[C:22]([F:25])([F:24])[F:23]
Reactant: O=Cc1ccc(O)cc1
Reactant: FC(F)=C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F
Agent: C#Cc1cccc(OC(F)(F)C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: O=Cc1ccc(OC(F)(F)C(F)OC(F)(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F)cc1

Procedure:
In the dry box, tetrahydrofuran (25 mL) and 4-hydroxybenzaldehyde (0.61 g, 0.005 mol) were added to a round bottom flask equipped with a stirrer. Potassium carbonate (0.175 g, 0.00126 mol) was then added to the flask. 1,1,1,2,2,3,3-Heptafluoro-3-(1,1,1,2,3,3-hexafluoro-3-(1,2,2-trifluorovinyloxy)propan-2-yloxy)propane (3.24 g, 0.0075 mol) was then added via the addition funnel and the reaction was placed in an oil bath and heated to a gentle reflux for two hours. The content was analyzed by proton NMR and shown to be 1-ethynyl-3-(1,1,2-trifluoro-2-(1,1,2,3,3,3-hexafluoro-2-(perfluoropropoxy)propoxy)ethoxy)benzene.
Reaction SMILES: Br[C:2]1[C:3]([O:16][CH2:17][CH3:18])=[CH:4][C:5]([O:13][CH2:14][CH3:15])=[C:6]([O:9][CH2:10][O:11][CH3:12])[C:7]=1[CH3:8].CCCCCC.CN(C)[CH:27]=[O:28].[Cl-].[NH4+].C1C[O:35][CH2:34]C1>>[CH2:17]([O:16][C:3]1[C:4]([O:28][CH3:27])=[C:5]([O:13][CH2:14][CH3:15])[C:6]([O:9][CH2:10][O:11][CH3:12])=[C:7]([CH3:8])[C:2]=1[CH:34]=[O:35])[CH3:18]
Reactant: CCOc1cc(OCC)c(OCOC)c(C)c1Br
Reactant: CN(C)C=O
Reactant: C1CCOC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCCCCC
Product: CCOc1c(C=O)c(C)c(OCOC)c(OCC)c1OC
Temperature: -40 °C
Reaction time: 0.5 h

Procedure:
43.6 g of 5-bromo-2,4-diethoxy-6-methyl-1-methoxymethyloxybenzene prepared in Referential Example 8 was dissolved in 220 ml of THF, and 100 ml of n-buthyllithium (1.6 M n-hexane solution) was dropwise added thereto at -70° C. The mixture was stirred at -40° C. for 30 min, and 11.9 g of dimethylformamide was dropwise added thereto. The temperature of the reaction mixture was returned to room temperature, and an aqueous ammonium chloride solution was added thereto,-followed by extracting with ethyl acetate. The organic phase was washed with water, dried, concentrated and purified by silica gel column chromatography (eluent; n-hexane : ethyl acetate=90 : 10) to prepare 19.2 g of the product compound as a colorless oleaginous substance.
Reaction SMILES: [CH:1]([CH:4]1[S:9][CH2:8][CH2:7][CH2:6][S:5]1)([CH3:3])[CH3:2].C([Li])CCC.[CH:15](=[O:19])[CH2:16][CH2:17][CH3:18]>O1CCCC1>[CH:1]([C:4]1([CH:15]([OH:19])[CH2:16][CH2:17][CH3:18])[S:9][CH2:8][CH2:7][CH2:6][S:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)C1SCCCS1
Reactant: CCCC=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCC(O)C1(C(C)C)SCCCS1
Temperature: -20 °C
Reaction time: 4 h
Yield: 86.4 %

Procedure:
To a solution of (39) (4 g, 24.7 mmol) in anhydrous tetrahydrofuran (50 mL) at −20° C. was dropwise added n-butyl lithium (1.6M in hexane, 18.5 mL, 29.6 mmol). The stirred mixture was allowed to warrn room temperature over 4 h and then cooled to −20° C. again. To this solution was added slowly a solution of n-butyraldehyde (2.7 mL, 29.6 mmol) in anhydrous tetrahydrofuran (10 mL). The resulting mixture was stirred for 16 h between −20° C. and room temperature. The reaction was quenched with saturated ammonium chloride solution and the mixture extracted with ethyl acetate. The organic layer was separated and dried over Na2SO4. After removing the solvent under reduced pressure, flash column chromatography of the residue on silica gel, eluting with 5% ethyl acetate/hexane provided 5 g (85%) of the title compound as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 0.96 (t, J=7.2 Hz, 3H), 1.11 (d, J=6.8, Hz, 3H), 1.17 (d, J=6.8 Hz, 3H), 1.42-1.52 (m, 2H), 1.76 (m, 1H), 1.87-1.95 (m, 2H), 2.04 (m, 2H), 2.62 (m, 4H), 2.94 (m, 2H), 4.03 (d, J=5.2 Hz, 1H).
Reaction SMILES: [C:1](O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([C:13]1[CH:26]=[CH:25][C:16]([O:17][CH2:18][CH2:19][N:20]2[CH:24]=[CH:23][N:22]=[CH:21]2)=[CH:15][CH:14]=1)(=[O:12])[NH2:11].CO.C(OCC)(=O)C>CN(C)C=O>[C:1]([NH:11][C:10]([C:13]1[CH:14]=[CH:15][C:16]([O:17][CH2:18][CH2:19][N:20]2[CH:24]=[CH:23][N:22]=[CH:21]2)=[CH:25][CH:26]=1)=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccccc1
Reactant: NC(=O)c1ccc(OCCn2ccnc2)cc1
Solvent: CCOC(C)=O
Solvent: CO
Solvent: CN(C)C=O
Product: O=C(NC(=O)c1ccc(OCCn2ccnc2)cc1)c1ccccc1

Procedure:
Treatment of benzoic acid with N,N'-carbonyldiimidazole and 1-[2-(4-carbamoylphenoxy)ethyl]imidazole in dry N,N-dimethylformamide as described in Example 34 gave 1-[2-(4-benzoylcarbamoylphenoxy)ethyl]imidazole, m.p. 152°-154° C. (from methanol/ethyl acetate). Found: C, 67.66; H, 5.16; N, 12.59. C19H17N3O3 requires: C, 68.05; H, 5.11; N, 12.53%.
Reaction SMILES: [C:1]1([C:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[C:1]1([C:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCc1ccc(CCl)cc1
Reactant: c1ccc(-c2cc(-c3ccccc3)[nH]n2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OCc1ccc(Cn2nc(-c3ccccc3)cc2-c2ccccc2)cc1
Temperature: 120 °C
Reaction time: 1 h
Yield: 65.2 %

Procedure:
A mixture of 3,5-diphenylpyrazole (7.32 g, 33 mmol), [4-(chloromethyl)phenyl]methanol (5.00 g, 32 mmol), potassium carbonate (6.90 g, 50 mmol) and N,N-dimethylformamide (50 mL) was stirred at 120° C. for 1 hr. The reaction mixture was poured into 1 N hydrochloric acid and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (7.10 g, yield 63%) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]([CH3:24])[CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1)[CH:6]=[O:7].C(O)C.[BH4-].[Na+].O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:6][OH:7])[CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[N:14]([CH3:24])[CH:15]=[C:16]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:17]=1
Reactant: COc1cc(C=O)ccc1OCc1nc(-c2ccccc2)cn1C
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: COc1cc(CO)ccc1OCc1nc(-c2ccccc2)cn1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.4 %

Procedure:
To a solution of 3-methoxy-4-[(1-methyl-4-phenyl-1H-imidazol-2-yl)methoxy]benzaldehyde (1.37 g) in tetrahydrofuran (50 mL)-ethanol (10 mL) was gradually added sodium borohydride (0.16 g) at room temperature, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the precipitated crystals were collected by filtration to give {3-methoxy-4-[(1-methyl-4-phenyl-1H-imidazol-2-yl)methoxy]phenyl}methanol as colorless crystals (1.15 g, yield 85%). Recrystallization from ethyl acetate-hexane gave colorless needle crystals. melting point: 126-127° C.
Reaction SMILES: [CH2:1]([Sn:5](Cl)([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].O1[CH2:19][CH2:18][CH2:17][CH2:16]1>>[CH2:1]([Sn:5]([C:2]#[C:1][Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:16][CH2:17][CH2:18][CH3:19])([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4]
Reactant: C1CCOC1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Product: CCCC[Sn](C#C[Sn](CCCC)(CCCC)CCCC)(CCCC)CCCC

Procedure:
In synthetic route `C1` of FIG. 1, an alternate two step process for preparing BFPE consistant with the route in Sutherlin et al., Macromolecules, v.19, p.1260-1265 (1986) is shown. The first step is coupling commercially available tri-n-butyltin chloride (Aldrich Chemicals, Milwaukee, Wis.) with lithium acetylide ethylenediamine complex. These precursors are heated to reflux in anhydrous tetrahydrofuran (THF) under an argon blanket to form bis(tri-n-butylstannyl)ethyne. The THF solution of bis(tri-n-butylstannyl)ethyne is subsequently washed and then dried over anhydrous sodium sulfate.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH2:21][NH:22][CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)=[O:28]>>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH2:21][N:22]([C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=2)=[O:28])[CH2:23][CH3:24])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: CCNCc1ccc(C)cc1-c1cc(CC(=O)OCC)ccc1OC
Reactant: O=C(Cl)OCc1ccc(Cl)cc1
Product: CCOC(=O)Cc1ccc(OC)c(-c2cc(C)ccc2CN(CC)C(=O)OCc2ccc(Cl)cc2)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 6, using the following starting materials: (2′-ethylaminomethyl-6-methoxy-5′-methyl-biphenyl-3-yl)-acetic acid ethyl ester and 4-chlorobenzyl chloroformate.
Reaction SMILES: [C:1]([O:5][C:6](=[O:10])[C@H:7]([CH3:9])[NH2:8])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[C:18](O)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C=O)C>[C:1]([O:5][C:6](=[O:10])[C@H:7]([CH3:9])[NH:8][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@H](N)C(=O)OC(C)(C)C
Reactant: O=C(O)c1cccnc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C[C@H](NC(=O)c1cccnc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Alanine t-butyl ester (0.454 g, 2.50 mmol) was dissolved in 15 ml of CH2Cl2, then Et3N (0.252 g, 2.50 mmol) was added and the mixture was stirred for 10 minutes at room temperature. Then nicotinic acid (0.31 g, 5.0 mmol) in 8 ml of DMF and HOBt (0.43 g, 3.20 mmol) in 5 ml of DMF were added, followed by DCC (0.52 g, 3.0 mmol) in 10 ml of CH2Cl2. The mixture was stoppered and stirred overnight at room temperature. The DCU which formed was removed by filtration and the solvent was removed in vacuo. The residue was dissolved in 25 ml of CHCl3 and washed successively three times with 5% acetic acid/H2O, three times with 7% NaHCO3 /H2O and once with saturated NaCl solution. The organic layer was dried over anhydrous Na2SO4 for one hour, then the solvent was removed in vacuo to give nicotinoyl-alanine t-butyl ester. That product was dissolved in 25 ml of 1:1 TFA/CHCl3 and was stirred at room temperature for 30 minutes. The solvent was removed in vacuo, the residue was triturated three times with Et2O and then recrystallized from Et2O to give nicotinoyl-alanine (27). TLC showed one spot, Rf =0.42 in 1:9 CH3OH/CHCl3. Mass spectrum showed one major peak centered at m/z=195 (M+H+) which matched the calculated molecular weight. The product was obtained in 53% overall yield (0.257 g, 1.325 mmol).
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH:10]=[N:9][CH2:8][CH2:7]2.[CH3:16][C:17]([C:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=1)=[O:18].C1C2C(=CC=CC=2)CCN=1.CC(C1CCCC=1)=O>>[CH3:2][O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[CH:10]3[N:9]([CH2:8][CH2:7][C:6]=2[CH:5]=1)[CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[C:17](=[O:18])[CH2:16]3
Reactant: CC(=O)C1=CCCCC1
Reactant: COc1cc2c(cc1OC)CCN=C2
Agent: C1=NCCc2ccccc21
Agent: CC(=O)C1=CCCC1
Agent: Cl
Product: COc1cc2c(cc1OC)C1CC(=O)C3CCCCC3N1CC2

Procedure:
When in Example 6 appropriate amounts of 3,4-dihydro-6,7 -dimethoxyisoquinoline hydrochloride and 1-cyclohexen-1-yl methyl ketone respectively are substituted for 3,4-dihydroisoquinoline and 1-cyclopenten-1-yl methyl ketone, 2,3,4,4a,6,7,11b,12,13,13a-decahydro-9,10-dimethoxy-1H-dibenzo[a,f]quinolizin-13-one is obtained, M.P. 129°-141°C.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[CH:12]=[CH:11][C:9]([NH2:10])=[N:8][C:6]2=[O:7])[CH2:3][CH2:2]1.[C:13]([NH:16][C:17]1[CH:26]=[CH:25][C:20]([S:21](Cl)(=[O:23])=[O:22])=[CH:19][CH:18]=1)(=[O:15])[CH3:14].C(#N)C>C(N(CC)CC)C>[C:13]([NH:16][C:17]1[CH:26]=[CH:25][C:20]([S:21]([NH:10][C:9]2[CH:11]=[CH:12][N:5]([CH2:4][CH:1]3[CH2:2][CH2:3]3)[C:6](=[O:7])[N:8]=2)(=[O:23])=[O:22])=[CH:19][CH:18]=1)(=[O:15])[CH3:14]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccn(CC2CC2)c(=O)n1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccn(CC3CC3)c(=O)n2)cc1

Procedure:
A mixture of 495 mg. of 1-cyclopropylmethylcytosine, 702 mg. of N-acetylsulfanilyl chloride, 10 ml. of acetonitrile and 322 mg. of triethylamine was stirred and refluxed for 18 hours. The solvent was evaporated under reduced pressure, and the residue triturated with 10 ml. of water and 3 ml. of 10% aqueous sodium hydroxide. The alkaline solution was decanted from the dark insoluble portion and cleared by filtration. Addition of acetic acid to about pH 5 gave a gummy precipitate which solidified only very slowly. The aqueous solution was decanted and the gum triturated with 2 ml. of hot ethanol, and allowed to settle in an ice bath to obtain after filtration 280 mg. of product, melting at 222°-224°. A sample for analysis was recrystallized from aqueous ethanol; m.p. 225°-226°.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]#[N:10])=[CH:5][CH:4]=1.BrCC1C(C#N)=CC=CC=1.[CH3:21][N:22]=[C:23]=[O:24].[C:25]([CH2:27][C:28]([OH:30])=O)#[N:26]>>[NH2:26][C:25]1[N:10]([CH2:9][C:6]2[CH:7]=[CH:8][C:3]([C:2]#[N:1])=[CH:4][CH:5]=2)[C:23](=[O:24])[N:22]([CH3:21])[C:28](=[O:30])[CH:27]=1
Reactant: N#CCC(=O)O
Reactant: CN=C=O
Reactant: N#Cc1ccc(CN)cc1
Agent: N#Cc1ccccc1CBr
Product: Cn1c(=O)cc(N)n(Cc2ccc(C#N)cc2)c1=O

Procedure:
α-Amino-p-tolunitrile (prepared from α-bromotolunitrile in a modification of the method described by J. H. Short and T. D. Darby, J. Med. Chem., 10 (5), 833, 1967) was treated first with methyl isocyanate followed by cyanoacetic acid according to the method of V. Papesch and E. F. Schroeder (J. Org. Chem., 1951, 16, 1879) to yield 4-[(6-amino-1,2,3,4-tetrahydro-3-methyl-2,4-dioxo-1-pyrimidinyl)methyl]benzonitrile, which was then nitrosated, reduced, and condensed with 4-formylcinnamic acid following an analogous procedure to that of Example 3 to give the title compound as a yellow solid with a melting point greater than 350° C. Analysis for (C23H17N5O4): C, 64.63; H, 4.01; N, 16.38. Found: C, 64.58; H, 4.06; N, 16.36.
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=3)=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[OH:25][C@@H:26]1[CH2:30][CH2:29][NH:28][CH2:27]1>>[OH:25][C@@H:26]1[CH2:30][CH2:29][N:28]([CH2:6][CH2:7][C:8]2[O:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]4[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=4)=[CH:13][C:11]=3[CH:12]=2)[CH2:27]1
Reactant: CS(=O)(=O)OCCc1cc2cc(-c3ccc(C#N)cc3)ccc2o1
Reactant: O[C@@H]1CCNC1
Product: N#Cc1ccc(-c2ccc3oc(CCN4CC[C@@H](O)C4)cc3c2)cc1

Procedure:
The product from Example 1C and 3-(R)-hydroxypyrrolidine were processed as described in Example 1D to provide the titled compound. 1H NMR (300 MHz, CD3OD) δ 7.88 (m, 1H), 7.80 (m, 4H), 7.60 (m, 2H), 6.80 (s, 1H), 4.55 (bs, 1H), 3.8-3.9 (m, 4H), 3.25-3.5 (m, 4H), 2.05-2.4 (m, 2H); MS (DCI) m/z 333 (M+H)+;