Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:3](=[O:10])[NH:4][C:5](=[O:9])[NH:6][C:7]=1[CH3:8].[CH3:11][Si](C)(C)N[Si](C)(C)C>CN(C=O)C>[CH3:11][N:6]1[C:7]([CH3:8])=[C:2]([CH3:1])[C:3](=[O:10])[NH:4][C:5]1=[O:9]
Reactant: C[Si](C)(C)N[Si](C)(C)C
Reactant: Cc1[nH]c(=O)[nH]c(=O)c1C
Solvent: CN(C)C=O
Product: Cc1c(C)n(C)c(=O)[nH]c1=O
Temperature: 150 °C

Procedure:
6.00 g (42.9 mmol) 5,6-dimethyluracil was dissolved in 26 mL of hexamethyldisilazane and 2.1 mL DMF. The mixture was heated for 11 hours at 150° C. and the excess of hexamethyldisilazane was removed under reduced pressure. Toluene was added to the mixture and evaporated off under reduced pressure to remove any residual hexamethyldisilazane. The residue was dissolved in 25 mL of iodomethane, refluxed for 2 hours, the excess iodomethane then evaporated off under reduced pressure and the residue recrystallized from deionised water yielding after drying 5.76 g (87%) of 1,5,6-trimethyluracil (m.p. 254–257° C., lit. 256–258° C.).
Reaction SMILES: [C:1]([NH:8][C@@H:9]([C:12]#[CH:13])[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>C(Cl)Cl>[C:1]([NH:8][C@@H:9]([C:12]#[CH:13])[CH2:10][O:11][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: C#C[C@@H](CO)NC(=O)OC(C)(C)C
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: C#C[C@@H](CO[Si](C)(C)C(C)(C)C)NC(=O)OC(C)(C)C

Procedure:
(S)-N-Boc-2-amino-1(-tert-butyldimethylsilyloxy)-but-3-yne was prepared by the treatment of (S)-N-Boc-2-amino-but-3-yn-1-ol (120 mg, 0.65 mmol) (Example 115A above) with imidazole (110 mg, 1.29 mmol) (Aldrich) and tert-butyldimethylsilyl chloride (120 mg, 0.77 mmol) (Fluka) in CH2Cl2 (10 mL) according to the procedure described above in Example 104B. (Yield 190 mg, 98%).
Reaction SMILES: [C:1]([C:3]([C:25]#[N:26])=[C:4]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]C)[S:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]C)#[N:2].C(C(C#N)=C(SCCCCCCCCCCCCCC)SCCCCCCCCCCCCCC)#N.C(C(C#N)=C(SCCCCCCCCCCCCCCCCCC)SCCCCCCCCCCCCCCCCCC)#N.C(C(C#N)=C(SCC1C=CC(CCCCCCCCCCCC)=CC=1)SCC1C=CC(CCCCCCCCCCCC)=CC=1)#N>>[C:1]([C:3]([C:25]#[N:26])=[C:4]([S:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[S:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])#[N:2]
Reactant: CCCCCCCCCSC(SCCCCCCCCC)=C(C#N)C#N
Agent: CCCCCCCCCCCCCCCCCCSC(SCCCCCCCCCCCCCCCCCC)=C(C#N)C#N
Agent: CCCCCCCCCCCCCCSC(SCCCCCCCCCCCCCC)=C(C#N)C#N
Agent: CCCCCCCCCCCCc1ccc(CSC(SCc2ccc(CCCCCCCCCCCC)cc2)=C(C#N)C#N)cc1
Product: CCCCCCCCSC(SCCCCCCCC)=C(C#N)C#N

Procedure:
1,1-dicyano-2,2-bis-nonylthioethylene; 1,1-dicyano-2,2-bis-tetradecylthioethylene; 1,1-dicyano-2,2-bis-octadecylthioethylene; and 1,1-dicyano-2,2-bis-(4-dodecylbenzylthio)ethylene.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:11]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1>>[CH3:31][O:32][C:33]1[CH:34]=[CH:35][C:36]([S:39]([NH:1][C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[C:11]=2[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[C:5]([O:7][CH3:8])=[O:6])(=[O:41])=[O:40])=[CH:37][CH:38]=1
Reactant: COC(=O)c1cc(N)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Product: COC(=O)c1cc(NS(=O)(=O)c2ccc(OC)cc2)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1

Procedure:
Analogously to Example 86, by condensing methyl 3-amino-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate with 4-methoxybenzenesulphonyl chloride there was obtained methyl 3-(4-methoxy-benzenesulphonyl-amino)-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate and therefrom by treatment with 5.5M HCl there was obtained methyl 3-(2-hydroxy-ethoxy)-5-(4-methoxy-benzenesulphonylamino)-4-(3-methoxy-phenoxy)-benzoate.
Reaction SMILES: [O:1]=[C:2]1[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:17][C:18]#[CH:19].Cl[CH2:21][CH:22]=[N:23][OH:24].C(N(CC)CC)C>O1CCCC1>[CH3:21][C:22]1[CH:19]=[C:18]([CH2:17][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[N:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:2]2=[O:1])[O:24][N:23]=1
Reactant: ON=CCCl
Reactant: C#CCn1c(=O)c(C(=O)OCC)nc2ccccc21
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1nc2ccccc2n(Cc2cc(C)no2)c1=O
Temperature: 25 °C
Reaction time: 72 h
Yield: 92.8 %

Procedure:
3.0 g (11.7 mmol) of ethyl 2-oxo-1-(2-propynyl)-1,2-dihydroquinoxaline-3-carboxylate and 3.28 g (35.1 mmol) of chloroacetaldoxime were dissolved in tetrahydrofuran (30 mL), and 3.55 g (35.1 mmol) of triethylamine was added dropwise at a temperature in the range of 0° C. to 5° C. The mixture was stirred for 3 days at room temperature. After confirming the completion of the reaction, the solvent was distilled off under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of citric acid, dried over anhydrous sodium sulfate, and concentrated. The solid matter thus obtained was washed with diisopropyl ether, to obtain 3.4 g (yield: 93%) of ethyl 1-[(3-methylisoxazol-5-yl)methyl]-2-oxo-1,2-dihydroquinoxaline-3-carboxylate as a white powder.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])=[CH:2][CH3:3].C1(OCC=C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30]>O.CN(C)C=O>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH:28]([CH3:33])[C:29]([O:31][CH3:32])=[O:30])=[CH:2][CH3:3]
Reactant: COC(=O)C(C)Br
Reactant: CC=Cc1ccccc1O
Agent: C=CCOc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC=Cc1ccccc1OC(C)C(=O)OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 500 mg (3.72 mmol) of 2-propenylphenol (E/Z mixture), prepared by Claisen rearrangement of phenylallylether followed by double bond isomerisation, 1.02 g of potassium carbonate (0.74 mmol) and 745 mg of rac. methyl 2-bromopropionate (4.46 mmol) and 10 ml of dimethylformamide was stirred overnight at RT and then for 4 hours at 80° C. The reaction mixture was then added to 40 ml of water and extracted three times with 30 ml diethyl ether. The organic phase was washed with 5% sodium hydroxide solution, separated off, dried with Na2SO4 and concentrated by evaporation. 685 mg (83.6% of theory) of virtually pure methyl 2-(2-propenyl-phenyloxy)propionate were obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH3:10][N:11]([CH3:18])[C:12]([CH3:17])([CH3:16])[C:13](O)=[O:14].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:13](=[O:14])[C:12]([N:11]([CH3:18])[CH3:10])([CH3:17])[CH3:16])=[N:6][CH:7]=1
Reactant: NNc1ccc(F)cn1
Reactant: CN(C)C(C)(C)C(=O)O
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CN(C)C(C)(C)C(=O)NNc1ccc(F)cn1
Reaction time: 8 h

Procedure:
To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (200 mg, 1.57 mmol) in DMF (10.0 mL) was added 2-dimethylamino-2-methyl-propionic acid (206 mg, 1.57 mmol), EDC (332 mg, 1.73 mmol) and HOBt.H2O (21.0 mg, 0.16 mmol). The reaction was stirred overnight then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:7][CH:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[C:11]([C:16]#[C:17][CH:18]([OH:20])[CH3:19])=[C:10]([CH3:21])[CH2:9]1.O.Cl>COCCOCCOC.O1CCCC1>[OH:7][CH:8]1[CH2:13][C:12]([CH3:14])([CH3:15])[C:11]([CH:16]=[CH:17][CH:18]([OH:20])[CH3:19])=[C:10]([CH3:21])[CH2:9]1
Reactant: CC1=C(C#CC(C)O)C(C)(C)CC(O)C1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: COCCOCCOC
Solvent: O
Product: CC1=C(C=CC(C)O)C(C)(C)CC(O)C1
Yield: 55.5 %

Procedure:
To a suspension of 1.1 g of lithium aluminum hydride in 30 ml of anhydrous diglyme and 10 ml of anhydrous tetrahydrofuran (hereinafter "THF") was added dropwise 10 ml of an anhydrous THF solution containing 5 g of 4-(4-hydroxy-2,6,6-trimethylcyclohex-1-enyl)but-3-yn-2-ol in a nitrogen atmosphere, and the mixture was stirred at reflux for 15 hours. After completion of the reaction, the reaction mixture was cooled and carefully hydrolyzed with water under ice-cooling. The aqueous phase was neutralized with diluted hydrochloric acid and extracted with diethyl ether. The organic layers were combined, washed with water, and dried over anhydrous magnesium sulfate. The solvent, etc. were removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 2.8 g (yield: 55%) of 4-(4-hydroxy-2,6,6-trimethylcyclohex-1-enyl)but-3-en- 2-ol.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]1[S:20][C:19]2[C:18](=[O:21])[N:17]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[C:16](=[O:28])[N:15]([CH2:29][C:30]3[N:31]=[N:32][N:33]([CH2:35][CH3:36])[N:34]=3)[C:14]=2[CH:13]=1.[CH2:37]([O:39][C:40]1[C:49]([O:50][CH3:51])=[CH:48][C:47]2[C:46]([C:52]3[CH:53]=[C:54]([CH:58]=[CH:59][CH:60]=3)[C:55](O)=[O:56])=[N:45][C@@H:44]3[CH2:61][CH2:62][S:63][CH2:64][C@@H:43]3[C:42]=2[CH:41]=1)[CH3:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]1[S:20][C:19]2[C:18](=[O:21])[N:17]([CH:22]3[CH2:27][CH2:26][N:25]([C:55]([C:54]4[CH:58]=[CH:59][CH:60]=[C:52]([C:46]5[C:47]6[CH:48]=[C:49]([O:50][CH3:51])[C:40]([O:39][CH2:37][CH3:38])=[CH:41][C:42]=6[C@H:43]6[CH2:64][S:63][CH2:62][CH2:61][C@H:44]6[N:45]=5)[CH:53]=4)=[O:56])[CH2:24][CH2:23]3)[C:16](=[O:28])[N:15]([CH2:29][C:30]3[N:31]=[N:32][N:33]([CH2:35][CH3:36])[N:34]=3)[C:14]=2[CH:13]=1
Reactant: CCOc1cc2c(cc1OC)C(c1cccc(C(=O)O)c1)=N[C@@H]1CCSC[C@H]21
Reactant: CCn1nnc(Cn2c(=O)n(C3CCNCC3)c(=O)c3sc(-c4cc(OC)ccc4OC)cc32)n1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOc1cc2c(cc1OC)C(c1cccc(C(=O)N3CCC(n4c(=O)c5sc(-c6cc(OC)ccc6OC)cc5n(Cc5nnn(CC)n5)c4=O)CC3)c1)=N[C@@H]1CCSC[C@H]21

Procedure:
6-(2,5-dimethoxyphenyl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione hydrochloride (137 mg; compound B80) is reacted with 3-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (102 mg; compound C8) and HBTU (213 mg) in DCM (10 ml) in the presence of DIPEA (264 mg) according to the procedure described in example 2 to afford the title compound after purification by flash column chromatography [amino phase silica gel, eluation gradient: Cyclohexane/EtOAc/DCM, 100/0/0 to 50/40/10 to 30/60/10 to 0/90/10 (v/v/v)] and preparative HPLC as a solid.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][CH2:11][CH:12]([OH:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:8][C@@H:7]([N:21]2[CH:28]=[C:27]([CH2:29][CH3:30])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:6]1)(=[O:3])[CH3:2].[CH3:31][S:32](Cl)(=[O:34])=[O:33]>N1C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][CH2:11][CH:12]([O:20][S:32]([CH3:31])(=[O:34])=[O:33])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:8][C@@H:7]([N:21]2[CH:28]=[C:27]([CH2:29][CH3:30])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CCc1cn([C@H]2C[C@H](OC(C)=O)[C@@H](CCC(O)Cc3ccccc3)O2)c(=O)[nH]c1=O
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CCc1cn([C@H]2C[C@H](OC(C)=O)[C@@H](CCC(Cc3ccccc3)OS(C)(=O)=O)O2)c(=O)[nH]c1=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 300 mg of 3'-O-acetyl-5'-[2(RS)-hydroxy-3-phenylpropyl]-2',5'-dideoxy-5-ethyluridine and 0.2 ml of methanesulphonyl chloride in 5 ml of pyridine was left to stand at 0° C. overnight. The mixture was poured on to 40 ml of ice/water, stirred and extracted with 40 ml of ethyl acetate. The extract was dried over anhydrous sodium sulphate and evaporated to yield 330 mg of 3'-O-acetyl-2',5'-dideoxy-5-ethyl-5'-[2(RS)-methanesulphonyloxy-3-phenylpropyl]uridine.
Reaction SMILES: [OH-].[K+].Cl[CH:4]([C:15]#[N:16])[CH2:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=1>CO>[C:15]([CH:4]=[CH:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=1)#[N:16]
Reactant: N#CC(Cl)Cc1ccc(C(=O)O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: N#CC=Cc1ccc(C(=O)O)cc1

Procedure:
120 parts of potassium hydroxide are dissolved in 240 parts of methanol and this solution is poured slowly into a mixture of 209.5 parts of 4-(2-chloro-2-cyanoethyl) benzoic acid and 400 parts of methanol. The dehydrohalogenation reaction is very exothermic. Reflux is maintained for 30 minutes. The potassium salt of 4-(2-cyanovinyl) benzoic acid precipitates. It is filtered when cold and taken up in an acid medium to obtain the free acid. Thus, 160 parts of crude 4-(2-cyanovinyl) benzoic acid are obtained which are purified by sublimation under reduced pressure at about 190°-200° C. They are also sublimed under normal pressure at about 270° C.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:25])[NH:5][C:6]1[CH:7]=[C:8]([CH:21]=[CH:22][C:23]=1O)[CH2:9][C:10]1[N:14]2[CH:15]=[CH:16][C:17]([CH3:19])=[CH:18][C:13]2=[N:12][C:11]=1[CH3:20])[CH3:2].Cl.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O>[CH3:20][C:11]1[N:12]=[C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]2[C:10]=1[CH2:9][C:8]1[CH:21]=[CH:22][C:23]2[O:25][C:4]([NH:3][CH2:1][CH3:2])=[N:5][C:6]=2[CH:7]=1
Reactant: CCNC(=O)Nc1cc(Cc2c(C)nc3cc(C)ccn23)ccc1O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: CCNc1nc2cc(Cc3c(C)nc4cc(C)ccn34)ccc2o1
Reaction time: 1 h
Yield: 25.7 %

Procedure:
A mixture of 3-[3-(3-ethylureido)-4-hydroxybenzyl]-2,7-dimethylimidazo[1,2-a]pyridine (3.7 g) and polyphosphate ester (37 g) was stirred at 110° to 120° C. for one hour. The reaction mixture was dissolved in a mixture of ethyl acetate and water and the resultant solution was acidified to pH 1.0 with 10% hydrochloric acid. The separated aqueous layer was adjusted to pH 8.0 with aqueous 20% potassium carbonate and extracted with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was subjected to column chromatography on alumina. The fraction eluted with a mixture of chloroform and methanol (98:2 V/V) was collected and the solvent was evaporated in vacuo and the residue was recrystallized from a mixture of chloroform and diethyl ether to give 5-(2,7-dimethylimidazo[1,2-a]pyridin-3-ylmethyl)-2-ethylaminobenzoxazole (0.9 g).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12]([CH2:14][OH:15])=[CH:11][CH:10]=[CH:9]2.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O>ClCCl>[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12]([CH:14]=[O:15])=[CH:11][CH:10]=[CH:9]2
Reactant: COCc1cccc2cccc(CO)c12
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: COCc1cccc2cccc(C=O)c12
Reaction time: 1 h

Procedure:
(8-Methoxymethyl-naphthalen-1-yl)-methanol (Tetrahedron Lett. 1997; 38, 8161–8164) (0.36 g, 1.8 mmol) was dissolved in dichloromethane (10 mL). To the solution was then added 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3 (1H)-one, also known as Dess-Martin periodinane (1.5 g, 3.6 mmol). The reaction mixture was stirred for 1 hr, then partitioned with an aqueous saturated solution of thiosulfate and dichloromethane. The organic layer was washed with an aqueous saturated solution of thiosulfate, an aqueous saturated solution of sodium bicarbonate, brine, dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield crude 8-methoxymethyl-naphthalene-1-carbaldehyde which was used directly into the next step.
Reaction SMILES: [CH:1]1[C:13]2[C:12](=O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[C:4](C(Cl)=O)=[CH:3][CH:2]=1.S(C1C=CC(S)=CC=1)C1C=CC(S)=CC=1.C(N(CC)CC)C.[O:40]1CCCC1>>[C:1]1(=[O:40])[C:13]2[C:5]([C:6]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)=[CH:4][CH:3]=[CH:2]1
Reactant: C1CCOC1
Reactant: O=C(Cl)c1cccc2c1-c1ccccc1C2=O
Agent: Sc1ccc(Sc2ccc(S)cc2)cc1
Solvent: CCN(CC)CC
Product: O=C1C=CC=C2C1=Cc1ccccc12
Reaction time: 0.5 h

Procedure:
A 10.0 g quantity of 9-fluorenone-4-carbonyl chloride (0.04 mole, obtained from Aldrich Chemicals Co, Milwaukee, Wis. 53201, USA) and 100 ml of tetrahydrofuran (obtained from Aldrich) were added to a 250 ml, 3-neck round bottom flask equipped with a reflux condenser and a mechanical stirrer. The solution was stirred for about ½ hour, and then 5.16 g of 4,4′-thiobisbenzenethiol (0.02 mole, obtained from Aldrich) in 50 ml of tetrahydrofuran were added, followed by the addition of 4.17 g of triethylamine (0.04 mole, obtained from Aldrich). The solution was refluxed for 6 hours, filtered hot to remove triethylamine hydrochloride salt byproduct and the filtrate was evaporated to dryness to obtain a first dimeric fluorenone derivative. The first dimeric fluorenone derivative was recrystallized from tetrahydrofuran/methanol with activated charcoal. The first dimeric fluorenone derivative was dried at 60° C. vacuum oven for 6 hours to yield a yellow solid (6.85 g, 50% yield).
Reaction SMILES: C[O:2][C:3]([C:5]1[C:16]2[C:15](=[O:17])[CH:14]3[CH2:18][CH:10]([CH2:11][N:12]([CH2:19][CH:20]=[CH2:21])[CH2:13]3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=O.[BH4-].[Na+]>C(O)C>[CH2:19]([N:12]1[CH2:11][CH:10]2[CH2:18][CH:14]([CH:15]([OH:17])[C:16]3[C:9]2=[CH:8][CH:7]=[CH:6][C:5]=3[CH2:3][OH:2])[CH2:13]1)[CH:20]=[CH2:21]
Reactant: C=CCN1CC2CC(C1)c1cccc(C(=O)OC)c1C2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: C=CCN1CC2CC(C1)C(O)c1c(CO)cccc12
Reaction time: 18 h
Yield: 86.8 %

Procedure:
11-Allyl-8-oxo-11-aza-tricyclo[7.3.1.02,7]trideca-2(7),3,5-triene-6-carboxylic acid methyl ester (109 mg, 0.40 mmol) was stirred in ethanol (10 mL) and treated with NaBH4 (15 mg, 0.40 mmol). After 18 h, the reaction mixture was concentrated and treated with 1N HCl (50 mL) with stirring. After 30 min., the aqueous layer was extracted with Et2O (3×50 mL), basified with saturated aqueous Na2CO3 solution and extracted with EtOAc (3×50 mL). The organic layer was washed with saturated aqueous NaHCO3 solution (2×50 mL) and saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated to give an oil (90 mg, 90%). (TLC 35% EtOAc/hexanes Rf 0.23); 1H NMR (400 MHz, CDCl3) δ 7.27 (dd, J=7.5, 1.5 Hz, 1H), 7.18 (t, J=7.5 Hz, 1H), 7.01 (dd, J=7.5, 1.5 Hz, 1H), 5.62 (m, 1H), 5.27 (t, J=4.0 Hz, 1H), 5.05 (m, 1H), 4.88 (d, J=12.1 Hz, 1H), 4.41 (d, J=12.1 Hz, 1H), 4.27 (OH), 3.72 (OH), 3.31 (ddd, J=12.4, 2.5, 1.7 Hz, 1H), 2.85 (m, 3H), 2.52 (m, 1H), 2.38 (m, 1H), 2.05 (dd, J=11.4, 1.7 Hz, 1H), 1.80 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 143.2, 140.3, 139.1, 134.9, 128.9, 127.7, 127.2, 118.5, 68.7, 64.0, 61.5, 59.9, 55.1, 36.3, 33.3, 32.1; IR (cm−1) 3376, 3071, 2920, 2788, 1642, 1468, 1051, 796; APCl MS m/z 260.2 (M+1)+.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([O:14][C:15]1[CH:47]=[CH:46][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([C:25](OCC)=[O:26])[C:22]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:34][CH:33]=3)=[N:21]2)=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O>O1CCCC1>[CH2:7]([O:14][C:15]1[CH:47]=[CH:46][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][OH:26])[C:22]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:34][CH:33]=3)=[N:21]2)=[CH:17][CH:16]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(=O)c1cn(Cc2ccc(OCc3ccccc3)cc2)nc1OCc1ccc(OCc2ccccc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cn(Cc2ccc(OCc3ccccc3)cc2)nc1OCc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70 %

Procedure:
Lithium aluminium hydride (1.52 g) was added to a solution of ethyl 1-(4-benzyloxybenzyl)-3-(4-benzyloxybenzyloxy)-1H-pyrazole-4-carboxylate (11.00 g) in tetrahydrofuran (200 ml) at 0° C., and the mixture was stirred at room temperature for one hour. After water was added to the reaction mixture, the precipitate was removed by filtration and the filtrate was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and then concentrated. The crystals obtained were collected by filtration to yield [1-(4-benzyloxybenzyl)-3-(4-benzyloxybenzyloxy)-1H-pyrazol-4-yl]methanol (7.11 g, yield: 70%). This was recrystallized from tetrahydrofuran-hexane. Melting point: 128–129° C.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH2:8][O:9][N:10]=[C:11]([C:18]2[N:22]([CH3:23])[N:21]=[N:20][N:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[CH:4][CH:3]=1.N#N.[CH:26]#[C:27][CH2:28][CH2:29][CH2:30][CH3:31].C(N(C(C)C)C(C)C)C>C1COCC1.CCOC(C)=O.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:26]([C:2]1[N:7]=[C:6]([CH2:8][O:9][N:10]=[C:11]([C:18]2[N:22]([CH3:23])[N:21]=[N:20][N:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[CH:4][CH:3]=1)#[C:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: Cn1nnnc1C(=NOCc1cccc(Br)n1)c1ccccc1
Reactant: C#CCCCC
Agent: I[Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: N#N
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCC#Cc1cccc(CON=C(c2ccccc2)c2nnnn2C)n1
Reaction time: 0.05 h
Yield: 94.7 %

Procedure:
To a stirred solution of N-[(6-bromopyridin-2-yl)methoxy]-1-(1-methyl-1H-tetrazol-5-yl)-1-phenylmethanimine (0.20 g, 0.536 mmol, 1 eq.) in 2 ml dry THF “degassed” with N2, was added hexyne (0.176 g, 2.14 mmol, 4 eq.) followed by N-ethyldiisopropylamine (0.361 g, 2.79 mmol, 4 eq.), Copper Iodide (0.031 g, 0.161 mmol, 0.3 eq.) and Tetrakis(triphenylphosphine)palladium (0.186 g, 0.161 mmol, 0.3 eq.). The reaction was microwaved 120° C./normal/fixed hold/pre stir 100 s for 180 s. The reaction was diluted with EtOAc and filtered through a “celite” plug. The solvent was evaporated and the residue purified by chromatography on silica gel to give N-{[6-(hex-1-yn-1-yl)pyridin-2-yl]methoxy}-1-(1-methyl-1H-tetrazol-5-yl)-1-phenylmethanimine (0.19 g, 85% yield) as a yellow viscous oil.
Reaction SMILES: C(O[C:9]([NH:11][C@H:12](C(O)=O)[CH2:13][CH2:14][C:15]([OH:17])=[O:16])=O)C1C=CC=CC=1.[CH2:21]=[O:22].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>C(O)(=O)C.ClCCl.C(OCC)(=O)C.CO.ClCCl>[O:22]1[CH2:21][CH2:9][NH:11][CH:12]1[CH2:13][CH2:14][C:15]([OH:17])=[O:16]
Reactant: O=C(O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: C=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: O=C(O)CCC1NCCO1
Temperature: 25 °C

Procedure:
Into a 250 mL round bottomed flask equipped with an Dean-Stark distilling trap was charged 8 g (28.4 mmole) of N-benzyloxycarbonyl-L-glutamic acid, 1.45 g (50 mmole) paraformaldehyde, 28.5 mg p-toluenesulfonic acid monohydrate and 150 mL benzene. The mixture was refluxed for 8 hr during which the solution turned yellowish in color and solid appeared in the condenser and trap. Evaluation with TLC (silica gel GF, solvent: 5% methanol/dichloromethane or ethyl acetate:dichloromethane:acetic acid=1:1:0.05) indicated the reaction was complete. The reaction mixture was cooled down to room temperature, and then rotary evaporated to dryness. The residue was taken into ethyl acetate and washed with benzene. The ethyl acetate solution was dried over magnesium sulfate, filtered, and concentrated to yield the oxazolidine propionic acid product (quantitative recovery)