Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:23]=[CH:22][C:8]([NH:9][CH:10]=[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:7][CH:6]=1.[C:24](N1C=CN=C1)(N1C=CN=C1)=[O:25].C1(C)C=CC=CC=1.P([O-])([O-])([O-])=O>C(OCC)(=O)C>[O:25]=[C:24]1[N:4]([C:5]2[CH:6]=[CH:7][C:8]([NH:9][CH:10]=[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:22][CH:23]=2)[CH2:3][CH2:2][O:1]1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCOC(=O)C(=CNc1ccc(NCCO)cc1)C(=O)OCC
Agent: O=P([O-])([O-])[O-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=CNc1ccc(N2CCOC2=O)cc1)C(=O)OCC
Yield: 88.7 %

Procedure:
To a flask containing diethyl 2-({4-[(2-hydroxyethyl)amino]anilino}methylene)-malonate (0.48 g) and 1,1'-carbonyldiimidazole (0.32 g) is added toluene (15 mL). The reaction mixture is heated to reflux under an argon atmosphere overnight. The reaction mixture is cooled to room temperatue and partioned between ethyl acetate and phosphate buffer (pH=7, 1M). The phases are separated and the aqueous layer is extracted with two additional portions of ethyl acetate. The combined organic layers are washed with buffer, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is chromatographed on silica eluting with ethyl acetate. The product-containing fractions are evaporated to give 0.46 g of diethyl 2-{[4-(2-oxo-1,3-oxazolidin-3-yl)anilino]methylene}malonate as a creme solid.
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[O:6][C@H:7]([C:16]([NH:18][CH3:19])=O)[O:8][C@H:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.B#B>C1COCC1>[ClH:1].[Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[O:6][C@H:7]([CH2:16][NH:18][CH3:19])[O:8][C@H:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1
Reactant: CNC(=O)[C@H]1Oc2ccc(Cl)cc2[C@@H](c2ccccc2)O1
Agent: B#B
Solvent: C1CCOC1
Product: CNC[C@H]1Oc2ccc(Cl)cc2[C@@H](c2ccccc2)O1
Product: Cl

Procedure:
To a stirred solution, under nitrogen, of 8.0 g (26.4 mmoles) of cis-6-chloro-N-methyl-4-phenyl-1,3-benzodioxan-2-carboxamide was added dropwise, at room temperature, 150 ml (150 mmoles) of diborane (1M as BH3) in THF solution. After addition was complete, the solution was stirred and refluxed for 21 hours.
Reaction SMILES: [H][H].[N+:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[O:16][C:15]([NH2:17])=[N:14][N:13]=1)([O-])=O>>[NH2:3][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[O:16][C:15]([NH2:17])=[N:14][N:13]=1
Reactant: Nc1nnc(-c2ccccc2[N+](=O)[O-])o1
Reactant: [H][H]
Product: Nc1nnc(-c2ccccc2N)o1

Procedure:
Hydrogen was introduced at atmospheric pressure into the solution of 350 mg of 5-(2-nitrophenyl)-[1,3,4]oxadiazol-2-ylamine until the theoretical amount had been taken up. After filtering off the catalyst with suction and concentrating the mixture under reduced pressure, the remaining oily residue was purified by column chromatography (solvent: 95:5 dichloromethane/methanol; silica gel).
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([OH:17])[C:11]([OH:18])=[N:10]2>S(=O)(=O)(O)O>[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[N+:1]([O-:4])=[O:2])[N:13]=[C:12]([OH:17])[C:11]([OH:18])=[N:10]2
Reactant: Oc1nc2ccc(Cl)cc2nc1O
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: O=[N+]([O-])c1cc2nc(O)c(O)nc2cc1Cl
Yield: 87.8 %

Procedure:
Finely powdered potassium nitrate (1.01 g, 10 mmol) was added during 5 min. to a stirred solution of 6-chloro-2,3-dihydroxyquinoxaline (1.97 g, 10 mmol) in 50 ml of conc. sulfuric acid at 0° C. (icebath). After 1 h the icebath was removed and stirring was continued for 21/2 h at room temperature. The mixture was poured into 200 ml of ice/water and the precipitate was isolated, washed with water, ethanol, and ether. The product was dissolved in 70 ml of hot 2N sodium hydroxide, filtered while hot, and reprecipitated with conc. hypochloric acid to give 2.12 g (88%) of pure title compound; m.p. >300° C.;
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17]([OH:19])=O)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[CH3:63][NH:64][C@H:65]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[CH2:68][CH2:67][CH2:66]1>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17](=[O:19])[N:64]([CH3:63])[C@H:65]2[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH2:68][CH2:67][CH2:66]2)[N:16]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CN(CC#Cc1nc(C(=O)O)cs1)C(=O)OC(C)(C)C
Reactant: CN[C@@H]1CCCc2ccccc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: C[NH3+]
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(CC#Cc1nc(C(=O)N(C)[C@@H]2CCCc3ccccc32)cs1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 61.3 %

Procedure:
To a solution of 2-[3-(tert-butoxycarbonyl-methyl-amino)-prop-1-ynyl]-thiazole-4-carboxylic acid (1.11 g, 3.75 mmol) in DMF (20 mL) was added diisopropylethylamine (1.93 mL, 11.3 mmol), followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1.57 g, 4.13 mmol). After stirring 15 min at RT, (1R)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (0.60 g, 3.75 mmol) was added to the reaction mixture. After stirring overnight at RT, solvent was evaporated and the resulting brown oil was dissolved in ethylacetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (50 mL), 1M HCl solution (50 mL), and brine (50 mL). The organic layer was dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 2:8 to 3:7) to give methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydronaphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester (1.01 g, 61%). 1H-NMR (400 MHz, CDCl3): δ=7.75 (s, 1H (conformers)), 7.03-6.92 (m, 4H), 5.58-5.46 (m, 1H (conformers)), 4.18-4.09 (br, 2H), 2.75 (s, 3H (conformers)), 2.61 (s, 3H), 2.11-1.63 (m, 6H), 1.33 (s, 9H (conformers)). MS: m/z=462 (M+23).
Reaction SMILES: [CH2:1]([N:3]1[CH2:7][CH2:6][CH2:5][CH:4]1[CH2:8][NH:9][C:10](=[O:22])[C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([Cl:19])[C:12]=1[O:20]C)[CH3:2].B(Br)(Br)Br>C(Cl)Cl>[ClH:19].[CH2:1]([N:3]1[CH2:7][CH2:6][CH2:5][CH:4]1[CH2:8][NH:9][C:10](=[O:22])[C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([Cl:19])[C:12]=1[OH:20])[CH3:2]
Reactant: CCN1CCCC1CNC(=O)c1c(OC)ccc(Cl)c1OC
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCN1CCCC1CNC(=O)c1c(OC)ccc(Cl)c1O
Product: Cl

Procedure:
9.1 g (0.025 mole) of (-)-N-ethyl-2-(3-chloro-2,6-dimethoxybenzamidomethyl)pyrrolidine is dissolved in 250 ml of methylene chloride. 2.6 ml (0.027 mole) of boron tribromide is added. The mixture is left over night at room temperature. It is then washed with 2×100 ml of 2N NH3 and 100 ml of water, dried over Na2SO4 and evaporated. The residue is dissolved in diluted HCl and extracted with ether. The water phase is made alkaline with NH3 and is extracted with chloroform. The extract is dried over Na2SO4 and evaporated. The residue is dissolved in ether and HCl-ether is added. The precipitate is filtered off and dried over P2O5. M.p. sinterring at 100° C. Yield 7.4 g [α]D20 =-51.4° (2% ethanol; pH 10.3).
Reaction SMILES: C(C1CN([O:14][CH2:15][C:16]2[CH:39]=[CH:38][C:19]([O:20][CH2:21][C:22]3[N:23]=[C:24]([C:28]4[O:32][C:31]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:30][CH:29]=4)[O:25][C:26]=3[CH3:27])=[C:18]([O:40][CH3:41])[CH:17]=2)N(C2C=CC=CC=2)C=1)=O.[Cl-].[CH2:43]([C:45]1[S:46][CH:47]=[C:48]([CH2:50][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:49]=1)[CH3:44].C(=O)([O-])[O-].[K+].[K+].[CH3:76][N:77]([CH3:80])C=O>O>[CH2:43]([C:45]1[S:46][CH:47]=[C:48](/[CH:50]=[CH:27]\[C:26]2[C:22]([O:14][CH2:15][C:16]3[CH:39]=[CH:38][C:19]([O:20][CH2:21][C:22]4[N:23]=[C:24]([C:28]5[O:32][C:31]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:30][CH:29]=5)[O:25][C:26]=4[CH3:27])=[C:18]([O:40][CH3:41])[CH:17]=3)=[N:23][N:77]([C:80]3[CH:38]=[CH:39][CH:16]=[CH:17][CH:18]=3)[CH:76]=2)[N:49]=1)[CH3:44]
Reactant: CN(C)C=O
Reactant: CCc1nc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cs1
Reactant: CCOC(=O)c1ccc(-c2nc(COc3ccc(CON4CC(C=O)=CN4c4ccccc4)cc3OC)c(C)o2)o1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: O
Product: CCOC(=O)c1ccc(-c2nc(COc3ccc(COc4nn(-c5ccccc5)cc4/C=C\c4csc(CC)n4)cc3OC)c(C)o2)o1
Temperature: 25 °C
Reaction time: 15 h
Yield: 32 %

Procedure:
A mixture of ethyl 5-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-2-yl)oxy]methyl}-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}-2-furancarboxylate (1.39 g), [(2-ethyl-1,3-thiazol-4-yl)methyl]triphenylphosphonium chloride (1.61 g), potassium carbonate (0.53 g) and N,N-dimethylformamide (30 mL) was stirred at room temperature for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:1, v/v) to give ethyl 5-[4-({4-[({4-[(Z)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]-2-methoxyphenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]-2-furancarboxylate as colorless crystals (0.54 g, yield 32%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 133-135° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:5]=[C:4]([NH2:16])[N:3]=1.C1(C)C=C(C)C=C(C)C=1S([NH:28]O)(=O)=O.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH:37]=O>>[NH2:16][C:4]1[N:3]2[N:28]=[C:37]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=3)[N:1]=[C:2]2[CH:7]=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:5]=1
Reactant: Nc1cc(C(=O)c2ccccc2)cc(N)n1
Reactant: Cc1cc(C)c(S(=O)(=O)NO)c(C)c1
Reactant: O=Cc1ccccn1
Product: Nc1cc(C(=O)c2ccccc2)cc2nc(-c3ccccn3)nn12

Procedure:
The title compound, MS m/e (%): 316 (M+H+, 100), was prepared in accordance with the general method of example 373 from (2,6-diamino-pyridin-4-yl)-phenyl-methanone, o-mesitylene-sulfonylhydroxylamine, and pyridine-2-carbaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:28]=[CH:27][C:21]4[CH2:22][CH2:23][NH:24][CH2:25][CH2:26][C:20]=4[CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11].[C:29]([O:33]C(C)(C)C)(=[O:32])[CH:30]=[CH2:31].C(N(C(C)C)CC)(C)C>CO>[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:28]=[CH:27][C:21]4[CH2:22][CH2:23][N:24]([CH2:31][CH2:30][C:29]([OH:33])=[O:32])[CH2:25][CH2:26][C:20]=4[CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11]
Reactant: CC(C)Oc1ccc(-c2nc(-c3ccc4c(c3)CCNCC4)no2)cc1Cl
Reactant: C=CC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: CC(C)Oc1ccc(-c2nc(-c3ccc4c(c3)CCN(CCC(=O)O)CC4)no2)cc1Cl
Temperature: 90 °C
Reaction time: 5 h
Yield: 46.2 %

Procedure:
A mixture of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (Example 17) (200 mg, 0.52 mmol), 1,1-dimethylethyl 2-propenoate (151 μL, 1.04 mmol) and diisopropylethylamine (453 μL, 2.60 mmol) in methanol (5 ml) was heated in the microwave at 90° C. for 30 minutes before the solvent was removed in vacuo. The residue was dissolved in 4M HCl (2 ml) in dioxane and the mixture stirred at room temperature for 5 h. The solvent was removed in vacuo and the residue purified by MDAP. To the product containing fractions was added 2M HCl and the solution concentrated in vacuo to give the title compound as a white solid (116 mg, 0.24 mmol). δH (d6DMSO, 400 MHz): 12.73 (1H, br.s), 10.76 (1H, br.s), 8.19 (1H, d), 8.11 (1H, dd), 7.98 (1H, d), 7.93 (1H, dd), 7.46 (1H, d), 7.45 (1H, d), 4.89 (1H, septet), 3.76-3.64 (2H, m), 3.44-3.31 (4H, hidden under H2O peak), 3.25-3.03 (4H, m), 2.89 (2H, t), 1.37 (6H, d). MS (ES): C24H2635ClN3O4 requires 455; found 456 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]=[N+]=[N-])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[CH:14]1[CH:19]=[CH:18][C:17]([CH:20]([OH:23])[CH2:21]N)=[CH:16][CH:15]=1>C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][CH2:21][CH:20]([C:17]1[CH:18]=[CH:19][CH:14]=[CH:15][CH:16]=1)[OH:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: NCC(O)c1ccccc1
Reactant: CC(C)(C)OC(=O)N=[N+]=[N-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)NCC(O)c1ccccc1
Reaction time: 8 h

Procedure:
28 g of t-butoxycarbonyl azide were added at room temperature to 200 ml of a methylene chloride solution containing 25.3 g of DL-2-amino-1-phenylethanol and 45 ml of triethylamine, and the reaction mixture was allowed to stand overnight at room temperature. The reaction mixture was then condensed by evaporation under reduced pressure, and water and diisopropyl ether were added to the condensate. The mixture was thoroughly stirred. yielding the title compound in the form of insoluble crystals melting at 123°-124° C. in a yield of 20.6 g. These crystals were filtered off. The organic layer in the filtrate was separated and washed with an aqueous solution of potassium hydrogen sulfate and with an aqueous solution of sodium bicarbonate. The resulting solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The crystals of the title compound in the residue were collected by filtration and washed with a mixture of diisopropyl ether and petroleum ether, yielding a further 18.7 g.
Reaction SMILES: S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:7]=1[CH2:15][C:16]([OH:18])=[O:17].[CH3:19][CH2:20]O>>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:7]=1[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]
Reactant: O=C(O)Cc1cc([N+](=O)[O-])ccc1Cl
Reactant: CCO
Solvent: O=S(Cl)Cl
Product: CCOC(=O)Cc1cc([N+](=O)[O-])ccc1Cl
Yield: 99 %

Procedure:
Thionyl chloride (16.7 g, 0.14 mol) was added dropwise to a 0° C. solution of (2-chloro-5-nitro-phenyl)acetic acid (15 g, 0.07 mol) in EtOH (300 mL) and the resultant mixture was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure and the residue was poured into ice water, and extracted with EtOAc (2×300 mL). The combined organics were washed with brine and saturated NaHCO3 solution, were dried over Na2SO4, and were concentrated in vacuo to give ethyl 2-(2-chloro-5-nitrophenyl)acetate (17 g, 99% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.35 (d, J= 2.8 Hz, 1 H), 8.12 (dd, J=8.4, 2.8 Hz, 1 H), 7.72 (d, J=8.4 Hz, 1 H), 4.10 (q, J=7.2 Hz, 2 H), 3.96 (s, 2 H), 1.15 (t, J=7.2 Hz, 3 H).
Reaction SMILES: [CH3:1][N:2]1[C:7]2=[CH:8][C:9]3[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11][C:10]=3[CH:23]=[C:6]2[O:5][CH2:4][C:3]1=[O:24].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][N:2]1[C:7]2=[CH:8][C:9]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11][C:10]=3[CH:23]=[C:6]2[O:5][CH2:4][C:3]1=[O:24]
Reactant: CN1C(=O)COc2cc3c(cc21)CCN(C(=O)OC(C)(C)C)CC3
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN1C(=O)COc2cc3c(cc21)CCNCC3

Procedure:
1,1-Dimethylethyl 4-methyl-3-oxo-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate (0.16 g) was treated with TFA (2 ml) in DCM (4 ml) for 3 h at 25° C. After elimination of volatiles under reduced pressure the residue was partitioned between aqueous NaHCO3 and DCM. The organic layer was collected and the aqueous phase extracted twice with DCM. The combined DCM layers were dried (Na2CO3), filtered and concentrated to give the title compound as a colourless solid which was used without further analysis (0.11 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[C:13]=2[CH3:20])=[C:6]([CH2:8]I)[CH:7]=1.CS(C)=O.[C-:25]#[N:26].[K+]>ClCCl.C(O)(C)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[C:13]=2[CH3:20])=[C:6]([CH2:8][C:25]#[N:26])[CH:7]=1
Reactant: [C-]#N
Reactant: COc1cccc(CCc2ccc(Br)cc2CI)c1C
Agent: [K+]
Solvent: ClCCl
Solvent: CC(C)O
Solvent: CS(C)=O
Product: COc1cccc(CCc2ccc(Br)cc2CC#N)c1C
Temperature: 42 °C
Reaction time: 16.5 h
Yield: 46 %

Procedure:
To 5-bromo-2-[2-(3-methoxy-2-methylphenyl)-ethyl]-phenyliodomethane 9 (5.56 g; 12.5 mmol) in dichloromethane (10 mL), isopropyl alcohol (10 mL), and DMSO (3 mL), was added potassium cyanide (1.22 g; 18.8 mmol). The mixture was stirred at 42° C. for 16.5 hours and concentrated in vacuo. The resultant residue was taken up in dichloromethane and water. The solution was shaken and the layers were separated. The organic layer was washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo to give an amber oil. The oil was chromatographed using SiO2 and hexane/ethyl acetate (3:2) as eluent to give compound 10, 1.99 g; 46% yield.
Reaction SMILES: [CH2:1]([S:8][CH2:9][C:10]1[N:18]=[C:17]2[C:13]([N:14]=[CH:15][N:16]2[C@H:19]2[C@H:23]([OH:24])[C@H:22]([OH:25])[C@@H:21]([CH2:26][O:27][CH3:28])[O:20]2)=[C:12]([NH:29][CH2:30][CH:31]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[OH:45].[Na+].OOS([O-])=O.[K+].ClCCl.[OH2:58]>CC(C)=O.C(OCC)(=O)C>[CH2:1]([S:8]([CH2:9][C:10]1[N:18]=[C:17]2[C:13]([N:14]=[CH:15][N:16]2[C@H:19]2[C@H:23]([OH:24])[C@H:22]([OH:25])[C@@H:21]([CH2:26][O:27][CH3:28])[O:20]2)=[C:12]([NH:29][CH2:30][CH:31]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:11]=1)(=[O:45])=[O:58])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])O
Reactant: O
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CSCc4ccccc4)nc32)[C@H](O)[C@@H]1O
Agent: O=S([O-])OO
Agent: [K+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Solvent: ClCCl
Product: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CS(=O)(=O)Cc4ccccc4)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 60 h

Procedure:
(2R,3R,4S,5R)-2-{2-[(Benzylsulfanyl)methyl]-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (100 mg, 0.17 mmol) (example 76) was dissolved in stirred acetone (3 ml) and solid sodium hydrogen carbonate (100 mg, 1.2 mmol) added. A solution of Oxone (trade mark) (potassium peroxymonosulphate) (410 mg, 0.68 mmol) dissolved in water (2 ml) was then added dropwise to the original solution over the course of 30 min. Dichloromethane (2 ml) was also added and the reaction mixture stirred at room temperature for 60 hr. The reaction mixture was then diluted with ethyl acetate (100 ml) and water (50 ml). The organic layer was separated, dried with anhydrous magnesium sulfate and the solvent removed under reduced pressure to give a residue which was purified by column chromatography on silica gel eluting with a solvent gradient of ethyl acetate:hexane (4:1) increasing in polarity to ethyl acetate:methanol (96:4). This gave the title compound (50 mg) as a gum. MS: 630 (MH+).
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([N:10]2[CH:15]([OH:16])[CH2:14][CH2:13][N:12]([CH3:17])[C:11]2=[O:18])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:19][N:20]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=1)[C:21](Cl)=[O:22].N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([C:5]1[S:9][C:8]([N:10]2[CH:15]([O:16][C:21](=[O:22])[N:20]([CH3:19])[C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=3)[CH2:14][CH2:13][N:12]([CH3:17])[C:11]2=[O:18])=[N:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(C(=O)Cl)c1ccc(Cl)c(Cl)c1
Reactant: CN1CCC(O)N(c2nnc(C(C)(C)C)s2)C1=O
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CN1CCC(OC(=O)N(C)c2ccc(Cl)c(Cl)c2)N(c2nnc(C(C)(C)C)s2)C1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole), N-methyl-N-(3,4-dichlorophenyl)carbamoyl chloride (0.06 mole), pyridine (0.06 mole) and toluene (150 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 3 hours. After this time the reaction mixture is cooled to room temperature and is filtered to remove pyridine hydrochloride. The filtrate is then washed with water, dried over anhydrous magnesium sulfate and stripped of solvent leaving a residue. The residue is recrystallized to yield the desired product tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-[N-methyl-N-(3,4-dichlorophenyl)carbamoyloxy]-2(1H)-pyrimidinone.
Reaction SMILES: [C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[Na+].[CH2:11]=[C:12]1[O:16][C:14](=[O:15])[CH2:13]1>>[O:16]=[C:12]([CH3:11])[CH2:13][C:14]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:15]
Reactant: CC(C)(C)O
Reactant: C=C1CC(=O)O1
Agent: CC(=O)[O-]
Agent: [Na+]
Product: CC(=O)CC(=O)OC(C)(C)C

Procedure:
To tert-butyl alcohol [79 g (1.07 mol.)] heated at 80° to 85° C. was added, while stirring, anhydrous sodium acetate [0.4 g (4.8 mmol.)]. To the mixture was then added dropwise diketene [96 g (1.14 mol.)] in the course of 2.5 hours. During the initial 15 minutes, the addition was carried out at 60° to 70° C., then while heating up to 110° to 115° C. After the dropwise addition of diketene, the resulting blackish brown reaction mixture was stirred for further 30 minutes, immediately followed by distillation under reduced pressure to afford tert-butyl 3-oxobutyrate, b.p. 85° C./20mmHg. The yield was 135 g (80%).
Reaction SMILES: C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O.[CH2:12]([O:19][CH:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][OH:26])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)Cl>[CH2:12]([O:19][CH:20]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[O:26])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCCCCCCCC(CCCCCO)OCc1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCCCCCCCC(CCCCC=O)OCc1ccccc1
Reaction time: 2 h

Procedure:
PCC (9.7 g, 45 mmol) was added in portions to a solution containing 6-benzyloxy-1-tetradecanol (7.5 g, 30 mmol) in methylene chloride (100 ml) at RT. The black mixture was stirred for 2 hours, then filtered through a bed of silica gel using hexane:ethyl acetate (90:10). The corresponding aldehyde, 6-benzyloxy-tetradecanal, was produced at a yield of 6.1 g (81%). This aldehyde compound was mixed with carbethoxymethylene triphenylphosphorane (10 g, 29 mmol) in 100 ml of methylene chloride at RT. The mixture was allowed to stir overnight, after which the solvent was removed and replaced with hexane. Solid precipitates were removed by filtration. Following chromatography on silica gel using hexane:ethyl acetate at a ratio of 90:10, the corresponding ester was detected at 8.4 g scale (90%). The chemical shift of the ester, 8-benzyloxyhexadec-2-enoa- to ethyl ester, is as follows: .sup.1H-NMR (CDCl3).delta. 0.89 (m, 6H, CH3), 1.2-1.5 (m, 20H, CH2), 2.2 (m, 2H, CH2-C.dbd.), 3.35 (m, 2H, CH2O), 4.2 (q, 2H, MeCH2-O), 4.55 (dd, 2H, CH2-O), 5.8 (d, 1H, CH.dbd.C), 6.95 (d,t 1H, CH.dbd.C), 7.35 (m, 5H, benzyl).