Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]([O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].FC(F)(F)C(O)=O.[CH2:17]([O:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[N:30]=[CH:29][N:28]=[C:27]3[N:31]([CH:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[N:32]=[CH:33][C:26]=23)=[C:22]([F:42])[CH:21]=1)[CH3:18].C(N(C(C)C)CC)(C)C.O>ClCCl>[CH:5]1([O:4][C:2]([N:37]2[CH2:38][CH2:39][CH:34]([N:31]3[C:27]4=[N:28][CH:29]=[N:30][C:25]([O:24][C:23]5[CH:40]=[CH:41][C:20]([O:19][CH2:17][CH3:18])=[CH:21][C:22]=5[F:42])=[C:26]4[CH:33]=[N:32]3)[CH2:35][CH2:36]2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: CCOc1ccc(Oc2ncnc3c2cnn3C2CCNCC2)c(F)c1
Reactant: O=C(Cl)OC1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCOc1ccc(Oc2ncnc3c2cnn3C2CCN(C(=O)OC3CCCC3)CC2)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.3 %

Procedure:
Cyclopentyl chloroformate (12 mg, 0.078 mmol) was added to a mixture of 4-(4-ethoxy-2-fluoro-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 29; 28 mg, 0.078 mmol), diisopropylethylamine (30 mg, 0.235 mmol) in dichloromethane (2 mL). The reaction was stirred at room temperature overnight. Water was added to quench the reaction and the aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried (sodium sulfate), filtered, evaporated and purified by flash chromatography on silica gel, eluting with 4% methanol/dichloromethane to give 4-[4-(4-ethoxy-2-fluorophenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid cyclopentyl ester (36 mg, 99%) as a white solid. Mass spectrum MH+=470.
Reaction SMILES: CO[C:3]([C:5]1[C:10](=[O:11])[N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[N:8]2[CH:23]=[CH:24][CH:25]=[C:7]2[C:6]=1[OH:26])=[O:4].[NH2:27][C@H:28]([C:30]([OH:32])=[O:31])[CH3:29].C[O-].[Na+]>>[OH:26][C:6]1[C:7]2[N:8]([CH:23]=[CH:24][CH:25]=2)[N:9]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=2)[C:10](=[O:11])[C:5]=1[C:3]([NH:27][C@@H:28]([CH3:29])[C:30]([OH:32])=[O:31])=[O:4]
Reactant: C[C@H](N)C(=O)O
Reactant: COC(=O)c1c(O)c2cccn2n(Cc2ccc(C(F)(F)F)cc2)c1=O
Agent: C[O-]
Agent: [Na+]
Product: C[C@H](NC(=O)c1c(O)c2cccn2n(Cc2ccc(C(F)(F)F)cc2)c1=O)C(=O)O

Procedure:
Prepared according to the reaction condition used in Example 19 step a) from 4-hydroxy-2-oxo-1-(4-trifluoromethyl-benzyl)-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid methyl ester, L-alanine and NaOMe. ESI (m/z): 424 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH2:6][C:5](=[O:7])[N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[N:3]=1.C1(C)C=CC(S([N:26]=[N+:27]=[N-])(=O)=O)=CC=1.C(N(CC)CC)C>CO>[N+:26](=[C:6]1[C:5](=[O:7])[N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[N:3]=[C:2]1[CH3:1])=[N-:27]
Reactant: CC1=NN(c2ccc(C(=O)O)cc2)C(=O)C1
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Solvent: CO
Solvent: CCN(CC)CC
Product: CC1=NN(c2ccc(C(=O)O)cc2)C(=O)C1=[N+]=[N-]
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A solution of 4-(3-methyl-5-oxo-2-pyrazolin-1-yl)benzoic acid (5.0 g, 0.023 mol) and p-toluenesulfonylazide (5.03 g, 0.026 mol) in methanol (30.0 mL) was treated with triethylamine (5.2 g; 0.051 mol.) and the reaction was stirred at room temperature for 5 hours.
Reaction SMILES: [CH3:1][CH:2]([CH2:18][CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])[CH2:3][CH2:4][O:5][C:6](=[O:17])[CH2:7][CH2:8][CH:9]([OH:16])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].N1C=CC=CC=1.[CH2:30]([O:38][C:39](Cl)=[O:40])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.O>O1CCCC1>[CH3:1][CH:2]([CH2:18][CH2:19][CH:20]=[C:21]([CH3:23])[CH3:22])[CH2:3][CH2:4][O:5][C:6](=[O:17])[CH2:7][CH2:8][CH:9]([O:16][C:39]([O:38][CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:40])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: O=C(Cl)OCCc1ccccc1
Reactant: CCCCCCC(O)CCC(=O)OCCC(C)CCC=C(C)C
Solvent: c1ccncc1
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCC(CCC(=O)OCCC(C)CCC=C(C)C)OC(=O)OCCc1ccccc1
Reaction time: 16 h
Yield: 89.7 %

Procedure:
To a mixture of 3 g 4-hydroxy-decanoic acid 3,7-dimethyl-oct-6-enyl ester and 1.45 g pyridine in 7 ml tetrahydrofuran was slowly added a solution of 1.87 g chlorocarbonic acid phenethyl ester (Schiving et al., Bull. Soc. Chim. Fr. (4), 43, 1928, 858) in 7 ml tetrahydrofuran. The mixture was stirred for 16 hours. Water was added and the mixture extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, 2N hydrochloric acid, water, dried over magnesium sulfate and evaporated to dryness. The residue was chromatographed on silica gel to give 3.91 g of a colorless liquid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[N:7]2)([O-])=O.CS(C)=O>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[N:7]2
Reactant: O=[N+]([O-])c1ccc2nccnc2c1
Agent: [Pd]
Solvent: CS(C)=O
Solvent: CCO
Product: Nc1ccc2nccnc2c1
Yield: 90 %

Procedure:
6-Nitro-quinoxaline (3, 5 mmol) was hydrogenated in the presence of 5% Pd/C (50 mg) under at room temperature in ethanol (30 ml) for 6-10 h. After the reaction 2 ml DMSO was added to the mixture and filtered. The filtrate was poured into water (200 ml) and the precipitate was filtered to give 6-amino-quinoxaline (4a-d) (90-95%).
Reaction SMILES: CO[C:3](=[O:16])[CH:4]=[CH:5][C:6]1[C:11]([O:12]C)=[CH:10][CH:9]=[CH:8][C:7]=1[O:14]C.B(Br)(Br)Br.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.C(OCC)(=O)C>[OH:12][C:11]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:6]=1[CH:5]=[CH:4][C:3](=[O:16])[O:14]2
Reactant: COC(=O)C=Cc1c(OC)cccc1OC
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: O=c1ccc2c(O)cccc2o1
Yield: 89.6 %

Procedure:
To a cold (-30° C.) solution of 2,6-dimethoxycinnamic acid methyl ester (5.2 g, 23.4 mmol, prepared as described above), in chloroform (250 ml), was added boron tribromide (80 ml of a 1M solution in methylene chloride). The mixture was allowed to stir under anhydrous conditions was poured into saturated aqueous sodium hydrogen carbonate solution (400 ml). [Caution Frothing] The organic phase was diluted with ethyl acetate (250 ml), the mixture was transferred to a separating funnel and extracted thoroughly. The organic phase was isolated, dried (MgSo4) and evaporated in vacuo to give a dark red oil which did not crystallize. The oil was purified further by chromatography on silica gel to give 5-hydroxycoumarin (3.4 g, 89%), as a pale-yellow crystalline powder. M.p. 226°-229° C. (Das Gupta et al. J. Chem. Soc. (C), 29, 1969 give m.p. 224°-225 ° C.) 1H NMR (DMSO-d6): 8.11 (dd, J=9,6,0.6 Hz, 1H), 7.40 (t, J=8.4 Hz, 1H), 6.78 (m, 2H), 6.34 (d, J=9.6 Hz, 1H).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[C:9](Cl)[N:8]=[C:7]([S:12][CH3:13])[N:6]=1)[CH2:2][CH:3]=[CH2:4].CCN(C(C)C)C(C)C.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>O1CCOCC1>[CH2:1]([C:5]1[N:6]=[C:7]([S:12][CH3:13])[N:8]=[C:9]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:10]=1)[CH2:2][CH:3]=[CH2:4]
Reactant: C=CCCc1cc(Cl)nc(SC)n1
Reactant: C1COCCN1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: C=CCCc1cc(N2CCOCC2)nc(SC)n1
Temperature: 80 °C

Procedure:
To a solution of 4-(3-buten-1-yl)-6-chloro-2-(methylthio)-pyrimidine (26.66 mmol) and DIPEA (5.1 mL, 29.33 mmol) in 1,4-dioxane (100 mL) at room temperature was added morpholine (2.6 mL, 29.33 mmol). The reaction mixture was stirred and heated at 80° C. overnight. After the reaction was completed, the volatiles were removed by evaporation in vacuo. The residue was purified by column chromatography (hexane/EtOAc=8:1 to 4:1) to provide the title compound. MH+266.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[C:19](=O)[C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=3[N:16](COCC[Si](C)(C)C)[S:15]2(=[O:34])=[O:33])[CH2:10][CH2:9]1)=O)(C)(C)C.[BH4-].[Na+].O.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41]([S:44]([OH:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1>CO>[C:38]1([CH3:48])[CH:39]=[CH:40][C:41]([S:44]([OH:47])(=[O:45])=[O:46])=[CH:42][CH:43]=1.[NH:8]1[CH2:9][CH2:10][CH:11]([C:14]2[S:15](=[O:33])(=[O:34])[NH:16][C:17]3[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=3[CH:19]=2)[CH2:12][CH2:13]1
Reactant: CC(C)(C)OC(=O)N1CCC(C2C(=O)c3ccccc3N(COCC[Si](C)(C)C)S2(=O)=O)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=S1(=O)Nc2ccccc2C=C1C1CCNCC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 65 %

Procedure:
4-[2,2,4-Trioxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2,3,4-tetrahydro-2λ6-2,1-benzothiazin-3-yl]-piperidine-1-carboxylic acid tert-butyl ester (865 mg, 1.7 mmol) was dissolved in methanol (25 mL). Mixture was cooled to 0° C. Sodium borohydride (100 mg, 2.6 mmol) was added to the mixture in three portions. Reaction stirred at 0° C. for 3 hours. Mixture was concentrated by roto-vap. Residue was treated with 1N hydrochloric acid. Material was extracted twice with ethyl acetate. Organic phase was dried (magnesium sulfate), filtered and concentrated to dryness. Residue was dissolved in benzene (20 mL). p-Toluenesulfonic acid monohydrate (475 mg, 2.5 mmol) was added to the mixture. Reaction was heated to reflux and held with stirring for 1 hour. Mixture was cooled to room temperature. Solids were filtered off. The sticky solid was treated with hot isopropyl alcohol (10 mL). Mixture was cooled to room temperature and allowed to stand overnight. Solids were filtered off, washed with isopropyl alcohol and then dried under high vacuum. Title compound was obtained as tan solid in 65% yield. MS m/e (M+H)+=265.2.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[CH:5]=[CH:6][CH:7]=O.[NH2:13][NH:14][C:15]([NH2:17])=[S:16]>>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[CH:5]=[CH:6][CH:7]=[N:13][NH:14][C:15]([NH2:17])=[S:16]
Reactant: COc1ccccc1C=CC=O
Reactant: NNC(N)=S
Product: COc1ccccc1C=CC=NNC(N)=S
Yield: 45 %

Procedure:
The compound is prepared according to the method described in Example 1A from 2-methoxycinnamaldehyde (6 mmol) and from thiosemicarbazide (6 mmol). Yield 45%.
Reaction SMILES: C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6]([NH:14][CH2:15][CH3:16])[CH:5]=1.[OH-].[Na+]>C(O)C>[CH2:15]([NH:14][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=1)[C:3]([OH:17])=[O:2])[CH3:16]
Reactant: CCNc1cc(C(=O)OC)cc(C(F)(F)F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCNc1cc(C(=O)O)cc(C(F)(F)F)c1
Temperature: 70 °C
Reaction time: 4 h

Procedure:
A mixture of 3-ethylamino-5-(trifluoromethyl)-benzoic acid methyl ester (1.38 g, 5.6 mmol), 5.5 mL 1M aqueous sodium hydroxide solution in 12 mL ethanol is shaken for 4 hours at 70° C. After cooling, the mixture is evaporated to dryness under reduced pressure. The resulting residue is dissolved in water, the pH adjusted to 5 with 1M hydrochloric acid. The precipitate is filtered off, washed with water and dried in vacuo to give the title compound.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1CN(C)[CH2:7][NH:6][C:5]1=[N:11][N+:12]([O-:14])=[O:13].O(C[CH:24]1[CH2:28][CH2:27][O:26][CH2:25]1)S(C(F)(F)F)(=O)=O.Cl.C(=O)(O)[O-].[Na+]>CN(C=O)C>[O:26]1[CH2:27][CH2:28][CH:24]([CH2:7][NH:6][C:5]([NH:4][CH3:3])=[N:11][N+:12]([O-:14])=[O:13])[CH2:25]1
Reactant: CN1CNC(=N[N+](=O)[O-])N(C)C1
Reactant: O=S(=O)(OCC1CCOC1)C(F)(F)F
Agent: Cl
Agent: O=C([O-])O
Agent: [H-]
Solvent: CN(C)C=O
Product: CNC(=N[N+](=O)[O-])NCC1CCOC1
Temperature: 25 °C
Yield: 53.4 %

Procedure:
A mixture comprising 10.0 g of (tetrahydro-3-furanyl)methanol, 29.5 g of trifluoromethanesulfonic anhydride, 10.0 g of pyridine and 200 ml of dichloromethane was stirred for an hour at room temperature. Water was poured into the reaction solution to separate the organic layer, which was washed with 1 N hydrochloric acid, water and a saturated saline solution, dried, and concentrated to obtain 20 g of 3-tetrahydro-furanylmethyl triflate. 3.25 g of 60% sodium hydride were added to 12.5 g of 1,5-dimethyl-2-nitroiminohexahydro-1,3,5-triazine and 60 ml of DMF at room temperature, followed by stirring for an hour. 20.0 g of the 3-tetrahydrofuranylmethyl triflate were added thereto, and the mixture was stirred at 50° C. for 2 hours. After cooling the mixture to room temperature, 50 ml of 2 N hydrochloric acid were added thereto, followed by stirring at 50° C. for 2 hours. The resultant mixture was neutralized with sodium bicarbonate and extracted with dichloromethane, and the extract was dried and concentrated. The residue thus obtained was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/1) to obtain 7.8 g of 1-{(tetrahydro-3-furanyl)methyl}-2-nitro-3-methylguanidine.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C:13]2[C:21]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[NH:15][C:14]=2[CH:22]=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH2:24]([S:26]([C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33](=[O:38])[CH2:32]2)(=[O:28])=[O:27])[CH3:25]>>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C:13]2[C:21]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[NH:15][C:14]=2/[CH:22]=[C:32]2\[C:33](=[O:38])[NH:34][C:35]3[C:31]\2=[CH:30][C:29]([S:26]([CH2:24][CH3:25])(=[O:28])=[O:27])=[CH:37][CH:36]=3)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCN(CCCc2c(C=O)[nH]c3c2CCCC3)CC1
Reactant: CCS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Product: CCS(=O)(=O)c1ccc2c(c1)/C(=C/c1[nH]c3c(c1CCCN1CCN(C(C)=O)CC1)CCCC3)C(=O)N2
Yield: 65 %

Procedure:
3-[3-(4-Acetyl-piperazin-1-yl)-propyl]-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (70 mg, 0.22 mmol), prepared as described in Example 10 above, was condensed with 5-ethylsulfonyloxindole (69.5 mg, 1.01 eq, 72% pure) following the procedure used in Example 1 above. The formed solid was purified by flash chromatography using (dichloromethane: methanol 50/1, 30/1) to give 75 mg of the desired product.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH2:11][O:10][C:9](=[O:12])[C:8]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)=[CH:15][CH:14]=2)=[CH:3][CH:2]=1.[CH3:31][NH2:32]>CO>[OH:10][CH2:11]/[C:7](/[C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1)=[C:8](/[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=2)=[CH:15][CH:14]=1)\[C:9]([NH:32][CH3:31])=[O:12]
Reactant: O=C1OCC(c2ccncc2)=C1c1ccc(OCc2ccc3ccccc3n2)cc1
Reactant: CN
Solvent: CO
Product: CNC(=O)/C(=C(\CO)c1ccncc1)c1ccc(OCc2ccc3ccccc3n2)cc1
Yield: 86 %

Procedure:
A solution of 4-(pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)furan-2(5H)-one (1.0 g, 0.002 mol) and MeNH2 in MeOH (25 mL) was refluxed for 1 h. The reaction mixture was concentrated in vacuo to afford (Z)-4-hydroxy-N-methyl-3-(pyridin-4-yl)-2-(4-(quinolin-2-ylmethoxy)-phenyl) but-2-enamide (920 mg, 86%) as a solid.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][C:7]=3[C:8](=O)[O:9]2)=[CH:4][CH:3]=1.[Li+].[BH4-]>C1COCC1>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][C:7]=3[CH2:8][O:9]2)=[CH:4][CH:3]=1
Reactant: O=c1oc2cc(Br)ccc2c2ccc(Br)cc12
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Brc1ccc2c(c1)COc1cc(Br)ccc1-2
Temperature: 25 °C
Reaction time: 3 h
Yield: 85.7 %

Procedure:
To a solution of 3,8-dibromo-benzo[c]chromen-6-one (650 mg, 1.85 mmol) in THF (20 mL) was added 2 M solution of LiBH4 in THF (3.7 mL, 7.4 mmol). The mixture was stirred for 3 hours at room temperature. Quenched slowly with ammonium chloride solution. The mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was suspended in 85% phosphoric acid (20 mL) and heated at 160° C. for 4 h. The mixture was extracted with ethyl acetate, washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product 3,8-Dibromo-6H-benzo[c]chromene as a white solid (539 mg, 86%).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC.OS([O-])(=O)=O.[K+]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[C@@H:15]([CH3:26])[CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=C(CCCCc1ccccc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Product: C[C@@H](CCCc1ccccc1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 43.5 %

Procedure:
To a stirring solution consisting of (S)-4-benzyl-3-(5-phenylpentanoyl)oxazolidin-2-one (21ma, 1.24 g, 3.68 mmol) in THF (20 mL) at −78° C. was slowly added lithium bis-(trimethylsilyl)amide solution (4.41 mL, 4.41 mmol, 1 M solution in THF). The reaction mixture was stirred at −78° C. for one hour, after which time iodomethane (0.27 mL, 4.2 mmol) was slowly added. The resulting reaction mixture was allowed to rise to room temperature with stirring overnight. The mixture was acidified with 5% KHSO4 and extracted twice with ethyl acetate. The organic layer was washed twice with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. Elution with ethyl acetate-heptane (25:75 v/v) afforded the title compound (563 mg, 43.6%) as a clear oil; TLC Rf 0.53 (solvent system: 25:75 v/v ethyl acetate-heptane; MS (ESI+) m/z 352.3 (M+H)+374.2 (M+Na)+.
Reaction SMILES: C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18]3[N:22]([CH2:23][CH:24]=[CH2:25])[CH:21]=[CH:20][N:19]=3)[C:15](=[O:26])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[SH:27][C:28]1[S:29][CH:30]=[N:31][N:32]=1.B(F)(F)F.CCOCC>C(#N)C>[CH2:23]([N:22]1[CH:21]=[CH:20][N:19]=[C:18]1[NH:17][CH:16]1[C:15](=[O:26])[N:10]2[C:11]([C:12]([OH:14])=[O:13])=[C:6]([CH2:5][S:27][C:28]3[S:29][CH:30]=[N:31][N:32]=3)[CH2:7][S:8][C@H:9]12)[CH:24]=[CH2:25]
Reactant: Sc1nncs1
Reactant: C=CCn1ccnc1NC1C(=O)N2C(C(=O)O)=C(COC(C)=O)CS[C@H]12
Agent: FB(F)F
Solvent: CCOCC
Solvent: CC#N
Product: C=CCn1ccnc1NC1C(=O)N2C(C(=O)O)=C(CSc3nncs3)CS[C@H]12
Yield: 11.4 %

Procedure:
To a suspension of 3-acetoxymethyl-7-(3-allylimidazol-2-yl)aminoceph-3-em-4-carboxylic acid (0.038 g.) and 2-mercapto-1,3,4-thiadiazole (0.012 g.) in acetonitrile (0.2 ml.) was added boron trifluoride etherate (48% w/w, 32 μl) and the mixture heated at 60° for 2.5 hours. The solvent was evaporated and the residue dissolved in water/MeOH/HOAc 70:30:1 v/v/v (2 ml.). The solution was decanted from the residual tar and then purified by HPLC using water/MeOH/HOAc 70:30:1 then 60:40:1 v/v/v as eluants to give 7-(3-allylimidazol-2-yl)amino-3-(1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylic acid (5 mg.) having the following n.m.r. in d6DMSO+CD3CO2D: 3.20 (d, 2H); 3.50 (d, 1H); 3.75 (d, 1H); 4.31 (d, 1H); 4.60 (d, 1H); 5.0-5.38 (m, 3H); 5.52 (d, 1H); 5.8 (m, 1H); 6.5 (s, 1H); 9.49 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:5]2.[H-].[Na+].[CH3:19]OCCOC.CI>C(O)C.O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH:12]([CH3:19])[C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:5]2
Reactant: COC(=O)Cc1ccc2cc(C)ccc2c1
Reactant: COCCOC
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Solvent: CI
Solvent: O
Product: COC(=O)C(C)c1ccc2cc(C)ccc2c1

Procedure:
To a mixture of 22 g. of methyl 6-methyl-2-naphthylacetate, 2.5 g. of sodium hydride and 150 ml. of 1,2-dimethoxyethane, 25 g. of methyliodide are added. The reaction mixture is allowed to stand for several hours; then it is diluted with ethanol followed by water and extracted with methylene chloride. The extracts are combined, washed with water to neutrality, dried over sodium sulfate, filtered, and evaporated to yield methyl 6-methyl-2-naphthyl-α-methylacetate. This derivative is hydrolyzed by means of the process described in Part H of Example 2 to obtain 6-methyl-2-naphthyl-α-methylacetic acid.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([Cl:12])[Cl:11].C1(S(O)(=O)=O)C=CC=CC=1>[Pt].C1(C)C=CC=CC=1>[CH2:1]([CH2:9][SiH:10]([Cl:12])[Cl:11])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C[SiH](Cl)Cl
Reactant: C=Cc1ccccc1
Agent: [Pt]
Agent: O=S(=O)(O)c1ccccc1
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CCCc1ccccc1
Yield: 19 %

Procedure:
Reaction between styrene and methyldichlorosilane with platinum catalyst in the presence of trimethylsilyl ester of benzenesulfonic acid. 624 mg Styrene and 732 mg methyldichlorosilane were introduced into a glass tube, and 54 mg of a trimethylsilyl ester of benzenesulfonic acid were added with a microsyringe. 0.9 mg of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) was added. The tube was sealed with Teflon tape and a rubber septum and then placed in a 50° C. oil bath where it was heated for 30 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 27% and a phenethylmethyldichlorosilane yield of 19%. The ratio between the phenethylmethyldichlorosilane and the (α-methylbenzyl)methyldichlorosilane was 4.2:1.
Reaction SMILES: [C:1](OC)(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[C:16]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19]>CCCCCC.O1CCCC1>[OH:4][C:3]1[CH2:5][C:16]([CH2:17][CH:18]([CH3:20])[CH3:19])([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[O:21][C:1](=[O:6])[CH:2]=1
Reactant: CC(C)CC(=O)c1ccccc1
Reactant: COC(=O)CC(C)=O
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)CC1(c2ccccc2)CC(O)=CC(=O)O1

Procedure:
The title compound was prepared as described in General Method 1 using 12 g methyl acetoacetate, 4.3 g of NaH 60% dispersion in oil, 64.5 mL of 1.6M n-butyl lithium in hexane, 10 g of iso-valerophenone, and 300 mL of tetrahydrofuran.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH2:11]=[C:12]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:13](OC)=[O:14].C(OCC)(=O)C.CCCCCC>C(Cl)Cl>[CH2:11]=[C:12]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:13][OH:14]
Reactant: C=C(CCCCCCCCCCCCCC)C(=O)OC
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: ClCCl
Product: C=C(CO)CCCCCCCCCCCCCC
Reaction time: 0.5 h

Procedure:
A solution of diisobutylaluminum hydride in CH2Cl2 (47 ml of a 1M solution, 0.047 mole, Aldrich Chem. Co.) was stirred under nitrogen in a round-bottom flask and cooled in an ice-water bath. To this was added dropwise over a period of 4 minutes a solution of 2-methylenehexadecanoic acid, methyl ester (2.82 g, 20 mmole) in CH2Cl2 (20 ml). The reaction was complete within 30 minutes as determined by TLC (20% ethyl acetate-hexane) of a sample quenched in brine-ether. The reaction was worked up after one hour by diluting with methylene chloride (300 ml) and adding several milliliters each of methanol and water. A gelatinous mass formed which broke up upon vigorous swirling. The mixture was filtered through Celite and the filtrate dried over MgSO4. Following filtration and concentration, an oily residue was obtained. The residue crystallized and was recrystallized by dissolving in hexane at room temperature then cooling in the freezer. Crystals were collected from the cold hexane by rapid filtration. 2-Methylenehexadecan-1-ol (22) was obtained in a first crop (1.718 g) of colorless crystals, mp 33°-34° C., and a second crop (0.081 g, total 1.799 g, 0.0071 mole, 71%).