Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:36]=[CH:35][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:27]=[CH:26][C:25]([CH2:28][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[CH:24][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([O:22]C)=[O:21])[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:27]=[CH:26][C:25]([CH2:28][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[CH:24][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]2)=[O:7])=[CH:35][CH:36]=1
Reactant: COC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccc(F)cc3)[nH]c3ccc(CN4CCOCC4)cc32)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(/N=c1\[nH]c2ccc(CN3CCOCC3)cc2n1[C@H]1CC[C@@H](C(=O)O)CC1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of cis-methyl 4-((E)-2-(4-fluorobenzoylimino)-6-(morpholinomethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (2.3 g, 4.65 mmol) in MeOH (46.5 mL) was added 1 N aqueous sodium hydroxide (46.5 mL, 46.5 mmol). The suspension wa stirred overnight at RT. The resulting solution was concentrated, adjusted to a pH of approximately 4 with 2 N aqueous HCl, and extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to generate cis-4-((E)-2-(4-fluorobenzoylimino)-6-(morpholinomethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid as a white powder (2.29 g, 102% yield). MS, m/z (C26H29FN4O4): calcd, 480.2. found, 480.2 (M).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:6][CH2:5]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]([F:35])([F:34])[F:33]>CN(C)C=O>[F:33][C:32]([F:34])([F:35])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH2:25][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:6][CH2:5]2
Reactant: FC(F)(F)c1ccccc1CBr
Reactant: CC(C)S(=O)(=O)NC1CCc2cc(O)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)S(=O)(=O)NC1CCc2cc(OCc3ccccc3C(F)(F)F)ccc21
Temperature: 60 °C
Reaction time: 3 h
Yield: 42 %

Procedure:
N-(5-hydroxy-2,3-dihydro-1H-inden-1-yl)propane-2-sulfonamide (50 mg, 0.196 mmol) was dissolved in N,N-dimethylformamide (dry) (2 mL), potassium carbonate (54.1 mg, 0.392 mmol) and 1-(bromomethyl)-2-(trifluoromethyl)benzene (94 mg, 0.392 mmol) were added and the mixture was stirred at 60° C. for 3 hr. After this time, the reaction mixture was partitioned between EtOAc and H2O, the organic layer separated and solvent evaporated in vacuo. Purification by flash chromatography (0-100% EtOAc in heptane) afforded the title compound as a colourless oil (34 mg, 42%). MS (ESI): m/z [M−H]− 412.0
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[C:10](OC(=O)C)(=[O:12])[CH3:11]>O>[C:10]([NH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)(=[O:12])[CH3:11]
Reactant: CC(=O)OC(C)=O
Reactant: N#Cc1ccc(N)cc1
Solvent: O
Product: CC(=O)Nc1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To 4-aminobenzonitrile (7.26 g) was added acetic anhydride (20 ml) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with water and the separated crystals were collected by suction, washed with water and dried under reduced pressure to give 9.40 g of 4-acetamidobenzonitrile.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[OH:11])=[O:3].CI.[C:14](=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[O:11][CH3:14])=[O:3]
Reactant: CC(=O)c1ccc(F)cc1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Solvent: CI
Product: COc1cc(F)ccc1C(C)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.6 %

Procedure:
A solution of 4-fluoro-2-hydroxyacetophenone (1 g, 6.5 mmol), methyl iodide (0.4 ml), potassium carbonate (1.34 g, 9.7 mmol) in anhydrous dimethylsulfoxide (20 ml) was allowed to stir at room temperature for 2 hours. The mixture was poured into water (100 ml) and extracted with methylene chloride (3×100 ml). The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was removed under vacuum to afford 1.1 g (100%) of product as a light yellow solid: mp 50-51.5° C.
Reaction SMILES: O.Cl.[O:3]=[C:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Br[CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14].C([O-])([O-])=O.[K+].[K+].CCN(CC)CC>CC(C)=O>[O:3]=[C:4]1[CH2:9][CH2:8][N:7]([CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH2:6][CH2:5]1
Reactant: O=C1CCNCC1
Reactant: COC(=O)CCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Solvent: O
Product: COC(=O)CCN1CCC(=O)CC1
Yield: 41.5 %

Procedure:
To a suspension of 4-oxopiperidine hydrochloride monohydrate (10.0 g, 65.1 mmol) and methyl 3-bromopropanoate (7.8 ml, 71.6 mmol) in acetone (100 ml) was added K2CO3 (9.9 g, 71.6 mmol) and Et3N (9.1 ml, 65.3 mmol). The mixture was refluxed for 24 hours. The solid was removed by filtration and the solvent was evaporated. The residue was partitioned between EtOAc and H2O. The organic extracts were combined and dried over Na2SO4. The solvent was evaporated to give the title compound (15.0 g, 27.0 mmol, 42%) as an oil. 1H NMR (300 MHz, CDCI) δ 3.70 (s, 3H), 2.75-2.85 (mult, 6H), 2.52-2.57 (mult, 2H), 2.42-2.46 (mult, 4H).
Reaction SMILES: [CH2:1]([O:4][C:5]1[C:6]2[N:7]=[CH:8][N:9]([C:32]=2[N:33]=[C:34]([NH2:36])[N:35]=1)[C@@H:10]1[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@@H:12]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:11]1)[CH:2]=[CH2:3].[Si]([N:41]=[N+:42]=[N-])(C)(C)C>>[CH2:1]([O:4][C:5]1[C:6]2[N:7]=[CH:8][N:9]([C:32]=2[N:33]=[C:34]([N:36]=[N+:41]=[N-:42])[N:35]=1)[C@@H:10]1[O:31][C@H:21]([CH2:22][O:23][Si:24]([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:26])[CH3:25])[C@@H:12]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])[CH2:11]1)[CH:2]=[CH2:3]
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: C=CCOc1nc(N)nc2c1ncn2[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O1
Product: C=CCOc1nc(N=[N+]=[N-])nc2c1ncn2[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O1
Yield: 63 %

Procedure:
As described for the synthesis of 2a, this compound was prepared by a reaction 1b (3.0 g, 5.6 mmol) with TMS—N3 (10 molar equiv) and t-BuONO (10 molar equiv). Chromatographic purification of the crude material on a silica gel column using 20% EtOAc in hexanes afforded 1.98 g (63% yield) of 2b as a viscous, yellow oil. Rf(SiO2/30% EtOAc in hexanes)=0.63. IR (neat): 2956, 2930, 2857, 2130, 1600 cm−1. 1H NMR (CDCl3): δ 8.18 (s, 1H, Ar—H), 6.42 (t, 1H, H-1′, J=6.4 Hz), 6.18-6.11 (m, 1H, ═CH), 5.49 (dd, 1H, ═CHtrans, J=1.4, 17.2 Hz), 5.33 (dd, 1H, ═CHcis, J=1.4, 10.2 Hz), 5.11 (d, 2H, OCH2, J=5.8 Hz), 4.61-4.59 (m, 1H, H-3′), 4.01 (app q, 1H, H-4′, Japp˜3.4 Hz), 3.88 (dd, 1H, H-5′, J=4.0, 10.2 Hz), 3.79 (dd, 1H, H-5′, J=3.0, 10.2 Hz), 2.56 (app quint, 1H, H-2′, Japp˜6.5 Hz), 2.43 (ddd, 1H, H-2′, J=3.9, 5.9, 10.3 Hz), 0.93 and 0.92 (2s, 18H, t-Bu), 0.11 (s, 12H, SiCH3). Resonances of the tetrazolyl form (<5%): δ 8.25 (s, 1H, Ar—H), 4.64-4.63 (m, 1H, H-3′), 2.64-2.62 (m, 1H, H-2′). 13C NMR (CDCl3): δ 161.0, 155.8, 153.0, 140.6, 132.1, 119.3, 88.1, 84.5, 71.9, 68.6, 68.2, 62.9, 41.6, 26.1, 25.9, 18.5, 18.1, −4.4, −4.6, −5.3. 1H NMR (DMSO-d6): δ 8.47 (s, 1H, Ar—H), 6.32 (t, 1H, H-1′, J=6.4 Hz), 6.16-6.09 (m, 1H, ═CH), 5.46 (d, 1H, ═CHtrans, J=18.0 Hz), 5.33 (d, 1H, ═CHcis, J=10.7 Hz), 5.07 (d, 2H, OCH2, J=5.4 Hz), 4.62 (m, 1H, H-3′), 3.58 (d, 1H, H-4′, J=4.0 Hz), 3.78 (dd, 1H, H-5′, J=5.9, 11.2 Hz), 3.67 (dd, 1H, H-5′, J=4.4, 11.2 Hz), 2.90 (app quint, 1H, H-2′, Japp˜6.5 Hz), 2.34 (dd, 1H, H-2′, J=5.2, 11.2 Hz), 0.93 and 0.83 (2s, 18H, t-Bu), 0.12, 0.01, and 0.0.1 (3s, 12H, SiCH3). Resonances of the tetrazolyl form (<10%): δ 8.57 (s, 1H, Ar—H), 4.70 (m, 1H, H-3′), 0.81 (s, 18H, t-Bu), 0.13, 0.04, and −0.03 (3s, 12H, SiCH3). HRMS calculated for C25H43N7O4Si2Na [M+Na]+: 584.2807 found: 584.2818.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:4]=[C:5]([NH:9][NH2:10])[CH:6]=[CH:7][CH:8]=1.[C:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.S(=O)(=O)(O)O>C(O)C>[C:11](=[N:10][NH:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([Br:2])[CH:4]=1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: NNc1cccc(Br)c1
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=S(=O)(O)O
Solvent: CCO
Product: Brc1cccc(NN=C(c2ccccc2)c2ccccc2)c1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 97.1 %

Procedure:
(3-Bromophenyl)hydrazine hydrochloride (10 g, 44 mmol, 1 eq.), benzophenone (8.14 g, 44 mmol, 1 eq.) and ethanol (100 mL) are placed in a 250 mL round-bottomed flask. 2 mL of concentrated sulfuric acid are then added. The resulting suspension is heated at a temperature in the region of 80° C. After 30 minutes at this temperature, the suspension becomes a solution. The solution is stirred at this temperature for 18 hours, and is then concentrated to 95%. The residue is diluted with ethyl acetate and washed with sodium hydrogen carbonate solution. After drying over magnesium sulfate, the solution is concentrated and the residue is purified by chromatography on a column of silica gel, eluting with an ether/heptane mixture (3/97 by volume). 15 g (95%) of N-benzhydrylidene-N′-(3-bromophenyl)hydrazine are thus obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:11][CH2:12][CH2:13][CH:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:10])=[CH:4][CH:3]=1.CS(C)=O.[OH-].[Na+].[C:33]([C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37]Br)#[N:34]>O>[C:33]([C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37][O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH:9]([NH:11][CH2:12][CH2:13][CH:14]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:10])=[CH:6][CH:7]=1)#[N:34]
Reactant: CC(Cc1ccc(O)cc1)NCCC(c1ccccc1)c1ccccc1
Reactant: N#Cc1ccccc1CBr
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CC(Cc1ccc(OCc2ccccc2C#N)cc1)NCCC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
The mixture of 10.0 g 1-(4-hydroxyphenyl)-2-(3,3-diphenylpropylamino)-propane, 50 ml of dimethylsulfoxide and 2.4 g of sodium hydroxide in 10 ml of water is stirred at 60° for a half hour, whereupon 5.9 g of 2-cyanobenzyl bromide are added and the whole is stirred at room temperature for 20 hours. The mixture is diluted with water, extracted with ethyl acetate & the extract dried and evaporated. The residue is dissolved in the minimum amount of isopropanol, the solution neutralized with isopropanolic oxalic acid and the crude precipitate chromatographed on silica gel, using chloroform eluate, followed by chloroform-methanol (1:1). The initial fraction yields the 1-[4-(2-cyanobenzyloxy)-phenyl]-2-(3,3-diphenylpropylamino)-propane, showing I. R. bands at 2220 and 907 cm-1, and the second fraction the 1-[4-(2-carbamoylbenzyloxy)-phenyl]-2-(3,3-diphenylpropylamino)-propane, showing I. R. bands at 1655 and 1450 cm-1. The latter amide is taken up in aqueous ammonia, the mixture extracted with ethyl acetate & the extract dried and acidified with ethereal hydrogen chloride, to yield the corresponding hydrochloride melting at about 100° with decomposition.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1>C1COCC1.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[NH2:8]
Reactant: O=[N+]([O-])c1ccc(N2CCCCC2)c(F)c1
Agent: [Pd]
Solvent: C1CCOC1
Product: Nc1ccc(N2CCCCC2)c(F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1-(2-fluoro-4-nitrophenyl)piperidine (14.00 g, 62 mmol) in THF (80 mL) was added Pd/C (3.00 g). The reaction mixture was stirred at rt under H2 overnight. The mixture was filtered, and the filtrate was concentrated in vacuo to give the title compound as a claybank solid (11.00 g, 87%).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:10](=O)[C:9](=[CH:12]N3CCOCC3)[CH2:8][CH2:7][C:5]=2[N:6]=1.[N+]([O-])(O)=O.[N:23]1([C:29]2[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH2:38])=[NH:37])=[CH:31][CH:30]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.[OH-].[Na+]>COCCO>[CH3:1][C:2]1[S:3][C:4]2[C:10]3[N:38]=[C:36]([NH:35][C:32]4[CH:31]=[CH:30][C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[CH:34][CH:33]=4)[N:37]=[CH:12][C:9]=3[CH2:8][CH2:7][C:5]=2[N:6]=1
Reactant: Cc1nc2c(s1)C(=O)C(=CN1CCOCC1)CC2
Reactant: N=C(N)Nc1ccc(N2CCOCC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: COCCO
Product: Cc1nc2c(s1)-c1nc(Nc3ccc(N4CCOCC4)cc3)ncc1CC2
Yield: 2.1 %

Procedure:
A mixture of 2-methyl-6-morpholin-4-ylmethylene-5,6-dihydro-4H-benzothiazol-7-one (200 mg, 7.6 mmol), N-(4-morpholin-4-yl-phenyl)-guanidine nitrate (215 mg, 7.6 mmol), NaOH (30 mg, 7.6 mmol), and 2-methoxyethanol (2 mL) was heated under reflux for 20 h. The reaction mixture was concentrated under vacuum. Flash column chromatography (5% MeOH:CH2Cl2), followed by crystallisation from EtOAc gave the pure title product as dark orange crystals (60 mg, 21%): mp 236-237° C. Anal. RP-HPLC: tR 13.4 min (0-60% MeCN, purity 100%). 1H-NMR (DMSO-d6): δ 9.26 (s, 1H, NH), 8.20 (s, 1H, Py-H), 7.58 (d, 2H, J 9.2, Ph-H), 6.84 (d, 2H, J 9.2, Ph-H), 3.70 (t, 4H, J 4.8, 2×CH2), 2.99 (t, 4H, J 4.8, 2×CH2), 2.90 (m, 4H, CH2—CH2), 2.66 (s, 3H, CH3).
Reaction SMILES: [CH3:1][Zn]C.[I:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[I:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]([OH:10])[CH3:1])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1
Reactant: C[Zn]C
Reactant: O=Cc1ccc(I)cc1[N+](=O)[O-]
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: ClCCl
Product: CC(O)c1ccc(I)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 48.2 %

Procedure:
Titanium(IV) isopropoxide (1.2 mL, 4.04 mmol) was dissolved in anhydrous dichloromethane (8 mL) under a nitrogen atmosphere. The solution was cooled to 0° C. and dimethylzinc (2 M in toluene, 8.67 mL, 17.34 mmol) was added dropwise. The mixture was stirred at 0° C. for 45 minutes followed by addition of 4-iodo-2-nitrobenzaldehyde (800 mg, 2.89 mmol). The mixture was stirred at 0° C. for 36 hours, then quenched by 1M HCl (CAUTION: vigorous gas evolution!) and extracted with ethyl either (50 mL) three times. The combined organic phase was washed with water (50 mL), saturated NaHCO3 solution (50 mL) and brine (50 mL), dried over Na2SO4, concentrated in vacuo, and purified by column chromatography to yield racemic (RS)-1-(4-Iodo-2-nitrophenyl)ethanol (408 mg, 48%). 1H NMR (400 MHz, CDCl3): δ 8.21 (dd, 1H, J=1.8 and 5.3 Hz, Ph-H), 7.96 (m, 1H, Ph-H), 7.58 (d, 1H, J=8.3 Hz, Ph-H), 5.38 (q, 1H, J=6.1 Hz, Ph-CH), 2.34 (br s, 1H, OH), 1.54 (d, 3H, J=6.1 Hz, CH3); 13C NMR (100 MHz, CDCl3): δ 147.98 (C), 142.49 (CH), 140.68 (C), 132.77 (CH), 131.31 (CH), 91.60 (C), 65.40 (CH), 24.28 (CH3).
Reaction SMILES: [CH3:1][C:2]1([CH3:39])[CH2:11][CH:10]=[C:9]([C:12]2C=C[C:15](O[Si](CC(C)C)(C)C)=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:26]#[C:27][C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)[CH:5]=[CH:4][C:3]1=2.CC1(C)CC=C(O[S:52](C(F)(F)F)(=O)=O)C2C=C(C#CC3C=CC(C(OCC)=O)=CC=3)C=CC1=2>>[CH3:1][C:2]1([CH3:39])[CH2:11][CH:10]=[C:9]([C:12]2[S:52][CH:15]=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:26]#[C:27][C:28]3[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][CH:29]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(O[Si](C)(C)CC(C)C)cc2)=CCC3(C)C)cc1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(OS(=O)(=O)C(F)(F)F)=CCC3(C)C)cc1
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2cccs2)=CCC3(C)C)cc1

Procedure:
Employing the same general procedure as for the preparation of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl)ethynyl]benzoate (Compound 1), 250.0 mg (0.52 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-2-naphthalenyl)ethynyl]benzoate (Compound G) was converted into the title compound (colorless solid) using 186.8 mg (1.37 mmol) of zinc chloride 37.1 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) and 2-lithiothiophene (prepared by the addition of 65.9 mg (0.69 ml, 1.03 mmol) of n-butyllithium (1.5M solution in hexane) to a cold solution (−78° C.) of 86.5 mg (1.03 mmol) of thiophene in 1.0 ml of THF). PMR (CDCl3): δ 1.33 (6H, s), 1.36 (3H, t, J=7.1 Hz), 2.38 (2H, d, J=4.7 Hz), 4.34 (2H, q, J=7.2 Hz), 6.25 (1H, t, J=4.7 Hz), 7.13 (2H, m), 7.47 (4H, m), 7.62 (2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz).
Reaction SMILES: Cl.[F:2][C:3]([F:8])([F:7])[CH2:4][CH2:5][NH2:6].[CH3:9][O:10][CH:11]([O:14][CH3:15])[CH:12]=O.C(=O)(O)[O-].[Na+]>CO.[Pd]>[CH3:9][O:10][CH:11]([O:14][CH3:15])[CH2:12][NH:6][CH2:5][CH2:4][C:3]([F:8])([F:7])[F:2]
Reactant: COC(C=O)OC
Reactant: NCCC(F)(F)F
Agent: [Pd]
Agent: Cl
Agent: O=C([O-])O
Solvent: CO
Product: COC(CNCCC(F)(F)F)OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 3,3,3-trifluoropropan-1-amine hydrochloride (0.165 g) in methanol (3 mL) was added 2,2-dimethoxyacetaldehyde (60% in water, 0.17 mL) followed by sodium bicarbonate (0.093 g) and the mixture was stirred at ambient temperature overnight. A slurry of palladium on carbon 10% (50 mg) in methanol (1 mL) was added and the mixture was hydrogenated at 5 bar pressure for 4 hours. The mixture was filtered and concentrated in vacuo. The resulting gummy solid was suspended in DCM (5 mL) and dried over sodium sulphate, filtered and evaporated to give the titled compound as a yellow gum. Yield 0.152 g.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([C:7](=[S:9])[OH:8])[O:4][N:3]=1.C1CCN2C(=NCCC2)CC1.N1C=CC=C(C)C=1.CC(O[CH2:32][C:33]1[CH2:42][S:41][C@@H:36]2[C@H:37]([NH2:40])[C:38](=[O:39])[N:35]2[C:34]=1[C:43]([OH:45])=[O:44])=O.Cl>C(O)(C)C.O>[NH2:40][CH:37]1[C:38](=[O:39])[N:35]2[C:34]([C:43]([OH:45])=[O:44])=[C:33]([CH2:32][S:9][C:7]([C:5]3[O:4][N:3]=[C:2]([CH3:1])[CH:6]=3)=[O:8])[CH2:42][S:41][C@H:36]12
Reactant: Cc1cc(C(O)=S)on1
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Agent: Cl
Solvent: CC(C)O
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Product: Cc1cc(C(=O)SCC2=C(C(=O)O)N3C(=O)C(N)[C@H]3SC2)on1
Reaction time: 1.5 h
Yield: 76.6 %

Procedure:
4.29 g (3 cmole) of 3-methylisoxazole-5-thiocarboxylic acid were dissolved in 300 ml of 60% isopropanol-water and there were added 1.6 ml of DBU (Example 9) and 3 ml of beta-picoline. At 65° C., there were added in one shot 3.0 g of 7-aminocephalosporanic acid, 90%. The mixture was stirred for 90 minutes and the reaction isoelectric pH was held to 5.5. The precipitate which formed was isolated after adjusting the pH to 4.0 at 25° C. by concentrated hydrochloric acid. The precipitate was filtered, washed with water and acetone to give 3.0 g of the compound of the title, with an 80% yield. The infrared and proton magnetic resonance spectra are consistent with its structure.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[N:15]1[CH:20]=[CH:19][C:18]([CH:21]=O)=[CH:17][CH:16]=1.COC1C=C(OC)C=C2C=1C(=O)NC(C1C=CC=CN=1)=N2>>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:21]([C:18]1[CH:19]=[CH:20][N:15]=[CH:16][CH:17]=1)=[N:1]2
Reactant: COc1cc(N)c(C(N)=O)c(OC)c1
Reactant: O=Cc1ccncc1
Agent: COc1cc(OC)c2c(=O)[nH]c(-c3ccccn3)nc2c1
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccncc3)nc2c1
Yield: 63 %

Procedure:
5,7-Dimethoxy-2-(pyridin-4-yl)quinazolin-4(3H)-one was synthesized from 2-amino-4,6-dimethoxybenzamide and 4-pyridine carboxaldehyde, using the method described for 5,7-dimethoxy-2-(pyridin-2-yl)quinazolin-4(3H)-one. 5,7-Dimethoxy-2-(pyridin-4-yl)quinazolin-4(3H)-one (142 mg, 63%) was isolated as a pale brown solid and then converted to the corresponding hydrochloride (yellow solid). Selected data: MS (m/z): 284.06; MP 294-295° C. (hydrochloride).
Reaction SMILES: [C:1]1([CH:7]([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH:14]1([C:19](Cl)=[O:20])[CH2:18][CH2:17][CH2:16][CH2:15]1>ClCCl>[CH:14]1([C:19]([C:4]2[CH:5]=[CH:6][C:1]([CH:7]([CH3:9])[CH3:8])=[CH:2][CH:3]=2)=[O:20])[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: O=C(Cl)C1CCCC1
Reactant: CC(C)c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(C)c1ccc(C(=O)C2CCCC2)cc1
Reaction time: 2 h

Procedure:
To a solution of cumene (16.4 g, 137 mmol) and aluminum chloride (21.9 g, 164 mmol) in dichloromethane (200 mL) was added cyclopentanecarbonyl chloride (20 g, 151 mmol) at −50° C. (the inside temperature), and the mixture was stirred for two hours until the temperature reached −10° C. (the inside temperature).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:10])=[CH:11][CH:12]=1)([O-:3])=[O:2]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: Nc1ccccc1
Solvent: O
Product: O=C(Nc1ccccc1)c1ccc([N+](=O)[O-])cc1

Procedure:
A mixture of 167 parts of p-nitrobenzoic acid and 93 parts of aniline is heated at 210° C. with the water formed during the reaction being distilled off. After heating for 3 hours, 18 parts of water have been collected, which shows that the reaction is ended. 242 parts of N-(4'-nitrobenzoyl)-aniline melting at 215° C. are obtained according to the instructions in the literature, i.e. a yield of 99% by weight. The infra-red spectrum confirms the formula of the product: