Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]1[C:7]([C:8]2[S:18][C:11]3[N:12]=[CH:13][N:14]=[C:15]([S:16][CH3:17])[C:10]=3C=2)=[C:6]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:5]=[CH:4]1)[CH3:2].CSC1C2N=C(C=O)SC=2[N:30]=CN=1.CSC1C2C=C(C=O)SC=2N=CN=1>>[CH2:1]([N:3]1[C:7]([C:8]2[S:18][C:11]3[N:12]=[CH:13][N:14]=[C:15]([S:16][CH3:17])[C:10]=3[N:30]=2)=[C:6]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:5]=[CH:4]1)[CH3:2]
Reactant: CSc1ncnc2sc(C=O)nc12
Reactant: CCn1cnc(-c2ccccc2)c1-c1cc2c(SC)ncnc2s1
Agent: CSc1ncnc2sc(C=O)cc12
Product: CCn1cnc(-c2ccccc2)c1-c1nc2c(SC)ncnc2s1

Procedure:
The title compound was prepared by a similar process to that described for Intermediate 70 but using 7-(methylthio)[1,3]thiazolo[5,4-d]pyrimidine-2-carbaldehyde (Intermediate 77) in place of 4-(methylthio)thieno[2,3-d]pyrimidine-6-carbaldehyde (Intermediate 15). Yellow solid (103 mg, 58%);
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:14][CH2:13]1)([O-])=O.C(O)C.O>Cl>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][N:12]1[CH2:13][CH2:14][CH:15]([NH:18][C:19](=[O:26])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:17]1
Reactant: O=C(NC1CCN(CCc2ccccc2[N+](=O)[O-])CC1)c1ccccc1
Agent: Cl
Solvent: O
Solvent: CCO
Product: Nc1ccccc1CCN1CCC(NC(=O)c2ccccc2)CC1
Reaction time: 4 h
Yield: 42.4 %

Procedure:
A solution of 1-[2-(o-nitrophenyl)ethyl]-4-benzamidopiperidine (4.25 g.) inabsolute ethanol (150 ml.) was added over 50 minutes to stirred stannous chloride (10.82 g.) in concentrated hydrochloric acid (12 ml.). and water (7.5 ml.) at 60°-70° C. After addition, the mixture was stirred at this temperature for 4 hours before cooling and evaporating theethanol. Continuous extraction into chloroform of the neutralised (with 2N sodium hydroxide solution) aqueous fraction gave the title compound (1.65 g.). The aqueous layer after extraction was made alkaline with 2N sodium hydroxide solution and extracted with more chloroform to give a further batch of the title compound (2.36 g.). The total product was crystallised from ethanolic hydrogen chloride and ether to give the hydrochloride of the title compound (2.75 g.), m.p. 263.8° C. (Found: C, 60.3; H, 7.0; N, 10.5. C20H25N3O. 2HCl requires C, 60.6; H, 6.9; N, 10.60%).
Reaction SMILES: [CH:1]1([C:7]([N:9]2[CH2:14][C:13](=[O:15])[N:12]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:11](=[O:24])[CH2:10]2)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+].O.ClCCl>C(O)C>[CH:1]1([C:7]([N:9]2[CH2:10][C:11](=[O:24])[N:12]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:13]([OH:15])[CH2:14]2)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(C1CCCCC1)N1CC(=O)N(CCc2ccccc2)C(=O)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: ClCCl
Product: O=C(C1CCCCC1)N1CC(=O)N(CCc2ccccc2)C(O)C1
Reaction time: 1 h
Yield: 73 %

Procedure:
15.2 g (0.046 mol) of 4-(cyclohexylcarbonyl)-2,6-dioxo-1-phenethyl piperazine are dissolved in 600 ml of ethanol. In an inert atmosphere, at 0° C., there are added 8.7 g (0.0509 mol) of dihydrated cupric chloride and the mixture is left for 1 hour at 0° C. To the reaction medium, kept at 0° C., are added in portions 8.8 g (0.23 mol) of sodium borohydride and left for 45 minutes at 0° C. The excess of reducing agent is destroyed by adding acetone. The insoluble salts are filtered and the filtrate is evaporated to dryness. The residue obtained is treated with a mixture of water and dichloromethane. The organic phase is decanted, dried over dry sodium sulphate and evaporated to dryness. The residue which is obtained is purified by filtration on a silica bed (elutrient: ethyl acetate). Beige crystals, m.p.=134° C., yield: 73%.
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].[Cl-].[Ca+2].[Cl-]>C([O-])(=O)C.[Cu]>[O:8]=[CH:6][C@@H:5]([C@H:4]([C@@H:3]([C@@H:2]([CH2:1][OH:23])[OH:7])[OH:22])[OH:21])[OH:20]
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Agent: [Cu]
Agent: CC(=O)[O-]
Agent: [Ca+2]
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reaction time: 0.17 h

Procedure:
The activity of the present β-fructofuranosidase is assayed as follows: Sucrose as a substrate was dissolved in 20 mM acetate buffer (pH 6.0) containing 5 mM calcium chloride to give a concentration of 0.1 w/v %. To 5 ml of the solution was added 0.2 ml of a test sample, and the mixture was incubated at 40° C. for 10 min, followed by suspending the enzymatic reaction by the addition of 0.2 ml of the Somogyi copper solution and assaying the reducing power of the reaction mixture by the Somogyi-Nelson's method. As a control, a control solution, which was preheated at 100° C. for 10 min to inactivate the enzyme, was treated similarly as above. Under the above reaction conditions, one unit β-fructofuranosidase activity is defined as the amount of enzyme or polypeptide which gives a reducing power equal to that of 2μ mole of glucose per minute.
Reaction SMILES: [Si:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li]C(CC)C.[B:31](OC(C)C)([O:36]C(C)C)[O:32]C(C)C>C1COCC1.C1CCCCC1.O>[Si:1]([N:8]1[C:16]2[C:11](=[C:12]([B:31]([OH:36])[OH:32])[C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)n1ccc2cc(F)ccc21
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: O
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CC(C)(C)[Si](C)(C)n1ccc2c(B(O)O)c(F)ccc21
Temperature: -78 °C
Reaction time: 2 h
Yield: 20.5 %

Procedure:
To a mixture of the product of Step 1 (4.98 g, 20 mmol) and TMEDA (2.32 g, 20 mmol) in THF at −78° C. was slowly added a 1.3M solution of s-BuLi (15.4 mL, 20 mmol) in cyclohexane and the mixture was stirred for 2 h at −78° C. Triisopropyl borate (3.76 g, 20 mmol) was added to the mixture at −78° C. and stirred for another 1 h and then warmed to −20° C. Water was added and the mixture was extracted with EtOAc and the organic layer was dried over Na2SO4 and evaporated. The residue was re-crystallized (EtOAc and n-hexane) to give the title compound (1.2 g, 20.7%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH2:6][NH2:7].C(N(CC)CC)C.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[C:22]([NH:7][CH2:6][C:5]1[CH:8]=[C:9]([O:13][CH3:14])[C:10]([O:11][CH3:12])=[C:3]([O:2][CH3:1])[CH:4]=1)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COc1cc(CN)cc(OC)c1OC
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1cc(CNC(=O)c2ccccc2)cc(OC)c1OC
Temperature: -2 °C
Reaction time: 1 h
Yield: 89.7 %

Procedure:
To a mixture of 3,4,5-trimethoxybenzylamine (20.0 g, 0.101 mol), THF (88.0 mL) and triethylamine (14.9 g, 0.147 mol) was added dropwise benzoyl chloride (14.3 g, 0.101 mol) at −6-−3° C., and the dropping funnel was washed with THF (10 mL). The reaction mixture was stirred under a nitrogen atmosphere at −6-2° C. for 1 hr. The consumption of the starting material was confirmed by TLC (hexane/ethyl acetate (1:1)). To the reaction mixture was added water (44 mL) at 2-10° C., and the mixture was extracted three times with ethyl acetate (17, 40, 18 mL). The combined organic layers were washed twice with 18% brine (20 mL), and dried over magnesium sulfate (7.4 g). Silica gel (5.1 g) was added thereto, and the mixture was stirred for 11 min, and filtered through silica gel (19 g). The filtrate was concentrated to 35 g under reduced pressure in a bath at 35° C. To the concentrate was added ethyl acetate, and the solid was dissolved with heating. The solvent was evaporated under reduced pressure (content 52 g) in a bath at 40-30° C. until the content ceased to flow. During evaporation, seed crystals were added thereinto. Ethyl acetate in an amount necessary for filtration was added thereto, and the crystals were collected by filtration, washed with ethyl acetate, and dried under reduced pressure at 50° C. or lower to give N-benzoyl-3,4,5-trimethoxybenzylamine (27.3 g, 89.3%) as white crystals.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=3)=[CH:9][N:10]=2)[N:7]=1.[NH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(OC(C)(C)C)(C)(C)C.[Na].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[O:27]1[CH2:28][CH2:29][CH:24]([CH2:23][NH:22][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C:11]4[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=4)=[CH:9][N:10]=3)[N:7]=2)[CH2:25][CH2:26]1
Reactant: NCC1CCOCC1
Reactant: FC(F)(F)Oc1cccc(-c2cnc3ccc(Cl)nn23)c1
Agent: [Pd]
Agent: CC(C)(C)OC(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: FC(F)(F)Oc1cccc(-c2cnc3ccc(NCC4CCOCC4)nn23)c1
Temperature: 100 °C

Procedure:
Compound 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (0.2 g, 0.638 mmol), 4-aminomethyltetrahydropyran (0.145 g, 0.956 mmol), Sodium tertiarybutyloxide (0.172 g, 1.785 mmol), rac-BINAP (0.024 g, 0.038 mmol) and Pd2(dba)3 (0.018 g, 0.019 mmol) were combined in a 20 ml vial. Toluene (5 mL) was added and nitrogen was bubbled through the mixture for 5 minutes. The reaction mixture was then heated to 100° C. overnight. Silica gel was added to the reaction mixture and the solvent stripped off. The product was isolated via column chromatography (hexanes:EtOAc) with the Compound N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine eluting at 100% EtOAc.
Reaction SMILES: [Br-].[F:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][CH:4]=1.[C:29]1([Si:35]2(CCCCC)[CH2:40][CH2:39][CH:38]([CH:41]3[CH2:46][CH2:45][CH:44]([CH:47]=O)[CH2:43][CH2:42]3)[CH2:37][CH2:36]2)C=[CH:33][CH:32]=[CH:31][CH:30]=1>>[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][CH2:47][C@H:44]2[CH2:43][CH2:42][C@H:41]([C@H:38]3[CH2:39][CH2:40][Si@H:35]([CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:36][CH2:37]3)[CH2:46][CH2:45]2)=[CH:27][CH:28]=1
Reactant: Fc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCCC[Si]1(c2ccccc2)CCC(C2CCC(C=O)CC2)CC1
Agent: [Br-]
Product: CCCCC[Si@H]1CC[C@H]([C@H]2CC[C@H](CCc3ccc(F)cc3)CC2)CC1

Procedure:
The general procedure of Example 4 was repeated using 4-fluorobenzyltriphenylphosphonium bromide and 4-(4-phenyl-4-n-pentyl-4-silacyclohexyl)cyclohexane carbaldehyde, thereby obtaining trans-4-(trans-4-(2-(4-fiuorophenyl)ethyl)cyclohexyl)- 1-n-pentyl-1-silacyclohexane with the following results of IR and 13C-NMR analyses.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[C:9]3[C:14]([C:15]=2/[C:16](=[N:18]/[OH:19])/[NH2:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1.[H-].[Na+].[CH:30](OCC)=O>C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=3)[C:9]3[C:14]([C:15]=2[C:16]2[N:17]=[CH:30][O:19][N:18]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1
Reactant: CCOC=O
Reactant: Cc1noc(C)c1-c1c(/C(N)=N/O)c2ccccc2n1-c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1noc(C)c1-c1c(-c2ncon2)c2ccccc2n1-c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(Z)-2-(3,5-Dimethylisoxazol-4-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3 carboximidamide (Example 11) was dissolved in THF containing 4-Å powdered molecular sieves. The mixture was stirred for 30 min under N2. NaH (60% dispersion in mineral oil, 7.0 mg, 2.1 eq,) was added and the mixture was stirred at 60° C. for 20 min. After cooling to room temperature, ethyl formate (25.6 mg, 2.5 eq) in THF was added dropwise. The resulting mixture was heated at reflux for 1 h and then cooled to room temperature. The mixture was filtered and concentrated. The residue was filtered through silica and then purified using reversed phase HPLC to give 4-(2-(3,5-dimethylisoxazol-4-yl)-3-(1,2,4-oxadiazol-3-yl)-1H-indol-1-yl)phenol as a white powder: ES/MS m/z: 395.17 (M−H), 393.19 (M−H); 1H NMR (acetone-d6, 500 MHz): 9.21 (s, 1H), 8.40 (m, 1H), 7.37-7.31 (m, 2H), 7.26-7.22 (m, 3H), 6.98 (m, 2H), 2.17 (s, 3H) and 1.98 (s, 3H).
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH2:16][C:17]([OH:19])=[O:18]>C1C=CC=CC=1.CO>[Br:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH2:16][C:17]([O:19][CH3:1])=[O:18]
Reactant: O=C(O)CCc1ccccc1Br
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: c1ccccc1
Solvent: CO
Product: COC(=O)CCc1ccccc1Br
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Trimethylsilyldiazomethane (2M in hexanes, 5.0 mL, 10.0 mmol) was added to a solution of 3-(2-bromophenyl)propionic acid (1.376 g, 6.00 mmol) in anhydrous benzene (28 mL) and anhydrous methanol (8 mL). The reaction mixture was stirred at room temperature for 2 h, and then the volatiles were removed in vacuo, to yield crude methyl 3-(2-bromophenyl)propionate which was carried forward without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:20][C:19](=O)[C:11]2[C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][O:14][C:10]=2[CH2:9]1.[C:22]([NH:25][NH2:26])([NH2:24])=[NH:23].[ClH:27].Cl>C(O)C>[ClH:27].[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:20]/[C:19](=[N:26]\[NH:25][C:22]([NH2:24])=[NH:23])/[C:11]2[C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][O:14][C:10]=2[CH2:9]1
Reactant: N=C(N)NN
Reactant: O=C1CC(c2ccccc2Br)Cc2occ(C(F)(F)F)c21
Agent: Cl
Solvent: CCO
Product: N=C(N)N/N=C1\CC(c2ccccc2Br)Cc2occ(C(F)(F)F)c21
Temperature: 90 °C
Reaction time: 4 h
Yield: 35.6 %

Procedure:
To a mixture of 6-(2-bromophenyl)-3-trifluoromethyl-4,5,6,7-tetrahydrobenzofuran-4-one (0.29 g) and aminoguanidine hydrochloride (90 mg) were ethanol (16 ml) and 6N hydrochloric acid (0.070 ml), and the mixture was stirred at 90° C. for 4 hours and cooled. The reaction solution was concentrated under reduced pressure, and the residue was washed with ethanol, ethyl acetate and isopropylether, and dried to give (E)-6-(2-bromophenyl)-4-guanidinoimino-3-trifluoromethyl-4,5,6,7-tetrahydrobenzofuran hydrochloride (Compound 53) (0.13 g).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:13]=[CH:12][C:7](/[CH:8]=[CH:9]/[C:10]#[N:11])=[CH:6][C:5]=1[C:14]1[NH:15][CH2:16][C:17]2[N:22]([CH3:23])[N:21]=[C:20]([CH2:24][CH2:25][CH3:26])[C:18]=2[N:19]=1)[CH3:2].C(O)(=[O:29])C>[Ni]>[NH2:11][CH2:10][CH2:9][CH2:8][C:7]1[CH:12]=[CH:13][C:4]([O:3][CH2:1][CH3:2])=[C:5]([C:14]2[NH:15][C:16](=[O:29])[C:17]3[N:22]([CH3:23])[N:21]=[C:20]([CH2:24][CH2:25][CH3:26])[C:18]=3[N:19]=2)[CH:6]=1
Reactant: CCCc1nn(C)c2c1N=C(c1cc(/C=C/C#N)ccc1OCC)NC2
Reactant: CC(=O)O
Agent: [Ni]
Product: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(CCCN)ccc3OCC)nc12
Reaction time: 3 h
Yield: 38 %

Procedure:
A solution of (E)-4-ethoxy-3-(-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-5-yl)cinnamonitrile (0.25 g, 0.00064 mol) in glacial acetic acid (25 ml) was stirred with Raney nickel catalyst (25 mg) under hydrogen at room temperature and at 50 p.s.i. for 3 hours. The resulting mixture was filtered and the filtrate evaporated under vacuum. The residue was partitioned between saturated aqueous sodium carbonate solution (50 ml) and dichloromethane (30 ml), the layers separated and the aqueous phase further extracted with dichloromethane (2×30 ml). The organic solutions were combined, dried (Na2SO4) and evaported under vacuum to give a brown solid, crystallisation of which from hexane-ethyl acetate gave the title compound as fawn crystals (96 mg, 38%), m.p. 115°-117° C. Found C,65.29; H,7.35; N,18.66. C20H27N5O2 requires C,65.02; H,7.37; N,18.96%.
Reaction SMILES: [CH:1]([NH:3][C@@H:4]1[C:26](=[O:27])[N:6]2[CH:7]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=3)=[O:14])[C:8]([CH3:12])([CH3:11])[S:9](=[O:10])[C@H:5]12)=[O:2].[Cl:28]N1C(=O)CCC1=O.ClC(Cl)CCl>>[CH3:11][C:8](=[CH2:12])[CH:7]([N:6]1[C:26](=[O:27])[CH:4]([NH:3][CH:1]=[O:2])[CH:5]1[S:9]([Cl:28])=[O:10])[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1)=[O:14]
Reactant: CC1(C)C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@@H](NC=O)[C@H]2S1=O
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClCC(Cl)Cl
Product: C=C(C)C(C(=O)OCc1ccc([N+](=O)[O-])cc1)N1C(=O)C(NC=O)C1S(=O)Cl

Procedure:
A solution of 1.43 g. of p-nitrobenzyl 6β-formamido-2,2-dimethylpenam-3-carboxylate-1-oxide and 500 mg. of N-chlorosuccinimide in 40 ml. of dry 1,1,2-trichlorethane was refluxed for 90 minutes. The mixture was cooled, washed with water and brine, dried over MgSO4, and the solvent was evaporated. The nmr spectrum indicates conversion to the title compound.
Reaction SMILES: C[O:2][C:3](=[O:21])[C:4]([NH:7][C:8]([C:10]1[C:11]([OH:20])=[C:12]2[C:16](=[C:17]([CH3:19])[CH:18]=1)[CH2:15][CH2:14][CH2:13]2)=[O:9])([CH3:6])[CH3:5].Br[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1>>[CH3:6][C:4]([NH:7][C:8]([C:10]1[C:11]([O:20][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:28][CH:29]=2)=[C:12]2[C:16](=[C:17]([CH3:19])[CH:18]=1)[CH2:15][CH2:14][CH2:13]2)=[O:9])([CH3:5])[C:3]([OH:2])=[O:21]
Reactant: FC(F)(F)c1ccc(CBr)cc1
Reactant: COC(=O)C(C)(C)NC(=O)c1cc(C)c2c(c1O)CCC2
Product: Cc1cc(C(=O)NC(C)(C)C(=O)O)c(OCc2ccc(C(F)(F)F)cc2)c2c1CCC2

Procedure:
2-Methyl-2-{[7-methyl-4-(4-trifluoromethyl-benzyloxy)-indane-5-carbonyl]-amino}-propionic acid was prepared in analogy to example 1 via a sequence of an alkylation reaction of 2-[(4-Hydroxy-7-methyl-indane-5-carbonyl)-amino]-2-methyl-propionic acid methyl ester using 1-bromomethyl-4-trifluoromethyl-benzene and a basic hydrolysis of the amino acid ester to the free amino acid
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].[F:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13]Br)=[CH:11][CH:10]=1>CS(C)=O.C(Cl)Cl>[F:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)=[CH:11][CH:10]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: c1cn[nH]c1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: ClCCl
Product: Fc1ccc(Cn2cccn2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.8 %

Procedure:
To a stirred solution of pyrazole (300 mg, 4.4 mmol) in DMSO (2 ml) at RT was added NaH (176 mg, 4.4 mmol, 60% in mineral oil) portionwise. The mixture was stirred at RT for 1 h and 4-fluorobenzylbromide (1.0 g, 5.3 mmol) added dropwise. The mixture was stirred at 50° C. for 0.5 h, cooled to RT and diluted with DCM (20 ml). The resulting mixture was filtered and the filtrate washed with brine (10 ml). The organic layer was then dried (NaSO), filtered and concentrated at reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH 95:5) provided the title compound as colourless oil (650 mg, 84%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]#[N:13])=[C:5]2[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1.C(N(CC)CC)C.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31].C(=O)(O)[O-].[Na+]>CN(C=O)C.C1COCC1>[C:12]([C:6]1[CH:7]=[N:8][C:9]2[C:4]([C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1)=[CH:3][C:2]([NH:1][C:29](=[O:32])[CH:30]=[CH2:31])=[CH:11][CH:10]=2)#[N:13]
Reactant: C=CC(=O)Cl
Reactant: Cc1cccc(Nc2c(C#N)cnc3ccc(N)cc23)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: C=CC(=O)Nc1ccc2ncc(C#N)c(Nc3cccc(C)c3)c2c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 39.8 %

Procedure:
Dissolved 500 mg (1.82 mmol) of 6-amino-4-[(3-methylphenyl)amino]-3-quinolinecarbonitrile in 1.0 ml DMF and 6 ml THF and chilled to 0° C. under N2. Added 280 μl (2.00 mmol) triethylamine and 166 μl (2.00 mmol) acryloyl chloride. Removed ice bath at 15 minutes and at 1 hour, stripped solvent and slurried residue with dilute sodium bicarbonate. Collected crystals and washed with water. Boiled solids in ethyl acetate, collected and dried in vacuo, giving 238 mg of yellow-orange solid: mass spectrum (electrospray m/e): M+H=329.1.
Reaction SMILES: [N+]([NH:4][C:5]1[NH:10][C:9](=[O:11])[C:8]([CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:7][N:6]=1)([O-])=O.[CH3:19][N:20]([CH2:22][C:23]1[S:24][CH:25]=[C:26]([CH2:28][S:29][CH2:30][CH2:31]N)[N:27]=1)[CH3:21].C(O)C>O>[CH3:21][N:20]([CH2:22][C:23]1[S:24][CH:25]=[C:26]([CH2:28][S:29][CH2:30][CH2:31][NH:4][C:5]2[NH:10][C:9](=[O:11])[C:8]([CH2:12][C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)=[CH:7][N:6]=2)[N:27]=1)[CH3:19]
Reactant: O=c1[nH]c(N[N+](=O)[O-])ncc1Cc1cccnc1
Reactant: CN(C)Cc1nc(CSCCN)cs1
Solvent: CCO
Solvent: O
Product: CN(C)Cc1nc(CSCCNc2ncc(Cc3cccnc3)c(=O)[nH]2)cs1

Procedure:
A reaction mixture prepared from 1.24 g. of 2-nitroamino-5-(3-pyridyl)methyl-4-pyrimidone, 1.14 g. of 2-(2-dimethylaminomethyl-4-thiazolylmethylthio)ethylamine and 6 ml. of anhydrous ethanol was refluxed for about 1 day under a nitrogen atmosphere. The volatile constitutents were removed by evaporation to yield an oily residue. Water was added and the aqueous layer extracted with ether and with ethyl acetate. The organic extracts were combined, dried and evaporated to dryness to yield 2-[2-(2-dimethylaminomethyl-4-thiazolylmethylthio)ethyl]amino-5-(3-pyridyl)methyl-4-pyrimidone as a residue which was crystallized from ether. Recrystallization from an ethanol-ether solvent mixture yielded 2-[2-(2-dimethylaminomethyle-4-thiazolylmethylthio)ethyl]amino-5-(3-pyridyl)methyl-4-pyrimidone melting at 122°-123° C.; yield=0.68 g.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[C:9](O)(=[O:13])[CH2:10][CH2:11][CH3:12].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:9]([NH:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1)(=[O:13])[CH2:10][CH2:11][CH3:12]
Reactant: Nc1cccc(O)c1
Reactant: CCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCC(=O)Nc1cccc(O)c1

Procedure:
3-aminophenol (550 mg; 5 mmol) is added to a solution of butyric acid (1.4 mL; 15 mmol) in DCM (20 mL) at room temperature and stirred vigorously. To this solution DCC (2.48 g; 12 mmol) is added followed by DMAP (24 mg) and the contents stirred overnight at room temperature. The reaction mixture is then filtered and washed with DCM. The filtrate is concentrated and redissolved in methanol, added with 10% aqueous sodium bicarbonate solution and stirred vigorously until diacylated byproduct disappeared (as detected by LC-MS) to yield 3-butyramidophenol as the only product. The product was used for further transformation without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:10])[CH2:5][C:6](=[O:9])[CH2:7][CH3:8])[CH3:2].Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:15][CH:14]=1>>[CH2:1]([O:3][C:4](=[O:10])[CH:5]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:24])[C:20]([CH3:22])([CH3:21])[CH3:23])=[CH:15][CH:14]=1)[C:6](=[O:9])[CH2:7][CH3:8])[CH3:2]
Reactant: CCOC(=O)CC(=O)CC
Reactant: CC(C)(C)C(=O)c1ccc(CBr)cc1
Product: CCOC(=O)C(Cc1ccc(C(=O)C(C)(C)C)cc1)C(=O)CC

Procedure:
The title compound was prepared by the method of Preparation 3a using 3-oxo-pentanoic acid ethyl ester and 1-(4-bromomethylphenyl)-2,2-dimethylpropan-1-one.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2>C(O)(=O)C>[NH2:1][CH:2]1[CH2:10][CH2:9][CH:8]2[CH:4]([CH2:5][CH2:6][NH:7]2)[CH2:3]1
Reactant: Nc1ccc2[nH]ccc2c1
Solvent: CC(=O)O
Product: NC1CCC2NCCC2C1

Procedure:
A 1.0 g sample of 5-aminoindole was hydrogenated at 4 atm H2 in 50 mL of acetic acid over 2 g of Pt2O at room temperature for 90 hours. The solution was filtered, and the solvent was removed.