Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH2:6].C(=O)([O-])O.[Na+].Cl[C:16]([O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:17]>O.C(Cl)Cl>[C:19]1([O:18][C:16](=[O:17])[NH:6][CH2:5][C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([OH:1])[CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: NCc1cccc(O)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: O=C(NCc1cccc(O)c1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Hydroxybenzylamine (200 mg, 1.62 mmol) and sodium hydrogen carbonate (273 mg, 3.25 mmol) suspended in water/DCM (4 mL, 1:1) is treated with phenyl chloroformate (0.204 mL, 1.62 mmol). After stirring at RT overnight, the reaction mixture is diluted with more DCM/water and the organic phase is separated. The organic portion is concentrated in vacuo to afford the titled compound. (MH+244)
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH2:11][N:12]2[C:16]([Br:17])=[C:15]([Br:18])[N:14]=[C:13]2Br)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1.C([Mg]Br)C.O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:11][N:12]2[C:16]([Br:17])=[C:15]([Br:18])[N:14]=[CH:13]2)=[CH:4][C:5]2[O:9][CH2:8][O:7][C:6]=2[CH:10]=1
Reactant: Clc1cc2c(cc1Cn1c(Br)nc(Br)c1Br)OCO2
Agent: CC[Mg]Br
Solvent: O
Solvent: ClCCl
Product: Clc1cc2c(cc1Cn1cnc(Br)c1Br)OCO2
Temperature: 25 °C

Procedure:
The operation is carried out as in Stage 2 of Example 1 starting with 6 g of the product obtained in Stage 1 of Example 1 in 300 ml of a methylene chloride/sulphuric ether mixture (60/240), to which 4.6 ml of ethyl magnesium bromide is added dropwise, then the whole is maintained under agitation for 30 minutes at ambient temperature and then 100 ml of ice-cooled water is introduced into the reaction medium obtained.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)(=[O:3])[CH3:2].[Cl:23]CCCl>C(O)(=O)C.O.C(=O)(O)[O-].[Na+].S(=O)(O)[O-].[Na+]>[CH2:15]([O:14][C:12]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)=[C:4]([C:1](=[O:3])[CH2:2][Cl:23])[CH:13]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: ClCCCl
Reactant: CC(=O)c1cc(OCc2ccccc2)cc2[nH]c(=O)ccc12
Agent: O=C([O-])O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: O=C(CCl)c1cc(OCc2ccccc2)cc2[nH]c(=O)ccc12
Temperature: 65 °C
Reaction time: 4.5 h

Procedure:
5-acetyl-7-benzyloxy-1H-quinolin-2-one (7.0 g, 23.86 mmol) is dissolved in a mixture of 1,2-dichloroethane (147 mL), glacial acetic acid (43 mL) and water (7 mL) and combined with N-benzyl-trimethylammonium-dichloriodate (19.0 g, 54.58 mmol). The mixture is stirred for 4.5 hours at 65° C., then diluted with sodium bicarbonate solution and 5% sodium bisulphite solution and stirred for 5 minutes. The precipitate formed is filtered off, washed with water (2×20 mL) and dried in the oven. Yield: 6.0 g (77%); mass spectroscopy: [M+H]+=328.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([CH3:28])([CH3:27])[CH2:11][O:12][C:13]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].CI.[CH3:31][Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.ClCCl>[C:1]([O:5][C:6]([N:8]([CH3:31])[CH2:9][C:10]([CH3:28])([CH3:27])[CH2:11][O:12][C:13]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: COC(=O)c1ccc(C(C)(C)C)cc1OCC(C)(C)CNC(=O)OC(C)(C)C
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Solvent: ClCCl
Product: COC(=O)c1ccc(C(C)(C)C)cc1OCC(C)(C)CN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 60 h
Yield: 61.8 %

Procedure:
To a solution of methyl 2-(3-tert-butoxycarbonylamino-2,2-dimethylpropoxy)-4-tert-butylbenzoate (2.50 g, 6.35 mmol) in THF at 0° C. under N2 was added methyl iodide (4.51 g, 31.8 mmol, 5 eq), followed by sodium bis(trimethylsilyl)amide (12.7 mL, 12.7 mmol, 1.0 M in THF). The cooling bath was allowed to slowly warm to room temperature. The reaction was stirred at room temerature for 2.5 days, then diluted with dichloromethane, washed with water and brine, dried, and concentrated in vacuo to give 1.60 g (61.8%) of the desired product as a viscous oil which was used without further purification.
Reaction SMILES: [CH2:1]([CH:4]1[C:8](O)([CH3:9])[CH:7]=[CH:6][C:5]1=[O:11])[CH:2]=[CH2:3].[CH3:12][NH:13][OH:14]>>[CH2:1]([C:4]1[C:5](=[O:11])[CH2:6][CH:7]([N:13]([OH:14])[CH3:12])[C:8]=1[CH3:9])[CH:2]=[CH2:3]
Reactant: C=CCC1C(=O)C=CC1(C)O
Reactant: CNO
Product: C=CCC1=C(C)C(N(C)O)CC1=O
Reaction time: 1 h
Yield: 91.2 %

Procedure:
2-Allyl-3-hydroxy-3-methyl-4-cyclopentenone (15.2 g) was dropwise added to a 25% aqueous solution of N-methylhydroxylamine (30 g) in the same flask as used in Example 1 at a temperature of 15° to 25° C. for 1 hour. At the same temperature, the reaction mixture was kept for 2 hours. After completion of the reaction, the mixture was treated and purified in the same manner as in Example 5 to obtain 2-allyl-3-methyl-4-(N-hydroxy-N-methylamino)-2-cyclopentenone (16.5 g). Yield, 91%. nD20 1.5102.
Reaction SMILES: C(N(CC)CC)C.[C:8]1(B(O)O)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O:17]=[C:18]1[C:27]([C:28]#[N:29])=[C:26]([N:30]2[CH2:35][CH2:34][N:33]([C:36]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[O:37])[CH2:32][CH2:31]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19]1>ClCCl>[O:17]=[C:18]1[C:27]([C:28]#[N:29])=[C:26]([N:30]2[CH2:35][CH2:34][N:33]([C:36]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[O:37])[CH2:32][CH2:31]2)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:19]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: OB(O)c1ccccc1
Reactant: N#Cc1c(N2CCN(C(=O)c3cccs3)CC2)c2ccccc2[nH]c1=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#Cc1c(N2CCN(C(=O)c3cccs3)CC2)c2ccccc2n(-c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 31 %

Procedure:
Cupric acetate (497 mg, 2.74 mmol), triethylamine (380 μL, 2.74 mmol), and phenyl boronic acid (335 mg, 2.74 mmol) were added successively to a solution of Compound 116 (500 mg, 1.37 mmol) in dichloromethane. The solution was stirred at room temperature for 48 h. The solution was filtered through celite and washed successively by saturated NaHCO3 solution, water, and brine. The organic phase was dried over Na2SO4 and evaporated to yield a residue which was purified by flash chromatography eluting with 0–1% MeOH in dichloromethane gradient to get 187 mg (31%) of white solids. M.P. 289° C. 1H NMR (DMSO-d6): δ 3.78 (m, 4H), 4.02 (m, 4H), 6.60 (d, J=7.6 Hz, 1H), 7.22 (m, 1H), 7.38 (m, 3H), 7.57–7.71 (m, 5H), 7.88 (dd, J=0.8, 4.8 Hz, 1H), 8.02 (d, J=7.2 Hz, 1H). EIMS m/z 441 (M+1). Anal. (C25H20N4O2S) C, H, N.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH:5]=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.[C-:28]#[N:29].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:28]#[N:29])[CH:7]=[CH:8][C:9]=1[Cl:10]
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Reactant: C1COCCN1
Reactant: [C-]#N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Solvent: C1CCOC1
Product: N#CC(c1ccc(Cl)c(Cl)c1)N1CCOCC1

Procedure:
A mixture of 3,4-dichlorobenzaldehyde, p-toluenesulfonic acid, morpholine and sodium cyanide in tetrahydrofuran is reacted to give α-(3,4-dichlorophenyl)-4-morpholineacetonitrile.
Reaction SMILES: CN(C)[CH:3]=[O:4].S(Cl)(Cl)=O.[CH3:10][CH:11]1[CH:16]=[C:15]([C:17]([OH:19])=[O:18])[N:14]2[C:20](=[O:23])[CH:21]([NH2:22])[C@H:13]2[S:12]1.C([Si]([CH:31]([Si](CC)(CC)CC)[C:32](N)=[O:33])(CC)CC)C>O.ClCCl>[CH3:10][CH:11]1[CH:16]=[C:15]([C:17]([OH:19])=[O:18])[N:14]2[C:20](=[O:23])[CH:21]([NH:22][C:3](=[O:4])[CH:32]([OH:33])[C:31]3[S:12][CH:11]=[CH:16][CH:15]=3)[C@H:13]2[S:12]1
Reactant: CN(C)C=O
Reactant: CC[Si](CC)(CC)C(C(N)=O)[Si](CC)(CC)CC
Reactant: CC1C=C(C(=O)O)N2C(=O)C(N)[C@H]2S1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Solvent: O
Product: CC1C=C(C(=O)O)N2C(=O)C(NC(=O)C(O)c3cccs3)[C@H]2S1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 148.5 %

Procedure:
A mixture of dimethylformamide (0.805 g) and thionyl chloride (1.55 g) was warmed for 30 minutes at 50° C. with enough shaking, and then excess thionyl chloride was removed under reduced pressure. The residual crystals were washed twice with a small amount of absolute ether, and then ether was removed under reduced pressure. The residual crystals were dissolved in dried dichloromethane (40 ml), and to the solution was added at 0° C. thienylglycolic acid (0.95 g). The mixture was cooled at -50° C., and to the mixture was dropwise added over 30 minutes a solution of triethylamine (1.11 g) in dried dichloromethane (10 ml), after which the mixture was stirred for 30 minutes at the same temperature. To the solution was dropwise added over 30 minutes at -50° C. a solution which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (1.075 g), bis(triethylsilyl)acetamide (2.04 g) and dried dichloromethane (25 ml) for 2 hours at room temperature. The mixture was stirred for 2 hours at the same temperature and for 1 hour at -20° to -30° C. After the reaction, water (10 ml) was added at 0° C. to the reaction mixture, and then dichloromethane was removed under reduced pressure. To the residue was added water (40 ml), after which the solution was extracted twice with ethyl acetate (50 ml). The extract was extracted three times with a sodium bicarbonate aqueous solution (50 ml), and the aqueous extract was washed with ethyl acetate (50 ml), adjusted to pH 2 with 5% sulfuric acid and extracted three times with ethyl acetate (30 ml), after which the extract was washed with water and dried. After the solvent was distilled off, the residue was pulverized by adding isopropyl ether to give pale yellow powder of 2-methyl-7-[2-hydroxy-2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (1.32 g), mp 91° to 96° C. (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:13][CH2:12][C:11](=O)[N:10]([C:15]([CH3:24])([CH3:23])[CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CO.C(OCC)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:15]([CH3:24])([CH3:23])[CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(Cc1ccccc1)N1CC(c2cccc(Cl)c2)OCC1=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(Cc1ccccc1)N1CCOC(c2cccc(Cl)c2)C1
Product: Cl

Procedure:
The title compound, m.p. 235° C. (methanol-ethyl acetate), was prepared from 2-[3-chlorophenyl]-4-[1,1-dimethyl-2-phenylethyl]-5-oxomorpholine and lithium aluminium hydride by an analogous procedure to that described in Example 10.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([C:6](Cl)=[O:7])[C:3](Cl)=[O:4].N1C=CC=CC=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[CH2:24][NH:25][OH:26]>C1(C)C=CC=CC=1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[CH2:24][N:25]1[C:3](=[O:4])[C:2]([CH3:9])([CH3:1])[C:6](=[O:7])[O:26]1
Reactant: CC(C)(C(=O)Cl)C(=O)Cl
Reactant: ONCc1cc(Cl)ccc1Cl
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CC1(C)C(=O)ON(Cc2cc(Cl)ccc2Cl)C1=O
Reaction time: 16 h
Yield: 39 %

Procedure:
To a stirred solution of 4.1 grams (0.024 mole) of dimethylmalonyl chloride and 3.8 grams (0.048 mole) of pyridine in 100 ml of dry toluene at 0° C., 4.7 grams (0.024 mole) of N-(2,5-dichlorophenylmethyl)hydroxylamine (Intermediate D) was added dropwise over 30 minutes, while the temperature was maintained at 0°±5° C. The reaction mixture was allowed to rise to ambient temperature and was stirred about 16 hours. A white solid was separated and washed with toluene. Filtrate and washings were combined, washed with water and saturated aqueous sodium chloride solution, and dried over sodium sulfate. Sodium sulfate was separated, and the liquid was concentrated under reduced pressure to a viscous liquid, and ultimately to a solid. Recrystallization from hexane-ethyl acetate yielded 2.7 grams of solid product; mp 78°-80° C. The nmr and ir spectra were consistent with the assigned structure.
Reaction SMILES: [CH3:1][N:2]([CH3:8])[C:3](=[NH:7])[N:4]([CH3:6])[CH3:5].S(OC)(O[CH3:13])(=O)=O>CN(C=O)C>[CH3:1][N:2]([CH3:8])[C:3](=[N:7][CH3:13])[N:4]([CH3:6])[CH3:5]
Reactant: COS(=O)(=O)OC
Reactant: CN(C)C(=N)N(C)C
Solvent: CN(C)C=O
Product: CN=C(N(C)C)N(C)C

Procedure:
Tetramethlguanidine functionalized perfluorinated polymers were further treated with dimethyl sulfate (DMS) in DMF at 90° C. for 24 hr. Pentamethylguanidine functionalized perfluorinated polymer was obtained. Guanidine functionalized perfluorinated polymers was further treated with 1 M NaOH followed by washing with water.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].C1(CN)CCCCC1.[O:17]=[C:18]1[C:26]2([CH2:30][O:29][C:28]3[CH:31]=[C:32]4[C:36](=[CH:37][C:27]2=3)[CH2:35][CH2:34][O:33]4)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]1[CH2:38][C:39]1[CH:47]=[CH:46][CH:45]=[CH:44][C:40]=1[C:41](O)=[O:42].O=C1C2(COC3C=C4C(=CC2=3)CCO4)C2C(=CC=CC=2)N1CC1C=C(C=CC=1)C(O)=O>>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:41](=[O:42])[C:40]1[CH:44]=[CH:45][CH:46]=[CH:47][C:39]=1[CH2:38][N:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:26]2([CH2:30][O:29][C:28]3[CH:31]=[C:32]4[C:36](=[CH:37][C:27]2=3)[CH2:35][CH2:34][O:33]4)[C:18]1=[O:17]
Reactant: O=C(O)c1ccccc1CN1C(=O)C2(COc3cc4c(cc32)CCO4)c2ccccc21
Reactant: Nc1ccccc1F
Agent: NCC1CCCCC1
Agent: O=C(O)c1cccc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)c1
Product: O=C(Nc1ccccc1F)c1ccccc1CN1C(=O)C2(COc3cc4c(cc32)CCO4)c2ccccc21

Procedure:
Following the procedure as described in EXAMPLE 12 and making non-critical variations using 2-fluoroaniline to replace cyclohexanemethylamine, and 2-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzoic acid to replace 3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzoic acid, N-(2-fluorophenyl)-2-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzamide was obtained (57%) as a colorless solid: mp 195-197° C.; 1H NMR (300 MHz, DMSO-d6) δ10.37 (s, 1H), 7.75-7.59 (m, 2H), 7.51-7.35 (m, 2H), 7.34-7.11 (m, 6H), 7.00 (dd, J=7.4, 7.4 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 6.52 (s, 1H), 6.40 (s, 1H), 5.19-5.00 (m, 2H), 4.85 (d, J=9.4 Hz, 1H), 4.70 (d, J=9.4 Hz, 1H), 4.47 (t, J=8.8 Hz, 2H), 2.93 (t, J=8.8 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ177.8, 161.6, 161.2, 142.8, 135.8, 134.6, 132.7, 131.1, 129.1, 128.6, 127.8, 127.4, 127.3, 127.0, 126.0, 125.8, 124.8, 124.7, 124.2, 123.6, 120.9, 120.4, 119.6, 116.4, 116.2, 109.7, 92.9, 80.5, 72.6, 57.5, 41.4, 28.8; MS (ES+) m/z 529.2 (M+23).
Reaction SMILES: [C:1]([C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[CH:5]=[C:6]([C:11]([CH:13]([O:16][CH3:17])[O:14][CH3:15])=O)[C:7]([O:9][CH3:10])=[O:8])#[N:2].[NH2:22]/[C:23](/[CH3:31])=[CH:24]\[C:25]([O:27]C(C)C)=[O:26]>C(OCC)(=O)C>[C:1]([C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[CH:5]1[C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:11]([CH:13]([O:16][CH3:17])[O:14][CH3:15])[NH:22][C:23]([CH3:31])=[C:24]1[C:25]([OH:27])=[O:26])#[N:2]
Reactant: C/C(N)=C/C(=O)OC(C)C
Reactant: COC(=O)C(=Cc1ccccc1C#N)C(=O)C(OC)OC
Solvent: CCOC(C)=O
Product: COC(=O)C1=C(C(OC)OC)NC(C)=C(C(=O)O)C1c1ccccc1C#N
Temperature: 120 °C
Reaction time: 8 h
Yield: 68.9 %

Procedure:
A mixture of methyl 2-(2-cyanobenzylidene)-4,4-dimethoxyacetoacetate (10.1 g) and isopropyl 3-aminocrotonate (5.51 g) was heated for 40 minutes at 78° C. and for 5.5 hours at 120° C. with stirring, followed by heating for an hour at 125° C. without the stirring. After the reaction mixture was allowed to stand overnight, it was dissolved in ethyl acetate. This solution was washed twice with water, dried and then evaporated to dryness under reduced pressure to give a residue, which was crystallized from ethyl ether. The crystals were collected by filtration and washed with a small amount of ethyl ether to give crude powder of isopropyl ester of 4-(2-cyanophenyl)-5-methoxycarbonyl-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid (8.96 g). Further, the crude product (0.77 g) was recovered from the filtrate. 0.5 g Of this crude product was recrystallized from isopropyl ether to give purified white powder of the same product (0.37 g), mp 171°-172.5° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[C:25]([NH:29][S:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([NH:29][S:30]([C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([C:2]2[CH:7]=[C:6]([C:8]3[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=4)[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:26])[CH3:27]
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccnc(Cl)c2)n1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccnc(-c3cccc(S(=O)(=O)NC(C)(C)C)c3)c2)n1

Procedure:
N-tert-Butyl-3-{4-[4-methyl-6-(4-trifluoromethyl-phenyl)-pyrimidin-2-yl]-pyridin-2-yl}-benzenesulfonamide was prepared from 2-(2-chloro-pyridin-4-yl)-4-methyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.46) (0.29 g, 0.83 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.26 g, 1.0 mmol) according to the general procedure VI. Obtained as a light brown solid (0.23 g), which was subsequently deprotected.
Reaction SMILES: [NH2:1][CH2:2][C:3]([CH3:7])([CH3:6])[CH2:4][OH:5].[CH2:8]([O:15][C:16](ON1C(=O)CCC1=O)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O>O1CCCC1>[CH2:8]([O:15][C:16]([NH:1][CH2:2][C:3]([CH3:7])([CH3:6])[CH2:4][OH:5])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(CN)CO
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(CO)CNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a solution of 3-amino-2,2-dimethyl-1-propanol (2 g) in tetrahydrofuran (20 mL) was added N-(benzyloxycarbonyloxy)-succinimide (7.25 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1-1/1) to give 3-benzyloxycarbonylamino-2,2-dimethyl-1-propanol (4.6 g) To this material were added carbon tetrachloride (40 mL), acetonitrile (40 mL), water (48 mL), sodium periodate (11.6 g) and ruthenium trichloride (0.2 g) successively, and the mixture was stirred at room temperature overnight. To the reaction mixture were added sodium periodate (11.6 g) and ruthenium trichloride (0.2 g), and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in a saturated aqueous potassium carbonate solution. The solution was washed with ethyl acetate, and the aqueous layer was acidified with 2 mol/L hydrochloric acid. The mixture was extracted with ethyl acetate, and the extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid (3.6 g). This material was dissolved in tetrahydrofuran (25 mL). To the solution was added 1,1′-carbonylbis-1H-imidazole (3.39 g), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 28% aqueous ammonia solution (25 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-benzyloxycarbonylamino-2,2-di(methyl)-propionamide (3.35 g). The obtained 3-benzyloxycarbonylamino-2,2-di(methyl)propionamide (0.13 g) was dissolved in methanol (5 mL). To the solution was added 10% palladium-carbon powder (30 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (61 mg).
Reaction SMILES: [NH2:1][CH:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[O:13]=[C:14]([CH3:17])[CH:15]=O>>[O:13]=[C:14]([CH3:17])/[CH:15]=[N:1]/[CH:2]1[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]1
Reactant: CC(=O)C=O
Reactant: CC(C)(C)OC(=O)N1CC(N)C1
Product: CC(=O)/C=N/C1CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
A mixture of tert-butyl 3-aminoazetidine-1-carboxylate (16.8 g, 97.5 mmol) and 2-oxopropanal (10 g, 140 mmol) was stirred for 5 minutes at room temperature. The resulting material was purified via silica gel chromatography (Eluant: 1:1 petroleum ether: ethyl acetate) to give the product as an oil, which was used directly in the next step. Yield: 12.5 g, 55.2 mmol, 57%.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:26](Cl)(=[O:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>C(#N)C>[C:26]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[C:9]2[N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[CH:4][CH:3]=1)(=[O:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CCCCCC(=O)Cl
Reactant: CN1CCN(c2cccc3ccc(N)cc23)CC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCCCC(=O)Nc1ccc2cccc(N3CCN(C)CC3)c2c1
Yield: 37.8 %

Procedure:
The title product was prepared following the procedure of example 16 from 7-amino-1-(4-methyl-1-piperazinyl)-naphthalene (0.182 g, 0.755 mmol) and triethylamine (0.201 mL, 1.51 mmol) and hexanoyl chloride (0.211 mL, 1.51 mmol)in acetonitrile (10 mL) with an overnight reflux. The product was purified by recrystallization from ethyl acetate/hexane to yield 0.097g (37%) of the title compound: mp 144°-146° C. Analysis calculated for C21H29N3O: C, 74.30; H, 8.61; N, 12.38. Found: C, 73.91; H, 8.52; N, 12.22.