Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH:18]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]3)[C:13]([NH:31][C:32](=[O:37])[CH2:33][N:34]([CH3:36])[CH3:35])=[CH:12][N:11]=2)=[N:7][CH:8]=1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10]2[N:11]=[CH:12][C:13]([NH:31][C:32](=[O:37])[CH2:33][N:34]([CH3:35])[CH3:36])=[C:14]([O:16][CH2:17][CH:18]3[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]3)[CH:15]=2)=[N:7][CH:8]=1)#[N:2]
Reactant: CN(C)CC(=O)Nc1cnc(Nc2cnc(C#N)cn2)cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN(C)CC(=O)Nc1cnc(Nc2cnc(C#N)cn2)cc1OCC1CCNCC1
Yield: 72.6 %

Procedure:
A solution of tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(2-(dimethylamino)acetamido) pyridin-4-yloxy)methyl)piperidine-1-carboxylate (24 mg, 0.047 mmol) and trifluoroacetic acid (2 mL) in dichloromethane (10 mL) was stirred for 45 minutes. The solution was concentrated and the residue was loaded onto a MP-TsOH SPE cartridge. Elution with 2M ammonia in methanol gave N-(6-(5-cyanopyrazin-2-ylamino)-4-(piperidin-4-ylmethoxy)pyridin-3-yl)-2-(dimethylamino)acetamide as a yellow solid (14 mg, 72%).
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[Si:9]([O:26][CH:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CS(C)=O.O>[C:22]([Si:9]([O:26][CH:27]1[CH2:32][CH2:31][C:30]2([O:33][CH2:4]2)[CH2:29][CH2:28]1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([CH3:25])([CH3:23])[CH3:24]
Reactant: C[S+](C)(C)=O
Reactant: CC(C)(C)[Si](OC1CCC(=O)CC1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CC(C)(C)[Si](OC1CCC2(CC1)CO2)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred suspension of sodium hydride (60% in mineral oil, 441 mg, 11.0 mmol) in dimethylsulfoxide (7 mL) was added trimethylsulfoxonium iodide (2.53 g, 11.5 mmol) at room temperature, and the mixture was stirred at room temperature for 30 min. To this mixture was added a solution of 4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexanone (3.53 g, 10.0 mmol, Okamura, William H. et al., J. Org. Chem., 1993, 58, 600) in dimethylsulfoxide (35 mL) dropwise at room temperature, and the mixture was stirred at room temperature for 2 h. Then the mixture was diluted with water (600 mL), and extracted with diethyl ether (200 mL×4). The combined organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:10), and then purified with plate TLC eluting with ethyl acetate/n-hexane (1:15) to give 459 mg (13%, trans) and 390 mg (11%, cis) of the title compound as a colorless oil respectively.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[CH:31]1([C:34]2[CH:35]=[N:36][N:37]([CH2:39][C:40](O)=[O:41])[CH:38]=2)[CH2:33][CH2:32]1>>[C:25]([Si:22]([CH3:23])([CH3:24])[O:21][CH2:20][C:19]([N:12]1[C:13]2[N:14]=[CH:15][N:16]=[CH:17][C:18]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:40](=[O:41])[CH2:39][N:37]3[CH:38]=[C:34]([CH:31]4[CH2:32][CH2:33]4)[CH:35]=[N:36]3)[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1)([CH3:30])[CH3:29])([CH3:28])([CH3:27])[CH3:26]
Reactant: O=C(O)Cn1cc(C2CC2)cn1
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N)c2)c2cncnc21
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(NC(=O)Cn3cc(C4CC4)cn3)c2)c2cncnc21

Procedure:
The title compound was prepared according to the method described for Example 1 using (5-Amino-pyridin-3-yl)-{7-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone (Preparation 38) and (4-Cyclopropyl-1H-pyrazol-1-yl)acetic acid (Preparation 88) to afford the title compound as an an off-white solid in 41% yield, 55 mg.
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH:13]2[C:15](=O)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C.Cl.[NH2:21][OH:22]>N1C=CC=CC=1>[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15](=[N:21][OH:22])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1C2CCC1CN(Cc1ccccc1)C2
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: ON=C1C2CCC1CN(Cc1ccccc1)C2
Temperature: 100 °C

Procedure:
The mixture of 19 g (88 mmole) of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one (J. Med. Chem. 1994, 37, 2831), 200 ml of ethanol, 8.78 g (126.4 mmole) of hydroxylamine hydrochloride and 13 ml of pyridine are heated and stirred on a 100° C. oil-bath, then the mixture is evaporated. To the residue 65 ml of 2.5 N sodium hydroxide solution is added, the resulting solution is extracted with 3×120 ml of ethyl acetate. The extractum is dried over sodium sulphate and evaporated. The resulting oil is purified by column chromatography (n-hexane-ethyl acetate from 9:1 to 1:1) to obtain 11.05 g (54%) of white, crystalline material. M.p.: 92-95° C. (MH+)=231.
Reaction SMILES: [C:1]([NH:8][C:9]1[S:10][C:11]([CH:17]([CH3:19])[CH3:18])=[CH:12][C:13]=1[N+:14]([O-])=O)([C:3](OCC)=[O:4])=[O:2].S(S([O-])=O)([O-])=O.[Na+].[Na+]>O1CCOCC1.O>[CH:17]([C:11]1[S:10][C:9]2[NH:8][C:1](=[O:2])[C:3](=[O:4])[NH:14][C:13]=2[CH:12]=1)([CH3:19])[CH3:18]
Reactant: CCOC(=O)C(=O)Nc1sc(C(C)C)cc1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)c1cc2[nH]c(=O)c(=O)[nH]c2s1
Yield: 8.8 %

Procedure:
2-Ethoxalylamino-5-isopropyl-3-nitrothiophene (i g, 3.5 mmol) was dissolved in 10 ml of dioxane at 50° C., 6 ml of water was added, and the solution was treated with 12.2 g (70 mmol) of sodium dithionite dissolved in 50 ml of warm water (50° C.) over a period of 30 minutes. The mixture was cooled and extracted with 4×25 ml of ethyl acetate. The combined organic phases were washed with water, dried (MgSO4), and concentrated to 15 ml, whereby a crop of crystals separated which was filtered off and dried to yield 65 mg (8%) of the title compound, melting over 300° C. 1H-NMR (DMSO-D6, δ): 1.2 (d, 6H) ,3.1 (m, 1H), 6.5 (s, 1H), 11.8 (broad, 1H), 12.2 (broad, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([CH:8]=[C:9]2[S:13][C:12](=[O:14])[NH:11][C:10]2=[O:15])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:18]N(C)C=O.[H-].[Na+].IC>O>[CH3:18][N:11]1[C:10](=[O:15])[C:9](=[CH:8][C:7]2[CH:16]=[CH:17][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[S:13][C:12]1=[O:14]
Reactant: CN(C)C=O
Reactant: O=C1NC(=O)C(=Cc2ccc([N+](=O)[O-])cc2)S1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: CN1C(=O)SC(=Cc2ccc([N+](=O)[O-])cc2)C1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 95 %

Procedure:
To a mixture of 5-(4-nitrobenzylidene)-1,3-thiazolidine-2,4-dione (4.0 g) and N,N-dimethylformamide (100 mL) was added sodium hydride (60% in oil, 0.7 g) at room temperature. The reaction mixture was stirred at room temperature for 30 min. and iodomethane (6.81 g) was added to the reaction mixture. The mixture was further stirred at room temperature for 15 hrs. Water was added to the reaction mixture and the precipitated crystals were collected by filtration to give 3-methyl-5-(4-nitrobenzylidene)-1,3-thiazolidine-2,4-dione as yellow crystals (4.02 g, yield 95%). Recrystallization thereof from tetrahydrofuran-hexane gave yellow prism crystals. melting point: 233-234° C.
Reaction SMILES: [C:1]([O:4]C(=O)C)(=[O:3])[CH3:2].[S:8]([O-])([O-:11])(=[O:10])=[O:9].[Na+:13].[Na+].S(=O)(=O)(O)O>C(O)(=O)C>[S:8]([O-:11])([O:4][C:1](=[O:3])[CH3:2])(=[O:10])=[O:9].[Na+:13]
Reactant: O=S(=O)([O-])[O-]
Reactant: CC(=O)OC(C)=O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(=O)OS(=O)(=O)[O-]
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A sulfating mixture comprising sodium acetyl sulfate was prepared as follows: 162.9 grams acetic anhydride and 52.5 grams glacial acetic acid were added to a 1 liter jacketed resin flask. 30.8 grams of sodium sulfate were added and the contents stirred for 5 minutes. 20.15 grams of concentrated sulfuric acid (98% by weight) were added dropwise at such a rate that the temperature of the reactor contents did not exceed 55° C. The rate of addition of sulfuric acid may be increased, if desired, if cooling is applied by circulating ice water through the jacket of the reactor. The reactor was stirred for 30 minutes after the addition of the sulfuric acid was completed.
Reaction SMILES: CN([CH:4]=[C:5]1[CH2:11][C:10](=[O:12])[NH:9][C:8]2[CH:13]=[CH:14][CH:15]=[CH:16][C:7]=2[C:6]1=O)C.[N+]([O-])(O)=O.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([NH:32][C:33]([NH2:35])=[NH:34])[CH:27]=[CH:28][C:29]=1[O:30][CH3:31]>>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([NH:32][C:33]2[N:35]=[CH:4][C:5]3[CH2:11][C:10](=[O:12])[NH:9][C:8]4[CH:13]=[CH:14][CH:15]=[CH:16][C:7]=4[C:6]=3[N:34]=2)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31]
Reactant: CN(C)C=C1CC(=O)Nc2ccccc2C1=O
Reactant: COc1ccc(NC(=N)N)cc1OC
Solvent: O=[N+]([O-])O
Product: COc1ccc(Nc2ncc3c(n2)-c2ccccc2NC(=O)C3)cc1OC

Procedure:
In a manner similar to that described for method I, 4-dimethylaminomethylene-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-c) and N-(3,4-dimethoxyphenyl)guanidine nitrate were converted to I-27 (58%): HRMS Calcd. for C20H18N4O3: 363.1457, Found 363.1441.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]2[S:16]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)(=[O:18])=[O:17].[Br:25]N1C(=O)CCC1=O>CN(C)C=O>[NH2:1][C:2]1[C:3]([Br:25])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]2[S:16]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)(=[O:18])=[O:17]
Reactant: CCOC(=O)c1[nH]c2ccc(N)cc2c1S(=O)(=O)N1CCOCC1
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Product: CCOC(=O)c1[nH]c2ccc(N)c(Br)c2c1S(=O)(=O)N1CCOCC1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Ethyl 5-amino-3-(morpholin-4-ylsulfonyl)-1H-indole-2-carboxylate (189 mg, 0.53 mmol, 1.0 equiv) was dissolved in 4 mL of dimethylformamide and cooled to 0° C. N-bromosuccinimide (95 mg, 0.54 mmol, 1.0 equiv) was added and the reaction was stirred for 15 minutes. The reaction mixture was partitioned between dichloromethane and aqueous saturated NaHCO3, which was extracted three times with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 50% ethyl acetate/dichloromethane) provided the titled compound. Proton NMR for the product was consistent with the titled compound. ESI+MS: 432.1 [M+H]+.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]2[CH:11]=[C:10]([C:12]3[N:13]=[N:14][N:15]([CH3:17])[N:16]=3)[CH:9]=[CH:8][C:5]=2[S:6][CH:7]=1.[C-:18]#[N:19].[Na+].O>CS(C)=O>[C:18]([CH2:2][C:3]1[C:4]2[CH:11]=[C:10]([C:12]3[N:13]=[N:14][N:15]([CH3:17])[N:16]=3)[CH:9]=[CH:8][C:5]=2[S:6][CH:7]=1)#[N:19]
Reactant: Cn1nnc(-c2ccc3scc(CBr)c3c2)n1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Cn1nnc(-c2ccc3scc(CC#N)c3c2)n1
Temperature: 100 °C
Reaction time: 2 h
Yield: 51.4 %

Procedure:
The crude 3-bromomethyl-5-(2-methyl-tetrazol-5-yl)benzo[b]thiophene (0.145 g) in DMSO (0.3 ml) was added to a mixture of sodium cyanide (29.9 mg, 0.6 mmol) in DMSO (0.2 ml) and the mixture was stirred at 100° C. for 2 h. After cooling, the mixture was poured into water (10 ml) and a brown solid was filtered off, washed with water and dried in a vacuum pistol to leave 73.5 mg. The filtrate was extracted with dichloromethane (3×30 ml) and the combined extracts were dried (Na2SO4) and evaporated in vacuo to leave 44.7 mg. This was combined with the original solid and chromatographed on flash silica, eluting with 20-50% ethyl acetate/petroleum ether to yield 61.5 mg (38%) of the title product as a white solid. δ (CDCl3) 3.99 (2H, s), 4.43 (3H, s), 7.59 (1H, s), 8.00 (1H, d, J=8.5 Hz), 8.19 (1H, dd, J=8.5 and 1.5 Hz), 8.47 (1H, s).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[CH:23]([C:26]1[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[O:34])=[CH:28][CH:27]=1)([CH3:25])[CH3:24]>C1(C)C=CC=CC=1>[CH:23]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:22][C:19]2[CH:18]=[CH:17][C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][CH:7]=3)=[CH:21][CH:20]=2)=[O:34])=[CH:28][CH:27]=1)([CH3:25])[CH3:24]
Reactant: CC(C)c1ccc(N=C=O)cc1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccc(C(C)C)cc4)cc3)c2cc1OC
Yield: 90 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (51 mg) was dissolved in toluene (3 ml) with heat, 4-isopropylphenyl isocyanate (0.2 ml) was added, and the admixture was refluxed with heat for 26 minutes. The resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 70 mg of the title compound (yield: 90%).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:33]=[CH:32][C:16]([CH2:17][NH:18][CH2:19][C:20]3[CH:31]=[CH:30][C:23]([O:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[C:34](Cl)(=[O:40])[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]>>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:30][CH:31]=3)[C:34](=[O:40])[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[CH:32][CH:33]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C#Cc2ccc(CNCc3ccc(OCC(=O)OC)cc3)cc2)cc1
Reactant: CCCCCC(=O)Cl
Product: CCCCCC(=O)N(Cc1ccc(C#Cc2ccc(CCCC)cc2)cc1)Cc1ccc(OCC(=O)OC)cc1

Procedure:
The titled compound was prepared following the procedure B using methyl {4-[({4-[(4-butylphenyl)ethynyl]benzyl}amino)methyl]phenoxy}acetate and hexanoyl chloride as a colorless oil (79%). 1H NMR (CDCl3, 300 MHz) δ 7.41-7.50 (m, 4H), 7.03-7.16 (m, 6H), 6.85 (m, 2H), 4.62 (s, 1H), 4.60 (s, 1H), 4.55 (s, 1H), 4.51 (s, 1H), 4.41 (s, 1H), 4.36 (s, 1H), 3.80 (s, 1.5H), 3.79 (s, 1.51, 2.60 (t, J=7.6 Hz, 2H), 2.38 (m, 2H), 1.56-1.67 (m, 4H), 1.30-1.37 (m, 6H), 0.91 (m, 6H). M+ (ESI): 540.4. HPLC, Rt: 5.85 min (Purity: 99.3%).
Reaction SMILES: [SiH3:1][SiH2:2][SiH2:3][SiH2:4][SiH2:5][SiH2:6][SiH2:7][SiH2:8][SiH2:9][SiH2:10][SiH2:11][SiH2:12][SiH2:13][SiH2:14][SiH2:15][SiH3:16].[F:17][C:18]([F:24])([F:23])[S:19]([OH:22])(=[O:21])=[O:20]>ClCCl>[F:17][C:18]([F:24])([F:23])[S:19]([O:22][SiH2:16][SiH2:15][SiH2:14][SiH2:13][SiH2:12][SiH2:11][SiH2:10][SiH2:9][SiH2:8][SiH2:7][SiH2:6][SiH2:5][SiH2:4][SiH2:3][SiH2:2][SiH3:1])(=[O:21])=[O:20]
Reactant: [SiH3][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH3]
Reactant: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Product: O=S(=O)(O[SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH2][SiH3])C(F)(F)F

Procedure:
In an argon atmosphere, to a tetrahydrofuran solution (1 ml) of 52 mg (0.15 mmol) of octaethylcyclotetrasilane was added 0.58 ml (0.15 mmol) of a tetrahydrofuran solution (0.27M) of phenyldimethylsilyllithium, and stirred at 0° C. for 15 minutes. Then, tetrahydrofuran was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (Solution 1). A dichloromethane solution (1 ml) of 68 mg (0.05 mmol) of hexadecasilane (9) obtained in Example 9 was treated with 7.5 mg (0.05 mmol) of trifluoromethanesulfonic acid at room temperature for 30 minutes to give 1-(trifluoromethanesulfonyloxy)hexadecasilane. Then, dichloromethane was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (solution 2). The Solution 1 was added to the Solution 2 at -78° C. and stirred for 15 minutes. Methanol (0.1 ml) and triethylamine (0.1 ml) were added, then saturated aqueous sodium bicarbonate solution (2 ml) was added, stirred, the hexane layer was separated, and dried with magnesium sulfate. The resulting crude product was purified by a silica gel column chromatography (hexane) to give 137 mg (39% yield) of eicosasilane (10) as a colorless crystal.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH2:10][CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.C1C=C(Cl)C=C(C(OO)=[O:19])C=1>C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][N+:5]([O-:19])=[C:4]2[CH2:8][CH2:9][CH2:10][C:3]=12
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Clc1ncnc2c1CCC2
Solvent: ClC(Cl)Cl
Product: [O-][n+]1cnc(Cl)c2c1CCC2
Temperature: 25 °C
Reaction time: 16 h
Yield: 46.7 %

Procedure:
To a solution of 4-chloro-6,7-dihydro-5H-cyclopenta[d]pyrimidine (5.69 g, 36.8 mmol) in chloroform (200 mL) was added MCPBA (19 g, 84.8 mmol) in chloroform (50 mL) dropwise. The mixture was stirred at room temperature for 16 hour. After cooling with ice-water, the mixture was quenched with Na2S2O3 (27.5 g) in water (110 mL) dropwise and followed by Na2CO3 (14 g) in water (52 mL) dropwise. The organic phase was separated and the aqueous phase was extracted with chloroform (3×200 mL). The organic phase was dried and concentrated at low temperature (<25° C.). The residue was subject to chromatography on silica gel, eluting by ethyl acetate to afford 4-chloro-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide (2.93 g, 47%). MS (APCI+) [M+H]+171.
Reaction SMILES: [C:1]([OH:6])#[C:2][CH2:3][CH2:4][CH3:5].[Si:7](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CCN(CC)CC.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[C:20]([Si:7]([O:6][CH2:1][CH2:2][CH2:3][C:4]#[CH:5])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:23])([CH3:21])[CH3:22]
Reactant: CCCC#CO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C#CCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 97.9 %

Procedure:
A mixture of pentynol (8.0 g, 95 mmol), t-butyldiphenylsilylchloride (28 g, 114 mmol) and Et3N (14 g, 138 mmol) in CH2Cl2 is stirred at room temperature for 16 h, treated with 1M K2CO3 and extracted with CH2Cl2. The combined extracts are dried over MgSO4 and concentrated in vacuo. The residue is purified by filtration on a silica pad to obtain 30 g of t-butylpent-4-ynyloxy diphenyl silane (yield: 98%
Reaction SMILES: [C-:1]#[N:2].[Na+].[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:20]3[C:15](=[C:16]([CH2:21]Cl)[CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][N:12]=2)=[CH:7][CH:6]=1>>[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([CH2:21][C:1]#[N:2])[C:15]=3[CH:14]=[CH:13][N:12]=2)=[CH:7][CH:6]=1
Reactant: [C-]#N
Reactant: Fc1ccc(-c2nccc3c(CCl)cccc23)cc1
Agent: [Na+]
Product: N#CCc1cccc2c(-c3ccc(F)cc3)nccc12

Procedure:
Sodium cyanide and 1-(4-fluorophenyl)-5-chloromethylisoquinoline were reacted in the same way as in step (b) in Example 2 to afford 1-(4-flurophenyl)isoquinoline-5-acetonitrile having a melting point of 136° to 136.5° C.
Reaction SMILES: [OH-].[Na+].[CH3:3][CH:4]([N:6]1[C:14]2[CH:13]=[C:12]([S:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)(=[O:17])=[O:16])[CH:11]=[C:10]([C:24]([O:26]C)=[O:25])[C:9]=2[CH:8]=[N:7]1)[CH3:5]>C(O)C>[CH3:5][CH:4]([N:6]1[C:14]2[CH:13]=[C:12]([S:15]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)(=[O:16])=[O:17])[CH:11]=[C:10]([C:24]([OH:26])=[O:25])[C:9]=2[CH:8]=[N:7]1)[CH3:3]
Reactant: COC(=O)c1cc(S(=O)(=O)N2CCOCC2)cc2c1cnn2C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)n1ncc2c(C(=O)O)cc(S(=O)(=O)N3CCOCC3)cc21

Procedure:
Sodium hydroxide (0.980 mL, 0.980 mmol) was added to a solution of methyl 1-(1-methylethyl)-6-(4-morpholinylsulfonyl)-1H-indazole-4-carboxylate (90 mg, 0.245 mmol) in ethanol (30 mL) and heated at reflux for 1 hour. The solvent was removed in vacuo and the residue suspended in water (20 mL). The contents were acidified by addition of acetic acid, and extracted with DCM (4×30 mL). The combined organic layers were washed with water, brine, dried over MgSO4, filtered, and concentrated in vacuo. The product was collected as 90 mg. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.63-1.78 (m, 6H), 3.02-3.24 (m, 4H), 3.67-3.88 (m, 4H), 5.00 (dt, J=13.20, 6.66 Hz, 1H), 8.21 (s, 1H), 8.31 (s, 1H), 8.71 (s, 1H), LCMS (ES) [M+H]+ 354.2
Reaction SMILES: C[O:2][B:3]([O:6]C)OC.Br[C:9]1[CH:10]=[CH:11][C:12]([F:17])=[C:13]([CH:16]=1)[C:14]#[N:15].C([Li])CCC>C1(C)C=CC=CC=1.C1COCC1>[C:14]([C:13]1[CH:16]=[C:9]([B:3]([OH:6])[OH:2])[CH:10]=[CH:11][C:12]=1[F:17])#[N:15]
Reactant: N#Cc1cc(Br)ccc1F
Reactant: COB(OC)OC
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: N#Cc1cc(B(O)O)ccc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 20 %

Procedure:
Trimethylborate (1.37 mL, 12 mmol) was added to a solution of 5-bromo-2-fluorobenzonitrile (2.0 g, 10 mmol) in toluene (16 mL) and THF (4 mL) at −78° C. n-Butyl lithium (2.5M in hexane; 4.8 mL) was slowly added over 1 h and the solution was stirred for 30 min after which it was warmed to rt for 1 h. The reaction was cooled to 0° C. and quenched with 20 mL of 1 N HCl. The product was extracted with ethyl acetate (2×200 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography eluting with 5% methanol/methylene chloride afforded 0.33 g of the desired product.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:50])[C@@H:15]([O:48][CH3:49])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][C:26]2[N:27]=[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[O:29][C:30]=2[CH3:31])=[CH:19][C:18]=1[O:38][Si](C)(C)C(C)(C)C(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH4+].[F-]>CO.CCOC(C)=O>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:50])[C@@H:15]([O:48][CH3:49])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][C:26]2[N:27]=[C:28]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[O:29][C:30]=2[CH3:31])=[CH:19][C:18]=1[OH:38])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CO[C@@H](Cc1ccc(OCCc2nc(-c3ccccc3)oc2C)cc1O[Si](C)(C)C(C)(C)C(C)C)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: [F-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CO[C@@H](Cc1ccc(OCCc2nc(-c3ccccc3)oc2C)cc1O)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Reaction time: 2 h

Procedure:
To a solution of (S)-4-benzyl-3-(3-{2-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-2-(2S)-methoxy-propionyl)-oxazolidin-2-one (1.6 g, 2.29 mmol) in 10 ml methanol, was added NH4F (169 mg, 4.58 mmol) and the reaction mixture kept at r.t. for 2 hours. It was then diluted with AcOEt, washed with water/ice and brine, the aqueous layer was extracted with AcOEt, the combined organic layers dried over Na2SO4 and evaporated. The crude product (1.22 g) was found to be a mixture of the title compound and of (S)-3-{2-hydroxy-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methoxy-propionic acid methyl ester and used without purification for the last step.