Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C1C=CC=CC=1C(Cl)=O.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH3:27])[N:22]=[CH:21][CH:20]=[C:19]2[O:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][C:30]=1[F:36].[F:37][C:38]([F:51])([F:50])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:45]([N:47]=[C:48]=[S:49])=[O:46]>C1(C)C=CC=CC=1.C(O)C>[F:50][C:38]([F:37])([F:51])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:45]([N:47]=[C:48]=[S:49])=[O:46].[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH3:27])[N:22]=[CH:21][CH:20]=[C:19]2[O:28][C:29]1[CH:35]=[CH:34][C:32]([NH:33][C:48]([NH:47][C:45](=[O:46])[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[C:38]([F:37])([F:51])[F:50])=[S:49])=[CH:31][C:30]=1[F:36]
Reactant: COc1cc2nccc(Oc3ccc(N)cc3F)c2cc1OC
Agent: O=C(Cl)c1ccccc1C(F)(F)F
Agent: O=C(N=C=S)c1ccccc1C(F)(F)F
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4C(F)(F)F)cc3F)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 73 %

Procedure:
2-(Trifluoromethyl)-1-benzenecarbonyl isothiocyanate was prepared using commercially available 2-(trifluoromethyl)-1-benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-3-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 2-(trifluoromethyl)-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 73%).
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][C:9]1[N:10]([CH2:33][CH:34]([CH3:36])[CH3:35])[C:11](=[O:32])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:16][C:15]([O:27][CH2:28][C:29]([NH2:31])=[O:30])=[CH:14][CH:13]=2)(C)(C)C.[H][H].[Cl-:40]>C(OCC)(=O)C>[ClH:40].[NH2:7][CH2:8][C:9]1[N:10]([CH2:33][CH:34]([CH3:36])[CH3:35])[C:11](=[O:32])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:16][C:15]([O:27][CH2:28][C:29]([NH2:31])=[O:30])=[CH:14][CH:13]=2
Reactant: CC(C)Cn1c(CNC(=O)OC(C)(C)C)c(OCCCC(F)(F)F)c2cc(OCC(N)=O)ccc2c1=O
Reactant: [H][H]
Reactant: [Cl-]
Solvent: CCOC(C)=O
Product: CC(C)Cn1c(CN)c(OCCCC(F)(F)F)c2cc(OCC(N)=O)ccc2c1=O
Product: Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.8 %

Procedure:
To a solution of tert-butyl[6-(2-amino-2-oxoethoxy)-2-isobutyl-4-(4,4,4-trifluorobutoxy)-1-oxo-1,2-dihydro-3-isoquinolinyl]methylcarbamate (0.18 g, 0.35 mmol) in ethyl acetate (5 mL) was added a solution of 4N hydrogen, chloride in ethyl acetate (5 mL) and the obtained solution was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure, and the precipitated crystals were recrystallized from methanol-diisopropyl ether to give 2-[[3-(aminomethyl)-2-isobutyl-1-oxo-4-(4,4,4-trifluorobutoxy)-1,2-dihydro-6-isoquinolinyl]oxy]acetamide hydrochloride (0.15 g, 93.8%) as crystals.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[N:9][N:10]([CH2:18][C:19]([O:21]CC)=[O:20])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:24]([N:26]([CH2:29][CH2:30][CH2:31][NH2:32])[CH2:27][CH3:28])[CH3:25]>CCOCC>[OH2:20].[CH2:24]([N:26]([CH2:27][CH3:28])[CH2:29][CH2:30][CH2:31][NH:32][C:19](=[O:21])[CH2:18][N:10]1[C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=[N:9]1)[CH3:25].[CH2:24]([N:26]([CH2:29][CH2:30][CH2:31][NH:32][C:19](=[O:21])[CH2:18][N:10]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]=[N:9]1)[CH2:27][CH3:28])[CH3:25]
Reactant: CCN(CC)CCCN
Reactant: CCOC(=O)Cn1ncc(-c2ccccc2)c1-c1ccccc1
Solvent: CCOCC
Product: CCN(CC)CCCNC(=O)Cn1ncc(-c2ccccc2)c1-c1ccccc1
Product: O
Yield: 82.3 %

Procedure:
A mixture of 8 g (0.026 mol) of ethyl 4,5-diphenyl-1H-pyrazole-1-acetate of example 1 and 40 mL (0.25 mol) of diethylaminopropylamine was heated on a steam bath under nitrogen for 14 hours. The excess diethylaminopropylamine was stripped in vacuo and the residue dissolved in ether. The ether solution was washed two times with water, once with saturated sodium chloride, dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting white residue was dissolved in ether and a small amount of undesired material was removed by filtration after addition of some pentane. The filtrate was stripped, redissolved in ether, dried over magnesium sulfate, treated with decolorizing carbon, filtered and evaporated. The resulting residue was triturated in water filtered and rinsed with water to yield 8.55 g (82%) of N-[3-(diethylamino)propyl]-4,5-diphenyl-1H-pyrazole-1-acetamide hemihydrate, mp 70°-74° C. The product can be recrystallized from wet ether.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]([CH3:15])[CH3:14])=[C:8]([CH3:16])[CH:7]=2)[CH2:2]1.[C:17]1([C:23]2[O:27][C:26]([C:28](OCC)=[O:29])=[N:25][N:24]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH3:14][N:13]([CH2:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH:3]2[CH2:2][N:1]([C:28]([C:26]3[O:27][C:23]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[N:24][N:25]=3)=[O:29])[CH2:4]2)=[CH:7][C:8]=1[CH3:16])[CH3:15]
Reactant: CCOC(=O)c1nnc(-c2ccccc2)o1
Reactant: Cc1cc(OC2CNC2)ccc1CN(C)C
Product: Cc1cc(OC2CN(C(=O)c3nnc(-c4ccccc4)o3)C2)ccc1CN(C)C
Temperature: 120 °C
Reaction time: 2 h
Yield: 94.2 %

Procedure:
Intermediate 20C (0.16 g, 0.73 mmol) and ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate (0.17 g, 0.80 mmol) were mixed together in a microwave vial. The vial was sealed and the mixture was then stirred at 120° C. for 2 hours using an oil bath. The mixture was cooled to room temperature. The product was purified by column chromatography eluting with DCM and MeOH (saturated with ammonia)/DCM (gradient, 0.5-2%). The solvent was removed by evaporation and the semi solid residue was triturated with Et2O. There was obtained 0.27 g (93%) of the product as a crystalline solid m.p. 135° C. 1H NMR (600 MHz, CDCl3): δ 2.21 (s, 6H), 2.34 (s, 3H), 3.31 (s, 2H), 4.28-4.35 (m, 1H), 4.59-4.67 (m, 1H), 4.70-4.78 (m, 1H), 5.01-5.15 (m, 2H), 6.54 (d, 1H), 6.60 (s, 1H), 7.15 (d, 1H), 7.49-7.62 (m, 3H), 8.16 (d, 2H), MS (APCI+) m/z 393 [M+H]+, LC purity: 99%.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:14]([NH2:16])=[N:13][CH:12]=[N:11][C:10]=3[N:9]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][CH2:25][NH:26]CCO)[CH:18]=3)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:30]>>[C:1]1([C:7]2[C:15]3[C:14]([NH2:16])=[N:13][CH:12]=[N:11][C:10]=3[N:9]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][CH2:25][Cl:30])[CH:18]=3)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:26][CH2:25][CH2:24][OH:23]
Reactant: Nc1ncnc2c1c(-c1ccccc1)cn2-c1cccc(OCCNCCO)c1
Reactant: Cl
Product: NCCO
Product: Nc1ncnc2c1c(-c1ccccc1)cn2-c1cccc(OCCCl)c1

Procedure:
5-Phenyl-7-[3-(2-(2-hydroxyethylamino)ethoxy)phenyl]-4-aminopyrrolo[2,3-d]-pyrimidine, m.p. 188°-189° C., or a salt thereof, e.g. the hydrochloride. The free compound is obtained by reaction of 5-phenyl-7-[3-(2-chloroethoxy)phenyl]-4-aminopyrrolo[2,3-d]-pyrimidine (see Example 108) and 2-aminoethanol.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1.FC(F)(F)S(O[CH2:23][CH2:24][C:25]([F:37])([F:36])[C:26]([F:35])([F:34])[C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])(=O)=O.Cl>C1C=CC=CC=1.C(COC)OC>[OH:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:23][CH2:24][C:25]([F:36])([F:37])[C:26]([F:34])([F:35])[C:27]([F:32])([F:33])[C:28]([F:31])([F:30])[F:29])=[CH:12][CH:11]=2)=[CH:8][CH:9]=1
Reactant: Oc1ccc(-c2ccc(O)cc2)cc1
Reactant: O=S(=O)(OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: c1ccccc1
Product: Oc1ccc(-c2ccc(OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 27.2 %

Procedure:
First, 3.0 g of 60% sodium hydride and 120 ml of dehydrated dimethoxyethane were put in an argon-replaced 300 ml flask. Then, 9.93 g of 4,4′-dihydroxybiphenyl was added while icing, and stirred at room temperature for two hours. The reaction solution was cooled again to −60° C., and 28.7 g of 2-(perfluorobutyl)ethyl trifluoromethanesulfonate was dropped into the reaction solution. After the resultant reaction solution was left to resume room temperature, it was stirred for 12 hours. After the reaction, dilute hydrochloric acid and benzene were added to the reaction solution to separate an organic layer. The organic layer was washed with a saturated brine and dried with sodium sulfate. The solvent was then distilled off. The residue was purified by silica gel column chromatography (eluent:benzene/ethyl acetate=9/1), and recrystallized from toluene to obtain 6.26 g (Y: 27.1%) of 4-hydroxy-4′-[2-(perfluorobutyl)ethyloxy]biphenyl. The purity of the resultant compound was 98.4% as measured by GC.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][CH:4]=1)#[N:2].[O:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][NH2:21])[CH2:15][CH2:14]1>CC(C)=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:21][CH2:20][CH2:19][N:16]2[CH2:17][CH2:18][O:13][CH2:14][CH2:15]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: NCCN1CCOCC1
Solvent: CC(C)=O
Product: N#Cc1ccc(S(=O)(=O)NCCN2CCOCC2)cc1
Temperature: 25 °C

Procedure:
A mixture of 4-cyanobenzene sulphonyl chloride (5.15 g) in acetone (70 ml) was stirred at ambient temperature and then a solution of 2-morpholinoethylamine (6.7 ml) in acetone (15 ml) was added dropwise with stirring. The mixture was stirred at ambient temperature for 2 hours and then the acetone was removed by evaporation and the residue was eluted through a silica pad using ethyl acetate to give 4-cyano-N-2-morpholinoethyl-benzenesulphonamide.
Reaction SMILES: CC[O:3]CC.C[Si](C)(C)[N:8]([CH2:13][C:14]#[C:15][CH2:16]OC)[Si](C)(C)C.[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[Mg]Br.[NH4+].[OH-]>Cl[Ni]Cl.C(OC(=O)C)C>[NH4+:8].[OH-:3].[C:15](=[C:14]([C:22]1[S:21][CH:25]=[CH:24][CH:23]=1)[CH2:13][NH2:8])=[CH2:16]
Reactant: Br[Mg]c1cccs1
Reactant: COCC#CCN([Si](C)(C)C)[Si](C)(C)C
Reactant: CCOCC
Agent: Cl[Ni]Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: C=C=C(CN)c1cccs1
Yield: 87 %

Procedure:
NiCl2 (dppp) catalyst (170 mg; 3M %) was added to dry ether (30 ml) in a 100 ml 3-necked flask with mechanical stirrer, thermometer and nitrogen bubbler. III (2.47g, 10.2 mM) was added via syringe with stirring and immediately thereafter 3M thienylmagnesium bromide (7 ml, 21 mM) was added via syringe. After stirring at room temperature for 20 hours the reaction was complete as shown by G C analysis. The silylated product was isolated by shaking with dilute NH4OH and extraction into ethylacetate (three times, each into 100 ml). After drying over K2CO3 and concentration, 2.68 g crude product was obtained. Purification and desilyation by flash chromatography (300 g silica gel, eluted with CHCl3, then CHCl3 :MeOH:conc. NH4OH 100:10:1) gave 1.22 g (87%) of the desired product as a light tan oil after drying under high vacuum.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N:19]([CH3:21])[CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[C:22]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](O)=[O:29])(=[O:24])[CH3:23].CCN=C=NCCCN(C)C.C(Cl)[Cl:46].CO>CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl-:46].[C:22]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([N:19]([CH3:21])[CH3:20])[CH:17]=3)[NH+:12]=[CH:11][CH:10]=2)=[CH:6][CH:7]=1)=[O:29])(=[O:24])[CH3:23]
Reactant: ClCCl
Reactant: CC(=O)c1cccc(C(=O)O)c1
Reactant: CN(C)c1ccc2nccc(Nc3ccc(N)cc3)c2c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: CO
Solvent: CN(C)C=O
Product: CC(=O)c1cccc(C(=O)Nc2ccc(Nc3cc[nH+]c4ccc(N(C)C)cc34)cc2)c1
Product: [Cl-]
Temperature: 20 °C
Reaction time: 0.08 h

Procedure:
A mixture of N4-(4-Aminophenyl)-N6,N6-dimethyl-4,6-quinolinediamine (181 mg, 0.58 mmol), 3-acetylbenzoic acid (M1) (97 mg, 0.58 mmol) and EDCI (220 mg, 0.1.16 mmol) in DMF (5 mL) was stirred at 20° C. for 5 min. Then DMAP (140 mg, 1.16 mmol) was added and the reaction mixture was stirred at 20° C. for 24 h. The solvent was removed under reduced pressure and residue was stirred in aqueous NaHCO3 for 1 h. The resulting precipitate was filtered and purified by chromatography in SiO2 eluting with a gradient (0-7.5%) of MeOH/DCM to give M2 (113 mg, 42%); mp (DCM/MeOH)>280° C.; 1HNMR [(CD3)2SO] δ14.02 (br, 1 H, N+H), 10.66 (s, 1 H, NH), 10.31 (s, 1 H, NH), 8.53 (t, J=1.6 Hz, 1 H, ArH), 8.28 (d, J=6.7 Hz, 1 H, ArH), 8.24 (td, J=8.1, 1.5 Hz, 1 H, ArH), 8.19 (td, J=7.8, 2.8 Hz, 1 H, ArH), 8.00 (d, J=6.8 Hz, 2 H, ArH), 7.87 (d, J=9.4 Hz, 1 H, ArH), 7.78 (t, J=7.8 Hz, 1 H, ArH), 7.64 (dd, J=9.4, 2.6 Hz, 1 H, ArH), 7.51 (d, J=2.5 Hz, 1 H, ArH), 7.47 (d, J=8.8 Hz, 2 H, ArH), 6.69 (d, J=6.7 Hz, 1 H, ArH), 3.09 [s, 6 H, (NCH3)2], 2.68 (s, 3 H, COCH3); APCI+ve 425.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C(O)C.O.NN>C1COCC1.[Ni]>[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1
Reactant: COc1ccc([N+](=O)[O-])cc1CN1CCOCC1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: COc1ccc(N)cc1CN1CCOCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 67 %

Procedure:
To a solution of 4-(2-methoxy-5-nitrobenzyl)morpholine (252 mg, 1.0 mmol) in THF:ethanol mixture (1:1) (25 mL) was added a catalytical amount of Raney-Nickel and hydrazine hydrate (450 mg; 9.0 mmol) and the mixture was stirred for 1 hour at ambient temperature, filtered through a Celite/silica gel pad. The filtrate was evaporated to yield the pure 4-methoxy-3-morpholin-4-ylmethylphenylamine (149 mg, 67%), which was used in the next step without purification.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=[N:7][OH:8])[CH2:3][CH2:2]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].[F:26][C:27]([F:35])([F:34])[C:28]([F:33])([F:32])[C:29]([OH:31])=[O:30]>>[F:32][C:28]([F:33])([C:27]([F:35])([F:34])[F:26])[C:29]([O:31][C:4]1([N:7]=[O:8])[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[O:30]
Reactant: O=C(O)C(F)(F)C(F)(F)F
Reactant: ON=C1CCOCC1
Agent: CC(=O)[O-]
Agent: [Pb+4]
Product: O=NC1(OC(=O)C(F)(F)C(F)(F)F)CCOCC1

Procedure:
4-Nitrosotetrahydro-2H-pyran-4-yl 2,2,3,3,3-pentafluoropropanoate was prepared from tetrahydro-pyran-4-one oxime, lead tetraacetate and pentafluoropropionic acid using conditions of General Method 3. 1H NMR (250 MHz, chloroform-d) δ 4.11-4.30 (2H, m), 3.46-3.83 (2H, m), 2.45-2.73 (2H, m), 1.68-2.02 (2H, m).
Reaction SMILES: C1(N2C=NC3C2=NC(OCC)=NC=3N)CCCC=C1.[CH:20]1([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][C:29]([O:36][CH2:37][CH:38]([CH3:40])[CH3:39])=[N:30][C:31]=3[NH2:35])[CH2:25][CH2:24][CH2:23][CH:22]=[CH:21]1>>[CH2:37]([O:36][C:29]1[N:28]=[C:27]2[C:32]([N:33]=[CH:34][N:26]2[CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)=[C:31]([NH2:35])[N:30]=1)[CH:38]([CH3:40])[CH3:39]
Reactant: CC(C)COc1nc(N)c2ncn(C3C=CCCC3)c2n1
Agent: CCOc1nc(N)c2ncn(C3C=CCCC3)c2n1
Product: CC(C)COc1nc(N)c2ncn(C3CCCCC3)c2n1
Yield: 60 %

Procedure:
The procedure of Example 8 was repeated except that the 9-(2-cyclohexenyl)-2-ethoxy-9H-adenine used therein was replaced by an equivalent weight of 9-(2-cyclohexenyl)-2-isobutoxy-9H-adenine. There was produced the title product in 60% yield; m.p. 123°-134° C. IR(neat): 3320, 3160, 2940, 1635, 1590, 1395, 1375 cm-1. UV: λmaxEtOH 253 nm(ε 7000), 269 nm(ε 11000). NMR(CDCl3): 1.05(6H, d, J=6.5 Hz), 1.90(11H, m), 4.05(2H, d, J=6.5 Hz), 4.24(1H, m), 6.14(2H, s), 7.55(1H, s).
Reaction SMILES: [N:1]([CH2:4][Si:5]([CH3:8])([CH3:7])[CH3:6])=[N+:2]=[N-:3].[C:9]([C:15]([O:17][CH3:18])=[O:16])#[C:10][C:11]([O:13][CH3:14])=[O:12]>C1C=CC=CC=1.C(OCC)(=O)C.CCCCCC>[CH3:14][O:13][C:11]([C:10]1[N:3]=[N:2][N:1]([CH2:4][Si:5]([CH3:8])([CH3:7])[CH3:6])[C:9]=1[C:15]([O:17][CH3:18])=[O:16])=[O:12]
Reactant: COC(=O)C#CC(=O)OC
Reactant: C[Si](C)(C)CN=[N+]=[N-]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: COC(=O)c1nnn(C[Si](C)(C)C)c1C(=O)OC

Procedure:
A solution of azidomethyl-trimethyl-silane (5.0 g, 38.69 mmol) and dimethyl acetylenedicarboxylate (4.74 mL, 38.69 mmol) in benzene (200 mL) was refluxed for 2 h. The solvent was removed in vacuo and the resultant crude material was diluted with water (100 mL), and extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and evaporated in vacuo. The product was obtained after purification by flash chromatography (using silica gel and 20% ethyl acetate/hexane) as colorless liquid (10 g, 36.9 mmol, 95.2%).
Reaction SMILES: C([Sn](=O)CCCC)CCC.[O:11]([C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)[C@@H:12]1[O:20][C@H:19]([CH2:21][OH:22])[C@H:17]([OH:18])[C@H:15]([OH:16])[C@H:13]1[OH:14].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(Cl)Cl.CO.N>O1CCOCC1>[CH2:32]([O:16][C@H:15]1[C@@H:17]([OH:18])[C@@H:19]([CH2:21][OH:22])[O:20][C@@H:12]([O:11][C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)[C@@H:13]1[OH:14])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: BrCc1ccccc1
Reactant: O=[N+]([O-])c1ccc(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)cc1
Agent: CCCC[Sn](=O)CCCC
Agent: N
Solvent: ClCCl
Solvent: CO
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](OCc3ccccc3)[C@H]2O)cc1
Reaction time: 3 h

Procedure:
Dibutyltin oxide (1.87 g, 7.5 mmol) is added to a solution of p-nitrophenyl β-D-galactopyranoside (1.5 g, 5.0 mmol) in absolute dioxane (40 ml) and the mixture is heated under reflux. After 3 hours, benzyl bromide (3.6 ml, 30 mmol) are added to the solution obtained and the batch is stirred under reflux for a further 48 hours. The solvent is then distilled off in vacuo and the residue is purified by flash chromatography (ethyl acetate/petroleum ether 2:1→1:1]. Colourless crystals (1.58 g 81%) are obtained; TLC [methylene chloride/methanol/ammonia (25%) 15:3:0.2]: Rf=0.69; melting point=127° C.
Reaction SMILES: [F:1][C:2]1[CH:27]=[C:26]([N+:28]([O-])=O)[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:23])[N:13]([CH2:15][CH2:16][CH2:17][N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])[CH3:14])[CH:6]=1.[H][H]>O1CCCC1.CO.[C].[Pd]>[NH2:28][C:26]1[CH:25]=[CH:24][C:3]([O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:23])[N:13]([CH2:15][CH2:16][CH2:17][N:18]([CH2:19][CH3:20])[CH2:21][CH3:22])[CH3:14])[CH:6]=2)=[C:2]([F:1])[CH:27]=1
Reactant: [H][H]
Reactant: CCN(CC)CCCN(C)C(=O)Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ncn1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CCN(CC)CCCN(C)C(=O)Nc1cc(Oc2ccc(N)cc2F)ncn1
Reaction time: 8 h
Yield: 68.4 %

Procedure:
3-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1-(3-diethylaminopropyl)-1-methylurea (54.0 mg) was dissolved in tetrahydrofuran (2 ml)-methanol (2 ml), and then 10% palladium carbon (27.2 mg) was added thereto, followed by replacing with hydrogen inside the system and stirring overnight. After replacing with nitrogen inside the system, the reaction mixture was filtered to remove the catalyst, which was washed with methanol. The filtrate was concentrated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:1, then ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to provide the titled compound (34.3 mg, 68.6%) as a pale yellow solid.
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5]1[N:6]=[C:7](C2CCNCC2)[O:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:2].Cl[CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:30]=1.[NH2:37][C@H:38](C(O)=O)[CH2:39][C:40]1C=C2C(C=CC=C2)=[CH:42][CH:41]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH:40]2[CH2:39][CH2:38][N:37]([CH2:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:35][CH3:36])=[C:29]([S:31]([NH2:34])(=[O:33])=[O:32])[CH:30]=3)[CH2:42][CH2:41]2)[CH2:7][O:8][C:9]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH3:2]
Reactant: N[C@@H](Cc1ccc2ccccc2c1)C(=O)O
Reactant: COc1ccc(CCCl)cc1S(N)(=O)=O
Reactant: CCOCc1nc(C2CCNCC2)oc1-c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CCOCC1=C(c2ccccc2)OCN1C1CCN(CCc2ccc(OC)c(S(N)(=O)=O)c2)CC1
Temperature: 100 °C

Procedure:
To 4-(4-ethoxymethyl-5-phenyl-oxazol-2-yl)-piperidine (0.150 g), prepared as in Intermediate 4, in dioxane is added 5-(2-chloro-ethyl)-2-methoxy-benzenesulfonamide (0.170 g), prepared as in Intermediate 1, Nal (0.012 g) and DIEA (0.274 ml). After heating at 100° C. for 18 hours, the reaction mixture is partitioned between EtOAc and dilute NaHCO3 solution. The organic phase is washed with saturated brine, dried (NaSO4) and concentrated. The residue is dissolved in 1:1 MeOH-CH2Cl2 and preadsorbed onto silica gel. Purification by flash chromatography on silica gel using a MeOH-EtOAc gradient (2-20%), affords the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2C(=C[CH:11]=1)N=[C:7]([CH2:12][N:13]1[C:21]([C:22]3[N:26]([CH3:27])[CH:25]=[C:24]([C:28]#[N:29])[CH:23]=3)=[C:20]3[C:15]([N:16]([CH2:32][CH:33]4[CH2:35][CH2:34]4)[C:17](=[O:31])[NH:18][C:19]3=S)=[N:14]1)[CH:6]=[CH:5]2.[CH:36]([NH:38][NH2:39])=O.[C:40](#[N:42])[CH3:41]>[Hg](Cl)Cl>[Cl:1][C:2]1[CH:11]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:42]=[CH:40][CH:41]=[C:7]2[CH2:12][N:13]1[C:21]([C:22]2[N:26]([CH3:27])[CH:25]=[C:24]([C:28]#[N:29])[CH:23]=2)=[C:20]2[C:19]3[N:18]([CH:36]=[N:38][N:39]=3)[C:17](=[O:31])[N:16]([CH2:32][CH:33]3[CH2:34][CH2:35]3)[C:15]2=[N:14]1
Reactant: CC#N
Reactant: Cn1cc(C#N)cc1-c1c2c(=S)[nH]c(=O)n(CC3CC3)c2nn1Cc1ccc2cc(Cl)ccc2n1
Reactant: NNC=O
Agent: Cl[Hg]Cl
Product: Cn1cc(C#N)cc1-c1c2c(nn1Cc1ccnc3ccc(Cl)cc13)n(CC1CC1)c(=O)n1cnnc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-[2-[(6-chloroquinolinyl)methyl]-7-(cyclopropylmethyl)-6-oxo-4-thioxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methyl- 1H-pyrrole-3-carbonitrile (0.14 g) in acetonitrile (5 mL) and formic hydrazide (80 mg) was added mercury(II) chloride (160 mg). After stirring overnight at rt, the reaction was warmed (Tb=70 C). After 5 h with heat, the reaction was filtered through a celite bed and concentrated. The residue was purified by flash chromatography using a FlashMaster™ yielding 44 mg, 1H NMR (300 MHz, CHLOROFORM-D) d ppm 0.57 (m, 4H) 1.48 (m, J=10.93 Hz, 1H) 3.45 (s, 3H) 4.15 (t, J=6.59 Hz, 2H) 5.86 (m, 2H) 6.68 (d, J=1.70 Hz, 1H) 6.83 (d, J=4.52 Hz, 1H) 7.40 (d, J=1.70 Hz, 1H) 7.72 (dd, J=8.95, 2.17 Hz, 1H) 7.88 (d, J=2.07 Hz, 1H) 8.13 (d, J=8.85 Hz, 1H) 8.84 (d, J=4.33 Hz, 1H) 8.93 (s, 1H);