Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1C=CC(S(O[CH2:12][C:13]2([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:14]2)(=O)=O)=CC=1.C1OCCOCCOCCOCCOCCOC1.[K].[C:43]1(=[O:53])[NH:47][C:46](=[O:48])[C:45]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:44]12>CN(C=O)C>[O:48]=[C:46]1[C:45]2[C:44](=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:43](=[O:53])[N:47]1[CH2:12][C:13]1([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:14][CH2:15]1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: Cc1ccc(S(=O)(=O)OCC2(NC(=O)OC(C)(C)C)CC2)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NC1(CN2C(=O)c3ccccc3C2=O)CC1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
To a solution of {1-[(tert-butoxycarbonyl)amino]cyclopropyl}methyl 4-methylbenzenesulfonate (100 g, 293 mmol) in DMF (1000 mL) was added 18-crown-6 (76.8 g, 291 mmol) and phthalimide potassium salt (80.5 g, 435 mmol). The reaction mixture was heated to 50° C. After 3 hours, the reaction mixture was cooled to ambient temperature, quenched with cold water (2000 mL), and filtered to afford crude solids. The solids were washed with petroleum ether (3×200 mL) and dried under reduced pressure to afford tert-butyl {1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]cyclopropyl}carbamate. The material was used without further purification.
Reaction SMILES: [F:1][CH:2]([F:5])[CH2:3]Cl.[Cl:6][C:7]1[N:12]=[CH:11][C:10]([CH2:13][NH2:14])=[CH:9][CH:8]=1.C(N(CC)CC)C.[Br-].[K+]>CN1CCCC1=O>[Cl:6][C:7]1[N:12]=[CH:11][C:10]([CH2:13][NH:14][CH2:3][CH:2]([F:5])[F:1])=[CH:9][CH:8]=1
Reactant: NCc1ccc(Cl)nc1
Reactant: FC(F)CCl
Agent: [Br-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Product: FC(F)CNCc1ccc(Cl)nc1
Temperature: 120 °C
Yield: 70.8 %

Procedure:
13.7 g (0.135 mol) of 2,2-difluoro-1-chloroethane, 10 g (0.067 mol) of 1-(6-chloropyridin-3-yl)methanamine and 8.2 g of triethylamine are initially charged with 31 g of N-methylpyrrolidone. In addition, 4 g (0.033 mol) of potassium bromide are added. The mixture is heated to 120° C. under autogenous pressure in an autoclave for 16 hours and then cooled again to 80° C. The N-methylpyrrolidone is distilled off at 80° C. under reduced pressure and the reaction mixture is poured onto 20 ml of 32% hydrochloric acid. The mixture is concentrated to dryness under reduced pressure and then adjusted to pH 12 with 10 ml of 45% NaOH. The mixture is extracted three times with 30 ml of toluene and the organic phases are distilled under reduced pressure. This gives 9.8 g of N-[(6-chloropyridin-3-yl)methyl]-2,2-difluoroethanamine (corresponds to 71% yield).
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=[O:8])=[O:4].O[N:14]1[C:18](=[O:19])[CH2:17][CH2:16][C:15]1=[O:20].C(N=C=NC(C)C)(C)C>C(OCC)(=O)C>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([O:9][N:14]1[C:18](=[O:19])[CH2:17][CH2:16][C:15]1=[O:20])=[O:8])=[O:4]
Reactant: COC(=O)N[C@H](C(=O)O)C(C)C
Reactant: O=C1CCC(=O)N1O
Agent: CC(C)N=C=NC(C)C
Solvent: CCOC(C)=O
Product: COC(=O)N[C@H](C(=O)ON1C(=O)CCC1=O)C(C)C
Temperature: 2.5 °C
Reaction time: 1 h
Yield: 76.1 %

Procedure:
To a mixture of (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (19.66 g, 112 mmol) and N-hydroxysuccinimide (13.29 g, 116 mmol) was added ethyl acetate (250 ml), and the mixture was cooled to 0-5° C. Diisopropylcarbodiimide (13.88 g, 110 mmol) was added and the reaction mixture was stirred at 0-5° C. for about 1 hour. The reaction mixture was warmed to room temperature. The solids (diisopropylurea by-product) were filtered and rinsed with ethyl acetate. The filtrate was concentrated in vacuo to an oil. Isopropyl alcohol (200 ml) was added to the oil and the mixture was heated to about 50° C. to obtain a homogeneous solution. Upon cooling, crystalline solids formed. The solids were filtered and washed with isopropyl alcohol (3×20 ml) and dried to give the title compound as a white solid (23.2 g, 77% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[OH:22].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31]1[CH:44]=[CH:43][CH:42]=[CH:41][C:32]=1[O:33][CH:34]([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:19])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[O:22][CH2:30][C:31]1[CH:44]=[CH:43][CH:42]=[CH:41][C:32]=1[O:33][CH:34]([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(O)c(Cl)cc2F)c1=O
Reactant: CCOC(=O)C(C)Oc1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)Oc1ccccc1COc1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)c(F)cc1Cl
Yield: 72.5 %

Procedure:
Into 10 ml of N,N-dimethylformamide was dissolved 0.3 g of 2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidine-1-yl]phenol; 0.159 g of anhydrous potassium carbonate was added; 0.305 g of ethyl 2-[2-(bromomethyl)phenoxy]propionate was added at room temperature under stirring and the mixture was stirred overnight at room temperature. The reaction solution was poured into a mixture of ice and a saturated aqueous ammonium chloride solution and the mixture was extracted twice with ethyl acetate. The organic layers were combined and washed once with a saturated aqueous ammonium chloride solution and once with saturated aqueous sodium chloride solution in turn, dried over magnesium sulfate and then concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give 0.35 g of ethyl 2-[2-({2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidine-1-yl]phenoxy}methyl)phenoxy]propionate [Compound 3-2].
Reaction SMILES: C(N(CC)[CH2:4][C:5]#[C:6][C@@H:7]([O:13][C:14](=[O:16])[CH3:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])C.N#C[Br:21]>CCOCC>[Br:21][CH2:4][C:5]#[C:6][C@@H:7]([O:13][C:14](=[O:16])[CH3:15])[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCC[C@@H](C#CCN(CC)CC)OC(C)=O
Reactant: N#CBr
Solvent: CCOCC
Product: CCCCC[C@@H](C#CCBr)OC(C)=O
Reaction time: 18 h

Procedure:
A solution of 1-diethylamino-4(S)-acetoxy-2-nonyne (50.6 g., 0.20 mole) and cyanogen bromide (21.2 g., 0.20 mole) in ether (250 ml.) is allowed to stand at 25°-27° C. for 18 hours. The ether solution is washed with 5% hydrochloric acid solution, water, and brine and dried over sodium sulfate. The ether is evaporated and the residual oil distilled. After a forerun of diethylcyanamide, there is collected 34.1 g. (65%) of 1-bromo-4(S)-acetoxy-2-nonyne, b.p. 97°-105°/0.2 mm.; [α]D26 -83° (C 3.7, CHCl3).
Reaction SMILES: [CH2:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])[CH2:2][CH2:3][CH3:4].[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOC(C)=O>CN(C=O)C>[CH2:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([NH:34][C:8]2[C:9](=[O:10])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[S:6](=[O:19])(=[O:18])[C:7]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:32][CH:33]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: Nc1ccc(OCc2ccccc2)cc1
Reactant: CCCCN1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCCN1C(=O)C(Nc2ccc(OCc3ccccc3)cc2)=C(c2ccccc2)S1(=O)=O
Temperature: 140 °C
Yield: 77.9 %

Procedure:
A mixture of 2-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.600 g, 2.001 mmol), [4-(benzyloxy)phenyl]amine (1.415 g, 6.004 mmol) and TEA (0.840 ml, 6.004 mmol) in DMF (5 ml) was heated in a microwave reactor at 140° C. for 25 mins. EtOAc was added to the mixture, and it was washed with brine, evaporated and the residue was purified by flash chromatography using a 5:1 EtOAc/petroleum ether 40-60° C. mixture as eluent to give the title compound (0.721 g, 78%). 1H NMR (500 MHz CDCl3); δ 7.42-7.33 (m, 4H), 7.22-7.17 (m, 1H), 7.15-7.09 (m, 5H), 6.65 (d, 2H), 6.61 (d, 2H), 4.96 (s, 2H), 3.79 (t, 2H), 1.92-1.84 (m, 2H), 1.54-1.44 (m, 2H), 1.01 (t, 3H); Mass Spectrum M+H+ 463.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([CH2:10][NH2:11])[CH2:9][CH2:8][CH2:7]1.[CH:12]1[N:17]=[C:16](Cl)[C:15]2[N:19]=[CH:20][N:21]([C@@H:22]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@H:23]3[OH:30])[C:14]=2[N:13]=1>>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([CH2:10][NH:11][C:16]2[C:15]3[N:19]=[CH:20][N:21]([C:14]=3[N:13]=[CH:12][N:17]=2)[C@@H:22]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@H:23]2[OH:30])[CH2:9][CH2:8][CH2:7]1
Reactant: NCC1(c2cccs2)CCC1
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Product: OC[C@H]1O[C@@H](n2cnc3c(NCC4(c5cccs5)CCC4)ncnc32)[C@H](O)[C@@H]1O
Yield: 76.2 %

Procedure:
The above amine (1.67 g, 10 mmol) is reacted with 6-chloropurine riboside (2.87 g, 10 mmol) as described in Example 1 and 7 is purified by column chromatography to give N6-(1-(thien-2-ylcyclobutyl)methyl)adenosine (3.18 g, 76%) as a colorless glass m.p. 84°-92° C. Found: C, 54.88; H, 5.69; N, 16.77; S, 7.55%. C19H23N5O4S calculated requires: C, 54.68; H, 5.52; N, 16.79; S, 7.67%.
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:11]3[C:24]([C:26]4[CH:39]=[CH:38][C:29]([O:30][CH2:31][CH2:32][N:33]5[CH2:37][CH2:36][CH2:35][CH2:34]5)=[CH:28][CH:27]=4)([CH3:25])[O:23][C:22]4[CH:21]=[C:20]([O:40][Si](C(C)(C)C)(C)C)[CH:19]=[CH:18][C:17]=4[C:12]=3[CH2:13][O:14][C:15]=2[CH:16]=1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[NH4+].[Cl-].C(OCC)(=O)C>C1COCC1>[CH3:25][C:24]1([C:26]2[CH:39]=[CH:38][C:29]([O:30][CH2:31][CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:28][CH:27]=2)[C:11]2[C:10]3[CH:9]=[CH:8][C:7]([OH:6])=[CH:16][C:15]=3[O:14][CH2:13][C:12]=2[C:17]2[CH:18]=[CH:19][C:20]([OH:40])=[CH:21][C:22]=2[O:23]1
Reactant: CC1(c2ccc(OCCN3CCCC3)cc2)Oc2cc(O[Si](C)(C)C(C)(C)C)ccc2C2=C1c1ccc(O[Si](C)(C)C(C)(C)C)cc1OC2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC1(c2ccc(OCCN3CCCC3)cc2)Oc2cc(O)ccc2C2=C1c1ccc(O)cc1OC2
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a solution of 1-(2-{4-[2,8-bis-(tert-butyl-dimethyl-silyloxy)-5-methyl-5,11-dihydro-chromeno[4,3-c]chromen-5-yl]-phenoxy}-ethyl)-pyrrolidine (84.5 mg, 0.12 mmol) in THF (7 mL) was added tetrabutylammonium fluoride (1M in THF, 241.4 μL, 0.24 mmol). The mixture was stirred at room temperature for 40 min. Saturated NH4Cl was added followed by addition of ethyl acetate. The resulting layers were separated, the organic layer was washed with brine, and dried over MgSO4. The solvent was evaporated and the residue dried under vacuum for 2 h at room temperature to yield the title compound which was carried on to the next step without further purification.
Reaction SMILES: [CH2:1]([O:3][CH2:4][O:5][C:6]1[C:13]([CH:14]([CH3:16])[CH3:15])=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8]O)[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C(=O)N([Br:43])C(=O)C1>ClCCl>[CH2:1]([O:3][CH2:4][O:5][C:6]1[C:13]([CH:14]([CH3:16])[CH3:15])=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8][Br:43])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOCOc1c(CO)cccc1C(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOCOc1c(CBr)cccc1C(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 87 %

Procedure:
To a stirred solution of 2-(ethoxymethoxy)-3-isopropylbenzyl alcohol (Ic) (2.04 g, 9.09 mmol) and PPh3 (3.82 g, 14.6 mmol) in dichloromethane (45 mL) was added NBS (2.59 g, 14.6 mmol) in portions at 0° C. The reaction was stirred at 0° C. for 30 min. The reaction was quenched by the addition of water (50 mL). The product was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were washed with water (50 mL), and brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification of the crude product by flash column chromatography (hexanes/ethyl acetate=10:1, v/v) provided the title compound (2.27 g, 86%) as a colorless oil.
Reaction SMILES: [OH-].[K+].CO.[Cl:5][C:6]1[C:7]([O:17][CH3:18])=[C:8]([C:13]([Cl:16])=[CH:14][CH:15]=1)[C:9]([NH:11][OH:12])=[O:10].[CH3:19][O:20][C:21](=[O:24])[CH2:22]Br>C(Cl)Cl>[Cl:5][C:6]1[C:7]([O:17][CH3:18])=[C:8]([C:13]([Cl:16])=[CH:14][CH:15]=1)[C:9]([NH:11][O:12][CH2:22][C:21]([O:20][CH3:19])=[O:24])=[O:10]
Reactant: COC(=O)CBr
Reactant: COc1c(Cl)ccc(Cl)c1C(=O)NO
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)CONC(=O)c1c(Cl)ccc(Cl)c1OC

Procedure:
To a solution of 2.15 g. of potassium hydroxide in 50 ml. of methanol was added 7.55 g. of 3,6-dichloro-2-methoxy benzohydroxamic acid followed by stirring until dissolution was obtained. To this solution was added dropwise 3.03 ml. methylbromoacetate in 25 ml. of methanol. The reaction mixture was refluxed for 2 hours and allowed to stir overnight at ambient temperature. To the reaction mixture was added 0.36 g. of additional potassium hydroxide and the mixture heated to reflux for 4 hours, then cooled, filtered, and the filtrate concentrated in vacuo to give a crude semi-solid product. This crude product was taken up in methylene chloride and washed with water, 5% aqueous NaHCO3, brine, then dried over MgSO4, filtered and evaporated in vacuo to give a viscuous oil. The oil crystallized from an ethyl acetate-hexane mixture to the title product as a white solid, m.p. 102°-105° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[C:3]=1I.[CH3:24][Si:25]([C:28]#[CH:29])([CH3:27])[CH3:26]>C(N(CC)CC)C.CN(C)C=O.O.CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[C:3]=1[C:29]#[C:28][Si:25]([CH3:27])([CH3:26])[CH3:24]
Reactant: Nc1c(I)c(C(F)(F)F)nn1-c1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: O
Product: C[Si](C)(C)C#Cc1c(C(F)(F)F)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Reaction time: 8 h

Procedure:
To a stirred solution of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodo-3-trifluoromethylpyrazole (28 g) in triethylamine (120 ml) and dimethylformamide (24 ml) at room temperature was added trimethylsilylacetylene (12 ml), cuprous iodide (0.6 g) and bis(triphenylphosphine)palladium(II) chloride (1.2 g). The mixture was heated under reflux for 4 hours and then left at room temperature overnight. The reaction mixture was diluted with water (500 ml) and ether (500 ml) and filtered. The filtrate's organic layer was separated, dried (MgSO4) and evaporated to give the crude product as an oil which was purified by column chromatography on silica gel eluted with dichloromethane:hexane (1:1). Combination and evaporation of appropriate fractions, followed by recrystallisation from hexane, provided the title compound as a buff solid, m.p. 120-123° C.
Reaction SMILES: [NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][CH:15]2[CH2:17][CH2:16]2)=[CH:9][CH:8]=1)[C:3]([CH3:6])([OH:5])[CH3:4].[Cl:18][C:19]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21](Cl)=[O:22].C(=O)(O)[O-].[Na+]>ClCCl>[Cl:18][C:19]1[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([NH:1][CH:2]([C:7]1[CH:8]=[CH:9][C:10]([S:13][CH2:14][CH:15]2[CH2:16][CH2:17]2)=[CH:11][CH:12]=1)[C:3]([OH:5])([CH3:6])[CH3:4])=[O:22]
Reactant: CC(C)(O)C(N)c1ccc(SCC2CC2)cc1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(O)C(NC(=O)c1cccc(C(F)(F)F)c1Cl)c1ccc(SCC2CC2)cc1
Reaction time: 16 h
Yield: 69.2 %

Procedure:
1-Amino-1-(4-[(cyclopropylmethyl)thio]phenyl)-2-methylpropan-2-ol (150 mg) and 2-chloro-3-(trifluoromethyl)benzoyl chloride (300 mg) in dichloromethane (2 mL) were treated with saturated sodium bicarbonate solution (2 mL) and stirred vigorously for 16 h. The organic phase was dried (MgSO4), concentrated and the residue purified by chromatography on silica (eluting with iso-hexane on a gradient of ethyl acetate) to give the title compound as a foam (189 mg). 1H NMR (500 MHz, CDCl3): δ 7.76 (1H, d, J=7.8 Hz), 7.64 (1H, d, J=7.6 Hz), 7.41 (1H, t, J=7.8 Hz), 7.34 (2H, d, J=8.2 Hz), 7.28 (2H, d, J=8.2 Hz), 7.05 (1H, br d, J=8.5 Hz), 4.98 (1H, d, J=8.5 Hz), 2.87 (2H, d, J=7.0 Hz), 1.45 (3H, s), 1.10 (3H, s), 1.09-1.04 (1H, m), 0.59 (2H, q, J=5:1 Hz), 0.26 (2H, q, J=5.1 Hz); m/z 457, 459.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10].CN(C)/C=C(\C1C=CC=CC=1C)/[C:17](OC)=[O:18]>>[OH:18]/[CH:17]=[C:8](/[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])\[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)/C(=C/N(C)C)c1ccccc1C
Reactant: COC(=O)Cc1ccccc1C
Product: COC(=O)/C(=C\O)c1ccccc1C

Procedure:
In a similar to manner to Example 1, methyl (2-methylphenyl)acetate was converted to methyl (E)-3-dimethylamino-2-(2-methylphenyl)prop-2-enoate, bp 125°-7°/0.1 mm, which on cooling gave a crystalline solid, mp 48°-49°. This was then hydrolysed in a similar manner to Example 1, but using Amberlite IR 120 resin instead of Amberlyst 15, to give methyl (Z)-3-hydroxy-2-(2-methylphenyl)prop-2-enoate, obtained as an oil and which had the following nmr spectral data: 2.15(3H,s,Me), 3.67(3H,s,CO2Me), 7.0-7.4(5H,m,ArH and =CH), 11.8(1H,d,OH)
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.[CH2:11]([NH2:14])[C:12]#[CH:13].O>C(#N)C>[Cl:8][C:6]1[N:5]=[C:4]([S:9][CH3:10])[N:3]=[C:2]([NH:14][CH2:11][C:12]#[CH:13])[CH:7]=1
Reactant: C#CCN
Reactant: CSc1nc(Cl)cc(Cl)n1
Solvent: O
Solvent: CC#N
Product: C#CCNc1cc(Cl)nc(SC)n1
Temperature: 60 °C
Reaction time: 12 h
Yield: 99.4 %

Procedure:
A mixture of 1.00 g (5.13 mmol) of 4,6-dichloro-2-(methylthio)pyrimidine and 0.7 ml (10.3 mmol) of propargylamine in 10 ml of acetonitrile was stirred for 12 hours at 60° C. The reaction solution was poured onto cold water. Then, the formed precipitate was filtered, washed several times with cold water and dried. 1.09 g of a light yellow solid were obtained.
Reaction SMILES: C([NH:9][C:10]([NH:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[C:20]2[N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)=[CH:15][CH:14]=1)=[S:11])(=O)C1C=CC=CC=1.[OH-].[Na+]>C(O)C.O>[NH2:9][C:10]([NH:12][C:13]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[C:20]2[N:23]2[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]2)=[CH:15][CH:14]=1)=[S:11]
Reactant: CN1CCN(c2cccc3ccc(NC(=S)NC(=O)c4ccccc4)cc23)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CN1CCN(c2cccc3ccc(NC(N)=S)cc23)CC1
Yield: 48.1 %

Procedure:
The title product of example 22 (1.09 g, 2.7 mmol) was slurried in ethanol (10 mL) and a solution of 1.4 g NaOH in water (14 mL) was added. The mixture was refluxed 3 hours; then the ethanol was removed with a stream of nitrogen. The aqueous residue was extracted with methylene chloride. The organic phase was washed with brine, dried over calcium sulfate, and concentrated to leave 0.39 g (48%) of the title product. A sample was recrystallized from acetonitrile for analysis: mp 194°-195° C. Analysis calculated for C16H20N4S·CH3CN·0.5 H2O; C, 62.96; H, 6.67; N, 19.32. Found: C, 62.86; H, 6.71; N, 19.69.
Reaction SMILES: O=[CH:2][C@@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].[NH:11]1[N:18]=[CH:17][C:15](=[O:16])[NH:14][C:12]1=[O:13].C[Si](N[Si](C)(C)C)(C)C.C[Si](C)(C)Cl.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+]>C(#N)C>[C@@H:2]1([N:11]2[N:18]=[CH:17][C:15](=[O:16])[NH:14][C:12]2=[O:13])[O:8][C@H:7]([CH2:9][OH:10])[C@@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: O=c1cn[nH]c(=O)[nH]1
Reactant: O=C[C@H](O)[C@H](O)[C@H](O)CO
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CC#N
Product: O=c1cnn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Temperature: 24 °C
Reaction time: 7 h

Procedure:
A mixture of 15 mmol (2.25 g) of dry D-ribose and 5 mmol (0.565 g) of 6-azauracil is silylated for 2 hours with 15 ml of HMDS and 0.1 ml of trimethylchlorosilane in 30 ml of boiling absolute acetonitrile. After concentrating by evaporation in vacuo, the residue is kept at 80°/1 mm for 2 hours and then dissolved in 40 ml of boiling absolute acetonitrile; 5.5 mmol (0.99 ml) of trimethylsilyl triflate in 10 ml of acetonitrile are then added at 80° C. and within the space of 45 minutes. After the mixture had been kept at 80° C. for 7 hours, 20 ml of a saturated, aqueous solution of NaHCO3 are added at 24° C. and the resulting dark-colored mixture is stirred at 24° C. for 4 hours. Following concentration, the dark-colored residue is extracted with 3×100 ml of boiling methanol and the extracts are concentrated. The residue is dissolved in approx. 10 ml of water and absorbed to approx. 20 g of SiO2, which is loaded onto a column of 200 g of SiO2 (previously treated for 4 hours with 25% NH3 (9:1) until a clear filtrate is obtained). Elution with ethanol/25% NH3 (9:1) first leads to 675 ml of eluate containing quantities of sugar and also traces of 6-azauracil. The following 650 ml yield 0.84 g (68.3%) of slightly colored crude 6-azauridine. The latter is treated in water with active charcoal and then crystallized from ethanol, yielding pure crystalline 6-azauridine (melting point 159°-161° C.).
Reaction SMILES: [OH:1][C:2]1[C:7]2[S:8][C:9]([C:11]([F:14])([F:13])[F:12])=[CH:10][C:6]=2[S:5](=[O:16])(=[O:15])[NH:4][C:3]=1[C:17]([O:19][CH3:20])=[O:18].[H-].[Na+].[CH3:23]I>CN(C)C=O>[OH:1][C:2]1[C:7]2[S:8][C:9]([C:11]([F:14])([F:13])[F:12])=[CH:10][C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:23])[C:3]=1[C:17]([O:19][CH3:20])=[O:18]
Reactant: CI
Reactant: COC(=O)C1=C(O)c2sc(C(F)(F)F)cc2S(=O)(=O)N1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1=C(O)c2sc(C(F)(F)F)cc2S(=O)(=O)N1C
Reaction time: 1.5 h

Procedure:
A solution, cooled to -2°, of 5.65 g of 4-hydroxy-3-methoxycarbonyl-6-trifluoromethyl-2H-thieno[2,3-e]-1,2-thiazine 1,1-dioxide in 62 ml of absolute dimethylformamide is treated portionwise under a strong nitrogen stream with 0.87 g of sodium hydride (washed with benzene), the mixture is stirred at 5° for an additional 1.5 hours, then 1.49 ml of methyl iodide are added thereto in one portion, the temperature rising to about 15°. The mixture is stirred at room temperature for an additional 1.5 hours and then evaporated in vacuo. The residue is partitioned between 2N hydrochloric acid and methylene chloride, the aqueous phase is extracted three times with methylene chloride, the combined organic extracts are dried over sodium sulfate and evaporated. The brown crystalline residue is digested with about 50 ml of ethanol, the almost colorless crystals are removed by filtration under suction and washed with methanol. After recrystallization from ethanol, there is obtained 4-hydroxy-3-methoxycarbonyl-2-methyl-6-trifluoromethyl-2H-thieno[ 2,3-e]-1,2-thiazine 1,1-dioxide of melting point 178°-180°.
Reaction SMILES: [OH-].[Na+].[NH2:3][C:4]1[C:5]2[C:10]([N:11]=[C:12]3[C:17]=1[C:16](=[O:18])[CH2:15][CH2:14][CH2:13]3)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH3:19]I>ClCCl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:19][NH:3][C:4]1[C:5]2[C:10]([N:11]=[C:12]3[C:17]=1[C:16](=[O:18])[CH2:15][CH2:14][CH2:13]3)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: CI
Reactant: Nc1c2c(nc3ccccc13)CCCC2=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CNc1c2c(nc3ccccc13)CCCC2=O
Reaction time: 0.5 h
Yield: 70 %

Procedure:
In 150 ml of dichloromethane and 100 ml of 50% NaOH were added 5.00 g of 9-amino-3,4-dihydroacridin-1(2H)-one and 0.80 g (0.1 eq) of tetrabutylammonium hydrogensulfate. The biphasic mixture was mechanically stirred for 0.5 hour and thereafter 4.4 ml (3 eq) of CH3I was added. The reaction mixture was stirred overnight. Analysis of the reaction mixture indicated that the starting material was completely consumed. The reaction mixture was poured into cold water and the dichloromethane layer was evaporated, dried over MgSO4 and filtered through alumina and the solvent was evaporated to afford a solid. The solid was recrystallized from dichloromethane/hexanes to yield 3.73 g (70%) of crystalline product after drying, melting point 116°-117° C.