Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:11](=[S:13])[NH2:12])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[CH2:15][C:16](=O)[CH3:17].C(=O)([O-])[O-].[Ca+2]>C(O)C>[CH3:17][C:16]1[N:12]=[C:11]([CH:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:5])[CH3:6])[CH3:10])[S:13][CH:15]=1
Reactant: CC(=O)CCl
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(N)=S
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CCO
Product: Cc1csc(C(C)NC(=O)OC(C)(C)C)n1
Temperature: 25 °C
Yield: 48 %

Procedure:
A mixture of BOC-alanine-thioamide (1.39 g, 6.81 mmoles), chloroacetone (0.65 mL, 8.18 mmoles) and calcium carbonate (1.0 g, 10.22 mmoles) were refluxed in ethanol (25 mL) for 4 h. The reaction was cooled to room temperature and quenched with 2OmL of saturated aq. NaHCO3 solution. Ethanol was evaporated under reduced pressure and extracted with ethyl acetate (2×30 mL). The combined organic layers was dried over Na2SO4 and concentrated. The residue was chromatographed on silica gel (20% ethyl acetate/80% hexane) to yield 48% of the desired product.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[C:6]([O:20]S(C)(=O)=O)=[C:7]([C:12]([N+:17]([O-:19])=[O:18])=[CH:13][C:14]=1[O:15][CH3:16])[C:8]([O:10][CH3:11])=[O:9].Cl>O1CCOCC1>[CH3:3][O:4][C:5]1[C:6]([OH:20])=[C:7]([C:12]([N+:17]([O-:19])=[O:18])=[CH:13][C:14]=1[O:15][CH3:16])[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)c1c([N+](=O)[O-])cc(OC)c(OC)c1OS(C)(=O)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COC(=O)c1c([N+](=O)[O-])cc(OC)c(OC)c1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 92 %

Procedure:
4N aqueous sodium hydroxide solution (17 ml) was added to an ice cooled suspension of methyl 3,4-dimethoxy-2-methanesulfonyloxy-6-nitrobenzoate (1.74 g, 0.0052 mol) in dioxane (9 ml) and the resulting orange solution stirred for 1 hour. The reaction mixture was acidified with 2N aqueous hydrochloric acid and extracted with dichloromethane (2×50 ml). The combined organic extracts were dried (MgSO4), filtered and evaporated under reduced pressure to give the subtitle compound as a white solid (1.23 g, 92%). MS m/z 275 (MNH4)+. 1H-NMR (CDCl3): δ=3.92 (9H, m), 6.86 (1H, s), 9.66 (1H, s).
Reaction SMILES: Cl.[CH2:2]([C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH2:14])=[NH:13])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N:18](=[C:20]([C:26]#[N:27])[C:21](OCC)=[O:22])[OH:19].[Na].O>C(O)C.C(O)(=O)C>[NH2:27][C:26]1[N:13]=[C:12]([C:11]2[CH:15]=[CH:16][CH:17]=[C:9]([CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:10]=2)[NH:14][C:21](=[O:22])[C:20]=1[N:18]=[O:19]
Reactant: CCOC(=O)C(C#N)=NO
Reactant: N=C(N)c1cccc(Cc2ccccc2)c1
Agent: Cl
Agent: [Na]
Solvent: CCO
Solvent: O
Solvent: CC(=O)O
Product: Nc1nc(-c2cccc(Cc3ccccc3)c2)[nH]c(=O)c1N=O
Reaction time: 5 h
Yield: 78.3 %

Procedure:
3-Benzylbenzamidine hydrochloride (12.3 g.) and ethyl α-oximinocyanoacetate (7.1 g.) were added to a solution of sodium (4.6 g.) in anhydrous ethanol (60 ml.). The mixture was heated under reflux with stirring for 5 hours and then allowed to stand at room temperature overnight. The mixture was poured into water (600 ml.), acidified to pH 5 with glacial acetic acid and chilled for 3 hours. The solid obtained was filtered off and washed with water to give 4-amino-2-(3-benzylphenyl)-5-nitrosopyrimid-6-one (11.95 g.), m.p. 145°-148° C. (with decomposition).
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([S:11]([NH2:14])(=[O:13])=[O:12])[C:4]=2[O:3]1.C[Al](C)C.C[O:21][C:22](=O)[NH:23][C:24]1[N:29]=[C:28]([O:30][CH3:31])[CH:27]=[C:26]([CH3:32])[N:25]=1.O>C(Cl)Cl.Cl.C(O)(=O)C>[CH3:31][O:30][C:28]1[CH:27]=[C:26]([CH3:32])[N:25]=[C:24]([NH:23][C:22]([NH:14][S:11]([C:10]2[C:4]3[O:3][C:2]([CH3:15])([CH3:1])[O:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)(=[O:13])=[O:12])=[O:21])[N:29]=1
Reactant: CC1(C)Oc2cccc(S(N)(=O)=O)c2O1
Reactant: COC(=O)Nc1nc(C)cc(OC)n1
Agent: C[Al](C)C
Agent: Cl
Solvent: ClCCl
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(C)nc(NC(=O)NS(=O)(=O)c2cccc3c2OC(C)(C)O3)n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 26.6 %

Procedure:
To a solution of 0.55 g 2,2-dimethyl-1,3-benzodioxole-4-sulfonamide, prepared in Example 1, in 30 ml methylene chloride at ambient temperature under nitrogen was added 1.2 ml of trimethylaluminum (2M in toluene). After stirring 15 minutes at ambient temperature, 0.47 g of methyl[4-methoxy-6-methylpyrimidin-2-yl]carbamate, prepared according to the procedure of Example 3, was added and the reaction mixture was heated at reflux 16 hours. The reaction mixture was cooled to ambient temperature and 75 ml H2O, 10 ml glacial acetic acid, and 10 drops hydrochloric acid were sequentially added. The organic phase was separated, dried, and the solvent removed under reduced pressure to give an oil. Crystallization of the oil from a mixture of butyl chloride, hexane and ether gave 0.25 g white solid, m.p. 180°-183° C. The infrared spectrum showed a carbonyl absorption at 1705 cm-1 indicative of the title compound.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([OH:10])=[O:9].[Br:12]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:12][CH2:11][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([OH:10])=[O:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccccc1CC(=O)O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(O)Cc1ccccc1CBr

Procedure:
o-Tolylacetic acid (40 g, 266 mmol), N-bromosuccinimide (52.147 g, 293 mmol) and benzoyl peroxide (0.174 g, catalytic) are dissolved in 300 ml of CCl4. The suspension is brought to and maintained at reflux for 12 hours. After cooling, the solid particles are separated out by filtration. and the CCl4 is evaporated off under vacuum, which allows a white solid to appear. This is sufficiently pure without recrystallization.
Reaction SMILES: [C:1]([NH:5][C:6]1[C:7]([NH2:16])=[CH:8][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[CH3:19][N:20]([CH3:23])C=O>>[C:1]([N:5]1[C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:14])([F:15])[F:13])=[CH:8][C:7]=2[N:16]=[C:4]1[C:1]1[CH:3]=[CH:23][N:20]=[CH:19][CH:2]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)Nc1ccc(C(F)(F)F)cc1N
Reactant: CN(C)C=O
Agent: [Na+]
Agent: [OH-]
Product: CC(C)(C)n1c(-c2ccncc2)nc2cc(C(F)(F)F)ccc21
Temperature: 150 °C
Reaction time: 0.17 h

Procedure:
A mixture of 0.47 g of N1-tert-butyl-4-trifluoromethylbenzene-1,2-diamine, 0.51 g of isonicotinealdehyde-bisulfite adduct and 5 ml of N,N-dimethylformamide was stirred for 10 minutes at 150° C. The reaction mixture was ice-cooled, then, a 10% sodium hydroxide aqueous solution was poured, and the mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over sodium sulfate, then, concentrated under reduced pressure to obtain a solid residue. The residue was washed with hexane, to obtain 0.26 g of 1-tert-butyl-2-(pyridin-4-yl)-5-trifluoromethyl-1H-benzimidazole (hereinafter, referred to as present active compound 220).
Reaction SMILES: [OH:1]/[N:2]=[C:3](\[NH2:17])/[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:6][CH:5]=1.[CH2:18]([O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=O)=[CH:28][CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>N1C=CC=CC=1>[CH2:18]([O:25][C:26]1[CH:27]=[CH:28][C:29]([C:30]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[CH:6][C:7]([O:10][C:11]4[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=4)=[CH:8][CH:9]=3)[N:17]=2)=[CH:33][CH:34]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: N/C(=N\O)c1ccc(Oc2ccncc2)cc1
Reactant: O=C(Cl)c1ccc(OCc2ccccc2)cc1
Solvent: c1ccncc1
Product: c1ccc(COc2ccc(-c3nc(-c4ccc(Oc5ccncc5)cc4)no3)cc2)cc1
Temperature: 25 °C
Yield: 27 %

Procedure:
(Z)-N′-Hydroxy-4-(pyridin-4-yloxy)benzamidine (20 mg, 88 μmol) and 4-benzyloxybenzoyl chloride (28 mg, 114 μmol) were suspended in pyridine (5.0 mL). The solution was refluxed for 21 hours, cooled to room temperature and the solvent was removed under reduced pressure. The solid residue was purified by silica gel column chromatography to give the product as a white solid (10 mg, 27%). 1H NMR (500 MHz, CDCL3) δ(ppm): 5.18 (2H, s), 6.55 (2H, d, J=7.8 Hz), 7.14 (2H, d, J=9.0 Hz), 7.36-7.47 (5H, m), 7.50 (2H, d, J=8.6 Hz), 7.68 (2H, d, J=7.8 Hz), 8.17 (2H, d, J=8.8 Hz), 8.33 (2H, d, J=8.6 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 70.5 (CH2), 115.7 (CH), 116.9, 119.5 (CH), 123.1 (CH), 127.6, 127.7 (CH), 128.6 (CH), 129.0 (CH), 129.7 (CH), 130.4 (CH), 136.1, 138.8 (CH), 145.1, 162.7, 167.7, 176.2, 179.3. MS (FAB+): 422 (MH+). HRMS for C26H19N3O3 (MH+): calculated: 422.1505; found 422.1494.
Reaction SMILES: [Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH:30]=[CH:31][NH:32]3)[CH:23]=1.[OH2:37]>CC(O)(C)C.C(O)C.C(O)(=O)C.[Zn]>[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:29]=2[CH2:30][C:31](=[O:37])[NH:32]3)[CH:23]=1
Reactant: c1cncc(-c2cccc3[nH]ccc23)c1
Reactant: O
Agent: [Br-]
Agent: [Zn]
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Solvent: CC(C)(C)O
Solvent: CCO
Product: O=C1Cc2c(cccc2-c2cccnc2)N1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
Pyridinium tribromide (90% (Aldrich), 5.5 g, 15.3 mmol) was added portion-wise over 10 minutes to a suspension of 4-pyridin-3-yl-1H-indole (1 g, 5.1 mmol) in 2-methyl-2-propanol (30 mL), ethanol (20 mL) and acetic acid (10 mL). The mixture was stirred at room temperature for 2 hours and then acetic acid (50 mL) was added. After stirring for an additional hour, water (0.5 mL) and zinc dust (3.3 g, 51 mmol) were added and stirring was continued for another hour. Residual zinc dust was filtered and washed with methanol. The filtrate was concentrated and the syrupy residue was stirred in water (100 mL) overnight. The solid which formed was filtered, washed with water to remove zinc and pyridine salts and dried under high vacuum to give 1.1 g (100%) of 4-pyridin-3-yl-1,3-dihydro-indol-2-one.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[C:5]([NH2:10])=[N:6][O:7][C:8]=1[CH3:9].[CH2:11]([C:13]1[S:21][C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[C:14]=1[S:22](Cl)(=[O:24])=[O:23])[CH3:12]>C1COCC1>[Cl:3][C:4]1[C:5]([NH:10][S:22]([C:14]2[C:15]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[S:21][C:13]=2[CH2:11][CH3:12])(=[O:24])=[O:23])=[N:6][O:7][C:8]=1[CH3:9]
Reactant: CCc1sc2ncccc2c1S(=O)(=O)Cl
Reactant: Cc1onc(N)c1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1sc2ncccc2c1S(=O)(=O)Nc1noc(C)c1Cl
Yield: 35.2 %

Procedure:
N-(4-chloro-5-methyl-3-isoxazolyl)-2-ethylthieno[2,3-bjpyridine-3-sulfonamide was prepared according to Example 1 (C), using NaH (44 mg, 1.9 mmoles), THF (5 ml), 4-chloro-5-methyl-3-aminoisoxazole (82 mg, 0.62 mmoles) and 2-ethylthieno[2,3-b]pyridine-3-sulfonyl chloride (0.19 g, 0.71 mmoles). Flash chromatography (50% EtOAc/hexanes) followed by recrystallization from EtOAc/hexanes provided 78 mg (35%) of the title compound as a light yellow solid, m.p. 172°-174° C.
Reaction SMILES: [CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)=[O:2].[N+:11]([CH:13](S(C1C=CC(C)=CC=1)(=O)=O)[CH3:14])#[C-:12].C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:14][C:13]1[N:11]=[CH:12][O:2][C:1]=1[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1
Reactant: [C-]#[N+]C(C)S(=O)(=O)c1ccc(C)cc1
Reactant: N#Cc1ccc(C=O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cc1ncoc1-c1ccc(C#N)cc1
Yield: 75 %

Procedure:
4-Formylbenzonitrile (1.61 g, 12.3 mmol), 1-(1-isocyanoethylsulfonyl)-4-methylbenzene (2.58 g, 12.3 mmol), and potassium carbonate (3.39 g, 24.5 mmol) in methanol (60 mL) was heated to reflux overnight. The reaction mixture was cooled and the volatiles evaporated. The residue was partitioned between water and ethyl acetate. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and evaporated. The solid was chromatographed on silica gel, eluting with 10% to 50% ethyl acetate:hexanes to afford 1.70 g (75% yield) of the title compound as a white solid.
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24]OS(C3C=CC(C)=CC=3)(=O)=O)[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1>>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: C1CCNC1
Reactant: Cc1ccc(S(=O)(=O)OCc2noc([C@H](CCCC3CCCCC3)CC(=O)OC(C)(C)C)n2)cc1
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CN2CCCC2)no1

Procedure:
Method as for preparation 5 using tert-butyl(3R)-6-cyclohexyl-3-[3-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1,2,4-oxadiazol-5-yl]hexanoate (preparation 177) (126 mg, 0.25 mmol) and pyrrolidine (1001, 1.20 mmol) as starting materials.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[C:5]([CH3:16])=[N:6][N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8]=1[NH2:9].[NH3:17]>O.C(O)C>[NH2:9][C:8]1[N:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:6]=[C:5]([CH3:16])[C:4]=1[N:3]=[C:4]1[C:8](=[NH:7])[NH:9][N:17]=[C:5]1[CH3:16]
Reactant: Cc1nn(-c2ccccc2)c(N)c1N
Reactant: N
Agent: Cl
Solvent: CCO
Solvent: O
Product: CC1=NNC(=N)C1=Nc1c(C)nn(-c2ccccc2)c1N
Reaction time: 17 h

Procedure:
2.6 g 4,5-diamino-3-methyl-1-phenyl-1H-pyrazole dihydrochloride were dissolved in a mixture of 30 ml water and 30 ml ethanol. The pH of the resulting solution was then adjusted to 9 with concentrated ammonia. Subsequently the reaction mixture was stirred for 17 hours with a gasifying stirrer. The precipitated dye compounds was separated by filtration, washed with water and dried. The yield amounted to 1.2 g.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)=[CH:4][N:3]=1.CCCCCC.C([Li])CCC.CN(C)[CH:26]=[O:27].O>O1CCCC1>[O:9]1[CH2:10][CH2:11][O:12][CH:8]1[C:5]1[CH:6]=[CH:7][C:2]([CH:26]=[O:27])=[N:3][CH:4]=1
Reactant: CN(C)C=O
Reactant: Brc1ccc(C2OCCO2)cn1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=Cc1ccc(C2OCCO2)cn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 36 %

Procedure:
To a solution of 2-bromo-5-(1,3-dioxolan-2-yl)pyridine (9.60 g) in tetrahydrofuran (150 mL) was slowly added a 1.6M n-butyllithium hexane solution (28.7 mL) at −78° C. The reaction mixture was stirred for 30 min, N,N-dimethylformamide (3.9 mL) in tetrahydrofuran (50 mL) was added, and the mixture was warmed to room temperature and stirred for 30 min. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate solution. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (2.70 g, yield 36%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (1:2, volume ratio). MS: 180 (MH+).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8]C)[C:3]=1[C:10]1[NH:11][C:12]([C:16]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])=[C:13]([CH3:15])[N:14]=1.Cl.C(N(CC)CC)C.[NH2:32][CH2:33][C@H:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=1)[OH:35]>C(O)(=O)C>[Cl:42][C:38]1[CH:37]=[C:36]([C@H:34]([OH:35])[CH2:33][NH:32][C:2]2[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=2[C:10]2[NH:11][C:12]([C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:41]=[CH:40][CH:39]=1
Reactant: COc1nccc(I)c1-c1nc(C)c(C(=O)N2CCOCC2)[nH]1
Reactant: NC[C@@H](O)c1cccc(Cl)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Product: Cc1nc(-c2c(NC[C@@H](O)c3cccc(Cl)c3)cc[nH]c2=O)[nH]c1C(=O)N1CCOCC1
Temperature: 90 °C
Yield: 25.7 %

Procedure:
(2-(4-Iodo-2-methoxypyridin-3-yl)-4-methyl-1H-imidazol-5-yl)(morpholino)methanone (0.007 g, 0.017 mmol) was dissolved in acetic acid (1 mL) and concentrated hydrochloric acid (1 mL) and this mixture was stirred at 100° C. for 1 hour. The mixture was then evaporated and the residue was dissolved in N,N-dimethylformamide (2 mL) and treated with triethylamine (100 μL, 0.72 mmol) and the hydrochloric acid salt of (S)-2-amino-1-[3-chlorophenyl]ethanol (0.010 g, 0.048 mmol). The mixture was heated at 90° C. for 4 hours, then the solvent was evaporated and the residue was purified by Prep HPLC (ammonium acetate/acetonitrile/water) to give the title compound (0.002 g, 25%) as a white solid. HPLC 100% (220 nm), LCMS (+ESI, M+H+) m/z 458; 1H NMR (400 MHz, methanol-d4) δ (ppm): 2.37 (3H, s), 3.45-4.0 (10H, m), 4.7-4.9 (1H, m, overlapped by D2O), 6.10 (1H, d, J=7.8 Hz), 7.10 (1H, d, J=7.6 Hz), 7.14-7.24 (3H, m), 7.36 (1H, s), 10.26 (1H, br s).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:18]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:19]=[C:20](Br)Br)[CH:16]=2)[C:11]([CH3:29])([CH3:28])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:18]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:19]#[CH:20])[CH:16]=2)[C:11]([CH3:28])([CH3:29])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCCCC(C=C(Br)Br)c1ccc2c(c1)N(C(=O)OC(C)(C)C)CCC2(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C#CC(CCCCC)c1ccc2c(c1)N(C(=O)OC(C)(C)C)CCC2(C)C
Temperature: -78 °C
Reaction time: 1 h
Yield: 88.4 %

Procedure:
A solution of 7-(3,3-dibromo-1-pentyl-allyl)-4,4-dimethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester (0.08 g, 0.15 mmole) in 2 mL of THF at −78° C. was treated with 0.13 mL of 2.5M butyllithium. The reaction mixture was stirred at −78° C. for 1 hour, then at room temperature for 2 hours, quenched by the successive addition of 5 mL water and 5 mL of saturated aqueous ammonium chloride solution and extracted with three 25 mL portions of ether. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. The product was purified by flash chromatography (SiO2, 5% ethyl acetate in hexanes) to yield 0.049 g of 4,4-dimethyl-7-(1-pentyl-prop-2-ynyl)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester as a colourless oil.
Reaction SMILES: [CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Cl)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[F:20][C:21]1[CH:22]=[C:23]([OH:27])[CH:24]=[CH:25][CH:26]=1>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([O:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([F:20])[CH:22]=2)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: Oc1cccc(F)c1
Reactant: CCCCOC(=O)c1nc(Cl)c2ccccc2c1O
Product: CCCCOC(=O)c1nc(Oc2cccc(F)c2)c2ccccc2c1O

Procedure:
Synthesized from 1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester and 3-Fluoro phenol in analogy to Example D-20 d); MS-(+)-ion: M+1=356.1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([OH:12])=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CN(C=O)C>C(Cl)Cl>[CH2:20]([O:12][C:8]1[CH:9]=[N:10][C:11]2[C:6]([CH:7]=1)=[N:5][CH:4]=[CH:3][C:2]=2[Cl:1])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: Oc1cnc2c(Cl)ccnc2c1
Reactant: ClCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Clc1ccnc2cc(OCc3ccccc3)cnc12
Temperature: 65 °C

Procedure:
A pyrex reaction tube was charged with 8-chloro-1,5-naphthyridin-3-ol (165 mg, 914 μmol), potassium carbonate (631 mg, 4568 μmol), 1-(chloromethyl)benzene (376 μl, 4568 μmol) and 3.7 mL DMF. The tube was sealed and the mixture was heated at 65° C. for 3 h. The reaction was diluted with DCM and washed with water. The organic portion was dried, filtered, and concentrated. The crude material was purified by silica gel chromatography, 0-25% EtOAc in DCM to provide product as a white solid. MS: [M+H]=271.
Reaction SMILES: C1(OC(=S)O[CH:10]2[CH:14]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:13]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[O:26][SiH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH:23]=[CH2:24])[O:12][CH:11]2[N:44]2[CH:52]=[N:51][C:50]3[C:45]2=[N:46][CH:47]=[N:48][C:49]=3[NH2:53])C=CC=CC=1.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1>[CH2:16]([O:15][CH:14]1[C:13]([C:25]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[O:26][SiH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH:23]=[CH2:24])[O:12][CH:11]([N:44]2[CH:52]=[N:51][C:50]3[C:45]2=[N:46][CH:47]=[N:48][C:49]=3[NH2:53])[CH2:10]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C=CC1(C(O[SiH2]C(C)(C)C)(c2ccccc2)c2ccccc2)OC(n2cnc3c(N)ncnc32)C(OC(=S)Oc2ccccc2)C1OCc1ccccc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: Cc1ccccc1
Product: C=CC1(C(O[SiH2]C(C)(C)C)(c2ccccc2)c2ccccc2)OC(n2cnc3c(N)ncnc32)CC1OCc1ccccc1
Temperature: 25 °C
Yield: 90 %

Procedure:
To a flask was added Thiocarbonic acid O-[2-(6-amino-purin-9-yl)-4-benzyloxy-5-(tert-butyl-diphenyl-silanyloxymethyl)-5-vinyl-tetrahydro-furan-3-yl]ester O-phenyl ester, toluene, tributyl tin hydride, and AIBN. The reaction was stirred at reflux, cooled back to room temperature, was extracted, and the solvent was removed to provide the titled compound in 90% yield.
Reaction SMILES: C1(C)C(C([O:9][C@@H:10]2[C@@H:14]([CH2:15][O:16]C(C3C(C)=CC=CC=3)=O)[O:13][C@@H:12]([N:26]3[CH2:31][N:30]([CH2:32][CH2:33][CH2:34][CH3:35])[C:29](=[O:36])[NH:28][C:27]3=[O:37])[CH2:11]2)=O)=CC=CC=1.C[O-].[Na+].C(=O)=O.S(=O)(=O)(O)O>CO.C(Cl)(Cl)Cl.O>[C@@H:12]1([N:26]2[CH2:31][N:30]([CH2:32][CH2:33][CH2:34][CH3:35])[C:29](=[O:36])[NH:28][C:27]2=[O:37])[O:13][C@H:14]([CH2:15][OH:16])[C@@H:10]([OH:9])[CH2:11]1
Reactant: CCCCN1CN([C@H]2C[C@H](OC(=O)c3ccccc3C)[C@@H](COC(=O)c3ccccc3C)O2)C(=O)NC1=O
Agent: C[O-]
Agent: O=C=O
Agent: O=S(=O)(O)O
Solvent: CO
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCCCN1CN([C@H]2C[C@H](O)[C@@H](CO)O2)C(=O)NC1=O
Yield: 76.7 %

Procedure:
A reaction mixture consisting of 1.5 gm. (0.0287 mole) of 1-(3,5-di-O-toluoyl-2-deoxy-β-D-ribofuranosyl)-5-n-butyl-5,6-dihydro-s-triazine-2,4-(1H,3H)-dione (prepared in Part B, above), 70 ml. methanol, and 0.4 ml. of a solution of 25% sodium methoxide in methanol is stirred for 18 hours at 22° C. Thin-layer chromatography (25% methanol in chloroform) indicates one spot with a Rf 0.7. At this time solid carbon dioxide chips are added until the pH of the solution is 7.0. The methanol is removed by evaporation under reduced pressure. The residue thus obtained is dispersed in a mixture consisting of 50 ml. chloroform and 100 ml. water. The aqueous phase is washed five times with chloroform. The layers are separated, and the water is evaporated under reduced pressure at 40° C. There is obtained 0.97 gm. of residue. The residue is placed on a prepacked E. Merck Silica-gel-60 Column, Type C. The column is developed with a solvent mixture consisting of 10 percent methanol in chloroform at the rate of 3 ml. per minute. Fractions containing desired material, i.e. those fractions indicating positive char with a 50% aqueous sulfuric acid spray, are collected and the solvent mixture is removed by evaporation under reduced pressure. There is thus obtained 0.632 gm. (76.7 percent yield) of preparation of 1-(2-deoxy-β-D-ribofuranosyl)-5-n-butyl-5,6-dihydro-s-triazine-2,4-(1H,3H)-dione as a clear glass.