Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:5]1[CH2:9][O:8][C:7](=[O:10])[CH2:6]1)[CH:2](C)C.[C:11](OC(=O)CC(CC(C)C)C(O)=O)(C)(C)C.CO>C1COCC1>[CH:1]([CH:5]1[CH2:9][O:8][C:7](=[O:10])[CH2:6]1)([CH3:2])[CH3:11]
Reactant: CC(C)CC(CC(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)CC1COC(=O)C1
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)C1COC(=O)C1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 89 %

Procedure:
Preparation of 4-Isobutyl-dihydro-furan-2-one (4): A solution of 2-isobutyl-succinic acid-4-t-butyl ester (8.0 g, 34.7 mmol) in 100 mL of THF is cooled to 0° C. under Ar and borane dimethyl sulphide complex (2.6 g, 34.7 mmol) is added. The reaction mixture is stirred at 0° C. for 10 minutes, and at room temperature overnight. The solution is cooled to 0° C. and 100 mL of MeOH is added. The solvents are evaporated, and the remaining oil is dried under hi-vacuum for 2 hrs. The oil remaining is taken up in 100 mL of THF, and a catalytic amount of p-toluene sulfonic acid is added. The solution is warmed to reflux overnight. After being cooled to room temperature, the solvent is evaporated, and the oil is taken up in Et2O (100 mL). The Et2O solution is extracted with 2.0N Na2CO3 (2×50 mL) followed by 100 mL of brine and dried over MgSO4. Evaporation of Et2O followed by medium pressure chromatography (MPLC) of the remaining oil in 20% EtOAc/Hexanes gives 4.4 g (89% yield) of 4-isopropyl-dihydro-furan-2-one as an oil. NMR (H1, 400 MHz, CDCl3) δ0.9 (6H, m); δ1.3 (2H, dd); δ1.5 (1H, m); δ2.1 (1H, m); δ2.6 (2H, m); δ3.6 (1H, m); δ4.4 (1H, m).
Reaction SMILES: [N:1]1([C:6]2[CH:13]=[CH:12][C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][C:7]=2[C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:23][C:24]1[N:29]=[C:28](Cl)[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:23][C:24]1[N:29]=[C:28]([C:11]2[CH:12]=[CH:13][C:6]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[C:7]([CH:10]=2)[C:8]#[N:9])[CH:27]=[CH:26][N:25]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: CC1(C)OB(c2ccc(N3CCCC3)c(C#N)c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: N#Cc1cc(-c2ccnc(Cl)n2)ccc1N1CCCC1
Temperature: 100 °C
Yield: 381.1 %

Procedure:
Pyrrolidin-1-yl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (200 mg, 0.67 mmol), 2,4-dichloropyrimidine (120 mg, 0.81 mmol), tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.07 mmol, 10 mol %) and sodium carbonate (213 mg, 2.01 mmol) were diluted with 1:1 1,4-dioxane-H2O (4.0 mL). The mixture was then heated at 100° C. in the microwave (300 W, stirring) for 10 minutes. The reaction was repeated four more times. The reaction mixtures were combined and the solvents evaporated in vacuo (Genevac™). The residue was partitioned between DCM (150 mL) and H2O (50 mL). The organic phase was washed with water (50 mL) and saturated brine solution (75 mL). The organic phase was then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (40-63 mesh silica gel, 70% isohexane-EtOAc) to provide the title compound as a yellow solid (727 mg, 76%); LC-MS, Rt=2.80 min (MeOH-FA method), m/z 285, 287 (MH+).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@@H:3]1[CH2:7][OH:8].[C:9]1(=O)[O:14][C:12](=[O:13])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]12>C1(C)C(C)=CC=CC=1>[OH:8][CH2:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][C@@H:2]1[N:1]1[C:12](=[O:13])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]2[C:9]1=[O:14]
Reactant: N[C@@H]1CCC[C@@H]1CO
Reactant: O=C1OC(=O)c2ccccc21
Solvent: Cc1ccccc1C
Product: O=C1c2ccccc2C(=O)N1[C@H]1CCC[C@H]1CO
Yield: 79.9 %

Procedure:
A mixture of (±) cis 1-amino-2-hydroxymethylcyclopentane (0.59 g, 5.1 mmol) and phthalic anhydride (0.76 g, 5.1 mmol) in xylene (40 ml) was heated under argon at reflux using a condenser fitted with a Dean and Stark trap. After 1.5 h the reaction was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluting with diethyl ether to give the title compound as a pale yellow oil (1.0 g).
Reaction SMILES: N[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[S:14]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)(=[O:16])=[O:15].O.[BrH:24].N([O-])=O.[Na+]>O1CCCC1>[Br:24][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[S:14]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)(=[O:16])=[O:15]
Reactant: Br
Reactant: NC(=O)c1[nH]c2c(N)cccc2c1S(=O)(=O)N1CCOCC1
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)c1[nH]c2c(Br)cccc2c1S(=O)(=O)N1CCOCC1
Temperature: 0 °C
Reaction time: 72 h

Procedure:
7-Amino-3-(morpholin-4-ylsulfonyl)-1H-indole-2-carboxamide (26 mg, 0.080 mmol, 1.0 equiv) was dissolved in 2 mL of a 1:1 solution of tetrahydrofuran:water to which 0.2 mL of concentrated aqueous HBr was added and the mixture was cooled to 0° C. NaNO2 (28 mg, 0.40 mmol, 5.0 equiv) was added in one portion, followed by CuBr (57 mg, 0.40 mmol, 5.0 equiv) 25 minutes later. The reaction was warmed to ambient temperature and stirred for 72 hours. The reaction mixture was partitioned between dichloromethane and water and extracted three times with dichloromethane. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by preparative reversed phase HPLC provided the titled compound. Proton NMR for the product was consistent with the titled compound. ESI+MS: 388.1 [M+H]+.
Reaction SMILES: FC(F)(F)C1C=CC(CBr)=CC=1.Cl.Br[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1.[CH3:22][C:23]1[N:24]=[C:25]([N:33]2[CH2:37][CH2:36][NH:35][C:34]2=[O:38])[S:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29]>>[CH3:22][C:23]1[N:24]=[C:25]([N:33]2[CH2:37][CH2:36][N:35]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[C:34]2=[O:38])[S:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29]
Reactant: CCOC(=O)c1sc(N2CCNC2=O)nc1C
Reactant: BrCc1ccccn1
Agent: Cl
Agent: FC(F)(F)c1ccc(CBr)cc1
Product: CCOC(=O)c1sc(N2CCN(Cc3ccccn3)C2=O)nc1C
Yield: 55 %

Procedure:
Following the procedure as described in Example 13, making variations as required to replace 4-(trifluoromethyl)benzyl bromide with 2-(bromomethyl)pyridine hydrochloride to react with ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate, the title compound was obtained as a colorless solid in 55% yield: MS (ES+) m/z 347.2 (M+1).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:17]=O)[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]([OH:34])([CH3:33])[CH3:32])[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:17][N:25]3[CH2:30][CH2:29][CH:28]([C:31]([OH:34])([CH3:33])[CH3:32])[CH2:27][CH2:26]3)[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1
Reactant: CC(C)(O)C1CCNCC1
Reactant: O=Cc1nc2c(N3CCOCC3)nc(Cl)nc2n1C1CCCCO1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)(O)C1CCN(Cc2nc3c(N4CCOCC4)nc(Cl)nc3n2C2CCCCO2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98.4 %

Procedure:
A mixture of 2-chloro-6-morpholino-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-8-carbaldehyde (245 mg, 0.696 mmol), 2-(4-piperidyl)-2-propanol (110 mg, 0.77 mmol) and sodium triacetoxyborohydride (162 mg, 0.77 mmol) in 1,2-dichloroethane (10 mL) was stirred at room temperature for 30 minutes. The reaction mixture was then diluted with saturated aqueous sodium bicarbonate. The aqueous layer was then extracted with DCM. The combined organic extracts were then washed with water, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography (0-100% gradient EtOAc-heptane) to give the title compound (328 mg, 98%). LCMS: M+H+=480.2.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][NH2:9])[CH:3]=1.ClC1C=C(N2[C:22]([C:23]3[CH:28]=[C:27]([O:29][C:30]([F:33])([F:32])[F:31])[CH:26]=[C:25]([F:34])[CH:24]=3)=[CH:21][C:20]([C:35]([OH:37])=[O:36])=N2)C=CC=1F>>[F:34][C:25]1[CH:24]=[C:23]([C:22]2[N:8]([C:4]3[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=3)[N:9]=[C:20]([C:35]([OH:37])=[O:36])[CH:21]=2)[CH:28]=[C:27]([O:29][C:30]([F:33])([F:32])[F:31])[CH:26]=1
Reactant: NNc1cccnc1
Reactant: O=C(O)c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2ccc(F)c(Cl)c2)n1
Agent: Cl
Product: O=C(O)c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1

Procedure:
1.82 g (4.71 mmol) of the compound from example 1A is reacted with 1.03 g (7.07 mmol) 3-pyridylhydrazine hydrochloride in a manner analogous to the synthesis of the compound from example 8A. Following hydrolysis, 1.12 g (65% of theoretical yield) of the title compound is produced.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19](=[O:22])[CH2:20]Br)=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23]([O-:26])(=[S:25])[CH3:24].[K+].ClCCl.C(O)(=S)C>CO>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19](=[O:22])[CH2:20][S:25][C:23](=[O:26])[CH3:24])=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC([O-])=S
Reactant: O=C(CBr)c1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1
Agent: CC(O)=S
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Product: CC(=O)SCC(=O)c1ccc2c(c1)CCN2S(=O)(=O)c1ccccc1

Procedure:
The mono-brominated sulfonamide from step 2 (0.194 g, 0.509 mmol) was was dissolved in methanol (2 ml) before potassium thioacetate (0.0639 g, 0.560 mmol) was added as a solid. LC-MS of the resulting yellow solution shows the reaction is complete in minutes. Evaporation of the volatiles leaves a tan residue which was taken up into dichloromethane (4 ml), during which the disulfide of the thioacetic acid was deposited and filtered. The desired thioester could then be recrystallized from dichloromethane/hexanes (0.080 g, 0.214 mmol, 42%). LC-MS (ES+): 376 [MH]+ m/e. 1H-NMR (DMSO): 7.87 (d, 3H), 7.78 (s, 1H), 7.7 (m, 1H), 7.57 (m, 3H), 4.41 (s, 2H), 3.99 (t, 2H), 3.06 (t, 2H), 2.34 (s, 3H)
Reaction SMILES: C1(C)C=CC(S([C:10]([C@H:13]2[C@H:17]([OH:18])[O:16][C:15](=[O:19])[CH2:14]2)([CH3:12])[CH3:11])(=O)=O)=CC=1.O.C(=O)([O-])[O-].[Na+].[Na+]>CO>[CH:17]([C:13](=[C:10]([CH3:12])[CH3:11])[CH2:14][C:15]([OH:19])=[O:16])=[O:18]
Reactant: Cc1ccc(S(=O)(=O)C(C)(C)[C@@H]2CC(=O)O[C@H]2O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)=C(C=O)CC(=O)O
Temperature: -5 °C
Yield: 82.6 %

Procedure:
0.788 g of the product of Step C was added to a solution of 20 ml of water and 2.4 ml of methanol and 0.790 g of sodium carbonate were added with stirring at -5° C. to the resulting mixture. The mixture was stirred at 20° C. for 2 hours and was extracted with ether. The aqueous phase was acidified to a pH of 3.5 by addition of 1 N aqueous hydrochloric acid. The mixture was extracted with chloroform and the organic phase was evaporated to dryness under reduced pressure to obtain 0.310 g of 3-formyl-4-methyl-pent-3-ene-1-oic acid melting at 102° C.
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].[N:17]1([C:22]2[CH:27]=[CH:26][C:25]([CH:28]([O:35][CH3:36])[C:29](N(OC)C)=[O:30])=[CH:24][CH:23]=2)[CH:21]=[CH:20][N:19]=[N:18]1>>[N:17]1([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([O:35][CH3:36])[C:29]([C:12]3[O:11][C:10]([C:5]4[CH:6]=[C:7]([O:8][CH3:9])[C:2]([Br:1])=[C:3]([O:15][CH3:16])[CH:4]=4)=[CH:14][CH:13]=3)=[O:30])=[CH:26][CH:27]=2)[CH:21]=[CH:20][N:19]=[N:18]1
Reactant: COc1cc(-c2ccco2)cc(OC)c1Br
Reactant: COC(C(=O)N(C)OC)c1ccc(-n2ccnn2)cc1
Product: COc1cc(-c2ccc(C(=O)C(OC)c3ccc(-n4ccnn4)cc3)o2)cc(OC)c1Br
Yield: 7 %

Procedure:
2-(4-(1H-1,2,3-Triazol-1-yl)phenyl)-1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxyethanone was prepared from 2-(4-bromo-3,5-dimethoxyphenyl)furan and 2-(4-(1H-1,2,3-triazol-1-yl)phenyl)-N,2-dimethoxy-N-methylacetamide according to the procedure used in Example 30. Purification by chromatography (50% EtOAc/hexanes) gave 2-(4-(1H-1,2,3-triazol-1-yl)phenyl)-1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxyethanone as a yellow solid (0.025 g, 7% yield). MS: m/z 498.2 [M+H]+.
Reaction SMILES: C(O[C:6](=O)[N:7](C)[C@@H:8]([C:16](=[O:27])[N:17]([CH3:26])[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:26][N:17]([CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[C:16](=[O:27])[C@H:8]([NH:7][CH3:6])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CN(CCc1ccccn1)C(=O)[C@@H](Cc1ccccc1)N(C)C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN[C@H](Cc1ccccc1)C(=O)N(C)CCc1ccccn1
Reaction time: 0.67 h

Procedure:
N-Methyl-N{(1R)-1-[N-methyl-N-(2-(2-pyridyl)ethyl)carbamoyl]-2-phenylethyl}carbamic acid tert-butyl ester was dissolved in dichloromethane (75 mL). Trifluoroacetic acid (75 mL, 0.978 mol) was added to the stirred solution. The reaction mixture was stirred for 40 min. The solvent was removed in vacuo. The product was dissolved in dichloromethane (30 mL) and sat. aqueous sodium hydrogen carbonate solution (20 mL). The reaction mixture was neutralised with solid sodium hydrogen carbonate. Dichloromethane (100 mL) was added and the aqueous phase was extracted with dichloromethane (2×150 mL). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo, to give 7.9 g of (2R)-N-Methyl-2-(methylamino)-3-phenyl-N-(2-(2-pyridyl)ethyl)propionamide.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([OH:12])=[O:11])[C:4]=2[CH:3]=[CH:2]1.[N+](=[CH2:15])=[N-].S([O-])([O-])(=O)=O.[Mg+2]>CO.C(OCC)C>[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:15])=[O:11])[C:4]=2[CH:3]=[CH:2]1
Reactant: C=[N+]=[N-]
Reactant: O=C(O)c1cccc2[nH]ccc12
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: CO
Solvent: CCOCC
Product: COC(=O)c1cccc2[nH]ccc12
Yield: 98 %

Procedure:
To a solution of indole-4-carboxylic acid (506 mg, 3.14 mmol) dissolved in a mixture of methanol (5 mL) and diethyl ether (10 mL) was added ethereal diazomethane until disappearance of starting acid was indicated by TLC. Anhydrous magnesium sulfate was then added and the solution filtered and concentrated in vacuo. Flash chromatography on 10 g of Merck silica gel eluted with 2:1, chloroform:hexanes, followed by 10:1, chloroform:diethyl ether afforded the title compound (540 mg, 98%).
Reaction SMILES: [CH3:1][O:2][CH2:3][C@H:4]([CH3:22])[O:5][C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=1)[C:9]([OH:11])=O.[CH2:23]([O:25][C:26](=[O:35])[CH2:27][S:28][C:29]1[S:33][C:32]([NH2:34])=[N:31][CH:30]=1)[CH3:24]>>[CH2:23]([O:25][C:26](=[O:35])[CH2:27][S:28][C:29]1[S:33][C:32]([NH:34][C:9](=[O:11])[C:8]2[CH:12]=[C:13]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:14]=[C:6]([O:5][C@@H:4]([CH3:22])[CH2:3][O:2][CH3:1])[CH:7]=2)=[N:31][CH:30]=1)[CH3:24]
Reactant: CCOC(=O)CSc1cnc(N)s1
Reactant: COC[C@H](C)Oc1cc(Oc2ccccc2)cc(C(=O)O)c1
Product: CCOC(=O)CSc1cnc(NC(=O)c2cc(Oc3ccccc3)cc(O[C@@H](C)COC)c2)s1

Procedure:
The title compound was prepared from 3-((S)-2-methoxy-1-methyl-ethoxy)-5-phenoxy benzoic acid and (2-amino-thiazol-5-ylsulfanyl)-acetic acid ethyl ester following general procedure A
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([CH:7]2[CH2:12][CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]2)[S:4][N:3]=1.[ClH:20]>ClCCl.CCO>[ClH:20].[CH3:1][C:2]1[N:6]=[C:5]([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[S:4][N:3]=1
Reactant: Cc1nsc(C2CCCN(C(=O)OC(C)(C)C)C2)n1
Agent: Cl
Solvent: CCO
Solvent: ClCCl
Product: Cc1nsc(C2CCCNC2)n1
Temperature: 35 °C

Procedure:
The Boc-protected intermediate 11a (0.87 g, 3.07 mmol) was stirred in dichloromethane (10 mL) and treated with 10 mL of a 2.53 M solution of HCl in EtOH. After warming to 35° C. for 2 hours, the mixture was concentrated under vacuum. The product was precipitated from IPA:MTBE (1:10). The product was recrystallized from IPA:MTBE three times to afford a high purity sample (42 mg) of white solid. MS (ESI) m/z 184 [M+1]+. NMR (CDCl3) δ 1.68-1.91 (m, 3H), 2.13-2.20 (d, 1H), 2.58 (s, 3H), 2.87-2.95 (dt, 1H), 3.14 (t, 1H), 3.25-3.28 (d, 1H), 3.54-3.59 (d, 1H), 3.65-3.73 (m, 1H), 9.10 (s, 2H).
Reaction SMILES: [CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:18]=[CH:17][C:16]([C:19]([OH:21])=O)=[CH:15][N:14]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].S(Cl)(Cl)=O.C(C1C=CC(C2N=CC(C(Cl)=O)=C[N:39]=2)=CC=1)CCCCC.N>O1CCOCC1>[CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:18]=[CH:17][C:16]([C:19]([NH2:39])=[O:21])=[CH:15][N:14]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCc1ccc(-c2ncc(C(=O)O)cn2)cc1
Reactant: CCCCCCc1ccc(-c2ncc(C(=O)Cl)cn2)cc1
Agent: N
Solvent: C1COCCO1
Solvent: O=S(Cl)Cl
Product: CCCCCCc1ccc(-c2ncc(C(N)=O)cn2)cc1

Procedure:
12.0 G. of 2-(p-n-hexylphenyl)-5-pyrimidinecarboxylic acid are reacted with 80 ml. of thionyl chloride with the exclusion of moisture and worked up in a manner analogous to that described in Example 7. The remaining 2-(p-n-hexylphenyl)-5-pyrimidinecarboxylic acid chloride is dissolved in 120 ml. of abslute dioxane while warming and added with stirring to a solution of 200 ml. of absolute dioxane saturated with ammonia at room temperature and treated further in a manner analogous to that described in Example 7. A sample of the obtained crude 2-(p-n-hexylphenyl)-5-pyrimidinecarboxamide is sublimed at 180° C. in a high vacuum for purification; melting point 250.2°-258.3° C.
Reaction SMILES: Cl.CN(C)CCC[N:7]=[C:8]=[N:9]CC.NC(N[C:17]1[N:18]([C@@H:25]2[O:31][C@H:30]([CH2:32][OH:33])[C@@H:28]([OH:29])[C@H:26]2[OH:27])[CH:19]=[C:20]([C:22]([OH:24])=[O:23])[N:21]=1)=O>O.CO>[CH:17]1[N:18]([C@@H:25]2[O:31][C@H:30]([CH2:32][OH:33])[C@@H:28]([OH:29])[C@H:26]2[OH:27])[C:19]2[N:7]=[C:8]([NH2:9])[O:24][C:22](=[O:23])[C:20]=2[N:21]=1
Reactant: NC(=O)Nc1nc(C(=O)O)cn1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: O
Solvent: CO
Product: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (78 mg, 0.41 mmol) was added to a solution of 5-[[(amino)carbonyl]amino-1-(β-D-ribofuranosyl)-1H-imidazole-4-carboxylic acid (19 mg, 0.063 mmol) in water (2 mL) and CH3OH (5 mL) and the mixture was stirred at room temperature overnight. The reaction was quenched by addition of excess 60% aqueous acetic acid. After 30 minutes, the mixture was diluted with water, concentrated to remove CH3OH and lyophilized. The resulting powder (100 mg) was chromatographed on reverse phase silica gel [10 g, flash, stepwise gradient elution: water (200 mL), 10% CH3OH in water (v/v, 100 mL), 20% CH3OH in water (v/v, 100 mL), 10-mL fractions]. Fractions containing the product were combined, concentrated under reduced pressure and lyophilized to give oxanosine: 16 mg (89%).
Reaction SMILES: [O:1]=[C:2]1[C:6](=[CH:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]3)=[CH:10][CH:9]=2)[S:5][C:4]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[N:3]1.[NH2:27][CH2:28][C@H:29]([OH:44])[CH2:30][O:31][C:32]1[CH:41]=[CH:40][C:39]([OH:42])=[C:38]2[C:33]=1[CH2:34][CH2:35][C:36](=[O:43])[NH:37]2>>[OH:42][C:39]1[CH:40]=[CH:41][C:32]([O:31][CH2:30][C@@H:29]([OH:44])[CH2:28][NH:27][CH:17]2[CH2:18][CH2:19][N:14]([C:11]3[CH:10]=[CH:9][C:8]([CH:7]=[C:6]4[S:5][C:4]([N:21]5[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]5)=[N:3][C:2]4=[O:1])=[CH:13][CH:12]=3)[CH2:15][CH2:16]2)=[C:33]2[C:38]=1[NH:37][C:36](=[O:43])[CH2:35][CH2:34]2
Reactant: NC[C@H](O)COc1ccc(O)c2c1CCC(=O)N2
Reactant: O=C1CCN(c2ccc(C=C3SC(N4CCCCC4)=NC3=O)cc2)CC1
Product: O=C1CCc2c(OC[C@@H](O)CNC3CCN(c4ccc(C=C5SC(N6CCCCC6)=NC5=O)cc4)CC3)ccc(O)c2N1

Procedure:
The title compound was prepared from 1-[4-(4-oxo-2-piperidin-1-yl-4H-thiazol-5-ylidenemethyl)-phenyl]-piperidin-4-one (which was obtained in Intermediate 25) and 5-((2S)-3-amino-2-hydroxy-propoxy)-8-hydroxy-3,4-dihydro-1H-quinolin-2-one (which was obtained in Intermediate 12) according to the procedure of Example 1 as a yellowish solid; mp>120° C. (dec.); 1H NMR (300 MHz, DMSO-d6) δ 1.20-1.40 (m, 2 H), 1.55-1.70 (m, 6 H), 1.85-2.00 (m, 2 H), 2.43 (t, J=7.9 Hz, 2.55-2.90 (m, 9 H), 3.60 (br s, 2 H), 3.70-3.95 (m, 6 H), 6.44 (d, J=9.0 Hz, 1 H), 6.69 (d, J=9.0 Hz, 1 H), 7.02 (d, J=9.0 Hz, 2 H), 7.44 (d, J=9.0 Hz, 2 H), 7.50 (s, 1 H), 8.82 (s, 1 H); MS (ES) m/z: 303.6 ((M+2H)2+, 100%); 606.1 (MH+, 10%); HRMS Calcd. for C32H40N5O5S (MH+): 606.2750. Found: 606.2711.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C[O:9][B:10](OC)[O:11]C.C([Li])(C)(C)C>C(OCC)C.CCCCC>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([B:10]([OH:11])[OH:9])[CH:3]=1
Reactant: Brc1cccnc1
Reactant: COB(OC)OC
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCOCC
Product: OB(O)c1cccnc1
Temperature: 25 °C

Procedure:
A solution of 4.0 ml (6.56 g, 42 mmol) of 3-bromopyridine and 9 ml (8 mmol) of trimethylborate in 100 ml of diethyl ether was cooled to -70° C. then treated slowly with 33 ml (83.8 mmol) of a 2.54M tert-butyllithium in pentane solution. After allowing the resulting slurry to warm to room temperature the solvents were evaporated under vacuum. The residual oil was treated carefully with 50 ml of a 1M hydrochloric acid solution. Several milliters of methylene chloride were added and the mixture was stirred until the oil had dissolved. The aqueous layer was washed with fresh methylene chloride. The pH of the aqueous solution was raised to 12 with 5M sodium hydroxide solution and the washing was repeated. The pH of the aqueous solution was then lowered to 6.5 with concentrated hydrochloric acid solution. After chilling, this solution was filtered, saturated with sodium chloride, then extracted several times with a 2:1 mixture of diethyl ether and isopropanol. Evaporation of these extracts produced a colorless solid. This material was further purified by dissolving in methanol, evaporating to a thick paste, adding a few milliters of water, concentrating further under vacuum, then chilling and collecting the crystalline product. Additional product in the aqueous mother liquor was isolated by repeating this process. Thorough drying of this hydrated product at 0.1 mm pressure afforded a fine powder weighing 2.2 g. Elemental analysis and a mass spectrum indicated the product so isolated was primarily the anhydride (tripyridylboroxane).