Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[CH2:10]([Al](CC)CC)[CH3:11]>O1CCOCC1.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:8][C:5]1[N:4]=[C:3]([CH2:10][CH3:11])[C:2]([NH2:1])=[CH:7][CH:6]=1
Reactant: CC[Al](CC)CC
Reactant: Nc1ccc(Cl)nc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: CCc1nc(Cl)ccc1N
Temperature: 100 °C
Reaction time: 3 h
Yield: 34.9 %

Procedure:
To a solution of 3-amino-2,6-dichloropyridine (8.1 g, 50 mmol, purchased from TCI) in 1,4-dioxane (248 ml) was added tetrakis(triphenylphosphine)palladium(0) (920 mg, 0.80 mmol) and triethylaluminum (52 mmol, 0.94 M in hexane) at room temperature, and the mixture was stirred for 3 hours at 100° C. The mixture was quenched with 2 M HCl aqueous solution after cooling, and then it was separated between the aqueous and organic phases. The aqueous phase was extracted with EtOAc. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by silica gel column chromatography, eluting with hexane/EtOAc (2:1), to give the title compound (2.73 g, 35%).
Reaction SMILES: F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[N:32]1([C:37]2[N:42]=[CH:41][C:40]([C:43]([OH:45])=O)=[CH:39][N:38]=2)[CH:36]=[CH:35][N:34]=[CH:33]1.[CH:46]1([NH:49][CH:50]2[CH2:55][CH2:54][N:53]([C:56]3[O:60][N:59]=[C:58]([C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=4)[N:57]=3)[CH2:52][CH2:51]2)[CH2:48][CH2:47]1>CN(C)C=O>[CH:46]1([N:49]([CH:50]2[CH2:51][CH2:52][N:53]([C:56]3[O:60][N:59]=[C:58]([C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=4)[N:57]=3)[CH2:54][CH2:55]2)[C:43]([C:40]2[CH:41]=[N:42][C:37]([N:32]3[CH:36]=[CH:35][N:34]=[CH:33]3)=[N:38][CH:39]=2)=[O:45])[CH2:48][CH2:47]1
Reactant: O=C(O)c1cnc(-n2ccnc2)nc1
Reactant: c1ccc(-c2noc(N3CCC(NC4CC4)CC3)n2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(c1cnc(-n2ccnc2)nc1)N(C1CC1)C1CCN(c2nc(-c3ccccc3)no2)CC1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (75 mg) and ethyldiisopropylamine (74 μL) are added to a solution of 2-imidazol-1-yl-pyrimidine-5-carboxylic acid (40 mg) in N,N-dimethylformamide (5 mL) at room temperature. The solution is stirred for 10 min prior to the addition of cyclopropyl-[1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]amine (60 mg). The resulting mixture is stirred at 60° C. for 3 h, cooled to room temperature over night, and concentrated in vacuo. The crude product is purified by HPLC(H2O/MeOH/TFA). LC (method 1): tR=1.50 min; Mass spectrum (ESI+): m/z=457 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:26])=[C:5]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:7]=1[C:8]([OH:10])=[O:9].[CH2:27](O)[CH2:28][CH2:29][CH2:30][CH2:31][CH3:32].C1(N=C=NC2CCCCC2)CCCCC1.C(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH3:1][C:2]1[NH:3][C:4]([CH3:26])=[C:5]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:7]=1[C:8]([O:10][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:9]
Reactant: CCCCCCO
Reactant: CC1=C(C(=O)O)C(c2cccc([N+](=O)[O-])c2)C(c2ccccn2)=C(C)N1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CCCCCCOC(=O)C1=C(C)NC(C)=C(c2ccccn2)C1c1cccc([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
350 mg (1 mmol) of 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-5-pyridylpyridine-3-carboxylic acid, 102 mg (1 mmol) of hexyl alcohol, 309 mg (1.4 mmol) of N,N'-dicyclohexylcarbodiimide, 134 mg (1.1 mmol) of 4-N,N-dimethylaminopyridine were dissolved in 10 ml of toluene, with application of heat thereto. This reaction mixture was refluxed with application of heat for 1 hour, and then cooled to room temperature. To this reaction mixture, 20 ml of chloroform was added. The reaction mixture was then washed with water and dried over anhydrous sodium sulfate. The solvents contained in the reaction mixture were then distilled of and the residue was chromatographed on a silica gel column, whereby the captioned compound was obtained. The yield was 389 mg (89.5%).
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:13][NH:14][CH2:15][CH2:16][N:17]([CH3:19])[CH3:18]>>[CH3:18][N:17]([CH3:19])[CH2:16][CH2:15][N:14]([CH3:13])[C:1](=[O:12])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCC/C=C/C(=O)O
Reactant: CNCCN(C)C
Product: CCCCCCC/C=C/C(=O)N(C)CCN(C)C

Procedure:
The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and N,N′,N′-trimethylethylenediamine as starting materials to give the aimed compound.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[B:12]1[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]1.I[C:22]1C(C)=CC(C)=C(C=1)C(OC)=O.IC1C=C(C=CC=1C)C(OC)=O>>[CH3:22][C:10]1[CH:11]=[C:2]([CH3:1])[C:3]([B:12]2[O:13][C:14]([CH3:20])([CH3:19])[C:15]([CH3:18])([CH3:17])[O:16]2)=[CH:4][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1cc(I)c(C)cc1C
Reactant: COC(=O)c1ccc(C)c(B2OC(C)(C)C(C)(C)O2)c1
Agent: COC(=O)c1ccc(C)c(I)c1
Product: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)c(C)cc1C

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5.4, except methyl 5-iodo-2,4-dimethylbenzoate (compound 31.1) was used in place of methyl 3-iodo-4-methylbenzoate (compound 5.3). m/z (ES+) 291(M+H)+.
Reaction SMILES: [OH:1][C:2]1[C:11](=[O:12])[C:10]2[C:5](=[C:6]([O:13][CH3:14])[CH:7]=[CH:8][CH:9]=2)[O:4][CH:3]=1.Cl[CH2:16][C:17]([O:19][CH3:20])=[O:18].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:20][O:19][C:17](=[O:18])[CH2:16][O:1][C:2]1[C:11](=[O:12])[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([O:13][CH3:14])[C:5]=2[O:4][CH:3]=1
Reactant: COc1cccc2c(=O)c(O)coc12
Reactant: COC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)COc1coc2c(OC)cccc2c1=O
Temperature: 100 °C
Reaction time: 4 h
Yield: 87 %

Procedure:
A mixture of 3-hydroxy-8-methoxychromone (1.92 g, 0.01 mole), methyl chloracetate (1.08 g, 0.01 mole) and potassium carbonate (1.0 g, 0.01 mole) in dimethylformamide (20 ml) is stirred at 100° C. under nitrogen for 4 hrs. The reaction mixture is allowed to stand at room temperature overnight, poured into water, filtered, washed with water and sucked dry. Recrystallization from ethanol gives white crystals (2.3 g, 88%), mp 137°-138° C.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH3:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH:11]=1.[C:26](=O)([O:29]C)[O:27][CH3:28]>C1COCC1>[CH3:28][O:27][C:26](=[O:29])[CH2:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:17]=[CH:18][C:19]([C:22]([F:25])([F:23])[F:24])=[CH:20][CH:21]=2)[CH:11]=1
Reactant: Cc1ccnc(-c2ccc(C(F)(F)F)cc2)c1
Reactant: COC(=O)OC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)Cc1ccnc(-c2ccc(C(F)(F)F)cc2)c1
Temperature: 0 °C
Yield: 70.8 %

Procedure:
A solution of LDA (2M in THF/heptane/ethyl benzene, 44 ml, 88 mmol) was added dropwise to a stirred solution of 4-methyl-2-[4-(trifluoromethyl)phenyl]pyridine (10.5 g, 44 mmol) in dry THF (300 ml) under N2, such that the internal temperature remained <−70° C. After 1 hour at this temperature, dimethyl carbonate (8.9 ml, 106 mmol) was added. After 30 minutes the cooling bath was removed. When the internal temperature had reached −20° C. the reaction was transferred to a cold bath at −10° C., and then allowed to warm slowly to 0° C. After 1 hour at 0° C. the reaction was quenched with aqueous NH4Cl (half saturated, 100 ml). The reaction mixture was concentrated in vacuo. The residue was diluted with H2O (200 ml) and extracted with EtOAc (2×200 ml). The combined extracts were washed with brine (×1), then dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica, eluting with 10-30% EtOAc/isohexane to give the ester (9.2 g, 71%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ: 3.72 (2H, s), 3.75 (3H, s), 7.24 (1H, dd, J 1.4, 5.0), 7.72 (3H, t, J 8.4), 8.11 (2H, d, J 8.2), 8.68 (1H, d, J 5.0).
Reaction SMILES: [CH3:1][CH:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22](Cl)[C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([CH:22]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:3][CH:2]2[CH3:1])=[CH:20][CH:21]=1
Reactant: Clc1ccc(C(Cl)c2ccc(Cl)cc2)cc1
Reactant: CC1CN(C(=O)OC(C)(C)C)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC1CN(C(=O)OC(C)(C)C)CCN1C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Temperature: 82 °C
Reaction time: 8 h
Yield: 39.1 %

Procedure:
A 100 mL round-bottom flask was charged with tert-butyl 3-methylpiperazine-1-carboxylate (2.00 g, 9.99 mmol, 1.00 equiv), 1-chloro-4-[chloro(4-chlorophenyl)methyl]benzene (5.46 g, 20.1 mmol, 2.01 equiv), potassium carbonate (6.90 g, 49.9 mmol, 5.00 equiv), acetonitrile (30 mL). The resulting solution was stirred overnight at 82° C. in an oil bath. The resulting solution was diluted with H2O (50 mL). The resulting solution was extracted with dichloromethane (3×20 mL) and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/4) to yield 1.70 g (53% yield) of tert-butyl 4-[bis(4-chlorophenyl)methyl]-3-methylpiperazine-1-carboxylate as a light yellow solid. LCMS: (ESI, m/z): 435 [M+H]+.
Reaction SMILES: [CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[C:21]([N:22]4[C:30](=[O:31])[C:29]5[C:28]([C:32]#[N:33])=[CH:27][CH:26]=[CH:25][C:24]=5[CH2:23]4)=[CH:20][N:19](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:16]3=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].[BH4-].[Na+]>C(Cl)Cl.CO>[NH2:33][CH2:32][C:28]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:29]=1[C:30](=[O:31])[N:22]([C:21]1[C:15]3[C:16](=[N:17][CH:18]=[C:13]([C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:8][CH:9]=4)[N:14]=3)[NH:19][CH:20]=1)[CH2:23]2
Reactant: CC(C)S(=O)(=O)c1ccc(-c2cnc3c(n2)c(N2Cc4cccc(C#N)c4C2=O)cn3C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CC(C)S(=O)(=O)c1ccc(-c2cnc3[nH]cc(N4Cc5cccc(CN)c5C4=O)c3n2)cc1
Reaction time: 3 h

Procedure:
2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]-3-oxo-isoindoline-4-carbonitrile (150 mg, 0.2143 mmol) dissolved in a mixture of DCM (10 mL) and MeOH (5 mL) under N2. CoCl2 (55.65 mg, 0.4286 mmol) added then the reaction mixture cooled in an ice bath. NaBH4 (81 mg, 2.143 mmol) added in one portion. Ice bath removed and mixture stirred for 3 h then cooled in an ice bath and water (˜5 mL) added. Mixture diluted with DCM (˜20 mL) and stirred vigorously for 20 mins. Layers separated and aqueous extracted with DCM. Aqueous phase basified by addition of sat NaHCO3 solution and extracted with DCM (×2). Combined organics dried and concentrated to a black foam. This material deprotected using Method E Step 2 to give the title compound after purification by hplc; 1H NMR (400 MHz, DMSO) δ 1.21 (6H, d), 3.50 (1H, sep), 4.17 (2H, s), 5.50 (2H, s), 7.51-7.53 (1H, m), 7.62-7.65 (3H, m), 8.00 (2H, d), 8.51-8.54 (3H, m), m 9.09 (1H, s) ppm; MS (ES+) 462.0.
Reaction SMILES: Br[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1.[CH3:17][C:18]1[NH:19][C:20]2[C:25]([C:26]=1[CH2:27][N:28]([CH3:33])[C:29](=[O:32])[CH:30]=[CH2:31])=[CH:24][CH:23]=[CH:22][CH:21]=2.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:33][N:28]([CH2:27][C:26]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][C:18]=1[CH3:17])[C:29](=[O:32])/[CH:30]=[CH:31]/[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7](=[O:14])[N:8]([CH2:10][CH2:11][O:12][CH3:13])[CH2:9][C:4]=2[CH:3]=1
Reactant: C=CC(=O)N(C)Cc1c(C)[nH]c2ccccc12
Reactant: COCCN1Cc2cc(Br)cnc2NC1=O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCC#N
Solvent: CCN(C(C)C)C(C)C
Product: COCCN1Cc2cc(/C=C/C(=O)N(C)Cc3c(C)[nH]c4ccccc34)cnc2NC1=O
Yield: 35.4 %

Procedure:
A solution of 6-bromo-3-(2-methoxyethyl)-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-one (0.86 g, 3.00 mmole), N-(2-methyl-1H-indol-3-ylmethyl)-N-methylacrylamide (see Example 1 (a), 0.68 g, 3.00 mmole), Pd(OAc)2 (0.07 g, 0.30 mmole), tri-ortho-tolylphosphine (0.18 g, 0.60 mmole) and diisopropylethylamine (1.31 mL, 7.50 mmole) in propionitrile (50 mL) was deoxygenated, then was heated at reflux under N2 overnight. The dark mixture was filtered through a pad of celite®, and the filter pad was rinsed with acetonitrile (250 mL). The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (10% EtOAc/EtOH). The title compound (0.46 g, 36%) was obtained as a light yellow solid after drying in vacuo: MS (ES) m/e 434 (M+H)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([OH:10])=O.[CH:11]([N:13]1[CH2:18][CH2:17][NH:16][CH:15]([CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:14]1)=[O:12].[ClH:25].[NH4+].[Cl-]>>[ClH:25].[CH:11]([N:13]1[CH2:18][CH2:17][N:16]([C:8](=[O:10])[CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH:15]([CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:14]1)=[O:12]
Reactant: O=C(O)Cc1ccccn1
Reactant: O=CN1CCNC(CN2CCCC2)C1
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Product: O=CN1CCN(C(=O)Cc2ccccn2)C(CN2CCCC2)C1

Procedure:
The compound was prepared by coupling of 2-pyridinylacetic acid with 4-formyl-2-(R,S)-[(1-pyrrolidinyl)methyl]piperazine; mp: (HCl salt) 125-128° C.; 1H NMR (free base, 200 MHz, CDCl3) δ1.5-1.7 (4H, m), 2.1-3.6 (10H, m), 3.7-4.9 (5H, m), 6.9-7.3 (2H, m), 7.6 (1H, m), 8.0 (1H, m), 8.6 (1H, m); MS (FAB) 317 (M+H)+; Anal. Calcd. for C17H24N4O2.2HCl.NH4Cl: C, 46.11; H, 6.83; N, 15.82. Found: C, 46.37; H, 6.51; N, 16.35.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11](Cl)(=[O:13])=[O:12])[CH:4]=[CH:3][CH:2]=1.[NH2:15][C:16]1[CH:17]=[C:18]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[C:19]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:20]>>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11]([NH:15][C:16]2[CH:17]=[C:18]([CH:28]=[CH:29][C:30]=2[O:31][CH3:32])[C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:20])(=[O:13])=[O:12])[CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1N
Reactant: O=S(=O)(Cl)c1cccc2cccnc12
Product: COc1ccc(C(=O)Nc2ccccc2)cc1NS(=O)(=O)c1cccc2cccnc12
Yield: 76.9 %

Procedure:
Prepared according to the procedure described for Example 126 using 8-quinolinesulfonyl chloride (0.68 g, 3.0 mmol) and 3-amino-4-methoxy-N-phenyl-benzamide (0.73 g, 3.0 mmol) to afford the product (1.0 g); m.p. 187-188° C. after trituration in diethyl ether and recrystallization from ethanol.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[C:20]1=[N:21][C:22](N)=[N:23][C:24]=2[Cl:28])(=[O:3])[CH3:2].C(ON=O)CC(C)C.[CH3:38][S:39]SC>C(#N)C>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[C:20]1=[N:21][C:22]([S:39][CH3:38])=[N:23][C:24]=2[Cl:28])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CSSC
Agent: CC(C)CCON=O
Solvent: CC#N
Product: CSc1nc(Cl)c2ncn([C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H]3OC(C)=O)c2n1
Temperature: 100 °C
Yield: 72.6 %

Procedure:
9-(2',3',5'-Tri-O-acetyl-β-D-ribofuranosyl)-2-amino-6-chloro-9H-purine (see Example 9) (4.0 g, 9.3 mmol) was dissolved in acetonitrile (100 ml). Isoamylnitrite (10.84 g, 93 mmol) was introduced followed by methyl disulphide (4.14 ml, 46 mmol) and the reaction mixture was heated at an oil bath temperature of 100° C. for 2h. The evolved gas was removed via a hypochlorite scrubber. The reaction mixture was cooled, evaporated and purified by flash chromatography on silica gel. Elution initially with dichloromethane, followed by dichloro-methane/methanol (100/1) provided 9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-methylthio-9H-purine (3.1 g, 72%) as a foam, 1H NMR (CDCl3) δ 2.12, 2.14, 2.18 (9H, 3s, 2', 3' and 5'-O-acetyl CH3), 2.66 (3H, s, --SCH3), 4.28-4.51 (3H, m, H-5'a, H-5'b and H-4'), 5.66 (1H, t, H-3'), 6.0 (1H, t, H-2'), 6.13 (1H, d, H-1'), 8.11 (1H, s, H-8).
Reaction SMILES: [C:1]([NH:8][C@@H:9]([C:13]([NH2:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[P-](F)(F)(F)(F)F.[CH2:23]([NH2:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCO>C(Cl)Cl>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([C:13](=[NH:15])[NH:30][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:10]([CH3:12])[CH3:11])([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)[C@@H](NC(=O)OC(C)(C)C)C(N)=O
Reactant: NCc1ccccc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCO
Product: CC(C)[C@@H](NC(=O)OC(C)(C)C)C(=N)NCc1ccccc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 201.6 %

Procedure:
To a stirred solution of Boc-D-Valine amide (10 g, 46 mMol) in CH2Cl2 (200 mL) was added Triethyloxoniuim hexafluorophosphate (13.0 g, 48 mMol). (The reaction started out as a suspension which gradually cleared.) The reaction was stirred for 48 h at RT, poured into a separatory funnel, washed with 1 N Na2CO3, dried (Na2SO4), filtered and concentrated under vacuum. To the remaining oil was added Benzylamine (5.0 mL, 23 mMol) and EtOH (20 mL). The reaction was stirred at 60° C. for 24 h. After cooling to RT the reaction was evaporated under vacuum. The title compound (14.16 g, >95% pure by LCMS) was obtained without purification as a pale yellow oil which eventually solidified to a waxy solid: MS (ES) m/e 306.4 (M+H)+.
Reaction SMILES: C(O[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=O)C.[OH2:20]>>[CH3:19][C:14]1[C:13]2[C:18](=[CH:4][N:6]=[C:7]3[C:8]=2[C:9](=[O:20])[CH2:10][CH:11]=[CH:12]3)[CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(=O)Nc1ccccc1-c1ccccc1C
Reactant: O
Product: Cc1cccc2cnc3c(c12)C(=O)CC=C3
Temperature: 170 °C
Yield: 65 %

Procedure:
The above compound, N-ethoxycarbonyl-2-amino-2′methyl biphenyl (6.7 g, 26 mmol) was added to polyphosphoric acid (15 g) and heated to 170° C. overnight. After cooling, water was added and the white precipitate collected by vacuum filtration to give the 10-methyl-phenanthridinone (3.5 g, 65% yield) whose structure was consistent with CGMS and NMR.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:11])=[CH:8][C:9]=1[OH:10])=O.CO.[H][H]>[Ni].[Pd].C(O)(=O)C>[CH2:2]([C:4]1[CH:5]=[CH:6][C:7]([OH:11])=[CH:8][C:9]=1[OH:10])[CH3:1]
Reactant: [H][H]
Reactant: CC(=O)c1ccc(O)cc1O
Agent: [Ni]
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: CCc1ccc(O)cc1O
Temperature: 72.5 °C
Reaction time: 8 h

Procedure:
2,4-Dihydroxy acetophenone (76 g, 0.5 mole) was charged in a 1 liter autoclave reactor along with methanol (300 ml), acetic acid (5 ml), and Raney Nickel (15.2 g washed several times with water and water/methanol) and 750 mg of Pd/C. The pH of the system was 5.0. The autoclave was checked for leaks with nitrogen. The autoclave was pressurized to 500 psi with hydrogen and stirred at 70-75° C. up to 8 hrs. During this time 97% of the theoretical value for hydrogen was consumed. The reaction was vented and the contents were filtered through a milipore filter to give a yellow solution. Concentration of this solution in vacuo gave a solid. This solid was crystalized from 1,2-dichloroethane to give 4-ethyl resorcinol in 85% isolated yield. The unreacted 2,4-dihydroxy acetophenone was recovered (−13%) from the reaction mixture and was recycled. The structure of 4-ethyl resorcinol and 2,4-dihydroxy acetophenone were characterized by NMR (see FIG. 1), Gas Chromatography (see FIG. 2), IR (See FIG. 3) and Mass spectroscopy. The mass spectroscopy indicated that the mass was 138.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[CH:7](=O)[CH2:8][CH2:9][CH3:10].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C1(C)C=CC=CC=1>[CH:7]([N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6])=[CH:8][CH2:9][CH3:10]
Reactant: CCCC=O
Reactant: O=C1CCCN1
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: Cc1ccccc1
Product: CCC=CN1CCCC1=O

Procedure:
A solution of 2-pyrrolidone (50 g, 0.588 mol), butanal (42.4 g, 0.588 mol) and P2O5 (2 g, 0.014 mol) in 300 ml toluene, were refluxed together for 10 hours using Dean-Stark apparatus to collect liberated water. The resulting solution was cooled and washed with 5% solution of sodium bicarbonate and dried over anhydrous sodium sulphate. After removing the solvent under reduced pressure, 1-(but-1-enyl) pyrrolidin-2-one (I) was obtained by distillation as a liquid. (68.2 g, 83.2%). 1H NMR (CDCl3): δ 1.02 (3H,t), 2.03-2.15 (4H, m), 2.45 (2H, t), 3.5 (2H, t), 5.01 (1H, m), and 6.85 (1H, d). 13C-NMR (CDCl3): δ 172.52, 122.91, 113.8, 45.09, 31.07, 23.03, 17.27, and 14.27. IR: 2962, 2930, 1698, 1663, 1253 Cm−1.
Reaction SMILES: [CH3:1][C:2]([CH3:13])([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3](O)=[O:4].C(Cl)(=O)C([Cl:17])=O>C(Cl)(Cl)Cl.CN(C)C=O>[CH3:1][C:2]([CH3:13])([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([Cl:17])=[O:4]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(C)(Cc1ccccc1)C(=O)O
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: CC(C)(Cc1ccccc1)C(=O)Cl
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 2,2-dimethyl-3-phenylpropanoic acid (0.856 g, 4.8 mmol) in chloroform (6 mL) at 0° C. was treated with oxalyl chloride (3.05 g, 24 mmol) and 1 drop of dimethylformamide. The reaction solution was stirred for 1 h at 0° C. The ice bath was removed and the reaction mixture stirred at room temperature over night. The solvent was removed under reduced pressure and dried under high vacuum to afford a quantitative amount of 2,2-dimethyl-3-phenylpropanoyl chloride. The oil was directly used in the following reaction.