Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH2:7][C:8]2[C:16]3[O:15][CH2:14][C:13](=[O:17])[C:12]=3[CH:11]=[CH:10][C:9]=2[O:18][CH3:19])=[C:5]([CH3:20])[NH:4][N:3]=1.[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([CH:30]=O)=[N:22]1.N1CCCCC1>CO>[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](/[CH:30]=[C:14]2\[O:15][C:16]3[C:8]([CH2:7][C:6]4[C:2]([CH3:1])=[N:3][NH:4][C:5]=4[CH3:20])=[C:9]([O:18][CH3:19])[CH:10]=[CH:11][C:12]=3[C:13]\2=[O:17])=[N:22]1
Reactant: O=Cc1n[nH]c2ccccc12
Reactant: COc1ccc2c(c1Cc1c(C)n[nH]c1C)OCC2=O
Solvent: C1CCNCC1
Solvent: CO
Product: COc1ccc2c(c1Cc1c(C)n[nH]c1C)O/C(=C\c1n[nH]c3ccccc13)C2=O
Temperature: 60 °C
Reaction time: 2 h
Yield: 61.7 %

Procedure:
A solution of 7-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-6-methoxybenzofuran-3(2H)-one (0.0427 g, 0.157 mmol) in methanol (0.6 mL) was added with 1H-indazole-3-carboxaldehyde (0.0229 g, 0.157 mmol) and piperidine (0.0107 g, 0.126 mmol), and the mixture was stirred at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, and the precipitated solid was collected by filtration to obtain (Z)-2-[(1H-indazol-3-yl)methylene]-7-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-6-methoxybenzofuran-3(2H)-one (0.0388 g, 61%).
Reaction SMILES: Cl[C:2]1[C:11]2[N:12]=[C:13]([CH2:27][O:28][CH2:29][CH3:30])[N:14]([CH2:15][CH2:16][N:17]3[C:21]4([CH2:25][CH2:24][CH2:23][CH2:22]4)[O:20][N:19]=[C:18]3[CH3:26])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH3:31]>CO>[CH2:29]([O:28][CH2:27][C:13]1[N:14]([CH2:15][CH2:16][N:17]2[C:21]3([CH2:25][CH2:24][CH2:23][CH2:22]3)[O:20][N:19]=[C:18]2[CH3:26])[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:31])[C:11]=2[N:12]=1)[CH3:30]
Reactant: N
Reactant: CCOCc1nc2c(Cl)nc3ccccc3c2n1CCN1C(C)=NOC12CCCC2
Solvent: CO
Product: CCOCc1nc2c(N)nc3ccccc3c2n1CCN1C(C)=NOC12CCCC2

Procedure:
The methods described in Part H of Example 10 were used to treat 4-chloro-2-(ethoxymethyl)-1-[2-(3-methyl-1-oxa-2,4-diazaspiro[4,4]non-2-en-4-yl)ethyl]-1H-imidazo[4,5-c]quinoline (770 mg, 1.80 mmol) with a solution of 7 M ammonia in methanol (20 mL) and isolate and purify the final product to provide 700 mg of 2-(ethoxymethyl)-1-[2-(3-methyl-1-oxa-2,4-diazaspiro[4,4]non-2-en-4-yl)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine as white needles, mp 211-213° C.
Reaction SMILES: [CH2:1]([C:4]1([O:17][CH2:18][CH:19]=[CH2:20])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)C=C>ClCCl.C=CC1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Ru]Cl>[O:17]1[C:4]2([CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:8][CH2:9]2)[CH2:1][CH:20]=[CH:19][CH2:18]1
Reactant: C=CCOC1(CC=C)CCN(C(=O)OC(C)(C)C)CC1
Agent: Cl[Ru]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C=Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC2(CC=CCO2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.9 %

Procedure:
Solutions of 1,1-dimethylethyl 4-(2-propenyl)-4-(2-propenyloxy)-1-piperidinecarboxylate (Description 130, 4.9 g, 17.4 mmol) in dichloromethane (1.2 L) and bis(tricyclohexylphosphine)benzylidine ruthenium (IV) dichloride (717 mg, 0.87 mmol) in dichloromethane (1.2 L) were added dropwise simultaneously to dichloromethane (600 mL) over a period of 8 hours, and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with 9:1 isohexane:ethyl acetate, to give the title compound (3.3 g, 75%). m/z (ES+) 254 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.[CH2:18]([N:25]=[C:26]=[S:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([NH:25][C:26]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)=[S:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: S=C=NCc1ccccc1
Reactant: CN1CCC(c2c[nH]c3ccc(N)cc23)CC1
Product: CN1CCC(c2c[nH]c3ccc(NC(=S)NCc4ccccc4)cc23)CC1
Yield: 68.6 %

Procedure:
Beginning with 15.0 mg (0.0655 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole and 14.63 mg (0.098 mMol) benzyl isothiocyanate, 17.0 mg (86%) of the title compound were recovered.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[N:8]([C:9]([C:11]2[N:12]=[C:13]([CH3:23])[S:14][C:15]=2[C:16]2[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=2)=[O:10])[CH2:7][C@H:6]2[C@@H:4]1[CH2:5]2.[C:24]1([C:34](O)=[O:35])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1>>[CH3:23][C:13]1[S:14][C:15]([C:16]2[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=2)=[C:11]([C:9]([N:8]2[CH2:7][C@H:6]3[C@H:4]([CH2:5]3)[C@H:3]2[CH2:2][NH:1][C:34]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][N:25]=2)=[O:35])=[O:10])[N:12]=1
Reactant: O=C(O)c1nccc2ccccc12
Reactant: Cc1cccc(-c2sc(C)nc2C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CN)c1
Product: Cc1cccc(-c2sc(C)nc2C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2nccc3ccccc23)c1

Procedure:
prepared by reaction of ((1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone with Isoquinoline-1-carboxylic acid.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][OH:8])[CH:5]=[N:4][CH:3]=[N:2]1.[CH2:9]=[O:10]>>[OH:10][CH2:9][C:5]1[N:1]([CH2:6][CH2:7][OH:8])[N:2]=[CH:3][N:4]=1
Reactant: C=O
Reactant: OCCn1cncn1
Product: OCCn1ncnc1CO
Temperature: 135 °C
Yield: 68 %

Procedure:
A solution of 2-(1,2,4-triazol-1yl)ethanol (5.0 g, 44 mmol) in 38% w/v aqueous formaldehyde (25 ml) was stirred and heated at 135° C. in a sealed tube for 18 hours. Upon cooling the volatiles were removed in vacuo (azeotroping with ethanol). The residue was purified by chromatography on silica gel, eluting with 5→10→15% methanol-dichloromethane to give the title compound (4.3 g, 68%) as a thick oil. 1H NMR (360 MHz, d6-DMSO) δ 3.69-3.74 (2H, m), 4.24 (2H, t, J=5.7 Hz), 4.60 (2H, d, J=5.7 Hz), 4.96 (1H, t, J=5.3 Hz), 5.51 (1H, t, J=5.8 Hz), 7.84 (1H, s); MS (ES+) m/e 144 [MH]+.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)[Br:21].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([CH3:36])([CH3:35])[CH:33]=O)=[CH:28][CH:27]=1>C(Cl)Cl.[Zn]>[Br:21][C:20]([Br:24])=[CH:36][C:32]([C:29]1[CH:28]=[CH:27][C:26]([Cl:25])=[CH:31][CH:30]=1)([CH3:33])[CH3:35]
Reactant: CC(C)(C=O)c1ccc(Cl)cc1
Reactant: BrC(Br)(Br)Br
Agent: [Zn]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C=C(Br)Br)c1ccc(Cl)cc1
Yield: 66.9 %

Procedure:
A solution of triphenyl phosphine (89.34 g, 0.34 mol) in methylene chloride is added dropwise to a mixture of zinc powder (22.27 g, 0.34 mol) and carbon tetrabromide (112.8 g, 0.34 mol) in methylene chloride at 20° C. over one hour. The resultant mixture is stirred at room temperature overnight, treated dropwise with a solution of 2-(p-chlorophenyl)-2-methylpropionaldehyde (31.1 g, 0.17 mol) in methylene chloride over 20 minutes, refluxed for 2 days, and poured into petroleum ether. The organic mixture is filtered through diatomaceous earth and concentrated in vacuo to obtain a residue. The residue is distilled to give the title product as an oil (38.5 g, bp 121°-123° C./0.3 mm Hg, 66.8% yield).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][OH:23])[CH2:18][CH2:17]1)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>ClCCl>[CH2:6]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][O:23][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:18][CH2:17]1)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CS(=O)(=O)Cl
Reactant: O=C(OCc1ccccc1)N1CCC(CO)CC1
Solvent: ClCCl
Product: CS(=O)(=O)OCC1CCN(C(=O)OCc2ccccc2)CC1
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A solution of methanesulphonylchloride (7.7 ml) in dichloromethane (50 ml) was added dropwise to a stirred solution of 1-benzyloxycarbonyl-4-hydroxymethylpiperidine (23.4 g) in dichloromethane (350 ml) cooled to 5° C. Stirring was continued for 1 hour, then the solution was washed with water (4×150 ml) and saturated aqueous sodium chloride (100 ml), dried and concentrated. The residue was crystallised from tetrachloromethane (250 ml) to give 1-benzyloxycarbonyl-4-methanesulphonyloxymethylpiperidine (20 g) as colourless prisms, m.p. 72°-74° C. NMR (CDCl3): δ 1.1-1.4(2H,m); 1.7-1.8(2H,d); 1.9-2.1(1H,m); 2.7-2.9(2H,t); 3.0(3H,s); 4.05(2H,d); 4.1-4.4(2H,d); 5.1(2H,s); 7.3(5H,m); m/e 328(M+H)+ 350 (M+Na)+ ; calculated for C15H21N5O5 : C, 55.0; H, 6.5; N, 4.3; found: C, 54.8; H, 6.6; N, 4.2%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1I.[Br:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[SH:18]>>[Br:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[S:18][C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[F:1]
Reactant: Cc1ccc(I)c(F)c1
Reactant: Fc1ccc(S)c(Br)c1
Product: Cc1ccc(Sc2ccc(F)cc2Br)c(F)c1

Procedure:
Prepared from 2-fluoro-1-iodo-4-methyl-benzene and 2-bromo-4-fluoro-benzenethiol.
Reaction SMILES: [C:1]1([N:7]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[S:8]([C:11]2[CH:30]=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:38].C(O)C.C(=O)([O-])[O-].[NH4+:46].[NH4+]>ClCCl.C(O)C>[ClH:38].[C:1]1([N:7]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[S:8]([C:11]2[CH:30]=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:46])[NH2:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)(=[O:9])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CCN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cc1)n2C
Reactant: [NH4+]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)CCN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C
Yield: 87 %

Procedure:
Prepared analogously to Example 25d from 1-methyl-2-[N-(4-cyanophenyl)aminomethyl]benzimidazol-5-yl-sulfonic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide, ethanolic hydrochloric acid, ethanol, and ammonium carbonate. Yield: 87% of theory, C27H30N6O4S (534.6); Rf value: 0.13 (silica gel; dichloromethane/ethanol=9:1); EKA mass spectrum: (M+H)+=535; (M+H+Na)++=279.
Reaction SMILES: [N:1]([C:4]1[C:13]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:5]=1[F:30])=[N+]=[N-].[H][H]>CO.[Pd]>[NH2:1][C:4]1[C:13]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:5]=1[F:30]
Reactant: [H][H]
Reactant: COC(=O)c1cc(SCc2ccccc2)c(N=[N+]=[N-])c(F)c1Nc1ccccc1Cl
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(SCc2ccccc2)c(N)c(F)c1Nc1ccccc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.9 %

Procedure:
To a solution of methyl 4-azido-5-(benzylthio)-3-fluoro-2-((2-chlorophenyl)amino)benzoate (9.84 g, 22.23 mmol) in MeOH (200 mL) was added and 10% palladium on carbon (1.55 g) under nitrogen atmosphere. Then the nitrogen atmosphere was completely changed to hydrogen atmosphere. The mixture was stirred for 2 h at ambient temperature. After the insoluble matter was filtered off, the solvent was evaporated in vacuo to give the desired product (9.26 g, 100%). 1H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 7.54 (s, 1H), 7.45 (m, 1H), 7.24 (m, 6H), 6.95 (m, 1H), 6.77 (m, 1H), 6.27 (s, 2H), 3.95 (s, 2H), 3.73 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH2:9]([O:11][C:12]([Sn](CCCC)(CCCC)CCCC)=[CH2:13])[CH3:10]>CN(C=O)C.CCOC(C)=O.[F-].[K+].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>[Br:8][C:5]1[CH:4]=[N:3][C:2]([C:9]([O:11][CH2:12][CH3:13])=[CH2:10])=[CH:7][N:6]=1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: Brc1cnc(Br)cn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=C(OCC)c1cnc(Br)cn1
Temperature: 100 °C
Reaction time: 0.33 h
Yield: 67.6 %

Procedure:
To a solution of 2,5-dibromopyrazine (1 g, 4.20 mmol) in DMF was added 1-ethoxyvinyltri-n-butyltin (1.420 mL, 4.20 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.148 g, 0.210 mmol). The reaction mixture was heated at 100° C. for 4 hrs. The reaction mixture was diluted with EtOAc and aq. KF. The two phase mixture was stirred for 20 min at rt before being filtered through diatomaceous earth (Celite®). The filtrate was washed with sat. NaHCO3, sat. NaCl, dried over anhydrous Na2SO4, concentrated. The crude product was purified by silica gel chromatography (0-100% EtOAc in hexane) to yield 2-bromo-5-(1-ethoxyvinyl)pyrazine (0.65 g). LC/MS (Cond. N-1): [M+H]+ 229.05, RT=3.799 min.
Reaction SMILES: [CH2:1]([N:8]1[C:14](=[O:15])[C:13]2[CH:16]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH:18]=[CH:19][C:12]=2[NH:11][C:10](=[O:30])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:31]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[CH2:1]([N:8]1[C:14](=[O:15])[C:13]2[CH:16]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH:18]=[CH:19][C:12]=2[N:11]([CH3:31])[C:10](=[O:30])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CN(Cc2ccccc2)C(=O)c2cc(-c3ccc(C(F)(F)F)cc3)ccc2N1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: CN1C(=O)CN(Cc2ccccc2)C(=O)c2cc(-c3ccc(C(F)(F)F)cc3)ccc21
Temperature: 60 °C
Reaction time: 2 h
Yield: 17.7 %

Procedure:
4-Benzyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (9.80 mg, 0.024 mmol) and K2CO3 (10 mg, 0.072 mmol, 3.0 equiv.) were placed in a 0.5-2 mL Smith process vial under a nitrogen atmosphere. To the vial were added DMF (0.5 mL) and iodomethane (2.25 μL, 0.036 mmol, d=2.28 g/cm3, 1.5 equiv) at room temperature. After heating, stirred, at 60° C. for 2 hours, the reaction mixture was concentrated en vacuo. The resulting crude mixture was diluted with acetonitrile (1 mL), filtered through a syringe filter and injected into a preparative HPLC to give desired product (4-benzyl-1-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione, 1.8 mg) as a yellow film.
Reaction SMILES: [CH2:1]([O:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:15]([O:22][C@H:23]1[CH2:32][C@H:31](O)[C@H:30]2[C:25]([CH:26]=[CH:27][C@H:28]([CH3:51])[C@@H:29]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH2:37]2)=[CH:24]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>>[Si:15]([O:22][C@H:23]1[CH2:32][C@H:31]([O:11][C:10](=[O:12])[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)([CH3:14])[CH3:13])[C@H:30]2[C:25]([CH:26]=[CH:27][C@H:28]([CH3:51])[C@@H:29]2[CH2:34][CH2:35][C@H:36]2[O:41][C:40](=[O:42])[CH2:39][C@H:38]([O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:45])[CH3:46])[CH2:37]2)=[CH:24]1)([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:17])[CH3:16]
Reactant: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Reactant: CC(C)(OCc1ccccc1)C(=O)O
Product: C[C@H]1C=CC2=C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](OC(=O)C(C)(C)OCc3ccccc3)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Yield: 78.8 %

Procedure:
A procedure similar to that described in Example 10, above, was followed, but using 705 mg of 2-benzyloxy-2-methylpropionic acid and 1.0 g of (4R,6R)-6-{(1S,2S,6S,8S,8aR)-2-[1,2,6,7,8,8a-hexahydro-6-t-butyldimethylsilyloxy-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyldimethylsilyloxy-2H-pyran-2-one [prepared as described in Example B, above], to give 1.04 g of the title compound as white crystals, melting at between 135° and 136° C.
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][N:19]=[C:18](F)[CH:17]=4)[N:12]=[CH:11][C:10]=3[N:9]([CH3:23])[C:8](=[O:24])[C@H:7]2[CH2:25][CH3:26])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:27]([CH3:29])[CH3:28].Cl.C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([N:27]([CH3:29])[CH3:28])[CH:17]=4)[N:12]=[CH:11][C:10]=3[N:9]([CH3:23])[C:8](=[O:24])[C@H:7]2[CH2:25][CH3:26])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CNC
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(-c3ccnc(F)c3)nc2N1C1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CC[C@@H]1C(=O)N(C)c2cnc(-c3ccnc(N(C)C)c3)nc2N1C1CCCC1
Temperature: 140 °C
Yield: 61 %

Procedure:
To the solution of (R)-8-cyclopentyl-7-ethyl-2-(2-fluoropyridin-4-yl)-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 16, 200 mg, 0.56 mmol) in 5 mL of DMSO, (CH3)2NH HCl (200 mg 5.6 mmol) and Na2CO3 (130 mg, 1.2 mmol) were added. The mixture was heated to 140° C. for 18 hr in a sealed tube, quenched with water and extracted with EtOAc. The combined organic phase was dried with Na2SO4, concentrated under reduced pressure, and chromatographed (CH2Cl2:CH3OH=15:1) to give the title compound as a white solid (130 mg, 60% yield). 1H NMR (CDCl3) δ: 8.27 (d, 1H), 7.97 (s, 1H) 7.49 (s, 1H), 7.43 (d, 1H), 4.35-4.29 (m, 2H), 3.39 (s, 3H), 3.18 (s, 6H), 2.1-1.7 (m, 10H) and 0.87 ppm (t, 3H); LCMS: 381.3 m/z (M+H)+; ret. Time: 1.44 min (Analytical Method E).
Reaction SMILES: BrC1C=CC=C2C=1C(C1C(O)=CC3OCOC=3C=1)[C:5](=[O:16])N2CCCCC.[OH:27][C:28]1[C:29]([CH:37]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][C:47]3[CH:48]=[C:49]([CH:54]=[CH:55][CH:56]=3)[C:50]([O:52][CH3:53])=[O:51])[C:38]2=[O:57])=[CH:30][C:31]2[O:35][CH2:34][O:33][C:32]=2[CH:36]=1>>[OH:27][C:28]1[C:29]([C:37]2([CH2:5][OH:16])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][C:47]3[CH:48]=[C:49]([CH:54]=[CH:55][CH:56]=3)[C:50]([O:52][CH3:53])=[O:51])[C:38]2=[O:57])=[CH:30][C:31]2[O:35][CH2:34][O:33][C:32]=2[CH:36]=1
Reactant: CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Reactant: COC(=O)c1cccc(CN2C(=O)C(c3cc4c(cc3O)OCO4)c3ccccc32)c1
Product: COC(=O)c1cccc(CN2C(=O)C(CO)(c3cc4c(cc3O)OCO4)c3ccccc32)c1

Procedure:
Following the procedure as described in PREPARATION 1E, and making non-critical variations to replace 4-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one with methyl 3-{[3-(6-hydroxy-1,3-benzodioxol-5-yl)-2-oxo-2,3-dihydro-1H-indol-1-yl]methyl}benzoate, the title compound was obtained (81%) as a white powder: MS (ES+) m/z 470.3 (M+23), 448.3 (M+1).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][NH2:13])[CH:7]=1.C(NC(C)C)(C)C.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([S:28](Cl)(=[O:30])=[O:29])[CH:23]=1.Cl>ClCCl>[CH3:2][O:3][C:4](=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][NH:13][S:28]([C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)(=[O:30])=[O:29])[CH:7]=1
Reactant: O=S(=O)(Cl)c1cccnc1
Reactant: COC(=O)Cc1cccc(CN)c1
Agent: Cl
Solvent: CC(C)NC(C)C
Solvent: ClCCl
Product: COC(=O)Cc1cccc(CNS(=O)(=O)c2cccnc2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (3-aminomethyl-phenyl)-acetic acid methyl ester hydrochloride (from Preparation 18, 0.56 g) and diisopropylamine (2.2 mL) in 10 mL dichloromethane was added pyridine-3-sulfonyl chloride (from Preparation 2, 0.601 g, 2.83 mmol) and the reaction was stirred at room temperature for 16 h. Aqueous 1N HCl was added and the solution was washed with CH2Cl2. The organic solution was washed with saturated NaHCO3, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound. Purification via flash chromatography on silica gel (2:1 hexanes:EtOAc) afforded the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.71 (d, 1H), 8.04 (d, 1H), 7.37 (m, 1H), 7.05-7.24 (m, 4H), 5.87 (bs, 1H), 4.14 (s, 2H), 3.62 (s, 3H), 3.52 (s, 2H).
Reaction SMILES: [CH:1]([C:3]1[S:7][C:6]([C:8]2[S:9][C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][CH:12]=2)=[CH:5][CH:4]=1)=[O:2].O.[C:19](OCC)(=O)[CH3:20]>C1COCC1>[OH:2][CH:1]([C:3]1[S:7][C:6]([C:8]2[S:9][C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][CH:12]=2)=[CH:5][CH:4]=1)[CH2:19][CH3:20]
Reactant: O=Cc1ccc(-c2ccc(-c3cccs3)s2)s1
Reactant: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CCC(O)c1ccc(-c2ccc(-c3cccs3)s2)s1
Temperature: 0 °C
Reaction time: 1 h
Yield: 70 %

Procedure:
3.5 g of 5-formyl-2,2':5',2"-terthiophene was dissolved in 200 ml of anhydrous THF under nitrogen stream. 7.9 ml of ethyl Grignard reagent was dropped in slowly under ice bath temperature and stirred at 0° C. for 1 hour. The reaction mixture was then heated to 70° C. in oil bath for 4 hours. The solution was monitored by thin layer chromatography to determine whether the reaction was completed. 50 ml of water and 300 ml of ethyl acetate were added and the ethyl acetate extract was purified by column chromatography. From the eluate of ethyl acetate/n-hexane (1/9) fraction, yellow solid was obtained and recrystallized to give granulate crystal. The melting point of the product was 89°-90° C. and the yield was about 70%.
Reaction SMILES: [CH2:1]([CH2:4][NH:5][C:6]([CH3:10])([CH3:9])[CH2:7][NH2:8])[CH:2]=[CH2:3].[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[Cl:21])[C:15](Cl)=[O:16]>C1C=CC=CC=1.C(OCC)(=O)C>[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[Cl:21])[C:15]([NH:8][CH2:7][C:6]([NH:5][CH2:4][CH2:1][CH:2]=[CH2:3])([CH3:10])[CH3:9])=[O:16]
Reactant: C=CCCNC(C)(C)CN
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: C=CCCNC(C)(C)CNC(=O)c1ccc(Cl)c(Cl)c1

Procedure:
A mixture of 2-allylmethylamino-2-methylpropylamine (1.3 g.,) and 3,4-dichlorobenzoyl chloride (3.15 g.,) was heated under reflux in dry benzene (150 ml.) for 1 hrs. The cooled mixture was washed with dilute sodium hydroxide solution (2 × 30 ml.), water (2 × 30 ml.), dried (MgSO4) and the solvent was removed in vacuo to give a yellow oil (3.9 g.). The oil was passed through a column of alumina 40 × 2.5 cm. using ethyl acetate as an eluent to give 3,4-dichloro-N-(2-allylmethylamino-2-methylpropyl)-benzamide as a pale yellow liquid (2.25 g., 71%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:26]4[C:25]5[N:24]=[CH:23][CH:22]=[CH:21][C:20]=5[N:19]=[CH:18][C:17]=4[N:16]=[C:15]3[CH3:27])[O:10][N:9]=2)=[CH:4][CH:3]=1.C1C=C(Cl)C=C(C(OO)=[O:36])C=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:26]4[C:25]5[N:24]=[CH:23][CH:22]=[CH:21][C:20]=5[N+:19]([O-:36])=[CH:18][C:17]=4[N:16]=[C:15]3[CH3:27])[O:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1nc2cnc3cccnc3c2n1Cc1cc(-c2ccc(F)cc2)no1
Product: Cc1nc2c[n+]([O-])c3cccnc3c2n1Cc1cc(-c2ccc(F)cc2)no1

Procedure:
The method described in Part E of Example 12 was used to treat 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-2-methyl-1H-imidazo[4,5-c][1,5]naphthyridine (1.15 g, 3.20 mmol) with mCPBA (0.94 g of 75% pure material followed by 0.25 g) to provide 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-2-methyl-5-oxido-1H-imidazo[4,5-c][1,5]naphthyridine as a dark yellow solid.