Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS[C:3](=[NH:8])[NH:4][N+:5]([O-:7])=[O:6].[CH2:9]([NH:11][CH2:12][CH3:13])[CH3:10]>C(#N)C>[CH2:9]([N:11]([CH2:12][CH3:13])[C:3]([NH:4][N+:5]([O-:7])=[O:6])=[NH:8])[CH3:10]
Reactant: CSC(=N)N[N+](=O)[O-]
Reactant: CCNCC
Solvent: CC#N
Product: CCN(CC)C(=N)N[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 6 h
Yield: 53.1 %

Procedure:
To a mixture of 1.35g of S-methyl-N-nitroisothiourea and 5ml of acetonitrile was added 0.88g of diethylamine, followed by stirring for 6 hours in an oil bath of 60° C. The reaction mixture was concentrated and the residue was purified by a column chromatography [developing solvent: dichloromethanemethanol (20:1)] to afford 0.85g of N,N-diethyl-N'-nitroguanidine as a white solid.
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH2:6][CH2:5]1.[C:28](O)(=[O:32])[CH:29]([CH3:31])[CH3:30]>>[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH2:6][CH2:5]1
Reactant: CC(C)C(=O)O
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4c3CCO4)CC2)CC1
Agent: Cl
Product: CC(C)C(=O)N[C@H]1CC[C@H](CCN2CCN(c3nccc4c3CCO4)CC2)CC1

Procedure:
The title compound, white solid (62 mg, 62%), MS (ISP) m/z=401.5 [(M+H)+], mp 219° C., was prepared in accordance with the general method of example 32 from trans-4-{2-[4-(2,3-dihydrofuro[3,2-c]pyridin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexanamine trihydrochloride (intermediate C) (110 mg, 0.25 mmol) and isobutyric acid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][NH2:9])[C:5]([O:10][CH3:11])=[CH:4][N:3]=1.C(O)(C)C.[N:16]#[C:17]Br.C([O-])([O-])=O.[Na+].[Na+]>O>[NH2:16][C:17]1[N:7]2[C:2]([Cl:1])=[N:3][CH:4]=[C:5]([O:10][CH3:11])[C:6]2=[N:8][N:9]=1
Reactant: N#CBr
Reactant: COc1cnc(Cl)nc1NN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)O
Product: COc1cnc(Cl)n2c(N)nnc12
Temperature: 42 °C
Reaction time: 3.5 h
Yield: 173.2 %

Procedure:
A 5 liter (L) 3-neck round bottom flask with thermowell was fitted with a condenser/N2 inlet, mechanical stirrer and an addition funnel. The pot was charged with 2-chloro-4-hydrazino-5-methoxypyrimidine (136 g of 70.7 wt. %, 96 g active, 0.55 mol) and isopropyl alcohol (IPA; 1100 mL). Cyanogen bromide (185 g of 34.6 wt. % in CH3CN, 64 g active, 0.6 mol) was added rapidly causing a slow endotherm from 22 to 15° C. and then a slow exotherm to 27° C. During the exotherm the mixture goes through a very thick stage which lasts several minutes. The slurry was then warmed to 42° C. and held there for 3.5 h at which time high pressure liquid chromatography (HPLC) analysis indicated the reaction was complete. The slurry was cooled to room temperature and treated with a solution of Na2CO3 (64 g, 0.6 mol) in water (1100 mL) over a 30 minute (min) period causing the temperature to exotherm 4° C. The mixture was stirred at ambient temperature for 2 h and then the solid was collected by filtration. The filter cake was washed with water (400 mL) and then pressed as dry as possible under aspirator pressure. This provided the title compound (190.1 g of wet cake, 51 wt % by HPLC, 97 g active, 88%) as a brown solid. Drying a sample to a constant weight resulted in the following data: MS(GC, 70eV) 201(15%), 200 (30%), 199 (70%), 198 (100%); 1 H NMR (300 MHz, DMSO-d6) 3.92 (s, 3H), 6.51 (br s, 2H), 7.11 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][NH2:12].[CH:13]1([C:20]2[CH:29]=[CH:28][C:23]3[NH:24][C:25](=[O:27])[O:26][C:22]=3[CH:21]=2)[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1>>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][NH:12][C@H:16]1[CH2:17][CH2:18][C@H:13]([C:20]2[CH:29]=[CH:28][C:23]3[NH:24][C:25](=[O:27])[O:26][C:22]=3[CH:21]=2)[CH2:14][CH2:15]1
Reactant: NCCCc1ccc(F)cc1Cl
Reactant: O=C1CCC(c2ccc3[nH]c(=O)oc3c2)CC1
Product: O=c1[nH]c2ccc([C@H]3CC[C@H](NCCCc4ccc(F)cc4Cl)CC3)cc2o1

Procedure:
Condensation of 3-(2-Chloro-4-fluorophenyl)-1-propylamine (1.5 g, 6.5 mmol) and ketone 5 (1.5 g, 6.5 mmol), following the procedure described in Example 1, gave 6-{trans-4-[3-(2-chloro-4-fluorophenyl)-propylamino]cyclohexyl}-3H-benzoxazol-2-one (535 mg, 21%), as a white solid: 1H NMR (500 MHz, DMSO-d6): δ 7.41-7.35 (m, 2H), 7.17-7.13 (m, 2H), 6.99-6.94 (m, 2H), 3.60-2.90 (br s, 2H), 2.72 (t, J=8 Hz, 2H), 2.59 (t, J=8 Hz, 2H), 2.49-2.40 (m, 2H), 1.95 (br d, J=12 Hz, 2H), 1.77 (br d, J=12 Hz, 2H), 1.69-1.66 (m, 2H), 1.44 (dddd, J=13, 13, 13, 3 Hz, 2H), 1.13 (dddd, J=13, 13, 13, 3 Hz, 2H).
Reaction SMILES: C[O-].[Na+].[C:4](=[O:9])(OC)[O:5]C.[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:26]=[C:25]3[C:20]([CH2:21][CH2:22][CH2:23][C:24]3=O)=[CH:19][CH:18]=2)=[CH:13][CH:12]=1>>[CH3:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:26]=[C:25]3[C:20]([CH2:21][CH2:22][C:23]([C:4]([OH:5])=[O:9])=[CH:24]3)=[CH:19][CH:18]=2)=[CH:15][CH:16]=1
Reactant: COC(=O)OC
Reactant: Cc1ccc(-c2ccc3c(c2)C(=O)CCC3)cc1
Agent: C[O-]
Agent: [Na+]
Product: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CC3)cc1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A mixture of sodium methoxide (5.63 g), dimethyl carbonate (33 ml) and 7-(4-methylphenyl)-1-tetralone (4.93 g) was refluxed for 30 minutes. The reaction mixture was cooled to 0° C., and to the mixture was gradually added 3Nhydrochloricacid(80 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in THF (30 ml), and to the mixture was added sodium boron hydride (494 mg) at 0° C. and then was dropwise added methanol (3 ml) for 30 minutes. The reaction mixture was stirred at 0° C. for 4 hours, and to the mixture was added water (500 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in methanol (20 ml), and to the mixture was added IN sodium hydroxide (20 ml). The mixture was refluxed for 4 hours, cooled, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in Diglyme (20 ml), and to the mixture was added concentrated hydrochloric acid (4 ml). The mixture was stirred at 100° C. for 2 hours, and to the mixture was added water (500 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, and concentrated under reduced pressure. The residue was dissolved in 0.5N sodium hydroxide (400 ml), and the mixture was washed with diethylether. The aqueous layer was separated and acidified with concentrated hydrochloric acid. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give 7-(4-methyl-phenyl)-3,4-dihydronaphthalene-2-carboxylic acid (1.96 g) as pale brown crystals.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[NH2:7][C:8]1[N:12]([CH2:13][CH2:14][O:15][C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:11]=[CH:10][C:9]=1[C:35]#[N:36].[F-].[Na+].ClCCl>O1CCCC1.O>[NH2:7][C:8]1[N:12]([CH2:13][CH2:14][O:15][C:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:11]=[CH:10][C:9]=1[CH2:35][NH2:36]
Reactant: N#Cc1cnn(CCOC(c2ccccc2)(c2ccccc2)c2ccccc2)c1N
Agent: [Al+3]
Agent: [F-]
Agent: [H-]
Solvent: O
Solvent: ClCCl
Solvent: C1CCOC1
Product: NCc1cnn(CCOC(c2ccccc2)(c2ccccc2)c2ccccc2)c1N
Yield: 77.2 %

Procedure:
To a suspension of lithium aluminum hydride (4.89 g, 129 mmol) in tetrahydrofuran (318 ml) was added 5-amino-1-[2-(trityloxy)ethyl]pyrazole-4-carbonitrile (25.4 g, 64.4 mmol) at room temperature. The mixture was stirred under reflux for 12 hours. After cooling on an ice bath, sodium fluoride (25.4 g), tetrahydrofuran (100 ml), dichloromethane (200 ml) and water (10 ml) were added to the reaction mixture. The insoluble materials were removed by filtration. The filtrate was concentrated in vacuo to give {5-amino-1-[2-(trityloxy)ethyl]pyrazol-4-yl}methylamine (19.8 g) as a solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:17][C:18]([C:20]2[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[CH:22][CH:21]=2)=[O:19])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7](C1CCCCO1)[CH:6]=2.[CH3:28][C:29]1[NH:40][C:32]2=[N:33][CH:34]=[CH:35][C:36](B(O)O)=[C:31]2[CH:30]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CO.O>[CH3:27][CH:25]([N:24]1[C:20]([C:18]([NH:17][C:4]2[CH:3]=[C:2]([C:36]3[CH:35]=[CH:34][N:33]=[C:32]4[NH:40][C:29]([CH3:28])=[CH:30][C:31]=34)[CH:10]=[C:9]3[C:5]=2[CH:6]=[N:7][NH:8]3)=[O:19])=[CH:21][CH:22]=[N:23]1)[CH3:26]
Reactant: CC(C)n1nccc1C(=O)Nc1cc(Br)cc2nn(C3CCCCO3)cc12
Reactant: Cc1cc2c(B(O)O)ccnc2[nH]1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Solvent: C1COCCO1
Product: Cc1cc2c(-c3cc(NC(=O)c4ccnn4C(C)C)c4cn[nH]c4c3)ccnc2[nH]1
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
A microwave vial was charged with N-[6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide (70 mg), (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (29 mg), tripotassium phosphate (103 mg) and Solvias catalyst (9 mg), 1,4-dioxane (1.2 ml) and water (0.24 ml). The reaction was heated under microwave irradiation at 100° C. for 30 min, twice. Further (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (10 mg) and Solvias catalyst (9 mg) were added and the reaction heated under microwave irradiation at 100° C. for 30 min. Again further (2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)boronic acid (11 mg), tripotassium phosphate (30 mg) and Solvias catalyst (9 mg) were added and the reaction heated under microwave irradiation at 100° C. for 30 min. The reaction was passed through a silica cartridge, preconditioned with methanol, washing with methanol. The solvent was evaporated and the residue was dissolved in DMSO:methanol (1:1, v/v) and purified by MDAP (Method A). Appropriate fractions were evaporated to dryness, dissolved in methanol (2 ml) and 2 M HCl (aq) (0.5 ml) and left at room temperature for 30 min. The solvent was evaporated, the residue was dissolved in DMSO:methanol (1:10, v/v) and passed through an aminopropyl cartridge preconditioned with methanol, washing with methanol. The solvent was evaporated and the residue was purified by MDAP (method A). Purified fractions were evaporated to dryness, dissolved in methanol, passed through an aminopropyl cartridge preconditioned with methanol, washing with methanol, then evaporated to dryness to give title compound, 19 mg.
Reaction SMILES: [CH:1]1([NH:7][C:8]2[N:13]3[N:14]=[C:15]([NH2:17])[N:16]=[C:12]3[CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:18]1([CH2:23][CH2:24][C:25]2[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][N:26]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1>>[CH:1]1([NH:7][C:8]2[N:13]3[N:14]=[C:15]([NH:17][C:29](=[O:30])[C:28]4[CH:32]=[CH:33][C:25]([CH2:24][CH2:23][N:18]5[CH2:22][CH2:21][CH2:20][CH2:19]5)=[N:26][CH:27]=4)[N:16]=[C:12]3[CH:11]=[CH:10][CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Nc1nc2cccc(NC3CCCCC3)n2n1
Reactant: O=C(Cl)c1ccc(CCN2CCCC2)nc1
Product: O=C(Nc1nc2cccc(NC3CCCCC3)n2n1)c1ccc(CCN2CCCC2)nc1

Procedure:
The title compound was prepared following procedure described for intermediate B1 but starting from N5-cyclohexyl[1,2,4]triazolo[1,5-a]pyridine-2,5-diamine ((A9), 116 mg; 0.5 mmol; 1.0 eq.) and 6-(2-pyrrolidin-1-ylethyl)nicotinoyl chloride (239 mg, 1.0 mmol; 2.0 eq.) as a white powder (130 mg, 60%). HPLC, Rt: 2.67 min. (purity 99.9%). LC/MS, M+(ESI): 434.1, M−(ESI): 432.1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:12]([C:13]([N:15]3[CH2:20][CH2:19][C:18]([CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)([CH2:21][N:22]4[C:26]([CH3:28])([CH3:27])[CH2:25][O:24][C:23]4=[O:29])[CH2:17][CH2:16]3)=[O:14])[CH2:11][C@@H:10]([N:36]([CH3:52])S(C3C=CC([N+]([O-])=O)=CC=3[N+]([O-])=O)(=O)=O)[CH2:9]2)=[CH:4][CH:3]=1.C(N)CC>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:9][C@H:10]([NH:36][CH3:52])[CH2:11][C@H:12]2[C:13]([N:15]2[CH2:20][CH2:19][C:18]([CH2:21][N:22]3[C:26]([CH3:27])([CH3:28])[CH2:25][O:24][C:23]3=[O:29])([CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)[CH2:17][CH2:16]2)=[O:14])=[CH:4][CH:3]=1
Reactant: CN([C@@H]1C[C@@H](C(=O)N2CCC(CN3C(=O)OCC3(C)C)(C3CCCCC3)CC2)[C@H](c2ccc(Cl)cc2)C1)S(=O)(=O)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Solvent: CCCN
Solvent: ClCCl
Product: CN[C@@H]1C[C@@H](C(=O)N2CCC(CN3C(=O)OCC3(C)C)(C3CCCCC3)CC2)[C@H](c2ccc(Cl)cc2)C1
Temperature: 25 °C
Yield: 31.4 %

Procedure:
A 10 mL round bottom flask equipped with a magnetic stir bar was charged with 0.184 g (0.24 mmol) of the product of Step G dissolved in 2 mL of methylene chloride and the reaction mixture was stirred at room temperature. Propylamine (50 μL, 0.49 mmol) was added via syringe and the reaction mixture developed an intense yellow color. Stirring was continued an additional 15 min, at which point TLC analysis (75% ethyl acetate-hexanes) revealed complete reaction of the starting material. The reaction mixture was concentrated in vacuo, and the residue was applied to two 1000 micron preparative TLC plates. Elution of the plates with a mixture of methylene chloride-methanol-14.8 N aqueous ammonium hydroxide (90:9:1) followed by recovery of the product band from the silica gel afforded 0.040 g of the title compound.
Reaction SMILES: [H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5](C)=O.CS(C1[N:17]=[N:18][C:19]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:21]=1)(=O)=O>C1COCC1>[C:22]1([C:20]2[N:21]=[C:5]([CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])[N:17]=[N:18][C:19]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CS(=O)(=O)c1nnc(-c2ccccc2)c(-c2ccccc2)n1
Reactant: CCOC(=O)CC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)Cc1nnc(-c2ccccc2)c(-c2ccccc2)n1
Temperature: 60 °C
Reaction time: 0.25 h

Procedure:
To a suspension of NaH (41 mg, 1.61 mmol) in THF (2 ml) at 0° C. was added ethyl acetoacetate (105 mg. 0.80 mmol) dropwise. After the mixture was stirred for 15 min, a solution of 3-(methylsulfonyl)-5,6-diphenyl-1,2,4-triazine (Compound 87) (250 mg, 0.80 mmol) in THF (3 ml) was cannulated into the solution, and the resulting solution was heated to 60° C. for 2 hours. The reaction was then quenched with water. The product was extracted with ethyl acetate. The organic layer was washed with water, and brine, and dried over Na2SO4. The filtered solvent was concentrated in vacuo, and the residue was purified by silica gel chromatography (20% ethyl acetate in hexane) to give title compound as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[O:9][CH2:8][CH2:7][C:6]=2[CH:14]=1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[C:28]([O:29][CH:30]3[CH2:34][CH2:33][O:32][CH2:31]3)=[CH:27][CH:26]=[CH:25][C:24]=2[F:35])[C:19]([Cl:36])=[CH:18][N:17]=1>>[Cl:36][C:19]1[C:20]([NH:22][C:23]2[C:28]([O:29][CH:30]3[CH2:34][CH2:33][O:32][CH2:31]3)=[CH:27][CH:26]=[CH:25][C:24]=2[F:35])=[N:21][C:16]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH3:12])[C:10](=[O:13])[O:9][CH2:8][CH2:7][C:6]=3[CH:14]=2)=[N:17][CH:18]=1
Reactant: Fc1cccc(OC2CCOC2)c1Nc1nc(Cl)ncc1Cl
Reactant: CN1C(=O)OCCc2cc(N)ccc21
Product: CN1C(=O)OCCc2cc(Nc3ncc(Cl)c(Nc4c(F)cccc4OC4CCOC4)n3)ccc21

Procedure:
Title compound was prepared from 2-Amino-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one and (2,5-Dichloro-pyrimidin-4-yl)-[2-fluoro-6-(tetrahydro-furan-3-yloxy)-phenyl]-amine in an analogous manner to Example 1221d. Title compound was isolated as a pale yellow solid (28 mg, 32%) HPLC purity=99%, LCMS=502.27 (M+H), HNMR (DMSO) 9.37 (s, 1H), 8.55 (bs, 1H), 8.11 (s, 1H), 7.37-7.34 (m, 2H), 7.23 (d, J=7.8 Hz, 1H), 7.00-6.95 (m, 3H), 5.00 (bt, 1H), 4.26-4.23 (m, 2H), 3.81-3.77 (m, 1H), 3.62-3.59 (m, 2H), 3.57-3.53 (m, 1H), 3.19 (s, 3H), 2.62-2.59 (m, 2H), 2.06-2.01 (m, 1H), 1.81-1.78 (m, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:33][N:32]=[C:31]2[C:7]=1[CH2:8][CH:9]1[CH:22]3[CH:13]([C:14]4[CH:15]=[CH:16][C:17]([O:23]CC5C=CC=CC=5)=[CH:18][C:19]=4[CH2:20][CH2:21]3)[CH2:12][CH2:11][C:10]12[CH3:34])=[O:5])[CH3:2]>[Pd].C1COCC1.C(O)C>[CH2:1]([O:3][C:4]([C:6]1[NH:33][N:32]=[C:31]2[C:7]=1[CH2:8][CH:9]1[CH:22]3[CH:13]([C:14]4[CH:15]=[CH:16][C:17]([OH:23])=[CH:18][C:19]=4[CH2:20][CH2:21]3)[CH2:12][CH2:11][C:10]12[CH3:34])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1[nH]nc2c1CC1C3CCc4cc(OCc5ccccc5)ccc4C3CCC21C
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CCOC(=O)c1[nH]nc2c1CC1C3CCc4cc(O)ccc4C3CCC21C
Reaction time: 72 h

Procedure:
Palladium on charcoal (100 mg, 5%Pd) was added to a solution of 2-Benzyloxy-6a-methyl-4b,5,6,6a,8,10,10a,10b,11,12-decahydro-7,8-diaza-pentaleno[2,1-a]phenanthrene-9-carboxylic acid ethyl ester (913 mg, 2.0 mmol, CAB03049) in THF (30 mL) and ethanol (30 mL). The resulting mixture was stirred under a hydrogen-atmosphere (balloon) for 72 hours, filtered through a 3 cm layer of celite and concentrated under reduced pressure. The residue was crystallised from acetone/cyclohexane. Yield: 602 mg (82%) pale yellow crystals. 1H-NMR (DMSO-d6, 400 MHz), δ: 0.92 (s, 3H, —CH3), 1.12-2.84 (m, 16H), 4.14-4.40 (m, 2H, OCH2CH3), 6.45 (d, J=2.3 Hz, 1H), 6.50 (dd, J=8.6, 2.3 Hz, 1H), 7.05,(d, J=8.6 Hz, 1H), 9.01 (s, 1H, —OH), 13.07 (s, 1H, NH). LRMS (FAB+): 367.2 (100, [M+H]+). HRMS (FAB+): 367.203796 C22H27N2O3 requires 367.202168
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[C:18]1([S:24](Cl)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:18]1([S:24]([NH:1][C:2]2[N:7]=[C:6]3[C:8]([CH:11]4[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]4)=[CH:9][NH:10][C:5]3=[CH:4][CH:3]=2)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CN1CCC(c2c[nH]c3ccc(N)nc23)CC1
Reactant: O=S(=O)(Cl)c1ccccc1
Product: CN1CCC(c2c[nH]c3ccc(NS(=O)(=O)c4ccccc4)nc23)CC1
Yield: 76.5 %

Procedure:
Beginning with 0.40 gm (1.74 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.267 mL (2.09 mMol) phenylsulfonyl chloride, 0.493 gm (76%) of the title compound were prepared as an orange solid essentially by the procedure described in Example 4. An analytical sample was crystallized from aqueous ethanol.
Reaction SMILES: Cl.Cl.[Cl:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([CH2:14][S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[C:9]=1[CH3:22].[CH2:23]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl>C(#N)C.O>[ClH:3].[CH2:23]([N:30]1[CH2:35][CH2:34][N:33]([CH2:4][CH2:5][CH2:6][S:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH2:14][S:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[C:9]=2[CH3:22])[CH2:32][CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: Cc1c(SCCCCl)ccnc1CSc1ccccn1
Reactant: c1ccc(CN2CCNCC2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC#N
Solvent: O
Product: Cc1c(SCCCN2CCN(Cc3ccccc3)CC2)ccnc1CSc1ccccn1
Yield: 81 %

Procedure:
4-(3-Chloropropylthio)-3-methyl-2-[(2-pyridinylthio)methyl]-pyridine dihydrochloride (0.59 g; 1.5 mmol) is stirred at 100° C. for 24 h in acetonitrile (10 ml) with benzylpiperazine (2.0 mmol) with addition of potassium carbonate (7.5 mmol) and catalytic amounts of sodium iodide. After addition of water, the mixture is extracted with dichloromethane (2×10 ml), the combined organic phases are washed with water, dried and concentrated, and the crude product (yellow oil) is chromatographed on silica gel. The pure product fractions are combined, concentrated, dissolved in ethanol and treated with 3.5 equivalents of conc. hydrochloric acid. The precipitated solid is filtered off, washed with diisopropyl ether and dried. The title compound is obtained as colorless crystals; m.p. 170-172° C.; yield 81% of theory.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([OH:27])[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][C:35](B(O)O)=[CH:36][CH:37]=2)[CH:32]=[CH:31]1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Si:1]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([O:27][C:35]2[CH:34]=[C:33]3[C:38](=[CH:37][CH:36]=2)[N:30]([CH3:29])[CH:31]=[CH:32]3)[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: C[C@@H](CO[Si](C)(C)C(C)(C)C)Oc1cc(O)cc(C(=O)Nc2ccn(C)n2)c1
Reactant: Cn1ccc2cc(B(O)O)ccc21
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@@H](CO[Si](C)(C)C(C)(C)C)Oc1cc(Oc2ccc3c(ccn3C)c2)cc(C(=O)Nc2ccn(C)n2)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 47.9 %

Procedure:
A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (202 mg, 0.5 mmol), 1-methylindole-5-boronic acid (131 mg, 0.75 mmol), copper (II) acetate (138 mg, 0.75 mmol), triethylamine (0.35 mL, 2.5 mmol) and freshly activated 4A molecular sieves (1 g) in DCM (10 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through Celite, washed with DCM (2×10 mL), the DCM removed in vacuo and the residual oil partitioned between ethyl acetate (25 mL) and water (25 mL). The ethyl acetate layer was separated, washed with aqueous sodium hydrogen carbonate solution, brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 40% ethyl acetate in iso-hexane, to give the desired compound (128 mg).