Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH:21]([CH3:23])[CH3:22])(=[O:20])=[O:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[NH2:30][C:31]1[N:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1>>[O:27]1[CH2:28][CH2:29][N:24]([C:4]2[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:17][CH2:16][N:15]([S:18]([CH:21]([CH3:23])[CH3:22])(=[O:20])=[O:19])[CH2:14][CH2:13]4)=[CH:8][C:6]=3[N:7]=[C:2]([C:34]3[CH:33]=[N:32][C:31]([NH2:30])=[N:36][CH:35]=3)[N:3]=2)[CH2:25][CH2:26]1
Reactant: CC(C)S(=O)(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Reactant: CC1(C)OB(c2cnc(N)nc2)OC1(C)C
Product: CC(C)S(=O)(=O)N1CCN(Cc2cc3nc(-c4cnc(N)nc4)nc(N4CCOCC4)c3s2)CC1

Procedure:
2-Chloro-4-morpholin-4-yl-6-[4-(propane-2-sulfonyl)-piperazin-1-ylmethyl]-thieno[3,2-d]pyrimidine was reacted with 2-aminopyrimidine-5-boronic acid pinacol ester using General Procedure A. Purification on silica yielded 116. (400 MHz, CDCl3): 1.28 (6H, d (J=6.85), CH3), 2.54-2.56 (4H, m, CH2), 3.12 (1H, m, CH), 3.34-3.37 (4H, m, CH2), 3.79 (2H, s, CH2), 3.80-3.82 (4H, m, CH2), 3.94-3.97 (4H, m, CH2), 5.13 (2H, b, NH2), 7.21 (1H, s, ar), 9.21 (2H, s, ar). (M+H)+519.27
Reaction SMILES: O=[O+][O-].[Cl:4][C:5]1[CH:6]=[C:7]([N:11]2[N:15]=[N:14][C:13]([C:16]([CH3:24])=CC3C=CC=CC=3)=[N:12]2)[CH:8]=[CH:9][CH:10]=1.[O:25]=O.[BH4-].[Na+]>CO.ClCCl>[Cl:4][C:5]1[CH:6]=[C:7]([N:11]2[N:15]=[N:14][C:13]([CH:16]([OH:25])[CH3:24])=[N:12]2)[CH:8]=[CH:9][CH:10]=1
Reactant: O=O
Reactant: CC(=Cc1ccccc1)c1nnn(-c2cccc(Cl)c2)n1
Agent: O=[O+][O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CC(O)c1nnn(-c2cccc(Cl)c2)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87 %

Procedure:
Ozone was bubbled through a solution of 2-(3-chlorophenyl)-5-[1-methyl-2-phenylvinyl]-2H-tetrazole (2.73 g, 9.2 mmol) in methanol (75 mL) and dichloromethane (75 mL) at −78° C. When the color lightened and the starting material had disappeared by TLC, oxygen was bubbled through the mixture for approximately 2-3 minutes. Sodium borohydride (635 mg, 16.8 mmol) was added. The reaction was allowed to warm to room temperature, stirred for 30 minutes and quenched with water (5 mL) and saturated ammonium chloride (5 mL). After removal of the solvent in vacuo, the product was partitioned between dichloromethane and water, dried over sodium sulfate, and the solvent was removed in vacuo. Flash chromatography (15-35% ethyl acetate in hexane) yielded the title compound as a yellow solid (1.795 g, 87%). 1H NMR (CDCl3) δ (ppm): 8.19 (m, 1H), 8.06 (m, 1H), 7.50 (m, 2H), 5.3 (m, 1H), 2.54 (m, 1H), 1.78 (d, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[C:8]([CH2:19][NH2:20])=[CH:7]2.[NH2:21][C:22]1[N:30]=[C:29]2[C:25]([NH:26][CH:27]=[N:28]2)=[C:24](Cl)[N:23]=1.C(N(CC)C(C)C)(C)C>C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[C:8]([CH2:19][NH:20][C:24]1[N:23]=[C:22]([NH2:21])[N:30]=[C:29]3[C:25]=1[N:26]=[CH:27][NH:28]3)=[CH:7]2
Reactant: Nc1nc(Cl)c2[nH]cnc2n1
Reactant: NCc1cc2cccc(Cl)c2nc1-c1ccccc1Cl
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Nc1nc(NCc2cc3cccc(Cl)c3nc2-c2ccccc2Cl)c2nc[nH]c2n1
Reaction time: 8 h

Procedure:
A mixture of (8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methanamine (144.8 mg, 0.478 mmol), 2-amino-6-chloropurine (89.1 mg, 0.525 mmol) and N,N-diisopropylethylamine, redestilled, 99.5% (0.166 mL, 0.955 mmol) in 1-butanol, anhydrous, 99.8% (5.24 mL) was heated to reflux and stirred overnight. The reaction was cooled solvents removed and subjected to chromatography, 89:9:1 (DCM/MeOH,NH4OH)gradient, 1H NMR (400 MHz, DMSO-d6) δ ppm 12.08 (1H, br. s.), 8.36 (1H, s), 8.01 (1H, d, J=8.2 Hz), 7.92 (1H, d, J=6.3 Hz), 7.47-7.71 (8H, m), 5.56 (2H, br. s.), 4.59 (2H, br. s.) Mass Spectrum (ESI) m/e=436.1 (M+1).
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:16]3[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[OH:24])[N:8]=2)[CH2:3]1.N1([C:30]([O:32][CH2:33][CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][O:35]2)=[O:31])C=CN=C1.C(N(CC)CC)C>C(Cl)Cl>[OH:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:9]1[N:8]=[C:7]([N:4]2[CH2:5][CH2:6][C@@H:2]([NH:1][C:30](=[O:31])[O:32][CH2:33][CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][O:35]3)[CH2:3]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:17])=[CH:14][CH:15]=2)[N:10]=1
Reactant: Cc1ccc2c(N3CC[C@@H](N)C3)nc(-c3ccccc3O)nc2c1
Reactant: O=C(OCC1CCCCO1)n1ccnc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc2c(N3CC[C@@H](NC(=O)OCC4CCCCO4)C3)nc(-c3ccccc3O)nc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (100 mg, 0.31 mmol) and (tetrahydro-2H-pyran-2-yl)methyl 1H-imidazole-1-carboxylate (98 mg, 0.47 mmol) was added 1.04 mL CH2Cl2 and triethylamine (65 μL, 47 mg, 0.46 mmol). The mixture was stirred at room temperature overnight. An additional equivalent of (tetrahydro-2H-pyran-2-yl)methyl 1H-imidazole-1-carboxylate (100 mg, 0.47 mmol) was added to the mixture, and the reaction was heated at 45° C. for 4 hours. Purification via silica gel chromatography using 10-100% ethyl acetate/hexanes gave (tetrahydro-2H-pyran-2-yl)methyl (R)-1-(2(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate. LC/MS: m/z 463.4 (M+H)+ at 2.66 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Cl[CH2:13][C:14]([NH:16][CH2:17][CH2:18][N:19]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH3:20])=[O:15]>CN(C=O)C.CCOC(C)=O>[CH:21]1([N:19]([CH3:20])[CH2:18][CH2:17][NH:16][C:14](=[O:15])[CH2:13][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: c1ccc2[nH]ccc2c1
Reactant: CN(CCNC(=O)CCl)C1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN(CCNC(=O)Cn1ccc2ccccc21)C1CCCCC1
Temperature: 25 °C

Procedure:
Indole (20 mg, 0.17 mmol) was dissolved in DMF (400 μL) and NaH (60% dispersed in mineral oil, 9 mg, 0.22 mmol) was added and the resultant mixture was stirred at 60° C. for 30 minutes. The mixture was then cooled to room temperature to it was added crude chloride 2a (˜50 mg; excess). The reaction solution was then heated to 60° C. for 2 hours. The reaction solution was cooled to room temperature and diluted in EtOAc and the organic solution was washed with H2O (2×) and brine (1×). The organic layer was dried (MgSO4) and concentrated to provide crude 3a which was purified by preparative TLC (2:1:0.4 EtOAc/hexanes/Et3N) to give the desired product 3a (7 mg, 13% yield): LC-MS (Method B, retention time=0.448 min. MS calc'd for C19H28N3O (MH+): 314.2. Found 314.5.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH3:10])=[CH:5][CH:4]=1.Cl.[N+:13]([C:16]1[CH:24]=[CH:23][C:19]([CH2:20][O:21][NH2:22])=[CH:18][CH:17]=1)([O-:15])=[O:14]>>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([CH2:20][O:21]/[N:22]=[C:9](/[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)\[CH3:10])=[CH:23][CH:24]=1)([O-:15])=[O:14]
Reactant: COc1ccc(C(C)=O)cc1
Reactant: NOCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Product: COc1ccc(/C(C)=N/OCc2ccc([N+](=O)[O-])cc2)cc1
Yield: 67.9 %

Procedure:
4′-Methoxyacetophenone (21) (150 mg, 1.00 mmol) was condensed with compound 19 (225 mg, 1.10 mmol) according to the general procedure II-A defined above. After heating the reaction mixture for 2 h it was cooled and the resulting solid filtered off and washed with cold isopropanol (3.0 mL) to afford the title compound CP30253 (204 mg, 68%) as a pale-yellow solid, m.p. 88.2-89.5° C.
Reaction SMILES: [OH-].[Li+].C([O:5][C:6](=[O:38])[CH:7]([S:34]([CH3:37])(=[O:36])=[O:35])[CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][C:13]([S:24]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)(=[O:26])=[O:25])([C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])[CH2:12][CH2:11]1)C.Cl>O.O1CCCC1>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([S:24]([C:13]2([C:16]3[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=3[F:23])[CH2:12][CH2:11][CH:10]([CH2:9][CH2:8][CH:7]([S:34]([CH3:37])(=[O:35])=[O:36])[C:6]([OH:38])=[O:5])[CH2:15][CH2:14]2)(=[O:25])=[O:26])=[CH:28][CH:29]=1
Reactant: CCOC(=O)C(CCC1CCC(c2cc(F)ccc2F)(S(=O)(=O)c2ccc(Cl)cc2)CC1)S(C)(=O)=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CS(=O)(=O)C(CCC1CCC(c2cc(F)ccc2F)(S(=O)(=O)c2ccc(Cl)cc2)CC1)C(=O)O
Reaction time: 12 h
Yield: 82 %

Procedure:
A solution of lithium hydroxide (21 mg, 0.88 mmol) in water (700 mL) was added to the product from Example 108 (100 mg, 0.18 mmol) in tetrahydrofuran (2 mL). The resulting mixture was stirred vigorously for 12 hours, then poured into 1M aqueous hydrochloric acid (20 mL) and extracted with ethyl acetate (2×40 mL). The combined organic layers were dried (NaSO4), and concentrated. The residue was purified using column chromatography on silica, eluting with 95/5/0.5 dichloromethane/methanol/acetic acid to give the title compound (79 mg).
Reaction SMILES: O[C:2]1[C:7]2[C:8](=[O:12])O[IH](=O)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[O:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1>>[CH2:8]([O:12][C:14]1[CH:4]=[CH:3][CH:2]=[CH:7][C:15]=1[CH2:16][CH:17]=[O:13])[C:7]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1O[IH](=O)c2cccc(O)c21
Reactant: C1CCOC1
Product: O=CCc1ccccc1OCc1ccccc1

Procedure:
0.104 mol of hydroxy-1-oxo-benzo[d][1,2]iodoxol-3-one is added to 0.08 mol of [2-(2-benzyloxy)phenyl]ethanol in 500 ml of tetrahydrofuran. The reaction mixture is heated at reflux for 2 hours and then cooled. The precipitate is filtered off and the filtrate is evaporated.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:14])=[N:8][C:9](Cl)=[C:10]([Br:12])[CH:11]=1)=[O:5])[CH3:2].[OH:15][CH2:16][CH:17]1[CH2:19][CH2:18]1.C1CCN2C(=NCCC2)CC1>>[CH2:1]([O:3][C:4](=[O:5])[C:6]1[CH:11]=[C:10]([Br:12])[C:9]([O:15][CH2:16][CH:17]2[CH2:19][CH2:18]2)=[N:8][C:7]=1[CH3:14])[CH3:2]
Reactant: OCC1CC1
Reactant: CCOC(=O)c1cc(Br)c(Cl)nc1C
Solvent: C1CCC2=NCCCN2CC1
Product: CCOC(=O)c1cc(Br)c(OCC2CC2)nc1C
Temperature: 100 °C

Procedure:
A mixture of 5-bromo-6-chloro-2-methyl-3-pyridinecarboxylic acid ethyl ester (CAN 41598-77-0) (0.7 g, 2.5 mmol), hydroxymethylcyclopropane (0.57 mL, 6.2 mmol) and DBU (0.94 mL) was heated for 15 min in a microwave oven to 100° C. The reaction mixture was cooled to room temperature and partitioned between 10% citric acid and ethyl acetate. The phases were separated and the organic phase was purified by chromatography on silica gel with a cyclohexane:ethyl acetate gradient to yield the title compound as light yellow solid, MS (ISP) 314.0, 316.0 (M+H)+.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][C:9]1[CH:14]=[C:13](Cl)[C:12]([CH3:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[O:7]([C:13]1[C:12]([CH3:16])=[CH:11][C:10]([N+:17]([O-:19])=[O:18])=[C:9]([CH3:8])[CH:14]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1cc([N+](=O)[O-])c(C)cc1Cl
Reactant: Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc([N+](=O)[O-])c(C)cc1Oc1ccccc1

Procedure:
A solution of 4.44 g (47 mmol) of phenol and 8.76 g (47 mmol) of 2,5-dimethyl-4-chloro-nitrobenzene in 50 ml of DMF was admixed with 9.78 g (71 mmol) of K2CO3 and the mixture was heated under reflux for 10 h.
Reaction SMILES: Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:12]=[N:13][N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=2)[N:3]=1.[CH:24]1([CH:27]([N:31]2[CH:35]=[C:34](B3OC(C)(C)C(C)(C)O3)[CH:33]=[N:32]2)[CH2:28][C:29]#[N:30])[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COCCOC>O.CCOCC.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>[CH:24]1([CH:27]([N:31]2[CH:35]=[C:34]([C:2]3[N:7]4[CH:8]=[CH:9][N:10]=[C:6]4[CH:5]=[C:4]([C:11]4[CH:12]=[N:13][N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=4)[N:3]=3)[CH:33]=[N:32]2)[CH2:28][C:29]#[N:30])[CH2:26][CH2:25]1
Reactant: C[Si](C)(C)CCOCn1cc(-c2cc3nccn3c(Cl)n2)cn1
Reactant: CC1(C)OB(c2cnn(C(CC#N)C3CC3)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=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: O
Solvent: COCCOC
Product: C[Si](C)(C)CCOCn1cc(-c2cc3nccn3c(-c3cnn(C(CC#N)C4CC4)c3)n2)cn1
Temperature: 80 °C
Reaction time: 3.5 h
Yield: 75.1 %

Procedure:
A flask was charged with 5-chloro-7-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Step C, 150 mg, 0.429 mmol), 3-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile (Preparation P; 185 mg, 0.643 mmol) and K3PO4 (273 mg, 1.29 mmol). DME (2.5 mL) and H2O (1.5 mL) were added and the resulting solution was purged with N2 for 15 minutes. Pd(PPh3)4 (49.5 mg, 0.0429 mmol) was added, the flask sealed, and the mixture stirred at 80° C. for 3.5 hours. The mixture was cooled to ambient temperature and was diluted with H2O (5 mL). The mixture was extracted with 50% EtOAc/hexanes and the combined extracts were washed with saturated NaCl and dried over MgSO4/activated carbon. The dried solution was eluted through a SiO2 column eluting with 50% EtOAc/hexanes, EtOAc and 10% MeOH/EtOAc. The EtOAc and 10% MeOH/EtOAc pools were combined and concentrated to give a gold syrup. The syrup was dissolved in Et2O and concentrated to give the title compound (153 mg, 75.0% yield) as a brittle, light beige foam. MS (apci) m/z=475.3 (M+H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[C:16](=[O:17])[N:15]2[C@@H:10]1[CH2:11][S:12][CH:13]=[C:14]2[C:18]([O:20]CC(Cl)(Cl)Cl)=[O:19])=[O:7])([CH3:4])(C)C.Cl.[C:27](O)(=O)[CH3:28]>CN(C)C=O.O.[Zn]>[CH2:1]([O:5][C:6]([NH:8][C@H:9]1[C:16](=[O:17])[N:15]2[C@@H:10]1[CH2:11][S:12][CH:13]=[C:14]2[C:18]([OH:20])=[O:19])=[O:7])[CH2:4][CH2:27][CH3:28]
Reactant: CC(=O)O
Reactant: CC(C)(C)OC(=O)N[C@H]1C(=O)N2C(C(=O)OCC(Cl)(Cl)Cl)=CSC[C@H]12
Agent: Cl
Agent: [Zn]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCOC(=O)N[C@H]1C(=O)N2C(C(=O)O)=CSC[C@H]12
Reaction time: 3 h

Procedure:
To a solution of 43 mg (0.1 mmole) of trichloroethyl cis-7-t-butoxycarbonylamino-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate in 6 ml of dimethylformamide and 6 ml of acetic acid is added over a 1.5 hr period 250 mg (3.8 mmole) zinc dust. The mixture is stirred vigorously for 3 hrs and then diluted with 50 ml of water. The mixture is acidified with dilute HCl, filtered and extracted with ethyl acetate. The organic phase is extracted with 5% NaHCO3 which is acidified and reextracted into ethyl acetate. The final extracts are washed with brine, dried, and evaporated to give cis-7-butoxycarbonylamino-8-oxo-4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
Reaction SMILES: [CH:1]1([CH:6]=[C:7]2[CH2:16][CH2:15][C:14]3[CH:13]=[C:12]([C:17]([O:19][CH3:20])=[O:18])[CH:11]=[CH:10][C:9]=3[C:8]2=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[Cl:23][C:24]1[CH:31]=[C:30]([NH:32][NH2:33])[CH:29]=[CH:28][C:25]=1[C:26]#[N:27]>C(O)C>[Cl:23][C:24]1[CH:31]=[C:30]([N:32]2[CH:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH:7]3[C:8]([C:9]4[CH:10]=[CH:11][C:12]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][C:14]=4[CH2:15][CH2:16]3)=[N:33]2)[CH:29]=[CH:28][C:25]=1[C:26]#[N:27]
Reactant: N#Cc1ccc(NN)cc1Cl
Reactant: COC(=O)c1ccc2c(c1)CCC(=CC1CCCC1)C2=O
Agent: Cl
Solvent: CCO
Product: COC(=O)c1ccc2c(c1)CCC1C2=NN(c2ccc(C#N)c(Cl)c2)C1C1CCCC1
Temperature: 80 °C
Yield: 87.3 %

Procedure:
Methyl 6-(cyclopentylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (Preparation 18, 2.8 g, 9.9 mmol) was suspended in ethanol (100 mL) and 2-chloro-4-hydrazinylbenzonitrile hydrochloride (Preparation 1, 2.6 g, 12.8 mmol) was added. The solution was heated to 80° C. for eight hours. The solution was returned to ambient temperature. The resulting solid was collected by vacuum filtration and washed with cold ethanol to provide the title compound largely present as (±)-(3SR,3aRS)-methyl 2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate (3.75 g, 87% yield). LC/MS on 4.6×50 mm C-18 column, tR=7.45 minutes (10 to 90% acetonitrile/water over 8 minutes at 2 mL/minute with detection 254 nm, at 50° C.); ES-MS m/z 434 (M+H); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.54 (m, 6H), 1.62-1.74 (m, 1H), 1.73-1.87 (m, 1H), 1.99-2.09 (m, 1H), 2.21 (dd, J=7.79, 2.15 Hz, 1H), 2.82-2.94 (m, 2H), 3.09 (d, J=16.92 Hz, 1H), 3.54-3.66 (m, 1H), 3.84 (s, 3H), 4.95 (dd, J=9.67, 5.64 Hz, 1H), 7.19 (dd, J=9.26, 1.75 Hz, 1H), 7.39 (d, J=2.15 Hz, 1H), 7.67 (d, J=8.86 Hz, 1H), 7.82 (d, J=8.32 Hz, 1H), 7.86 (s, 1H), 8.10 (d, J=8.06 Hz, 1H).
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[Br:39][C:40]1[N:41]=[C:42]([CH:50]2[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)[N:43]2[CH:48]=[CH:47][N:46]=[C:45]([CH3:49])[C:44]=12>ClCCl.CN(C)C=O.O>[Br:39][C:40]1[N:41]=[C:42]([CH:50]2[CH2:55][CH2:54][N:53]([C:4](=[O:5])[CH2:3][N:2]([CH3:7])[CH3:1])[CH2:52][CH2:51]2)[N:43]2[CH:48]=[CH:47][N:46]=[C:45]([CH3:49])[C:44]=12
Reactant: Cc1nccn2c(C3CCNCC3)nc(Br)c12
Reactant: CN(C)CC(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1nccn2c(C3CCN(C(=O)CN(C)C)CC3)nc(Br)c12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 84.3 %

Procedure:
To N,N-dimethylglycine (0.445 mmol, 45.9 mg) in dichloromethane (1 ml) and N,N-dimethylformamide (0.5 ml). were added N,N-diisopropylethylamine (1.762 mmol, 0.291 ml) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.617 mmol, 198 mg) and stirred at room temperature for 10 minutes. Then 1-bromo-8-methyl-3-(piperidin-4-yl)imidazo[1,5-a]pyrazine (0.440 mmol, 130 mg) dissolved in dichloromethane (2 ml) and N,N-dimethylformamide (0.5 ml) was added. After stirring at room temperature for two hours water and dichloromethane were added, mixture was put on a phase separation filter and concentrated in vacuo. Purification by column chromatography (silica gel; dichloromethane with gradient 0 to 20% methanol) gave 1-(4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)piperidin-1-yl)-2-(dimethylamino)ethanone (141 mg).
Reaction SMILES: C1C2C(=O)C3C(=CC=CC=3)C(=O)C=2C=CC=1.[NH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]1[C:35]2[C:34](=[O:36])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27](=[O:37])[C:26]=2[C:25]([NH:38][CH2:39][CH2:40][CH2:41][NH2:42])=[CH:24][CH:23]=1.C(OC([NH:50][C@H:51]([C:59](O)=[O:60])[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=O)(C)(C)C.C(OC(NCC(O)=O)=O)(C)(C)C>>[NH2:42][CH2:41][CH2:40][CH2:39][NH:38][C:25]1[C:26]2[C:27](=[O:37])[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:34](=[O:36])[C:35]=2[C:22]([NH:21][CH2:20][CH2:19][CH2:18][NH:17][C:59](=[O:60])[C@H:51]([CH2:52][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[NH2:50])=[CH:23][CH:24]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: NCCCNc1ccc(NCCCN)c2c1C(=O)c1ccccc1C2=O
Agent: CC(C)(C)OC(=O)NCC(=O)O
Agent: O=C1c2ccccc2C(=O)c2ccccc21
Product: NCCCNc1ccc(NCCCNC(=O)[C@@H](N)Cc2ccccc2)c2c1C(=O)c1ccccc1C2=O

Procedure:
Example 29 was prepared by an equivalent procedure to that described for Example 24 except that the starting anthraquinone was 1,4-bis[(3-aminopropyl)amino]-anthracene-9,10-dione and N-tertiarybutoxycarbonyl-L-phenylalanine replaced N-tertiarybutoxycarbonylglycine.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2[NH:12][C:13]([NH:15][C:16]1[CH:21]=[N:20][CH:19]=[CH:18][N:17]=1)=[O:14].CC1(C)C(C)(C)OB(C2CCN(C(OC(C)(C)C)=O)CC=2)O1.[O:44]1[CH2:49][CH:48]=[C:47](B2OC(C)(C)C(C)(C)O2)[CH2:46][CH2:45]1>>[O:44]1[CH2:45][CH:46]=[C:47]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][CH:6]=[C:5]3[NH:12][C:13]([NH:15][C:16]2[CH:21]=[N:20][CH:19]=[CH:18][N:17]=2)=[O:14])[CH2:48][CH2:49]1
Reactant: CC1(C)OB(C2=CCOCC2)OC1(C)C
Reactant: O=C(Nc1cnccn1)Nc1ccnc2ccc(Br)cc12
Agent: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Product: O=C(Nc1cnccn1)Nc1ccnc2ccc(C3=CCOCC3)cc12

Procedure:
The title compound was prepared as described in example 27 step 2, substituting 1-(6-bromo-quinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea by 1-(6-bromoquinolin-4-yl)-3-(pyrazin-2-yl)urea and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate by 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][N:7]=[C:8]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>COCCOC.CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:23]1([C:2]2[C:10]3[C:5](=[CH:6][N:7]=[C:8]([C:11]4[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=4)[CH:9]=3)[NH:4][N:3]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: OB(O)c1ccccc1
Reactant: Ic1n[nH]c2cnc(-c3cccnc3)cc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Solvent: CCO
Product: c1ccc(-c2n[nH]c3cnc(-c4cccnc4)cc23)cc1
Yield: 60.2 %

Procedure:
To a solution of 3-iodo-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine from Example 4 (161 mg, 0.5 mmol) in DME:EtOH (5:1, 5 mL) was added Pd(dppf)Cl2 (20 mg), saturated solution of Na2CO3 (1 mL) and phenylboronic acid (74 mg, 0.6 mmol). The mixture was heated in argon under microwave radiation at 135 for 60 min. After cooling down, the solvent was removed under reduced pressure and the residue was purified by silica-gel column chromatography (mobile phase: EA:PE=1:1) to afford 116 (82 mg, 60%). 1H NMR (400 MHz, DMSO) δ 9.33 (s, 1H), 9.21 (s, 1H), 8.56 (s, 1H), 8.53-8.51 (m, 2H), 8.12-8.10 (m, 2H), 7.57-7.44 (m, 4H). ESI MS m/z=273.7 (M+1
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][OH:11])[C:5]([N:12]=NC2C=CC(Cl)=CC=2)=[C:4]([Cl:21])[N:3]=1.C(O)C.O>[Zn].C(O)(=O)C>[Cl:21][C:4]1[N:3]=[C:2]([NH2:1])[N:7]=[C:6]([NH:8][CH2:9][CH2:10][OH:11])[C:5]=1[NH2:12]
Reactant: Nc1nc(Cl)c(N=Nc2ccc(Cl)cc2)c(NCCO)n1
Agent: [Zn]
Solvent: CC(=O)O
Solvent: O
Solvent: CCO
Product: Nc1nc(Cl)c(N)c(NCCO)n1
Temperature: 70 °C
Yield: 18.1 %

Procedure:
To 2-amino-6-chloro-5-[(p-chlorophenyl)azo]-4-[(2-hydroxyethyl)amino]pyrimidine (3.0 g, 9.2 mmol) were added ethanol (76.0 ml), water (76.0 ml) and acetic acid (8.0 ml), and the mixture was heated to 70° C. A zinc powder (7.52 g) was added portionwise with stirring in a nitrogen stream and the mixture was stirred at the same temperature for 1.5 hours to give a solution. The reaction mixture was filtered and the solvent of the filtrate was distilled away under reduced pressure. Water was added to the residue and the mixture was extracted with chloroform, washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:methanol=20:1) to give pale-brown crystals (0.34 g, 18.3%), m.p. 164-167° C.