Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@:2]1([C:18]([F:21])([F:20])[F:19])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:9]=[C:4]2[NH:3]1.[H-].[Na+].[CH3:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>O1CCCC1>[CH3:1][C@@:2]1([C:18]([F:21])([F:19])[F:20])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[N:9]=[C:4]2[N:3]1[C:27]([C:26]1[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=1[CH3:24])=[O:28]
Reactant: Cc1ccccc1C(=O)Cl
Reactant: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccccc1C(=O)N1c2nc(N3CCOCC3)cc(=O)n2C[C@@]1(C)C(F)(F)F

Procedure:
The product can be prepared as described in Example 21, but using 200 mg of (2S)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one, 31 mg of sodium hydride at 60% in oil and 101 mg of 2-methylbenzoyl chloride in 4 ml of tetrahydrofuran. After purification by silica column chromatography (eluent: CH2Cl2/MeOH; gradient from 100/0 to 97/03), 44 mg of (2S)-2-methyl-1-[(2-methylphenyl)carbonyl]-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one are obtained in the form of an ivory-coloured foam, the characteristics of which are the following:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:24]=[C:22]([OH:23])[C:20]([OH:21])=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[C:27](Cl)(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29].Cl>O.C(OCC)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:24]=[C:22]([OH:23])[C:20]([OH:21])=[CH:19][CH:18]=1)[C:13]([O:15][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C(N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)C(=O)OC(=O)[C@H](Cc1ccc(O)c(O)c1)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 62.9 %

Procedure:
N-benzyloxycarbonyl-L-dopa (3.30 g) was dissolved in a mixture of 50 ml of water and 10 ml of ethyl ether. Under stirring with ice cooling, 10 ml of a 1N sodium hydroxide aqueous solution and 10 ml of an ethyl ether solution of 1.20 g pivaloyl chloride were added dropwise at the same time over a period of 30 minutes while keeping pH at 6.0 to 8.0 After the addition was over, the mixture was stirred at room temperature for 1 hour, and diluted with 50 ml of ethyl acetate. Subsequently, 2N hydrochloric acid was added to adjust pH to 2.0. An organic layer was taken out, water-washed and dried over anhydrous magnesium sulfate. After the drying agent was separated by filtration, the solvent was evaporated under reduced pressure. When the residue was purified by silica gel column chromatography (Wakogel C-100, 120 g, eluted with methylene chloride/methanol=5/1), 2.60 g (yield 62.6%) of N-benzyloxycarbonyl-mono-O-pivaloyl-L-dopa was obtained as a pale yellow glass solid.
Reaction SMILES: C1COCC1.[S:6]1[CH:10]=[CH:9][C:8]2[C:11]([N:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23][O:24][C:25]4[N:29]([CH3:30])[N:28]=[C:27]([CH2:31][O:32][Si](C(C)(C)C)(C)C)[CH:26]=4)[CH2:17][CH2:16]3)=[CH:12][CH:13]=[CH:14][C:7]1=2.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[S:6]1[CH:10]=[CH:9][C:8]2[C:11]([N:15]3[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][CH2:23][O:24][C:25]4[N:29]([CH3:30])[N:28]=[C:27]([CH2:31][OH:32])[CH:26]=4)[CH2:19][CH2:20]3)=[CH:12][CH:13]=[CH:14][C:7]1=2
Reactant: Cn1nc(CO[Si](C)(C)C(C)(C)C)cc1OCCCN1CCN(c2cccc3sccc23)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cn1nc(CO)cc1OCCCN1CCN(c2cccc3sccc23)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 79.3 %

Procedure:
A THF solution (8 ml) of 5-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3-(tert-butyl-dimethylsilanyloxymethyl)-1-methyl-1H-pyrazole (0.75 g, 1.5 mmol) was cooled on ice and a 1M THF solution of tetrabutyl ammonium fluoride (1.7 ml) was added thereto. The mixture was stirred at room temperature for 16 hours. Ethyl acetate was added to the reaction solution, which was washed with water. The organic layer was dried over anhydrous magnesium sulfate and thereafter concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=1:0→30:1→15:1). The purified product was concentrated under reduced pressure and the residue was recrystallized from a solvent mixture of ethyl acetate and diisopropyl ether to obtain 5-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)-propoxy]-3-hydroxymethyl-1-methyl-1H-pyrazole (0.46 g, 79% yield) as white powder.
Reaction SMILES: CN(C=O)C.[H-].[Na+].[CH3:8][CH:9]([CH3:12])[CH2:10][SH:11].[NH2:13][C:14]1[N:22]=[C:21](Cl)[N:20]=[C:19]2[C:15]=1[N:16]=[CH:17][N:18]2[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>[Cl-].[Na+].O>[NH2:13][C:14]1[N:22]=[C:21]([S:11][CH2:10][CH:9]([CH3:12])[CH3:8])[N:20]=[C:19]2[C:15]=1[N:16]=[CH:17][N:18]2[CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)CS
Reactant: Nc1nc(Cl)nc2c1ncn2Cc1ccccc1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)CSc1nc(N)c2ncn(Cc3ccccc3)c2n1
Temperature: 100 °C
Yield: 31.5 %

Procedure:
To DMF suspension (10 ml) containing sodium hydride (300 mg, 7.5 mmol, 60% in mineral oil) were added 2-methylpropane-1-thiol (1 ml, 11 mmol) and 6-amino-9-benzyl-2-chloropurine (200 mg, 0.77 mmol) in order. The mixture was stirred under heating at 100° C. for 5 hours. Brine was added thereto and the mixture was extracted with chloroform. The organic layer was dried on magnesium sulfate, filtered and the solvent in the filtrate was evaporated in vacuo. The residue was purified with silica gel chromatography (1% methanol/chloroform) to give the subject compound (76 mg, yield 31%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10](=[O:12])[CH3:11])=[CH:7][C:6]=2[CH:13]=1.[C:14]([Si:18]([CH3:21])([CH3:20])Cl)([CH3:17])([CH3:16])[CH3:15].N1C=CN=C1>CN(C=O)C.[Cl-].[Na+].O>[Si:18]([O:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10](=[O:12])[CH3:11])=[CH:7][C:6]=2[CH:13]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:21])[CH3:20]
Reactant: CC(=O)c1cc2cc(O)ccc2o1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [Cl-]
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1cc2cc(O[Si](C)(C)C(C)(C)C)ccc2o1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.8 %

Procedure:
To a solution of 1-(5-hydroxy-1-benzofuran-2-yl)ethanone (1.15 g, 6.53 mmol) in DMF (10 mL) were added tert-butyldimethylchlorosilane (1.07 g, 7.18 mmol) and imidazole (666 mg, 9.80 mmol), and the mixture was stirred at room temperature overnight. To the reaction mixture was added brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 7:3) to give the title compound (1.76 g, yield 98%).
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)CCC.[Br:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23](Br)[N:22]=1>O1CCCC1.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>[CH3:9][CH2:10][CH2:11][CH:6]([CH3:7])[CH3:21].[Br:20][C:21]1[N:22]=[C:23]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:24]=[CH:25][CH:26]=1
Reactant: Brc1cccc(Br)n1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cccnc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Brc1cccc(-c2cccnc2)n1
Product: CCCC(C)C
Temperature: 25 °C
Yield: 41 %

Procedure:
3-Tributylstannylpyridine (3.3 g, 9.0 mmol) was added to a degassed solution of 2,6-dibromopyridine (2.0 g, 8.3 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.48 g, 5 mol %) in dry tetrahydrofuran (30 ml), stirred under an atmosphere of nitrogen and heated to reflux for 48 h. After cooling to ambient temperature, solvent was removed in vacuo, the residue dissolved in dichloromethane and purified by chromatography on silica gel eluting with dichloromethane on a gradient of methanol (0-4%). Trituration with isohexane gave 6-bromo-2,3′-bipyridine (0.4 g) as a solid: δH (400 MHz, CDCl3) 7.42 (1H, dd, J 8 and 8), 7.49 (1H, d, J 7), 7.65 (1H, dd, J 7 and 7), 7.73 (1H, d, J 7), 8.35 (1H, m), 8.68 (1H, m), 9.16 (1H, s); m/z (ES+) 235/236 (M++H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][O:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([NH:27][C:28]([CH:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])[CH2:23][CH2:22]2)[C:10]=1[CH3:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:38]I.O>C1COCC1.CN(C=O)C>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:19][O:20][C@H:21]2[CH2:22][CH2:23][C@H:24]([N:27]([CH3:38])[C:28]([CH:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])[CH2:25][CH2:26]2)[C:10]=1[CH3:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CI
Reactant: Cc1c(CO[C@H]2CC[C@H](NC(=O)C3CCCC3)CC2)nc2ccccc2c1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(CO[C@H]2CC[C@H](N(C)C(=O)C3CCCC3)CC2)nc2ccccc2c1OCc1ccccc1

Procedure:
To a mixed solution (10 mL) of N-(trans-4-{[4-(benzyloxy)-3-methylquinolin-2-yl]methoxy}cyclohexyl)cyclopentanecarboxamide (260 mg) in THF-DMF (1:1) was added 60% sodium hydride (45 mg) under ice-cooling, followed by stirring at the same temperature. Methyl iodide (0.055 mL) was added thereto, followed by stirring at room temperature for 3.5 hours. The reaction mixture was ice-cooled, and 60% sodium hydride (45 mg) and methyl iodide (0.055 mL) were added thereto, followed by stirring at room temperature for another 17 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=100/0˜50/50), and the solvent was evaporated under reduced pressure. The residue was dried under vacuum at room temperature to obtain 93 mg of N-(trans-4-{[4-(benzyloxy)-3-methylquinolin-2-yl]methoxy}cyclohexyl)-N-methylcyclopentanecarboxamide as a colorless viscous substance.
Reaction SMILES: [N+:1]([C:4]1[CH:42]=[CH:41][C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3([C:25]4[CH:30]=[CH:29][C:28]([CH2:31][C:32]5[CH:37]=[CH:36][C:35]([N+:38]([O-])=O)=[CH:34][CH:33]=5)=[CH:27][CH:26]=4)[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O.O.[H][H]>O1CCCC1>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3([C:25]4[CH:26]=[CH:27][C:28]([CH2:31][C:32]5[CH:33]=[CH:34][C:35]([NH2:38])=[CH:36][CH:37]=5)=[CH:29][CH:30]=4)[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[CH:41][CH:42]=1
Reactant: [H][H]
Reactant: CCCCC1CCC(c2ccc(Cc3ccc([N+](=O)[O-])cc3)cc2)(c2ccc(Cc3ccc([N+](=O)[O-])cc3)cc2)CC1
Solvent: C1CCOC1
Solvent: O
Product: CCCCC1CCC(c2ccc(Cc3ccc(N)cc3)cc2)(c2ccc(Cc3ccc(N)cc3)cc2)CC1
Yield: 41.9 %

Procedure:
1,1-Bis[4-(4-nitrobenzyl)phenyl]-4-butylcyclohexane 38.0 g was dissolved in 500 ml of tetrahydrofuran, a Pd--C catalyst (5% purity, water content 55.9%) 4.0 g was added, and the mixture was cooled with water at atmospheric pressure and contacted with hydrogen gas with stirring. After the absorption of hydrogen stopped, the catalyst was filtered off and the solution was concentrated. The concentrate was recrystallized with mixture solvent of ethanol 87% and methanol 13% to obtain 1,1-bis[4-(4-aminobenzyl)phenyl]-4-butylcyclohexane 14.22 g which is a diamino compound of the present invention. The melting point was 58.5°-60.1° C.
Reaction SMILES: [C:1](C1C=C2C(=CC=1)C(=O)CCC2(C)C)#[CH:2].Br[C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[C:23]([CH3:28])([CH3:27])[CH2:22][CH2:21][CH:20]2[O:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH:30]1([O:29][CH:20]2[C:19]3[C:24](=[CH:25][CH:26]=[C:17]([C:1]#[CH:2])[CH:18]=3)[C:23]([CH3:28])([CH3:27])[CH2:22][CH2:21]2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: CC1(C)CCC(OC2CCCCC2)c2cc(Br)ccc21
Reactant: C#Cc1ccc2c(c1)C(C)(C)CCC2=O
Product: C#Cc1ccc2c(c1)C(OC1CCCCC1)CCC2(C)C

Procedure:
Employing the same general procedure as for the preparation of 6-ethynyl-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound K), 2.1 g (8.8 mmol) of 6-bromo-4-cyclohexyloxy-1,1-dimethyl-1,2,3,4-tetrahydronaphthalene (Compound J) was converted into the title compound using 1 g (10.2 mmol) of trimethylsilyl acetylene, 0.14 g (0.20 mmol) of bis(triphenylphosphine)palladium(II) chloride, 19 mg (0.1 mmol) of cuprous iodide and 80 mg (0.6 mmol) of K2CO3.
Reaction SMILES: Br[C:2]([CH3:16])([CH3:15])[C:3]([NH:5][C:6]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[O:8][N:7]=1)=[O:4].[Na+].[CH3:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([S:28]([O-:30])=[O:29])=[CH:24][CH:23]=1)(=[O:21])=[O:20].N1C=CC=CC=1.Cl>CN(C=O)C>[C:11]([C:9]1[O:8][N:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([S:28]([C:25]2[CH:24]=[CH:23][C:22]([S:19]([CH3:18])(=[O:21])=[O:20])=[CH:27][CH:26]=2)(=[O:30])=[O:29])([CH3:16])[CH3:15])[CH:10]=1)([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(Br)C(=O)Nc1cc(C(C)(C)C)on1
Reactant: CS(=O)(=O)c1ccc(S(=O)[O-])cc1
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CC(C)(C)c1cc(NC(=O)C(C)(C)S(=O)(=O)c2ccc(S(C)(=O)=O)cc2)no1
Temperature: 50 °C
Reaction time: 18 h
Yield: 19.9 %

Procedure:
To a solution of 160 mg (0.55 mmol) of 2-bromo-N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-propionamide in DMF (3 mL) were added 181 mg (0.71 mmol) of 4-methanesulfonyl-benzenesulfinic acid sodium salt in one portion. Pyridine (48 μL) was added and the reaction was stirred at 50° C. for 18 h. The mixture was acidified with 1M aqueous HCl solution (1 mL) and extracted with diethyl ether (3×3 mL). The combined organic layers were dried over Na2SO4 and the solvent removed under reduced pressure. The crude material was purified by column chromatography (silica, eluent heptanes, 0-20% ethyl acetate) to afford 47 mg of N-(5-tert-butyl-isoxazol-3-yl)-2-(4-methanesulfonyl-benzenesulfonyl)-2-methyl-propionamide.
Reaction SMILES: [C:1](/[C:3](/[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=1)=[CH:4]\[C:5]1[S:9][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17](=[O:23])[CH2:18][CH2:19][C:20]([O-:22])=O)[CH2:12][CH2:11]2)=[CH:7][CH:6]=1)#[N:2].[Cl:34]C1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[CH2:52]([N:54]([CH2:59][CH3:60])[CH2:55][CH2:56][NH:57][CH3:58])[CH3:53]>C(Cl)Cl>[ClH:34].[CH2:52]([N:54]([CH2:59][CH3:60])[CH2:55][CH2:56][N:57]([CH3:58])[C:20](=[O:22])[CH2:19][CH2:18][C:17]([O:16][CH:13]1[CH2:12][CH2:11][N:10]([C:8]2[S:9][C:5](/[CH:4]=[C:3](\[C:1]#[N:2])/[C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[C:26]([O:32][CH3:33])[CH:25]=3)=[CH:6][CH:7]=2)[CH2:15][CH2:14]1)=[O:23])[CH3:53]
Reactant: CCN(CC)CCNC
Reactant: COc1nc(Cl)nc(OC)n1
Reactant: COc1ccc(/C(C#N)=C/c2ccc(N3CCC(OC(=O)CCC(=O)[O-])CC3)s2)cc1OC
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CCN(CC)CCN(C)C(=O)CCC(=O)OC1CCN(c2ccc(/C=C(\C#N)c3ccc(OC)c(OC)c3)s2)CC1
Product: Cl
Reaction time: 0.5 h
Yield: 76 %

Procedure:
Compound 18 (500 mg) was dissolved in methylene chloride (10 mL), and 2-chloro-4,6-dimethoxy-1,3,5-triazine (224 mg) and N-methylmorpholine (129 μL) were added to the solution, followed by stirring with ice cooling for 30 minutes. Subsequently, N,N-diethyl-N′-methylethylenediamine (166 μL) and N-methylmorpholine (215 μL) were added to the mixture, followed by stirring at room temperature for 17 hours. The solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography (CHCl3-MeOH), to thereby yield the target product (yield: 503 mg, 76%).
Reaction SMILES: [CH:1]1[C:15]2=[C:16]3[C:8]([C:9]4[C:14]2=[CH:13][CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[CH:5][C:4]3=[C:3](B(O)O)[CH:2]=1.[Br:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C1(C)C=CC=CC=1>[Br:20][C:21]1[CH:26]=[CH:25][C:24]([C:5]2[CH:6]=[CH:7][C:8]3[C:9]4[C:14]([C:15]5[C:16]=3[C:4]=2[CH:3]=[CH:2][CH:1]=5)=[CH:13][CH:12]=[CH:11][CH:10]=4)=[CH:23][CH:22]=1
Reactant: Brc1ccc(I)cc1
Reactant: OB(O)c1ccc2c3c(cccc13)-c1ccccc1-2
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: Cc1ccccc1
Product: Brc1ccc(-c2ccc3c4c(cccc24)-c2ccccc2-3)cc1
Temperature: 100 °C
Reaction time: 8 h
Yield: 69.6 %

Procedure:
In the atmosphere of argon, 9.1 g of fluoranthene-3-boronic acid, 10.5 g of 4-bromoiodobenzene, 2.1 g of tetrakis(triphenylphosphine)palladium(0), 186 mL of toluene and 74 mL of an aqueous 2M solution of sodium carbonate were placed in a flask, and stirred at 100° C. for 8 hours. After cooling to room temperature, the reaction solution was extracted with toluene. After removing an aqueous phase, an organic phase was washed with saturated saline, and dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure, and residues were purified by silica gel column chromatography, whereby 9.2 g (yield 70%) of 3-(4-bromophenyl)fluoranthene as an intended product was obtained.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9](O)=O)[CH:4]=1.C[Si](C#N)(C)C.CO[C:20]1[CH:25]=[CH:24][N+]([O-])=[CH:22][CH:21]=1.C[N:28](C)C(Cl)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:22]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9]#[N:28])[CH:4]=1)[CH2:21][CH2:20][CH2:25][CH3:24]
Reactant: COc1ccnc(C(=O)O)c1
Reactant: COc1cc[n+]([O-])cc1
Reactant: CN(C)C(=O)Cl
Agent: C[Si](C)(C)C#N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCc1ccnc(C#N)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
4-Methoxypyridine-2-carboxylic acid, compound 10(b) (R9=methoxy), was made employing general Method P. To trimethylsilyl cyanide (0.95 g, 9.6 mmol), 4-methoxypyridine N-oxide (1 g, 8 mmol) in DCM (10 mL) was added, followed by dimethylcarbamoyl chloride (1.03 g, 9.6 mmol) in DCM (10 mL), dropwise. After stirring at room temperature overnight, sodium bicarbonate (100 mL, 10%) was added, and the organic layer was separated. The aqueous layer was extracted twice by DCM (50 mL each). The combined organic layer was dried over magnesium sulfate and the solvent was removed to obtain product, compound 10a (0.97 g, 90%):
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[N:3]=1.[CH:9]([N:12]=[CH:13]C)([CH3:11])[CH3:10].[Cl-].[NH4+].O1CCC[CH2:18]1>C([Li])CCC.CCCCCC>[OH:8][C:4]1[N:3]=[C:2]([CH:1]([CH3:18])[CH2:13][NH:12][CH:9]([CH3:11])[CH3:10])[CH:7]=[CH:6][CH:5]=1
Reactant: CC=NC(C)C
Reactant: Cc1cccc(O)n1
Reactant: C1CCOC1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Product: CC(C)NCC(C)c1cccc(O)n1

Procedure:
To the solution of 10.9 g of 2-methyl-6-hydroxypyridine in 400 ml of tetrahydrofuran, 88 ml of 2.5 molar n-butyllithium in hexane are added dropwise while stirring under nitrogen at 0°. After 2 hours 10.2 g of 1-isopropyliminoethane are added rapidly and the mixture stirred for 2 hours at 0°. It is poured into 200 ml of saturated aqueous ammonium chloride, the organic layer separated and the aqueous solution extracted 4 times with 150 ml of methylene chloride. The combined organic solutions are dried, filtered, evaporated and the residue is chromatographed on 300 g of silica gel with methanoldiethyl ether (5:1) as moving phase. The eluate is evaporated, the residue taken up in ethanol, neutralized with ethanolic fumaric acid and the resulting precipitate recrystallized from ethanol, to yield the mono-fumarate of N-[2-(6-hydroxy-2-pyridyl)propyl]-isopropylamine of Formula II, with R=OH, R'=H and CpH2p±1 =CH(CH3)2, melting at 193.5°-194°.
Reaction SMILES: [CH:1]1([NH:4][C:5](=O)[O:6]C2C=CC=CC=2)[CH2:3][CH2:2]1.CS(C)=O.[C:18]1([C:24]2[NH:40][C:27]3[N:28]=[CH:29][N:30]=[C:31]([O:32][C:33]4[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=4)[C:26]=3[CH:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O>[CH:1]1([NH:4][C:5]([NH:39][C:36]2[CH:37]=[CH:38][C:33]([O:32][C:31]3[C:26]4[CH:25]=[C:24]([C:18]5[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=5)[NH:40][C:27]=4[N:28]=[CH:29][N:30]=3)=[CH:34][CH:35]=2)=[O:6])[CH2:3][CH2:2]1
Reactant: Nc1ccc(Oc2ncnc3[nH]c(-c4ccccc4)cc23)cc1
Reactant: O=C(NC1CC1)Oc1ccccc1
Solvent: O
Solvent: CS(C)=O
Product: O=C(Nc1ccc(Oc2ncnc3[nH]c(-c4ccccc4)cc23)cc1)NC1CC1
Temperature: 80 °C
Reaction time: 4 h
Yield: 11.8 %

Procedure:
After adding 30 mg of phenyl cyclopropylcarbamate and 0.5 ml of dimethylsulfoxide to 40 mg of 4-(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenylamine, the mixture was stirred at 80° C. for 4 hours. The mixture was returned to room temperature, water was added, liquid separation and extraction were performed with ethyl acetate, and the solid obtained by concentration to dryness was washed with ether to obtain 6 mg of the title compound.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH2:20])[N:3]=1.[H-].[Na+].Br[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>CN(C=O)C>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]2[O:13][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[C:4]([NH2:20])[N:3]=1
Reactant: Nc1nc(N)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1
Reactant: CCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1cnc2c(N)nc(N)nc21
Yield: 39.4 %

Procedure:
2,6-Diamino-9-(β-D-ribofuranosyl)purine (50 g, 180 mmol) was treated with sodium hydride (8.8 g, 220 mmol) and bromononane (59 g, 54.4 ml, 285 mmol) in DMF (700 ml) as per the procedure of Example 2 (the diamino compound in DMF was cooled in an ice bath during the addition of NaH) to yield 83 g of crude product. 50 g of crude product was purified by silica gel chromatography. Fraction containing 2'-O-nonyl and 3'-O-nonyl product were combined to give a 77:23 mixture (29 g) of the 2' and 3' product. Pure 2'-O-nonyl product is obtained by chromatography. 1H NMR (DMSO-d6) δ0.95 (t, 3, CH3); 1.17 [m, 12, O--CH2 --CH2 --(CH2)6 ]; 1.42 [m, 2, O--CH2CH2 (CH2)6 ]; 3.27-3.70 (m, 2, H-5'); 3.50-3.70 [m, 2, O--CH2 (CH2)7 ]; 3.95 (m, 1, H-4'), 4.24 (m, 1, H-3'); 4.40 (m, 1, H-2'); 5.10 (d, 1, 3'-OH, J=5 Hz); 5.50 (t, 1, 5'-OH, J=6 Hz); 5.76 (s, 2, 2-NH2); 5.83 (d, 1, H-1', J=6.0 Hz); 6.81 (s, 2, 6-NH2); and 7.96 (s, 1, 8-H).