Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][NH:8][C:9]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:10]=2[NH2:11])=[CH:5][CH:4]=1.[N:22]#[C:23]Br>CN(C=O)C.C(N(CC)CC)C>[NH2:22][C:23]1[N:8]([CH2:7][C:6]2[CH:20]=[CH:21][C:3]([Cl:2])=[CH:4][CH:5]=2)[C:9]2[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][C:10]=2[N:11]=1
Reactant: Nc1cc(C(F)(F)F)ccc1NCc1ccc(Cl)cc1
Reactant: N#CBr
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Nc1nc2cc(C(F)(F)F)ccc2n1Cc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To an ice cooled solution of 2-(4-chlorobenzylamino)-5-trifluoromethylaniline hydrochloride (6.74 g, 20 mmol) in DMF (100 ml) and triethylamine (2.8 ml) was added cyanogen bromide (2.75 g, 26 mmol). The ice bath was removed after two hours and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with water and neutralized with an aqueous solution of sodium carbonate (5%). The product was filtered off and purified with activated charcoal and crystallization from ethanol. Yield 2.93 g (45%).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH2:4].[I-].[K+].[CH3:12][CH:13]([CH3:16])[CH2:14]O.ClCCl>O>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH:4][CH2:12][CH:13]([CH3:16])[CH3:14]
Reactant: CC(C)CO
Reactant: Nc1c(F)cccc1F
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CC(C)CNc1c(F)cccc1F
Temperature: 190 °C
Yield: 14.4 %

Procedure:
2,6-difluoroaniline (387 mg, 3 mmol), potassium iodide (996 mg, 6.00 mmol) and [Cp*IrCl2]2 (33.1 mg, 0.030 mmol) were dissolved in 2-methyl-1-propanol (3 mL, 32.4 mmol). The resulting mixture was heated by microwaves to 190° C. for 8 hours. To the reaction mixture was added dichloromethane (10 mL) and water (10 mL) and the organic phase separated (hydrophobic frit). Diethyl ether was added and the solution filtered through a silica cartridge (10 g) eluting with further diethyl ether. The filtrate was evaporated in vacuo, then purified by flash silica (Si) chromatography (using a 0-100% dichloromethane-cyclohexane gradient). The appropriate fractions were combined and concentrated to give the title product (80 mg) as a colourless oil. LCMS (M+1) 186, RT 1.26 mins.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Br:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:46])[CH:22]=2)(OC(C)(C)C)=O.O[CH2:48][CH2:49][N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1>>[Br:38][C:35]1[CH:36]=[C:37]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:27]1[C:28]([O:30][CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Br:46])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: OCCN1CCOCC1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Agent: c1ccc2[nH]ccc2c1
Product: Brc1ccc2[nH]c3c(OCCN4CCOCC4)c4[nH]c5ccc(Br)cc5c4cc3c2c1

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dibromo-6-hydroxyindolo[2,3-b]carbazole and the reagent is 4-(2-Hydroxyethyl)morpholine. 1H-NMR (400 MHz, CD3OD) δ ppm 8.44 (s, 1 H), 8.25 (d, J=2.0 Hz, 2 H), 7.42 (dd, J=8.4, 1.6 Hz, 2 H), 7.41 (d, J=2.0 Hz, 2 H), 4.42 (t, J=5.2 Hz, 2 H), 3.81 (t, J=4.8 Hz, 4H), 2.87 (t, J=5.2 Hz, 2 H), 2.70-2.60 (m, 4 H); MS (ESI) m/z 542.1 (M−H)−
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]1[NH:17][C:16]2[C:15](=[O:18])[N:13]([CH3:14])[C:12](=[O:19])[N:11]([CH3:20])[C:10]=2[N:9]=1.[CH3:21]OS(OC)(=O)=O.[OH-].[Na+]>O>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]1[N:17]([CH3:21])[C:16]2[C:15](=[O:18])[N:13]([CH3:14])[C:12](=[O:19])[N:11]([CH3:20])[C:10]=2[N:9]=1
Reactant: Cn1c(=O)c2[nH]c(NCCCCCO)nc2n(C)c1=O
Reactant: COS(=O)(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cn1c(=O)c2c(nc(NCCCCCO)n2C)n(C)c1=O

Procedure:
Beginning with 8-(5-hydroxypentylamino) theophylline in Example 3, 1.0 ml of dimethylsulfate (DMS) was added to 1.40 g of 8-(5-hydroxypentylamino) theophylline in 20 ml of water containing 0.3 g of sodiumhydroxide. The 1.0 ml DMS was added in 0.1 ml increments over of hour at: room temperature. A colorless crystalline solid separated and was collected by filtration. This solid was dried to provide 0.850 g of 8-(5-hydroxypentylamino) caffeine.
Reaction SMILES: [CH2:1]([N:3]([CH2:30][CH3:31])[C:4](=[O:29])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([N+:16]([O-])=O)[CH:14]=2)[CH2:9][CH2:8][N:7]1C(OCC1C=CC=CC=1)=O)[CH3:2].[ClH:32].CO>CO>[ClH:32].[ClH:32].[CH2:30]([N:3]([CH2:1][CH3:2])[C:4](=[O:29])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH2:16])[CH:14]=2)[CH2:9][CH2:8][NH:7]1)[CH3:31]
Reactant: CCN(CC)C(=O)CC1c2cc([N+](=O)[O-])ccc2CCN1C(=O)OCc1ccccc1
Agent: Cl
Solvent: CO
Product: CCN(CC)C(=O)CC1NCCc2ccc(N)cc21
Reaction time: 1 h

Procedure:
To a pressure bottle charged with N,N-diethyl-2-(phenylmethoxy)carbonyl-7-nitro-1,2,3,4-tetrahydroisoquinolin-1-acetamide (10 mmols) dissolved in methanol (150 ml) and saturated methanol-HCl (20 ml) was added 10% Pd--C (250 mg), and the reaction was hydrogenated for 1 h. The catalyst was removed by filtration and the solvent evaporated to yield N,N-diethyl-7-amino-1,2,3,4-tetrahydroisoquinolin-1-acetamide dihydrochloride which was used as such in the next step.
Reaction SMILES: Br[C:2]1(Br)[C:7]2=[N:8][C:9]3[C:14]([C:15](=[O:16])[N:6]2[CH2:5][CH2:4][CH2:3]1)=[CH:13][CH:12]=[CH:11][CH:10]=3.[C:18]1([NH:24][NH2:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])(=O)C.[Na+]>C(O)C>[C:18]1([NH:24][N:25]=[C:2]2[C:7]3=[N:8][C:9]4[C:14]([C:15](=[O:16])[N:6]3[CH2:5][CH2:4][CH2:3]2)=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=c1c2ccccc2nc2n1CCCC2(Br)Br
Reactant: NNc1ccccc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: O=c1c2ccccc2nc2n1CCCC2=NNc1ccccc1
Yield: 81 %

Procedure:
10.8 g. (0.03 mole) 6,6-Dibromo-6,7,8,9-tetrahydro-11-oxo-11H-pyrido[2,1-b]quinazoline and 13.0 g. (0.12 mole] of phenyl hydrazine are heated in 120 ml ethanol for 4 hours. The precipitated crystals are filtered after cooling. When evaporating the mother liquor further crystals are precipitating, which are filtered and washed with some alcohol. The combined filtered product is suspended in 150 ml. of water containing 8.4 g. (0.06 mole) of sodium acetate whereafter it is filtered and washed with water. 8.4 g. (81%) of 6-phenylhydrazono-6,7,8,9-tetrahydro-11-oxo-11H-pyrido[2,1-b]quinazoline are obtained which after recrystallization from isopropanol melts at 177°-179° C. and which does not give a degression of melting point when admixed with the product according to Example 16.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].[NH2:10][C:11]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=1[OH:20]>>[N:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:1][CH2:2][N:10]=[C:11]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][CH:12]1[OH:20]
Reactant: CC(=O)c1ccccn1
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Product: O=[N+]([O-])C1=CC(=NCCc2ccccn2)C(O)C=C1
Yield: 30 %

Procedure:
Ligand L28 was prepared following the same procedure as that used to prepare ligand L27 except that 300 μL (2 mmol) of 2-acetylpyridine were used as reagent 1 and 321 mg (2 mmol) of 2-amino-4-nitrophenol as reagent 2. 156 mg of ligand L28 were obtained as dark yellow solid with a yield of 30%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[CH3:10].C(N(C(C)C)C(C)C)C.[CH3:20][O:21][CH2:22]Cl.Cl>C(Cl)Cl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:20][O:21][CH3:22])=[CH:4][C:3]=1[CH3:10]
Reactant: COCCl
Reactant: Cc1cc(CO)ccc1Br
Agent: Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: COCOCc1ccc(Br)c(C)c1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
9.10 g of (4-bromo-3-methylphenyl)methanol was dissolved in 91 mL of methylene chloride and cooled to 5° C., to which 19.7 mL of N-ethyldiisopropylamine and 6.9 mL of chloromethyl methyl ether were successively added dropwise at 5 to 10° C., and then this mixture was stirred for 2.5 hours at room temperature. Water was added to the reaction mixture and adjusted to pH 7 with 6M hydrochloric acid, and then the organic phase was separated therefrom. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous sodium sulfate, and the solvent was distilled out under reduced pressure. The resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=5:1] to yield 10.44 g of 1-bromo-4-[(methoxymethoxy)methyl]-2-methylbenzene as yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH:5]=[CH:6][C:7]1[C:8](Cl)=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.[CH3:45][Si:46]([C:49]#[CH:50])([CH3:48])[CH3:47]>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.[Cu]I.CN(C=O)C>[CH2:1]([O:3][C:4](=[O:18])[CH:5]=[CH:6][C:7]1[C:8]([C:50]#[C:49][Si:46]([CH3:48])([CH3:47])[CH3:45])=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)[CH3:2]
Reactant: C#C[Si](C)(C)C
Reactant: CCOC(=O)C=Cc1ccc(C(F)(F)F)nc1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)C=Cc1ccc(C(F)(F)F)nc1C#C[Si](C)(C)C

Procedure:
Microwave vial was charged with 3-(2-chloro-6-trifluoromethyl-pyridin-3-yl)-acrylic acid ethyl ester (103 mg, 0.368 mmol), Pd(PPh3)2Cl2 (0.06 eq), CuI (0.06 eq), PPh3 (0.2 eq), Et3N (15 eq), (trimethylsilyl)acetylene and DMF (0.25 ml). The vial was irradiated in microwave synthesizer at 120° C. for 25 min. The contents of the vial were filtered through a Celite pad, which was washed out thoroughly with EtOAc. The filtrate was evaporated, and the residue was purified by column chromatography to 3-(6-trifluoromethyl-2-trimethylsilanylethynyl-pyridin-3-yl)-acrylic acid ethyl ester (58 mg, 46%).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][NH:9][C:10]2=[O:13])=[CH:5][CH:4]=1.Br[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([F:23])[CH:22]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.[Cu]I.O1CCOCC1>[F:23][C:21]1[CH:22]=[C:17]([N:9]2[CH:8]=[CH:7][C:6]3[C:11](=[CH:12][C:3]([C:2]([F:1])([F:14])[F:15])=[CH:4][CH:5]=3)[C:10]2=[O:13])[CH:18]=[N:19][CH:20]=1
Reactant: O=c1[nH]ccc2ccc(C(F)(F)F)cc12
Reactant: Fc1cncc(Br)c1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=c1c2cc(C(F)(F)F)ccc2ccn1-c1cncc(F)c1
Temperature: 25 °C
Yield: 46.9 %

Procedure:
7-Trifluoromethyl-2H-isoquinolin-1-one (I-29d: 0.1 g, 0.00046 mol) was reacted with 3-bromo-5-fluoropyridine (0.099 g, 0.00056 mol), 8-hydroxy quinoline (0.013 g, 0.00009 mol), K2CO3 (0.161 g, 0.0011 mol), CuI (0.017 g, 0.00009 mol) and 1,4-dioxane (5 mL) to afford the crude product. The reaction mass was cooled to room temperature, diluted with DCM, washed with ammonia solution and separated the layers. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (0.5% methanol in DCM), followed by hexane-wash afforded 66.5 mg of the product (47.14% yield).
Reaction SMILES: C([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([S:15](Cl)(=[O:17])=[O:16])=[CH:7][CH:6]=1)(=O)C.[CH2:19]([NH:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(N(CC)CC)C.[OH-].[K+].Cl>CCOCC.O.C(#N)C>[CH2:32]([N:31]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[S:15]([C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]([OH:4])=[CH:6][CH:7]=1)(=[O:16])=[O:17])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CCCCCCCCCCCCNCCCCCCCCCCCC
Reactant: CC(=O)Oc1ccc(S(=O)(=O)Cl)c2ccccc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCN(CCCCCCCCCCCC)S(=O)(=O)c1ccc(O)c2ccccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 18.1 g (0.063 mole) 1-acetoxy-4-naphthalenesulfonyl chloride, 22.4 g (0.063 mole) N,N-didodecylamine, 25 ml (18.1 g, 0.18 mole) triethylamine, and 200 ml acetonitrile was stirred at room temperature for 18 hrs. The mixture was diluted with ether and poured into water. The ether layer was separated, dried, and concentrated to 16.1 g of an amber oil, which was dissolved in 100 ml ethanol. To the solution was added 1.50 g (0.027 mole) potassium hydroxide; the mixture was stirred at room temperature for 2 days, acidified with hydrochloric acid, and diluted with water. The mixture was extracted with ether, and the extract was concentrated to 30.7 g of an amber oil, which partially crystallized.
Reaction SMILES: [O:1]([S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])S(C(F)(F)F)(=O)=O.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[O:24][C:25]3[CH:35]=[C:34]([N:36]([C:41]4[CH:46]=[CH:45][C:44](O)=[C:43]([F:48])[CH:42]=4)[S:37]([CH3:40])(=[O:39])=[O:38])[C:33]([CH:49]4[CH2:51][CH2:50]4)=[CH:32][C:26]=3[C:27]=2[C:28]([NH:30][CH3:31])=[O:29])=[CH:19][CH:18]=1.N1C=CC=CC=1.O>C(Cl)Cl>[F:15][C:12]([F:13])([F:14])[S:9]([O:1][C:44]1[CH:45]=[CH:46][C:41]([N:36]([C:34]2[C:33]([CH:49]3[CH2:51][CH2:50]3)=[CH:32][C:26]3[C:27]([C:28](=[O:29])[NH:30][CH3:31])=[C:23]([C:20]4[CH:19]=[CH:18][C:17]([Cl:16])=[CH:22][CH:21]=4)[O:24][C:25]=3[CH:35]=2)[S:37]([CH3:40])(=[O:38])=[O:39])=[CH:42][C:43]=1[F:48])(=[O:10])=[O:11]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CNC(=O)c1c(-c2ccc(Cl)cc2)oc2cc(N(c3ccc(O)c(F)c3)S(C)(=O)=O)c(C3CC3)cc12
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: CNC(=O)c1c(-c2ccc(Cl)cc2)oc2cc(N(c3ccc(OS(=O)(=O)C(F)(F)F)c(F)c3)S(C)(=O)=O)c(C3CC3)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
Tf2O (0.157 mL, 0.930 mmol) in CH2Cl2 (1 mL) was added dropwise to a suspension of 2-(4-chlorophenyl)-5-cyclopropyl-6-(N-(3-fluoro-4-hydroxyphenyl)methylsulfonamido)-N-methylbenzofuran-3-carboxamide (328 mg, 0.620 mmol) and pyridine (0.251 mL, 3.10 mmol) in CH2Cl2 (5 mL) under N2 at room temperature. The mixture was stirred at room temperature for 3 h then water was added. The mixture was extracted with CH2Cl2 and the combined organic phases were dried over Na2SO4, filtered, concentrated at reduced pressure, and purified by flash chromatography on silica gel eluted (0-40% EtOAc/hexane) to give the desired compound as a white solid (410 mg, 83% yield). LCMS (m/z, ES+)=661 (M+H+).
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=4)[C:12](=[O:23])[CH:11]3[C:24]([O:26][CH3:27])=[O:25])=[CH:4][C:3]=2[O:2]1>C1(C)C=CC=CC=1>[CH3:27][O:26][C:24]([C:11]1[C:12](=[O:23])[C:13]2[C:18]([C:10]=1[C:5]1[CH:6]=[CH:7][C:8]3[O:9][CH2:1][O:2][C:3]=3[CH:4]=1)=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][CH3:22])[CH:14]=2)=[O:25]
Reactant: CCCOc1ccc2c(c1)C(=O)C(C(=O)OC)C2c1ccc2c(c1)OCO2
Solvent: Cc1ccccc1
Product: CCCOc1ccc2c(c1)C(=O)C(C(=O)OC)=C2c1ccc2c(c1)OCO2
Temperature: 80 °C
Yield: 43.4 %

Procedure:
Methyl (1RS,2SR)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)-3-oxo-indane-2-carboxylate (26.2 g, 71 mmol) was dissolved in toluene (250 mL) and DDQ (dichlorodicyano-quinone) (16.5 g, 71 mmol) was added. The mixture was heated at 80° C. for 2 h. then cooled, filtered and the solvent removed in vacuo. The product was purified by flash column chromatography on silica gel (eluant: EtOAc/hexane, 20:80) to give the title compound as an orange solid (11.3 g, 44%); m.p. 125°-126° C. Anal. Calc. for C21H18O6 : C, 68.85; H, 4.95. Found: C, 68.45; H, 4.97.
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17](=O)[CH3:18])(=[O:9])=[O:8].[CH3:21][O:22][CH:23]([O:26][CH3:27])[CH2:24][NH2:25].C1(C)C(S(O)(=O)=O)=CC=CC=1.O>C1(C)C=CC=CC=1>[CH3:21][O:22][CH:23]([O:26][CH3:27])[CH2:24][N:25]=[C:17]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:10][S:7]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH3:20])(=[O:9])=[O:8])[CH3:18]
Reactant: CC(=O)c1ccccc1NS(=O)(=O)c1ccccc1C
Reactant: COC(CN)OC
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: O
Solvent: Cc1ccccc1
Product: COC(CN=C(C)c1ccccc1NS(=O)(=O)c1ccccc1C)OC

Procedure:
33.8 g of o-tolylsulfonylaminoacetophenone, 13.7 g of aminoacetaldehyde dimethylacetal and 0.4 g of toluenesulfonic acid in 400 ml of toluene are boiled for 4 hours in a water separator and concentrated to dryness in vacuo.
Reaction SMILES: Br[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:21]=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:7]=1)=[O:4].[C:22]([O-:25])(=[O:24])[CH3:23].[Na+]>C(#N)C.C(OCC)(=O)C>[C:22]([O:25][CH2:2][C:3](=[O:4])[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[CH:21]=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)[CH:7]=1)(=[O:24])[CH3:23]
Reactant: O=C(CBr)Nc1cccc(-c2cnc3ccccc3n2)c1
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(=O)OCC(=O)Nc1cccc(-c2cnc3ccccc3n2)c1
Yield: 74.6 %

Procedure:
A solution of 2-bromo-N-(3-(quinoxalin-2-yl)phenyl)acetamide (100 mg, 0.292 mmol) and sodium acetate (159 mg, 1.168 mmol) in acetonitrile (5 mL) was heated in microwave at 140° C. for 7.5 min. The dark-yellow solution was diluted with ethyl acetate (25 mL), washed with water (20 mL), dried over sodium sulphate and the solvent evaporated to afford 2-oxo-2-(3-(quinoxalin-2-yl)phenylamino)ethyl acetate (70 mg, 74% yield). LCMS calculated for C18H15N3O3 (M+H): 322.33. found 322. 1H-NMR (DMSO-d6, 400 Mhz) δH: 10.3 (1H, br.), 9.51 (1H, s), 8.52 (1H, m), 8.15-8.20 (2H, m), 8.08-8.10 (1H, m), 7.82-8.00 (3H, m), 7.55-7.60 (1H, m), 4.70 (2H, s), 2.15 (3H, s).
Reaction SMILES: NC1[C:3]([O:12][CH3:13])=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[C:6]([Br:8])[CH:7]=1.IC.C(=O)([O-])[O-].[K+].[K+].[CH3:22][N:23]([CH3:26])[CH:24]=O>C(OCC)(=O)C.O>[Br:8][C:6]1[CH:7]=[C:24]([N:23]([CH3:26])[CH3:22])[C:3]([O:12][CH3:13])=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=1
Reactant: COc1c(N)cc(Br)cc1C(C)=O
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CCOC(C)=O
Product: COc1c(C(C)=O)cc(Br)cc1N(C)C
Temperature: 65 °C
Reaction time: 2 h

Procedure:
A mixture of 1-(3-amino-5-bromo-2-methoxyphenyl)-1-ethanone (12.8 g), iodomethane (60 mL), potassium carbonate (14.4 g) and N,N-dimethylformamide (200 mL) was stirred at 60 to 70° C. for 2 hours. Water was added to the mixture, extraction was performed with ethyl acetate, and the organic layer was washed with brine and then dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (9.6 g) as a yellow oil.
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:14][N:15]([CH3:33])[C:16]([C:18]1[N:27]([CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:21]2[N:22]=[C:23](Cl)[N:24]=[CH:25][C:20]=2[CH:19]=1)=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+].CCCCCCC>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:14][N:15]([CH3:33])[C:16]([C:18]1[N:27]([CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[C:21]2[N:22]=[C:23]([NH:13][C:10]3[CH:9]=[CH:8][C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:12][N:11]=3)[N:24]=[CH:25][C:20]=2[CH:19]=1)=[O:17]
Reactant: CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCC1
Reactant: Nc1ccc(N2CCOCC2)cn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: CCCCCCC
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCOCC4)cn3)nc2n1C1CCCC1
Temperature: 110 °C
Reaction time: 1 h
Yield: 88 %

Procedure:
A mixture of 5-Morpholin-4-yl-pyridin-2-ylamine (0.61 g, 3.4 mmol; prepared using methods similar to those described in Example A and Example B), 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (1.00 g, 3.4 mmol), BINAP (106 mg, 0.17 mmol), palladium(II) acetate (38 mg, 0.17 mmol) and cesium carbonate (1.6 g, 4.9 mmol) in dioxan (20 mL) is heated to 110° C. for 6 h. After cooling to room temperature, heptane (30 mL) is added and the mixture is stirred for 1 h. The resulting suspension is filtered and the filtercake is suspended in water with vigorous stirring. The resulting suspension is again filtered and the filtercake is washed with water then diethylether before being dried in vacuo to provide 7-Cyclopentyl-2-(5-morpholin-4-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide as a tan solid (1.30 g, 88%) MS (ESI) m/z=436.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[O:22][CH:23]=[CH:24][CH:25]=2)[O:18][C:19]=1[CH3:20])[C:5](OCC)=[O:6].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[O:22][CH:23]=[CH:24][CH:25]=2)[O:18][C:19]=1[CH3:20]
Reactant: CCOC(=O)c1ccc(OCc2nc(-c3ccco3)oc2C)c(Cl)c1
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1oc(-c2ccco2)nc1COc1ccc(CO)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.5 %

Procedure:
To a solution of ethyl 3-chloro-4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}benzoate (9.50 g) in tetrahydrofuran (200 mL) was added lithium aluminum hydride (1.00 g) at 0° C. and the mixture was stirred at room temperature for 1 hr. Sodium sulfate decahydrate (8.47 g) was added to the reaction mixture, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate and the precipitate was filtered off. The filtrate was concentrated to give (3-chloro-4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}phenyl)methanol as colorless crystals (7.68 g, yield 91%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 143-144° C.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4](Br)=[CH:5][CH:6]=1.C([Sn](CCCC)(CCCC)[N:13]1[CH:17]=[CH:16][CH:15]=[N:14]1)CCC>C1(C)C=CC=CC=1.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>[Br:1][C:2]1[S:3][C:4]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)=[CH:5][CH:6]=1
Reactant: CCCC[Sn](CCCC)(CCCC)n1cccn1
Reactant: Brc1ccc(Br)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Brc1ccc(-n2cccn2)s1
Yield: 30.6 %

Procedure:
A solution containing 2,5-dibromothiophene (5.0 mL, 10.3 g, 44.4 mmol), 2-(tri-n-butylstannyl)pyrazole (4.09 g, 11.0 mmol), tetrakis(triphenylphosphine)palladium (0) (0.67 g, 0.58 mmol) in toluene (50 mL) was heated under reflux under an argon atmosphere for 6 h. The solution was evaporated and the residue was subjected to flash chromatography on silica using a gradient of 0-25% ethyl acetate/hexane as the eluant. Evaporation of the product-containing fractions gave the sub-title compound (771 mg) as a solid, m/z 241, 243 (MH+).