Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[S:6][C:5]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=2)=[O:8])=[CH:4][CH:3]=1.[CH2:18](O)[CH2:19][OH:20].C1(C)C(S(O)(=O)=O)=CC=CC=1>C1(C)C=CC=CC=1>[N+:15]([C:12]1[CH:13]=[CH:14][C:9]([C:7]2([C:5]3[S:6][CH:2]=[CH:3][CH:4]=3)[O:20][CH2:19][CH2:18][O:8]2)=[CH:10][CH:11]=1)([O-:17])=[O:16]
Reactant: OCCO
Reactant: O=C(c1ccc([N+](=O)[O-])cc1)c1ccc(Cl)s1
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1ccc(C2(c3cccs3)OCCO2)cc1

Procedure:
If one were to take 2 grams (12 mMole) of commercially available (5-chloro-thiophen-2-yl)-(4-nitro-phenyl)-methanone 1 (Reike Metals, Lincoln, Nebr.) and heat it under anhydrous conditions with an excess of ethylene glycol and catalytic amounts of toluene sulfonic acid in toluene, one would obtain the protected 2-(4-nitro-phenyl)-2-thiophen-2-yl-[1,3]dioxolane (2).
Reaction SMILES: [CH2:1]1[C:3]2([CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]2)[CH2:2]1.[H-].[Na+].[CH2:12]([O:14][C:15](=O)[O:16]CC)[CH3:13]>CN(C)C=O>[O:9]=[C:6]1[CH2:7][CH2:8][C:3]2([CH2:2][CH2:1]2)[CH2:4][CH:5]1[C:15]([O:14][CH2:12][CH3:13])=[O:16]
Reactant: CCOC(=O)OCC
Reactant: O=C1CCC2(CC1)CC2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1CC2(CCC1=O)CC2
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 35.9 %

Procedure:
To a stirred solution of spiro[2.5]octan-6-one (prepared according to the procedure reported in US2008176926) (0.900 g, 7.25 mmol) in dimethylformamide (10 ml) at 5° C. was added sodium hydride (0.580 g, 60%, 14.50 mmol) under a nitrogen atmosphere over a period of 10 min and the resulting mixture was stirred for an additional 20 min at the same temperature. To this reaction mixture, diethylcarbonate (1.72 g, 14.50 mmol) was added at 5° C. and stirred for 1 h and then allowed to stir at room temperature for 2 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to 0° C. and quenched with saturated ammonium chloride (10 ml) and diluted with water (30 ml). The resulting mixture was extracted with diethyl ether (2×20 ml), and the combined organic layer was washed with water (2×20 ml), dried over anhydrous sodium sulphate, filtered, and the solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh) using 1% ethyl acetate in hexane as eluent to yield the title compound (0.510 g, 35.9%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[O:17][CH3:18])=[O:5])[CH3:2].[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:26][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:13][CH:12]=[CH:11][C:10]=2[O:17][CH3:18])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cnc2c(OC)cccc2c1Cl
Reactant: NCc1ccccc1
Product: CCOC(=O)c1cnc2c(OC)cccc2c1NCc1ccccc1

Procedure:
4-Chloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester (250 mg, 0.94 mmol) was treated with benzylamine following general procedure B to afford 4-benzylamino-8-methoxy-quinoline-3-carboxylic acid ethyl ester (220 mg). Thus obtained amino-ester was hydrolyzed to the corresponding acid using general procedure D and then transformed into the corresponding ethylamide (180 mg) following general procedure E. The above ethylamide (0.54 mmol) was subjected to reaction with methyl chloroformate according to general procedure F to furnish 1-benzyl-3-ethyl-7-methoxy-1H-pyrimido[5,4-c]quinoline-2,4-dione (60 mg). LCMS: m/z 362 [M+1]+.
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]([F:24])([F:23])[C:11]1[CH:12]=[C:13]([CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1)[CH:14]=[O:15]>CS(C)=O>[F:9][C:10]([F:23])([F:24])[C:11]1[CH:12]=[C:13]([CH:14]2[CH2:4][O:15]2)[CH:16]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:18]=1
Reactant: C[S+](C)(C)=O
Reactant: O=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Product: FC(F)(F)c1cc(C2CO2)cc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
In a dry flask was placed NaH (1.09 g of 60% NaH, 27.27 mmol). DMSO (90 mL) was added followed by trimethylsulfoxonium iodide (7.0 g, 31.82 mmol). The reaction was stirred for 5 minutes and then 3,5-bis(trifluoromethyl)benzaldehyde (1.5 mL, 9.09 mmol) was added as a solution in DMSO (15 mL). The reaction was stirred at room temperature for 1 hour and then poured into ice/water (300 mL). The mixture was extracted with pentanes (3×150 mL). The pentane extracts were combined and filtered through a short plug of silica gel with 10% Et2O/pentanes. The filtrate was concentrated and the residue was purified by flash chromatography with 10% Et2O/pentanes to give 2-[3,5-bis(trifluoromethyl)phenyl]oxirane. Rf=0.42 (10% Et2O/pentanes). 1H NMR (CDCl3, 500 MHz) 7.82 (s, 1H), 7.74 (s, 2H), 3.99 (dd, J=3.9, 2.5 Hz, 1H), 3.23 (dd, J=5.2, 4.1 Hz, 1H), 2.79 (dd, J=5.5, 2.5 Hz, 1H).
Reaction SMILES: [C:1]1([C:7]([N:9]=[C:10]=[S:11])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:12][C:13]1[CH:19]=[C:18]([O:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)[CH:17]=[CH:16][C:14]=1[NH2:15].C1(C)C=CC=CC=1>C(O)C>[C:7]([NH:9][C:10]([NH:15][C:14]1[CH:16]=[CH:17][C:18]([O:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)=[CH:19][C:13]=1[Cl:12])=[S:11])(=[O:8])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(N=C=S)c1ccccc1
Reactant: COc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 48 %

Procedure:
Commercially available 1-benzenecarbonyl isothiocyanate (50 μl) was dissolved in ethanol (1 ml) to prepare a solution. 2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (36 mg, yield 48%).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:3]=1.Br.Br[CH2:18][C:19]([C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1)=[O:20]>>[NH2:7][C:6]1[C:5]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:9][CH:8]=2)[N:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:18]=1[C:19](=[O:20])[C:21]1[CH:26]=[CH:25][CH:24]=[N:23][CH:22]=1
Reactant: O=C(CBr)c1cccnc1
Reactant: CCOC(=O)Nc1cc(Cl)ccc1C#N
Agent: Br
Product: CCOC(=O)n1c(C(=O)c2cccnc2)c(N)c2ccc(Cl)cc21

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-(ethoxycarbonylamino)benzonitrile (Example 1, step 1) and 3-(bromoacetyl)pyridine hydrobromide (H. McKennis et al., J. Org. Chem., 1963, 387). 1H-NMR (CDCl3) δ: 8.95 (1H, dd, J=0.7, 2.2 Hz), 8.70 (1H, dd, J=1.8, 4.8 Hz), 8.23 (1H, d, J=1.5 Hz), 8.03-7.99 (1H, m), 7.57 (1H, d, J=8.4 Hz), 7.41-7.28 (2H, m), 6.08 (2H, br s), 3.87 (2H, q, J=7.0 Hz), 0.92 (3H, t, J=7.0 Hz)
Reaction SMILES: [C:1]([O-:4])(O)=[O:2].[Na+].C1C=C(Cl)C=C(C(OO)=O)C=1.O=[C:18]1[CH:25]2[CH2:26][C:21]3([NH:28][C:29](=[O:31])[CH3:30])[CH2:22][CH:23]([CH2:27][CH:19]1[CH2:20]3)C2.S(=O)(=O)(O)[O-].[Na+]>C(Cl)Cl>[O:2]=[C:1]1[CH:23]2[CH2:22][C:21]3([NH:28][C:29](=[O:31])[CH3:30])[CH2:20][CH:19]([CH2:18][CH:25]([CH2:26]3)[O:4]1)[CH2:27]2
Reactant: CC(=O)NC12CC3CC(C1)C(=O)C(C3)C2
Reactant: O=C([O-])O
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)NC12CC3CC(C1)OC(=O)C(C3)C2
Temperature: 25 °C
Yield: 90 %

Procedure:
Solid NaHCO3 (1.2 mol) and mCPBA (1 2 mmol, 77% purity) were added to a solution of ketone 1A (0.6 mmol) in DCM (5 mL) at 0° C. The reaction mixture was allowed to warm to rt and was maintained for 1 h. The reaction mixture was diluted with a saturated, aqueous solution of sodium bisulfate (10 mL) and was extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (10/90 to 30/70 EtOAc/hexane) to provide lactone 16A in 90% yield. Data: LC/MS (ESR) m/z 224 [M+1]+.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([N:21]3[C@H:30]4[C@@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]4)[CH2:24][CH2:23][CH2:22]3)=[O:20])[CH:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:21]1([C:19]([C:17]2[CH:18]=[C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[S:15][CH:16]=2)=[O:20])[C@H:30]2[C@@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:24][CH2:23][CH2:22]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2cc(C(=O)N3CCC[C@@H]4CCCC[C@H]43)cs2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(c1csc(C2CCNCC2)c1)N1CCC[C@@H]2CCCC[C@H]21
Yield: 69.5 %

Procedure:
trans-4-[4-(Octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidine-1-carboxylic acid t-butyl ester (0.09 g, 0.32 mmol) was dissolved in DCM (2 mL) and TFA (1 mL) and the reaction stirred at room temperature for 6 hours. The solvent was evaporated and the residue product was purified by flash chromatography on an SCX-2 cartridge, washing with acetonitrile and then eluting with 2 M ammonia in methanol. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.074 g). LCMS m/z 333.20 [M+H]+ RT=6.23 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.2 (s, 1H), 6.9 (s, 1H), 3.7 (m, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 3.2 (m, 2H), 2.9 (m, 1H), 2.7 (m, 2H), 2.2 (m, 1H), 2.0-1.9 (m, 4H) 1.8-1.0 (m, 13H).
Reaction SMILES: [Na].[F:2][C:3]([F:12])([F:11])[C:4]1[CH:5]=[C:6]([SH:10])[CH:7]=[CH:8][CH:9]=1.Cl[CH2:14][C:15]#[N:16].CCOCC>C(O)C>[F:12][C:3]([F:2])([F:11])[C:4]1[CH:5]=[C:6]([S:10][CH2:14][C:15]#[N:16])[CH:7]=[CH:8][CH:9]=1
Reactant: FC(F)(F)c1cccc(S)c1
Reactant: N#CCCl
Agent: [Na]
Solvent: CCOCC
Solvent: CCO
Product: N#CCSc1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To sodium (0.62 g, 27.0 mmol) dissolved in 40 mL of ethanol was added 4.79 g (26.9 mmol) of 3-trifluoromethylthiophenol and 2.04 g (27.0 mmol) of chloroacetonitrile. The reaction mixture was heated at reflux for 1 hour and then stirred overnight at room temperature. To the cooled reaction mixture was added one volume of ether and the precipitated solids were removed by filtration. The filtrate was evaporated on the rotary evaporator to give the product as an oil in essentially quantitative yield. This material was used in the following reaction without further purification.
Reaction SMILES: BrC1C=C[C:5](NCC(OC)=O)=[N:6]C=1.[F:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH3:24])[CH:19]=[C:18]2[CH:25]=O>>[F:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH3:24])[CH:19]=[C:18]2[CH2:25][NH:6][CH3:5]
Reactant: COC(=O)CNc1ccc(Br)cn1
Reactant: Cn1cc(C=O)c2cc(F)ccc21
Product: CNCc1cn(C)c2ccc(F)cc12
Yield: 35 %

Procedure:
According to the procedure of Preparation 11 (c), except substituting 5-fluoro-1-methyl-1H-indole-3-carboxaldehyde (0.3 g, 1.69 mmole) for the 1,3 dimethyl-1H-2-carboxaldehyde, the title compound (0.11 g, 35%) was prepared as a viscous oil: MS (ES) m/e 193 (M+H)+.
Reaction SMILES: FC(F)(F)C([N:5]1[CH2:11][CH:10]([CH3:12])[C:9]2[CH:13]=[C:14]([Br:19])[C:15]([O:17][CH3:18])=[CH:16][C:8]=2[CH2:7][CH:6]1[CH3:20])=O.[OH-].[Na+]>CO.O>[Br:19][C:14]1[C:15]([O:17][CH3:18])=[CH:16][C:8]2[CH2:7][CH:6]([CH3:20])[NH:5][CH2:11][CH:10]([CH3:12])[C:9]=2[CH:13]=1
Reactant: COc1cc2c(cc1Br)C(C)CN(C(=O)C(F)(F)F)C(C)C2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1cc2c(cc1Br)C(C)CNC(C)C2
Temperature: 20 °C
Reaction time: 8 h
Yield: 70.4 %

Procedure:
A solution of N-trifluoroacetyl-8-bromo-1,4-dimethyl-7-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine (21 mg, 0.055 mmol) in methanol (2 mL) was treated with 15% aqueous NaOH (2 mL), and stirred overnight at 20° C. The product mixture was diluted with water (5 mL), extracted twice with EtOAc (10 mL), the combined organic phases were washed with brine (10 mL), dried with Na2SO4 and concentrated to give 11 mg of a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.29 (s, 1H), 6.64 (s, 1H), 3.88 (s, 3H), 3.02 (m, 2H), 2.89 (dd, J=9, 14 Hz, 1H), 2.80 (m, 1H), 2.67 (d, J=14 Hz, 1H), 2.53 (dd, J=10, 13, 1H) 1.30 (d, J=7 Hz, 3H), 1.19 (d, J=6 Hz, 3H). MS calculated for C13H18BrNO+H: 284, observed: 284.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1I.[F:29][C:30]1[CH:35]=[CH:34][C:33]([S:36]([NH:39][C:40]2[C:41]([O:55][CH3:56])=[N:42][CH:43]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:45]=2)(=[O:38])=[O:37])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:1][C:2]1[C:3]([C:44]2[CH:45]=[C:40]([NH:39][S:36]([C:33]3[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=3)(=[O:37])=[O:38])[C:41]([O:55][CH3:56])=[N:42][CH:43]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3I)n(-c3ccccc3)c(=O)c12
Reactant: COc1ncc(B2OC(C)(C)C(C)(C)O2)cc1NS(=O)(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: COc1ncc(-c2c(N)ncnc2N[C@@H](C)c2nn3ccc(C)c3c(=O)n2-c2ccccc2)cc1NS(=O)(=O)c1ccc(F)cc1
Yield: 4.9 %

Procedure:
(S)-2-(1-((6-Amino-5-iodopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.16 mmol) was treated with 4-fluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide (124 mg, 0.27 mmol), a solution of sodium carbonate (2 M, 365 μl, 0.73 mmol) and 2′-(dimethylamino)-2-biphenylyl-palladium(II) chloride dinorbornylphosphine complex (5 mg, 0.01 mmol) according to the method described in Preparation 17. The residue was purified by reverse phase using SP1® Purification System to give 5 mg (5% yield) of the title compound as a solid.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][S:5]([NH:8][C:9](=[O:40])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)[CH2:26][CH2:25]3)[N:20]=[C:19]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])[N:18]=2)=[CH:12][CH:11]=1)(=[O:7])=[O:6].Br[CH2:42][CH2:43][CH2:44][CH2:45]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C:24]2([NH:23][C:21]3[N:20]=[C:19]([O:34][CH2:35][C:36]([F:37])([F:38])[F:39])[N:18]=[C:17]([NH:16][C:13]4[CH:12]=[CH:11][C:10]([C:9]([NH:8][S:5]([CH2:4][CH2:3][N:2]5[CH2:45][CH2:44][CH2:43][CH2:42]5)(=[O:7])=[O:6])=[O:40])=[CH:15][CH:14]=4)[N:22]=3)[CH2:26][CH2:25]2)=[CH:28][CH:29]=1
Reactant: BrCCCCBr
Reactant: NCCS(=O)(=O)NC(=O)c1ccc(Nc2nc(NC3(c4ccc(Cl)cc4)CC3)nc(OCC(F)(F)F)n2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: O=C(NS(=O)(=O)CCN1CCCC1)c1ccc(Nc2nc(NC3(c4ccc(Cl)cc4)CC3)nc(OCC(F)(F)F)n2)cc1
Temperature: 65 °C
Yield: 15.1 %

Procedure:
To a solution of N-(2-aminoethylsulfonyl)-4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamide HCl salt (20 mg, 0.031 mmol) in Acetonitrile (Volume: 2 mL) was added 1,4-dibromobutane (6.96 mg, 0.032 mmol) and POTASSIUM CARBONATE (21.23 mg, 0.154 mmol). The mixture was heated to 65° C. for 16 h. After cooling to rt, the mixture was diluted with EtOAc, washed with water, and brine. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by rev. phase preparative HPLC (Column: Sunfire prep C18 OBO 5 uM, 30×100 mm by Waters Corp) using a gradient of 20-100% ACN/water w/0.1% TFA modifier to give 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(2-(pyrrolidin-1-yl)ethylsulfonyl)benzamide (3 mg) as the TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17-1.48 (m, 4H), 1.80-2.12 (m, 4H), 3.37-4.41 (m, 8H), 5.00 (q, J=9.0 Hz, 2H), 7.15-7.44 (m, 4H), 7.67-7.86 (m, 3H), 7.93 (s, 1H), 8.86 (br. s., 1H), 9.71 (br. s., 1H), 10.13 (br. s., 1H); LC-MS (Condition A), MS m/z (M++H) 640.0.
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10](OS(C)(=O)=O)[CH2:9][C@H:8]1[CH2:17][O:18][CH2:19][CH2:20][NH:21][C:22]([NH2:24])=[O:23])=[O:6])[CH:2]=[CH2:3].[C:25]([O-:28])(=[S:27])[CH3:26].[K+]>CN(C)C=O>[C:25]([S:27][C@@H:10]1[CH2:11][N:7]([C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[C@H:8]([CH2:17][O:18][CH2:19][CH2:20][NH:21][C:22]([NH2:24])=[O:23])[CH2:9]1)(=[O:28])[CH3:26]
Reactant: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1COCCNC(N)=O
Reactant: CC([O-])=S
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCOC(=O)N1C[C@@H](SC(C)=O)C[C@H]1COCCNC(N)=O
Temperature: 0 °C
Yield: 80.4 %

Procedure:
A solution of (2S,4R)-1-allyloxycarbonyl-4-methane- sulfonyloxy-2-[(2-ureidoethyl)oxymethyl]pyrrolidine (1.00 g) and potassium thioacetate (0.48 g) in dimethylformamide (6 ml) was heated at 80°-85° C. for 30 minutes. The mixture was poured into ice-water (30 ml) and extracted with ethyl acetate (12 ml×3). The organic layer was washed with brine (18 ml×2), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (50 g) and eluted with a mixture of methanol and dichloromethane (5:95 v/v) to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-[(2-ureidoethyl)oxymethyl]pyrrolidine (0.76 g).
Reaction SMILES: [N:1]1[C:8]([NH2:9])=[N:7][C:5]([NH2:6])=[N:4][C:2]=1[NH2:3].[CH2:10]=[O:11]>>[CH2:10]([NH:3][C:2]1[N:4]=[C:5]([NH2:6])[N:7]=[C:8]([NH2:9])[N:1]=1)[OH:11]
Reactant: Nc1nc(N)nc(N)n1
Reactant: C=O
Product: Nc1nc(N)nc(NCO)n1

Procedure:
Applicant's copending application Ser. No. 08/704,259 of Aug. 26, 1996 which is a continuation of Ser. No. 08/468,141 filed Jun. 6, 1995 describes a method for preparing an A-stage stabilized phenolic resin melamine dispersion which includes reaction of a portion of the melamine with formaldehyde to produce methylolmelamine in the phenolic resin to reduce the free formaldehyde content in the resin to less than 0.5% by weight of the composition.
Reaction SMILES: N(C(C)C)C(C)C.[Li]CCCC.[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[O:25][CH3:26])[C:21](=[O:27])[CH2:20][CH2:19][CH2:18]2.[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1[CH:35]=O.Cl>C1COCC1>[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1/[CH:35]=[C:20]1/[C:21](=[O:27])[C:22]2[C:17]([CH2:18][CH2:19]/1)=[CH:16][C:15]([O:14][CH3:13])=[C:24]([O:25][CH3:26])[CH:23]=2
Reactant: COc1cc2c(cc1OC)C(=O)CCC2
Reactant: O=Cc1ccncc1Br
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COc1cc2c(cc1OC)C(=O)/C(=C/c1ccncc1Br)CC2
Reaction time: 0.25 h
Yield: 80 %

Procedure:
To a solution of (i-Pr)2NH (0.3 mL, 2.2 mmol) at 0° C. in dry THF (15 mL) was added n-BuLi (1.22 M solution in hexane, 2.7 mL, 2.2 mmol), the mixture was stirred for 15 min at this temperature, after which the 6,7-dimethoxy-1-tetralone (0.412 g, 2 mmol) in dry THF (7 mL) was slowly added at −78° C. After 30 min at this temperature, 3-bromo-4-pyridinecarboxaldehyde (0.446 g, 2.4 mmol) in dry THF (7 mL) was slowly added and the solution was stirred for 30 min at −78° C. before allowed to reach room temperature and being stirred for a night. Then, the mixture was hydrolyzed by HCl 1N and extracted by AcOEt to eliminate the possible excess of tetralone. The aqueous layer was neutralized by NaHCO3 and the compound was extracted by CH2Cl2 three times. The combined organic layers were dried over MgSO4 and concentrated to dryness. The residue was purified by column chromatography on SiO2 (gradient of EtOAc in petroleum ether) to afford the expected product 84 (Yield 598.7 mg, 80%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]3[N:13]=[CH:14][CH:15]=[C:16]([OH:17])[C:11]=3[C:10]([CH3:18])=[N:9]2)=[CH:5][CH:4]=1.F[C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:23]=1[CH3:31]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:22]4[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:23]=4[CH3:31])=[C:11]3[C:10]([CH3:18])=[N:9]2)=[CH:19][CH:20]=1
Reactant: COc1ccc(Cn2nc(C)c3c(O)ccnc32)cc1
Reactant: Cc1cc([N+](=O)[O-])ccc1F
Product: COc1ccc(Cn2nc(C)c3c(Oc4ccc([N+](=O)[O-])cc4C)ccnc32)cc1
Yield: 47.5 %

Procedure:
Prepared from 1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-ol (0.150 g, 0.557 mmol; prepared as in Example 5, Step B) and 1-fluoro-2-methyl-4-nitrobenzene (0.0864 g, 0.557 mmol) according to the procedure of Example 13, Step A. The crude product was purified by Biotage 40S column eluting with 3:1 hexane/EtOAc then EtOAc to obtain the product (107 mg, 48%) as a off white solid. 1H NMR (CDCl3, 400 MHz) δ 8.33 (d, J=5.5 Hz, 1H), 8.25 (m, 1H), 8.15 (m, 1H), 7.35 (d, J=8.6 Hz, 2H), 7.17 (d, J=9.0 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.18 (d, J=5.5 Hz, 1H), 5.57 (s, 2H), 3.77 (s, 3H), 2.64 (s, 3H), 2.36 (s, 3H). LRMS (esi pos) m/e 405 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@@:6]3([C:19]4([CH2:22][C:21]([CH2:25][F:26])([CH2:23][F:24])[CH2:20]4)[N:18]4[C@@H:13]([C:14](=[O:39])[O:15][C@@H:16]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[C@H:17]4[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C@@H:12]3[C:40]3[CH:45]=[C:44]([F:46])[CH:43]=[C:42]([Cl:47])[CH:41]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[NH2:48][C@H:49]1[CH2:54][CH2:53][C@H:52]([C:55]([N:57]([CH3:59])[CH3:58])=[O:56])[CH2:51][CH2:50]1>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([C@@H:12]([C:40]4[CH:45]=[C:44]([F:46])[CH:43]=[C:42]([Cl:47])[CH:41]=4)[C@H:13]([C:14]([NH:48][C@H:49]4[CH2:50][CH2:51][C@H:52]([C:55](=[O:56])[N:57]([CH3:58])[CH3:59])[CH2:53][CH2:54]4)=[O:39])[N:18]([C@H:17]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C@@H:16]([OH:15])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:19]43[CH2:20][C:21]([CH2:25][F:26])([CH2:23][F:24])[CH2:22]4)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: CN(C)C(=O)[C@H]1CC[C@H](N)CC1
Reactant: O=C1O[C@@H](c2ccccc2)[C@@H](c2ccccc2)N2[C@@H]1[C@H](c1cc(F)cc(Cl)c1)[C@@]1(C(=O)Nc3cc(Cl)ccc31)C21CC(CF)(CF)C1
Product: CN(C)C(=O)[C@H]1CC[C@H](NC(=O)[C@H]2[C@H](c3cc(F)cc(Cl)c3)C3(C(=O)Nc4cc(Cl)ccc43)C3(CC(CF)(CF)C3)N2[C@H](c2ccccc2)[C@@H](O)c2ccccc2)CC1

Procedure:
The compound (339 mg, 0.50 mmol) obtained in Step 1 of Example 164 and trans-4-amino-N,N-dimethylcyclohexanecarboxamide (144 mg, 0.85 mmol) were used as starting materials and treated in the same way as in Step 1 of Example 20 to give 178 mg (42%) of the title compound as a colorless solid.
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:18].C([O-])(O)=O.[Na+].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>ClCCl>[O:18]=[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[N:11][N:2]1[NH:1][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Nn1nc(-c2ccccc2)c2ccccc2c1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C(Nn1nc(-c2ccccc2)c2ccccc2c1=O)c1ccccc1

Procedure:
The general procedures described in Example 14, parts A and B are followed. The obtained 2-amino-4-phenyl-(2H)-1-phthalazinone (0.01 mol) is stirred with aqueous NaHCO3 and benzoylchloride (0.01 mol) in dichloromethane at room temperature overnight. The organic phase is washed with water, dried over Na2SO4 and dichloromethane is evaporated. The product is recrystallized to yield the title compound, N-(1-oxo-4-phenyl-(2H)-phthalazin-2-yl)benzamide (R1=benzyl, Y1=NH—C(O), R2=phenyl, A=phenyl, m=0, p=0).