Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([C:7]([C:9]2[C:10](=[O:19])[O:11][C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=O)=[CH:5][CH:4]=1.[NH2:22][C:23]1[CH:27]=[C:26]([CH3:28])[NH:25][N:24]=1.C([O-])(=O)C.[NH4+].C(OCC)C>C(O)(=O)C.CO>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([C:7]2[N:22]=[C:23]3[NH:24][N:25]=[C:26]([CH3:28])[C:27]3=[C:18]3[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[O:11][C:10](=[O:19])[C:9]=23)=[CH:5][CH:4]=1
Reactant: Cc1cc(N)n[nH]1
Reactant: COc1ccc(C(=O)c2cc3ccccc3oc2=O)cc1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(-c2nc3[nH]nc(C)c3c3c2c(=O)oc2ccccc23)cc1
Temperature: 110 °C
Reaction time: 3 h
Yield: 30.3 %

Procedure:
A mixture of 2.1 g (7.49 mmol) of 3-(4-methoxybenzoyl)-2H-chromen-2-one with 728 mg (7.49 mmol) of 3-amino-5-methyl-pyrazole in 15 ml of acetic acid is heated at 110° C. for 10 minutes. 2.3 g (30 mmol) of ammonium acetate is then added and then the mixture is carried at 150° C. for 3 h. The solution is placed at room temperature and then 30 ml of ethyl ether and 5 ml of methanol are added. The white solid formed is filtered and then rinsed with diethyl ether to yield 810 mg of 5-(4-methoxyphenyl)-1-methylchromeno[4,3-d]pyrazolo[3,4-b]pyridin-6(3H)-one.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:20](=[O:21])[CH:19]=[C:18]3[C:13]([N:14]=[C:15](Br)[CH:16]=[CH:17]3)=[CH:12]2)=[CH:6][CH:5]=1.[C:24]1([CH2:30][C:31]#[CH:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C>CN(C)C=O.[Cu]I.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>[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:20](=[O:21])[CH:19]=[C:18]3[C:13]([N:14]=[C:15]([C:32]#[C:31][CH2:30][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:16]=[CH:17]3)=[CH:12]2)=[CH:6][CH:5]=1
Reactant: C#CCc1ccccc1
Reactant: COC(=O)c1ccc(Cn2cc3nc(Br)ccc3cc2=O)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(Cn2cc3nc(C#CCc4ccccc4)ccc3cc2=O)cc1

Procedure:
The coupling of 4-(7-bromo-3-oxo-2H-8-azaisoquinolin-2-ylmethyl)benzoic acid methyl ester (0.35 g, 0.94 mmol) with 3-phenyl-1-propyne (0.29 mL, 2.35 mmol) using triethylamine (0.54 mL, 3.86 mmol), CuI (0.013 g, 0.07 mmol), and Pd(Ph3P)4 (0.043 g, 0.04 mmol) in dimethylformamide is carried out as described in Example 1, Step (2). Purification on a silica gel column eluted with hexane/ethyl acetate 2:1, followed by drying, will afford the desired product.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[Cl:15][CH2:16][C:17](Cl)=[O:18]>ClCCl>[Cl:15][CH2:16][C:17]([NH:1][C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:18]
Reactant: O=C(Cl)CCl
Reactant: Nc1ncccn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CCl)Nc1ncccn1
Temperature: 25 °C

Procedure:
A solution of 2 amino-pyrimidine (2.0 g) in dry dichloromethane (17 mL) under nitrogen at 0° C. was treated with triethylamine (2.6 mL) followed by slow addition of chloroacetyl chloride (1.5 mL 18.4 mmol). The reaction mixture was allowed to warm up to room temperature. After 2h, the mixture was partitioned between dichioromethane and water.
Reaction SMILES: O.C(COC)OC.[Cl:8][C:9]1[N:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[CH:12]=[CH:11][CH:10]=1.CCCCCC.[C:29](Cl)(Cl)=[S:30]>>[Cl:8][C:9]1[N:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]=[C:29]=[S:30])=[CH:18][CH:17]=2)[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1ccc(Oc2cccc(Cl)n2)cc1
Reactant: S=C(Cl)Cl
Solvent: O
Solvent: COCCOC
Solvent: CCCCCC
Product: S=C=Nc1ccc(Oc2cccc(Cl)n2)cc1

Procedure:
Thiophosgene (10.5 grams; 0.091 mole) was added to an agitated solution of water (170 ml.) and dimethoxyethane (25 ml.) 4-((6-Chloro-2-pyridinyl)oxy)benzenamine (20 grams; 0.0906 mole) was added in small portions (the dimethoxyethane aids in suspending the amine in the aqueous thiophosgene solution) to the stirred thiophosgene solution over a 20 minute period. The reactive temperature during the addition was 25°-30° C. Following the addition of the amine reactant, the reaction mixture was filtered to recover the product precipitate which formed during the reaction. The precipitate was then dissolved in boiling hexane and the resulting solution dried and cooled to give the desired 4-((6-chloro-2-pyridinyl)oxy)phenyl isothiocyanate product as a light yellow crystalline solid having a melting point of 59°-62° C. The product was found to have carbon, hydrogen, nitrogen, chlorine and sulfur contents of 55.5, 2.3, 10.9, 13.36 and 12.34 percent, respectively, as compared with the theoretical contents of 54.82, 2.69, 10.66, 13.5 and 12.2 percent, respectively, calculated for the named structure.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[CH:15][CH:16]=[C:17]2[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[Br:1][CH2:9][C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[CH:15][CH:16]=[C:17]2[C:20]([OH:22])=[O:21])=[CH:12][CH:11]=1
Reactant: Cc1ccc2cccc(C(=O)O)c2c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: O=C(O)c1cccc2ccc(CBr)cc12
Yield: 96.7 %

Procedure:
A suspension of N-bromosuccinimide (6.23 g, 0.035 mol) in a solution of 7-methylnaphthalene-1-carboxylic acid (6.2 g, 0.033 mol) in tetrachlomethane (200 mL) was refluxed in the presence trace amounts of benzoyl peroxide for 2 hours. The resulting white suspension was evaporated to dryness under reduced pressure, washed with hot water and dried to give the crude product (8.46 g, 95.8%). An analytical sample was recrystallized from benzene-ethanol mixture. M.p. 209.5-211° C. 1H NMR δ 13.20 (bs, 1H), 8.91 (bs, 1H), 8.30-7.95 (m, 3H), 7.72-7.54 (m, 2H), 4.92 (s, 2H). Anal. Calcd for C12H9BrO2: C, 54.37; H, 3.42. Found: C, 54.45; H, 3.44.
Reaction SMILES: [CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[CH:7][C:6]=1[NH2:15].[CH3:17][C:18]1([CH2:23][CH2:24][C:25](O)=[O:26])[O:22][CH2:21][CH2:20][O:19]1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>CN(C=O)C.CN(C)C1C=CN=CC=1>[CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[CH:7][C:6]=1[NH:15][C:25](=[O:26])[CH2:24][CH2:23][C:18]1([CH3:17])[O:22][CH2:21][CH2:20][O:19]1
Reactant: CC(C)CNc1c(N)cnc2ccccc12
Reactant: CC1(CCC(=O)O)OCCO1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC(C)CNc1c(NC(=O)CCC2(C)OCCO2)cnc2ccccc12
Temperature: 25 °C
Yield: 71.3 %

Procedure:
To a cooled solution of N4-(2-methylpropyl)quinoline-3,4-diamine (2.15 g, 10 mmol) in DMF (40 mL) was added 3-(2-methyl-1,3-dioxolan-2-yl)propanoic acid (2.40 g, 15 mmol), followed by 4-methylmorpholine (1.6 mL, 15 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2.9 g, 15 mmol). The resulting suspension was stirred at room temperature and 4-dimethylaminopyridine (0.12 g, 1 mmol) was added. The dark yellow solution was stirred at room temperature for 16 hours, then saturated aqueous sodium bicarbonate (100 mL) was added. The mixture was transferred to a separatory funnel and was extracted with dichloromethane (2×100 mL). The organic layers were combined, washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford an oil that was purified by flash chromatography (silica gel, elution with 5% methanol in dichloromethane) to provide 2.55 g of N-{4-[(2-methylpropyl)amino]quinolin-3-yl}-3-(2-methyl-1,3-dioxolan-2-yl)propanamide.
Reaction SMILES: [CH2:1]([C:8]1[C:9]2[C:10]3[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12](S)[C:11]=3[CH:18]=[CH:19][CH:20]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.N1C=CC=CC=1.[N:41]1([CH:46]([CH3:50])[CH2:47][CH2:48][NH2:49])[CH:45]=[CH:44][N:43]=[CH:42]1>C(O)C>[CH2:1]([C:8]1[C:9]2[C:10]3[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([NH:49][CH2:48][CH2:47][CH:46]([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)[CH3:50])[C:11]=3[CH:18]=[CH:19][CH:20]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: SC1=Nc2ccc(Cc3ccccc3)c3cccc1c23
Reactant: CC(CCN)n1ccnc1
Agent: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: c1ccncc1
Solvent: CCO
Product: CC(CCNC1=Nc2ccc(Cc3ccccc3)c3cccc1c23)n1ccnc1

Procedure:
The Wolff-Kishner-Huang Minlon reductive procedure is applied to 6-benzoylbenz(cd)indol-2-one to yield 6-benzylbenz(cd)indol-2(1H)-one which is converted to 6-benzylbenz(cd)indol-2-thiol by P2S5 in refluxing pyridine. The reaction of the latter compound with 3-(1H-imidazol-1-yl)butanamine and mercuric acetate in refluxing ethanol, under the conditions of Example 55, leads to the title compound.
Reaction SMILES: [Cl:1][C:2]1[N:3]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:5][C:6]=1[C:7](OCC)=[O:8].[H-].C([Al+]CC(C)C)C(C)C.Cl>O1CCCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:3]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:4]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:5][C:6]=1[CH2:7][OH:8]
Reactant: CCOC(=O)c1cc(-c2ccccc2)n(S(=O)(=O)c2ccccc2)c1Cl
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: O=S(=O)(c1ccccc1)n1c(-c2ccccc2)cc(CO)c1Cl
Temperature: -70 °C
Reaction time: 1 h
Yield: 77.8 %

Procedure:
A solution (30 mL) of ethyl 2-chloro-5-phenyl-1-(phenylsulfonyl)-1H-pyrrole-3-carboxylate (1.27 g) in tetrahydrofuran was cooled to −70° C., a 1.5 mol/L solution (7.6 mL) of diisobutylaluminum hydride in toluene was added dropwise by small portions. The mixture was further stirred at −70° C. for 1 hr, 1 mol/l hydrochloric acid (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3→1:1) to give the title compound as pale-red crystals (yield 882 mg, 78%).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6]Br)([O-:3])=[O:2].[C:12]1([CH3:19])[C:17]([OH:18])=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH3:19][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=1[O:18][CH2:6][C:5]1[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1CBr
Reactant: Cc1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccccc1OCc1ccccc1[N+](=O)[O-]

Procedure:
75 g (0.347 mol) of 2-nitrobenzyl bromide, 37 g (0.342 mol) of o-cresol and 56 g (0.405 mol) of potassium carbonate in 500 ml of dimethylformamide is stirred for 5 hours at room temperature (20° C.). The reaction mixture is diluted with water and the aqueous phase is extracted three times with ether. The ether phase is dried and evaporated down. The crystalline residue is stirred with methanol and suction filtered. There is obtained 73 g (0.300 mol=88%) of the title compound as a colorless solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([CH3:13])[C:10](O)=O)=[C:4](C=O)[CH:3]=1.C([O-])(=O)C.[Na+].[OH-].[Na+]>C(OC(=O)C)(=O)C.C1(C)C=CC=CC=1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:8][C:9]([CH3:10])=[CH:13][C:6]=2[CH:7]=1
Reactant: CC(Oc1ccc(Br)cc1C=O)C(=O)O
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CC(=O)OC(C)=O
Product: Cc1cc2cc(Br)ccc2o1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.6 %

Procedure:
A solution of 2-[(4-bromo-2-formylphenyl)oxy]propanoic acid (5.08 mmol) in acetic anhydride (6 mL) was treated with sodium acetate (15.25 mmol). The resulting solution was heated to reflux and stirred overnight. The brown reaction solution was allowed to cool to room temperature, and was diluted with toluene (10 mL). The solution was then treated with 1N aq NaOH (10 mL) and was stirred at room temperature for 20 min. The solution was then further diluted with water (50 mL) and was extracted using ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting brown residue was purified by flash chromatography (hexanes), affording the title compound as a clear oil (660 mg, 62% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.73 (d, J=2.02 Hz, 1H) 7.47 (d, J=8.59 Hz, 1H) 7.35 (dd, J=8.72, 2.15 Hz, 1H) 6.58 (s, 1H) 2.45 (d, J=1.01 Hz, 3H).
Reaction SMILES: [CH2:1]([C:5]1[N:6](C(C)(C)C)[N:7]=[C:8]2[C:17]=1[C:16]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:10]=[C:9]2[NH2:18])[CH2:2][CH2:3][CH3:4].[ClH:23]>O>[ClH:23].[CH2:1]([C:5]1[NH:6][N:7]=[C:8]2[C:17]=1[C:16]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:10]=[C:9]2[NH2:18])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1c2c(nn1C(C)(C)C)c(N)nc1ccccc12
Agent: Cl
Solvent: O
Product: CCCCc1[nH]nc2c(N)nc3ccccc3c12
Temperature: 25 °C

Procedure:
A solution of 1-butyl-2-tert-butyl-2H-pyrazolo[3,4-c]quinolin-4-amine (prepared as described in Example 43, 1.43 g, 4.60 mmol) in 6 M HCl in water (40 mL) was heated at 100° C. overnight. The reaction mixture was allowed too cool to room temperature and a white solid was isolated by filtration, washed with water to provide 1-butyl-2H-pyrazolo[3,4-c]quinolin-4-amine hydrochloride that was used in the next step without extensive drying. Alternatively, the product can be dried in a vacuum oven at 95° C.
Reaction SMILES: [H-].[Na+].[C:3](=[O:10])([O:7][CH2:8][CH3:9])OCC.[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18](=[O:20])[CH3:19].C(O)C>C1COCC1>[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18](=[O:20])[CH2:19][C:3]([O:7][CH2:8][CH3:9])=[O:10]
Reactant: CCOC(=O)OCC
Reactant: CC(=O)c1ccccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: CCOC(=O)CC(=O)c1ccccc1Cl
Temperature: 40 °C
Yield: 33.3 %

Procedure:
Sodium hydride (1.45 g, 36 mmol) and diethyl carbonate (2.14 g, 18 mmol) were suspended in 10 ml of THF. 1-(2-Chlorophenyl)ethanone (1.4 g, 9 mmol) was gradually added into the reaction flask, maintaining the reaction mixture temperature at 40° C. for 2 h. Then 1 mL of ethanol was added thereto and heated under reflux conditions for 4 h. After cooling, 1 mL of ethanol was added and the mixture was poured onto ice water, and extracted with ether. Ether extracts are combined, washed with water, dried with anhydrous magnesium sulfate, and evaporated. The resulting oil is purified by flash column chromatography (PE/EA=50/1) to afford the title compound (680 mg, 34%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 1.24 (3H, t, J=6.8 Hz), 4.03 (2H, s), 4.19 (2H, q, J=6.8 Hz), 7.31-7.36 (2H, m), 7.42-7.45 (2H, m). [M+H] Calc'd for C11H11ClO3, 227; Found, 227.
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.Cl.[NH2:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.ClC(Cl)CCCCCN=C=N.[2H]C(S(C([2H])([2H])[2H])=O)([2H])[2H].[2H]O[2H]>N1C=CC=CC=1>[C:1]([NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)(=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1
Reactant: NCCc1ccc(O)cc1
Reactant: O=C(O)c1cccnc1
Agent: Cl
Agent: N=C=NCCCCCC(Cl)Cl
Agent: [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H]
Solvent: c1ccncc1
Product: O=C(NCCc1ccc(O)cc1)c1cccnc1
Temperature: 0 °C
Reaction time: 24 h

Procedure:
To an ice cold suspension of 3.69 g (0.03 mol) nicotinic acid in a solution of 5.2 g (0.03 mol) tyramine hydrochloride in 100 ml of pyridine, 6.18 g (0.03 mol) of dichlorohexylcarbodiimide (DCC) was gradually added while stirring. Stirring was continued at room temperature for 24 hrs and the formed dichclohexylurea was removed by filtration. The pyridine was removed by distillation in vacuo and the residue was triturated with cold water, filtered and crystallized from 50% aqueous methanol. Yield, 6.25 g (86%), m.p. 179°-181° C. PMR (DMSO-d6 /D2O)δ 9.0-8.66 (m, 2H, C2 and C6 pyridine protons), 8.33-8.10 (m, 1H, C4 pyridine proton), 7.66-7.46 (m, 1H, C5 pyridine proton), 7.23-6.70 (m, rH, C6H4), 3.56 (t, 2H, ##STR42## 2.90 (t, 2H, CH2). Anal. (C14H14N2O2) C, H, N.
Reaction SMILES: [O:1]=[O+][O-].[CH2:4]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]1[C:22](=[O:27])[O:23][C@@H:24]([CH:25]=C)[C@H:17]1[CH2:16][CH2:15]2)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[BH4-].[Na+].CSC>ClCCl.CO>[CH2:4]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]1[C:22](=[O:27])[O:23][C@@H:24]([CH2:25][OH:1])[C@H:17]1[CH2:16][CH2:15]2)[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: O=[O+][O-]
Reactant: C=C[C@@H]1OC(=O)N2c3ccc(OCc4ccccc4)cc3CC[C@H]12
Agent: [BH4-]
Agent: [Na+]
Solvent: CSC
Solvent: ClCCl
Solvent: CO
Product: O=C1O[C@@H](CO)[C@H]2CCc3cc(OCc4ccccc4)ccc3N12
Temperature: -40 °C
Reaction time: 8 h

Procedure:
Ozone is sparged for 3 h 30 min into a solution of 12.5 g (0.039 mol) of trans-7-benzyloxy-3-ethenyl-3,3a,4,5-tetrahydro-1H-oxazolo[3,4-a]quinolin-1-one in 450 ml of dichloromethane and 350 ml of methanol, cooled to -40° C. The excess ozone is then stripped off with a stream of nitrogen, 14.8 g (0.39 mol) of sodium borohydride are added in small portions, followed by 12.6 g (0.195 mol) of dimethyl sulphide, and the mixture is left overnight at room temperature. It is extracted twice with dichloromethane, the organic phase is washed with water and then with saturated sodium chloride solution and dried, and the solvent is evaporated off under reduced pressure. After purification by chromatography on a column of silica, with a 95/5 mixture of dichloromethane and methanol, 10.9 g of product are obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].Br[CH2:13][CH2:14][CH2:15][Cl:16].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:16][CH2:15][CH2:14][CH2:13][O:11][C:3]1[CH:4]=[CH:5][C:6]([C:8](=[O:9])[CH3:10])=[CH:7][C:2]=1[CH3:1]
Reactant: CC(=O)c1ccc(O)c(C)c1
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)c1ccc(OCCCCl)c(C)c1
Yield: 95.1 %

Procedure:
A mixture of 25 g (0.166 mole) of 4-hydroxy-3-methylacetophenone, 45.8 g (0.33 mole) of 1-bromo-3-chloropropane and 69.1 g (0.5 mole) of anhydrous potassium carbonate in 500 ml of acetone was heated at reflux for 20 hr. The mixture was cooled, filtered, and the filtrate concentrated under reduced pressure to give an oil as residue. The oil was crystallized in petroluem ether. The solid was collected by filtration, washed with petroleum ether and dried to yield 35.8 g (95%) of an off-white powder. An analytical sample, m.p. 41.5°-42.5° C. was prepared from petroleum ether.
Reaction SMILES: P(OCC)(OCC)OCC.[CH3:11][C:12]1[CH:13]=[CH:14][C:15]([N+:31]([O-])=O)=[C:16]([CH:30]=1)[CH:17]=[N:18][C:19]1[C:20](=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>>[CH3:11][C:12]1[CH:13]=[CH:14][C:15]2[C:16](=[CH:17][N:18]([C:19]3[CH:29]=[CH:28][CH:27]=[CH:26][C:20]=3[C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:31]=2)[CH:30]=1
Reactant: CCOC(=O)c1ccccc1N=Cc1cc(C)ccc1[N+](=O)[O-]
Agent: CCOP(OCC)OCC
Product: CCOC(=O)c1ccccc1-n1cc2cc(C)ccc2n1
Yield: 64.3 %

Procedure:
Triethyl phosphite (5.8 ml, 34 mmol) was added to ethyl N-(5-methyl-2-nitrobenzylidene)anthranilate (3.10 g, 9.93 mmol) as obtained in Reference Example 2. The mixture was refluxed under heating for 4 hours, and the triethyl phosphite was evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel using a mixed solvent of hexane/ethyl acetate (5:1), whereby 1.79 g of ethyl 2-(5-methyl-2H-indazol-2-yl)benzoate was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:3]=1[CH2:4][NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([N:16]1[CH:20]=[C:19]([C:21]([O:23]CC)=[O:22])[CH:18]=[N:17]1)[NH:10][C:9]2=O.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>>[CH3:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:3]=1[CH2:4][NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([N:16]1[CH:20]=[C:19]([C:21]([OH:23])=[O:22])[CH:18]=[N:17]1)[N:10]=[C:9]2[N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1
Reactant: C1COCCN1
Reactant: CCOC(=O)c1cnn(-c2nc3ccc(NCc4c(C)cccc4C)cc3c(=O)[nH]2)c1
Product: Cc1cccc(C)c1CNc1ccc2nc(-n3cc(C(=O)O)cn3)nc(N3CCOCC3)c2c1

Procedure:
The above compound may be made analogous to Example 1 using ethyl 1-(6-((2,6-dimethylbenzyl)amino)-4-oxo-3,4-dihydroquinazolin-2-yl)-1H-pyrazole-4-carboxylate in step D and morpholine in step E. MS (ESI/CI): predicted mass C25H26N6O3, 458.2.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)=[O:13].[CH2:30]([NH2:36])[CH:31]1[O:35][CH2:34][CH2:33][CH2:32]1>>[CH3:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([NH:36][CH2:30][CH:31]2[CH2:32][CH2:33][CH2:34][O:35]2)=[C:3]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH:4]=1)(=[O:10])=[O:9]
Reactant: NCC1CCCO1
Reactant: CS(=O)(=O)c1ccc(I)c(C(=O)N2CCN(c3ccc(C(F)(F)F)cc3)CC2)c1
Product: CS(=O)(=O)c1ccc(NCC2CCCO2)c(C(=O)N2CCN(c3ccc(C(F)(F)F)cc3)CC2)c1
Yield: 28 %

Procedure:
The title compound was prepared according to the procedure described for example 301 from (2-Iodo-5-methanesulfonyl-phenyl)-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-methanone (compound CK) and tetrahydrofurfurylamine (28% yield, MS (m/e): 512.4 (M+H, 100%)
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4](Cl)[N:3]=1.[CH2:15]([NH2:19])[CH2:16][CH2:17][CH3:18]>C(N(CC)CC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:19][CH2:15][CH2:16][CH2:17][CH3:18])[N:3]=1
Reactant: CCCCN
Reactant: CC(C)n1cnc2c(Cl)nc(Cl)nc21
Solvent: CCN(CC)CC
Product: CCCCNc1nc(Cl)nc2c1ncn2C(C)C

Procedure:
2-Chloro-6-[(butyl)amino]-9-(2-propyl)purine is prepared from 2,6-dichloro-9-(2-propyl)purine (see Example 15 for preparation), butylamine, and triethylamine essentially as described above in Example 1, Scheme A, step b.
Reaction SMILES: [CH2:1]([NH2:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][C:18](O)=[O:19].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[CH2:1]([NH:8][C:18](=[O:19])[CH2:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[O:10][CH3:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCN
Reactant: COc1ccccc1CC(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCNC(=O)Cc1ccccc1OC
Temperature: 0 °C
Reaction time: 8 h
Yield: 87.5 %

Procedure:
Heptan-1-amine (1 g, 8.679 mmol was dissolved in DMF (10 ml), (2-methoxyphenyl)acetic acid (1.587 g, 9.547 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (3.065, 9.547 mmol) and N-ethyl-N,N-diisopropylamine (2.356 g, 18.226 mmol) were added. The solution was stirred overnight at room temperature. EtOAc (20 ml) was added and the organic phase was washed with two portions of NaHCO3 (2×20 ml, aq). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 2.00 g of N-heptyl-2-(2-methoxyphenyl)acetamide (yield 87.5%).