Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:20]=[CH:19][C:5]2[O:6][CH2:7][C:8]3([CH2:17][O:18][C:4]=2[CH:3]=1)[O:12]C(=O)[N:10]([CH:14]([CH3:16])[CH3:15])[CH2:9]3.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>O>[OH:12][C:8]1([CH2:9][NH:10][CH:14]([CH3:16])[CH3:15])[CH2:7][O:6][C:5]2[CH:19]=[CH:20][C:2]([OH:1])=[CH:3][C:4]=2[O:18][CH2:17]1
Reactant: CC(C)N1CC2(COc3ccc(O)cc3OC2)OC1=O
Agent: [Ba+2]
Agent: [OH-]
Solvent: O
Product: CC(C)NCC1(O)COc2ccc(O)cc2OC1
Reaction time: 1 h

Procedure:
A mixture of 7-hydroxy-3'-isopropyl-3,4-dihydro-2H-1,5-benzodioxepin-3-spiro-5'-oxazolidin-2'-one (200 mg.; 0.716 mmole), barium hydroxide octahydrate (1.08 g.; 3.42 mole) and water (3.2 ml.) in an evacuated sealed glass tube (a Carius tube) is heated in a rocking oven at 160°-165° C. for 16 hours. The reaction mixture then is poured into boiling water (60 ml.) with stirring and vigorous passage of carbon dioxide until all barium ions have been removed from solution (pH ca. 6.8 by narrow range paper: no precipitate when a small portion is tested with sulfate ions). The solution is filtered through a little celite and evaporated to dryness under reduced pressure, affording 187 mg. of pale brown scaly solid. The crude product is purified by dry column chromatography on silica gel deactivated with 15% of water, using 3% methanol in ether for the development. The desired product is the second component to be eluted from the column, 70.5 mg., (38.9%). After drying at 60° C. in air, the solid still contains water of crystallization and has m.p. ca. 108°-110° C. The anhydrous compound is obtained by drying the hydrate at 80° C./0.1 m.m. for 1 hour and then has m.p. 133°-134.5° C. Recrystallization from benzene (ca. 30 parts V/W) provides 3,7-dihydroxy-3-isopropylaminomethyl-3,4-dihydro-2H-1,5-benzodioxepin, m.p. 133.5°-135° C.
Reaction SMILES: [C:1](/[CH:5]=[CH:6]/[C:7]1[C:8](=[O:22])[NH:9][C:10](=[O:21])[N:11]([CH:20]=1)[C@@H:12]1[O:19][C@H:16]([CH2:17][OH:18])[C@@H:14]([OH:15])[CH2:13]1)([O:3]C)=[O:2]>[OH-].[Na+]>[C:1](/[CH:5]=[CH:6]/[C:7]1[C:8](=[O:22])[NH:9][C:10](=[O:21])[N:11]([CH:20]=1)[C@@H:12]1[O:19][C@H:16]([CH2:17][OH:18])[C@@H:14]([OH:15])[CH2:13]1)([OH:3])=[O:2]
Reactant: COC(=O)/C=C/c1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)/C=C/c1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
(E)-5-(2-carbomethoxyvinyl)-2′-deoxyuridine (6.0 g, 19.33 mmol) was dissolved in 300 mL of 1 M NaOH and the mixture stirred at room temperature for 3 hrs, filtered and the filtrate adjusted to pH 2 with 1M HCl. On cooling at 4° C. a white precipitate formed. This was filtered off and washed with cold water (2×20 ml) and acetone (2×20 mL) and dred to give a white solid (4.441 g, yield 77.1%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[C:11]1[NH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][N:15]=1.O.O.Cl[Sn]Cl>CCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:11]1[NH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][N:15]=1
Reactant: O=[N+]([O-])c1ccc(Cl)c(-c2ncc(-c3ccccc3)[nH]2)c1
Agent: Cl[Sn]Cl
Solvent: CCO
Solvent: O
Product: Nc1ccc(Cl)c(-c2ncc(-c3ccccc3)[nH]2)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of 2-(2-chloro-5-nitrophenyl)-5-phenyl-1H-imidazole (27 g, 90.3 mmol) in EtOH (200 ml) is added SnCl2.2H2O (71 g, 316 mmol). The mixture is refluxed for 2 hours, cooled to room temperature and then concentrated. Ethyl acetate (200 ml) and NaOH (25 g in 100 ml water) are added to the residue and the mixture is stirred for 10 minutes at room temperature. The solid is removed by filtering through celite pad. The filtrate is separated and the organic layer is further washed with brine, dried over anhydrous MgSO4 and concentrated. The crude product is purified by silica gel flash chromatography, eluted with 40% ethyl acetate in dichloromethane to afford 4-Chloro-3-(5-phenyl-1H-imidazol-2-yl) aniline as a brown solid. LC-MS m/z: 270.1 (M+1).
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:4]=1[CH2:5][N:6]1[CH2:10][C@@H:9]2[CH2:11][CH:12]([CH2:14][OH:15])[CH2:13][C@@H:8]2[CH2:7]1.C(N(CC)CC)C.O>CS(C)=O.C(OCC)(=O)C>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:4]=1[CH2:5][N:6]1[CH2:7][C@@H:8]2[CH2:13][CH:12]([CH:14]=[O:15])[CH2:11][C@@H:9]2[CH2:10]1
Reactant: OCC1C[C@@H]2CN(Cc3ccc(C(F)(F)F)cc3C(F)(F)F)C[C@@H]2C1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=CC1C[C@@H]2CN(Cc3ccc(C(F)(F)F)cc3C(F)(F)F)C[C@@H]2C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 64.6 %

Procedure:
To a solution of {(3aR,6aS)-2-[2,4-bis(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-5-yl}methanol (1.4 g) and triethylamine (3.19 mL) in DMSO (7 mL) and ethyl acetate (7 mL) was added sulfur trioxide pyridine complex (1.82 g) under cooling to 0° C. The reaction mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (900 mg).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[CH:9][C:10](=O)[NH:11][N:12]=1.P(Br)(Br)([Br:16])=O.C([O-])(O)=O.[Na+]>>[Br:16][C:10]1[N:11]=[N:12][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[CH:8][CH:9]=1
Reactant: O=c1ccc(-c2ccccn2)n[nH]1
Reactant: O=P(Br)(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Product: Brc1ccc(-c2ccccn2)nn1
Temperature: 0 °C
Yield: 75 %

Procedure:
1 g (5.78 mmol) of 6-(pyridin-2-yl)-2H-pyridazin-3-one 7 and an excess (5 g) of phosphorus oxybromide are refluxed for 12 hours. The reaction mixture is poured into 100 ml of ice-cold water and then neutralized, dropwise, with a saturated aqueous solution of NaHCO3. After extraction with dichloromethane (3×30 ml) the organic phase is dried over MgSO4 and then concentrated under reduced pressure, to give the brominated pyridazine 8b with a yield of 75%.
Reaction SMILES: N[C:2]1([NH2:16])[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]1=[N:4][CH:5]=[N:6]2.C([O-])([O-])=O.[K+].[K+].[O:23]1[CH2:32][CH:24]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C>[NH2:16][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:32][CH:24]([OH:23])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COCCOC1=NC(N)(N)C2=NC=NC2=N1
Reactant: c1ccc(CC2CO2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COCCOc1nc(N)c2ncn(CC(O)Cc3ccccc3)c2n1
Temperature: 70 °C
Reaction time: 5 h
Yield: 34.6 %

Procedure:
To a suspension of 6-amino-2-(2-methoxyethoxy)adenine Compound (15) (300 mg, 1.43 mmol) in DMF (3 ml) was added K2CO3. Then (2,3-epoxypropyl)benzene (285 μl, 34 mmol) was added and the reaction mixture was stirred at 70° C. for 5 h. The solvent was removed under vacuum and the residue was washed with brine. The aqueous phase was extracted with DCM and the combined organic layers were dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (eluting a linear gradient of 0-10% MeOH in DCM) to give 170 mg of Compound (22). 1H NMR (CDCl3) δ 2.82-2.85 (dd, 2H), δ 3.43 (s, 3H), δ 3.74 (t, 2H), δ 4.00-4.10 (m, 1H), δ 4.25-4.29 (m, 2H), δ 4.42 (t, 2H), δ 5.76 (bs, 2H), δ 7.21-7.34 (m, 5H), δ 7.50 (s, 1H); MS: 494.2 (M+H)+.
Reaction SMILES: [CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:10]=3[N:9]=[C:8]2[C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[N:25]=[C:24]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:23]=N3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:35]O>[Pt]=O>[CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:10]=3[N:9]=[C:8]2[C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[NH:25][CH:24]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:23][CH2:35]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CO
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4ccccc4)cnc3c1)n2C1CCCCC1
Agent: O=[Pt]
Product: O=C(O)c1ccc2c(c1)nc(-c1ccc3c(c1)CCC(c1ccccc1)N3)n2C1CCCCC1
Yield: 37 %

Procedure:
A solution of Compound 203 (100 mg, 0.23 mmol) and platinum oxide (12 mg, 0.048 mmol) in methanol (5 mL) was hydrogenated at 40 psi for 3 h. The reaction was evaporated to dryness, and purified via HPLC. The resulting compound was then converted to the HCl salt using the standard method, yielding 40 mg (37% yield) of the title compound.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[N:12]=[C:13]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)[S:14][C:10]=2[C:9](=[O:20])[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[N+:21]([O-])([OH:23])=[O:22]>S(=O)(=O)(O)O>[O:1]=[C:2]1[C:11]2[N:12]=[C:13]([C:15]3[O:16][C:17]([N+:21]([O-:23])=[O:22])=[CH:18][CH:19]=3)[S:14][C:10]=2[C:9](=[O:20])[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2
Reactant: O=[N+]([O-])O
Reactant: O=C1c2ccccc2C(=O)c2sc(-c3ccco3)nc21
Agent: O=S(=O)(O)O
Product: O=C1c2ccccc2C(=O)c2sc(-c3ccc([N+](=O)[O-])o3)nc21
Yield: 34 %

Procedure:
To 5 g (17.8 mmol) of 4,9-dihydro-4,9-dioxo-2-(furan-2-yl)naphtho[2,3-d]thiazole, one adds 20 mL of fuming nitric acid and 20 mL of concentrated sulfuric acid at room temperature. The reaction mixture is heated to reflux for 72 h; the precipitate formed is filtered through fritted glass, washed with water, and rinsed with ether. The dark yellow powder obtained is recrystallized in DMF after color removal with animal black. In this manner, 2 g of 4,9-dihydro-4,9-dioxo-2-(5-nitro-furan-2-yl)naphtho-[2,3-d]thiazole are produced in the form of a dark yellow solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([C:15](OC)=[O:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2.CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([CH2:15][OH:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2
Reactant: COCCc1cc(C(=O)OC)c2ccccc2c1
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Product: COCCc1cc(CO)c2ccccc2c1

Procedure:
Methyl 3-[2-(methyloxy)ethyl]-1-naphthalenecarboxylate (1 eq.) from the previous step was taken up in toluene (0.1 M). To this solution was then added DIBAl-H (1.5 M toluene solution, 2.4 eq.) and the resulting solution was vigorously stirred at RT for 4 h. The reaction mixture thus obtained was quenched with 1 N aq. HCl and extracted with ether. The combined organic extracts were washed further with water and brine, dried over Na2SO4 and filtered. Concentration of the filtrate in vacuo afforded the title compound as a colorless oil.
Reaction SMILES: C(O[C:4]([C:6]1[N:7]=[C:8]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=2[F:22])[N:9]([CH3:14])[C:10](=[O:13])[C:11]=1[OH:12])=[O:5])C.[CH3:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1>>[CH3:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:29][C:4]([C:6]2[N:7]=[C:8]([C:15]3[C:16]([F:22])=[CH:17][CH:18]=[CH:19][C:20]=3[F:21])[N:9]([CH3:14])[C:10](=[O:13])[C:11]=2[OH:12])=[O:5])=[CH:26][CH:25]=1
Reactant: Cc1ccc(CN)cc1
Reactant: CCOC(=O)c1nc(-c2c(F)cccc2F)n(C)c(=O)c1O
Product: Cc1ccc(CNC(=O)c2nc(-c3c(F)cccc3F)n(C)c(=O)c2O)cc1

Procedure:
Prepared according to the procedure described for example 2 from 2-(2,6-difluoro-phenyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl ester (31 mg, 0.1 mmol) and 4-methylbenzylamine (61 mg, 0.5 mmol). The title product was obtained as an off-white solid (32 mg, 83% yield). 1HNMR (500 MHz, CDCl3) δ: 12.39 (1H, s), 7.55 (1H, br s), 7.51–7.45 (1H, m), 7.20 (2H, d, J=7.94 Hz), 7.14 (2H, d, J=7.63 Hz), 7.03 (2H, d, J=8.55, 7.33 Hz), 4.54 (2H, d, J=6.10 Hz), 3.40 (3H, s), 2.32 (3H, s). HRMS (ESI) calcd for C20H18F2N3O3 (M+H): 386.1316; found: 386.1313.
Reaction SMILES: C(OC([N:7]1[C@:11]2([C@@H:16]([F:17])[CH2:15][C@@H:14]3[C@H:12]2[C@H:13]3[C:18]([OH:20])=[O:19])[C:10](=[O:21])[O:9]C1)=O)C=C.Br[CH2:23][C:24]1[O:25][C:26](=[O:30])[O:27][C:28]=1[CH3:29]>>[NH2:7][C@@:11]1([C:10]([OH:9])=[O:21])[C@@H:16]([F:17])[CH2:15][C@@H:14]2[C@H:12]1[C@H:13]2[C:18]([O:20][CH2:23][C:24]1[O:25][C:26](=[O:30])[O:27][C:28]=1[CH3:29])=[O:19]
Reactant: C=CCOC(=O)N1COC(=O)[C@]12[C@H]1[C@@H](C[C@@H]2F)[C@@H]1C(=O)O
Reactant: Cc1oc(=O)oc1CBr
Product: Cc1oc(=O)oc1COC(=O)[C@H]1[C@@H]2C[C@H](F)[C@@](N)(C(=O)O)[C@@H]21
Yield: 27 %

Procedure:
(1S,2S,3S,5R,6S)-3′-((Allyloxy)carbonyl)-3-fluoro-5′-oxospiro[bicyclo[3.1.0]hexan-2,4′-oxazolidine]-6-carboxylic acid (A-1-2, 660 mg) and 4-(bromomethyl)-5-methyl-1,3-dioxol-2-one (639 mg) were treated in the same manner as in Example A-1 (3) and (4) to give the title compound (A-16, 188 mg) as a pale yellow solid.
Reaction SMILES: [NH2:1][N:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:19].[F:20][C:21]([F:33])([F:32])[C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29](O)=[O:30])=[CH:24][CH:23]=1>>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3](=[O:19])[N:2]([NH:1][C:29](=[O:30])[CH2:28][C:25]3[CH:24]=[CH:23][C:22]([C:21]([F:32])([F:20])[F:33])=[CH:27][CH:26]=3)[N:11]=2)=[CH:13][CH:14]=1
Reactant: O=C(O)Cc1ccc(C(F)(F)F)cc1
Reactant: Nn1nc(-c2ccc(Cl)cc2)c2ccccc2c1=O
Product: O=C(Cc1ccc(C(F)(F)F)cc1)Nn1nc(-c2ccc(Cl)cc2)c2ccccc2c1=O

Procedure:
The product of Example 86A and 2-[4-(trifluoromethyl)phenyl]acetic acid were treated using a method similar to that described in Example 57 to give the title compound. 1H NMR (500 MHz, DMSO-d6/Deuterium Oxide) δ ppm 8.40-8.42 (m, 1H), 7.93-8.04 (m, 2H), 7.72-7.74 (m, 3H), 7.59-7.69 (m, 6H), 3.83-3.84 (bs, 2H); MS (ESI−) M/Z 456 (M−H)−.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:17][C:16](=O)[C:11]2[C:12]([CH3:15])=[CH:13][S:14][C:10]=2[CH2:9]1.[C:19]([NH:22][NH2:23])([NH2:21])=[NH:20].Cl.Cl.O>C(O)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:17][C:16](=[N:23][NH:22][C:19]([NH2:21])=[NH:20])[C:11]2[C:12]([CH3:15])=[CH:13][S:14][C:10]=2[CH2:9]1
Reactant: N=C(N)NN
Reactant: Cc1csc2c1C(=O)CC(c1ccccc1Cl)C2
Agent: Cl
Solvent: O
Solvent: CCO
Product: Cc1csc2c1C(=NNC(=N)N)CC(c1ccccc1Cl)C2
Yield: 171.3 %

Procedure:
A mixture of 6-(2-chlorophenyl)-3-methyl-4,5,6,7-tetrahydrobenzothiophene-4-one (0.07 g), aminoguanidine hydrochloride (0.034 g), concentrated hydrochloric acid (0.063 ml), water (0.063 ml) and ethanol (10 ml) was refluxed for 4 hours. Under reduced pressure, the solvent was evaporated, and the residue was recrystallized from ethanol to give 6-(2-chlorophenyl)-4-guanidinoimino-3-methyl-4,5,6,7-tetrahydrobenzothiophene hydrochloride (Compound 117) (80 mg) as colorless crystals.
Reaction SMILES: FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:15][C:16]1[N:25]2[CH2:26][CH2:27][N:28]=[C:24]2[C:23]2[CH:22]=[CH:21][C:20]([OH:29])=[C:19]([O:30][CH3:31])[C:18]=2[N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:43][C@@H:44]1[O:46][CH2:45]1)(=O)=O>CN(C=O)C>[CH3:31][O:30][C:19]1[C:18]2[N:17]=[C:16]([NH2:15])[N:25]3[CH2:26][CH2:27][N:28]=[C:24]3[C:23]=2[CH:22]=[CH:21][C:20]=1[O:29][CH2:43][C@H:44]1[CH2:45][O:46]1
Reactant: COc1c(O)ccc2c1N=C(N)N1CCN=C21
Reactant: CS(=O)(=O)OC[C@H]1CO1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: COc1c(OC[C@H]2CO2)ccc2c1N=C(N)N1CCN=C21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 42.7 %

Procedure:
To a solution of 5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol bis(trifluoroacetate) (Intermediate E, 0.30 g, 0.65 mmol) in DMF (8 mL) was added caesium carbonate to generate a white suspension. The suspension was stirred at room temperature for 1.5 hr, then (R)-glycidyl methanesulfonate (Intermediate F, Step 1, 3.9 mL of 0.34 M solution in DMF, 1.30 mmol, 2.0 equiv.) was added, and the resulting solution was stirred at 60° C. for 20 h. The resulting suspension was concentrated under reduced pressure and the residue was treated separated between a saturated sodium bicarbonate solution (30 mL) and a 4:1 CH2Cl2/isopropanol solution (30 mL). The aqueous phase was extracted with a 4:1 CH2Cl2/isopropanol solution (30 mL). The combined organic phases were dried (anh. sodium sulfate) and concentrated under reduced pressure. The residue was purified using MPLC (Isolute Flash NH2 reverse phase column; 100% CH2Cl2 for 5 min., gradient to 95% CH2Cl2: 5% MeOH over 15 minutes; gradient to 90% CH2Cl2: 10% MeOH over 15 min.; gradient to 80% CH2Cl2: 20% MeOH over 15 min.; and gradient to 75% CH2Cl2: 25% MeOH over 15 min.) to give 7-methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (0.080 g, 43%): 1H NMR (DMSO-d6+1 drop TFA-d) δ 2.71 (dd, J=2.5, 4.8 Hz, 1H), 2.85, (t, J=4.6 Hz, 1H), 3.34-3.40 (br m, 1H), 3.75 (s, 3H), 3.82 (s, 3H), 4.30 (dd, J=6.6, 11.4 Hz, 1H), 4.10 (br t, J=9.7 Hz, 2H), 4.31 (br t, J=9.7 Hz, 2H), 4.54 (dd, J=2.3, 11.6 Hz, 1H), 7.26 (d, J=9.4 Hz, 1H), 7.84 (d, J=9.1 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:20][CH2:21][CH3:22])=[C:6]([C:8]2[NH:13][C:12](=[O:14])[C:11]([CH2:15][CH3:16])=[C:10]([CH2:17][CH3:18])[N:9]=2)[CH:7]=1.[CH2:23]([N:25]=[C:26]=[O:27])[CH3:24]>>[CH2:17]([C:10]1[N:9]=[C:8]([C:6]2[CH:7]=[C:2]([NH:1][C:26]([NH:25][CH2:23][CH3:24])=[O:27])[CH:3]=[CH:4][C:5]=2[O:19][CH2:20][CH2:21][CH3:22])[NH:13][C:12](=[O:14])[C:11]=1[CH2:15][CH3:16])[CH3:18]
Reactant: CCN=C=O
Reactant: CCCOc1ccc(N)cc1-c1nc(CC)c(CC)c(=O)[nH]1
Product: CCCOc1ccc(NC(=O)NCC)cc1-c1nc(CC)c(CC)c(=O)[nH]1
Yield: 90 %

Procedure:
The title compound was prepared by reacting the compound of example 42 with ethyl isocyanate in the same manner as that of example 35. Yield: 90%. 1H NMR (DMSO-d6) δ: 11.76 (1H, br), 8.46 (1H, br), 7.77 (1H, d), 7.57 (1H, dd), 7.06 (1H, d), 6.01 (1H, t), 4.00 (2H, t), 3.09 (2H, m), 2.56 (2H, q), 2.45 (2H, q), 1.73 (2H, m), 1.19 (3H, t), 1.03 (6H, t), 0.97 (3H, t).
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=2[CH:12]=[C:11](Br)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(COC)OC>O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6](=[O:21])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=2[CH:12]=[C:11]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1ccccc1
Reactant: CC(C)(C)OC(=O)COc1cc(Br)cc2c1CCCC2=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)COc1cc(-c2ccccc2)cc2c1CCCC2=O
Temperature: 95 °C
Yield: 69.6 %

Procedure:
To a mixture of (3-bromo-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (XIIIb, 78 mg, 0.22 mmol), phenylboronic acid (55.3 mg, 0.44 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24.1 mg, 0.033 mmol), and cesium carbonate (144.8 mg, 0.44 mmol) was added dimethoxyethane (2 mL) at room temperature under nitrogen. The resulting brown reaction mixture was heated at 95° C. for 15 h. Then, the reaction mixture was cooled to room temperature, and diluted with water (20 mL) and ethyl acetate (20 mL). The aqueous layer was separated and extracted with ethyl acetate (20 mL), and the combined organic extracts were washed with water (50 mL) and brine solution (50 mL), then dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the colored residue. Chromatography using an ISCO (12 g) column, (gradient elution with 2-25% ethyl acetate in hexanes) afforded (5-oxo-3-phenyl-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (54 mg, 70%) as a white solid: ES(+)-HRMS m/e calcd. for C22H24O4 (M+Na)+375.1567, obsd. 375.1567.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[CH2:9]([O:11][C:12](=[O:33])[CH:13]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH3:10]>C1(C)C=CC=CC=1>[N:5]1[CH:6]=[CH:7][C:2]([CH:1]=[CH:13][C:12]([O:11][CH2:9][CH3:10])=[O:33])=[CH:3][CH:4]=1
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccncc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C=Cc1ccncc1
Temperature: 100 °C
Reaction time: 3 h
Yield: 82.2 %

Procedure:
A mixture of isonicotinaldehyde (25 g), ethyl(triphenylphosphoranylidene)acetate (82 g) and toluene (300 ml) is stirred for 3 hours at 100° C. After cooling, the crystals that precipitated are removed by filtration, and the filtrate is concentrated in vacuo. The residue is dissolved in a mixture of ethyl acetate and petroleum ether (1:1, 400 ml), and the resulting solution is extracted with 5% hydrochloric acid (500 ml). The aqueous layer is extracted with ethyl acetate (50 ml) and neutralized with potassium carbonate. After cooling, the resulting crystals are collected by filtration and dried to give ethyl 3-(4-pyridyl)acrylate (34 g) as colorless prisms, mp 64°-66° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([NH:11][CH:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=2)[C:13]([OH:15])=[O:14])[CH:7]=[CH:8][C:9]=1F)(=[O:3])[NH2:2].NC1C=C2C(=CC=1)[C:33](=[O:37])[NH:32]NC2=O.COC1C=C(B(O)O)C=CC=1OC.O.C(O)(=O)C=O>>[CH3:25][O:24][C:18]1[CH:17]=[C:16]([CH:12]([NH:11][C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[C:33](=[O:37])[NH:32][NH:2][C:1]3=[O:3])[C:13]([OH:15])=[O:14])[CH:21]=[CH:20][C:19]=1[O:22][CH3:23]
Reactant: Nc1ccc2c(=O)[nH][nH]c(=O)c2c1
Reactant: COc1ccc(C(Nc2ccc(F)c(C(N)=O)c2)C(=O)O)cc1OC
Agent: COc1ccc(B(O)O)cc1OC
Agent: O=CC(=O)O
Solvent: O
Product: COc1ccc(C(Nc2ccc3c(=O)[nH][nH]c(=O)c3c2)C(=O)O)cc1OC
Yield: 95 %

Procedure:
15A was prepared in a procedure similar to that of 13A using 6-amino-2,3-dihydrophthalazine-1,4-dione, 3,4-dimethoxyphenylboronic acid and glyoxylic acid monohydrate. Yield: 95%. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.73 (s, 3H) 3.74 (s, 3H) 5.15 (d, J=7.03 Hz, 1H) 6.95 (d, 1H) 7.01-7.06 (m, 1H) 7.13 (d, J=2.20 Hz, 1H) 7.25 (d, J=7.03 Hz, 2H) 7.74 (s, 1H), LCMS: 344 (M+1).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:9][N:10]=[C:11]2[C:15](=O)[O:14][C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:12]2)[CH:5]=[CH:6][C:7]=1[F:8].[NH4+:23].[OH-].Cl.O>CC(C)=O>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:12][C:11]([C:15]([NH2:23])=[O:14])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: [NH4+]
Reactant: Cc1cc(NN=C2N=C(c3ccccc3)OC2=O)ccc1F
Agent: Cl
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: Cc1cc(-n2nc(C(N)=O)nc2-c2ccccc2)ccc1F
Yield: 55.2 %

Procedure:
3.0 g (0.01 mole) of 4-(3-methyl-4-fluorophenylhydrazono)-2-phenyl-oxazoline-5-one (R1 =3--CH3, R2 =4--F and R3 =H in the formula II) was suspended in 16 ml of acetone. To the suspension, 1.57 ml of 29% solution of NH4OH (0.013 mole) was added dropwise at room temperature. After refluxing the reaction mixture for 25 minutes, heating was stopped and 1.57 ml of concentrated hydrochloric acid was added dropwise. After the addition was over, the reaction mixture was refluxed again for 5 minutes. Then 40 ml of water was added to the reaction mixture, and the resulting crystal was filtered out, washed with acetone containing water and dried. The obtained crystal was recrystallized from a mixture of 20 ml of ethanol and 5 ml of water to obtain 1.7 g of almost colorless crystal, m.p. 123°-126° C., with a yield of 55.2%.