Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[F:2][C:3]([F:13])([F:12])[C:4]1[N:5]=[C:6]([C:9]([NH2:11])=[NH:10])[S:7][CH:8]=1.C([O:16][C:17]([C:19]([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:20][O-])=O)C.[Na+].CC[O-].[Na+]>CCO>[O:22]([C:19]1[C:17]([OH:16])=[N:10][C:9]([C:6]2[S:7][CH:8]=[C:4]([C:3]([F:2])([F:12])[F:13])[N:5]=2)=[N:11][CH:20]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: N=C(N)c1nc(C(F)(F)F)cs1
Reactant: CCOC(=O)C(=C[O-])Oc1ccccc1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: Oc1nc(-c2nc(C(F)(F)F)cs2)ncc1Oc1ccccc1
Temperature: 90 °C
Reaction time: 2 h
Yield: 81 %

Procedure:
To a solution of compound 282 (280 mg, 1 eq.) in dry EtOH (6 mL) was added compound 291 (1.38 g, 5 eq.) under nitrogen, followed by NaOEt (165 mg, 1 eq.). The reaction mixture was stirred at 90° C. for 2 hrs. EtOH was evaporated and a DCM/water mixture was added. Aqueous layer was acidified to pH 5 with aqueous 1N HCl and was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by chromatography on silica gel (DCM/MeOH) to yield compound A1l as a beige oil in 81% yield. MS (ESI, EI+): m/z=340 (MH+).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][NH2:11])[CH:7]=[CH:8][CH:9]=1.[Br:14][C:15]1[S:19][C:18]2=[N:20][C:21]([C:23](O)=[O:24])=[CH:22][N:17]2[CH:16]=1>>[Br:14][C:15]1[S:19][C:18]2=[N:20][C:21]([C:23]([NH:11][CH2:10][C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:12])([F:13])[F:1])[CH:5]=3)=[O:24])=[CH:22][N:17]2[CH:16]=1
Reactant: NCc1cccc(OC(F)(F)F)c1
Reactant: O=C(O)c1cn2cc(Br)sc2n1
Product: O=C(NCc1cccc(OC(F)(F)F)c1)c1cn2cc(Br)sc2n1

Procedure:
The title compound was prepared by essentially following the same procedures described for Intermediate XLIV, using (3-(trifluoromethoxy)phenyl)methanamine and 2-bromoimidazo[2,1-b]thiazole-6-carboxylic acid as starting materials.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:28]3[C:29]([CH:32]=[O:33])=[CH:30][CH:31]=[C:27]3[C:8]3([CH2:13][CH2:12][N:11]([C:14](=[O:26])[C:15]4[CH:20]=[CH:19][C:18]([O:21][CH:22]([CH3:24])[CH3:23])=[C:17]([CH3:25])[CH:16]=4)[CH2:10][CH2:9]3)[O:7][C:6]=2[CH:34]=1.[Mn]([O-])(=O)(=O)=[O:36].[K+]>CC(C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:28]3[C:29]([C:32]([OH:36])=[O:33])=[CH:30][CH:31]=[C:27]3[C:8]3([CH2:13][CH2:12][N:11]([C:14](=[O:26])[C:15]4[CH:20]=[CH:19][C:18]([O:21][CH:22]([CH3:24])[CH3:23])=[C:17]([CH3:25])[CH:16]=4)[CH2:10][CH2:9]3)[O:7][C:6]=2[CH:34]=1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: Cc1cc(C(=O)N2CCC3(CC2)Oc2cc(Cl)ccc2-n2c(C=O)ccc23)ccc1OC(C)C
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: Cc1cc(C(=O)N2CCC3(CC2)Oc2cc(Cl)ccc2-n2c(C(=O)O)ccc23)ccc1OC(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 13 %

Procedure:
To a solution of 7-chloro-1′-(4-isopropoxy-3-methylbenzoyl)spiro-[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde (130 mg, 0.27 mmol) in acetone (1.5 mL) was added a solution of potassium permanganate (43 mg, 16 μL, 0.27 mmol) in water (1.5 mL) and acetone (1.5 mL) dropwise at 0° C. The mixture was allowed to stir at room temperature for 2 h before it was concentrated onto Celite from methanol. Column chromatography on the residue (0-20% EtOAc/CH2Cl2) gave 7-chloro-1′-(4-isopropoxy-3-methylbenzoyl)spiro[benzo[b]-pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carboxylic acid (13%).
Reaction SMILES: Cl[C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]2[CH2:10][N:11]([CH2:14][CH2:15][C:16]3[CH:25]=[CH:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]=3)[C:12](=[O:13])[C:3]=12.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]3[CH2:10][N:11]([CH2:14][CH2:15][C:16]4[CH:25]=[CH:24][C:23]5[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=5)[N:17]=4)[C:12](=[O:13])[C:3]=23)=[CH:30][CH:29]=1
Reactant: Cn1cc2c(c(Cl)c1=O)C(=O)N(CCc1ccc3ccccc3n1)C2
Reactant: COc1ccc(B(O)O)cc1
Product: COc1ccc(-c2c3c(cn(C)c2=O)CN(CCc2ccc4ccccc4n2)C3=O)cc1

Procedure:
The title compound was prepared in analogy to the process of Example 13 starting from 7-chloro-5-methyl-2-(2-quinolin-2-yl-ethyl)-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (see Example c4)) and 4-methoxyphenylboronic acid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]([CH3:13])=[C:9]([Br:12])[C:10]=1[CH3:11])=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:21][C:22]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][N:26]=1)=[O:23]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:21][C:22](=[O:23])[NH:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][N:26]=2)[C:8]([CH3:13])=[C:9]([Br:12])[C:10]=1[CH3:11])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1[nH]c(C)c(Br)c1C
Reactant: O=C(CBr)Nc1ccc(Cl)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(C)c(Br)c(C)n1CC(=O)Nc1ccc(Cl)cn1
Reaction time: 2 h
Yield: 26.5 %

Procedure:
To a solution of 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester (492 mg) in DMF (5 mL) was added Cs2CO3 (912 mg). The mixture was stirred for 30 min at RT after which 2-bromo-N-(5-chloro-pyridin-2-yl)-acetamide (499 mg) was added. Stirring was continued for 2 h at RT whereupon the mixture was filtered and concentrated. The residue was subjected to preparative HPLC(CH3CN/H2O gradient+0.05% TFA) to give 4-bromo-1-[(5-chloro-pyridin-2-ylcarbamoyl)-methyl]-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester (220 mg).
Reaction SMILES: [NH2:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4].[CH3:7][O-:8].[Na+].CO[C:12]([C:14]1[CH:19]=[C:18]([NH2:20])[CH:17]=[C:16]([C:21]([O:23]C)=O)[CH:15]=1)=[O:13]>CO>[NH2:20][C:18]1[CH:19]=[C:14]([C:12]([NH:1][CH:2]([CH2:3][OH:4])[CH2:7][OH:8])=[O:13])[CH:15]=[C:16]([C:21]([NH:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4])=[O:23])[CH:17]=1
Reactant: COC(=O)c1cc(N)cc(C(=O)OC)c1
Reactant: NC(CO)CO
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: Nc1cc(C(=O)NC(CO)CO)cc(C(=O)NC(CO)CO)c1
Temperature: 25 °C
Yield: 93 %

Procedure:
2-Amino-1,3-dihydroxypropane (27.4 g, 300 mmol) and 1.5M solution of sodium methylate in methanol (14.3 mL, 21.5 mmol) are added to a suspension of 5-amino-1,3-benzenedicarboxylic acid dimethyl ester (30.0 g, 143 mmol) in methanol (0.2 L). The reaction mixture is heated to the reflux temperature to get a solution. After 2.5 hours of reflux and 4 hours at room temperature the reaction mixture is filtered and the solid on filter is washed with methanol (40 mL) and dried yielding the product of the title (43.5 g, 133 mmol, yield: 93%).
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]([S:26][CH3:27])=[CH:18]2)=[CH:13][CH:12]=1.O.C(Cl)Cl>CN(C=O)C>[Br:8][C:18]1[N:17]([C:14]2[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)[C:25]2[C:20]([C:19]=1[S:26][CH3:27])=[CH:21][CH:22]=[CH:23][CH:24]=2
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ccc(-n2cc(SC)c3ccccc32)cc1
Solvent: ClCCl
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(-n2c(Br)c(SC)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
NBS (529 mg, 2.97 mmol) was added to a cooled (0° C.) solution of 1-(4-methoxyphenyl)-3-(methylthio)-1H-indole (800 mg, 2.97 mmol) in 10 ml of DMF. The temperature was allowed to warm to RT and the mixture was stirred at RT for 30 min. Water and DCM were added and the phases were separated. After evaporation of the solvents, the residue was purified by flash chromatography with heptane/EtAc 20:1 to provide 2-bromo-1-(4-methoxyphenyl)-3-(methylthio)-1H-indole in 66% yield. ES/MS m/z: 348.04, 350.01 (M+H).
Reaction SMILES: Cl.[CH3:2][C:3]([C:7]1[CH:8]=[C:9]([CH3:13])[CH:10]=[CH:11][CH:12]=1)([CH3:6])[CH2:4][NH2:5].C(N(CC)CC)C.ClC(Cl)(O[C:25](=[O:31])OC(Cl)(Cl)Cl)Cl.FC(F)(F)C(O)=O.[CH3:40][C:41]1([NH2:49])[CH:46]2[CH2:47][CH2:48][N:43]([CH2:44][CH2:45]2)[CH2:42]1>>[CH3:6][C:3]([C:7]1[CH:8]=[C:9]([CH3:13])[CH:10]=[CH:11][CH:12]=1)([CH3:2])[CH2:4][NH:5][C:25]([NH:49][C:41]1([CH3:40])[CH:46]2[CH2:47][CH2:48][N:43]([CH2:44][CH2:45]2)[CH2:42]1)=[O:31]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Cc1cccc(C(C)(C)CN)c1
Reactant: CC1(N)CN2CCC1CC2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: Cc1cccc(C(C)(C)CNC(=O)NC2(C)CN3CCC2CC3)c1
Yield: 69.1 %

Procedure:
Using general procedure D, 2-methyl-2-(m-tolyl)propan-1-amine hydrochloride (100 mg, 0.501 mmol), triethylamine (279 uL, 2.00 mmol), triphosgene (47 mg, 0.18 mmol) and 3-methylquinuclidin-3-amine 2,2,2-trifluoroacetate (140 mg, 0.550 mmol) gave 1-(2-methyl-2-(m-tolyl)propyl)-3-(3-methylquinuclidin-3-yl)urea (41 mg, 25%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.23 (t, J=7.7 Hz, 1H), 7.18-7.12 (m, 2H), 7.04 (d, J=7.5 Hz, 1H), 4.12 (s, 1H), 4.08 (t, J=6.0 Hz, 1H), 3.39-3.22 (m, 2H), 2.81-2.62 (m, 6H), 2.34 (s, 3H), 1.98-1.89 (m, 1H), 1.80-1.63 (m, 2H), 1.51-1.23 (m, J=26.9 Hz, 2H), 1.37 (s, 3H), 1.30 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 157.9, 147.1, 138.2, 128.6, 127.1, 127.1, 123.3, 64.0, 52.2, 52.1, 46.9, 46.7, 39.2, 31.2, 27.1, 26.8, 25.4, 23.5, 22.7, 21.9. Purity: >99.9% UPLCMS (210 nm); retention time 0.79 min; (M+1) 330.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.[CH3:12][O:13]C(Cl)Cl>[Ti](Cl)(Cl)(Cl)Cl.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9]([CH:8]=[CH:7][CH:6]=[C:5]2[CH:12]=[O:13])=[CH:10][CH:11]=1
Reactant: COC(Cl)Cl
Reactant: Fc1ccc2ccccc2c1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Product: O=Cc1cccc2ccc(F)cc12
Yield: 21.1 %

Procedure:
By the method of Preparation 1, 2-fluoronaphthalene (10 g., 0.068 mole) in 200 ml. of methylene chloride was reacted with titanium tetrachloride (25.5 g., 14.7 ml. 0.136 mole) and 1,1-dichloromethyl methyl ether (10.1 g., 0.088 mole). The resulting crude product (11 g.) was first recrystallized from hexane to yield 7-fluoro-1-naphthaldehyde [2.5 g., m.p. 95°-96° C., Rf 0.25 (1:1 chloroform:hexane)]. The mother liquor was evaporated to dryness and the residue chromatographed on 400 g. of silica gel, eluting initially with 3:1 hexane:chloroform and then with 3:2 hexane:chloroform. The column was monitored by tlc. Fractions contain clean 2-fluoro-1-naphthaldehyde [Rf 0.31 (3:2 hexane:chloroform)] were combined and evaporated to dryness, yielding purified 2-fluoro-1-naphthaldehyde (2.8 g., m.p. 60°-62° C.).
Reaction SMILES: C([O:4][C:5]1[C:10]2[CH:11]=[C:12]([CH3:14])[O:13][C:9]=2[CH:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:6]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C.ClCCl>[OH:4][C:5]1[C:10]2[CH:11]=[C:12]([CH3:14])[O:13][C:9]=2[CH:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:6]=1
Reactant: CCOC(=O)c1cc(OC(C)=O)c2cc(C)oc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)c1cc(O)c2cc(C)oc2c1
Temperature: 60 °C
Reaction time: 3 h
Yield: 95 %

Procedure:
A mixture of ethyl 4-(acetyloxy)-2-methyl-1-benzofuran-6-carboxylate in absolute ethanol (500 mL) and potassium carbonate (18 g, 0.13 mol) was stirred for 3 h at 60° C. The mixture was diluted with 500 mL of dichloromethane and the suspension was filtered. The precipitate was washed with 200 mL of dichloromethane. The combined solutions was washed with 200 mL of a 10% aqueous solution of citric acid and evaporated in vacuum to dryness. The crude product introduced into a silica gel column and eluted with hexane/ethyl acetate mixture (2:1) to give 20 g (91 mmol, 95%) of desired compound as a yellow solid. 1HNMR (DMSO d-6): 1.30 (t, H), 2.45 (s, 3H), 4.30 (qt, 2H), 6.65 (s, 1H), 7.28 (2, 1H), 7.53 (s, 1H), 10.25 (s, 1H).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:27])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH2:9]1)C1C=CC=CC=1.CC(Cl)OC([Cl:39])=O>ClCCCl>[ClH:39].[NH:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C@:14]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)([OH:27])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH2:9]1
Reactant: OC(Cc1ccccc1OC(F)(F)F)(c1ccccc1)C1CN(Cc2ccccc2)CCO1
Reactant: CC(Cl)OC(=O)Cl
Solvent: ClCCCl
Product: Cl
Product: O[C@@](Cc1ccccc1OC(F)(F)F)(c1ccccc1)[C@H]1CNCCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.7 %

Procedure:
To a solution of 1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol (7 g, 1 equiv.) in dry 1,2-dichloroethane (40 mL) at 0° C. under nitrogen atmosphere was added ACE-Cl (20.33 g, 10 equiv.). The reaction mixture was left to warm to room temperature for 48 hours. All volatiles were evaporated under vacuum, and the resulting solid was taken-up with methanol (50 mL) and stirred at room temperature overnight. The solution was filtered through acid ion exchange column and the required fractions evaporated to dryness. The resulting solid was taken up with acetonitrile and the insoluble material filtered off. The mother liquor was concentrated in vacuo and purified via preparative HPLC. Both fractions were mixed (from slurry and from HPLC) and taken up in ethanol. Hydrogen chloride was added (large excess of 2M solution in diethyl ether) and the mixture stirred. Then all the volatiles were evaporated in vacuo, to give 1.9 g of the title compound as a white solid (33%). 1H NMR (300 MHz, DMSO D6) δ: 2.45-2.50 (m, 1H), 2.81-2.97 (m, 2H), 3.18-3.30 (m, 3H), 3.89-3.97 (m, 1H), 4.15-4.18 (m, 2H), 7.02-7.29 (m, 9H), 9.18 (bs, 2H). LCMS (12 minutes method) [M+H]+=368 @ Rt 4.88 min. single major peak. NET Ki=12.39 nM.
Reaction SMILES: C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][CH:9]=[CH:8]1.[Cl:12][C:13]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:14]=1[C:15](Cl)=[O:16]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[CH3:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:15]([C:14]1[CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=[CH:21][C:13]=1[Cl:12])=[O:16]
Reactant: Cn1cccc1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1Cl
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Product: Cn1cccc1C(=O)c1cc([N+](=O)[O-])ccc1Cl
Temperature: -70 °C
Reaction time: 1 h
Yield: 17.4 %

Procedure:
To a mixture of n-butyllithium (2.5 M in hexanes, 100 ml, 0.250 mol) and tetrahydrofuran at room temperature is added N-methylpyrrole (40.6 g, 0.500 mol) dropwise over 30 minutes. The resultant mixture is stirred 90 minutes at 35-40° C. and cooled to −70° C. Zinc chloride (0.5 M in tetrahydrofuran, 500 ml, 0.25 mol) is added dropwise such that the temperature does not exceed −60° C. The resultant mixture is allowed to warm to 0° C. and stirred one hour at 0° C. A solution of 2-chloro-5-nitrobenzoyl chloride (60.5 g, 0.275 mol) in tetrahydrofuran is added, followed by tetrakis triphenylphosphine palladium (5.00 g). The resultant mixture is allowed to warm to room temperature, stirred overnight, and quenched with 10% aqueous hydrochloric acid. The organic layer is saved and the aqueous layer is extracted with ethyl acetate. The organic layers are combined, washed with saturated sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. Concentration in vacuo affords a maroon gum, which is chromatographed on silica gel with hexanes-ethyl acetate to afford the title compound as a yellow solid (12.7 g, 19.2%, mp 108.5-109.5° C.) which is identified by IR and NMR spectral analysis. Using an essentially identical procedure and the appropriate heterocycle the following ketones are prepared:
Reaction SMILES: [O:1]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:15]([O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Cl)=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(NC2CCCCC2)CCCCC1>>[CH2:15]([O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][C:8]([CH3:14])([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)C(C)Oc1ccccc1
Reactant: ClCc1ccc(OCc2ccccc2)cc1
Agent: C1CCC(NC2CCCCC2)CC1
Product: CCOC(=O)C(C)(Cc1ccc(OCc2ccccc2)cc1)Oc1ccccc1
Yield: 40.2 %

Procedure:
In a similar manner to that described in Reference example 7(c), a reaction was carried out using ethyl 2-phenoxypropionate (6.15 g), 4-benzyloxybenzyl chloride (9.62 g) and dicyclohexylamine (5.78 g) instead of diisopropylamine and the reaction mixture was treated to afford the desired compound (4.97 g) as a syrup.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([OH:16])=[O:15])[C:5]2=[O:17].[C:18]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:23]=CC=C[CH:19]=1.N(C(OCC)=O)=NC(OCC)=[O:40]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:19][CH2:18][CH2:23][OH:40])=[O:15])[C:5]2=[O:17]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(Br)cnc21
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCn1cc(C(=O)OCCCO)c(=O)c2cc(Br)cnc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 75.3 %

Procedure:
6-Bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (2.0 g, 6.73 mM), propane-1,3-diol (Intermediate 22, 2.047 g, 26.93 mmol) and triphenylphosphine (7.058 g, 26.93 mmol) were dissolved in tetrahydrofuran (80 mL). Diethyl azodicarboxylate (DEAD) (3.51 g, 20.02 mmol) was added and the mixture was stirred for 16 h at room temperature. The solvent was evaporated under reduced pressure and water (100 mL) was added to the residue. The aqueous mixture was extracted with ethyl acetate (2×100 mL) and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a crude compound. The crude compound was purified by flash column chromatography over silica gel (100-200 mesh) and the product was eluted with a gradient of 50% ethyl acetate/petroleum ether to 100% ethyl acetate to afford 1.8 g (80%) of 3-hydroxypropyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1>CO.CN(C=O)C.O=[Pt]=O>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1
Reactant: Cc1cnc(Cl)nc1C#Cc1ccccc1C1(C(N)=O)CC1
Agent: O=[Pt]=O
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cnc(Cl)nc1CCc1ccccc1C1(C(N)=O)CC1
Temperature: 25 °C
Reaction time: 110 h

Procedure:
A mixture of 1-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide A39 (1.85 g, 5.93 mmol) and PtO2 (0.404 g, 1.78 mmol) in MeOH (10 mL) and DMF (40 mL) was stirred under an atmosphere of H2 for 110 hours at room temperature. The mixture was filtered through Celite and the volatiles were removed in vacuo. The residue was purified by column chromatography (Biotage Isolera, 40 g SiO2, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A40 as a white solid (1.65 g, 88%). LCMS-D: rt 3.20 min; m/z 316 [M+H]+.
Reaction SMILES: [CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[H][H].CC(O)=[O:31]>O=[Pt]=O>[CH3:1][CH2:2][C@@:3]1([OH:26])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[C:18]([OH:31])[CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11]
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Reactant: [H][H]
Reactant: CC(=O)O
Agent: O=[Pt]=O
Product: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3cc(O)ccc3nc2-1
Reaction time: 0.5 h

Procedure:
10-Hydroxycamptothecin was prepared by subjecting camptothecin (3.2 g 0.0092 mol), 0.8 g of Pt0 (prepared by pre-reduction of 8 g of amorphous PtO2 in 80 ml of HOAc for 1.5 hr under 1 atmosphere hydrogen pressure) and acetic acid to 1 atm. of H2 for 8.5 h after which theoretical amount of H2 absorbed (slightly more than 0.4 l) and uptake of H2 gets slowed down The reaction mixture was degassed under steam of Helium and filtered through celite and washed with HOAc (20 ml). The resulting solution of 1, 2, 6, 7 tetrahydroxy-camptothecin was treated immediately with Pb (OAc)4 (6.4 g 0.014 mol) in portions and reaction mixture, stirred vigorously under Helium for 30 min. Gumy residue was obtained on evaporation of solvent which was triturated with cold water (100 ml) to produce light brown solid. The solid was collected, washed with cold water and air dried overnight when a mixture of 10-HCPT (44%), 10-AcHOCPT (26%) and unreacted CPT (32%) on HPLC basis was obtained. This crude mixture was combined with 150 ml of 50% HOAc and heated under reflux conditions overnight The reaction mixture was cooled, concentrated to 20 ml and treated with cold water (100 ml) to produce precipitate, which is filtered, washed with more cold water and dried to afford 2.1 g of solid containing HCPT (70%) AcCPT (1.2%) and CPT (21.3%) on the basis HPLC. Mixture was triturating with 0.5% aq HCl to dissolve the water-soluble. When insoluble CPT was removed by filtration. Water-soluble was extracted with chloroform and crystallized from boiling solution of 20% of MeOH in CHCl3 by adding EtOAC dropwise until turbidity appeared to obtain pure yellow HCPT which gives orange colored spot on TLC (CHCl3, acetone, MeOH 7:2:1), C20H16N2O5 (m/s 364), mp 268-270° C. UV. λmax. 222, 266, 330 and 382 IR (KBr) 3480 (OH), 1740 (Lactone) and 1655 (pyridone) cm−1; 1H NMR 0.88 (t, 3, C-18), 1.85 (m, 2, C-19 CH3), 5.35 (s, 2, C-17), 6.40 (s, C-20 OH), 7.22 (s, 1H, C-14), 7.28 (m, C-11 and C-12), 7.26 (d, 1, C-9), 8.38 (1, s, C-7), 10.3 (s, br, C-10 OH).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[N:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:33]=[CH:32][C:21]([C:22]([NH:24][C:25]3[CH:26]=[N:27][CH:28]=[CH:29][C:30]=3[NH2:31])=[O:23])=[CH:20][CH:19]=2)=[CH:14][CH:13]=1>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:31][C:30]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[NH:24][C:22](=[O:23])[C:21]2[CH:20]=[CH:19][C:18]([C:15]3[CH:14]=[CH:13][N:12]=[CH:17][CH:16]=3)=[CH:33][CH:32]=2)=[O:8])=[CH:5][CH:4]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: Nc1ccncc1NC(=O)c1ccc(-c2ccncc2)cc1
Product: COc1ccc(C(=O)Nc2ccncc2NC(=O)c2ccc(-c3ccncc3)cc2)cc1
Yield: 4 %

Procedure:
Using 4-methoxybenzoyl chloride and a similar procedure to that described for Example 2, Part C, N3-[4-(4-pyridyl)-benzoyl]-3,4-pyridinediamine (55 mg, 0.19 mmol) yielded 3.2 mg (4%) of the title compound.
Reaction SMILES: [CH2:1]([C:6]1[CH:19]=[CH:18][C:17]2[C:16](=[O:20])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:21])[C:8]=2[CH:7]=1)[C:2]([CH3:5])([CH3:4])[CH3:3].C(C1C=CC=CC=1)C(C)(C)C.C1(=O)OC(=[O:37])C2=CC=CC=C12>>[CH2:1]([C:6]1[CH:19]=[CH:18][C:17]([C:16]([C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]([OH:21])=[O:37])=[O:20])=[CH:8][CH:7]=1)[C:2]([CH3:3])([CH3:4])[CH3:5]
Reactant: CC(C)(C)Cc1ccc2c(c1)C(=O)c1ccccc1C2=O
Reactant: O=C1OC(=O)c2ccccc21
Agent: CC(C)(C)Cc1ccccc1
Product: CC(C)(C)Cc1ccc(C(=O)c2ccccc2C(=O)O)cc1

Procedure:
We have found that this object is achieved by the novel compound 2-neopentylanthraquinone of the formula ##STR2## Furthermore, we have found a process for the preparation of 2-neopentylanthraquinone, wherein neopentylbenzene is acylated with phthalic anhydride by a Friedel-Crafts reaction to give 2-(4-neopentylbenzoyl)-benzoic acid and the latter is cyclized in the presence of a strong anhydrous acid to give 2-neopentylanthraquinone. We have also found that 2-neopentylanthraquinone is a catalyst for the preparation of hydrogen peroxide.