Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([NH2:3])=[O:2].[H-].[Na+].Cl[C:7]1[N:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([Cl:23])[CH:13]=2)[N:8]=1.O>CN(C=O)C>[Cl:23][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:3][CH:1]=[O:2])[N:16]=[C:15]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: NC=O
Reactant: Clc1ccc2nc(Cl)nc(-c3ccccc3)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=CNc1nc(-c2ccccc2)c2cc(Cl)ccc2n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 22.6 %

Procedure:
To a solution of 54 mg of dry formamide in DMF (5 ml) was added 48 mg of sodium hydride (60%), followed by stirring at room temperature for 30 minutes. To the reaction mixture was added 275 mg of 2,6-dichloro-4-phenylquinazoline (compound No. II-2), followed by warming to 85° C. and further stirring for 3 hours. The resulting reaction solution was poured into 100 ml of water and extracted with ethyl acetate, and then extract was concentrated. The resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3) to obtain 64 mg of the titled compound. Mp. 252.1° C. 1H NMR: 7.59-7.66 (3H, m), 7.72-7.81 (3H, m), 7.88 (1H, d, J=8.8 Hz), 8.02 (1H, d, J=2.0 Hz), 8.37 (1H, br. d, J=10.4 Hz), 9.71 (1H, d, J=10.4 Hz).
Reaction SMILES: Cl.[C:2]([NH:6][OH:7])([CH3:5])([CH3:4])[CH3:3].[N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=1.[O-]S([O-])(=O)=O.[Mg+2].CCN(CC)CC.N(CC)(CC)CC.Cl>CCOC(C)=O.C1(C)C=CC=CC=1>[C:2]([N+:6]([O-:7])=[CH:14][C:10]1[CH:9]=[N:8][CH:13]=[CH:12][CH:11]=1)([CH3:5])([CH3:4])[CH3:3]
Reactant: O=Cc1cccnc1
Reactant: CC(C)(C)NO
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)[N+]([O-])=Cc1cccnc1
Temperature: 105 °C
Reaction time: 4 h

Procedure:
According to a protocol of A. Dondoni, et al., (Synth. Commun. 1994, 24, 2537-2550), an ovendried 250 mL round-bottomed flask equipped with a magnetic stir bar, reflux condenser and adapter to an argon line was charged with 2.512 g (20.0 mmol) of N-tert-butylhydroxylamine hydrochloride (1), 2.144 g (20.0 mmol) of pyridine-3-carboxaldehyde (2b), and 2.889 g (22.0 mmol) of MgSO4.100 mL of anhydrous toluene were added followed by 2.024 g (20.0 mmol, 2.79 mL) of anhydrous Et3N. The reaction mixture was heated to 100-110° C. under atmosphere of argon, and the reaction course was followed by t.l.c. and GC/MS. After 3-5 h, the reaction was cooled to room temperature, MgSO4 was filtered off, and the solvent was evaporated under reduced pressure to yield a dark yellow-green mixture of product and Et3N HCl. The solids were dissolved in EtOAc and the solution was subsequently washed with a saturated aq. NaHCO3-solution (50 mL) to remove Et3N HCl, water (50 mL), and brine (50 mL), dried over MgSO4, filtered, and evaporated under reduced pressure. The crude product was purified by passing through a short plug of silica gel (EtOAc/hexanes (1: 1) to yield after evaporation 3.000 g (84%) of a pale yellow solid. Rf: 0.61 (EtOAc/hexanes=1:9, UV254-quenching). GC: Rt: 3.92 min. 1H NMR (300 MHz, CDCl3, room temp.): δ9.06 (dt, J=8.4,1.8 Hz, 1H, Ar-H), 8.93 (d, J=1.8 Hz, 1H, Ar-H), 8.53 (dd, J=8.8, 1.8 Hz, 1H, Ar-H), 7.56 (s, 1H, HC(═N)), 7.31 (dd, J=8.1, 4.8 Hz, 1H, Ar- H), 1.54 (s, 9H, C(CH3)3) ppm. 13C NMR (75 MHz, CDCl3, room temp.): δ150.20, 150.09, 134.57, 127.49, 126.91, 123.40, 71.43, 28.24 ppm. MS: m/z=178 (M+), 147, 122 (b.p., M+—H2C═C(CH3)2), 106, 79, 57.
Reaction SMILES: C([O:3][C:4](=O)[C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([F:16])=[CH:13][CH:14]=2)[NH:9][CH:8]=1)=O)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[K+]>C1COCC1>[F:16][C:12]1[CH:11]=[C:10]2[C:15]([C:7]([CH2:5][CH2:4][OH:3])=[CH:8][NH:9]2)=[CH:14][CH:13]=1
Reactant: CCOC(=O)C(=O)c1c[nH]c2cc(F)ccc12
Agent: [Al+3]
Agent: [H-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: OCCc1c[nH]c2cc(F)ccc12
Temperature: 0 °C

Procedure:
To a solution of 6-fluoro-3-indoleglyoxylic acid ethyl ester (2.01 g, 8.55 mmol) in dry THF (0.11 L) at 0° C. under argon was added LiAlH4 (1.68 g, 44.2 mmol). The reaction mixture was refluxed for 3 h, cooled to 0° C., and treated with H2O (1.7 mL), 15% aq KOH (1.7 mL), and H2O (5 mL). The mixture was filtered. The filtrate was diluted with EtOAc, and washed with H2O and brine. The EtOAc solution was dried, filtered, and concentrated to give the title compound: TLC Rf=0.33 (9:1 CH2Cl2/Me2CO); MS (ESI−) m/z 178.0; 1H NMR (CDCl3, 300 MHz) δ 8.38 (1H), 7.49 (1H), 7.01-6.63 (3H), 3.90 (2H), 2.99 (2H), 2.23 (1H).
Reaction SMILES: [I:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][CH:12]([OH:15])[CH2:13][OH:14])=[O:9])=[C:6]([I:16])[C:5]([C:17]([NH:19][CH2:20][CH:21]([OH:24])[CH2:22][OH:23])=[O:18])=[C:4]([I:25])[C:3]=1[NH:26][C:27]([NH:29][C:30]1[C:35]([I:36])=[C:34]([C:37]([NH:39][CH2:40][CH:41]([OH:44])[CH2:42][OH:43])=[O:38])[C:33]([I:45])=[C:32]([C:46]([NH:48][CH2:49][CH:50]([OH:53])[CH2:51][OH:52])=[O:47])[C:31]=1[I:54])=[O:28].[CH3:55]I>[OH-].[Na+]>[I:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][CH:12]([OH:15])[CH2:13][OH:14])=[O:9])=[C:6]([I:16])[C:5]([C:17]([NH:19][CH2:20][CH:21]([OH:24])[CH2:22][OH:23])=[O:18])=[C:4]([I:25])[C:3]=1[N:26]([CH3:55])[C:27]([NH:29][C:30]1[C:35]([I:36])=[C:34]([C:37]([NH:39][CH2:40][CH:41]([OH:44])[CH2:42][OH:43])=[O:38])[C:33]([I:45])=[C:32]([C:46]([NH:48][CH2:49][CH:50]([OH:53])[CH2:51][OH:52])=[O:47])[C:31]=1[I:54])=[O:28]
Reactant: CI
Reactant: O=C(Nc1c(I)c(C(=O)NCC(O)CO)c(I)c(C(=O)NCC(O)CO)c1I)Nc1c(I)c(C(=O)NCC(O)CO)c(I)c(C(=O)NCC(O)CO)c1I
Agent: [Na+]
Agent: [OH-]
Product: CN(C(=O)Nc1c(I)c(C(=O)NCC(O)CO)c(I)c(C(=O)NCC(O)CO)c1I)c1c(I)c(C(=O)NCC(O)CO)c(I)c(C(=O)NCC(O)CO)c1I
Temperature: 25 °C
Reaction time: 60 h

Procedure:
N,N'-bis[2,4,6-triiodo-3,5-bis(2,3-dihydroxypropylaminocarbonyl)phenyl]-urea (7.32 g, 5.1 mmol) was dissolved in 2 M aqueous NaOH (10 ml) and methyl iodide (0.95 ml) was added. The mixture was stirred at ambient temperature for 60 h, treated with a strongly acidic ion exchange resin (Amberlyst 15) evaporated and purified by preparative HPLC. Yield 4.7 g (63%) of the product as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][NH:5][C:6](=[O:8])[CH:7]=1.IC.[C:11](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:11])[C:6](=[O:8])[CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: O=c1cc(Cl)cn[nH]1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1ncc(Cl)cc1=O

Procedure:
A solution of 4-chloro-1H-pyridazin-6-one (6.000 mmol; 783.2 mg), Iodomethane (7.200 mmol; 1032 mg; 0.453 mL), and potassium carbonate (9.000 mmol; 1256 mg) in DMF (12 mL) was stirred at room temperature overnight. The mixture was filtered. The filtrate was partitioned between EtOAc and water. The organic layer was concentrated. The residue was purified on silica eluted with 0 to 40% EtOAc in DCM to afford 5-chloro-2-methyl-pyridazin-3-one as an off-white solid (514.7, 59%).
Reaction SMILES: [Br-].[NH2:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][N+:7]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:8]2.[CH3:20][Mg]Cl.[Cl-].[NH4+]>C1COCC1>[NH2:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][N:7]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:8]2[CH3:20]
Reactant: C[Mg]Cl
Reactant: Nc1cccc2c[n+](Cc3ccccc3)ccc12
Agent: [Br-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC1c2cccc(N)c2C=CN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 74.5 %

Procedure:
To solution of 5-aminoisoquinoline (15 g, 104 mmol) in acetone (400 ml) was added benzyl bromide (18.6 ml, 156 mmol). The mixture was stirred at room temp for 2 h before the precipitate was filtered off affording an orange solid (8.64 g). A second crop (4.02 g) was filtered after a further 2 h. To a solution of this 5-amino-2-benzyl-isoquinolinium bromide (8.46 g, 26.8 mmol) in THF (75 ml) at 0° C. under argon was added dropwise methyl magnesium chloride (17.89 ml, 56.6 mmol). The mixture was allowed to warm up to room temperature and was stirred for 2 h. The mixture was then poured into ammonium chloride solution and extracted with ether. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a light brown solid (5.0 g).
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[C:9](=[O:27])[N:10]1[CH2:13][C:12]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:11]1)(C)(C)C.[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>ClCCl>[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41].[NH2:7][C@H:8]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=1)[C:9]([N:10]1[CH2:11][C:12]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[CH2:13]1)=[O:27]
Reactant: CCCCCOC1(c2ccccc2C)CN(C(=O)[C@@H](Cc2ccc(OC)cc2)NC(=O)OC(C)(C)C)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCCCOC1(c2ccccc2C)CN(C(=O)[C@H](N)Cc2ccc(OC)cc2)C1
Temperature: 0 °C
Reaction time: 5 h
Yield: 97 %

Procedure:
2.81 g (5.5 mmol) of tert-butyl[(R)-1-(4-methoxy-benzyl)-2-oxo-2-(3-pentyloxy-3-o-tolylazetidin-1-yl)ethyl]carbamate are solubilized in 10 ml of dichloromethane. The reaction medium is cooled to 0° C. 6.5 ml of trifluoroacetic acid are then introduced. After a return to ambient temperature, the reaction medium is stirred for 5 hours and then concentrated to dryness. The crude product obtained is purified by silica gel chromatography (eluent 9/1 dichloromethane/methanol). 2.81 g in the form of a white powder are obtained with a yield of 97%.
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:22]2[C:9](=[CH:10][C:11]3[C:12](=O)[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[C:19](=O)[C:20]=3[CH:21]=2)[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.I.II>C(O)(=O)C>[CH3:1][C:2]1([CH3:25])[C:22]2[C:9](=[CH:10][C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][C:20]=3[CH:21]=2)[CH:17]=[CH:16][CH:15]=[CH:14]4)[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2
Reactant: CC1(C)c2ccccc2-c2cc3c(cc21)C(=O)c1ccccc1C3=O
Agent: I
Agent: II
Solvent: CC(=O)O
Product: CC1(C)c2ccccc2-c2cc3cc4ccccc4cc3cc21
Yield: 58.6 %

Procedure:
13,13-dimethyl-6H-indeno[1,2-b]anthracene-6,11(13H)-dione (19 g, 0.058 mol) was dissolved in acetic acid (200 ml) and 57% HI (50 ml) was added thereto. The reaction mixture was stirred under reflux for 48 hours. After the reaction was terminated, the reaction solution was added with distilled water (500 ml). Then, the resultant solid was filtered and dissolved in toluene (200 ml), and iodine (4.56 g, 0.018 mol) was added thereto. The reaction mixture was stirred under reflux for 3 hours. After the reaction was terminated, the reaction solution was extracted and purified by column chromatography to give 13,13-dimethyl-13H-indeno[1,2-b]anthracene (10 g, yield=58%).
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:8]=1[O:9][CH2:10][CH2:11][CH:12]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][C:13]1=[O:22]>>[Cl:6][C:7]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:8]=1[O:9][CH2:10][CH2:11][CH:12]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([S:2]([Cl:1])(=[O:5])=[O:3])[CH:19]=2)[NH:14][C:13]1=[O:22]
Reactant: O=S(=O)(O)Cl
Reactant: O=C1Nc2ccccc2CC1CCOc1ccc(Cl)cc1Cl
Product: O=C1Nc2ccc(S(=O)(=O)Cl)cc2CC1CCOc1ccc(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 47 %

Procedure:
After cooling chlorosulfonic acid to 0° C. under N2, the 3-(2-(2,4-dichlorophenoxy)ethyl)-3,4-dihydroquinolin-2(1H)-one was added slowly and stirred at 0° C. for 1 h. The solution was heated to 50° C. for 10 minutes and cooled down to rt. After pouring the reaction mixture into ice, a white precipitate formed which was extracted with CH2Cl2. The organic layer was washed with H2O and brine, then dried over MgSO4 and concentrated in vacuo to complete dryness, giving the product as a white solid (2.4 g, 47% yield).
Reaction SMILES: [CH3:1][NH:2][CH2:3][C:4]1[O:8][C:7]([CH2:9][S:10][CH2:11][CH2:12][NH2:13])=[CH:6][CH:5]=1.[CH3:14][NH:15][C:16](SC)=[CH:17][N+:18]([O-:20])=[O:19]>>[CH3:1][NH:2][CH2:3][C:4]1[O:8][C:7]([CH2:9][S:10][CH2:11][CH2:12][NH:13][C:16]([NH:15][CH3:14])=[CH:17][N+:18]([O-:20])=[O:19])=[CH:6][CH:5]=1
Reactant: CNC(=C[N+](=O)[O-])SC
Reactant: CNCc1ccc(CSCCN)o1
Product: CNCc1ccc(CSCCNC(=C[N+](=O)[O-])NC)o1

Procedure:
A mixture of 2-[[[5-(methylamino)methyl-2-furanyl]methyl]thio]ethanamine (0.9 g) and N-methyl-1-methylthio-2-nitro-etheneamine was heated at 100°-120° for 30 mins under water pump pressure. The residue was purified by column chromatography (silica/methanol: 0.88 ammonia) to give N-[2-[[[5-(methylamino)methyl-2-furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine which was crystallised from acetonitrile m.p. 106°-108° (0.65 g).
Reaction SMILES: [Br:1][C:2]1[C:3](/[CH:16]=[C:17](\[CH3:23])/[C:18]([O:20]CC)=[O:19])=[C:4]([O:14][CH3:15])[C:5]2[C:10]([C:11]=1[O:12][CH3:13])=[CH:9][CH:8]=[CH:7][CH:6]=2.COC1C2C(=CC=CC=2)C(OC)=CC=1/C=C(\C)/C(O)=O>>[Br:1][C:2]1[C:3](/[CH:16]=[C:17](\[CH3:23])/[C:18]([OH:20])=[O:19])=[C:4]([O:14][CH3:15])[C:5]2[C:10]([C:11]=1[O:12][CH3:13])=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: CCOC(=O)/C(C)=C/c1c(Br)c(OC)c2ccccc2c1OC
Agent: COc1cc(/C=C(\C)C(=O)O)c(OC)c2ccccc12
Product: COc1c(Br)c(/C=C(\C)C(=O)O)c(OC)c2ccccc12

Procedure:
Compound 99e was prepared from 98e (0.314 g, 0.828 mmol) as described above for 29a to give 0.291 g (0.829 mmol, 100%) of the product as a white solid following recrystallization from Et2O/hexanes.
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].S(=O)(=O)(O)O.[CH3:11][C:12]1([CH3:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][C:14](=[O:22])[NH:13]1>>[CH3:11][C:12]1([CH3:23])[C:21]2[C:16](=[CH:17][C:18]([N+:1]([O-:4])=[O:2])=[CH:19][CH:20]=2)[CH2:15][C:14](=[O:22])[NH:13]1
Reactant: O=[N+]([O-])[O-]
Reactant: CC1(C)NC(=O)Cc2ccccc21
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CC1(C)NC(=O)Cc2cc([N+](=O)[O-])ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.6 %

Procedure:
With cooling with ice, 692 mg of potassium nitrate was added to 4 mL of sulfuric acid, and 1 g of 1,1-dimethyl-1,4-dihydroisoquinolin-3(2H)-one obtained in Production Example 33-1 was added thereto, and stirred overnight at room temperature. The reaction solution was processed with ice water, and the precipitated solid was taken out through filtration. This was washed with water, and dried at 50° C. under reduced pressure to obtain 937 mg of a mixture of the entitled compound with its position isomer, as a pale yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[CH:4][C:3]=1[CH:9]=O.Cl.[NH2:12][OH:13]>C(O)C.O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[CH:4][C:3]=1[CH:9]=[N:12][OH:13]
Reactant: NO
Reactant: O=Cc1cncc(Cl)c1Cl
Agent: Cl
Solvent: CCO
Solvent: O
Product: ON=Cc1cncc(Cl)c1Cl
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 95.5 %

Procedure:
A solution of 4,5-dichloropyridine-3-carbaldehyde (8.01 g, 45.51 mmol) in ethanol (50 ml) was added to a rapidly stirred solution of hydroxylamine hydrochloride (3.48 g, 50.06 mmol) in water (50 ml). The reaction was stirred at room temperature for 45 min then partitioned between ethyl acetate (100 ml) and water (100 ml). The aqueous layer was extracted with ethyl acetate (2×50 ml) and the combined organic layers were dried over magnesium sulfate before being concentrated in vacuo to afford the title compound as a white solid (8.3 g, 96%).
Reaction SMILES: [C:1]([C:3]1[CH:15]=[CH:14][C:6]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=1)#[CH:2].I[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C.[Cl-].[NH4+]>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.[Cu]I.O.CN(C=O)C>[OH:24][CH2:23][C:20]1[CH:21]=[CH:22][C:17]([C:2]#[C:1][C:3]2[CH:15]=[CH:14][C:6]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:5][CH:4]=2)=[CH:18][CH:19]=1
Reactant: OCc1ccc(I)cc1
Reactant: C#Cc1ccc(OCC(=O)OCC)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CCOC(=O)COc1ccc(C#Cc2ccc(CO)cc2)cc1

Procedure:
To a dried Schlenk flask filled with nitrogen was added Pd(PPh3)4 (19.6 mg, 0.017 mmol), CuI (4.6 mg, 0.024 mmol), ethyl 2-(4-ethynylphenoxy)acetate (49.6 mg, 1.50 mmol), and (4-iodophenyl)methanol (68.2 mg, 0.291 mmol) was added. The flask was evacuated, equipped with a septum, and filled with nitrogen. DMF (5 mL) and DIPEA (0.1 mL, 0.486 mmol) were added through the septum. The reaction was stirred over night and was neutralized with saturated aqueous ammonium chloride (5 mL). Water (5 mL) was added and the mixture was extracted with EtOAc (3×15 mL). The combined EtOAc phases was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The product was purified on a dry silica column (EtOAc:hexanes 1:90→90:1 v/v). The final product was white/yellow and solid (58.0 mg, 77%). Rf=0.36 (EtOAc:hexanes 1:1 v/v). 1H-NMR (CDCl3): □ 1.29 (t, 3H, J=7.2 Hz, CH2CH3); 1.80 (m, 1H, OH); 4.27 (q, 2H, J=7.2 Hz, CH2CH3); 4.63 (s, 2H, OCH2); 4.69 (d, 2H, J=5.4 Hz, CH2OH); 6.82 (m, 2H, Ph); 7.40 (m, 7H, Ph, OH). 13C-NMR (CDCl3): □ 14.1 (CH2CH3); 61.5 (CH2CH3); 65.0 (CH2OH); 65.3 (OCH2); 88.2 (CC); 89.1 (CC); 114.7, 116.5, 122.7, 126.8, 131.6, 133.1, 140.8, 157.8 (Ph); 168.6 (COO).
Reaction SMILES: O1CCN([CH2:7][C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]=2[OH:18])CC1>[Pd].C(O)C>[CH3:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]=1[OH:18]
Reactant: Oc1c(CN2CCOCC2)ccc2ccccc12
Agent: [Pd]
Solvent: CCO
Product: Cc1ccc2ccccc2c1O
Yield: 64.8 %

Procedure:
Research Disclosure, January 1975, 27, concerns incorporated dye-forming blocked developers. In accordance with the process disclosed, a mixture of 65.7 g (0.37 mole) of 2-morpholinomethyl-1-naphthol, 15 g of 10% Pd/C, and 540 ml of ethanol was hydrogenated at ambient temperature and at an initial pressure of 62 psi. The theoretical amount of hydrogen was absorbed in approximately one hour. The catalyst was removed by filtration and the filtrate was concentrated under vacuum. The residue was taken up in ether, extracted with 10% hydrochloric acid then with saturated aqueous NaCl, dried over anhydrous sodium sulfate, then concentrated under vacuum to yield 37.9 g 2-methyl-1-naphthol (65% yield). The acetate (1) was prepared in a yield of 61% using acetic anhydride-pyridine. The overall yield was 40%. This prior art process is disadvantageous in that the intermediate compound, 2-morpholinomethyl-1-naphthol, does not precipitate from water, thus an extraction step is required. Moreover, high loading (20%) of 10% Pd/C is required. Still further, both an extraction step and acetylation step are necessary. Thus, the entire process disadvantageously requires three steps.
Reaction SMILES: [C:1]1(=[O:39])[N:5]([CH2:6][C:7](=[O:33])[CH2:8][NH:9][C@@H:10]([C:14]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:22](=[O:31])[C:21]3[C:16](=[CH:17][C:18]([Cl:32])=[CH:19][CH:20]=3)[N:15]=2)[CH:11]([CH3:13])[CH3:12])[C:4](=[O:34])[C:3]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:2]12.CCN(CC)CC.[C:47]1([CH3:56])[C:48]([C:53](Cl)=[O:54])=[CH:49][CH:50]=[CH:51][CH:52]=1>C(Cl)Cl>[C:47]1([CH3:56])[C:48]([C:53]([N:9]([CH2:8][C:7](=[O:33])[CH2:6][N:5]2[C:4](=[O:34])[C:3]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:2]3[C:1]2=[O:39])[C@@H:10]([C:14]2[N:23]([CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:22](=[O:31])[C:21]3[C:16](=[CH:17][C:18]([Cl:32])=[CH:19][CH:20]=3)[N:15]=2)[CH:11]([CH3:13])[CH3:12])=[O:54])=[CH:49][CH:50]=[CH:51][CH:52]=1
Reactant: CC(C)[C@@H](NCC(=O)CN1C(=O)c2ccccc2C1=O)c1nc2cc(Cl)ccc2c(=O)n1Cc1ccccc1
Reactant: Cc1ccccc1C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccccc1C(=O)N(CC(=O)CN1C(=O)c2ccccc2C1=O)[C@@H](c1nc2cc(Cl)ccc2c(=O)n1Cc1ccccc1)C(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 72.9 %

Procedure:
To 2-[(R)-1-(3-phthalimido-2-oxo-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one (7.22 g, 13.3 mMol) in CH2Cl2 (50 mL) was added Et3N (2.0 mL, 14.3 mMol) and toluoyl chloride (1.9 mL, 14.4 mMol). The reaction was stirred at RT for 18 h, concentrated under vacuum, taken up in EtOAc, washed with 1 N HCl, brine, dried (MgSO4) and evaporated to dryness. Purification by flash chromatography on silica gel (1% MeOH/CH2Cl2) followed by trituration with (1:1) Et2O/pet. ether, filtration and drying under vacuum gave the title compound (6.41 g, 73%) as a white solid. A side fraction (1.20 g) which contained mostly product was also obtained: 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=8.6 Hz, 1 H), 7.69-7.78 (m, 5 H), 7.45-7.49 (m, 3 H), 7.34 (t, 2 H), 7.25-7.29 (m, 3 H), 7.15 (d, J=8.1 Hz, 2 H), 6.19 (d, J=15.9 Hz, 1H), 5.82 (d, J=10.6 Hz, 1H), 5.12 (d, J=15.9 Hz, 1H), 4.56 (d, J=18.8 Hz, 1 H), 4.26 (d, J=18.8 Hz, 1 H), 4.09 (d, J=17.6 Hz, 1 H), 3.90 (d, J=17.6 Hz, 1H), 2.62 (n, 1 H), 2.42 (s, 3 H), 0.93 (d, J=6.8 Hz, 3 H), 0.32 (d, J=6.4 Hz, 3 H); MS (ES) m/e 661.2 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]([CH3:28])([CH2:22][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:9]([CH:11](C(OCC)=O)[C:12](OCC)=[O:13])=[O:10])=[CH:4][CH:3]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O.Cl>CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O1CCCC1>[CH3:26][C:24]([CH3:25])([CH3:27])[CH2:23][CH2:22][C@@:8]1([CH3:28])[C:5]2[C:4](=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[C:12]([OH:13])=[CH:11][C:9]1=[O:10]
Reactant: CCOC(=O)C(C(=O)OCC)C(=O)[C@@](C)(CCC(C)(C)C)c1ccc(F)cc1
Agent: CS(=O)(=O)O
Agent: Cl
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)CC[C@]1(C)C(=O)C=C(O)c2cc(F)ccc21
Temperature: 70 °C
Yield: 50.2 %

Procedure:
The compound of Example 25D (1.68 g, 4.25 mmol) was dissolved in Eaton's reagent (15 mL, 1:10 (w/w) phosphorus pentoxide in methanesulfonic acid, cf. P. E. Eaton, et al. J. Am. Chem. Soc. 1973, 38, 4071) and warmed at 70° C. for 18 h. The solution was cooled to 25° C. and added to a mixture of ice and water. The mixture was extracted with dichloromethane (3×) and the combined organic layers dried (Na2SO4) and concentrated in vacuo. The oil obtained was dissolved in tetrahydrofuran (30 mL) and treated with 1 N HCl solution, followed by warming at reflux for 18 h. The mixture was cooled and extracted with ethyl acetate (2×). The combined organic layers were extracted with water (2×) and saturated NaCl solution. Drying (Na2SO4) and concentration in vacuo afforded a brown solid, which was triturated with ether-hexane and the resulting solid collected by filtration. These procedures afforded the title compound (590 mg, 50%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 0.32 (m, 1 H) 0.71 (m, 10 H) 1.43 (s, 3 H) 1.91 (s, 1 H) 2.05 (m, 1 H) 5.73 (s, 1 H) 7.43 (m, 1 H) 7.57 (dd, J=9.56, 2.57 Hz, 1 H) 7.71 (s, 1 H) 11.79 (s, 1 H). Specific rotation: [α]D−27.7°(c 2.11, EtOH).