Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC1N[CH2:6][CH2:7][N:8]=1)C.[OH-:9].[Na+].S>O>[NH2:8][C@H:7]([C:6]([OH:9])=[O:9])[CH2:7][CH2:6][O:9][NH:8][C:7]([CH3:6])=[NH:8]
Reactant: CCOC1=NCCN1
Reactant: [OH-]
Agent: S
Agent: [Na+]
Solvent: O
Product: CC(=N)NOCC[C@H](N)C(=O)O
Yield: 16 %

Procedure:
The ethylene analog of canavanine 8, was obtained by treatment of the copper salt of L-canaline (1 mmol, 7), prepared as described for 4, with 2-ethoxyimidazoline (240 mg, 1.8 mmol) in water (5 mL) at 45° C. for 4 days. After adjusting the solution to pH 5.0 with 1N NaOH, hydrogen sulfide was bubbled through for 5 min. The acidic reaction mixture was filtered and the filtrate adjusted to pH 3.4 with 1N NaOH. This solution was applied to a 25 cm3 column of Dowex 50×8 (NH4+) and the resin was washed with distilled water (500 mL) followed by 0.2N NH4OH (400 mL). The ammonia wash was evaporated to dryness by rotary evaporation in vacuo, and the resulting residue was purified by cellulose column chromatography (25×1 cm) by elution with n-BuOH:AcOH:H2O (4:1:1). Fractions containing 8 were combined and the solvent was removed by rotary evaporation in vacuo to give pure 8 (29 mg, 16%) as a glassy solid; [α]D23 =+9.6° (c=2.4, H2O); 1H-NMR (D2O): δ4.08-4.17 (m, 2H, 4-CH2), 3.90 (t, J=6.0 Hz, 1H, 2-CH), 3.80 (s, 4H, NCH2CH2N), 2.27 (dt, J=6.0 Hz, 2H, 3-CH2) ppm; 13C-NMR (CDCl3): δ176.66 (C-1), 164.09 (C=N), 75.72 (C-4), 54.99 (C-2), 45.75 (2×NCH2), 31.51 (C-3) ppm; HRFABMS calcd. for C7H14N4O3 203.1144 (MH+), found 203.1128.
Reaction SMILES: [OH:1][C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(NC(C)C)(C)C.[I:26]N1C(=O)CCC1=O>C(Cl)Cl>[OH:1][C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13](=[O:18])[C:14]([F:17])([F:15])[F:16])[CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[I:26]
Reactant: O=C1CCC(=O)N1I
Reactant: O=C(N1CCc2cccc(O)c2CC1)C(F)(F)F
Solvent: CC(C)NC(C)C
Solvent: ClCCl
Product: O=C(N1CCc2ccc(I)c(O)c2CC1)C(F)(F)F
Temperature: 15 °C
Yield: 64.9 %

Procedure:
Add 6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.037 g, 4.0 mmol) and diisopropylamine (60.7 mg, 0.6 mmol) to anhydrous DCM (350 mL) and stir at 10-20° C. Add slowly a solution of N-iodosuccinimide (1.035 g, 4.6 mmol) in DCM (100 mL) over a period of 3 h. Stir the reaction mixture overnight and gradually warm to RT. Quench the reaction with saturated aqueous sodium bicarbonate, separate the organic layer, wash the organic layer with 0.1 N HCl, brine, dry (sodium sulfate) concentrate and purify (silica gel chromatography, eluting with 5:95 to 10:90 EtOAc:hexanes) to give the title compound as a white solid (1.0 g, 65%).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([NH:6][CH2:7][C:8]2[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:25]=O>C(O)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([O:12][C:13]([CH3:19])([CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:21][CH:22]=2)[CH3:25])=[CH:23][CH:24]=1
Reactant: C=O
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CNc2ccc(Cl)cc2)cc1
Solvent: O=CO
Product: CCOC(=O)C(C)(C)Oc1ccc(CN(C)c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To 2.9 g of ethyl 2-[4-(4-chloroanilinomethyl)phenoxy]-2-methylpropionate are added 10 ml of formaldehyde and 20 ml of formic acid to prepare a solution, which is stirred at room temperature for 30 minutes and then at 50° C. for 1 hour. The formaldehyde and formic acid are distilled off from the reaction mixture under reduced pressure, and ethanol is added to the residue. After filtering off the insolubles from the resulting solution, the ethanol is distilled off from the filtrate. The resulting oily residue is dissolved in ether, washed with water and dried. The ether is distilled off from the dried solution to given an oily residue (2.8 g), which is purified by silica gel column chromatography, using chloroform as an eluent to give 2.3 g of ethyl 2-[4-{N-(4-chlorophenyl)-N-methylaminomethyl}phenoxy]-2-methylpropionate, an oily product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[C:7]2[CH:25]=[CH:24][NH:23][C:8]=2[N:9]=[C:10]([NH:12][C:13]2[CH:14]=[N:15][N:16]([CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])[CH:17]=2)[N:11]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[CH3:21][N:20]([CH3:22])[CH2:19][CH2:18][N:16]1[CH:17]=[C:13]([NH:12][C:10]2[N:11]=[C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:29](=[O:32])[CH:30]=[CH2:31])[CH:28]=[CH:27][CH:26]=3)[C:7]3[CH:25]=[CH:24][NH:23][C:8]=3[N:9]=2)[CH:14]=[N:15]1
Reactant: C=CC(=O)Cl
Reactant: CN(C)CCn1cc(Nc2nc(Oc3cccc(N)c3)c3cc[nH]c3n2)cn1
Solvent: C1CCOC1
Product: C=CC(=O)Nc1cccc(Oc2nc(Nc3cnn(CCN(C)C)c3)nc3[nH]ccc23)c1
Temperature: 10 °C
Reaction time: 3 h
Yield: 11 %

Procedure:
To a solution of 4-(3-aminophenoxy)-N-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine in THF (5 mL) which was cooled to 10° C. was added prop-2-enoyl chloride (47.8 mg, 0.528 mmol) and stirred at 10° C. for 3 hrs. The volatiles were removed in vacuo and the residue purified by HPLC (Phenominex Gemini C18, 21.2×100 mm, 5 μm column using the water/acetonitrile with 10 mM ammonium acetate, with the flow rate 40 mL/min with gradient 55%-67% acetonitrile in 6 min) which was then lyophilized to afford the title compound (28.5 mg, 11% yield) as a tan solid. 1H NMR (600 MHz, DMSO-D6) δ ppm 11.06-11.23 (m, 1H) 9.96-10.08 (m, 1H) 8.56-8.64 (m, 1H) 7.56-7.66 (m, 2H) 7.39-7.47 (m, 2H) 7.30-7.36 (m, 1H) 6.94-7.02 (m, 2H) 6.37-6.47 (m, 1H) 6.18-6.30 (m, 2H) 5.68-5.80 (m, 1H) 3.89-4.04 (m, 2H) 2.57-2.64 (m, 2H) 2.18 (s, 6H). m/z (ESI+) for C22H24N8O2 433.2 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][N:7]2[C:16]=1[C:15]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:9][CH2:8]2)([O-:3])=[O:2].[CH2:17](N(CC)CC)C>C(O)C.CI>[N+:1]([C:4]1[CH:5]=[N:6][N:7]2[C:16]=1[C:15]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:9]([CH3:17])[CH2:8]2)([O-:3])=[O:2]
Reactant: CCN(CC)CC
Reactant: O=[N+]([O-])c1cnn2c1-c1ccccc1NC2
Solvent: CCO
Solvent: CI
Product: CN1Cn2ncc([N+](=O)[O-])c2-c2ccccc21
Reaction time: 8 h
Yield: 87 %

Procedure:
2.15 g (0.01 mole) of 1-nitro-5,6-dihydropyrazolo[1,5-c]quinazoline are dissolved in a mixture of 10 ml of ethanol and 20 ml of methyl iodide. 10 ml of triethylamine are added to the boiled mixture. The reaction mixture is boiled for 8 hours, then evaporated to dryness, the residue is dissolved in chloroform, washed with water, dried and evaporated. Thus, 2.0 g (87%) of 1-nitro-6-methyl-5,6-dihydropyrazolo[1,5-c]quinazoline are obtained. M.p.: 172°-173° C.
Reaction SMILES: [NH2:1][C:2]1[C:7](F)=[CH:6][C:5](Br)=[CH:4][C:3]=1[CH2:10]O.[NH2:12][C:13](N)=[O:14]>O>[OH:14][C:13]1[N:12]=[CH:10][C:3]2[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:1]=1
Reactant: Nc1c(F)cc(Br)cc1CO
Reactant: NC(N)=O
Solvent: O
Product: Oc1ncc2ccccc2n1
Temperature: 175 °C
Reaction time: 0.25 h

Procedure:
A mixture of (2-amino-5-bromo-3-fluorophenyl)methanol (5.6 g, 23.7 mmol, obtained from step 3) and urea (21 g, 15 equiv.) was heated to 175° C. with vigorous stirring for 15 min. The reaction was cooled to room temperature and water was added. The solid was collected by filtration. Air-dried to give 2-hydroxyquinazoline as a light brown solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:9]=[C:8]2[N:10]=[CH:11][C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13](O)[C:7]2=[N:6][CH:5]=1)[CH3:2].P(Cl)(Cl)([Cl:22])=O>>[Cl:22][C:13]1[C:7]2[C:8](=[N:9][C:4]([O:3][CH2:1][CH3:2])=[CH:5][N:6]=2)[N:10]=[CH:11][C:12]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCOC(=O)c1cnc2nc(OCC)cnc2c1O
Product: CCOC(=O)c1cnc2nc(OCC)cnc2c1Cl
Temperature: 50 °C

Procedure:
Ethyl 3-ethoxy-8-hydroxypyrido[2,3-b]pyrazine-7-carboxylate (2.5 g) was added to a stirred solution of phosphorus oxychloride (50 ml) with stirring. The mixture was heated at 50° C. for 3 hours and then worked up as described in Example B1 to give ethyl 8-chloro-3-ethoxypyrido[2,3-b]pyrazine-7-carboxylate which was used directly.
Reaction SMILES: CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10](=[O:26])[C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[NH:17][C:18]2[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=2[F:25])[CH2:4][O:3]1.FC(F)(F)C(O)=O>ClCCl>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10](=[O:26])[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=1[F:25]
Reactant: CC1(C)OC[C@H](CONC(=O)c2ccncc2Nc2ccc(I)cc2F)O1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(NOC[C@H](O)CO)c1ccncc1Nc1ccc(I)cc1F
Temperature: 25 °C

Procedure:
A suspension of N-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-3-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (synthesis described below) (3.0 g, 6.16 mmol) in dichloromethane (20 mL) was treated with trifluoroacetic acid (20 mL) and the clear-yellow solution was stirred at room temp. After stirring for 8 h, the contents were concentrated to a yellow oil, which was dissolved in ethyl acetate (100 mL) and poured into water (150 mL). The pH of the biphasic mixture was adjusted between 6 and 7 with 2.0 N aqueous sodium hydroxide and the layers were separated. The organics were dried over sodium sulfate, concentrated to a yellow oil and placed under high vacuum at 40° C. The resultant yellow, solid foam weighed 2.39 g (5.34 mmol, 87%) after drying for 18 h. LC/MS [5.22 min; 448 (M+1)]
Reaction SMILES: [CH:1]1([C:4](=O)[CH:5]([N:7]2[CH:12]=[C:11]([I:13])[CH:10]=[CH:9][C:8]2=[N:14]S(C2C=CC(C)=CC=2)(=O)=O)[CH3:6])[CH2:3][CH2:2]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C1COCC1>[CH:1]1([C:4]2[N:14]=[C:8]3[CH:9]=[CH:10][C:11]([I:13])=[CH:12][N:7]3[C:5]=2[CH3:6])[CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)N=c2ccc(I)cn2C(C)C(=O)C2CC2)cc1
Solvent: C1CCOC1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: Cc1c(C2CC2)nc2ccc(I)cn12
Reaction time: 3 h

Procedure:
To a solution of N-(1-(1-cyclopropyl-1-oxopropan-2-yl)-5-iodopyridin-2(1H)-ylidene)-4-methylbenzenesulfonamide (30.5 g) in THF (300 mL) was added trifluoroacetic anhydride (18.3 mL) dropwise, and the mixture was stirred for 3 hr. The resulting precipitate was collected by filtration, and washed with diethyl ether to give a salt of the title compound as a white solid. The obtained solid was dissolved in 1 N sodium hydroxide, and the solution was extracted with ethyl acetate/THF. Then the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The obtained solid was washed with diisopropyl ether to give the title compound (17.7 g) as a yellow solid.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1B(O)O.Br[C:14]1[CH:15]=[C:16]([NH:20][C:21](=[O:38])[CH2:22][O:23][CH2:24][C:25]([NH:27][C:28]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:29]=2[C:30]([OH:32])=[O:31])=[O:26])[CH:17]=[CH:18][CH:19]=1>>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:14]1[CH:15]=[C:16]([NH:20][C:21](=[O:38])[CH2:22][O:23][CH2:24][C:25]([NH:27][C:28]2[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:29]=2[C:30]([OH:32])=[O:31])=[O:26])[CH:17]=[CH:18][CH:19]=1
Reactant: O=C(COCC(=O)Nc1ccc(Cl)cc1C(=O)O)Nc1cccc(Br)c1
Reactant: OB(O)c1cc2ccccc2o1
Product: O=C(COCC(=O)Nc1ccc(Cl)cc1C(=O)O)Nc1cccc(-c2cc3ccccc3o2)c1

Procedure:
Using the same method as in Example 19-(ii), 2-benzofuran boronic acid was reacted with the 2-[((2-[(3-bromophenyl)amino]-2-oxoethoxy)acetyl)amino]-5-chlorobenzoic acid.methyl ester obtained in Example 19-(i) to give 2-([(2-([3-(1-benzofuran-2-yl)phenyl]amino)-2-oxoethoxy)acetyl]amino)-5-chlorobenzoic acid.methyl ester (yield: 44%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:23])[C:9]1[CH:14]=[C:13]([N+]([O-])=O)[CH:12]=[CH:11][C:10]=1N1C=NN=C1.C=O>C1(C)C(C)=CC=CC=1>[C:8]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:23])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=1
Reactant: O=C(c1ccccc1Cl)c1cc([N+](=O)[O-])ccc1-n1cnnc1
Agent: C=O
Solvent: Cc1ccccc1C
Product: O=C(c1ccccc1)c1ccccc1

Procedure:
In the manner given in Example 2, 2'-chloro-5-nitro-2-(4H-1,2,4-triazol-4-yl)benzophenone in xylene is heated with paraformaldehyde to 118°-124° C to give 2'-chloro-5-nitro-2-]3,5-bis(hydroxymethyl)-4H-1,2,4-triazol-4-yl]benzophenone.
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH2:28][CH2:29][NH2:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH2:28][CH2:29][NH:30][C:11](=[O:13])[C:10]1[CH:14]=[CH:15][CH:16]=[C:8]([NH:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:9]=1
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Reactant: O=C(O)c1cccc(Nc2ccccc2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1cccc(Nc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 25.4 %

Procedure:
A mixture of 3-(phenylamino)benzoic acid (0.155 g, 0.727 mmol), 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.168 g; 0.727 mmol), HATU (0.303 g; 0.799 mmol) and N,N-diisopropylethyldiamine (0.313 mL; 1.82 mmol) in DMF (5 mL), was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulphate, the organic layer was washed with sodium carbonate, brine, dried and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica (eluent 20 to 100% ethyl acetate in heptane) to yield 0.072 g (25%) of the title compound as a pink solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19]C)[N:11]=[C:10]([CH:21]3[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][C:23]([CH3:30])([CH3:29])[CH2:22]3)[CH:9]=2)=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[OH:19])[N:11]=[C:10]([CH:21]3[CH2:26][C:25]([CH3:28])([CH3:27])[O:24][C:23]([CH3:30])([CH3:29])[CH2:22]3)[CH:9]=2)=[CH:4][CH:3]=1
Reactant: COc1ccccc1-n1nc(C2CC(C)(C)OC(C)(C)C2)cc1-c1ccc(Cl)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC1(C)CC(c2cc(-c3ccc(Cl)cc3)n(-c3ccccc3O)n2)CC(C)(C)O1
Yield: 58.4 %

Procedure:
To a solution of 5-(4-chloro-phenyl)-1-(2-methoxy-phenyl)-3-(2,2,6,6-tetramethyl-tetrahydro-pyran-4-yl)-1H-pyrazole (Example 1) (105 mg, 0.25 mmol) in mL of DCM at −78° C. was added a 1M solution of boron tribromide (0.33 mL, 0.33 mmol) in DCM. After 1 hr at −78° C. the reaction was quenched with 3 mL of 1N HCl and then diluted with 50 mL of EtOAc. The organic layer was washed with 50 mL of NaHCO3 and brine, and dried over Na2SO4. The crude product was purified by silica gel chromatography (Thomson Scientific 12-g cartridge, 2-40% EtOAc in heptane in column volumes) to give 60 mg (59%) of the title compound as a white solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[N:3]=1.[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][OH:25])[CH:19]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[C:5]([C:11]#[N:12])=[C:6]([O:25][CH2:24][C:20]2[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=2)[N:7]=1
Reactant: OCc1cccnc1
Reactant: CS(=O)c1nc(N)nc(-n2cccn2)c1C#N
Solvent: C1CCC2=NCCCN2CC1
Solvent: COCCOC
Product: N#Cc1c(OCc2cccnc2)nc(N)nc1-n1cccn1

Procedure:
From 2-amino-4-methanesulfinyl-6-pyrazol-1-yl-pyrimidine-5-carbonitrile, 3-pyridinemethanol and DBU in DME. EI-MS m/e (%): 293 (M+, 100), 92 (60), 65 (29), 39 (24).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]2[N:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([N:19]4[N:28]=[CH:27][C:26]5[C:21](=[C:22]([F:33])[CH:23]=[C:24]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH:25]=5)[C:20]4=[O:34])[C:14]=3[CH2:35][OH:36])[CH:9]=[C:10]([C:11]#[N:12])[C:5]2=[CH:4][CH:3]=1.C([OH:39])C>O>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([N:19]4[N:28]=[CH:27][C:26]5[C:21](=[C:22]([F:33])[CH:23]=[C:24]([C:29]([CH3:31])([CH3:32])[CH3:30])[CH:25]=5)[C:20]4=[O:34])[C:14]=3[CH2:35][OH:36])[CH:9]=[C:10]([C:11]([NH2:12])=[O:39])[C:5]2=[CH:4][CH:3]=1
Reactant: CC(C)(C)c1cc(F)c2c(=O)n(-c3cccc(-n4cc(C#N)c5ccc(Br)nc54)c3CO)ncc2c1
Reactant: CCO
Solvent: O
Product: CC(C)(C)c1cc(F)c2c(=O)n(-c3cccc(-n4cc(C(N)=O)c5ccc(Br)nc54)c3CO)ncc2c1
Temperature: 45 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
In a 25 mL round-bottomed flask, 6-bromo-1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (14 mg, 25.6 μmol) and [hydrogen bis(dimethylphosphinito-kP)]platinum (II) (110 μg, 0.256 μmol, Eq: 0.01) were combined with Ethanol (2.99 ml) and Water (2.99 ml) to give a colorless solution. The reaction mixture was heated to 45° C. and stirred for 1 h. The crude reaction mixture was concentrated in vacuo. Purification by HPLC gave 6-bromo-1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid amide (11 mg, 77%, [M+H]+ 565).
Reaction SMILES: [N:1]1[CH:2]=[C:3]([C:10]2[CH:11]=[C:12]([NH2:16])[CH:13]=[CH:14][CH:15]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.Br[C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.CC([O-])(C)C.[Na+].N#N>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1[CH:2]=[C:3]([C:10]2[CH:11]=[C:12]([NH:16][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: Brc1cccnc1
Reactant: Nc1cccc(-c2cnc3ccccn23)c1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: N#N
Solvent: C1COCCO1
Product: c1cncc(Nc2cccc(-c3cnc4ccccn34)c2)c1
Temperature: 100 °C

Procedure:
A mixture 3-imidazo[1,2-a]pyridin-3-yl-phenylamine (315 mg, 1.5 mmol), 3-bromopyridine (160 μl, 1.66 mmol), (±)-Binap (93 mg, 0.15 mmol), and NaOtBu (440 mg, 4.6 mmol) in dry dioxane (3 ml) was deoxygenated by evacuation/refill with N2 (×3). Pd2 dba3 (70 mg, 0.08 mmol) was added and the mixture was deoxygenated again (×3). The reaction was stirred and heated at 100° C. for 18 hours under N2. The mixture was partitioned between EtOAc/H2O, then filtered. The aqueous layer was extracted with EtOAc (×2). The combined extracts were dried (MgSO4), filtered and evaporated. The residue was purified by chromatography to give the title compound. MS: [M+H]+ 287
Reaction SMILES: [Br-].[C:2]([CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#[N:3].[OH-].[Na+].[F:26][C:27]1[CH:41]=[CH:40][C:30]([O:31][C:32]2[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=2)=[CH:29][CH:28]=1>O.C(Cl)Cl>[F:26][C:27]1[CH:41]=[CH:40][C:30]([O:31][C:32]2[CH:39]=[CH:38][C:35]([CH:36]=[CH:4][C:2]#[N:3])=[CH:34][CH:33]=2)=[CH:29][CH:28]=1
Reactant: N#CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccc(Oc2ccc(F)cc2)cc1
Agent: [Br-]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: N#CC=Cc1ccc(Oc2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 91.2 %

Procedure:
To a solution of (cyanomethyl)triphenylphosphonium bromide (10.61 g, 27.8 mmol) and NaOH (1.387 g, 34.7 mmol) in water (30 mL) and DCM (15 mL) was added 4-(4-fluorophenoxyl)benzaldehyde (5 g, 23.13 mmol) at 0° C. The mixture was stirred at room temperature for 4 h. DCM (50 mL) and water (50 mL) was added to the mixture, the organic phase was washed with water (50 mL), brine (50 mL), dried over anhydrous sodium sulfate and concentrated. Purification via flash chromatography afforded the title compound (5.1 g, 21.09 mmol, 91% yield) as white solid. LCMS: rt=1.60 min, [M+H+]=240
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]=[N:11][C:12]1[CH:17]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:15]=[C:14]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:13]=1[OH:26])([O-])=O.C1(C)C=CC=CC=1.[OH-].[Na+].[H][H]>[C].[Pd].O.CC(O)C>[OH:26][C:13]1[C:14]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:15][C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:17][C:12]=1[N:11]1[N:10]=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]2=[N:1]1
Reactant: [H][H]
Reactant: CC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)C)c1
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)c1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)C)c1
Yield: 73 %

Procedure:
35.5 g (0.1 mol) of 2-nitro-2'-hydroxy-3',5'-di-t-butylazobenzene, 0.125 g of 5% palladium carbon, 100 ml of toluene, 100 ml of IPA, 100 ml water and 8.3 g of caustic soda were charged into a 500-ml stainless autoclave equipped with an agitator. After the air in the autoclave had been replaced by hydrogen, the pressure of hydrogen was set to 10 kg/cm2. Reaction was effected in the same way as that employed in Example 1. After the reaction had been completed, the catalyst was filtered off. When part of the filtrate was subjected to quantitative analysis using GC, it was found that the yield of 2-(2'-hydroxy-3',5'-di-t-butylphenyl)benzotriazole is 82%. After the solvent had been distilled off from the filtrate, the residual solid was crystallized by IPA, washed with IPA and then dried to obtain 23.6 g of 2-(2'-hydroxy-3',5'-di-t-butylphenyl)benzotriazole (yield, 73%; melting point, 150° to 152° C.).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:26])[C:22]([O:24][CH3:25])=[O:23])=[CH:17][CH:16]=1.C(N(C(C)C)CC)(C)C.C1(C)C=CC=CC=1>O1CCOCC1>[CH2:8]([O:7][C:5]([C:4]1[CH:3]=[C:2]([NH:1][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([C:21](=[O:26])[C:22]([O:24][CH3:25])=[O:23])=[CH:19][CH:20]=2)[CH:12]=[CH:11][CH:10]=1)=[O:6])[CH3:9]
Reactant: COC(=O)C(=O)c1ccc(CBr)cc1
Reactant: CCOC(=O)c1cccc(N)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Solvent: C1COCCO1
Product: CCOC(=O)c1cccc(NCc2ccc(C(=O)C(=O)OC)cc2)c1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
To a solution of ethyl 3-aminobenzoate (7.3 ml) and methyl 2-[4-(bromomethyl)phenyl]-2-oxoacetate (6.4 g) in dioxane (40 ml) was added diisopropylethylamine (6.4 ml), and the mixture was stirred at 60° C. for 2 hrs. The mixture was allowed to return to room temperature and toluene (330 ml) was added. The mixture was left standing at 0° C. for 5 hrs and the precipitated diisopropylethylamine hydrobromide was filtered off. The filtrate was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and water. The ethyl acetate layer was separated, washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane-ethyl acetate:4-1 v/v) to give the object compound (7.61 g) as a syrup.