Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#N)=[CH:6][N:5]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1.C(O)=[O:18]>[Ni].O>[NH2:1][C:2]1[C:7]([CH:8]=[O:18])=[CH:6][N:5]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1
Reactant: O=CO
Reactant: N#Cc1cnc(Nc2ccccc2)nc1N
Agent: [Ni]
Solvent: O
Product: Nc1nc(Nc2ccccc2)ncc1C=O
Reaction time: 0.33 h

Procedure:
4-Amino-2-phenylamino-pyrimidine-5-carbonitrile (2.00 g) obtained from Example 71 was combined with wet Raney nickel (2.00 g), 98% formic acid (60 mL) and water (40 mL) in a Parr shaker. The reaction was placed under hydrogen (42 psi) and shaken for 20 minutes. The reaction was filtered, and the filtrate was concentrated in vacuo. The residue was suspended in water, made basic with saturated sodium bicarbonate, and extracted with ethyl acetate three times. The aqueous layer was filtered through a fiberglass filter to disperse the emulsion that was present. The aqueous filtrate was washed with ethyl acetate. The ethyl acetate washes were combined, filtered, washed with saturated sodium chloride, dried with magnesium sulfate and concentrated in vacuo. Chromatography down silica gel, eluting with ethyl acetate:hexane (2:1) gave 0.73 g of the title compound, CIMS (1% NH3 in CH4): 243=M+ +C2H5, 215=M+ +H (Base), 214=M+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][C:11](=[O:17])[NH:12]3)=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21]([C:23]1[C:27]([CH2:28][CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[C:26]([CH:38]=O)[NH:25][C:24]=1[CH3:40])=[O:22])[CH3:19]>C(O)C.N1CCCCC1>[CH2:18]([O:20][C:21]([C:23]1[C:27]([CH2:28][CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[C:26]([CH:38]=[C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[CH:16][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[NH:12][C:11]2=[O:17])[NH:25][C:24]=1[CH3:40])=[O:22])[CH3:19]
Reactant: O=C1Cc2c(cccc2-c2ccc(Cl)cc2)N1
Reactant: CCOC(=O)c1c(C)[nH]c(C=O)c1CCCN1CCN(C)CC1
Solvent: C1CCNCC1
Solvent: CCO
Product: CCOC(=O)c1c(C)[nH]c(C=C2C(=O)Nc3cccc(-c4ccc(Cl)cc4)c32)c1CCCN1CCN(C)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 28.4 %

Procedure:
To a solution of 4-(4-chloro-phenyl)-1,3-dihydro-indol-2-one (60.9 mg, 0.25 mmol) and 5-formyl-2-methyl-4-[3-(4-methyl-piperazin-1-yl)-propyl]-1H-pyrrole-3-carboxylic acid ethyl ester (80.3 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 5-[4-(4-chloro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-2-methyl-4-[3-(4-methyl-piperazin-1-yl)-propyl]-1H-pyrrole-3-carboxylic acid ethyl ester as a yellow solid (38.8 mg, 28%).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:10])[CH2:8][CH2:7][CH2:6][C:5]1=[O:9].[CH2:11]([O:13][C:14](=[O:20])[C:15](OCC)=[O:16])[CH3:12].CC[O-].[Na+]>CCO>[CH2:11]([O:13][C:14](=[O:20])[C:15]([CH:6]1[CH2:7][CH2:8][C:4]([CH3:10])([CH3:3])[C:5]1=[O:9])=[O:16])[CH3:12]
Reactant: CCOC(=O)C(=O)OCC
Reactant: CC1(C)CCCC1=O
Agent: CC[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(=O)C1CCC(C)(C)C1=O
Temperature: 25 °C

Procedure:
Sodium hydride (0.428 g, 17.8 mmol) was added slowly to a NaCl ice bath containing EtOH (5.4 mL, 3.3 M) stirring under N2. 2,2-dimethylcyclopentanone (2.00 g, 17.83 mmol) and diethyloxalate (2.42 mL, 17.8 mmol) were mixed together, and then added to the chilled NaOEt solution. After stirring for 15 minutes, the reaction was warmed to room temperature and stirred for 6 hours, at which point the reaction was judged complete by TLC. The reaction was quenched at 0° C. with 1N HCl and extracted 2× with CH2Cl2. The combined organics were washed with H2O, dried with Na2SO4, filtered, and concentrated to yield 3.4084 g (90.0%) of crude 2 that was sufficiently pure by NMR to go on to the next step without further purification. Note: NaOEt purchased from Aldrich may be substituted for the NaOEt synthesized in situ. 1H (CDCl3, 400 MHz): δ 4.29 (2H, q, J=7.3 Hz), 2.82 (2H, t, J=7.3 Hz), 1.76 (2H, t, J=7.3 Hz), 1.32 (3H, t, J=7.3 Hz), 1.07 (6H, s) ppm. 13C (CDCl3, 100 MHz): δ 218, 162.89, 153.15, 115.98, 62.12, 46.16, 36.39, 23.98, 23.87, 14.22 ppm.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][CH3:8].[C:9]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:14]=[CH:13][C:12]([CH2:15][C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:17](O)=[O:18])=[CH:11][CH:10]=1.CN(C=O)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:9]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:10]=[CH:11][C:12]([CH2:15][C@H:16]([NH:20][C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[C:17]([N:7]([CH2:6][C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)[CH3:8])=[O:18])=[CH:13][CH:14]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(-c2ccccc2)cc1)C(=O)O
Reactant: CNCc1ccco1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CN(Cc1ccco1)C(=O)[C@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a solution of 1-(furan-2-yl)-N-methylmethanamine (195 mg, 1.76 mmol), (S)-3-(biphenyl-4-yl)-2-(tert-butoxycarbonylamino)propanoic acid (500 mg, 1.45 mmol), in CH2Cl2 (3 mL) and DMF (3 mL) was added TEA (0.61 mL, 4.39 mmol) and HATU (724 mg, 1.90 mmol). The mixture was stirred at room temperature for 1 hour. The mixture was quenched with aq. NaHCO3 and extracted with EtOAc. The organic layer was washed with aq. NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography using 30%-EtOAc/heptane to 90% EtOAc/heptane to give (S)-tert-butyl 3-(biphenyl-4-yl)-1-((furan-2-ylmethyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (614 mg). HPLC retention time=1.80 minutes (condition B); MS (m+1)=435.1; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (s, 9H, minor rotamer), 1.34 (s, 9H, major rotamer), 2.61 (s, 3H, major rotamer), 2.83 (s, 3H, minor rotamer), 2.87-2.98 (m, 4H), 4.15-4.32 (m, 2H, minor isomer), 4.20 (d, J=15.1 Hz, 1H, major rotamer), 4.62 (d, J=15.1 Hz, 1H, major rotamer), 4.77 (q, J=7.3 Hz, 1H, major rotamer), 4.95 (q, J=7.3 Hz, 1H, minor rotamer), 5.30 (d, J=8.6 Hz, 1H, minor rotamer), 5.39 (d, J=8.6 Hz, 1H, major rotamer), 6.05 (d, J=2.8 Hz, 1H, minor rotamer), 6.10 (d, J=2.8 Hz, 1H, major rotamer), 6.18 (br. s., 1H, minor rotamer), 6.23 (dd, J=3.2, 1.9 Hz, 1H, major rotamer), 7.10-7.50 (m, 18H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([O:13]C)=[O:12])[S:10][C:5]2=[N:4][CH:3]=1.[OH-].[Na+]>C1COCC1.C(O)C.Cl>[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]([OH:13])=[O:12])[S:10][C:5]2=[N:4][CH:3]=1
Reactant: COC(=O)c1cc2nc(Cl)cnc2s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)c1cc2nc(Cl)cnc2s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.9 %

Procedure:
To a solution of methyl 2-chlorothieno[3,2-b]pyrazine-6-carboxylate 22 (1.23 g, 5.38 mmol) in THF (10 mL) and ethanol (10 mL) was added a solution of 2N sodium hydroxide (13.45 mL, 26.9 mmol). The reaction was stirred at rt for 1 h. The reaction mixture was poured in 2N HCl solution and the resulting precipitate was collected, washed with water and dried to give crude 2-chlorothieno[3,2-b]pyrazine-6-carboxylic acid 23 (1.027 g, 89%). NMR (400 MHz, DMSO-d6) 8.18 (s, 1H), 8.90 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:14][CH2:13][C:12](=[O:15])[NH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25]Cl)=[CH:21][N:20]=1.[Al]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:14][CH2:13][C:12](=[O:15])[N:11]([CH2:25][C:22]3[CH:21]=[N:20][C:19]([Cl:18])=[CH:24][CH:23]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: ClCc1ccc(Cl)nc1
Reactant: O=C1CNC(c2ccc(F)c(Br)c2)=NN1
Agent: [Al]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1CNC(c2ccc(F)c(Br)c2)=NN1Cc1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
DMF was stirred for 10 min while being degassed with dry N2. 3-(3-bromo-4-fluorophenyl)-4,5-dihydro-1,2,4-triazin-6(1H)-one (200 mg 0.74 mmol) was then added and the mixture was degassed an additional 5 min. NaH (21 mg. 0.88 mmol) was added and the solution turned yellow; the solution was purged continuously with N2, then 2-chloro-5-chloromethypyridine (143 mg. 0.88 mmol) was added. The flask was covered with aluminum foil and stirred at approximately 25° C. for approximately 48 hours. TLC indicated a mixture of the desired product and three other components. The reaction mixture was poured into 20 mL water and 30 mL EtOAc, extracted 2× with EtOAc and the combined organics were washed with brine, dried over MgSO4, filtered and evaporated. The crude residue was purified via flash column (50% EtOAc/Hex) and evaporation of the product fractions gave ˜165 mg of material which (by NMR) appeared to be a mixture of the materials shown below.
Reaction SMILES: [CH2:1]([NH2:4])[CH2:2][NH2:3].[C:5]1(=O)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>[Pt]>[CH:5]1([NH:3][CH2:2][CH2:1][NH2:4])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: NCCN
Reactant: O=C1CCCCC1
Agent: [Pt]
Product: NCCNC1CCCCC1
Reaction time: 6 h

Procedure:
In this example the ratio of ethylenediamine:cyclohexanone, the reaction temperature, and the H2 :feed ratio were varied using as a catalyst 0.3 weight percent platinum (sulfided) on gamma-alumina in a non-aqueous environment. Samples were taken every 6 hours to afford the results in Table 1.
Reaction SMILES: CS(O[CH:6]([C:8]1[N:9]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:7])(=O)=O.[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C)C=O>[N:24]([CH:6]([C:8]1[N:9]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:7])=[N+:25]=[N-:26]
Reactant: CC(OS(C)(=O)=O)c1cc2ccccc2n1-c1cccc(F)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(N=[N+]=[N-])c1cc2ccccc2n1-c1cccc(F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 49 %

Procedure:
To the crude 1-[1-(3-fluorophenyl)-1H-indol-2-yl]ethyl methanesulfonate in N,N-dimethylformamide (5 mL) was added sodium azide (0.20 g, 3.0 mmol). The reaction was stirred at room temperature for 2 hr, quenched with water, and extracted with EtOAc. The combined organic layers were dried over MgSO4, concentrated and purified on silica gel (eluting with 0-30% EtOAc in hexane) to give the desired product (0.14 g, 49%). LCMS calculated for C16H13FN(M-N3)+: m/z=238.1. Found: 238.1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]=[C:13]([CH3:18])[C:12]([C:19]([OH:21])=O)=[CH:11]3)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:44][N:45]([CH2:52][C:53]1[CH:59]=[CH:58][C:56]([NH2:57])=[CH:55][CH:54]=1)[CH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>CN(C=O)C.C(N(CC)CC)C>[CH3:44][N:45]([CH2:52][C:53]1[CH:54]=[CH:55][C:56]([NH:57][C:19]([C:12]2[C:13]([CH3:18])=[N:14][C:15]3[C:10]([CH:11]=2)=[CH:9][C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)=[CH:17][CH:16]=3)=[O:21])=[CH:58][CH:59]=1)[CH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1
Reactant: CN(Cc1ccc(N)cc1)C1CCOCC1
Reactant: Cc1ccc(-c2ccc3nc(C)c(C(=O)O)cc3c2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1ccc(-c2ccc3nc(C)c(C(=O)Nc4ccc(CN(C)C5CCOCC5)cc4)cc3c2)cc1
Reaction time: 2 h
Yield: 39.5 %

Procedure:
To a solution of 6-(4-methylphenyl)-2-methylquinoline-3-carboxylic acid (120 mg) and 1-hydroxy-benzotriazole (88 mg) in DMF (5 ml) was added 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (125 mg) at room temperature, and the mixture was stirred for 2 hours. To the mixture was added a solution of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline (105 mg) and triethylamine (0.2 ml) in DMF (5 ml), and the mixture was stirred for 18 hours and concentrated under reduced pressure. To the residue was added water, and the mixture was extracted with chloroform. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethanol/ethyl acetate=1:2), and recrystallized from ethyl acetate-hexane to give N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]phenyl]-6-(4-methylphenyl)-2-methylquinoline-3-carboxamide (Compound 216) (82 mg) as pale yellow crystals.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][CH2:6][CH2:7][C:8](Cl)=[O:9].[C:11]1([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(=S)=S>[Cl:5][CH2:6][CH2:7][C:8]([C:14]1[CH:15]=[CH:16][C:11]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:12][CH:13]=1)=[O:9]
Reactant: O=C(Cl)CCCl
Reactant: COC(=O)CCCCCc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: COC(=O)CCCCCc1ccc(C(=O)CCCl)cc1
Reaction time: 0.17 h

Procedure:
17.2 g of AlCl3, 18.5 ml of CS2 and 3.6 ml of β-chloro-propionyl chloride are placed in a stirring flask with a reflux condenser. 7.06 g of methyl 6-phenylcaproate are allowed to drop into this mixture at room temperature within 10 minutes (rinsing is carried out with 4 ml of CS2). The reaction mixture is subsequently stirred for a further 15 minutes, warmed slightly and then cooled. The reaction mixture is then pipetted into a stirred mixture of ice, water and ether. The organic phase is washed neutral with bicarbonate solution and water. After drying over MgSO4 the solvent is removed, 10.2 g of crystalline product identified as methyl p-[β-chloropropionyl]-6-phenyl-caproate are obtained.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:11]=[CH:10][C:9]2[N:12]=[C:13]([C:15]3[CH:16]=[N:17][N:18]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:19]=3)[S:14][C:8]=2[C:7]=1[OH:27])=[O:5])[CH3:2].[Br:28]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:11]=[C:10]([Br:28])[C:9]2[N:12]=[C:13]([C:15]3[CH:16]=[N:17][N:18]([CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:19]=3)[S:14][C:8]=2[C:7]=1[OH:27])=[O:5])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1ncc2nc(-c3cnn(Cc4ccccc4)c3)sc2c1O
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Product: CCOC(=O)c1nc(Br)c2nc(-c3cnn(Cc4ccccc4)c3)sc2c1O

Procedure:
A suspension of 2-(1-benzyl-1H-pyrazol-4-yl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester, example 91(c)(0.48 g, 1.26 mmol), N-bromosuccinimide (0.24 g, 1.32 mmol), and benzoyl peroxide (30.5 mg, 0.126 mmol) in 4.2 mL of benzene was heated at reflux temperature for 5 h. The reaction mixture was washed successively with saturated sodium bicarbonate, brine, saturated ammonium chloride solution, and brine. The organic solution was dried, filtered, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-100% ethyl acetate in hexanes to produce 0.44 g of a white solid. MS: (+) m/z 459.2 (M+1).
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([NH2:7])=[N:4][C:3]=1[C:8]([F:11])([F:10])[F:9].Cl.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19](Cl)=[O:20]>C(Cl)Cl>[Br:1][C:2]1[S:6][C:5]([NH:7][C:19](=[O:20])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=2)=[N:4][C:3]=1[C:8]([F:11])([F:10])[F:9]
Reactant: O=C(Cl)c1ccccn1
Reactant: Nc1nc(C(F)(F)F)c(Br)s1
Agent: Cl
Solvent: ClCCl
Product: O=C(Nc1nc(C(F)(F)F)c(Br)s1)c1ccccn1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a stirred solution of 5-bromo-4-(trifluoromethyl)thiazol-2-amine (0.204 g, 0.826 mmol) ethyldiisopropylamine (0.36 mL, 2.1 mmol) in methylene chloride (4 mL) at 0° C. was added picolinoyl chloride hydrochloride (0.162 g, 0.908 mmol) and the reaction mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with methylene chloride and washed with saturated NaHCO3, dried, filtered and concentrated under vacuum to give the crude product. The residue was purified by column chromatography eluting with ethyl acetate/hexanes 0 to 30% to give the product.
Reaction SMILES: C1(C)C=CC=C[C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19](C3C=CC=CC=3C)=[CH:18][CH:17]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[Br:30]N1C(=O)CCC1=O>C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[Br:30][CH2:2][C:7]1[CH:12]=[CH:11][C:10]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccccc1-c1ccc(S(=O)(=O)c2ccc(-c3ccccc3C)cc2)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=S(=O)(c1ccccc1)c1ccc(CBr)cc1
Yield: 171.6 %

Procedure:
A solution of p-tolyl phenylsulphone (20 g) in refluxing CCl4 (400 ml) containing dibenzoyl peroxide (0.4 g) was treated with N-bromosuccinimide (15.3 g) in portions rapidly. The mixture was heated under reflux for 30 min., filtered whilst hot and the filtrate allowed to cool. Evaporation gave the title compound (26.8 g), m.p. (103°-104°.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C:18]([I:22])=[N:17][N:16]=[C:15]3I)=[O:11])[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].[O:28]1CCOCC1.Cl>O>[F:1][C:2]([F:25])([F:24])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C:18]([I:22])=[N:17][N:16]=[C:15]3[OH:28])=[O:11])[CH:6]=[CH:7][CH:8]=1
Reactant: O=C(Nc1cccc(C(F)(F)F)c1)c1ccc2c(I)nnc(I)c2c1
Reactant: C1COCCO1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1ccc2c(I)nnc(O)c2c1
Temperature: 50 °C
Reaction time: 16 h

Procedure:
A mixture of 1,4-di-iodo-phthalazine-6-carboxylic acid (3-trifluoromethyl-phenyl)-amide (0.15 g, 0.264 mmol), 2N NaOH (1.32 mL, 2.64 mmol) and dioxane (3 mL) was stirred at 50° C. for 16 h. The reaction mixture was diluted with water, acidified with conc. HCl to ˜pH 4 and extracted with EtOAc (×3). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated to afford 1-iodo-4-hydroxy-phthalazine-6-carboxylic acid (3-trifluoromethyl-phenyl)-amide (27 mg), 1H NMR (600 MHz, CDCl3) δ: 7.20 (d, 1H), 7.31 (t, 1H), 7.72 (d, 1H), 7.96 (d, 1H), 8.00 (s, 1H), 8.33 (dd, 1H), 8.86 (s, 1H), 10.40 (s, 1H), 12.39 (s, 1H) ppm. m/z 460.07; and 4-iodo-1-hydroxy-phthalazine-6-carboxylic acid (3-trifluoromethyl-phenyl)-amide (27 mg), 1H NMR (500 MHz, CDCl3) δ: 7.27 (d, 1H), 7.38 (t, 1H), 8.00 (m, 2H), 8.24 (m, 2H), 8.30 (d, 1H), 10.32 (s, 1H), 12.34 (s, 1H) ppm. m/z 460.07.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.[C:11]([O:15][CH3:16])(=[O:14])[CH:12]=[CH2:13]>C(O)(C)(C)C>[CH3:16][O:15][C:11](=[O:14])[CH2:12][CH2:13][C:8]([C:9]#[N:10])([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:13][CH2:12][C:11]([O:15][CH3:16])=[O:14]
Reactant: C=CC(=O)OC
Reactant: N#CCc1ccc(F)cc1
Solvent: CC(C)(C)O
Product: COC(=O)CCC(C#N)(CCC(=O)OC)c1ccc(F)cc1
Yield: 72.2 %

Procedure:
A mixture of 25 g. (0.185 mole) of the known compound p-fluorophenylacetonitrile and 86 ml. of methyl acrylate in 90 ml. of t-butyl alcohol is heated to reflux. The heat is removed and 28.1 ml. of 40% methanolic Triton B in 42 ml. of t-butyl alcohol quickly added. After about 4 hours of heating at reflux the mixture is allowed to cool and taken up in water and benzene. The organic layer is washed successively with 2.5 N hydrochloric acid, water and brine and then evaporated to dryness. The residue is distilled under vacuum, first at 40 mm. of mercury to remove methyl acrylate and then at 0.25 to 0.30 mm. to give 41 g. (72.2% yield) of dimethyl-4-cyano-4-(4-fluorophenyl)pimelate having a boiling point of 179° to 181°C. The NMR spectrum of the compound confirms its expected structure.
Reaction SMILES: [CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][O:21][CH3:22])=[C:16]([O:23][C:24]1[CH:29]=[CH:28][C:27](Cl)=[CH:26][N:25]=1)[CH:15]=[CH:14][CH:13]=3)=[O:6])([CH3:3])[CH3:2].C(N(CC)CC)C>CC(O)C.[Pd]>[CH:1]([O:4][C:5]([C:7]1[N:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:19]=1[CH2:20][O:21][CH3:22])=[C:16]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH:15]=[CH:14][CH:13]=3)=[O:6])([CH3:3])[CH3:2]
Reactant: COCc1c(C(=O)OC(C)C)ncc2[nH]c3cccc(Oc4ccc(Cl)cn4)c3c12
Agent: [Pd]
Solvent: CC(C)O
Solvent: CCN(CC)CC
Product: COCc1c(C(=O)OC(C)C)ncc2[nH]c3cccc(Oc4ccccn4)c3c12

Procedure:
A suspension of 124 mg of 5-(5-chloro-2-pyridyloxy)-4-methoxymethyl-β-carboline-3-carboxylic acid isopropyl ester in 15 ml of 2-propanol is combined with 50 mg of triethylamine and 120 mg of Pd-C (10%) and hydrogenated at room temperature and under normal pressure. After absorption of the stoichiometric quantity of hydrogen the mixture is filtered, the filtrate is concentrated, and the residue is recrystallized from 2-propanol, thus obtaining 96 mg (84%), mp 188°-189° C.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1.[NH2:15][OH:16]>C(O)C>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1[CH:14]=[CH:13][C:10]([C:11](=[N:15][OH:16])[NH2:12])=[CH:9][CH:8]=1
Reactant: N#Cc1ccc(CC2OCCO2)cc1
Reactant: NO
Solvent: CCO
Product: NC(=NO)c1ccc(CC2OCCO2)cc1
Yield: 73 %

Procedure:
To a solution of 4-((1,3-dioxolan-2-yl)methyl)benzonitrile (1.40 g, 7.41 mmol) in ethanol (10 mL), was added 50% aqueous hydroxylamine (5 mL), and the resultant mixture was heated at 80° C. for 16 hours. The solvent was evaporated at reduced pressure, and the residue partitioned between ethyl acetate and brine. The organic phase was removed, and the aqueous phase was extracted with further ethyl acetate (×2). The combined organic extracts were dried with aqueous magnesium sulfate and evaporated at reduced pressure to afford the title compound (1.21 g, 73%).
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[C:12]([O:16][CH2:17][CH2:18][OH:19])(=[O:15])[CH:13]=[CH2:14]>C(N(CC)CC)C>[C:12]([O:16][CH2:17][CH2:18][O:19][C:4](=[O:5])[C:3]1[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:1]([OH:6])=[O:11])(=[O:15])[CH:13]=[CH2:14]
Reactant: C=CC(=O)OCCO
Reactant: O=C1OC(=O)c2ccccc21
Solvent: CCN(CC)CC
Product: C=CC(=O)OCCOC(=O)c1ccccc1C(=O)O
Temperature: 75 °C
Reaction time: 6 h

Procedure:
Phthalic anhydride (112.1 grams), 2-hydroxyethyl acrylate (87.9 grams), and triethylamine (0.44 grams) were mixed in a round bottom flask. A small amount of dry air was bubbled into the liquid reaction mixture. The reaction mixture was mixed and heated to 75° C. and held at that temperature for six hours. The product was cooled to room temperature. NMR was used to confirm that the product was phthalic acid mono-(2-acryloyloxy-ethyl)ester. The product partially crystallized over time. The product was mixed with 1-methoxy-2-propanol to obtain a 50 weight percent solution.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1)[CH3:2].C(N(CC)CC)C.[C:18](OC(=O)C)(=[O:20])[CH3:19].Cl>ClCCl>[CH2:1]([O:3][C:4]1[CH:10]=[CH:9][C:7]([NH:8][C:18](=[O:20])[CH3:19])=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCOc1ccc(N)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOc1ccc(NC(C)=O)cc1
Reaction time: 1 h

Procedure:
4-Ethoxyaniline (40 g, 0.29 mol) and triethylamine (61 mL, 0.44 mol) were dissolved in dichloromethane (200 mL). Acetic anhydride (30 mL, 0.32 mol) was added in drops thereto, and the mixture was stirred for 1 h at 0° C. to room temperature. 1N hydrochloric acid solution was added, and the reaction mixture was extracted with ethyl acetate, washed with sodium chloride solution, and dried over anhydrous magnesium sulfate to give the title compound.