Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:3]([C:22]2[CH2:23][CH2:24][NH:25][CH2:26][CH:27]=2)=[N:4][C:5]2[N:6]([N:9]=[CH:10][C:11]=2[C:12]2[CH:13]=[N:14][C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=1[NH2:8].C(N(CC)C(C)C)(C)C.Br[CH2:38][C:39]([O:41]C(C)(C)C)=[O:40]>CN(C=O)C>[NH2:8][C:7]1[N:6]2[N:9]=[CH:10][C:11]([C:12]3[CH:13]=[N:14][C:15]4[C:20]([CH:21]=3)=[CH:19][CH:18]=[CH:17][CH:16]=4)=[C:5]2[N:4]=[C:3]([C:22]2[CH2:23][CH2:24][N:25]([CH2:38][C:39]([OH:41])=[O:40])[CH2:26][CH:27]=2)[C:2]=1[Br:1]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: Nc1c(Br)c(C2=CCNCC2)nc2c(-c3cnc4ccccc4c3)cnn12
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Nc1c(Br)c(C2=CCN(CC(=O)O)CC2)nc2c(-c3cnc4ccccc4c3)cnn12
Temperature: 50 °C
Reaction time: 18 h

Procedure:
6-Bromo-3-(quinolin-3-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (0.035 mmol) was charged to a 20 mL scintillation vial. Then DMF (1 ml), N,N-diisopropylethylamine (0.14 mmol, 25 μL), and tert-butyl 2-bromoacetate (0.035 mmol, 5.2 μL) were added, respectively. The resulting reaction mixture was stirred at 50° C. 18 hours. After 18 hours, the reaction was concentrated in vacuo and treated with 1 mL TFA. This reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo and purified via reverse-phase preparatory HPLC to yield 2-(4-(7-amino-6-bromo-3-(quinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-5,6-dihydropyridin-1(2H)-yl)acetic acid as yellow solid. (m+H=479.17, retention time=2.09 min)
Reaction SMILES: [F:1][CH2:2][CH2:3][NH:4][C:5]1[CH2:9][O:8][C:7](=[O:10])[CH:6]=1.[H-].[Na+].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[CH:16][N:15]=1.CO>O1CCCC1.C(OCC)(=O)C>[Cl:13][C:14]1[N:15]=[CH:16][C:17]([CH2:20][N:4]([CH2:3][CH2:2][F:1])[C:5]2[CH2:9][O:8][C:7](=[O:10])[CH:6]=2)=[CH:18][CH:19]=1
Reactant: ClCc1ccc(Cl)nc1
Reactant: O=C1C=C(NCCF)CO1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1C=C(N(CCF)Cc2ccc(Cl)nc2)CO1
Temperature: 25 °C
Yield: 50.9 %

Procedure:
1.00 g (6.89 mmol) of 4-[(2-fluoroethyl)amino]furan-2(5H)-one (VI-1) and 0.55 g (13.78 mmol) of a 60% dispersion of sodium hydride in mineral oil in 200 ml of tetrahydrofuran are heated under reflux for 2 h. After cooling to room temperature, 2.23 g (13.78 mmol) of 2-chloro-5-chloromethylpyridine are added, and the mixture is heated under reflux for a further 4 hours. The reaction mixture is cooled to room temperature, and methanol is added. After concentration of the reaction mixture under reduced pressure, the residue is taken up in ethyl acetate and the mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and once with saturated sodium chloride solution. The organic phase is then dried over sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (9:1) gives 949 mg (50% of theory) of 4-[[(6-chloropyridin-3-yl)methyl](2-fluoroethyl)amino]furan-2(5H)-one.
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]1[CH2:10][C@@H:9]([N:11]2[CH:19]=[N:18][C:17]3[C:16](=O)[NH:15][C:14]([NH2:21])=[N:13][C:12]2=3)[CH:8]=[CH:7]1)(=[O:3])[CH3:2].P(Cl)(Cl)([Cl:24])=O.C(N(CC)C1C=CC=CC=1)C>C(OCC)(=O)C>[C:1]([O:4][CH2:5][C@H:6]1[CH2:10][C@@H:9]([N:11]2[CH:19]=[N:18][C:17]3[C:12]2=[N:13][C:14]([NH2:21])=[N:15][C:16]=3[Cl:24])[CH:8]=[CH:7]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H]1C=C[C@H](n2cnc3c(=O)[nH]c(N)nc32)C1
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)c1ccccc1
Solvent: CCOC(C)=O
Product: CC(=O)OC[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(N)nc32)C1

Procedure:
(1S,4R)-[4-(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl acetate (50 mg, 0.17 mmole), phosphoryl chloride (2 mL), and N,N-diethyl aniline (38 μL) were refluxed for 3 minutes. Volatiles were evaporated, and ice-water (5 mL) was added to the residual oil. The solution was neutralized and extracted with methylene chloride (3×20 mL). The methylene chloride layers were dried (MgSO4) and evaporated to give crude product. Chromatography on silica gel (5% methanol-chloroform) gave (1S,4R)-[4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl acetate as pale yellow crystals from ethyl acetate, m.p. 124°-127°; 1H-NMR (DMSO-d6) 8.01 (s, 1, purine H-8), 6.90 (s, 2, NH2), 6.11 and 5.99 (both m, 2, CH=CH), 5.46 (m, 1, CH--N), 4.06 (d, J=6.2, 2, CH2O), 3.1 (m, 1, CH--N), 2.7 and 1.65 (both m, 2, CH2), 1.98 (s, 3, CH3CO).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:17][CH2:16][CH2:15]2)[C:11]([C:18]([F:21])([F:20])[F:19])=[CH:10][C:9]=1[NH:22][C:23](=[O:46])[CH2:24][C:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]2[C:36]([CH2:37][O:38]C3CCCCO3)=[CH:35][N:34]=[N:33]2)[CH:27]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:14]1([C:12]2[C:11]([C:18]([F:20])([F:21])[F:19])=[CH:10][C:9]3[NH:22][C:23](=[O:46])[CH2:24][C:25]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([N:32]5[C:36]([CH2:37][OH:38])=[CH:35][N:34]=[N:33]5)[CH:27]=4)=[N:7][C:8]=3[CH:13]=2)[CH2:15][CH2:16][CH2:17]1
Reactant: CC(C)(C)OC(=O)Nc1cc(N2CCC2)c(C(F)(F)F)cc1NC(=O)CC(=O)c1cccc(-n2nncc2COC2CCCCO2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C1CC(c2cccc(-n3nncc3CO)c2)=Nc2cc(N3CCC3)c(C(F)(F)F)cc2N1

Procedure:
The title compound was prepared from (RS)-[5-azetidin-1-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M54) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (182 mg).
Reaction SMILES: [NH2:1][C:2]1[C:3]([N+:11]([O-])=O)=[CH:4][C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[H][H]>CCO.[Pd]>[NH2:1][C:2]1[C:3]([NH2:11])=[CH:4][C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1
Reactant: Nc1cc2c(cc1[N+](=O)[O-])OCC2
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1cc2c(cc1N)OCC2

Procedure:
The product obtained in Step 5 (2.5 g, 13.9 mmol) and Pd/C (0.5 g) were dissolved in EtOH (50 mL), hydrogenated in a Parr hydrogenation apparatus at room temperature and a hydrogen pressure of 50 PSI for 12 h. The catalyst was removed by filtration, the ethanol solution of the product was directly used in the next step of reaction.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([NH2:27])[C:5]2[C:11]([CH3:12])=[C:10]([CH2:13][CH:14]([C:17]3[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[CH:19][CH:18]=3)[CH2:15][CH3:16])[CH:9]=[N:8][C:6]=2[N:7]=1.[OH-].[Na+]>C(Cl)(Cl)Cl.CO>[NH2:1][C:2]1[N:3]=[C:4]([NH2:27])[C:5]2[C:11]([CH3:12])=[C:10]([CH2:13][CH:14]([C:17]3[CH:26]=[CH:25][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=3)[CH2:15][CH3:16])[CH:9]=[N:8][C:6]=2[N:7]=1
Reactant: CCC(Cc1cnc2nc(N)nc(N)c2c1C)c1ccc(C(=O)OC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CCC(Cc1cnc2nc(N)nc(N)c2c1C)c1ccc(C(=O)O)cc1
Reaction time: 20 h

Procedure:
A solution of 4 (190 mg, 0.521 mmol) in Me2SO (17 mL) was treated with 1 N NaOH (0.75 mL). After 20 hours at 20°-23° C., the solution was found by TLC (CHCl3 -MeOH, 4:1) examination to contain a small amount of unchanged 4. More 1N NaOH (0.50 mL) was added to the solution, kept at 20°-23° C., and 2 hours later TLC showed completed disappearance of 4. The Me2SO was then removed by distillation in vacuo (less than 1 mm, bath to 45° C). The residue was dissolved in H2O (3 mL), and the resulting clear solution was carefully treated dropwise with 1N HCl to produce pH 5 and cause precipitation of 5 as a pale-beige solid. The mixture was chilled in a refrigerator for several hours before the solid was collected and dried; yield 165 mg (82%). Anal. Calcd. for C19H21N5O2.2H2O: C, 58.90; H, 6.50; N, 18.08. Found: C, 59.40; H, 6.14; N, 17.63. Spectral data: mass, m/z 352, MH+ for C19H21N5O2 ; UV λmax 234 nm (ε 39 300), 322 (7730) at pH 1; 235 nm (ε 37 800), 335 (6050) at pH 7; 236 nm (ε 37 600), 346 (6730) at pH 13.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([OH:16])=[C:14]([C:17](=O)[CH3:18])[C:13]([CH3:20])=[N:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][O:22][C:23]([C:25]1[CH:34]=[CH:33][C:28]([C:29]([NH:31][NH2:32])=[O:30])=[CH:27][C:26]=1[N+:35]([O-:37])=[O:36])=[O:24]>CN(C=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15](=[O:16])[C:14](=[C:17]([NH:32][NH:31][C:29](=[O:30])[C:28]3[CH:33]=[CH:34][C:25]([C:23]([O:22][CH3:21])=[O:24])=[C:26]([N+:35]([O-:37])=[O:36])[CH:27]=3)[CH3:18])[C:13]([CH3:20])=[N:12]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(C(=O)NN)cc1[N+](=O)[O-]
Reactant: CC(=O)c1c(C)nn(-c2ccc(C(C)(C)C)cc2)c1O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C(=O)NNC(C)=C2C(=O)N(c3ccc(C(C)(C)C)cc3)N=C2C)cc1[N+](=O)[O-]
Yield: 54.5 %

Procedure:
DMF solution (2.0 mL) of 1-(1-(4-tert-butylphenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)-ethanone (54.5 mg, 0.20 mmol) and 4-methoxycarbonyl-3-nitrobenzhydrazide (47.8 mg, 0.20 mmol) was heated at 110° C. for 6 hours After removing solvent, the residue was purified by column chromatography to give the title compound (53.8 mg, 55%) as a brown solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[Cl:9].[NH2:10][C:11]1[CH:12]=[C:13]2[C:17]3=[C:18]([CH2:20][S:21][CH2:22][CH2:23][N:16]3[C@H:15]3[CH2:24][CH2:25][N:26](C(OC(C)(C)C)=O)[CH2:27][C@@H:14]23)[CH:19]=1>>[Cl:9][C:3]1[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=1[NH:10][C:11]1[CH:12]=[C:13]2[C:17]3=[C:18]([CH2:20][S:21][CH2:22][CH2:23][N:16]3[C@H:15]3[CH2:24][CH2:25][NH:26][CH2:27][C@@H:14]23)[CH:19]=1
Reactant: CC(C)(C)OC(=O)N1CC[C@H]2[C@@H](C1)c1cc(N)cc3c1N2CCSC3
Reactant: Clc1cccc(Br)c1Cl
Product: Clc1cccc(Nc2cc3c4c(c2)[C@@H]2CNCC[C@@H]2N4CCSC3)c1Cl

Procedure:
Using 1-bromo-2,3-dichlorobenzene and following the procedures described in EXAMPLE 33, Parts C and D, tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B was converted into the title compound of EXAMPLE 37 as a powder. 1H NMR(CDCl3, 300 MHz) δ 1.79-1.89 (m, 2H), 2.58-2.69 (m, 1H), 2.79-3.25 (m, 7H), 3.41-3.50 (m, 1H), 3.60-3.68 (m, 2H), 3.74 (s, 2H), 6.01 (s, 1H), 6.73 (d, 1H, J=2 Hz), 6.81-6.85 (m, 3H), 6.95-6.98 (m 1H). LRMS (ES)+: 406 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[F:21])[N:17]=[C:16](O)[N:15]=[CH:14]3)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(=O)(O)[O-].[Na+].O=P(Cl)(Cl)[Cl:30]>>[Cl:30][C:16]1[N:15]=[CH:14][C:13]2[C:18](=[CH:19][C:20]([F:21])=[C:11]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=3)[CH:12]=2)[N:17]=1
Reactant: COc1cc(OC)cc(-c2cc3cnc(O)nc3cc2F)c1
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: COc1cc(OC)cc(-c2cc3cnc(Cl)nc3cc2F)c1
Temperature: 25 °C
Yield: 52 %

Procedure:
A solution of 6-(3,5-dimethoxyphenyl)-7-fluoroquinazolin-2-ol (2.0 g, 6.7 mmol) in POCl3 (30 mL) was heated at 135° C. for 2 hours. After that, the reaction solution was cooled to room temperature and dropwise added to saturated sodium bicarbonate solution (800 mL) at 0° C. The mixture was extracted with ethyl acetate (200 mL*3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (1.1 g, 52%) as a pale yellow solid. MS (ES+) C16H12ClFN2O2 requires: 318, found: 319 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:8](=[O:9])[C:7]2[C:10](Br)=[CH:11][CH:12]=[CH:13][C:6]=2[NH:5][C:4](=[O:15])[CH2:3]1.[C-:16]#[N:17].[Na]>CN(C)C=O.O>[CH3:1][N:2]1[C:8](=[O:9])[C:7]2[C:10]([C:16]#[N:17])=[CH:11][CH:12]=[CH:13][C:6]=2[NH:5][C:4](=[O:15])[CH2:3]1
Reactant: CN1CC(=O)Nc2cccc(Br)c2C1=O
Reactant: [C-]#N
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: CN1CC(=O)Nc2cccc(C#N)c2C1=O
Temperature: 110 °C
Reaction time: 0.17 h
Yield: 42.4 %

Procedure:
2.3 g of 3,4-dihydro-4-methyl-6-bromo-2H-1,4-benzodiazepine-2,5(1H)-dione (U.S. Pat. No. 4,352,817 ex.9) and 1.26 g of cupro cyanide was dissolved in 5 ml dimethyl formamide. This mixture was heated to 110° C. for 30 minutes. This mixture was then cooled to 50° C. and 2.4 g sodium in 6 ml water was added. The resulting mixture was then stirred for 10 minutes, whereafter 30 ml water was added. This mixture was extracted two times with 25 ml ethyl acetate. The organic phase was dryed with calcium chloride. After filtration the organic solution was evaporated in vacuo to give 0.78 g of the title compound. M.p. 261°-69° C.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[N:13]=[CH:12]1.[CH:20]1([N:26]([CH3:37])[C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([CH2:34]Br)=[CH:30][CH:29]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>C1COCC1.C(OCC)(=O)C.CO.O>[CH:20]1([N:26]([CH3:37])[C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:11]3[C:19]4[CH:18]=[CH:17][N:16]=[CH:15][C:14]=4[N:13]=[CH:12]3)=[CH:30][CH:29]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: c1cc2[nH]cnc2cn1
Reactant: CN(C(=O)c1ccc(CBr)cc1)C1CCCCC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: C1CCOC1
Product: CN(C(=O)c1ccc(Cn2cnc3cnccc32)cc1)C1CCCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 5.6 %

Procedure:
Sodium bis (trimethylsilyl)amide (22 ml of 1 M solution in THF) was added to a stirred solution of imidazo[4,5-c]pyridine (2.60 g, 0.02 mol) in dry THF (200 ml) under argon. A fine white precipitate formed. After 90 m the mixture was treated with N-cyclohexyl-N-methyl-4-bromomethylbenzamide (6.20 g, 0.02 mol) dissolved in dry THF (50 ml). The mixture was allowed to warm to ambient temperature and stirred overnight. Methanol (1 ml) was added, followed by water and the product extracted using ethyl acetate (3×150 ml). The combined organic layers were washed with water (2×100 ml), dried over anhydrous potassium carbonate and the soilvent removed to give the crude product. Flash chromatography (flash silica: 10% methanol in ethyl acetate) followed by repeated fractional crystallisation (6 times from ethyl acetate/DIPE) gave the desired regioisomer N-cyclohexyl-N-methyl-4-(1H-imidazo[4, 5-c]pyridylmethyl)benzamide (0.39 g, 5%) as an off white crystalline solid.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8].COCCOC.[F:15][C:16]([F:22])([F:21])[S:17](Cl)(=[O:19])=[O:18].C(N(CC)CC)C>C(Cl)Cl>[F:15][C:16]([F:22])([F:21])[S:17]([O:1][N:2]1[C:6](=[O:7])[CH2:5][CH2:4][C:3]1=[O:8])(=[O:19])=[O:18]
Reactant: O=C1CCC(=O)N1O
Reactant: O=S(=O)(Cl)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: O=C1CCC(=O)N1OS(=O)(=O)C(F)(F)F
Temperature: 25 °C
Yield: 71.6 %

Procedure:
N-Trifluoromethanesulfonyloxysuccinimide was prepared by the following procedure. To a dried flask equipped with a stirrer, under nitrogen, were added N-hydroxysuccinimide (2.10 g, 18.2 mmol), 60 mL of dried DME, and trifluoromethanesulfonyl chloride (2.00 mL, 18.7 mmol). The mixture was cooled in ice, and triethylamine (3 mL, 22 mmol) was added dropwise by syringe. After warming the reaction mixture to room temperature, 150 mL of methylene chloride was added and the organic layer was washed with water (3×100 mL) and dried. Evaporation of the solvent left 3.80 g of a white solid. Recrystallization from methylene chloride-hexane gave 3.22 g (71.6%) of N-trifluoromethanesulfonyloxysuccinimide: mp 122°-123°. A doubly recrystallized sample was prepared: mp 126°-127°; ir (KBr) 1695 (s), 1440 (s), 1230 (m), 1210 (m), 1140 (m), 1120 (m), 1030 (m), 790 (s), 590 (s); uv (CH3CN) 234 nm (shoulder) (ε=130); nmr (CDCl3) 2.85 (s); 19F nmr -71.54 ppm (s); mass spectrum 246.9781 (calcd for C5H4NO5F3S: 246.9762). Anal. Calcd for C5H4NO5F3S: C, 24.30; H, 1.63; N, 5.67; O, 32.37; F, 23.06; S, 12.97. Found: C, 24.16; H, 1.57; N, 5.95.
Reaction SMILES: C(N(CC)CCCC1C=CC=CC=1S(CC1C(C(OC)=O)=C(OC)C(C2C=COC=2)=CC=1)(=O)=O)C.[C:36]1([S:42]([CH2:45][C:46]2[CH:55]=[CH:54][C:53]3[C:48](=[C:49]([O:57][CH3:58])[CH:50]=[CH:51][C:52]=3Br)[C:47]=2[C:59]([O:61][CH3:62])=[O:60])(=[O:44])=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>>[C:36]1([S:42]([CH2:45][C:46]2[CH:55]=[CH:54][C:53]3[C:48](=[C:49]([O:57][CH3:58])[CH:50]=[CH:51][CH:52]=3)[C:47]=2[C:59]([O:61][CH3:62])=[O:60])(=[O:44])=[O:43])[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: COC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc2c(Br)ccc(OC)c12
Agent: CCN(CC)CCCc1ccccc1S(=O)(=O)Cc1ccc(-c2ccoc2)c(OC)c1C(=O)OC
Product: COC(=O)c1c(CS(=O)(=O)c2ccccc2)ccc2cccc(OC)c12

Procedure:
Prepared by proceeding in a similar manner to Intermediate 4, starting from methyl 2-(benzenesulphonylmethyl)-5-bromo-8-methoxynaphthalene-1-carboxylate (Intermediate 188), as a white solid.
Reaction SMILES: Br[C:2]1[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:5]2[CH:6]=[N:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:10])[C:4]=2[C:3]=1[CH2:28][CH3:29].BrC1N(COCC[Si](C)(C)C)C2C=NN(COCC[Si](C)(C)C)C(=O)C=2C=1C.[F:58][CH:59]([F:82])[O:60][C:61]1[CH:62]=[CH:63][C:64](B2OC(C)(C)C(C)(C)O2)=[C:65]2[C:70]=1[O:69][C:68]([CH3:72])([CH3:71])[CH:67]=[CH:66]2.C1(OC2C=C(B3OC(C)(C)C(C)(C)O3)C=CC=2OC(F)F)CC1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>>[F:82][CH:59]([F:58])[O:60][C:61]1[CH:62]=[CH:63][C:64]([C:2]2[N:19]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:5]3[CH:6]=[N:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:16])[CH3:17])[C:9](=[O:10])[C:4]=3[C:3]=2[CH2:28][CH3:29])=[C:65]2[C:70]=1[O:69][C:68]([CH3:71])([CH3:72])[CH:67]=[CH:66]2
Reactant: CCc1c(Br)n(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Reactant: CC1(C)C=Cc2c(B3OC(C)(C)C(C)(C)O3)ccc(OC(F)F)c2O1
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC1(C)OB(c2ccc(OC(F)F)c(OC3CC3)c2)OC1(C)C
Agent: Cc1c(Br)n(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Product: CCc1c(-c2ccc(OC(F)F)c3c2C=CC(C)(C)O3)n(COCC[Si](C)(C)C)c2cnn(COCC[Si](C)(C)C)c(=O)c12
Yield: 101.3 %

Procedure:
Reaction and post treatment were carried out in the same manner as in Example 4-(a) except for using 794 mg (1.57 mmol) of 2-bromo-3-ethyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in the following Reference example 19-(d) in place of 2-bromo-3-methyl-1,5-bis(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one, using 1.08 g (3.06 mmol) of 2-(8-difluoromethoxy-2,2-dimethyl-2H-chromen-5-yl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane obtained in the following Reference example 1-(i) in place of 2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane, and using 57 mg of tricyclohexylphosphine in place of butyl-di-1-adamantylphosphine, whereby 1.03 g of the title compound was obtained as a brownish oil substantially quantitatively.
Reaction SMILES: [N:1]([CH:4]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:19])([F:18])[F:17])[CH:10]=2)[C:5]1=[O:20])=[N+]=[N-].C(N(CC)CC)C.O>C(S)CCS>[NH2:1][CH:4]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]([F:17])([F:18])[F:19])[CH:10]=2)[C:5]1=[O:20]
Reactant: [N-]=[N+]=NC1CCN(c2cccc(OC(F)(F)F)c2)C1=O
Agent: SCCCS
Solvent: O
Solvent: CCN(CC)CC
Product: NC1CCN(c2cccc(OC(F)(F)F)c2)C1=O
Reaction time: 16 h
Yield: 70.4 %

Procedure:
A stirred solution of crude 3-azido-1-(3-trifluoromethoxyphenyl)-2-pyrrolidinone (3.50 g) in 1,3-propanedithiol (10 ml) was treated with triethylamine (4 ml). The solution was stirred for 16 hours then poured into water. The resultant mixture was extracted with diethyl ether (x3), the combined ether extracts washed with brine and dried (MgSO4). Evaporation of the solvent under reduced pressure left a yellow oil which was separated by chromatography on silica-gel, eluting with ethyl acetate followed by a 1:1 mixture of ethyl acetate and methanol, to give the sub-title compound as a clear solid (2.24 g).
Reaction SMILES: Cl.[S:2]1[C:6]([C:7]2([N:17]([CH3:19])[CH3:18])[CH2:16][CH2:15][C:10]3(OCC[O:11]3)[CH2:9][CH2:8]2)=[CH:5][C:4]2[CH:20]=[CH:21][CH:22]=[CH:23][C:3]1=2.Cl>O>[S:2]1[C:6]([C:7]2([N:17]([CH3:18])[CH3:19])[CH2:16][CH2:15][C:10](=[O:11])[CH2:9][CH2:8]2)=[CH:5][C:4]2[CH:20]=[CH:21][CH:22]=[CH:23][C:3]1=2
Reactant: CN(C)C1(c2cc3ccccc3s2)CCC2(CC1)OCCO2
Agent: Cl
Solvent: O
Product: CN(C)C1(c2cc3ccccc3s2)CCC(=O)CC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
(8-Benzo[b]thiophen-2-yl-1,4-dioxa-spiro[4.5]dec-8-yl)-dimethyl-amine hydrochloride (0.60 g, 1.7 mmol) was dissolved in water (0.8 ml), concentrated hydrochloric acid (1.04 ml, 151 mmol) was added and the mixture was stirred at room temperature for 3 d. When the hydrolysis had ended, the reaction mixture was extracted with diethyl ether (2×25 ml) and the aqueous phase was rendered alkaline with 5 N sodium hydroxide solution, the mixture was extracted with methylene chloride (3×25 ml) and the extract was dried over sodium sulfate and concentrated i. vac. Yield: 0.44 g (95%) Ket-6
Reaction SMILES: Br[C:2]1[C:19]2[C:20]3[C:5]([C:6]4[C:21]5[C:10]6=[C:11]([C:22]([N:24]([C:27]7[C:32]([CH:33]([CH3:35])[CH3:34])=[CH:31][CH:30]=[CH:29][C:28]=7[CH:36]([CH3:38])[CH3:37])[C:25](=[O:26])[C:9]6=[CH:8][CH:7]=4)=[O:23])[CH:12]=[CH:13][C:14]=5[C:15]=3[CH:16]=[CH:17][CH:18]=2)=[CH:4][CH:3]=1.[C:39]([O:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]#[CH:48])(=[O:41])[CH3:40].Cl>O1CCCC1.N1CCCCC1.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>[CH:36]([C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([CH:33]([CH3:35])[CH3:34])[C:27]=1[N:24]1[C:25](=[O:26])[C:9]2[C:10]3[C:21]4[C:6](=[CH:7][CH:8]=2)[C:5]2[C:20]5[C:19]([C:2]([C:48]#[C:47][CH2:46][CH2:45][CH2:44][CH2:43][O:42][C:39](=[O:41])[CH3:40])=[CH:3][CH:4]=2)=[CH:18][CH:17]=[CH:16][C:15]=5[C:14]=4[CH:13]=[CH:12][C:11]=3[C:22]1=[O:23])([CH3:38])[CH3:37]
Reactant: C#CCCCCOC(C)=O
Reactant: CC(C)c1cccc(C(C)C)c1N1C(=O)c2ccc3c4cccc5c(Br)ccc(c6ccc(c2c36)C1=O)c54
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: C1CCOC1
Solvent: C1CCNCC1
Product: CC(=O)OCCCCC#Cc1ccc2c3ccc4c5c(ccc(c6cccc1c62)c53)C(=O)N(c1c(C(C)C)cccc1C(C)C)C4=O
Temperature: 70 °C
Reaction time: 1 h
Yield: 89.7 %

Procedure:
2.0 g (3.56 mmol) of 9-bromo—N-(2,6-diisopropylphenyl)perylene-3,4-dicarboximide (prepared in analogy to Example 6a of WO 96/22 332 using N-(2,6-diisopropylphenyl)perylene-3,4-dicarboximide from Example 28 of WO 97/22 607 as starting material) was dissolved in 500 ml of a mixture of one part by volume of absolute tetrahydrofuran (THF) and one part by volume of dry piperidine under inert gas, admixed in succession with 4 mol % of Pd(PPh3)4 (164 mg, 0.14 mmol), 5 mol % of CuI (32 mg, 0.18 mmol) and 1.14 g (7.12 mmol) of 6-acetoxy-1-hexyne; this mixture was slowly heated to 70° C. and held at this temperature for 1 h. After cooling to room temperature, the reaction mixture was added to three times the volume of a mixture of ice and concentrated hydrochloric acid in a volume ratio of 3:1, the organic phase was separated off, the aqueous phase was extracted with 3 times 200 ml of methylene chloride, the combined organic extracts were dried over magnesium sulfate and the solvent was removed under reduced pressure. Chromatography on silica gel using methylene chloride as eluent gave 1.98 g (90%) of N-(2,6-diisopropylphenyl)-9-(6-acetoxy-1-hexynyl)perylene-3,4-dicarboximide as a red powder having a melting point >300° C.