Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24](I)[CH:23]=3)=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:30]([O:32][CH3:33])=[O:31])#[N:2].[CH3:34][C:35]1[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>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.O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:23]=[C:24]([C:36]4[CH:37]=[CH:38][CH:39]=[C:40]([CH3:41])[C:35]=4[CH3:34])[CH:25]=[CH:26][CH:27]=3)=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:30]([O:32][CH3:33])=[O:31])#[N:2]
Reactant: Cc1cccc(B(O)O)c1C
Reactant: COC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4cccc(I)c4)cc3)c(C#N)cc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: COC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4cccc(-c5cccc(C)c5C)c4)cc3)c(C#N)cc21
Temperature: 100 °C
Reaction time: 17 h
Yield: 64 %

Procedure:
In a vial were placed methyl 6-cyano-7-(4-(3-iodophenylcarbamoyl)phenoxy)chroman-4-carboxylate (Preparation 3) (56 mg, 0.101 mmol), 2,3-dimethylphenylboronic acid (19.70 mg, 0.131 mmol), Na2CO3 (32.12 mg, 0.303 mmol), toluene (1 ml), and water (0.1 ml). The mixture was degassed with Argon for few minutes. Tetrakis(triphenylphosphine)palladium(0) (5.836 mg, 0.0050 mmol) was added and the vial was sealed. The mixture was stirred for 17 hours at 100° C. The crude mixture was purified on silica gel (EtOAc in hexanes gradient) to provide 34.4 mg of the title compound as a thin film (64%).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.N1C=CN=C1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18].O>CN(C=O)C>[O:1]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2)[Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]
Reactant: Oc1cccc2ncccc12
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1cccc2ncccc12
Temperature: 25 °C
Yield: 109.1 %

Procedure:
5-hydroxyquinoline (101 mg) was dissolved in DMF (5 ml) under an argon atmosphere, and the resultant solution was stirred at room temperature. Imidazole (113 mg) and t-butyldimethylsilyl chloride (162 mg) were added to the solution, and the mixture was stirred at room temperature. After disappearance of the raw materials was confirmed, water (5 ml) was added to the reaction solution, and the mixture was then extracted with ethyl acetate. The resultant organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated. The resultant residue was purified by column chromatography (silica gel:hexane/ethyl acetate=9/1) to obtain the object compound (197 mg, yield 100%).
Reaction SMILES: Br[CH2:2][CH3:3].C(=O)([O-])[O-].[K+].[K+].[C:10]1([N:16]2[C:24](=[O:25])[C:23]3[C@@H:22]4[C:26]([CH3:28])([CH3:27])[C@@:19]([CH3:29])([CH2:20][CH2:21]4)[C:18]=3[NH:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CC(C)=O.CO>[CH2:2]([N:17]1[C:18]2[C@@:19]3([CH3:29])[C:26]([CH3:28])([CH3:27])[C@H:22]([CH2:21][CH2:20]3)[C:23]=2[C:24](=[O:25])[N:16]1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH3:3]
Reactant: CC1(C)[C@@H]2CC[C@@]1(C)c1[nH]n(-c3ccccc3)c(=O)c12
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CO
Product: CCn1c2c(c(=O)n1-c1ccccc1)[C@H]1CC[C@]2(C)C1(C)C
Temperature: 25 °C
Yield: 8.7 %

Procedure:
A mixture of bromoethane (1.05 mL, 14.1 mmol), potassium carbonate (3.58 g, 25.9 mmol), and (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 1.74 g, 6.5 mmol) in acetone (20 mL) and methanol (3 mL) was stirred at room temperature over the weekend then the solvent was evaporated and the residue was partitioned between water and dichloromethane. The organic layer was evaporated, and the residue was chromatographed (0-50% ethyl acetate/hexanes) and recrystallized from ethyl acetate to give (4S,7R)-1-ethyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (168 mg, 9%) as a white solid. APCI-MS (M+H) 297.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH:16](OS(C)(=O)=O)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[SH:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32]([NH:36][C:37](=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[N:31][CH:30]=[CH:29]2>CN(C=O)C>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH:16]([S:25][C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[C:32]([NH:36][C:37](=[O:44])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[N:31][CH:30]=[CH:29]3)[CH2:15]1)=[O:13])([CH3:8])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)N1CCCC(OS(C)(=O)=O)C1
Reactant: O=C(Nc1nccc2cc(S)ccc12)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCCC(Sc2ccc3c(NC(=O)c4ccccc4)nccc3c2)C1

Procedure:
Potassium carbonate (44 mg, 0.32 mmol) and 3-methanesulfonyloxypiperidine-1-carboxylic acid tert-butyl ester (70 mg, 0.264 mmol) were added to a solution of the above N-(6-mercaptoisoquinolin-1-yl)-benzamide residue in DMF (2 ml). The mixture was irradiated in a microwave at 160° C. for 600 s then concentrated in vacuo to give a residue. The residue was purified by preparative HPLC to give 3-(1-benzoylaminoisoquinolin-6yl-sulfanyl)piperidine-1--carboxylic acid tert-butyl ester (18 mg), EIMS: m/z=464.3 [M+H]+ and m/z=486.5 [M+Na]+.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[Cl:19])[C:4]1=[O:20].C(N(CC)CC)C.[S:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[CH:30]=[C:29]1[S:37](Cl)(=[O:39])=[O:38]>CC#N>[Cl:19][C:12]1[C:11]2[C:16](=[CH:17][CH:18]=[C:9]([CH2:8][N:5]3[CH2:6][CH2:7][C@H:3]([NH:2][S:37]([C:29]4[S:28][C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=5[CH:30]=4)(=[O:38])=[O:39])[C:4]3=[O:20])[CH:10]=2)[N:15]=[CH:14][CH:13]=1
Reactant: N[C@H]1CCN(Cc2ccc3nccc(Cl)c3c2)C1=O
Reactant: O=S(=O)(Cl)c1cc2ccccc2s1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C1[C@@H](NS(=O)(=O)c2cc3ccccc3s2)CCN1Cc1ccc2nccc(Cl)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.5 %

Procedure:
3-(S)-Amino-1-(4-chloroquinolin-6-ylmethyl)-pyrrolidin-2-one hydrochloride (0.12 g, 0.38 mmol) is suspended in 15 mL CH3CN. To this solution is added triethylamine (110 mL, 0.79 mmol) followed by benzothiophene-2-sulfonyl chloride (0.094 g, 0.40 mmol). The mixture is stirred overnight at room temperature, subjected to aqueous work up then concentrated to dryness. The crude product is purified by column chromatography eluting with 2-10% MeOH/CH2Cl2 to give the title compound (0.11 g, 0.23 mmol) as an off-white solid.
Reaction SMILES: [CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([F:13])[CH:6]=[CH:7][C:8]=2[F:12])[CH2:3]1.OS(O)(=O)=O.[N+:19]([O-])([OH:21])=[O:20].[OH-].[Na+]>>[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5]([F:13])[C:6]([N+:19]([O-:21])=[O:20])=[CH:7][C:8]=2[F:12])[CH2:3]1
Reactant: CN1CCc2c(F)ccc(F)c2C1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CN1CCc2c(F)cc([N+](=O)[O-])c(F)c2C1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
An ice-cooled mixture of 0.94 g (5.1 mmol) 2-methyl-5,8-difluoro-1,2,3,4-tetrahydro-isoquinoline and 2.8 ml conc. H2SO4 is slowly combined with 0.36 ml 65% nitric acid. Then the mixture is stirred for 2.5 h while cooling with ice and it is then poured onto ice water. It is made alkaline with NaOH, extracted 3× with EtOAc, the organic phases are dried with Na2SO4, filtered and concentrated.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14]([N+:17]([O-:19])=[O:18])[C:15]=1[OH:16])[C:5]([CH2:7][C:8](OCC)=[O:9])=O.O.[NH2:21][NH2:22]>C(O)C>[OH:9][C:8]1[NH:22][N:21]=[C:5]([C:4]2[CH:3]=[C:2]([OH:1])[C:15]([OH:16])=[C:14]([N+:17]([O-:19])=[O:18])[CH:13]=2)[CH:7]=1
Reactant: NN
Reactant: CCOC(=O)CC(=O)c1cc(O)c(O)c([N+](=O)[O-])c1
Solvent: O
Solvent: CCO
Product: O=[N+]([O-])c1cc(-c2cc(O)[nH]n2)cc(O)c1O
Reaction time: 0.08 h

Procedure:
2.0 g of ethyl (3,4-dihydroxy-5-nitrobenzoyl)acetate are suspended in 50 ml of ethanol. After treatment with 0.4 g of hydrazine hydrate the mixture is held at the reflux temperature for 16 hours. After distillation of the solvent, the residue is held at the boiling temperature for 5 minutes with 50 ml of ethyl acetate. The separated precipitate is filtered under suction and the filtrate is concentrated to 10 ml. The crystals, which separate in the cold, are filtered under suction. There is obtained 5-(5-hydroxypyrazol-3-yl)-3-nitropyrocatechol in form of orange crystals of m.p. 228° (dec.).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=2)[C:10]([OH:12])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:16]1C=CC=CC=1.CO.C[Si](C=[N+]=[N-])(C)C>CCCCCC>[C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=2)[C:10]([O:12][CH3:16])=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccnc(-c2ccccc2)c1
Reactant: c1ccccc1
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CCCCCC
Solvent: CO
Product: COC(=O)c1ccnc(-c2ccccc2)c1
Reaction time: 6 h

Procedure:
Preparation H1, Step 2: A solution of 2-phenylisonicotinic acid (459 mg, 2.30 mmol) in 9:1 benzene/methanol (20 mL) was cooled to 0° C., and treated with the dropwise addition of a 2.0 M hexane solution of (trimethylsilyl)diazomethane (1.15 mL, 2.30 mmol). The mixture was allowed to come to room temperature and stirred for 6 h. Analysis by TLC indicated incomplete reaction, so the mixture was treated with additional (trimethylsilyl)diazomethane solution (230 μL, 0.23 mmol), and the reaction was stirred for an additional 2 h. TLC of the mixture remained unchanged. The solvent was stripped, and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The layers were separated, the organic phase was washed 2× with saturated sodium bicarbonate, the combined aqueous phases were extracted with ethyl acetate, and the combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified over silica gel, eluting with 20% ethyl acetate/heptane, to yield 372 mg of methyl 2-phenylisonicotinate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.83 (d, J=5.27 Hz, 1H), 8.29 (s, 1H), 8.04 (d, J=7.03 Hz, 2H), 7.77 (d, J=3.52 Hz, 1H), 7.51-7.42 (m, 3H), 3.98 (s, 3H).
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9](F)=[C:8]([Cl:13])[CH:7]=1)(=[O:5])=[O:4])[CH3:2].[Cl:14][C:15]1[CH:16]=[C:17]([CH2:22][C:23]([OH:25])=[O:24])[CH:18]=[C:19]([OH:21])[CH:20]=1>>[Cl:14][C:15]1[CH:16]=[C:17]([CH2:22][C:23]([OH:25])=[O:24])[CH:18]=[C:19]([O:21][C:9]2[CH:10]=[CH:11][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:7][C:8]=2[Cl:13])[CH:20]=1
Reactant: CCS(=O)(=O)c1ccc(F)c(Cl)c1
Reactant: O=C(O)Cc1cc(O)cc(Cl)c1
Product: CCS(=O)(=O)c1ccc(Oc2cc(Cl)cc(CC(=O)O)c2)c(Cl)c1

Procedure:
The title compound was prepared by the method of example 2 step (iii) using the product of example 3 step (i) and the product of example 18 step (iv).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[N:11]=[CH:12][N:13]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:25][C@H:24]([CH2:26]OS(C)(=O)=O)[O:23][C:22]3=[O:32])=[CH:17][C:16]=2[F:33])[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N-:34]=[N+:35]=[N-:36].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[N:34]([CH2:26][C@@H:24]1[O:23][C:22](=[O:32])[N:21]([C:18]2[CH:19]=[CH:20][C:15]([N:13]3[CH:14]=[C:10]([CH2:9][O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[N:11]=[CH:12]3)=[C:16]([F:33])[CH:17]=2)[CH2:25]1)=[N+:35]=[N-:36]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)[Si](C)(C)OCc1cn(-c2ccc(N3C[C@H](COS(C)(=O)=O)OC3=O)cc2F)cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCc1cn(-c2ccc(N3C[C@H](CN=[N+]=[N-])OC3=O)cc2F)cn1
Temperature: 80 °C
Yield: 82.3 %

Procedure:
(5R)-3-(4-(4-t-Butyldimethylsilyloxymethylimidazol-1-yl)-3-fluorophenyl)-5-methanesulfonyloxymethyloxazolidin-2-one (13.6 g) was dissolved in dry N,N-dimethylformamide (110 ml). Sodium azide (3.53 g) was added, and the mixture was heated at 80° C. for 3.5 hours. The mixture was cooled, diluted with water (1.1 L) containing sodium bicarbonate (2 g), and extracted with ethyl acetate (2×800 ml). Combined organics were washed with water (2×300 ml), then brine, and dried over magnesium sulfate. The solution was evaporated to a small volume (˜100 ml), and insolubles filtered. The ethyl acetate soluble material was columned on silica (100 g), eluting with ethyl acetate. Product fractions were combined and evaporated to give a gum (10.0 g).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@@H:6]2[OH:12].N1C=CN=C1.[C:18]([Si:22]([CH3:25])([CH3:24])Cl)([CH3:21])([CH3:20])[CH3:19].O>CN(C)C=O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@@H:6]2[O:12][Si:22]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:25])[CH3:24]
Reactant: O[C@H]1CCc2c(Br)ccc(F)c21
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CCc2c(Br)ccc(F)c21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol (6.8 g) and imidazol (5 g) are dissolved at 0° C. in N,N-dimethylformamide (NMP, 25 mL), treated with tert.-butyldimethylchlorosilane (6.3 g) and stirred for 2 hours at room temperature. Water is added and the mixture is stirred for 10 minutes. Then the mixture is partitioned between 1 M hydrochloric acid and ethyl acetate. The organic phase is dried (MgSO4) and concentrated to give the title compound. Yield: 9.25 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]1=[CH:15][C:16](=[O:20])[NH:17][C:18](=[O:19])[N:8]1[CH2:7][CH2:6]2.[CH:21](I)([CH3:23])[CH3:22]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]1=[CH:15][C:16](=[O:20])[N:17]([CH:21]([CH3:23])[CH3:22])[C:18](=[O:19])[N:8]1[CH2:7][CH2:6]2
Reactant: COc1cc2c(cc1OC)-c1cc(=O)[nH]c(=O)n1CC2
Reactant: CC(C)I
Product: COc1cc2c(cc1OC)-c1cc(=O)n(C(C)C)c(=O)n1CC2
Yield: 50 %

Procedure:
In a manner analogous to that of Example 3, 9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido(6,1-a)isoquinolin-2,4-dione is reacted with isopropyl iodide. Yield 50%; melting point 190°-192° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH2:14].[C:16]([O:20][C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH:27]([NH:31][C:32]([O:34][CH2:35][CH:36]1[C:48]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[C:42]2[C:37]1=[CH:38][CH:39]=[CH:40][CH:41]=2)=[O:33])[C:28](O)=[O:29])=[O:22])([CH3:19])([CH3:18])[CH3:17].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH:14][C:28](=[O:29])[CH:27]([NH:31][C:32]([O:34][CH2:35][CH:36]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:42]=2[C:43]2[C:48]1=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:33])[CH2:26][CH2:25][CH2:24][NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22]
Reactant: CC(C)(C)OC(=O)NCCCC(NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Reactant: COC(=O)c1ccc(C(=O)OC)c(N)c1
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: COC(=O)c1ccc(C(=O)OC)c(NC(=O)C(CCCNC(=O)OC(C)(C)C)NC(=O)OCC2c3ccccc3-c3ccccc32)c1
Temperature: -15 °C
Reaction time: 1 h
Yield: 73.9 %

Procedure:
In anhydrous pyridine (30 ml), 2-amino-terephthalic acid dimethyl ester (manufactured by Merck Ltd.) (1.46 g) and 5-t-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-valeric acid (manufactured by Watanabe Chemical Industries, Ltd.) (3.18 g) were dissolved. The whole was cooled to −15° C. and added with phosphorus oxychloride (0.718 ml), followed by stirring at room temperature for 1 hour. After completion of the reaction, the whole was poured in ice-cold water and subjected to extraction with ethyl acetate. The extract was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution and dried with magnesium sulfate. After the solvent was distilled off, the resultant was subjected to azeotropic distillation with toluene. The residue was purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (3.33 g) as a white crystal.
Reaction SMILES: [CH:1]([O:4][C:5]1[N:10]=[C:9]([OH:11])[CH:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[N:6]=1)([CH3:3])[CH3:2].P(OCC)(OCC)OCC.[CH3:26][O:27][CH:28]=[C:29]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:40]Br)[C:30]([O:32][CH3:33])=[O:31].S>CCCCCCCC.O.[Cu].[Cu].O>[CH3:26][O:27][CH:28]=[C:29]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:40][O:11][C:9]1[CH:8]=[C:7]([C:12]([F:14])([F:15])[F:13])[N:6]=[C:5]([O:4][CH:1]([CH3:3])[CH3:2])[N:10]=1)[C:30]([O:32][CH3:33])=[O:31]
Reactant: COC=C(C(=O)OC)c1ccccc1CBr
Reactant: CC(C)Oc1nc(O)cc(C(F)(F)F)n1
Agent: [Cu]
Agent: CCOP(OCC)OCC
Agent: S
Solvent: O
Solvent: CCCCCCCC
Product: COC=C(C(=O)OC)c1ccccc1COc1cc(C(F)(F)F)nc(OC(C)C)n1
Temperature: 100 °C
Reaction time: 5 h
Yield: 57.7 %

Procedure:
2.22 g of 2-isopropoxy-6-trifluoromethyl-4-hydroxypyrimidine and 0.86 g of copper suboxide were suspended in 30 ml of octane. The suspension was refluxed until no water was recognized to form, while formed water was being taken into a quantitative water receiver. 1.86 g of triethyl phosphite was added, and, 30 minutes later, 3.65 g of methyl 3-methoxy-2-(2-bromomethylphenyl)acrylate was added at an instance. The reaction was carried out for 5 hours at reflux of octane. The solution was cooled down to 100° C. Hydrogen sulfide gas was blown into the solution at a rate of 15-30 ml/min for an hour. The resultant was stirred for 30 minutes. The formed precipitate was filtrated and washed with 9 ml of octane. The mixed solution of the obtained filtrate and washing was analyzed with high-performance liquid chromatography. The reaction yield was 72%. Octane was concentrated under reduced pressure. To the residue were added 10.3 ml of ethanol and 3.9 ml of water, and heated to 64° C. to dissolve. The resulting solution was left to cool over night. 2.8 ml of a mixed solution of ethanol/water (7/1) was added to it and cooled down to 5° C. to deposit crystals fully. The crystals were filtrated, washed with 1.4 ml of a mixed solution of ethanol/water (7/1) twice to give 2.46 g (yield 67%) of the target compound with melting point of 109˜110° C.
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH2:2][OH:3].[CH2:7]([O:9][CH:10]=[CH2:11])[CH3:8].CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C(OCC)C>[CH2:7]([O:9][CH:10]([O:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])[CH3:11])[CH3:8]
Reactant: C=COCC
Reactant: COC(=O)CO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCOC(C)OCC(=O)OC
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 87.8 %

Procedure:
A solution of methyl glycolate (0.193 g, 2.15 mmol) in THF (21 ml) was treated with ethylvinyl ether (EVE) (1.03 ml, 10.7 mmol) and a catalytic amount of p-TsOH (41 mg). After stirring for 15 min at 0° C., the mixture was diluted with ethyl ether, washed with saturated NaHCO3 aqueous solution, brine, dried (Na2SO4) and evaporated to give methyl (1-ethoxyethoxy)acetate (0.306 g, 87%).
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[O:12](C1C=C(C=CC=1)N)C1C=CC(N)=CC=1.NC1C=C(C=CC=1)OC1C=CC=C(OC2C=CC=C(N)C=2)C=1.C1(=O)OC(=O)C2=CC=CC=C12>CN1CCCC1=O>[CH:8]1[CH:7]=[C:3]([C:4]([NH2:5])=[O:6])[C:2]([C:1]([OH:11])=[O:12])=[CH:10][CH:9]=1
Reactant: Nc1ccc(Oc2cccc(N)c2)cc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: Nc1cccc(Oc2cccc(Oc3cccc(N)c3)c2)c1
Agent: O=C1OC(=O)c2ccccc21
Solvent: CN1CCCC1=O
Product: NC(=O)c1ccccc1C(=O)O
Temperature: 25 °C
Reaction time: 6 h

Procedure:
The following example illustrates the synthesis of a phthalimide-terminated imide oligomer with theoretical number average molecular weight of 12,000 g/mole. 3,4'-Oxydianiline (3,4'-ODA) (20.00 mmole, 4.0049 g) and 1,3-bis(3-aminophenoxy)benzene (APB) (20.00 mmole, 5.8467 g) were dissolved in N-methylpyrrolidinone (NMP) (~35 mL) in a flask equipped with a mechanical stirrer, condenser and nitrogen inlet. Pyromellitic dianhydride (PMDA)] (38.596 mmole, 8.4187 g) and phthalic anhydride (PA) (2.808 mmole, 0.4159 g) were added to the solution with enough NMP to total 74.8 g (20% solids). The reaction was stirred at 25° C. for 6 h to form the phthalamide acid-terminated polyamide acid. The inherent viscosity (ηinh) of the phthalamide acid-terminated polyamide acid was 0.40 dL/g in NMP at 25° C. To imidize, toluene (40 mL) was added and the reaction was heated at 160° C. for 24 h. After cooling, a powder precipitated which was washed twice in water and dried ~230° C. in a vacuum to afford a yellow solid in high yield. The resulting phthalimide-terminated polyimide was insoluble in NMP and had a glass transition temperature 250° C. A film cast from the polyamide acid solution and dried 1 hour each at 100, 225, and 371° C. had a Tg of 252 and a small Tm at 400° C. and was brittle.
Reaction SMILES: [Cl:1][C:2]1[N:6]2[N:7]=[C:8]([CH:20]([CH3:22])[CH3:21])[C:9]([CH2:18][OH:19])=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:5]2=[CH:4][CH:3]=1.[H-].[Na+].[C:25](OCCBr)(=[O:27])[CH3:26]>CN(C)C=O>[C:25]([O:19][CH2:18][C:9]1[C:8]([CH:20]([CH3:22])[CH3:21])=[N:7][N:6]2[C:2]([Cl:1])=[CH:3][CH:4]=[C:5]2[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)(=[O:27])[CH3:26]
Reactant: CC(C)c1nn2c(Cl)ccc2c(-c2ccc(F)cc2)c1CO
Reactant: CC(=O)OCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)OCc1c(C(C)C)nn2c(Cl)ccc2c1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 92.8 %

Procedure:
To a solution of (7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[1,2-b]pyridazin-3-yl)methanol (40 mg) in N,N-dimethylformamide (1 mL) was added 40% sodium hydride in oil (5.5 mg) in an ice-water bath. After 20 minutes, to the mixture was added 2-bromoethyl acetate (31 mg) at the temperature. After 15 minutes, the reaction mixture was stirred at ambient temperature for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate=10-1) to give [7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[1,2-b]pyridazin-3-yl]methyl acetate as a pale yellow solid (42 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-])=O.[H][H]>[Ni].CO>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[NH2:12]
Reactant: CS(=O)(=O)c1ccc(N)c([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: CS(=O)(=O)c1ccc(N)c(N)c1

Procedure:
2 G. of 1-amino-4-methylsulfonyl-2-nitrobenzene is treated in 200 ml. methanol with hydrogen at 4 atmospheres pressure in the presence of Raney nickel catalyst. The catalyst is removed by filtration and the filtrate concentrated to yield 1,2-diamino-4-methylsulfonylbenzene.