Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:24][CH2:25][CH2:26][O:27][CH:28]([CH3:30])[CH3:29])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:23]=1)[CH3:2].C(#N)C1C=CC=CC=1.C(=O)(O)[O-:40].[Na+].OO>CO>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:24][CH2:25][CH2:26][O:27][CH:28]([CH3:29])[CH3:30])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:12][C:11]=3[N+:10]([O-:40])=[CH:9][C:8]=2[N:23]=1)[CH3:2]
Reactant: O=C([O-])O
Reactant: CCOCc1nc2cnc3cc(N4CCOCC4)ccc3c2n1CCCOC(C)C
Agent: OO
Agent: [Na+]
Solvent: N#Cc1ccccc1
Solvent: CO
Product: CCOCc1nc2c[n+]([O-])c3cc(N4CCOCC4)ccc3c2n1CCCOC(C)C
Reaction time: 8 h

Procedure:
2-Ethoxymethyl-1-(3-isopropoxypropyl)-7-(morpholin-4-yl)-1H-imidazo[4,5-c]quinoline (1.0 g), benzonitrile (0.44 mL) and sodium bicarbonate (0.15 g) were slurried in methanol. Hydrogen peroxide (55% by weight in water, 0.395 mL) was added dropwise over 1 hour. The reaction was stirred overnight. The methanol was removed under reduced pressure and the residue was purified by column chromatography on a Biotage Horizon™ High Performance Flash Chromatography instrument. The purification was carried out eluting with chloroform:CMA in a gradient from 98:2 to 75:25. 2-Ethoxymethyl-1-(3-isopropoxypropyl)-7-(morpholin-4-yl)-1H-imidazo[4,5-c]quinoline 5-oxide was isolated as a yellow oil (0.166 g).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:14][CH2:13]2)=[CH:6][CH:5]=1)([O-])=O>[Pt]=O>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:12]2[CH2:13][CH2:14][CH:15]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:17]2)=[CH:6][CH:5]=1
Reactant: O=C(NC1CCN(CCc2ccc([N+](=O)[O-])cc2)CC1)c1ccccc1
Agent: O=[Pt]
Product: Nc1ccc(CCN2CCC(NC(=O)c3ccccc3)CC2)cc1
Reaction time: 3 h

Procedure:
1-[2-(p-Nitrophenyl)ethyl]-4-benzamidopiperidine (3.0 g.) was hydrogenated in absolute alcohol (400 ml.) at 50 p.s.i. and 20° C. for 3 hours in the presence of 300 mg. of platinum oxide as catalyst. The catalyst was filtered off and the solution evaporated to give the crude product as a foam. Crystallisation from a mixture of benzene and n-hexane gave the title compound, m.p. 193°-195° C. (Found: C, 74.4; H, 7.9 N, 12.9. C20H25N3O requires C, 74.3; H, 7.8; N, 13.0%).
Reaction SMILES: [CH3:1][C:2]([N:7]1[C:12](=[O:13])[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:10]([CH3:20])[O:9][CH2:8]1)([CH3:6])[C:3]([OH:5])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:40][C:41]1[CH:42]=[C:43](O)[CH:44]=[C:45]([Cl:47])[CH:46]=1.C(N(CC)CC)C>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[CH3:6][C:2]([N:7]1[C:12](=[O:13])[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:10]([CH3:20])[O:9][CH2:8]1)([CH3:1])[C:3]([O:5][C:43]1[CH:42]=[C:41]([Cl:40])[CH:46]=[C:45]([Cl:47])[CH:44]=1)=[O:4]
Reactant: Oc1cc(Cl)cc(Cl)c1
Reactant: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C(=O)O)CO1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1=C(c2ccccc2)C(=O)N(C(C)(C)C(=O)Oc2cc(Cl)cc(Cl)c2)CO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 41.8 %

Procedure:
To a suspension of 2-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid (1.1 g) in 14 ml of CCl4 --CH2Cl2 (1:1) was added triphenylphosphin (1.38 g), then the mixture was refluxed for 40 min. The reaction mixture was ice-cooled and 3,5-dichlorophenol (0.65 g) and triethylamine (0.4 g) were slowly added, then it was stirred at room temperature for 1 h. After evaporation of the solvent, the residue was dissolved in ethyl acetate. The insolubles were filtered off and the filtrate was evaporated. The residue was purified by chromatography on a silica gel column to get the captioned compound (0.7 g).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH2:6][C:7]1[N:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:10][C:11]=1[CH3:12].[OH:23][C:24]1[CH:25]=[C:26]([CH2:30][C:31]([O:33]C)=[O:32])[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:12][C:11]1[O:10][C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:8][C:7]=1[CH2:6][O:5][C:4]1[CH:19]=[CH:20][CH:21]=[CH:22][C:3]=1[CH2:2][O:23][C:24]1[CH:25]=[C:26]([CH2:30][C:31]([OH:33])=[O:32])[CH:27]=[CH:28][CH:29]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccccc1CCl
Reactant: COC(=O)Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccccc1COc1cccc(CC(=O)O)c1
Temperature: 80 °C
Reaction time: 5 h
Yield: 88.3 %

Procedure:
A mixture of 4-(2-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.21 g), methyl 2-(3-hydroxyphenyl)acetate (0.60 g), anhydrous potassium carbonate (0.65 g) and N,N-dimethylformamide (10 mL) was stirred at 80° C. for 5 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was subjected to silica gel column chromatography to give an oil from a fraction eluted with ethyl acetate-hexane (1:4, v/v). To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added a 1N aqueous sodium hydroxide solution (5 mL) and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was concentrated, and dilute hydrochloric acid was added to acidify the residue. The precipitated solid was collected by filtration and dried with air to give crystals (1.37 g, 88%) of 2-[3-[2-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 104-105° C.
Reaction SMILES: [Na+].[I-:2].Cl[CH2:4][Si:5]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1.N1C=CN=N1>CC(C)=O>[I:2][CH2:4][Si:5]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: CCOc1ccc([Si]2(CCl)CCCC2)cc1
Reactant: [I-]
Agent: [Na+]
Agent: c1c[nH]nn1
Solvent: CC(C)=O
Product: CCOc1ccc([Si]2(CI)CCCC2)cc1

Procedure:
In the same apparatus as Example 1, 7.2 g (0.048 mol) of NaI was added and dissolved with 90 ml of acetone. To the flask, 8.13 g (0.032 mol) of 1-chloromethyl-1-(4-ethoxyphenyl) -1-silacyclopentane was added, and then the mixture was reacted under reflux for 5 hrs. After filtering the produced NaCl off and evaporating to remove acetone, the residue was extracted with n-hexane. The hexane solution was treated with dilute aqueous solution of Na2S2O3 and dried on anhydrous MgSO4, and filtered to remove the solvent. After confirming by NMR analysis that the halogen exchange reaction was completely carried out, the following triazole substitution reaction was directly carried out without any purification.
Reaction SMILES: [Br:1][CH:2]1[CH2:6][CH:5]([O:7][CH3:8])[CH2:4][CH:3]1[OH:9].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl.O>[Br:1][CH:2]1[CH2:6][CH:5]([O:7][CH3:8])[CH2:4][C:3]1=[O:9]
Reactant: COC1CC(O)C(Br)C1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: O
Solvent: ClCCl
Product: COC1CC(=O)C(Br)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 134.6 %

Procedure:
Into a round-bottom flask, was placed a solution of 2-Bromo-4-methoxycyclopentanol (compound 461.3, 1.00 g, 3.08 mmol, 1.00 equiv, 60%) in dichloromethane (100 mL). Dess-Martin periodinane (2.00 g, 4.72 mmol, 1.10 equiv) was added in portions and the mixture was stirred overnight at room temperature. The mixture was then diluted with water (20 mL) and quenched with Na2S2O4 (4 g). The aqueous was extracted with dichloromethane (100 mL) and the combined organics was washed with brine (30 mL), dried (Na2SO4), filtered and concentrated in vacuo to obtain the title compound as a brown oil (800 mg, 81%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][C:17]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:39][CH:40]([NH2:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](=[O:21])[NH:47][CH:40]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH3:39])=[CH:18][C:17]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:37])[CH3:38])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:11][CH:10]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)c1ccc2c(Nc3cc(C(=O)O)ccc3Sc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2n1
Reactant: CC(N)c1ccccc1
Product: CC(C)c1ccc2c(Nc3cc(C(=O)NC(C)c4ccccc4)ccc3Sc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2n1
Yield: 78 %

Procedure:
According to the procedure in Example 385F, the title compound was prepared using 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid (prepared in Example 385E) and (RS)-α-methylbenzylamine: yield 78%.
Reaction SMILES: C(OC([NH:8][C@@H:9]([CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1)[C:10]([N:12]1[CH2:20][C@H:19]([O:21][CH2:22][C:23]2[CH:24]=[C:25]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]=[CH2:36])[CH:30]=3)[CH:26]=[CH:27][CH:28]=2)[CH2:18][C@H:13]1[C:14]([O:16][CH3:17])=[O:15])=[O:11])=O)(C)(C)C.[ClH:43]>O1CCOCC1>[ClH:43].[NH2:8][C@@H:9]([CH:37]1[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42]1)[C:10]([N:12]1[CH2:20][C@H:19]([O:21][CH2:22][C:23]2[CH:24]=[C:25]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]=[CH2:36])[CH:30]=3)[CH:26]=[CH:27][CH:28]=2)[CH2:18][C@H:13]1[C:14]([O:16][CH3:17])=[O:15])=[O:11]
Reactant: C=Cc1cccc(-c2cccc(CO[C@@H]3C[C@@H](C(=O)OC)N(C(=O)[C@@H](NC(=O)OC(C)(C)C)C4CCCCC4)C3)c2)c1
Agent: Cl
Solvent: C1COCCO1
Product: C=Cc1cccc(-c2cccc(CO[C@@H]3C[C@@H](C(=O)OC)N(C(=O)[C@@H](N)C4CCCCC4)C3)c2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Methyl (4R)-1-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl}-4-[(3′-vinylbiphenyl-3-yl)methoxy]-L-prolinate 107 was suspended in 4M solution of HCl in dioxane (final conc. 1.3 M) and stirred at RT for 2 h. The solvent was removed under reduced pressure, the residue was taken up with Et2O and evaporated to dryness to afford the title compound 108 (95% crude yield) as a white foam. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 8.15 (bs, 3H), 7.46 (s, 1H), 7.72-7.64 (m, 2H), 7.60 (d, J 7.6, 1H), 7.57-7.46 (m, 3H), 7.40 (d, J 7.6, 1H), 6.87 (dd, J 17.7, 11.1, 1H), 5.98 (d, J 17.7, 1H), 5.37 (d, J 11.1, 1H), 4.65 (s, 2H), 4.46 (t, J 8.5, 1H), 4.36 (bs, 1H), 4.25-4.18 (m, 1H), 4.10 (d, J 11.4, 1H), 3.72-3.65 (m, 1H), 3.68 (s, 3H), 2.60-2.55 (m, partially obscured by residual DMSO-d6, 1H), 2.11-2.00 (m, 1H), 1.89-1.61 (m, 6H), 1.32-1.02 (m, 5H). MS (ES+) m/z 477 (M+H)+
Reaction SMILES: Cl.[F:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:4]=1[C:5]#[N:6].[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23](Cl)=[O:24].C(N(CC)CC)C>>[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23]([N:16]1[CH2:17][CH2:18][CH:13]([CH2:12][O:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:3]([F:2])[C:4]=2[C:5]#[N:6])[CH2:14][CH2:15]1)=[O:24]
Reactant: N#Cc1c(F)cccc1OCC1CCNCC1
Reactant: O=C(Cl)c1cccc(Cl)c1
Agent: Cl
Solvent: CCN(CC)CC
Product: N#Cc1c(F)cccc1OCC1CCN(C(=O)c2cccc(Cl)c2)CC1
Yield: 77 %

Procedure:
A mixture of 2-fluoro-6-(piperidin-4-ylmethoxy)-benzonitrile hydrochloride (200 mg; 0.7 mmol) (Example 123, Step 3) was stirred at room temperature with 3-chlorobenzoyl chloride (129 mg; 0.7 mmol) and triethylamine (0.3 mL; 2.1 mmol) for 16 hours. Reaction was cooled and quenched with dilute HCl and mixture extracted with ethyl acetate (2×20 mL). Combined organics washed with water, saturated sodium bicarbonate, brine and dried over Na2SO4. Crude material was purified by chromatography using 0.5-2% methanol/DCM gradient to afford 2-[1-(3-chloro-benzoyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile as a white solid. (200 mg; 77% yield).
Reaction SMILES: [OH-].[Na+].[CH3:3][N:4]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[N:5]1.Br[C:19]1[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=1)[CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28]>O.CC1CCCO1>[CH3:3][N:4]1[CH:8]=[C:7]([C:19]2[CH:20]=[C:21]([CH:30]=[CH:31][CH:32]=2)[CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH:6]=[N:5]1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: O=C(O)CCOCCc1cccc(Br)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC1CCCO1
Product: Cn1cc(-c2cccc(CCOCCC(=O)O)c2)cn1
Temperature: 20 °C
Yield: 5.9 %

Procedure:
2-Methyltetrahydrofuran (142.1 mL) was added to Pd-118 (4.52 g) to give a red solution. To this solution was added a solution of sodium hydroxide (41.6 g) in water (473.5 mL), followed by a solution of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (81.81 g) in 2-methyltetrahydrofuran (142.1 mL), followed by the solution of 3-(3-bromophenethoxy)propanoic acid (94.7 g, prepared as in Preparation 3, Step (ii)) in 2-methyltetrahydrofuran (585 mL solution volume). The mixture was then heated to reflux and at reflux for 30 min then allowed to cool to 20° C. The mixture was filtered through GF/F filter paper then the layers separated. 20% w/w Citric acid (568.2 mL) was added to the separated aqueous layer, followed by 2-methyltetrahydrofuran (568.2 mL). After mixing, the layers were separated, the organic layer diluted with 2-methyltetrahydrofuran (to make the solution up to 950 mL) and filtered to give a small sample of the subtitled compound as an off-white solid (5.63 g). 800 mL of the filtrate (total volume 930 mL) was passed through a cartridge filter containing charcoal. The solution was partially evaporated under vacuum to give a solution measuring 490 mL and split into 2 portions. Firstly half of the solution was cooled to 20° C. and added to dibutyl ether (400 mL) at 20° C. to give a precipitate which was stirred at 20° C. for 2 h. The suspension was filtered, washed with dibutyl ether (100 mL) and dried at 50° C. under vacuum to afford the sub-titled compound (34.1 g). The second half of the solution was added to dibutyl ether (400 mL) at 65° C. to give a precipitate which was maintained at 65° C. for 10 min then cooled to 15° C. and stirred for 1 h. The suspension was filtered, washed with dibutyl ether (100 mL) and dried at 50° C. under vacuum to afford the subtitled compound as a white solid (30.5 g). MS [M+H]+=275.2 (MultiMode+) 1H NMR (400 MHz, DMSO-d6) δ 12.15 (s, 1H), 8.09 (s, 1H), 7.83 (s, 1H), 7.43 (s 1H), 7.37 (d, 1H), 7.24 (t, 1H), 7.05 (d, 1H), 3.86 (s, 3H), 3.62 (t, 2H), 3.61 (t, 2H), 2.80 (t, 2H), 2.45 (t, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][OH:9])=[CH:4][CH:3]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>O.C(Cl)Cl>[O:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[O:9][CH2:8][CH2:7][O:6][C:5]1[CH:10]=[CH:11][C:2]([Br:1])=[CH:3][CH:4]=1
Reactant: C1=COCCC1
Reactant: OCCOc1ccc(Br)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: Brc1ccc(OCCOC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a mixture of 12.0 g (55.4 mmol) 2-(4-bromophenoxy)ethanol, 100 ml dry methylene chloride and 5.1 g (60.9 mmol) dihydropyran is added, at RT, 0.42 g (2.2 mmol) p-toluenesulfonic acid.water. The mixture is stirred for 3 days at RT, after which 50 ml methylene chloride, 50 ml water and 10 ml aqueous 15% potassium carbonate are added. The organic phase is separated and washed with water (60 ml) and with saturated aqueous sodium chloride, and is then dried over calcium sulfate. Solvent is removed by rotary evaporation to yield 4-(2-tetrahydropyranyloxyethoxy)bromobenzene.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[C:11](OC(=O)C)(=[O:13])[CH3:12]>>[C:11]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)(=[O:13])[CH3:12]
Reactant: CC(=O)OC(C)=O
Reactant: O=C(O)c1ccc(O)cc1
Product: CC(=O)Oc1ccc(C(=O)O)cc1
Temperature: 150 °C

Procedure:
In a glass flask, were placed under a nitrogen stream 1,380 g of p-hydroxybenzoic acid and 1,120 g of acetic anhydride. The mixture was refluxed at 150° C. for 2 hours and then the temperature was raised while removing acetic acid by distillation. When the temperature reached 230° C., the p-acetoxybenzoic acid formed by acetylation was transferred into a double-arm kneader which had been heated to 230° C. At this stage, the p-acetoxybenzoic acid was liquid. While agitating at low speed, the temperature of this liquid was raised to 330° C. taking a period of one hour. When the temperature had reached 310° C., an increase in torque was observed. Polymerization was continued with increased speed of agitation until the mixture in the kneader was transformed into powder. 100 Grams of the powder were tested for particle diameter. It was found that 73% of the sample had a particle diameter of 0.1 mm or less. The polymerization was continued at 330° C. The degree of conversion when the polymerization system was transformed into a powder was 95%. After a further 2 hours of reaction, there were obtained 1,130 g of fine powder, corresponding to a yield of 94%. Ninety-one percent of the fine powder was found to have a particle diameter of 0.1 mm or less. On differential thermal analysis, the powder showed a heat absorption at 342° C. The loss on heating in the air at 370° C. for one hour was 0.65% by weight. The number average molecular weight was 11,000.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH3:3].[Cl:6][C:7]1[C:15]2[CH:14]=[C:13]([C:16](N(OC)C)=[O:17])[S:12][C:11]=2[CH:10]=[CH:9][CH:8]=1.O.Cl>O1CCCC1>[Cl:6][C:7]1[C:15]2[CH:14]=[C:13]([C:16](=[O:17])[CH2:1][CH2:2][CH3:3])[S:12][C:11]=2[CH:10]=[CH:9][CH:8]=1
Reactant: CON(C)C(=O)c1cc2c(Cl)cccc2s1
Reactant: CCC[Mg]Cl
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: CCCC(=O)c1cc2c(Cl)cccc2s1
Temperature: 25 °C
Reaction time: 2.33 h

Procedure:
Propylmagnesium chloride (2M solution in ether; 4.3 ml) was added under nitrogen over 15 minutes to a stirred solution of 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide (2 g) in tetrahydrofuran (25 ml) then the mixture was stirred at ambient temperature for 2.33 hours. Further propylmagnesium chloride (2M solution in ether; 0.5 ml) was added, the mixture was stirred at ambient temperature for 0.5 hours, then water (150 ml) and 5M hydrochloric acid (15 ml) were added. The product was extracted into dichloromethane (3×40 ml), the combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by column chromatography over silica using dichloromethane as eluant. Appropriate fractions were combined and the solvents removed in vacuo to leave 1-(4-chlorobenzo[b]thiophen-2-yl)butan-1-one (0.95 g) which was used without further purification.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH:10]#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(N(CC)CC)C>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:10]([C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1)#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: O=Cc1cccc(Br)n1
Reactant: C#CCCCCCCCCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCC#Cc1cccc(C=O)n1
Temperature: 40 °C
Reaction time: 8 h
Yield: 29 %

Procedure:
To a solution of 6-bromo-2-pyridinecarboxaldehyde (3.0 g) in tetrahydrofuran (10 ml), was added sequentially bis(triphenylphosphine)palladium(II) chloride (0.178 g), copper(I)iodide (0.024 g), 1-dodecyne (3.25 ml), and triethylamine (2.12 ml). The solution was stirred at 40° C. overnight. The reaction mixture was cooled to room temperature, charged again with bis(triphenylphosphine)palladium (II) chloride (0.024 g), copper (I) iodide (0.024 g), and triethylamine (2.12 ml), and 1-dodecyne (3.25 ml), and tetrahydrofuran (5.0 ml), and heated at 40° C. for 5 hrs. The reaction mixture was again cooled and recharged as above, and heated lit 40° C. for 24 hrs. The cooled mixture was concentrated, taken up in ethyl acetate (100 ml), washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was taken up in ethyl acetate (100 ml) and filtered. The filtrate was combined with material from a similar reaction run 1.43 g of the carboxaldehyde and proportionate amounts of the catalysts, 1-dodecyne, and solvent. The filtrate was concentrated. The residue was purified by flash chromatography using 1.5% ethyl acetate/hexane followed by 1% ethyl acetate/hexane as eluents. The appropriate fractions were collected and concentrated to yield 2.24 g (29%) of product, as an oil.
Reaction SMILES: [Al].[Cl:2][C:3]1[C:4]2[C:11](I)=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15].C(N(CC)CC)C>C1COCC1.[Cu]I.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.CN(C=O)C>[Cl:2][C:3]1[C:4]2[C:11]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])=[CH:10][NH:9][C:5]=2[N:6]=[CH:7][N:8]=1
Reactant: C#C[Si](C)(C)C
Reactant: Clc1ncnc2[nH]cc(I)c12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Al]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C[Si](C)(C)C#Cc1c[nH]c2ncnc(Cl)c12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a 250 ml round-bottomed flask, protected from light with aluminum foil, are added 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (1.3 g, 4.6 mmol), copper(I) iodide (0.17 g, 0.93 mmol), trimethylsilylacetylene (0.96 ml, 6.97 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.26 g, 0.23 mmol) dissolved in anhydrous THF (60 ml), anhydrous DMF (20 ml) and triethyl amine (0.64 ml, 4.65 mmol). The reaction mixture is stirred at room temperature under nitrogen for 16 hrs. The solvent is removed in vacuo, and the residue is dissolved in methylene chloride (250 ml). The reaction mixture is washed with water (3×50 ml), and the combined organic layer is dried over Na2SO4, and concentrated in vacuo. The crude residue is purified by flash-chromatography on silica gel and eluted with 70% EtOAc in cyclohexane. Fractions containing the desired product (TLC) are pooled and evaporated to afford 4-chloro-5-trimethylsilylethynyl-7H-pyrrolo[2,3-d]pyrimidine as a tan white solid.