Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li]CCCC.[C:6]1([C:12]2[C:13]([NH2:25])=[C:14]([NH2:24])[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:26]([O:28]C(OCC)C(OCC)=O)[CH3:27].[Li+].[OH-].Cl>C1COCC1.O.C(OCC)C.C(O)(=O)C>[C:18]1([C:15]2[C:14]3[N:24]=[C:27]([CH:26]=[O:28])[NH:25][C:13]=3[C:12]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:17][CH:16]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CCOC(=O)C(OCC)OCC
Reactant: Nc1c(-c2ccccc2)ccc(-c2ccccc2)c1N
Agent: Cl
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: O=Cc1nc2c(-c3ccccc3)ccc(-c3ccccc3)c2[nH]1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution of 11.1 ml (27.72 mmol) n-BuLi (2.5 M in hexanes) was added dropwise to a cooled to −78° C. solution of 3.4 g (13.2 mmol) 1,1′:4′,1″-terphenyl-2′,3′-diamine in 110 ml THF. The reaction mixture was stirred at −78° C. for 1 hour and 2.4 ml (13.5 mmol) dry ethyl diethoxyacetate were added dropwise over 1 min. The solution was then stirred at 78° C. for 30 min, allowed to slowly warm up room temperature, stirred for another 30 min and the heated at reflux for 2 hours. Formation of white precipitate (LiOH) was observed during the reflux. After cooling to room temperature and addition of 60 ml water the reaction mixture was carefully neutralized with the addition of 5N acetic acid. Diethyl ether (200 ml) was then added, the formed biphasic mixture was vigorously stirred and the organic layer separated. It was washed with water (3×100 ml) and dried over anhydrous sodium sulfate. Evaporation of the solvent afforded an yellow-brown oil which was dissolved in 15 ml THF and 60 ml 4N HCl were added. The mixture was stirred at reflux for 2 hours, cooled to room temperature and 120 ml icy water was added. The mixture was stirred vigorously for 10 min at ˜0° C. and then filtered. The solid was suspended in 70 ml water and neutralized with 10% aqueous sodium carbonate. The solid was filtered again, washed with water and dried at room temperature under reduced pressure. Yield—2.85 g (72.4%). 1H NMR (250 MHz, CDCl3), δ, ppm: 7.54 (m, 10H), 8.03 (br. s, 2H), 10.06 (s, 1H), 10.31 (br. s, 1H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:8][C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[CH:14]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>C1COCC1.O.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>[Cl:8][C:9]1[CH:14]=[C:13]([CH:12]=[C:11]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:10]=1)[C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)c1cc(Cl)cc(B(O)O)c1
Reactant: Brc1ccccn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1cc(Cl)cc(-c2ccccn2)c1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
A mixture of commercially available 2-bromopyridine (294 mg; 1.86 mmol), 3-chloro-5-(methoxycarbonyl)phenylboronic acid (400 mg; 1.86 mmol), K2CO3 (515 mg; 3.73 mmol), and PdCl2(PPh3)2 (130 mg; 0.18 mmol) in THF (4 ml) and water (4 ml) was stirred at rt, under nitrogen, for 17 h. Water and AcOEt were added. The separated aq. layer was further extracted with AcOEt. The mixed organic layers were washed with brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=15/1) afforded methyl 3-chloro-5-(pyridin-2-yl)benzoate as a colorless solid. LC-MS (conditions A): tR=0.79 min.; [M+H]+: 247.95 g/mol.
Reaction SMILES: [C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[NH2:7][C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([Cl:19])[CH:12]=2.C(N(CC)CC)C>O1CCCC1>[Cl:19][C:13]1[CH:12]=[C:11]2[C:16]([C:17]([OH:18])=[C:8]([NH:7][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[CH:9]=[N:10]2)=[CH:15][CH:14]=1
Reactant: Nc1cnc2cc(Cl)ccc2c1O
Reactant: CCCC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCC(=O)Nc1cnc2cc(Cl)ccc2c1O
Temperature: 25 °C
Yield: 59.2 %

Procedure:
Under a nitrogen atmosphere, butyryl chloride (0.76 mL, 7.3 mmol) was added dropwise to a mixture of 3-amino-7-chloro-4-hydroxyquinoline (1.3 g, 6.7 mmol), triethylamine (3.0 mL, 21.5 mmol) and anhydrous tetrahydrofuran (20 mL). The reaction mixture was maintained at ambient temperature overnight. The resulting precipitate was isolated by filtration, washed with water followed by tetrahydrofuran, and then vacuum dried to provide 1.05 g of N-(7-chloro-4-hydroxyquinolin-3-yl)butanamide as a tan powder.
Reaction SMILES: [C:1]([C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:21])=[CH:12][C:13]([CH3:20])=[C:14]([CH:19]=2)[C:15]([O:17][CH3:18])=[O:16])=[C:7]([CH3:9])[N:8]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO>[OH:3][CH:1]([C:4]1[NH:5][C:6]([C:10]2[C:11]([CH3:21])=[CH:12][C:13]([CH3:20])=[C:14]([CH:19]=2)[C:15]([O:17][CH3:18])=[O:16])=[C:7]([CH3:9])[N:8]=1)[CH3:2]
Reactant: COC(=O)c1cc(-c2[nH]c(C(C)=O)nc2C)c(C)cc1C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1cc(-c2[nH]c(C(C)O)nc2C)c(C)cc1C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of methyl 5-(2-acetyl-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoate (compound 198.2, 300 mg, 1.10 mmol) in methanol (30 mL). This was followed by the addition of NaBH4 (84 mg, 2.22 mmol) in portions at 0° C. The resulting solution was stirred for 1 h at room temperature, then carefully quenched with 1 mL of aqueous hydrogen chloride (2 M). The resulting mixture was concentrated under reduced pressure. This resulted in 330 mg (crude) of the title compound as a white solid.
Reaction SMILES: [Na].[CH2:2]([O:9][C:10]1[CH:11]=[CH:12][C:13]([N:19]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]2)[C:20]([O:22][CH2:23][CH:24]([CH3:26])[CH3:25])=[O:21])=[C:14]([CH:18]=1)[C:15](O)=[O:16])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:73]([NH2:84])[C:74]1[CH:83]=[CH:82][C:79]([O:80][CH3:81])=[C:76]([O:77][CH3:78])[CH:75]=1>CN(C=O)C>[CH2:2]([O:9][C:10]1[CH:11]=[CH:12][C:13]([N:19]([C:20]([O:22][CH2:23][CH:24]([CH3:25])[CH3:26])=[O:21])[CH:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:29][CH2:28]2)=[C:14]([C:15](=[O:16])[NH:84][CH2:73][C:74]2[CH:83]=[CH:82][C:79]([O:80][CH3:81])=[C:76]([O:77][CH3:78])[CH:75]=2)[CH:18]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: COc1ccc(CN)cc1OC
Reactant: CC(C)COC(=O)N(c1ccc(OCc2ccccc2)cc1C(=O)O)C1CCN(C(=O)OC(C)(C)C)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Na]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccc(CNC(=O)c2cc(OCc3ccccc3)ccc2N(C(=O)OCC(C)C)C2CCN(C(=O)OC(C)(C)C)CC2)cc1OC
Reaction time: 0.25 h

Procedure:
A mixture of 6 g of sodium salt of 5-(benzyloxy)-2-({1-[(1,1-dimethylethoxy)carbonyl]piperidin-4-yl}[(2-methylpropoxy)carbonyl]amino)benzoic acid obtained in stage 1.3 and 4.42 g of DIEA in 250 ml of DMF is stirred at AT for 15 min. 6.48 g of HBTU are added and the mixture is left stirring for 30 min. 2.48 g of veratrylamine are added and the reaction mixture is stirred for 48 h 00. It is evaporated under reduced pressure, the residue is taken up in AcOEt, washed with a saturated NH4Cl solution and with a saturated NaHCO3 solution, dried over Na2SO4 and filtered, and the solvent is evaporated under reduced pressure. The residue is chromatographed on silica gel, elution being carried out with an AcOEt/heptane mixture, (20/80, v/v) as far as (60/40, v/v), to give 7.5 g of expected product.
Reaction SMILES: [NH:1](C(OC(C)(C)C)=O)[C@@H:2]([C:7]([NH:9][C@H:10]([C:15]([NH:17][C@H:18]([C:40]([N:42]1[CH2:51][CH2:50][CH2:49][C@H:43]1[C:44]([NH:46][CH2:47][CH3:48])=[O:45])=[O:41])[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[NH:39])[NH:24][S:25]([C:28]1[C:37]([CH3:38])=[C:35]([CH3:36])[C:32]([O:33][CH3:34])=[CH:31][C:29]=1[CH3:30])(=[O:27])=[O:26])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5]>C(O)=O>[NH2:1][C@@H:2]([C:7]([NH:9][C@H:10]([C:15]([NH:17][C@H:18]([C:40]([N:42]1[CH2:51][CH2:50][CH2:49][C@H:43]1[C:44]([NH:46][CH2:47][CH3:48])=[O:45])=[O:41])[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[NH:39])[NH:24][S:25]([C:28]1[C:37]([CH3:38])=[C:35]([CH3:36])[C:32]([O:33][CH3:34])=[CH:31][C:29]=1[CH3:30])(=[O:26])=[O:27])=[O:16])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])[CH2:3][CH:4]([CH3:5])[CH3:6]
Reactant: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)NS(=O)(=O)c1c(C)cc(OC)c(C)c1C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)OC(C)(C)C
Solvent: O=CO
Product: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)NS(=O)(=O)c1c(C)cc(OC)c(C)c1C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](N)CC(C)C

Procedure:
According to general procedure for BOC-cleavage, 500 mg crude Boc-D-Leu-Leu-Arg(Mtr)-Pro-NHEt was treated with 2 ml formic acid yielding 350 mg crude D-Leu-Leu-Arg (Mtr)-Pro-NHEt (yield based on HPLC: 80%).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:3])[CH3:2].Cl.[CH2:19]([S:21]([C:24]1[S:28][C:27]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[N:26][CH:25]=1)(=[O:23])=[O:22])[CH3:20]>>[CH2:19]([S:21]([C:24]1[S:28][C:27]([N:29]2[CH2:30][CH2:31][N:32]([C:7]([C:6]3[CH:10]=[C:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:12]=[CH:13][C:5]=3[O:4][CH:1]([CH3:2])[CH3:3])=[O:9])[CH2:33][CH2:34]2)=[N:26][CH:25]=1)(=[O:23])=[O:22])[CH3:20]
Reactant: CCS(=O)(=O)c1cnc(N2CCNCC2)s1
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Agent: Cl
Product: CCS(=O)(=O)c1cnc(N2CCN(C(=O)c3cc(S(C)(=O)=O)ccc3OC(C)C)CC2)s1
Yield: 71 %

Procedure:
Prepared in analogy to example 1 (b) from 2-isopropoxy-5-methanesulfonyl-benzoic acid (Example A1) and 1-(5-ethanesulfonyl-thiazol-2-yl)-piperazine hydrochloride (Example 32(c)). The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) followed by trituration in ether to yield the title compound as a white crystalline solid (yield 71%). MS (m/e): 502.3 (M+H+, 100%), 519.3 (M+NH4+, 82%).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:22]=[CH:21][N:20]=[CH:19][C:7]=3[CH2:8][N+:9]([O-])=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:17])[C:4]=2[CH:3]=1.P(Cl)(Cl)Cl.[OH-].[NH4+]>C(Cl)Cl>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:22]=[CH:21][N:20]=[CH:19][C:7]=3[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:17])[C:4]=2[CH:3]=1
Reactant: [O-][N+]1=C(c2ccccc2Cl)c2cc(Cl)ccc2-c2ncncc2C1
Agent: [NH4+]
Agent: [OH-]
Solvent: ClP(Cl)Cl
Solvent: ClCCl
Product: Clc1ccc2c(c1)C(c1ccccc1Cl)=NCc1cncnc1-2

Procedure:
A mixture of 0.5 g (1.3 mmol) of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d][2]benzazepine-6-oxide and 1.0 ml (10 mmol) of phosphorous trichloride in 20 ml of methylene chloride was refluxed for 3 hr. The mixture was cooled, poured over ice, basified with ammonium hydroxide and extracted with methylene chloride. The methylene chloride solution was washed with water, dried over anhydrous sodium sulfate and concentrated at reduced pressure. The residue crystallized upon the addition of ether to give colorless prisms, mp 121°-123° C.
Reaction SMILES: [N:1]([CH:4]([CH2:8][CH2:9][CH3:10])[C:5](O)=[O:6])=[N+:2]=[N-:3].C(Cl)(=O)C([Cl:14])=O.CN(C)C=O>ClCCl>[N:1]([CH:4]([CH2:8][CH2:9][CH3:10])[C:5]([Cl:14])=[O:6])=[N+:2]=[N-:3]
Reactant: CCCC(N=[N+]=[N-])C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCC(N=[N+]=[N-])C(=O)Cl
Yield: 89 %

Procedure:
A solution of (2R and 2S) 2-azidopentanoic acid (2.213 g, 15.46 mmol) in dry dichloromethane (20 ml) was treated with oxalyl chloride (1.57 ml, 18.55 mmol) and a drop of N,N-dimethyl formamide. After the evolution of gas had ceased (2 h), the solvent was evaporated under reduced pressure and the residual liquid was distilled off (bulb to bulb) under vacuum to give 2.224 g (89%) of a clear oil: bp 50°-55° C./5 torr (air bath temperature); ir (film) νmax : 2105 (N3), 1785 cm-1 (C=O); 1Hmr (CDCl3) δ: 4.1 (1H, dd, J=7, J=6, H-2), 2.2-1.2 (4H, m, H-3 and H-4), and 0.98 ppm (3H, distorted t, J=6, H-5).
Reaction SMILES: Cl.Cl.[F:3][C:4]1[C:12]([C:13]2[C:21]3[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=3[N:15]([CH3:23])[CH:14]=2)=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][NH:8]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:57][C:58]([F:70])([F:69])[C:59]1[CH:60]=[C:61]([CH2:65][C:66](O)=[O:67])[CH:62]=[CH:63][CH:64]=1>CN(C=O)C.CO.C(Cl)Cl>[F:3][C:4]1[C:12]([C:13]2[C:21]3[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=3[N:15]([CH3:23])[CH:14]=2)=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][N:8]2[C:66](=[O:67])[CH2:65][C:61]1[CH:62]=[CH:63][CH:64]=[C:59]([C:58]([F:69])([F:57])[F:70])[CH:60]=1
Reactant: O=C(O)Cc1cccc(C(F)(F)F)c1
Reactant: Cn1cc(-c2ccc3c(c2F)CCN3)c2c(N)ncnc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cn1cc(-c2ccc3c(c2F)CCN3C(=O)Cc2cccc(C(F)(F)F)c2)c2c(N)ncnc21
Temperature: 0 °C
Yield: 69.2 %

Procedure:
To a suspension of 5-(4-fluoro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride (200 mg, 0.56 mmol, 1 equiv) and HATU (235 mg, 0.62 mmol, 1.1 equiv) in DMF (2 mL) at room temperature was added DIEA (314 uL, 1.80 mmol, 3.2 equiv) in one portion. To this mixture was added [3-(trifluoromethyl)phenyl]acetic acid (115 mg, 0.56 mmol, 1 equiv) portionwise over a 1 h period. After a total of 1.5 hours, LCMS showed conversion complete. The mixture was poured into 20 mL of ice cold water to give a suspension, which was filtered. The cake was washed with water and dried under house vacuum. The solid residue was dissolved in 10% MeOH in DCM and absorbed onto a dryload cartridge. Purification was done on an SF25-40 g silica gel cartridge using gradient elution of 1% A in CHCl3 to 60% A in CHCl3 (A was a mixture of 3200/800/80 CHCl3/MeOH/NH4OH, gradient: 0-5 min: 1% A, 5-35 min 5-60% A). The desired product eluted from 27-32% A. The combined fractions were conc in vacuo to give the product, which LCMS showed was only 89% pure. The sample was dissolved in 10% MeOH in DCM and absorbed onto a dryload cartridge. Purification was done on an SF25-60 g silica gel cartridge using gradient elution of 1% A in EtOAc 100% A (A was a mixture of 10% MeOH in EtOAc). The desired product eluted from 67-87% A. The combined fractions were conc in vacuo. The residue was dissolved in 10 mL of 10% MeOH in DCM and concentrated in vacuo to a suspension (about 2 mL). This mixture was diluted with 12 mL of MTBE. The resulting suspension was filtered. The cake was washed with MTBE (3×4 mL) and hexane (3×4 mL), and dried under vacuum at 65° C. for 18 h to afford 5-(4-fluoro-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (182 mg) as white solids. LC-MS (ES) m/z=470 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.28 (t, J=8.1 Hz, 2H), 3.74 (s, 3H), 4.04 (s, 2H), 4.34 (t, J=8.3 Hz, 2H), 5.88-6.16 (br s, 1.6H), 7.20 (t, J=8.0 Hz, 1H), 7.27 (s, 1H), 7.54-7.73 (m, 4H), 7.92 (d, J=8.3 Hz, 1H), 8.14 (s, 1H).
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH2:8]([C:10]([CH2:15][OH:16])([CH2:13][OH:14])[CH2:11][CH3:12])[OH:9]>O>[C:4]1(=[O:5])[O:6][C:1](=[O:7])[CH:2]2[CH2:12][CH2:11][CH:10]=[CH:8][CH:3]12.[CH2:8]([C:10]([CH2:15][OH:16])([CH2:13][OH:14])[CH2:11][CH3:12])[OH:9]
Reactant: O=C1C=CC(=O)O1
Agent: CCC(CO)(CO)CO
Solvent: O
Product: O=C1OC(=O)C2CCC=CC12
Temperature: 90 °C
Reaction time: 10 h

Procedure:
29.4 grams of maleic anhydride and 13.4 grams of trimethylol propane crosslinker are reacted with stirring for 10 hours at 90° C. to form a clear water-soluble first intermediate reaction product containing unsaturated double bonds capable of undergoing free-radical polymerization and hydroxyl and carboxylic acid end groups. A second intermediate reaction product is formed by the reaction of 45.6 grams of tetrahydrophthalic anhydride and 13.4 grams of trimethylol propane under the same reaction condition. The two intermediate reaction products next are dissolved with stirring in 200 grams of water containing 25 grams of triethanol amine crosslinker, and 1.0 gram of cumyl hydroperoxide free radical initiator to form a homogenous solution. The homogenous solution next is coated on a multifilamentary glass roving and is cured as described in Example 1. A free-radical polymerization reaction and a cross-linking reaction take place via an esterification reaction. The resulting cured product is similarly stable and displays a high resistance upon exposure to boiling water that is assisted by the free-radical polymerization of the first intermediate reaction product that is made possible by the inclusion of the free-radical initiator.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH3:11])[S:7][C:6]1=[NH:12].CCN(CC)CC.[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]([CH3:10])=[C:8]([CH3:11])[S:7]/[C:6]/1=[N:12]\[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COCCn1c(C)c(C)sc1=N
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COCCn1c(C)c(C)s/c1=N\C(=O)c1ccccc1
Yield: 34.5 %

Procedure:
The product of Example 126A (0.20 g, 1.1 mmol), Et3N (0.45 mL, 3.2 mmol) and benzoyl chloride (Aldrich, 0.16 mL, 1.4 mmol) in 15 mL THF were processed using the method described in Example 129 to afford the title compound (0.11 g, 0.38 mmol, 35% yield). 1H NMR (300 MHz, CDCl3) δ ppm 2.24 (s, 3H), 2.27 (d, J=0.7 Hz, 3H), 3.32 (s, 3H), 3.82 (t, J=5.3 Hz, 2H), 4.41 (t, J=5.3 Hz, 2H), 7.38-7.51 (m, 3H), 8.27-8.34 (m, 2H); MS (DCI/NH3) m/z291 (M+H)+; Anal. calculated for C15H18N2O2S: C, 62.04; H, 6.25; N, 9.65. Found: C, 62.02; H, 6.05; N, 9.56.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[CH2:14][C:13](=[O:15])[CH2:12][C:11](=[O:16])[CH2:10]1.[H-].[Na+].Cl[CH2:22][C:23](=O)[CH3:24]>CN(C=O)C>[CH3:24][C:23]1[C:12]2[C:13](=[O:15])[CH2:14][CH:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:2]([F:17])([F:18])[F:1])[CH2:10][C:11]=2[O:16][CH:22]=1
Reactant: CC(=O)CCl
Reactant: O=C1CC(=O)CC(c2ccccc2C(F)(F)F)C1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1coc2c1C(=O)CC(c1ccccc1C(F)(F)F)C2
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 5-(2-trifluoromethylphenyl)cyclohexane-1,3-dione (mp198-199° C.; 1.28 g) in DMF (20 ml) was added 60% sodium hydride (0.22 g), and the mixture was stirred, under argon atmosphere, at room temperature for 15 minutes. To the mixture was added chloroacetone (0.45 ml), and the mixture was stirred at 150° C. overnight (14 hours). The reaction solution was cooled, and to the mixture was added ice-water. The mixture was extracted with ethyl acetate. The upper layer was washed with saturated brine, dried (anhydrous magnesium sulfate), and concentrated under reduced pressure, and the residue was subjected to silica gel chromatography and eluted with ethyl acetate/hexane to give 3-methyl-6-(2-trifluoromethylphenyl)-4,5,6,7-tetrahydrobenzofuran-4-one (0.28 g).
Reaction SMILES: [F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[CH3:14][Si:15]([CH3:24])([CH3:23])[C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C1N2CCN(CC2)C1>C1(C)C=CC=CC=1>[CH3:14][Si:15]([CH3:24])([CH3:23])[C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:12][CH:11]=[CH:10][C:9]=2[F:13])=[O:8])=[CH:18][CH:17]=1
Reactant: C[Si](C)(C)c1ccc(N)cc1
Reactant: O=C=NC(=O)c1c(F)cccc1F
Agent: C1CN2CCN1CC2
Solvent: Cc1ccccc1
Product: C[Si](C)(C)c1ccc(NC(=O)NC(=O)c2c(F)cccc2F)cc1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
A solution of 6.0 g of 2,6-difluorobenzoylisocyanate in 20 ml of toluene was added dropwise at room temperature to a mixture of 5.4 g of 4-trimethylsilylaniline, 50 ml of toluene and 100 mg of Dabco®. The reaction mixture obtained was subsequently stirred at 60° C. for 3 hours. The reaction mixture was concentrated by evaporation, and the residue was recrystallised from acetone to obtain 1-(4-trimethylsilylphenyl)-3-(2,6-difluorobenzoyl)-urea of the formula ##STR8## as a white powder having a melting point of 187°-189° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:8]1[S:9][CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:12]=1.C(N(CC)CC)C.C1C=CC=CC=1>O>[N:1]1([C:8]2[S:9][CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1CCNCC1
Reactant: CCOC(=O)c1csc(Cl)n1
Solvent: c1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1csc(N2CCCCC2)n1

Procedure:
A mixture comprising 2.1 g of piperidine, 4 g of ethyl 2-chlorothiazole-4-carboxylate, 4.2 g of triethylamine and 20 ml of benzene was refluxed for 12 hours. The reaction mixture was poured into water and extracted with benzene. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[CH2:12]([O:14][CH:15]([O:20][CH2:21][CH3:22])[CH2:16][CH2:17][CH2:18][NH2:19])[CH3:13].NCCN1CCNCC1>ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:5]([O:4][C:2](=[O:3])[NH:19][CH2:18][CH2:17][CH2:16][CH:15]([O:14][CH2:12][CH3:13])[O:20][CH2:21][CH3:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCOC(CCCN)OCC
Reactant: O=C(Cl)OCc1ccccc1
Agent: NCCN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(CCCNC(=O)OCc1ccccc1)OCC
Reaction time: 0.83 h

Procedure:
Three portions of benzyl chloroformate (260 ml) in dichloromethane (170 ml) were added sequentially over 1 h 40 min to a vigorously stirred mixture of 4-aminobutyraldehyde diethyl acetal (910 ml) in dichloromethane (3 l) and aqueous sodium carbonate (1M, 3 l). Stirring was continued for 50 min until gas evolution ceased. N-(2-aminoethyl)piperazine (40 ml) was added and stirring was continued for 1 h 15 min. The layers were separated and the organic layer was washed with aqueous citric acid (1M, 3.8 l) and saturated aqueous sodium bicarbonate (2 l), dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a yellow oil (1.6 kg). T.l.c. (Ether) Rf 0.5.
Reaction SMILES: [CH3:1][Si:2]([CH3:25])([CH3:24])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:15]2[CH:14]=[C:13]([C:16]3[CH:17]=[N:18][CH:19]=[C:20]([CH:22]=[CH2:23])[CH:21]=3)[N:12]=[CH:11][C:10]=2[CH:9]=[N:8]1.[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[CH2:22]([C:20]1[CH:21]=[C:16]([C:13]2[N:12]=[CH:11][C:10]3[CH:9]=[N:8][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:24])([CH3:1])[CH3:25])[C:15]=3[CH:14]=2)[CH:17]=[N:18][CH:19]=1)[CH3:23]
Reactant: [H][H]
Reactant: C=Cc1cncc(-c2cc3c(cn2)cnn3COCC[Si](C)(C)C)c1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: CCc1cncc(-c2cc3c(cn2)cnn3COCC[Si](C)(C)C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.9 %

Procedure:
To a solution of trimethyl-[2-[[6-(5-vinyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]methoxy]ethyl]silane (543.4 mg) in Ethanol (50 mL) in a 250 mL round bottom flask was added Pearlman's catalyst (0.1850 mmol; 129.9 mg). The flask was vacuumed and connected with a balloon of Hydrogen. The mixture was stirred at room temperature overnight. The mixture was filtered through Celite. The filtrate was concentrated. The residue was purified on silica eluted with 0 to 5% MeOH in DCM to afford 2-[[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]methoxy]ethyl-trimethyl-silane (87 mg, 27%).