Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1([F:27])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:26])([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[C:8]([O:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH3:18])[CH2:13][CH2:12]2)=[O:9])[CH2:3]1.[CH2:28]([I:30])[CH3:29]>>[I-:30].[F:27][C:2]1([F:1])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:26])([C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)[C:8]([O:10][CH:11]2[CH2:16][CH2:15][N+:14]([CH2:28][CH3:29])([CH2:17][CH3:18])[CH2:13][CH2:12]2)=[O:9])[CH2:3]1
Reactant: CCI
Reactant: CCN1CCC(OC(=O)[C@](O)(c2ccc(Cl)cc2)[C@@H]2CCC(F)(F)C2)CC1
Product: CC[N+]1(CC)CCC(OC(=O)[C@](O)(c2ccc(Cl)cc2)[C@@H]2CCC(F)(F)C2)CC1
Product: [I-]
Temperature: 70 °C
Reaction time: 12 h

Procedure:
A solution formed by dissolving 1-ethylpiperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-(4-chlorophenyl)-ethanoate in 1 ml of ethyl iodide at room temperature was stirred for 12 hours at 70° C. Excessive reagent was distilled off under reduced pressure, and the residue was purified on preparative thin layer chromatography (Aluminiumoxide™60F254, Art5713 (Merck), chloroform/methanol=3/1) to provide 14 mg of the title compound as a colorless solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:34][C:35](=[O:45])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH2:43]I)([CH3:33])([CH3:32])[CH3:31]>>[C:30]([O:34][C:35](=[O:45])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH2:43][C:13]1[CH:12]=[CH:11][C:10]([N:16]2[CH2:17][C:18](=[O:29])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[S:20]2(=[O:22])=[O:21])=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:14]=1)([CH3:33])([CH3:32])[CH3:31]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1CI
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Product: CC(C)(C)OC(=O)Nc1ccccc1Cc1ccc(N2CC(=O)N(CC[Si](C)(C)C)S2(=O)=O)c(OCc2ccccc2)c1

Procedure:
The title compound is prepared from 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one and (2-iodomethylphenyl)-carbamic acid tert-butyl ester analogous to Example 57, step B.
Reaction SMILES: C(OC(=O)C[CH2:12][C:13]1[CH:18]=[C:17]([N:19]2[N:23]=[C:22]3[CH:24]=[CH:25][CH:26]=[C:27](Cl)[C:21]3=[N:20]2)[C:16]([OH:29])=[C:15]([C:30](C)(C)C)[CH:14]=1)CCCCCCC.[CH2:35](C(CCCC)COC(=O)CCC1C=C(N2N=C3C=CC(Cl)=CC3=N2)C(O)=C(C(C)(C)C)C=1)[CH3:36]>>[CH3:12][C:13]1[CH:18]=[C:17]([N:19]2[N:23]=[C:22]3[C:21]([CH:27]=[CH:26][CH:25]=[CH:24]3)=[N:20]2)[C:16]([OH:29])=[C:15]([CH2:30][CH:35]=[CH2:36])[CH:14]=1
Reactant: CCCCC(CC)COC(=O)CCc1cc(-n2nc3ccc(Cl)cc3n2)c(O)c(C(C)(C)C)c1
Reactant: CCCCCCCCOC(=O)CCc1cc(-n2nc3cccc(Cl)c3n2)c(O)c(C(C)(C)C)c1
Product: C=CCc1cc(C)cc(-n2nc3ccccc3n2)c1O

Procedure:
Mixture of octyl-3-[3-tert-butyl-4-hydroxy-5-(chloro-2H-benzotriazole-2-yl)phenyl]propionate and 2-ethylhexyl-3-[3-tert-butyl-4-hydroxy-5-(5-chloro-2H-benzotriazole-2-yl)phenyl]propionate (TINUVIN109, product of Ciba Specialty Chemicals Inc.)
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]([C:11]1[NH:12][CH:13]=[CH:14][N:15]=1)[CH3:10].N1C=CC=CC=1.[C:22](Cl)(Cl)=[O:23].[CH2:26]([O:28][CH2:29][CH:30]([OH:35])[CH2:31][O:32][CH2:33][CH3:34])[CH3:27].C(=O)([O-])O.[Na+]>ClCCl>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]([C:11]1[N:15]([C:22]([O:35][CH:30]([CH2:31][O:32][CH2:33][CH3:34])[CH2:29][O:28][CH2:26][CH3:27])=[O:23])[CH:14]=[CH:13][N:12]=1)[CH3:10]
Reactant: Cc1cccc([C@H](C)c2ncc[nH]2)c1C
Reactant: O=C(Cl)Cl
Reactant: CCOCC(O)COCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOCC(COCC)OC(=O)n1ccnc1[C@@H](C)c1cccc(C)c1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a mixture of Example 58 (500 mg, 2.5 mmol) and pyridine (0.44 ml, 5.5 mmol) in anhydrous dichloromethane (5 ml), at 0° C. and under nitrogen, was added phosgene (20% in toluene, 1.44 ml, 2.75 mmol). The mixture was stirred at 0° C. for 20 min, before addition of 1,3-diethoxypropan-2-ol (407 mg, 2.75 mmol). The reaction mixture was stirred at room temperature for 30 min and then poured into ice water (10 ml). The mixture was adjusted to pH 7 by addition of solid sodium hydrogen carbonate and the two layers were separated. The aqueous phase was extracted with dichloromethane (2×10 ml) and the combined extracts were dried (MgSO4) and concentrated in vacuo.
Reaction SMILES: [NH:1]([CH:19]1[CH2:24][C:23]([CH3:26])([CH3:25])[NH:22][C:21]([CH3:28])([CH3:27])[CH2:20]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][NH:8][CH:9]1[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]1.[CH2:29]([O:32][C:33]1[N:38]=[C:37](Cl)[N:36]=[C:35]([NH:40][C:41]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:43])[CH3:42])[N:34]=1)[CH:30]=[CH2:31].[OH-:49].[Na+]>C1(C)C(C)=CC=CC=1>[CH3:25][C:23]1([CH3:26])[CH2:24][CH:19]([N:1]([C:37]2[N:38]=[C:33]([O:49][CH2:31][CH:30]=[CH2:29])[N:34]=[C:35]([NH:40][C:41]([CH2:44][C:45]([CH3:46])([CH3:48])[CH3:47])([CH3:43])[CH3:42])[N:36]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]([C:37]2[N:38]=[C:33]([O:32][CH2:29][CH:30]=[CH2:31])[N:34]=[C:35]([NH:40][C:41]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:43])[CH3:42])[N:36]=2)[CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:17])([CH3:18])[CH2:10]2)[CH2:20][C:21]([CH3:28])([CH3:27])[NH:22]1
Reactant: [OH-]
Reactant: CC1(C)CC(NCCCCCCNC2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1
Reactant: C=CCOc1nc(Cl)nc(NC(C)(C)CC(C)(C)C)n1
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: C=CCOc1nc(NC(C)(C)CC(C)(C)C)nc(N(CCCCCCN(c2nc(NC(C)(C)CC(C)(C)C)nc(OCC=C)n2)C2CC(C)(C)NC(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)n1
Yield: 68.3 %

Procedure:
A stirred mixture of 4,4'(hexamethylenediimino)bis(2,2,6,6-tetramethylpiperidine) (10.0 grams; 0.025 mole), 2-allyloxy-4-chloro-6-t-octylamino-1,3,5-triazine (15.1 grams; 0.05 mole), and powdered sodium hydroxide (2.0 grams; 0.05 mole) in xylene (150 mls) is heated at reflux for 24 hours while removing by-product water by means of a trap. The reaction mixture is filtered while hot to remove insolubles. Upon cooling the filtrate, a white crystalline solid precipitates. The solid is recovered by filtration and dried to obtain 15.7 grams of the desired product, mp 210°-212° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4](F)[CH:3]=1.[C:12]1([CH2:18][NH2:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C=O)C.O>[CH2:18]([NH:19][C:4]1[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: NCc1ccccc1
Reactant: O=[N+]([O-])c1ccc(Br)cc1F
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc(Br)cc1NCc1ccccc1
Temperature: 120 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-bromo-2-fluoro-1-nitrobenzene (500 mg, 2.27 mmol) in DMF (6 mL) were added phenylmethanamine (268 mg, 2.5 mmol) and TEA (345 mg, 3.4 mmol). The reaction mixture was stirred at 120° C. for 30 min under microwave. The reaction solution was diluted with water (40 mL), and the resulting precipitate was collected by filtration, washed with water and dried in vacuo. The crude product was used in next step without further purification. LCMS (m/z): 307.1/308.1 [M+H]+/[M+2H]+
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].S(=O)(=O)(O)O.[CH3:18]O>>[CH3:18][O:11][C:10](=[O:12])[CH2:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=1
Reactant: O=C(O)Cc1ccc(F)c(F)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1ccc(F)c(F)c1
Temperature: 25 °C
Yield: 99 %

Procedure:
A solution of 3,4-difluorophenylacetic acid (5.00 g, 29.05 mmol) in methanol (73 mL) was slowly treated with concentrated sulfuric acid (4 mL). The resulting reaction mixture was heated under reflux for 65 h. The reaction mixture was allowed to cool to 25° C. and then concentrated in vacuo to remove methanol. The resulting residue was slowly diluted with a saturated aqueous sodium bicarbonate solution (300 mL) and then extracted with ethyl acetate (1×300 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford (3,4-difluoro-phenyl)-acetic acid methyl ester (5.38 g, 99%) as a yellow oil which was used without further purification.
Reaction SMILES: [C:1]([NH2:12])(=[S:11])[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1.[C:13]1([C:19]([CH:21](Cl)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(O)C>[CH2:6]1[O:7][C:8]2[CH:9]=[CH:10][C:2]([C:1]3[S:11][C:19]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:12]=3)=[CH:3][C:4]=2[O:5]1
Reactant: O=C(c1ccccc1)C(Cl)c1ccccc1
Reactant: NC(=S)c1ccc2c(c1)OCO2
Solvent: CCO
Product: c1ccc(-c2nc(-c3ccc4c(c3)OCO4)sc2-c2ccccc2)cc1
Yield: 67.1 %

Procedure:
Thiopiperonylamide (18.1g, 0.10 mole) and desyl chloride (23.1g, 0.10 mole) are heated under reflux in 95% ethanol (100 ml) for two hours. An oil precipitates which solidifies when the reaction mixture is cooled. The solid is collected and recrystallized from ethanolethyl acetate to give 24.0g (67% yield) of 2-(3,4-methylenedioxyphenyl)-4,5-diphenylthiazole, m.p. 121°-124° C. Thiopiperonylamide is also prepared from the corresponding nitrile by the method of Fairfull et al., J. Chem. Soc. 1952, 742.
Reaction SMILES: [N:1]1([C@:4]23[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]2[C@@H:6]2[C@@:19]([CH3:22])([CH2:20][CH2:21]3)[C@@:18]3([CH3:23])[C@@H:9]([C@:10]4([CH3:36])[C@@H:15]([CH2:16][CH2:17]3)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]3[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=3)=[CH:12][CH2:11]4)[CH2:8][CH2:7]2)CC1.[CH:43]([N:46]([CH2:50][CH3:51])[CH:47]([CH3:49])[CH3:48])([CH3:45])C.C1C[O:55]CC1>>[C@H:45]12[CH2:48][C@H:47]([N:46]([CH2:50][CH2:51][NH:1][C@:4]34[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]3[C@@H:6]3[C@@:19]([CH3:22])([CH2:20][CH2:21]4)[C@@:18]4([CH3:23])[C@@H:9]([C@:10]5([CH3:36])[C@@H:15]([CH2:16][CH2:17]4)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=4)=[CH:12][CH2:11]5)[CH2:8][CH2:7]3)[CH2:43]1)[CH2:49][O:55]2
Reactant: C1CCOC1
Reactant: CCN(C(C)C)C(C)C
Reactant: C=C(C)[C@@H]1CC[C@]2(N3CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Product: C=C(C)[C@@H]1CC[C@]2(NCCN3C[C@@H]4C[C@H]3CO4)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 100 °C
Reaction time: 68 h
Yield: 32.4 %

Procedure:
Methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (200 mg, 0.351 mmol), (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane, HCl (238 mg, 1.755 mmol), and 4° A molecular sieves (250 mg, 0.351 mmol) were combined in a 20 mL scintillation vial. The mixture was dried in a 50° C. vacuum oven for 1 h. THF (5 mL) and N,N-diisopropylethylamine (0.428 mL, 2.457 mmol) were added. The solution was purged with N2 (g) and stirred at 100° C. After 68 h, reaction was concentrated to a viscous brown oil which was purified by reverse phase HPLC using HPLC method 6 and dried under vacuum to give the title compound (104 mg, 0.114 mmol, 32.4% yield) as a white solid. LC/MS: m/e 669.5 (M+H)+, 4.42 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.91 (d, J=8.1 Hz, 2H), 7.18 (d, J=8.1 Hz, 2H), 5.28 (d, J=4.9 Hz, 1H), 4.78 (s, 1H), 4.69 (s, 1H), 4.64 (br. s., 1H), 4.28 (br. s., 1H), 4.17 (d, J=9.8 Hz, 1H), 3.90 (s, 3H), 3.79 (d, J=9.5 Hz, 1H), 3.74-3.61 (m, 1H), 3.44 (br. s., 2H), 3.36 (br. s., 1H), 2.77 (d, J=6.8 Hz, 1H), 2.27-1.99 (m, 6H), 1.98-1.83 (m, 2H), 1.77 (d, J=12.2 Hz, 1H), 1.69 (s, 3H), 1.66-1.61 (m, 1H), 1.59-1.30 (m, 13H), 1.21 (d, J=6.4 Hz, 1H), 1.10 (s, 3H), 1.04 (s, 3H), 0.98 (s, 3H), 0.93 (s, 6H). 13C NMR (101 MHz, CHLOROFORM-d) δ 167.2, 148.5, 146.8, 146.2, 130.0, 128.5, 127.9, 123.8, 111.9 (br. s., 1C), 74.9, 73.1 (br. s., 1C), 64.3 (br. s., 1C), 61.3 (br. s., 1C), 54.1, 52.8, 51.9, 49.3, 49.0, 45.4, 42.0, 41.7, 40.7, 38.8 (br. s., 1C), 37.4, 37.3, 36.2, 33.5, 32.5, 29.4, 28.0, 27.5, 26.3, 25.0, 20.9, 20.8, 19.6, 18.8, 18.4, 17.2, 16.4, 15.4, 14.5, 11.8.
Reaction SMILES: [N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:41])[C:20]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:23]([OH:33])=[C:22]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[CH:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([O-])([O-])=O.[K+].[K+].[CH2:48]([O:50][C:51](=[O:57])[CH2:52][CH2:53][CH2:54][CH2:55]Br)[CH3:49].O>CN(C=O)C>[Cl:32][C:28]1[CH:27]=[C:26]([C:24]2[CH:25]=[C:20]([C:19](=[O:41])[NH:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=[CH:2]3)[CH:21]=[C:22]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[C:23]=2[O:33][CH2:55][CH2:54][CH2:53][CH2:52][C:51]([O:50][CH2:48][CH3:49])=[O:57])[CH:31]=[CH:30][CH:29]=1
Reactant: O=C(NCCCCCCCCn1ccc2ccccc21)c1cc(-c2cccc(Cl)c2)c(O)c(-c2cccc(Cl)c2)c1
Reactant: CCOC(=O)CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCOc1c(-c2cccc(Cl)c2)cc(C(=O)NCCCCCCCCn2ccc3ccccc32)cc1-c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 89 %

Procedure:
A mixture of N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)-4-hydroxybenzamide (0.399 g, 0.68 mmol), K2CO3 (0.116 g, 0.84 mmol), and ethyl-5-bromovalerate (0.176 g, 0.84 mmol) in DMF was stirred at room temperature under nitrogen. After ˜48 h, the reaction mixture was poured into water (40 ml) and extracted with EtOAc (1×20 ml, 4×10 ml). The combined extracts were washed with water (3×10 ml), brine (2×10 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The crude product was purified by flash chromatography (alumina, hexane, 10% and 60% EtOAc/Hex) to give the desired product as a light yellow oil (0.432 g, 86%); (400 MHz, DMSO-d6) δ 1.12–1.30 (m, 15H), 1.44–1.55 (m, 2H), 1.67–1.76 (m, 2H), 1.92 (t, J=7 Hz, 2H), 3.16–3.27 (m, 4H), 3.98 (q, J=7 Hz, 2H), 4.12 (t, J=7.2 Hz, 2H), 6.38 (d, J=3.1 Hz, 1H), 6.95–6.99 (m, 1H), 7.06–7.10 (m, 1H), 7.32 (d, J=3.3 Hz, 1H), 7.40–7.52 (m, 6H), 7.56–7.59 (m, 2H), 7.68 (t, J=1.8 Hz, 2H), 7.87 (s, 2H), 8.53 (t, J=5.7 Hz, 1H); IR (film) 3320, 2940, 2950, 1730, 1630, 1540, cm−1; mass spectrum [(+)APCI], m/z 713 (M+H)+.
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(O[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=O)C.C(OC1C=CC=CC=1)(=O)C1C=CC=C(C(OC2C=CC=CC=2)=O)C=1>>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: CC(=O)Oc1ccccc1
Reactant: O=C(O)c1ccc(O)cc1
Agent: O=C(Oc1ccccc1)c1cccc(C(=O)Oc2ccccc2)c1
Product: O=C(Oc1ccccc1)c1ccc(O)cc1
Temperature: 180 °C

Procedure:
An aromatic polyester useful as a cross-linking agent for the prepolymer of Example 1 is produced as follows. 414 g. (3 moles) of p-hydroxybenzoic acid, 510 g (3.75 moles) of phenyl acetate and 954 g. (3 moles) of diphenyl isophthalate are charged into a fournecked resin kettle equipped with a thermometer, stirrer, distilling head and a combination nitrogen-HCl inlet tube. The reaction mixture is stirred constantly under a nitrogen atmosphere throughout the run. The reaction mixture is heated to 180°C, and HCl is then bubbled through the mixture for 7 hours, the temperature being held at 180°C. Phenyl p-hydroxybenzoate is thereby produced. The HCl flow is discontinued, the reaction mixture is heated to 200°C at a rate of 10°C/hour, 363 g. (3.3 moles) of hydroquinone is added, and the temperature is further increased to 250°C over a period of 2.5 hours. The distilling head is then heated to 190°C by external heating means to prevent condensation in the distilling head of distillate subsequently to be produced. The reaction mixture is heated to 320°C over a period of 6 hours, held at 320°C for 16 hours, heated to 340°C and held there for 3 hours. During this stage, condensation occurs between the phenyl p-hydroxybenzoate, diphenyl isophthalate and hydroquinone, accompanied by the distillation of phenol. A total of 1127 g. of distillate is collected during the entire run, the distillate containing acetic acid, phenol and the excess phenyl acetate.
Reaction SMILES: C1(C)C(S([CH2:10][N+:11]#[C-:12])(=O)=O)=CC=CC=1.[NH3:14].[CH3:15][C:16]([CH3:22])([CH2:20][CH3:21])[CH2:17][CH:18]=O.Cl>CO>[CH3:15][C:16]([CH3:22])([CH2:20][CH3:21])[CH2:17][C:18]1[N:14]=[CH:10][NH:11][CH:12]=1
Reactant: CCC(C)(C)CC=O
Reactant: N
Reactant: [C-]#[N+]CS(=O)(=O)c1ccccc1C
Agent: Cl
Solvent: CO
Product: CCC(C)(C)Cc1c[nH]cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Toluenesulfonylmethyl isocyanide (154 g, 0.9 mol) was added to an ambient temperature, saturated solution of ammonia in methanol (7 L). After stirring at ambient temperature for 1 h, 3,3-dimethylpentanal (0.6 mol) was added over 20 min. After stirring at reflux for 3 h, the reaction mixture was poured into cold 1 N hydrochloric acid and washed with hexane. The aqueous layer was basified with 10 N aqueous sodium hydroxide and extracted with ether. The combined organic extracts were washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. Chromatography over silica eluting with 5-10% methanol/methylene chloride afforded 4-(2,2-dimethylbutyl)-1H-imidazole.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14](=[N:16][OH:17])[CH3:15])=[CH:4]1)[CH3:2].[Li][CH2:19]CCC.CN(C=O)C.OS(O)(=O)=O>C1COCC1.O>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]2[CH:15]=[CH:19][O:17][N:16]=2)=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(C)=NO)c2ccc(OC)cc21
Reactant: [Li]CCCC
Agent: O=S(=O)(O)O
Solvent: O
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCn1cc(-c2ccon2)c2ccc(OC)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 12.5 %

Procedure:
1-(1-Ethyl-6-methoxy-1-H-indole-3-yl)ethanone oxime (100 mg, 0.43 mmol) is dissolved in THF (900 μL) at 0° C. n-BuLi (450 μL, 2.5 M in hexanes, 1.12 mol) is added dropwise, resulting in instant precipitation of solids. DMF (70 μL, 0.9 mol) in 260 μL of is then added dropwise. This is stirred at 0° C. for 1 h, then at room temperature for 1 h. The reaction mixture is pipetted into a mixture containing 1 mL of H2O, 1 mL of THF, and 100 μL of concentrated H2SO4. This mixture is heated at 75° C. for 1 h and then is partitioned between H2O and EtOAc. The organic phase is dried and concentrated. Purification by column chromatography (CH2Cl2) yields 1-ethyl-3-isoxazol-3-yl-6-methoxy-1-H-indole product as a white solid (13 mg, 12%).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][CH:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][O:9][C:8]2[CH:17]=[CH:18][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:20][C:7]1=2)=[O:4].[NH:25]1[CH:29]=[CH:28][N:27]=[CH:26]1>C1(C)C=CC=CC=1>[N:25]1([CH2:2][C:3]([NH:5][CH:6]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH2:10][O:9][C:8]3[CH:17]=[CH:18][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:20][C:7]2=3)=[O:4])[CH:29]=[CH:28][N:27]=[CH:26]1
Reactant: c1c[nH]cn1
Reactant: COC(=O)c1ccc2c(c1)C(NC(=O)CCl)c1ccccc1CO2
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc2c(c1)C(NC(=O)Cn1ccnc1)c1ccccc1CO2

Procedure:
Crude methyl 11-chloroacetamido-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate, 3.0 g, was heated to reflux for 4 hours in 100 ml of toluene together with 0.9 g of imidazole. After allowing to cool, the solvent was distilled off under reduced pressure. The obtained residue was extracted with 300 ml of methylene chloride. The extract was washed successively with saturated sodium bicarbonate aqueous solution and saturated sodium chloride aqueous solution. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was subjected to silica gel column chromatography .(eluting solvent; chloroform:methanol=10:1) to give 1.6 g of the product.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1/[CH:13]=[CH:14]/[C:15]1[CH:33]=[CH:32][C:18]([CH2:19][O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH2:27][C:28]([O:30]C)=[O:29])=[CH:17][CH:16]=1.O1CCCC1.[OH-].[Na+].Cl>O.C(O)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1/[CH:13]=[CH:14]/[C:15]1[CH:16]=[CH:17][C:18]([CH2:19][O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH2:27][C:28]([OH:30])=[O:29])=[CH:32][CH:33]=1
Reactant: COC(=O)Cc1ccccc1OCc1ccc(/C=C/c2nc(-c3ccccc3)oc2C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: Cc1oc(-c2ccccc2)nc1/C=C/c1ccc(COc2ccccc2CC(=O)O)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 72.8 %

Procedure:
To a mixture of methyl 2-[2-[4-[(E)-2-(5-methyl-2-phenyl-4-oxazolyl)ethenyl]benzyloxy]phenyl]acetate (0.44 g), tetrahydrofuran (2 mL) and ethanol (2 mL) was added a 1N aqueous sodium hydroxide solution (2 mL) and the mixture was stirred at room temperature for 15 hrs. 1N Hydrochloric acid and water were added to acidify the reaction mixture, and the, mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give crystals (0.31 g, 72%) of 2-[2-[4-[(E)-2-(5-methyl-2-phenyl-4-oxazolyl)ethenyl]benzyloxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave pale-yellow prism crystals. melting point: 189-190° C.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([NH:12][C:13]([NH:15][C:16]1[N:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH3:25])[N:17]=1)=[O:14])(=[O:11])=[O:10].[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.[K+].[Br-]>CN(C)C=O>[ClH:1].[N:26]1([CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[S:9]([NH:12][C:13]([NH:15][C:16]2[N:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH3:25])[N:17]=2)=[O:14])(=[O:11])=[O:10])[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: COc1cc(OC)nc(NC(=O)NS(=O)(=O)c2ccccc2CCl)n1
Reactant: C1CCNC1
Agent: [Br-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc(OC)nc(NC(=O)NS(=O)(=O)c2ccccc2CN2CCCC2)n1
Product: Cl
Reaction time: 3.5 h

Procedure:
A slurry of 2-(chloromethyl)-N-[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]benzenesulfonamide (1.00 g) in dimethylformamide (5 ml) was contacted with pyrrolidine (0.45 ml) and stirred for 3.5 hrs. Volatiles were removed under vacuum and the residue was taken up in methanol. Solvent was removed and the water (15 ml) was added and the pH was adjusted to 6.0 by addition of dilute hydrochloric acid. Cooling and scratching produced a white solid which was collected and dried to give 488 mg, m.p. 117°-123°. A 400 mg sample was crystallized from acetonitrile to give 269 mg. m.p. 132°-134° C. 1H nmr δCDCl3TMS 13.0-11.0 (brds 2H), 8.63 (s, 1 NH), 8.37-8.20, 8.05-7.90, and 7.70-7.33 (m, 4H), 5.68 (s, 1H), 5.00 (s, 2H), 3.90 (s, 6H), 3.70-2.90 (m, 4H), 2.30-1.90 (m, 4H). IR (KBr) 3650-2200, 1710, 1610, 1580, 1450, 1360, 1200, 1165 are major absorption bands.