Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:35]([CH3:37])=[O:36])[C@@H:2]([C:18]([N:20]1[CH2:34][CH2:33][CH2:32][C@@H:21]1[C:22]([NH:24][C@@H:25]([C:29]([NH2:31])=[O:30])[CH:26]([CH3:28])[CH3:27])=[O:23])=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7]C(OCC1C=CC=CC=1)=O.CC(O)=O.O.[H][H]>CCO.[Pd]>[NH:1]([C:35]([CH3:37])=[O:36])[C@@H:2]([C:18]([N:20]1[CH2:34][CH2:33][CH2:32][C@@H:21]1[C:22]([NH:24][C@@H:25]([C:29]([NH2:31])=[O:30])[CH:26]([CH3:28])[CH3:27])=[O:23])=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7]
Reactant: [H][H]
Reactant: CC(=O)N[C@H](CCCCNC(=O)OCc1ccccc1)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](C(N)=O)C(C)C
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: CC(=O)N[C@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)N[C@@H](C(N)=O)C(C)C
Temperature: 50 °C
Reaction time: 1 h
Yield: 98.8 %

Procedure:
107 g of Ac-D-Lys(Z)-D-Pro-D-Val-NH2 are dissolved in 535 ml of EtOH, added with 214 ml of AcOH and of 21.4 g of Pd/C at 10% at 50% water. The hydrogenation is conducted at 20° C., under a 1 bar hydrogen pressure for 16 hours. The reaction completion is CCM controlled. The catalyst is filtered and the filtrate is vacuum concentrated until refusal. The residue is recovered with 107 ml of EtOH, added with 430 ml of iPrOH and the blend is heated at 50° C., then added dropwise at 50° C. with 1500 ml of diisopropyl ether. The expected product crystallizes. The medium is cooled down to 20° C. and stirred for 1 hour. The solid is filtered and washed with 500 ml of diisopropyl ether before being vacuum dried at 25° C. so to provide 78.3 g of Ac-D-Lys-D-Pro-D-Val-NH2 under the form of an acetate salt (yield 85.4%). The thus obtained product purity is HPLC controlled.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH:11]([O:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[C:15]=2[CH3:22])[CH3:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]>C1(C)C=CC=CC=1>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:18]([CH3:20])=[CH:17][C:16]([CH3:21])=[C:15]([CH3:22])[C:14]=3[O:13][C:11]=2[CH3:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: Cc1cc(C)c(C)c(OC(C)C(=O)c2ccc(C(C)C)cc2)c1
Solvent: Cc1ccccc1
Product: Cc1cc(C)c2c(-c3ccc(C(C)C)cc3)c(C)oc2c1C
Temperature: 80 °C
Yield: 96 %

Procedure:
A mixed solution of 1-(4-isopropylphenyl)-2-(2,3,5-trimethylphenoxy)propan-1-one obtained in Reference Example 346 (61.3 g, 194 mmol), Amberlyst 15 (61.0 g) and a molecular sieve MS 4A (30 g) in toluene (200 mL) was heated under reflux at 80° C. for 2 hours. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:100) to obtain 54.4 g (yield 96%) of the title compound. Oily matter.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([OH:14])=[O:13])=[CH:8]2.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:4]([O:13][C:12]([C:9]1[NH:10][C:11]2[C:7]([CH:8]=1)=[CH:6][CH:5]=[CH:4][C:3]=2[O:2][CH3:1])=[O:14])[CH2:3][CH2:11][CH3:7]
Reactant: COc1cccc2cc(C(=O)O)[nH]c12
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CCCCOC(=O)c1cc2cccc(OC)c2[nH]1
Yield: 105.7 %

Procedure:
A suspension of 6.0 g of 7-methoxyindole-2carboxylic acid in 100 ml of toluene is combined with 4.3 ml of thionyl chloride; the mixture is heated under stirring for 3 hours to 90° C., then concentrated under vacuum. The residue is combined with 50 ml of n-butanol and heated for one hour under reflux Then the mixture is evaporated to dryness under vacuum, the oily residue is boiled with 60 ml of petroleum ether, the clear solution is decanted from the dark residue, and cooling of the solution yields 4.1 g of 7-methoxyindole-2-carboxylic acid n-butyl ester, mp 66°-69° C.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[C:6]([CH3:12])[CH:7]=[CH:8][C:9]=2[CH3:11])[NH:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14].N1C=CC=CC=1.[C:23](Cl)(=[O:25])[CH3:24].O>C1COCC1>[C:23]([NH:1][C:2]1[C:10]2[C:5](=[C:6]([CH3:12])[CH:7]=[CH:8][C:9]=2[CH3:11])[NH:4][C:3]=1[C:13]([O:15][CH3:16])=[O:14])(=[O:25])[CH3:24]
Reactant: COC(=O)c1[nH]c2c(C)ccc(C)c2c1N
Reactant: CC(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: COC(=O)c1[nH]c2c(C)ccc(C)c2c1NC(C)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 27.9 %

Procedure:
A mixture of 0.6 g (2.75 mmol) of methyl 3-amino-4,7-dimethylindole-2-carboxylate, 0.22 ml (3.3 mmol) of pyridine and 15 ml of anhydrous THF was cooled to 0° C. 10 ml of a solution of 0.24 ml (3.3 mmol) of acetyl chloride in anhydrous THF was added dropwise over a period of 30 minutes. After completion of the addition, the reaction mixture was stirred for 30 minutes. The reaction mixture was poured into 200 ml of water and extracted with 30 ml of ethyl acetate three times. The ethyl acetate layers were combined, washed with 100 ml of water once, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to provide 200 mg of white crystals. Yield: 28%
Reaction SMILES: [CH2:1]([C@H:3]1[CH2:8][C@H:7]2[C@H:9]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C@H:4]1[O:22][C:23](=[O:26])[CH2:24]Br)[C@@H:17]1[C:12](=[CH:13][C:14](=[O:21])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3)[CH3:2].[C:27]([O-:31])(=[O:30])[CH2:28][CH3:29].[K+]>CC(C)=O.O>[CH2:1]([C@H:3]1[CH2:8][C@H:7]2[C@H:9]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C@H:4]1[O:22][C:23](=[O:26])[CH2:24][O:31][C:27](=[O:30])[CH2:28][CH3:29])[C@@H:17]1[C:12](=[CH:13][C:14](=[O:21])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3)[CH3:2]
Reactant: CCC(=O)[O-]
Reactant: CC[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]2(C)[C@H]1OC(=O)CBr
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CCC(=O)OCC(=O)O[C@H]1[C@@H](CC)C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21C
Temperature: 25 °C
Reaction time: 72 h
Yield: 35.4 %

Procedure:
In a mixture of 50 ml of acetone and 12 ml of water are dissolved 2.5 g of 16β-ethyl-17β-bromoacetoxy-4-estren-3-one and 0.7 g of potassium propionate. The solution is stirred at room temperature (17°-25° C.) for 3 days and concentrated under reduced pressure. The residue is extracted with 200 ml of ethyl acetate. The organic layer is separated, washed with water and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure and the residue is subjected to column chromatography. Following passage of 1000 ml isopropyl ether-n-hexane (2:3), elution is carried out with 2000 ml of the same solvent system. The eluate is evaporated under reduced pressure to remove the solvent, giving 0.87 g of the above-identified compound as white crystals.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[CH2:18](Cl)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[CH2:18]([O:11][CH:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: ClCc1ccccc1
Reactant: OC1CCC2(CC1)OCCO2
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: c1ccc(COC2CCC3(CC2)OCCO3)cc1
Reaction time: 1 h
Yield: 83.2 %

Procedure:
225 g of 1,4-dioxa-spiro[4.5]decan-8-ol were dissolved in 1100 ml of dimethyl-formamide, and 198 g of potassium tert.-butoxide were added in portions, with stirring. After one hour, 223 g of benzyl chloride were added dropwise over 30 minutes, and stirred overnight. The batch was added to 1500 ml of water/ice mixture and extracted with ethyl acetate. The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product was subjected to fractional distillation under a high vacuum. At 150° C. and a pressure of about 0.1 mbar, 294 g of 8-benzyloxy-1,4-dioxaspiro[4.5]decane were obtained.
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[CH:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C([N-]CC(C)C)C(C)C.[Li+].Cl[C:31]([O:33][CH3:34])=[O:32]>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][C:31]([O:33][CH3:34])=[O:32])=[CH:16][CH:17]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: C#Cc1ccc(-c2ccc(CCCCC)cc2)cc1
Reactant: COC(=O)Cl
Agent: CC(C)C[N-]CC(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCCCCc1ccc(-c2ccc(CCC(=O)OC)cc2)cc1
Temperature: 25 °C

Procedure:
To a solution of 4-(4-Pentylphenyl)phenylacetylene (2.09 g) in tetrahydrofuran (30 ml) was added dropwise a solution of lithium diisobutylamide in a mixture of tetrahydrofuran and n-hexane (1.60 M, 5.6 ml) at −75° C., and the resultant mixture was stirred for an hour at −78° C. To the mixture was added methyl chloroformate (0.72 ml), and the reaction mixture was allowed to warm to ambient temperature. The solution was diluted with ethyl acetate, and washed in turn with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude product, which was subjected to column chromatography on silica gel (150 ml), and eluted with a mixture of (n-hexane:ethyl acetate=100:0-9:1, V/V) to give Methyl 3-[4-(4-pentylphenyl)phenyl]propionate (2.20 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8](=O)[NH:7][C:6]=2[CH:17]=1.[C:18]1([CH:24]2[CH2:29][NH:28][CH2:27][CH2:26][NH:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[C:8]([N:28]3[CH2:27][CH2:26][NH:25][CH:24]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH2:29]3)=[N:7][C:6]=2[CH:17]=1
Reactant: O=C1Nc2cc(Cl)ccc2Nc2ccccc21
Reactant: c1ccc(C2CNCCN2)cc1
Product: Clc1ccc2c(c1)N=C(N1CCNC(c3ccccc3)C1)c1ccccc1N2
Yield: 69.4 %

Procedure:
8-Chloro-5,10-dihydro-dibenzo[b,e][1,4]diazepine-11-one (25 mg, 0.1 mmol) and 2-phenylpiperazine (162 mg, 1.0 mmol) were reacted according to GP4 to give 27 mg of the title compound (160FE45). MS (ESI) 389 (MH+). Purity for MH+ (UV/MS) 100/89.
Reaction SMILES: Cl.[C:2]12([CH2:12][CH2:13][NH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH2:3]1)[CH2:9]2.[C:20](Cl)(=[O:27])[CH2:21][O:22][CH2:23][C:24](Cl)=[O:25].C(N(CC)CC)C.[CH3:36][OH:37]>ClCCl>[C:2]12([CH2:12][CH2:13][N:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:20](=[O:27])[CH2:21][O:22][CH2:23][C:24]([O:37][CH3:36])=[O:25])[CH2:9][CH:8]3[CH2:7][CH:6]([CH2:5][CH:4]([CH2:10]3)[CH2:3]1)[CH2:11]2
Reactant: CO
Reactant: O=C(Cl)COCC(=O)Cl
Reactant: CCCCCNCCC12CC3CC(CC(C3)C1)C2
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCN(CCC12CC3CC(CC(C3)C1)C2)C(=O)COCC(=O)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 60 %

Procedure:
2-(1-Adamantyl)-N-pentylethylamine hydrochloride (Intermediate No. 1-1) (0.50 g, 1.7 mmol) was added to a solution of diglycolyl chloride (0.31 ml, 2.6 mmol) and triethylamine (0.70 ml, 5.1 mmol) in anhydrous dichloromethane (6 ml) under ice-cooling, and the mixture was stirred at room temperature overnight. Methanol (5 ml) was added to the reaction mixture, and the whole was stirred for three hours. The solvent was evaporated under reduced pressure, the residue was distributed with ethyl acetate and water (15 ml respectively), and the organic layer was washed with a saturated aqueous sodium chloride solution (5 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the resulting residue was purified by silica gel column chromatography to give 0.39 g (60%) of 2-methoxycarbonylmethoxyacetic acid N-[2-(1-adamantyl)ethyl]-N-pentylamide as an oily matter.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH:22]=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:24]1([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH2:33]([O:32][C:30]([N:24]1[CH2:25][CH2:26][N:27]([CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[CH2:28][CH2:29]1)=[O:31])[CH3:34]
Reactant: CCOC(=O)N1CCNCC1
Reactant: O=CC1(c2ccc(OCCCN3CCCC3)cc2)CCOCC1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CCO
Product: CCOC(=O)N1CCN(CC2(c3ccc(OCCCN4CCCC4)cc3)CCOCC2)CC1

Procedure:
4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (500 mg, 1.58 mmol), ethyl piperazine-1-carboxylate (471 mg, 3.00 mmol), absolute ethanol (20 ml), activated 3 Å molecular sieves (500 mg), titanium (IV) isopropoxide (2.31 ml, 7.88 mmol) and STAB (2.84 g, 13.6 mmol) were reacted in accordance with the general procedure D. The isolated crude product was purified by column chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1) to give the title compound as a white solid containing residual 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (350 mg). The material was dissolved in DCM (14 ml) and PS-AMPS (loading 2.04 mmol-1 g, 23 mg) was added and shaken for 24 hours. The resin was filtered and the solution concentrated in vacuo at 30° C., the crude material was subjected to chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1) to give the title compound as a white solid (130 mg, 18%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 6.86 (d, 2H), 4.08 (q, 2H), 4.02 (t, 2H), 3.79-3.70 (m, 2H), 3.57-3.47 (m, 2H), 3.27 (br s, 4H), 2.63 (t, 2H), 2.53 (br s, 4H), 2.38 (s, 2H), 2.21-1.73 (m, 14H), 1.21 (t, 3H).
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)C=O.F[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=1[N+:24]([O-:26])=[O:25]>O>[N+:24]([C:15]1[CH:16]=[C:17]([C:20]([F:21])([F:22])[F:23])[CH:18]=[CH:19][C:14]=1[N:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)([O-:26])=[O:25]
Reactant: C1CCCNCC1
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(C(F)(F)F)ccc1N1CCCCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
Hexahydro-1H-azepine (682 μl, 6.05 mmol, commercially available product) was added at 0° C. to an N,N-dimethylformamide (DMF; 2 ml) solution of 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (506 mg, 2.42 mmol, commercially available product). The resulting mixture was warmed to room temperature and stirred for one hour. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20 g, hexane/ethyl acetate=7/1). Thus, hexahydro-1-[2-nitro-4-(trifluoromethyl)phenyl]-1H-azepine (680 mg, 97.5%) was yielded as an orange-colored solid.
Reaction SMILES: [Cl-].[NH4+:2].C([O-])(=O)C.[Na+].[Cl:8][C:9]1[C:10]([CH2:27][CH:28]=O)=[C:11]([CH:25]=O)[C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)=[C:13]([CH:15]([OH:17])[CH3:16])[CH:14]=1.O1CCCC1>O>[Cl:8][C:9]1[CH:14]=[C:13]([CH:15]([OH:17])[CH3:16])[C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)=[C:11]2[C:10]=1[CH:27]=[CH:28][N:2]=[CH:25]2
Reactant: [NH4+]
Reactant: CC(O)c1cc(Cl)c(CC=O)c(C=O)c1-c1cccc(F)c1
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC(O)c1cc(Cl)c2ccncc2c1-c1cccc(F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of ammonium chloride (28.5 mg, 0.533 mmol) and sodium acetate (43.7 mg, 0.533 mmol) in water (0.4 mL) was added to a solution of 4-chloro-3′-fluoro-6-(1-hydroxyethyl)-3-(2-oxoethyl)biphenyl-2-carbaldehyde (0.171 g, 0.533 mmol) in tetrahydrofuran (0.4 mL, 5 mmol). The reaction mixture was stirred at room temperature overnight and then extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, concentrated to dryness under reduced pressure. The crude product was used in the next step (0.16 g, 99%). LCMS calculated for C17H14ClFNO (M+H)+: m/z=302.1; Found: 302.1
Reaction SMILES: COC[O:4][C:5]1[C:6]([C:16](=[O:18])[CH3:17])=[CH:7][C:8]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[N:9][CH:10]=1.CC(O)C.C1COCC1>Cl>[OH:4][C:5]1[C:6]([C:16](=[O:18])[CH3:17])=[CH:7][C:8]([CH2:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[N:9][CH:10]=1
Reactant: COCOc1cnc(CC(C)(C)C)cc1C(C)=O
Agent: Cl
Solvent: C1CCOC1
Solvent: CC(C)O
Product: CC(=O)c1cc(CC(C)(C)C)ncc1O

Procedure:
A solution of 1-(5-(methoxymethoxy)-2-neopentylpyridin-4-yl)ethanone (21.6 g, 86 mmol) in (2:1:1) 5 M HCl: i-PrOH:THF (800 mL) was stirred 4 h at rt. The mixture was concentrated to remove the THF and i-PrOH. The resulting solution consisting of the product in aqueous HCl was quenched by slow addition to a solution of saturated aqueous NaHCO3 (500 mL) containing excess solid NaHCO3 (50 g). The aqueous layer was extracted with CH2Cl2 (3×250 mL), the organic layers combined and washed with saturated aqueous NaCl (250 mL), dried (MgSO4), and concentrated to give 1-(5-hydroxy-2-neopentylpyridin-4-yl)ethanone as a brown oil.
Reaction SMILES: [O:1]([C:9]1C=C[C:12]([NH2:13])=[CH:11][CH:10]=1)[C:2]1C=CC(N)=C[CH:3]=1.C1(=O)OC(=[O:20])C=C1.C1C(C(C2C=CC3C(OC(=O)C=3C=2)=O)=O)=CC2C(OC(=O)C=2C=1)=O>CC(N(C)C)=O>[C:12]1(=[O:20])[NH:13][C:9](=[O:1])[CH:10]=[CH:11]1.[CH:2]#[CH:3]
Reactant: Nc1ccc(Oc2ccc(N)cc2)cc1
Reactant: O=C1C=CC(=O)O1
Agent: O=C(c1ccc2c(c1)C(=O)OC2=O)c1ccc2c(c1)C(=O)OC2=O
Solvent: CC(=O)N(C)C
Product: C#C
Product: O=C1C=CC(=O)N1

Procedure:
A maleimide-acetylene terminated monomeric material was prepared. A solution of 0.05 moles (200.242 g/mol) 4,4'-oxydianiline (ODA) and 0.05 moles (98.06 g/mol) maleic anhydride (MA) in 50 ml of DMAc was combined with a solution of 0.05 moles (322.234 g/mol) benzophenonetetracarboxylic dianhydride (BTDA) and 0.05 moles (117.1512 g/mol) APA in 50 ml DMAc. The solutions were blended, cyclized, filtered, and dried as in Example 1. The resulting monomeric material had the following primary structure: ##STR5##
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[NH2:12][CH2:13][CH2:14][NH:15][C:16]1[N:17]([CH3:26])[C:18](=[O:25])[N:19]([CH3:24])[C:20](=[O:23])[C:21]=1[CH3:22]>CO>[O:5]([CH2:1][CH:2]([OH:4])[CH2:3][NH:12][CH2:13][CH2:14][NH:15][C:16]1[N:17]([CH3:26])[C:18](=[O:25])[N:19]([CH3:24])[C:20](=[O:23])[C:21]=1[CH3:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: c1ccc(OCC2CO2)cc1
Reactant: Cc1c(NCCN)n(C)c(=O)n(C)c1=O
Solvent: CO
Product: Cc1c(NCCNCC(O)COc2ccccc2)n(C)c(=O)n(C)c1=O

Procedure:
3.4 g. Phenyl glycidyl ether and 9.6 g. 4-(2-aminoethylamino)-1,3,5-trimethylpyrimidine-2,6(1H,3H)-dione are stirred for about 24 hours at 70° C. The reaction mixture is dissolved in methanol and then separated by column chromatography, using a weakly acidic cation exchanger ("Amberlite" CG 50 II pract. (Serva)). The column is pre-treated with about 1.5 liters 0.1M methanolic triethylammonium acetate solution. The elution agent used is 0.1M methanolic triethylammonium acetate solution. The fractions containing the pure substance are evaporated, then rendered alkaline with 2N aqueous sodium hydroxide solution, extracted with methylene chloride and the extracts dried and evaporated. The light colored oil obtained becomes crystalline upon triturating with diethyl ether. After recrystallized from ethyl acetate, there are obtained 3.6 g. (44% of theory) of the desired product in the form of colorless crystals; m.p. 104°-106° C.
Reaction SMILES: [F:1][C:2]1[S:6][C:5]([C:7]2[C:11]([C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)=[CH:10][NH:9][N:8]=2)=[CH:4][CH:3]=1.Br[CH:19]([CH2:21][CH3:22])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH:19]([N:9]1[CH:10]=[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[C:7]([C:5]2[S:6][C:2]([F:1])=[CH:3][CH:4]=2)=[N:8]1)([CH2:21][CH3:22])[CH3:20].[CH:19]([N:8]1[C:7]([C:5]2[S:6][C:2]([F:1])=[CH:3][CH:4]=2)=[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[CH:10]=[N:9]1)([CH2:21][CH3:22])[CH3:20]
Reactant: Fc1ccc(-c2n[nH]cc2-c2ccncc2)s1
Reactant: CCC(C)Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCC(C)n1cc(-c2ccncc2)c(-c2ccc(F)s2)n1
Product: CCC(C)n1ncc(-c2ccncc2)c1-c1ccc(F)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 16 %
Yield: 60 %

Procedure:
To a solution of 4-[3-(5-fluoro-2-thienyl)-1H-pyrazol-4-yl]pyridine (0.61 mmol) in 3 mL N,N-dimethylformamide were added 2-bromobutane (0.91 mmol) and cesium carbonate (0.67 mmol). The reaction mixture was stirred overnight at room temperature and the solvent was then evaporated. The residue was diluted with water and extracted three times with ethyl ether. The combined organic extracts were dried over MgSO4 filtered and concentrated. The residue was purified by chromatography on silica gel (dichloromethane:ethyl acetate 20:1 to 5:1) to afford 112 mg of 4-[1-secbutyl-3-(5-fluoro-2-thienyl)-1H-pyrazol-4-yl]pyridine (60% yield) and 30 mg of 4-[1-secbutyl-5-(5-fluoro-2-thienyl)-1H-pyrazol-4-yl]pyridine (16% yield).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:12]=[C:11]2[C:6]([C:7]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([S:20]([N:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)(=[O:22])=[O:21])=[CH:16][CH:15]=3)=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH3:38][N:39]([CH3:44])[S:40](Cl)(=[O:42])=[O:41]>CN(C)C=O>[CH3:38][N:39]([CH3:44])[S:40]([N:26]1[CH2:25][CH2:24][N:23]([S:20]([C:17]2[CH:16]=[CH:15][C:14]([NH:13][C:7]3[C:6]4[C:11](=[CH:12][C:3]([C:2]([F:29])([F:1])[F:30])=[CH:4][CH:5]=4)[N:10]=[CH:9][CH:8]=3)=[CH:19][CH:18]=2)(=[O:22])=[O:21])[CH2:28][CH2:27]1)(=[O:42])=[O:41]
Reactant: CN(C)S(=O)(=O)Cl
Reactant: O=S(=O)(c1ccc(Nc2ccnc3cc(C(F)(F)F)ccc23)cc1)N1CCNCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN(C)S(=O)(=O)N1CCN(S(=O)(=O)c2ccc(Nc3ccnc4cc(C(F)(F)F)ccc34)cc2)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a mixture of [[4-[(7-trifluoromethyl-4-quinolinyl)amino]phenyl]sulfonyl]piperazine (prepared as in Example 9, part D) and triethylamine, in dimethyl formamide, is added dropwise an equimolar quantity of dimethylsulfamoyl chloride. The reaction mixture is stirred at room temperature for 15 to 25 hours and is then partitioned with methylene chloride-aqueous sodium carbonate. The organic phase is dried over sodium sulfate and is concentrated and purified by conventional methods to give 1-(dimethylaminosulfonyl)-4-[[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]phenyl]sulfonyl]piperazine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH2:11][OH:12])[CH:5]=[CH:6][C:7]=1[Cl:8].N1C=CC=CC=1.CN(C1C=CC=CN=1)C.[C:28](Cl)(=[O:30])[CH3:29].Cl>ClCl>[C:28]([O:12][CH2:11][CH:10]=[CH:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)(=[O:30])[CH3:29]
Reactant: OCC=Cc1ccc(Cl)c(Cl)c1
Reactant: CC(=O)Cl
Agent: CN(C)c1ccccn1
Agent: Cl
Agent: ClCl
Solvent: c1ccncc1
Product: CC(=O)OCC=Cc1ccc(Cl)c(Cl)c1
Temperature: 23 °C

Procedure:
Combine a solution of the product of Step 2 (13.2 g, 65 mmol) in CH2 Cl2 (250 mL) at 0° C. with pyridine (7.89 mL, 97.5 mmol) and dimethylaminopyridine (DMAP) (397 mg, 3.25 mmol), followed by acetyl chloride (6.48 mL, 74.7 mmol). Allow the mixture to warm to 23° C., pour into 1M HCl (100 mL) and wash the resulting organic layer with 1M HCl (100 mL) followed by water (5×100 mL; pH=6.5-7). Dry the organic layer over Na2SO4 and concentrate, providing 3-(3,4-dichloro-phenyl)-2-propene-1-ol acetate as a colorless oil, 15.4 g (62.9 mmol, 97%).