Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22]CC)=[O:21])=[CH:18][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].C(O)C.O.Cl>O>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]2[CH:17]=[CH:18][C:19]([C:20]([OH:22])=[O:21])=[CH:25][CH:26]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1ccc(NCCCCCCCCc2ccccc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)c1ccc(NCCCCCCCCc2ccccc2)cc1

Procedure:
A mixture of 7 g. of ethyl p-[(8-phenyloctyl)amino]benzoate (prepared as described in Example 32), 7 g. of potassium hydroxide and 100 ml. of ethanol-water (9:1) is refluxed for 3.5 hours. The mixture is acidified while hot with concentrated hydrochloric acid, diluted with water, chilled and filtered. The solid is washed with water to give off-white crystals, m.p. 113°-115° C. Recrystallization from ethanol gives white crystals, m.p. 113°-115° C.
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]([N:5]([CH2:15][C:16]1([C:29]([O:31][CH3:32])=[O:30])[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:4].C(O)(C(F)(F)F)=O>ClCCl>[F:34][C:2]([F:1])([F:33])[C:3]([N:5]([CH2:15][C:16]1([C:29]([O:31][CH3:32])=[O:30])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:4]
Reactant: COC(=O)C1(CN(C(=O)C(F)(F)F)[C@@H]2C[C@H]2c2ccccc2)CCN(C(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)C1(CN(C(=O)C(F)(F)F)[C@@H]2C[C@H]2c2ccccc2)CCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.3 %

Procedure:
To a solution of 1-tert-butyl 4-methyl 4-((2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)acetamido)methyl)piperidine-1,4-dicarboxylate (150 mg, 0.310 mmol) in dichloromethane (DCM) (2 mL) was added TFA (0.5 mL, 6.49 mmol), and the mixture was stirred at room temperature for 2 h. The mixture was concentrated and the residue was treated with saturated NaHCO3 aqueous solution, extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated to give 110 mg of product as oil. MS: (M+H)+=385.2. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.37-1.67 (m, 4H), 2.11-2.32 (m, 2H), 2.42 (ddd, J=10.17, 6.51, 3.54 Hz, 1H), 2.57 (m, J=12.60, 12.60, 5.87, 2.78 Hz, 2H), 2.90-3.07 (m, 2H), 3.17 (dt, J=7.45, 3.60 Hz, 1H), 3.52-3.58 (m, 3H), 3.70-3.84 (m, 2H), 7.10 (d, J=7.07 Hz, 2H), 7.19-7.26 (m, 1H), 7.28-7.35 (m, 2H).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[NH:13]1[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][OH:21])[CH2:15][CH2:14]1>>[Cl:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:13]1[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][OH:21])[CH2:15][CH2:14]1)[CH:11]=[CH:10]2
Reactant: Clc1ccc2nc(Cl)ccc2c1
Reactant: OCCC1CCNCC1
Product: OCCC1CCN(c2ccc3cc(Cl)ccc3n2)CC1

Procedure:
The process is performed as described in Example 4 (step 4.1). Starting with 2 g (10.10 mmol) of 2,6-dichloroquinoline and 1.44 g (11.10 mmol) of 2-(4-piperidyl)ethanol, and after chromatography on silica gel, eluting with a 98/2 mixture of dichloromethane and methanol, 2.54 g of pure product are obtained in the form of a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[O:20][C:19](=[O:21])[NH:18][N:17]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-])=O.O.O.Cl[Sn]Cl>CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:11][CH2:12][CH:13]([C:16]3[O:20][C:19](=[O:21])[NH:18][N:17]=3)[CH2:14][CH2:15]2)=[CH:8][CH:9]=1
Reactant: O=c1[nH]nc(C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)o1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CO
Product: Nc1ccc(N2CCC(c3n[nH]c(=O)o3)CC2)cc1
Yield: 84.9 %

Procedure:
To a stirred solution of 4-fluoro nitrobenzene (1a, 3.1 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80° C. for 10 h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(4-nitrophenyl)-4-piperidinecarboxy-late (3a, 4.93 g, 85%). To a stirred solution of ester (3a, 4.75 g, 18 mmol) in ethanol, NH2NH2. H2O (2.25 g, 45 mmol) is added and refluxed for 24 h. After completion of the reaction ethanol is evaporated under vacuum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(4-nitrophenyl)-4-piperidinecarbohydrazide (4a, 3.99 g, 84%). Addition N,N-dimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4a, 3.17 g, 12 mmol) in pyridine at room temperature (27° C.) and followed by reflux at temperature 85° C. for 2.5 h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.39 g, 40%). Nitro compound (5a, 1.16 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65° C. for 4 h, after completion of reaction methanol is evaporated under vacuum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 884 mg, 85%). To a stirred solution of 5-nitro2-furanoic acid (0.16 g, 1 mmol) in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide)) (0.19 g, 1 mmol) and amine compound (7a, 0.26 g, 1 mmol) and stirred for 2 h at room temperature (27° C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8a, 323 mg, 81%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=2)=[O:21])=[CH:16][CH:15]=1.I[CH2:35][CH3:36]>>[CH2:35]([N:22]([CH2:23][C:24]1[CH:33]=[CH:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=1)[C:20]([C:17]1[CH:16]=[CH:15][C:14]([C:3]2[CH:4]=[C:5]([C:8]3[O:9][C:10]([CH3:13])=[N:11][N:12]=3)[CH:6]=[CH:7][C:2]=2[CH3:1])=[CH:19][CH:18]=1)=[O:21])[CH3:36]
Reactant: CCI
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)NCc4ccc5ccccc5c4)cc3)c2)o1
Product: CCN(Cc1ccc2ccccc2c1)C(=O)c1ccc(-c2cc(-c3nnc(C)o3)ccc2C)cc1

Procedure:
N-Ethyl-2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(naphth-2-ylmethyl)-1,1′-biphenyl-4-carboxamide was prepared from 2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(naphth-2-ylmethyl)-1,1′-biphenyl-4-carboxamide and iodoethane using method L. NMR; δH [2H6]—DMSO 7.94-7.36,(14H, m), 4.89-4.70,(2H, m), 3.46-3.25,(2H, m), 2.55,(3H, s), 2.33-2.28,(3H, m), 1.16-1.09,(3H, b). LCMS; retention time 3.77 min, MH+ 462.
Reaction SMILES: [C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][NH:8][CH2:9][C:10]2[CH:11]=[C:12]([CH:22]=[CH:23][CH:24]=2)[CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:3][CH:2]=1.[Cl:31][C:32]1[C:33]([OH:43])=[C:34]([S:39](Cl)(=[O:41])=[O:40])[CH:35]=[C:36]([Cl:38])[CH:37]=1.CCN(CC)CC>C(Cl)Cl>[C:1]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]([CH2:9][C:10]2[CH:11]=[C:12]([CH:22]=[CH:23][CH:24]=2)[CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[S:39]([C:34]2[CH:35]=[C:36]([Cl:38])[CH:37]=[C:32]([Cl:31])[C:33]=2[OH:43])(=[O:40])=[O:41])=[CH:3][CH:2]=1
Reactant: CC(C)(C)OC(=O)NCc1cccc(CNCc2ccc(-c3ccccc3)cc2)c1
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCc1cccc(CN(Cc2ccc(-c3ccccc3)cc2)S(=O)(=O)c2cc(Cl)cc(Cl)c2O)c1
Reaction time: 1.5 h
Yield: 73.7 %

Procedure:
To a solution of tert-butyl 3-((biphenyl-4-ylmethylamino)methyl)benzylcarbamate (2.42 g, 6.01 mmol) in CH2Cl2 (30.0 mL) was added a solution of 3,5-dichloro-2-hydroxybenzene-1-sulfonyl chloride (1.65 g, 6.31 mmol) in CH2Cl2 (8.0 mL) at ice bath temperature followed by Et3N (2.5 mL, 18.0 mmol). The reaction mixture was stirred at ice bath temperature for 1.5 h and concentrated in vacuo. The residue was purified by flash chromatography on SiO2 eluting with CH2Cl2 to 8% of ethyl acetate in CH2Cl2 to give the product as a white glassy solid (2.78 g, 72.5%). 1H NMR (CDCl3): δ 9.18 (bs, 1H), 7.59-7.38 (m, 9H), 7.28-7.21 (m, 4H), 7.06 (m, 2H), 4.48 (s, 2H), 4.43 (s, 2H), 4.25 (s, 2H), 1.49 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17]([CH3:19])=O)[N:3]=1.SC[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17][CH2:19][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[N:3]=1
Reactant: SCCc1ccccn1
Reactant: CS(=O)c1nc(N)nc(-c2ccc(F)cc2)c1C#N
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(SCCc2ccccn2)nc(N)nc1-c1ccc(F)cc1

Procedure:
From 2-amino-4-(4-fluoro-phenyl)-6-methanesulfinyl-pyrimidine-5-carbonitrile, 2-mercaptoethylpyridine and DBU in DME. ES-MS m/e (%): 352 (M+H+, 100).
Reaction SMILES: [C:1]1([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:23]1([CH2:29][CH2:30][CH2:31]Cl)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>CC(C)=O.C(=O)([O-])[O-].[K+].[K+]>[C:1]1([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:16]2[CH:17]=[CH:18][C:19]([O:22][CH2:31][CH2:30][CH2:29][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:20][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccc(-c2nc3ccccc3n2-c2ccccc2)cc1
Reactant: ClCCCN1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: c1ccc(-n2c(-c3ccc(OCCCN4CCCCC4)cc3)nc3ccccc32)cc1

Procedure:
The title compound was prepared by reacting the compound of Example 29 with 3-(piperdin-1-yl)propyl chloride in acetone and potassium carbonate as previously described. mp 86° C., NMR, MS 412.
Reaction SMILES: [NH2:1][C:2]1[C:3](C#N)=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8].O.[C:13](=[O:16])(O)[O-:14].[Na+]>S(=O)(=O)(O)O>[NH2:1][C:2]1[C:3]([C:13]([OH:14])=[O:16])=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8]
Reactant: O=C([O-])O
Reactant: N#Cc1nc(Cl)cc(Cl)c1N
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Nc1c(Cl)cc(Cl)nc1C(=O)O
Temperature: 100 °C
Reaction time: 1 h

Procedure:
3-Amino-4,6-dichloro-pyridine-2-carbonitrile (121 mg) was dissolved in concentrated sulfuric acid (1 mL) and stirred for 1 h at 100° C. The reaction mixture was cooled to room temperature and water (1 mL) was slowly added. The reaction mixture was warmed again to 100° C. and stirred at this temperature for 2 h. Water was added after cooling to room temperature, the pH was adjusted to ˜10 by addition of solid sodium bicarbonate and the aqueous solution was washed 2× with MTB-ether. The aqueous layer was then adjusted to pH ˜2 by addition of 2 M hydrochloric acid and extracted 3× with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 99 mg of the title compound of the formula
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4]/[C:5](/[C:21]1O[C:23]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:24][N:25]=1)=[CH:6]\[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:17]=[C:16]([CH3:18])[N:15]=[CH:14]2)=[C:9]([O:19][CH3:20])[CH:8]=1.C([O-])(=O)C.[NH4+:37]>C(O)(=O)C>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]2[N:37]=[C:21]3/[C:5](=[CH:6]/[C:7]4[CH:12]=[CH:11][C:10]([N:13]5[CH:17]=[C:16]([CH3:18])[N:15]=[CH:14]5)=[C:9]([O:19][CH3:20])[CH:8]=4)/[CH2:4][CH2:3][CH2:2][N:25]3[N:24]=2)=[CH:27][CH:28]=1
Reactant: COc1cc(/C=C(\CCCCl)c2nnc(-c3ccc(F)cc3)o2)ccc1-n1cnc(C)c1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Product: COc1cc(/C=C2\CCCn3nc(-c4ccc(F)cc4)nc32)ccc1-n1cnc(C)c1
Temperature: 25 °C
Yield: 43.6 %

Procedure:
A solution of 2-{4-chloro-1-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}butyl}-5-(4-fluorophenyl)-[1,3,4]oxadiazole (85 mg) and ammonium acetate (290 mg) in acetic acid (3 mL) was heated under reflux for 10 hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. Methylene chloride and a 1 N sodium hydroxide solution were added to the residue, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex™ NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 34 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:27])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22][C:23]([F:26])([F:25])[F:24])[CH2:9]1)C1C=CC=CC=1.CCN(C(C)C)C(C)C.[CH3:43][CH:44](Cl)[O:45]C(Cl)=O>O1CCCC1>[C:44]([O:27][C@:14]([C@@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22][C:23]([F:25])([F:26])[F:24])(=[O:45])[CH3:43]
Reactant: CC(Cl)OC(=O)Cl
Reactant: OC(Cc1ccccc1SC(F)(F)F)(c1ccccc1)C1CN(Cc2ccccc2)CCO1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)O[C@@](Cc1ccccc1SC(F)(F)F)(c1ccccc1)[C@H]1CNCCO1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1-(4-benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethylsulfanyl-phenyl)-ethanol (218 mg g, 1 equiv.) and solid supported Hunig's base (available from Argonaut, 1 g, 5 equiv.) in dry tetrahydrofuran (4 mL) at 0° C. under nitrogen atmosphere was added ACE-Cl (502 μL, 10 equiv.). The reaction mixture was left to warm to room temperature for 48 hours. All volatiles were evaporated under vacuum, and the resulting solid was taken-up with methanol (50 mL) and stirred at room temperature overnight. The solution was filtered through acid ion exchange column and the required fractions evaporated to dryness. The resulting solid was purified via preparative HPLC to give 62 mg of the title compound as a colourless oil. 1H NMR (300 MHz, CDCl3) δ: 2.01 (s, 3H), 2.43-2.47 (m, 1H), 2.63-2.70 (m, 1H), 2.81-2.94 (m, 2H), 3.24 (d, 1H, J=13.57 Hz), 3.85-3.96 (m, 2H), 4.01-4.05 (m, 1H), 4.09-4.13 (m, 1H), 4.45 (bs, 4H), 6.90-6.93 (m, 1H), 7.13-7.26 (m, 7H), 7.55-7.58 (m, 1H) ppm. LCMS (12 minute method) [M+H]+=384 @ Rt 5.13 min. single peak.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([C:13]([F:16])([F:15])[F:14])[CH:6]=1.O[C:23]1[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:25][CH:24]=1>>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([N:4]([CH2:17][C:18]([F:19])([F:20])[F:21])[CH2:3][CH2:2][O:1][C:23]2[CH:28]=[CH:27][C:26]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)=[CH:6][C:7]=1[C:13]([F:15])([F:16])[F:14])#[N:10]
Reactant: NS(=O)(=O)c1ccc(O)cc1
Reactant: N#Cc1ccc(N(CCO)CC(F)(F)F)cc1C(F)(F)F
Product: N#Cc1ccc(N(CCOc2ccc(S(N)(=O)=O)cc2)CC(F)(F)F)cc1C(F)(F)F

Procedure:
Synthesized as described in Example 1C using 4-[(2-hydroxyethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile and 4-hydroxybenzenesulfonamide: MS (APCI) m/z 468 (M+1).
Reaction SMILES: [CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][O:12][C:13]1[CH:51]=[CH:50][C:16]([CH2:17][O:18][CH2:19][C@H:20]([CH3:49])[C@H:21]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[C@@H:22]([CH3:40])[CH2:23][CH2:24][C:25]([N:27]2[C@H:31]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:30][O:29][C:28]2=[O:39])=[O:26])=[CH:15][CH:14]=1.CI>C1COCC1>[CH3:11][O:12][C:13]1[CH:51]=[CH:50][C:16]([CH2:17][O:18][CH2:19][C@H:20]([CH3:49])[C@H:21]([O:41][Si:42]([C:45]([CH3:46])([CH3:48])[CH3:47])([CH3:44])[CH3:43])[C@@H:22]([CH3:40])[CH2:23][C@@H:24]([CH3:1])[C:25]([N:27]2[C@H:31]([CH2:32][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:30][O:29][C:28]2=[O:39])=[O:26])=[CH:15][CH:14]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: COc1ccc(COC[C@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)CCC(=O)N2C(=O)OC[C@H]2Cc2ccccc2)cc1
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Product: COc1ccc(COC[C@H](C)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](C)C[C@@H](C)C(=O)N2C(=O)OC[C@H]2Cc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 73.4 %

Procedure:
NaHMDS (1 M in THF, 14.9 mL, 14.9 mmol) was added dropwise over a 30 min period to a cooled (−78° C.) suspension of the imide 25 (7.91 g, 13.6 mmol) in THF (45 mL). After 15 min of stirring, the resulting cold solution was treated with MeI (2.53 mL, 40.8 mmol) and allowed to stir at −78° C. for 3 h before being warmed to 25° C. overnight (12 h) The reaction was quenched with H2O (100 mL), and the aqueous layer was extracted with Et2O (3×150 mL). The combined organic extracts were dried (MgSO4), concentrated in vacuo and chromatographed (EtOAc/hexane 1:9) to provide 5.97 g (74%) of 26 as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.42-7.26 (m, 7H), 6.95-6.92 (m, 2H), 4.71 (m, 1H), 4.51 (m, 2H), 4.18 (m, 2H), 3.95 (m, 1H), 3.84 (s, 3H), 3.63 (dd, J=8.9, 3.8 Hz, 1H), 3.57 (dd, J=6.4, 2.7 Hz, 1H), 3.35 (t, J=8.5 Hz, 1H), 3.28 (dd, J=13.3, 3.1 Hz, 1H), 2.83 (dd, J=13.3, 9.4 Hz, 1H), 2.10-1.95 (m, 2H), 1.68 (m, 1H), 1.38 (ddd, J=14.1, 9.8, 4.9 Hz, 1H), 1.31 (d, J=6.8 Hz, 3H), 1.04 (d, J=6.9 Hz, 3H), 0.98 (s, 9H), 0.95 (d, J=6.7 Hz, 3H), 0.14 (s, 3H), 0.13 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 176.8, 158.8, 152.8, 135.1, 130.8, 129.3, 128.9, 128.7, 127.1, 113.5, 77.6, 72.6, 72.4, 65.7, 55.0, 38.9, 38.0, 37.6, 35.3, 33.8, 26.0, 18.8, 18.3, 14.9, 13.8, −3.8, −4.2.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][C:3]=1[C:11]1[N:15]([CH3:16])[N:14]=[CH:13][CH:12]=1.C1C(=O)N([Br:24])C(=O)C1>O1CCCC1>[Br:24][C:12]1[CH:13]=[N:14][N:15]([CH3:16])[C:11]=1[C:3]1[CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[S:6][C:2]=1[CH3:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc(-c2ccnn2C)c(C)s1
Solvent: C1CCOC1
Product: COC(=O)c1cc(-c2c(Br)cnn2C)c(C)s1

Procedure:
A solution of methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (580 mg, 2.45 mmol) and n-bromosuccinimide (437 mg, 2.45 mmol) in tetrahydrofuran (12.300 ml) was stirred in a sealed tube for 1 h at 70° C. The solution was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated then purified via column chromatography (silica, 20% EtOAc in hexanes) yielding methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate (600 mg, 1.90 mmol, 78° A yield) as a yellow oil: LCMS (ES) m/e 314, 316 (M, M+H)+.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH2:25][C:26](O)=[O:27])[C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:29]([NH:31][CH2:32][C:33]1[S:34][CH:35]=[CH:36][N:37]=1)[CH3:30]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[CH2:25][C:26]([N:31]([CH2:29][CH3:30])[CH2:32][C:33]2[S:34][CH:35]=[CH:36][N:37]=2)=[O:27])(=[O:12])=[O:13])=[CH:7][CH:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)(C)c1ccc(S(=O)(=O)N(CC(=O)O)c2ccc3ncccc3c2)cc1
Reactant: CCNCc1nccs1
Product: CCN(Cc1nccs1)C(=O)CN(c1ccc2ncccc2c1)S(=O)(=O)c1ccc(C(C)(C)C)cc1

Procedure:
prepared by reaction of [(4-tert-butyl-benzenesulfonyl)-quinolin-6-yl-amino]-acetic acid with ethyl-thiazol-2-ylmethyl-amine
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2([CH2:12][CH2:13][OH:14])[CH2:11][CH2:10][NH:9][CH2:8]2)[CH:2]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([O:28][CH3:29])[C:25]=1[O:26][CH3:27])[C:20](Cl)=[O:21]>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2([CH2:12][CH2:13][OH:14])[CH2:11][CH2:10][N:9]([C:20](=[O:21])[C:19]3[CH:18]=[C:17]([O:16][CH3:15])[C:25]([O:26][CH3:27])=[C:24]([O:28][CH3:29])[CH:23]=3)[CH2:8]2)[CH:2]=1
Reactant: OCCC1(c2cccnc2)CCNC1
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Product: COc1cc(C(=O)N2CCC(CCO)(c3cccnc3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of example 3.1 using 2-[3-(pyridin-3-yl)-pyrrolidin-3-yl]-ethanol (23 mmol) and 3,4,5-trimethoxy-benzoyl chloride (23 mmol). Chromatograph on silica gel to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:22][CH:21]=2)[N:9]2C(=O)C3C(=CC=CC=3)C2=O)=[N:4][CH:5]=[CH:6][N:7]=1.NN.CCO>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH:8]([NH2:9])[C:20]2[CH:21]=[CH:22][C:23]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:24][CH:25]=2)=[N:4][CH:5]=[CH:6][N:7]=1
Reactant: O=C1c2ccccc2C(=O)N1C(c1ccc(Oc2ccccc2)cc1)c1nccnc1Cl
Agent: NN
Solvent: CCO
Solvent: ClCCl
Product: NC(c1ccc(Oc2ccccc2)cc1)c1nccnc1Cl
Yield: 79.5 %

Procedure:
A solution of 2-[(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-isoindole-1,3-dione (1.04 g, 0.0023 mol) and anhydrous hydrazine (0.247 mL, 0.0078 mol) in DCM (8.8 mL)/EtOH (6 mL) was stirred at rt overnight. The white precipitate (phthalic hydrazide) was filtered and washed with DCM. The filtrate was collected and concentrated in vacuo and purified by flash column chromatography using 10%-30% EtOAc in hexanes to afford 570 mg of the title compound as an orange oily solid. 1H NMR (400 MHz, CDCl3): δ 2.38 (br. s., 2H), 5.54 (s, 1H), 6.89-7.01 (m, 4H), 7.09 (t, J=7.45 Hz, 1H), 7.27-7.36 (m, 4H), 8.26 (d, J=2.27 Hz, 1H), 8.53 (d, J=2.53 Hz, 1H). MS (ES+): m/z 294.72 (90) [MH+]. HPLC: tR=2.15 min (Open Lynx, polar—5 min).
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.[CH3:12][C:13]1[CH:18]=[C:17]([NH:19][CH2:20][CH2:21][NH2:22])[N:16]2[N:23]=[CH:24][N:25]=[C:15]2[N:14]=1.O>CS(C)=O>[O:5]([CH2:1][CH:2]([OH:4])[CH2:3][NH:22][CH2:21][CH2:20][NH:19][C:17]1[N:16]2[N:23]=[CH:24][N:25]=[C:15]2[N:14]=[C:13]([CH3:12])[CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: Cc1cc(NCCN)n2ncnc2n1
Reactant: c1ccc(OCC2CO2)cc1
Solvent: O
Solvent: CS(C)=O
Product: Cc1cc(NCCNCC(O)COc2ccccc2)n2ncnc2n1
Reaction time: 48 h

Procedure:
3.6 g. Phenyl glycidyl ether and 9.0 g. 5-methyl-7-(2-aminoethylamino)-s-triazolo[1,5-a]pyrimidine are dissolved in dimethyl sulphoxide and left to stand for 48 hours at 45° C. The reaction mixture is then poured into water, extracted with methylene chloride, dried and purified chromatographically in the manner described in Example 28. There are obtained 2.0 g. (24% of theory) of the desired product in the form of colorless crystals; m.p. 126°-127° C., after recrystallization from isopropyl alcohol.
Reaction SMILES: [O:1]=[C:2]([CH:4]=[C:5]([CH3:7])[CH3:6])[CH3:3].[CH3:8][C:9]([CH3:11])=O>>[CH3:6][C:5](=[CH:4][C:2](=[O:1])[CH:3]=[C:9]([CH3:11])[CH3:8])[CH3:7]
Reactant: CC(=O)C=C(C)C
Reactant: CC(C)=O
Product: CC(C)=CC(=O)C=C(C)C

Procedure:
Acetone, first percolated through a bed of alumina, was passed through a reactor containing 0.54 g of ZSM-5 zeolite having a silica-to-alumina ratio of 26,000 to 1 and an Na content of 1.48%. No condensation products were observed at reaction temperatures below 200° C. (392° F.). When the reactor containing zeolite was heated to 280° to 370° C. (536°-698° F.), about 10% of the acetone fed was converted to mesityl oxide. Some phorone was also formed.