Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([CH:11]1[CH2:22][CH2:21][C:14]2([O:18][CH2:17][CH:16]([C:19]#[N:20])[CH2:15]2)[CH2:13][CH2:12]1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([CH:11]1[CH2:22][CH2:21][C:14]2([O:18][CH2:17][CH:16]([CH2:19][NH2:20])[CH2:15]2)[CH2:13][CH2:12]1)([CH3:10])([CH3:8])[CH3:9]
Reactant: CC(C)(C)C1CCC2(CC1)CC(C#N)CO2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)C1CCC2(CC1)CC(CN)CO2
Yield: 65.7 %

Procedure:
To a solution of lithium aluminum hydride (LAH) (2.19 g, 58 mmol) in THF (100 ml) was added 8-t-butyl-3-cyano-1-oxaspiro-(4,5)decane (8.5 g, 38.5 mmol) in THF (25 ml). The reaction mixture was refluxed for 3 hours. After cooling excess LAH was carefully destroyed by addition of saturated, aqueous sodium sulfate solution. The reaction mixture was filtrated from insoluble material and the filtrate was evaporated in vacuo. The pale yellow oil (8.6 g) was purified by Kugelrohr distillation (125°-135° C., 0.05 mbar) to yield the product as a colourless liquid (5.7 g, nD22 : 1.4817).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[CH:10]12[O:15][CH:14]1[CH2:13][CH2:12][CH2:11]2.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)CCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C@@H:13]2[CH2:12][CH2:11][CH2:10][C@H:14]2[OH:15])=[CH:4][C:3]=1[F:9]
Reactant: C1CC2OC2C1
Reactant: Oc1ccc(Br)c(F)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCC#N
Product: O[C@@H]1CCC[C@H]1Oc1ccc(Br)c(F)c1

Procedure:
4-Bromo-3-fluorophenol (8.00 g, 41.9 mmol) and 6-oxabicyclo[3.1.0]hexane (8.25 mL, 95.2 mmol) were combined in butyronitrile (5.0 mL) and treated with sodium carbonate (4.04 g, 38.1 mmol). The reaction was subjected to microwave irradiation for 2 hours at 175° C., then filtered through Celite®. The filter cake was washed with ethyl acetate, then dichloromethane, and the combined filtrates were concentrated under reduced pressure to provide product as a dark brown oil. This material was used without additional purification. Yield: 11.59 g, >41.9 mmol, assumed quantitative. 1H NMR (400 MHz, CDCl3) δ 1.61-1.89 (m, 5H), 2.02-2.24 (m, 2H), 4.30 (m, 1H), 4.46 (m, 1H), 6.63 (ddd, J=8.9, 2.8, 1.1 Hz, 1H), 6.73 (dd, J=10.5, 2.8 Hz, 1H), 7.40 (dd, J=8.9, 8.0 Hz, 1H).
Reaction SMILES: Cl[Si:2]([Cl:9])([CH:6]([CH3:8])[CH3:7])[CH:3]([CH3:5])[CH3:4].[CH2:10]([Li])[CH2:11][CH2:12][CH3:13]>O1CCCC1>[CH2:10]([Si:2]([CH:3]([CH3:4])[CH3:5])([CH:6]([CH3:7])[CH3:8])[Cl:9])[CH2:11][CH2:12][CH3:13]
Reactant: [Li]CCCC
Reactant: CC(C)[Si](Cl)(Cl)C(C)C
Solvent: C1CCOC1
Product: CCCC[Si](Cl)(C(C)C)C(C)C

Procedure:
Dichlorodiisopropylsilane 1 is treated with n-butyllithium in tetrahydrofuran solution to yield butyldiisopropyl-chlorosilane 2, which is then reacted with lithium (trimethylsilyl)acetylide in situ to yield trimethylsilyl protected ethynyl butyldiisopropylsilane 3. Selective removal of the TMS group with potassium carbonate affords ethynyl butyldiisopropylsilane 4. Using a standard procedure, this ethynyl silane is lithiated with n-butyllithium then reacted with commercial flavanthrone to yield the diol intermediate 5, which is reductive-aromatized under acidic conditions to afford 6.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:12]4[C:17]([C:18](Br)=[C:19]5[C:24]=3[CH:23]=[CH:22][CH:21]=[CH:20]5)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=1.[C:36]1([C:42]2[CH:47]=[C:46](B(O)O)[CH:45]=[C:44]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:43]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(O)C>[C:36]1([C:42]2[CH:47]=[C:46]([C:18]3[C:19]4[C:24]([C:11]([C:8]5[CH:9]=[C:10]6[C:5]([CH:4]=[CH:3][C:2]([C:26]7[CH:35]=[CH:34][C:33]8[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=8)[CH:27]=7)=[CH:1]6)=[CH:6][CH:7]=5)=[C:12]5[C:17]=3[CH:16]=[CH:15][CH:14]=[CH:13]5)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:45]=[C:44]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:43]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: Brc1c2ccccc2c(-c2ccc3ccc(-c4ccc5ccccc5c4)cc3c2)c2ccccc12
Reactant: OB(O)c1cc(-c2ccccc2)cc(-c2ccccc2)c1
Agent: [Pd]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(-c2cc(-c3ccccc3)cc(-c3c4ccccc4c(-c4ccc5ccc(-c6ccc7ccccc7c6)cc5c4)c4ccccc34)c2)cc1
Temperature: 25 °C
Yield: 41.6 %

Procedure:
Under the nitrogen atmosphere, [9-([2,2′-binaphthalen]-7-yl)-10-bromoanthracene (2.0 g) as the tenth intermediate compound, [1,1′:3′,1″-terphenyl]-5′-ylboronic acid (1.0 g), Pd(dba)2 (0.03 g), tricyclohexyl phosphine (0.03 g), potassium phosphate (1.3 g), and a mixture solvent of toluene and ethanol (20 ml) (toluene/ethanol=4/1 (volume ratio)) were added to a flask and refluxed for 2 hours. Once the heating is completed, the reaction solution was cooled to room temperature. The reaction was terminated by adding water. The target compound was extracted with toluene. The solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (solvent: toluene) and also by active carbon column chromatography (solvent: toluene) to give 9-([1,1′:3′,1″-terphenyl]-5′-yl)-10-([2,2′-binaphthalen]-7-yl)anthracene (1.0 g) as the target compound represented by Formula (1-162). The scheme is shown in the following “Reaction 17”.
Reaction SMILES: O.[ClH:2].[NH:3]1[CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.[C:10]([O:14][C:15](=[O:18])[NH:16][NH2:17])([CH3:13])([CH3:12])[CH3:11]>CO>[ClH:2].[C:10]([O:14][C:15]([NH:16][N:17]=[C:6]1[CH2:7][CH2:8][NH:3][CH2:4][CH2:5]1)=[O:18])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)OC(=O)NN
Reactant: O=C1CCNCC1
Agent: Cl
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)NN=C1CCNCC1
Temperature: 25 °C

Procedure:
A mixture of 4-piperidone hydrochloride monohydrate (31.2 g, 203 mmol) and tert-butylcarbazate (26.8 g, 203 mmol) in 100 mL MeOH is stirred over weekend at RT and then concentrated in vacuo. The residue is crystallized from ethyl acetate. Yield: 47.5 g.
Reaction SMILES: [F:1][CH2:2][C:3]([CH2:9][F:10])([CH3:8])[C:4](=[O:7])[CH2:5]Br.[NH:11]1[CH:15]=[N:14][CH:13]=[N:12]1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:1][CH2:2][C:3]([CH2:9][F:10])([CH3:8])[C:4](=[O:7])[CH2:5][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: c1nc[nH]n1
Reactant: CC(CF)(CF)C(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(CF)(CF)C(=O)Cn1cncn1
Temperature: 40 °C
Reaction time: 8 h
Yield: 36.3 %

Procedure:
215 g (1 mole) of crude 3,3-bisfluoromethyl-1-bromo-butan-2-one were added dropwise to 84 g (1.2 moles) of 1,2,4-triazole and 165 g (1.2 moles) of ground potassium carbonate in 1 liter of ethanol at 30° to 35° C. The mixture was subsequently stirred at 40° C. overnight, the insoluble material was then filtered off and the filtrate was concentrated. The oily residue was extracted with methylene chloride and water and the extract was dried over sodium sulphate and concentrated. The residue was taken up in methylene chloride and 140 ml of ethereal hydrochloric acid were added. The crystalline product formed was filtered off with suction and extracted by stirring with 1 liter of methylene chloride and 1 liter of saturated aqueous sodium bicarbonate solution, and the extract was washed with 1 liter of water, dried over sodium sulphate and concentrated. 73.8 g (36.4% of theory) of 3,3-bisfluoromethyl-1-(1,2,4-triazol-1-yl)-butan-2-one were obtained as an oil, which could be further reacted directly. ##STR35##
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([SH:13])=[N:11][N:10]=[N:9]2)=[CH:4][CH:3]=1.[C:14](Cl)(=[O:18])[C:15]([CH3:17])=[CH2:16].[OH-].[Na+].Cl>C(#N)C.N1C=CC=CC=1>[C:14]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([SH:13])=[N:11][N:10]=[N:9]2)=[CH:4][CH:3]=1)(=[O:18])[C:15]([CH3:17])=[CH2:16]
Reactant: Nc1ccc(-n2nnnc2S)cc1
Reactant: C=C(C)C(=O)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Solvent: CC#N
Product: C=C(C)C(=O)Nc1ccc(-n2nnnc2S)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Thirty grams of 1-(p-aminophenyl)-1,2,3,4-tetrazole-5-thiol was dissolved in 300 ml of acetonitrile and 20 ml of pyridine, and 16 ml of methacrylic acid chloride was added dropwise to the resulting solution with agitation. After the addition of the methacrylic acid chloride, the mixture was agitated for 1 hour at room temperature. Thereafter, a 10% aqueous solution of sodium hydroxide was added and the mixture was agitated for a white. The mixture was rendered weakly acidic with dilute hydrochloric acid and the end compound was obtained as a white crystal in an amount of 29.4 g (yield, 72%).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[C:14]([C:23]([O:25][CH2:26][CH2:27][CH3:28])=[O:24])=[CH:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].Br[CH2:38][CH2:39][CH2:40][Cl:41].O>CN(C)C=O>[Cl:41][CH2:40][CH2:39][CH2:38][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[C:14]([C:23]([O:25][CH2:26][CH2:27][CH3:28])=[O:24])=[CH:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:29][CH3:30]
Reactant: CCCOC(=O)c1cc2ccccc2cc1Oc1ccnc2cc(O)c(OC)cc12
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCOC(=O)c1cc2ccccc2cc1Oc1ccnc2cc(OCCCCl)c(OC)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
Propyl 3-(7-hydroxy-6-methoxy-quinolin-4-yloxy)-naphthalene-2-carboxylate (240 mg) was dissolved in N,N-dimethylformamide (6 ml) to prepare a solution. Potassium carbonate (822 mg) and 1-bromo-3-chloropropane (0.29 ml) were added to the solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using acetone-chloroform to give the title compound (230 mg, yield 81%).
Reaction SMILES: CN(C)C=O.[C:6]([N:13]1[CH2:18][CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH2:15][CH2:14]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].Cl[C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:30]1[CH:31]=[C:32]([C:33]([O:35][CH3:36])=[O:34])[CH:37]=[CH:38][C:29]=1[C:16]1[CH2:15][CH2:14][N:13]([C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7])[CH2:18][CH:17]=1
Reactant: COC(=O)c1ccc(Cl)nc1
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C2=CCN(C(=O)OC(C)(C)C)CC2)nc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 22.3 %

Procedure:
N,N-dimethylformamide (100 mL) was added to commercially available 1-N—BOC-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine (4.68 g, 15.1 mmol), commercially available methyl 6-chloronicotinate (2.81 g, 16.4 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (1.17 g, 1.60 mmol), and potassium carbonate (7.02 g, 50.8 mmol). The reaction liquid was stirred under nitrogen atmosphere at 100° C. for 2 hours. The reaction liquid was allowed to stand to cool to room temperature and then diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed serially with a dilute aqueous ammonia solution and a saturated saline solution, and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and then the filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=9:1-1:1) to obtain the title compound (1.07 g, 22%).
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][C@:7]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:11]([C:12](=[O:33])[C@@H:13]([O:15][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH3:14])[N:10]=[C:9]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[F:41])[S:8]1)=[N+:2]=[N-:3].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1>[N:1]([CH2:4][CH2:5][CH2:6][C@:7]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[N:11]([C:12](=[O:33])[C@@H:13]([OH:15])[CH3:14])[N:10]=[C:9]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[F:41])[S:8]1)=[N+:2]=[N-:3]
Reactant: C[C@H](O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)C(=O)N1N=C(c2cc(F)ccc2F)S[C@@]1(CCCN=[N+]=[N-])c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@H](O)C(=O)N1N=C(c2cc(F)ccc2F)S[C@@]1(CCCN=[N+]=[N-])c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 52.8 %

Procedure:
To a solution of (S)-1-((S)-2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-(t-butyldiphenylsilyloxy)propan-1-one (121 mg, 0.18 mmol) in THF (5 mL) at 0° C. was added TBAF (0.31 mL, 1M, 0.31 mmol). After stirring at 0° C. for 1 hour and at room temperature for 1 hour, the mixture was treated with saturated NaHCO3 (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organics were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. The brown oil was chromatographed (4:1 hexanes/ethyl acetate) to provide the product (41 mg, 53%) as a pale yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[C:6]([N:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][CH3:25])[CH2:9][CH2:10][O:11]C1CCCCO1)=[O:7].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO>[OH:11][CH2:10][CH2:9][N:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][CH3:25])[C:6](=[O:7])[C:5]1[CH:26]=[CH:27][CH:28]=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1cccc(C(=O)N(CCOC2CCCCO2)c2ccccc2OC)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1cccc(C(=O)N(CCO)c2ccccc2OC)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 86.8 %

Procedure:
3-Methoxy-N-(2-methoxyphenyl)-N-(2-tetrahydropyranyloxyethyl)benzamide (501 mg, 1.30 mmol) was dissolved in methanol (4 ml) to which was subsequently added a catalytically effective amount of p-toluenesulfonic acid monohydrate and stirred for 3 hours at room temperature. The reaction solution was mixed with saturated sodium bicarbonate aqueous solution (10 ml) and extracted with ether, and then washed with water and saturated brine. The resulting organic layer was dried on anhydrous magnesium sulfate, the solvent was removed by evaporation and then the resulting colorless oily residue was purified by subjecting it to a silica gel column chromatography (ether:hexane=3:1) to obtain 340 mg (86.8%) of the title compound in the form of light yellow oil.
Reaction SMILES: [CH:1]1([NH2:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:7][O:8][CH:9]([O:12][CH3:13])[CH:10]=O>CO.O.[Pd]>[CH3:7][O:8][CH:9]([O:12][CH3:13])[CH2:10][NH:6][CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(C=O)OC
Reactant: NC1CCCC1
Agent: [Pd]
Solvent: O
Solvent: CO
Product: COC(CNC1CCCC1)OC
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a stirred solution of cyclopentanamine (5 g) in methanol (20 mL) was added 2,2-dimethoxyacetaldehyde 60% in water (8.86 mL) and the mixture stirred at ambient temperature for 5 h. A slurry of palladium on carbon (10%, 200 mg) in methanol (5 mL) was added and the mixture hydrogenated at 5 bar for 16 h. It was filtered and concentrated in vacuo to afford N-(2,2-dimethoxyethyl)cyclopentanamine (9.44 g) as a oil. 1H NMR (400 MHz, CDCl3) δ 4.47 (t, J=5.6 Hz, 1H), 3.39 (s, 6H), 3.05 (quintet, J=6.8 Hz, 1H), 2.72 (d, J=5.4 Hz, 2H), 1.89-1.80 (m, 2H), 1.73-1.62 (m, 2H), 1.58-1.48 (m, 2H), 1.36-1.27 (m, 2H)
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:19]=[CH:18][C:9]2[O:10][C:11]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[C:8]=2[CH:7]=1)=[O:4].[CH3:20][N:21]([CH3:26])[CH2:22][CH2:23][NH:24][CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:20][N:21]([CH3:26])[CH2:22][CH2:23][N:24]([CH3:25])[CH2:2][C:3]([NH:5][C:6]1[CH:19]=[CH:18][C:9]2[O:10][C:11]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[C:8]=2[CH:7]=1)=[O:4]
Reactant: CNCCN(C)C
Reactant: O=C(CCl)Nc1ccc2oc3c(c2c1)CCCCC3
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CN(C)CCN(C)CC(=O)Nc1ccc2oc3c(c2c1)CCCCC3
Yield: 37.5 %

Procedure:
Following the procedure of Example 40, 2-chloro-N-7,8,9,10-tetrahydro-6H-benzo[b]cyclohepta[d]furan-2-ylacetamide (0.13 g, 0.45 mmol), N,N,N′-trimethylethylenediamine (0.073 mL, 0.56 mmol), and cesium carbonate (0.29 g, 0.90 mmol) in acetonitrile (5 mL) provided N2-[2-(dimethylamino)ethyl]-N2-methyl-N1-7,8,9,10-tetrahydro-6H-benzo[b]cyclohepta[d]furan-2-ylglycinamide (0.058 g) as its hydrochloride salt after normal phase HPLC purification and treatment with 4 N hydrochloric acid in dioxane. MS (ESI) m/z 344 ([M+H]+).
Reaction SMILES: [C:1]1(=O)[O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>>[CH2:10]([N:9]1[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1=[O:7])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=C1CCCCCO1
Reactant: CCCCCCCCCN
Product: CCCCCCCCCN1CCCCCC1=O
Yield: 24 %

Procedure:
Following example 5, heating 22.83 g (0.2 M) of 6-hexanolactone and 28.65 g (0.2 M) of 1-aminononane at 180° for 20 hours gave 11.5 g (26%) of product; b.p. 155°-165°/0.6 mm.
Reaction SMILES: FC(F)(F)[C:3]([N:5]([C:7]1[C:8](=[O:33])[N:9]([CH2:19][C:20]([NH:22][CH:23]([CH:30]([CH3:32])[CH3:31])[C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])=[O:21])[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:11][CH:12]=1)C)=O.C(OCC)(=O)C>[Cl-].[Na+].O>[CH3:3][NH:5][C:7]1[C:8](=[O:33])[N:9]([CH2:19][C:20]([NH:22][CH:23]([CH:30]([CH3:31])[CH3:32])[C:24](=[O:29])[C:25]([F:26])([F:27])[F:28])=[O:21])[C:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:11][CH:12]=1
Reactant: CC(C)C(NC(=O)Cn1c(-c2ccccc2)ccc(N(C)C(=O)C(F)(F)F)c1=O)C(=O)C(F)(F)F
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CNc1ccc(-c2ccccc2)n(CC(=O)NC(C(=O)C(F)(F)F)C(C)C)c1=O

Procedure:
Using a procedure similar to that described above under Example 49.j. for the basic hydrolysis of the analogous 3-(N-trifluoroacetylamino) compound to the 3-amino-compound, but using the following extractive work-up, the title compound was prepared from 2-[3-(N-trifluoroacetyl-N-methylamino)-2-oxo-6-phenyl -1,2-dihydro-1-pyridyl]-N-(3,3,3-trifluoro-1-isopropyl -2-oxopropyl)acetamide. On completion of hydrolysis, ethyl acetate and brine were added. The organic phase was separated, washed (brine), dried (MgSO4), and evaporated. The resultant solid was triturated with diethyl ether, chromatographed, eluting with dichloromethane:methanol (96:4), and dried overnight under vacuum to give the title product as a white solid; TLC: Rf =0.20, dichloromethane:methanol (96:4); MS: m/z=410(M+1).
Reaction SMILES: [Cl:1][CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([N:11]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[C:13]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=3)=[N:12]2)[CH2:7][CH2:6]1)=[O:4].Cl.CO[C:32]1C=C(C2C3(CCCC3)C(=O)N(C3CCNCC3)N=2)C=C[C:37]=1OC.ClCC(OC(=O)CCl)=O>>[Cl:1][CH2:2][C:3]([N:5]1[CH2:6][CH2:7][CH:8]([N:11]2[N:12]=[C:13]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=3)[C:14]3([CH2:18][CH2:37][CH2:32][CH2:17]3)[C:15]2=[O:16])[CH2:9][CH2:10]1)=[O:4]
Reactant: COc1ccc(C2=NN(C3CCNCC3)C(=O)C23CCCC3)cc1OC
Reactant: COc1ccc(C2=NN(C3CCN(C(=O)CCl)CC3)C(=O)C2(C)C)cc1OC
Agent: Cl
Agent: O=C(CCl)OC(=O)CCl
Product: COc1ccc(C2=NN(C3CCN(C(=O)CCl)CC3)C(=O)C23CCCC3)cc1OC

Procedure:
Prepared analogously as described for A1 using 4-(3,4-dimethoxyphenyl)-2-piperidin-4-yl-2,3-diazaspiro[4.4]non-3-en-1-one hydrochloride (compound B10) and chloroacetic anhydride as starting compounds.
Reaction SMILES: [CH3:1][C:2]1([OH:8])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.C(OC(C)C)(C)C.[C:16]([O:21][CH2:22][CH2:23][N:24]=[C:25]=[O:26])(=[O:20])[C:17]([CH3:19])=[CH2:18].CS(O)(=O)=O.C([O-])(O)=O.[Na+]>CCCCCC>[C:16]([O:21][CH2:22][CH2:23][NH:24][C:25](=[O:26])[O:8][C:2]1([CH3:1])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1)(=[O:20])[C:17]([CH3:19])=[CH2:18]
Reactant: CC1(O)CCOCC1
Reactant: C=C(C)C(=O)OCCN=C=O
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCC
Solvent: CC(C)OC(C)C
Product: C=C(C)C(=O)OCCNC(=O)OC1(C)CCOCC1
Temperature: 5.5 °C
Reaction time: 10 h
Yield: 46.2 %

Procedure:
In a three-necked flask having an inner volume of 50 mL equipped with a thermometer and a stirring apparatus were charged 1.00 g (8.51 mmol) of 4-methyltetrahydropyran-4-ol, 1.0 mg of 4-acetamido-2,2,6,6-tetramethylpiperidine-N-oxyl, 4.0 g of isopropyl ether, and 1.42 g (8.94 mmol) of 2-methacryloyloxyethyl isocyanate. After the mixture was cooled by ice water to an inner temperature of 5° C., 250 mg (2.55 mmol) of methanesulfonic acid was added dropwise. After stirring the reaction mixture for 10 hours with the reaction temperature maintained at 5 to 6° C., 4.0 g of a saturated aqueous NaHCO3 solution was added dropwise with the inner temperature maintained at 10° C. or less and, after completion of the dropwise addition, the mixture was allowed to stand still for 30 minutes. The organic layer (upper layer) formed was separated and the aqueous layer (lower layer) was extracted twice with 4.0 g of isopropyl ether. All the separated organic layers were combined, washed with 4.0 g of distilled water, and the organic layer was concentrated under reduced pressure to obtain 2.29 g of a concentrate. The concentrate was dissolved in 10 g of hexane at 30° C. and the solution was cooled to −10° C. at a rate of 10° C./hour. The crystals which precipitated were separated by filtration and the crystals obtained were dried under vacuum (26.7 Pa) at 30° C. for 2 hours to obtain 1.10 g (purity 97.0%, 3.93 mmol, yield: 46.2%) of 4-methyltetrahydropyran-4-yl (2-methacryloyloxyethyl)carbamate.
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:10])[CH3:9].[Br:12][C:13]1[CH:21]=[CH:20][C:16]([CH2:17][NH:18][CH3:19])=[CH:15][CH:14]=1>ClCCl>[Br:12][C:13]1[CH:21]=[CH:20][C:16]([CH2:17][N:18]([CH3:19])[C:8](=[O:10])[CH3:9])=[CH:15][CH:14]=1
Reactant: CNCc1ccc(Br)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N(C)Cc1ccc(Br)cc1
Reaction time: 0.17 h

Procedure:
A solution of triethylamine (0.22 ml, 1.6 mmol) in dichloromethane (10 ml) was treated with acetyl chloride (0.08 ml, 1.10 mmol), followed by 4-bromo-N-methylbenzylamine (210 mg, 1.05 mmol). This mixture was then stirred under an atmosphere of argon for 10 minutes. The reaction mixture was washed twice with water and the organic layer was separated and dried over sodium sulphate, and the solvent removed via rotary evaporation to give a yellow oil which was purified on a 5 g sep-pak column eluting from 0-100% ethyl acetate in petroleum ether to give the title compound as a yellow oil.