Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][N:3]([CH:7]([CH3:27])[CH2:8][CH2:9][CH2:10][N:11]1[C:23]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N:16]=[CH:15][C:14]=2[N:13]=[C:12]1[CH2:24][CH2:25][CH3:26])[C:4](=[O:6])[CH3:5].CO[N:30](CCCCN1C2C3C=CC=CC=3N=CC=2N=C1CCC)C(=O)C.[OH-].[NH4+]>>[NH2:30][C:15]1[C:14]2[N:13]=[C:12]([CH2:24][CH2:25][CH3:26])[N:11]([CH2:10][CH2:9][CH2:8][CH:7]([N:3]([O:2][CH3:1])[C:4](=[O:6])[CH3:5])[CH3:27])[C:23]=2[C:22]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:16]=1
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCC(C)N(OC)C(C)=O
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCCN(OC)C(C)=O
Agent: [NH4+]
Agent: [OH-]
Product: CCCc1nc2c(N)nc3ccccc3c2n1CCCC(C)N(OC)C(C)=O

Procedure:
A modification to the general procedure of Part G of Example 6 was followed using N-methoxy-N-[1-methyl-4-(2-propyl-1H-imidazo-[4,5-c]quinolin-1-yl)butyl]-acetamide (1.0 g, 2.71 mmol) in lieu of N-methoxy-N-[4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]acetamide. The reaction mixture was cooled to 0° C. before addition of the ammonium hydroxide. Recrystallization from hot acetonitrile following flash column chromatography provided 0.059 g of N-[4-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-methylbutyl]-N-methoxyacetamide as a tan crystalline solid, mp 140-142° C. MS (APCI) m/z 384.1 (M+H+); Theor. Mass: 384.240 Da Meas. Mass: 384.2406 Da. Mass Dev. 1.6 ppm.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:7](=[O:10])([O-])[O-:8].[K+].[K+].[Br-].[K+]>CC(C)=O>[OH:8][C@@:7]1([O:10][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:5][CH:4]=[C:3]2[C:3]([CH:4]=[CH:5][CH:6]=[CH:2]2)=[C:2]1[C:4]1[C:5]2[C:3](=[CH:4][CH:5]=[CH:6][CH:6]=2)[CH:2]=[CH:2][CH:3]=1
Reactant: CCCCCI
Reactant: O=C([O-])[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCO[C@]1(O)CC=c2ccccc2=C1c1cccc2ccccc12
Temperature: 45 °C

Procedure:
The compounds (R)-(+)-2-hydroxy-2-pentoxy-1,1'-binaphthalene and (R)-(+)-2,2'-dipentoxy-1,1'-binaphthalene were prepared as follows. 1 g (3.49 mmol) (R)-(+)-2,2'-dihydroxy-1,1'-binaphthalene and 0.99 g (5 mmol) iodopentane were dissolved in 40 ml acetone while stirring. 6.99 g of potassium carbonate and 7.99 g (57.9 mmol) potassium bromide was added in one portion. After 24 hours stirring at room temperature, 1 g potassium carbonate was added. The reaction mixture was heated to 45° C. for 30 minutes. The excess potassium carbonate and potassium bromide were filtered and the solvent of the filtrate was removed with a rotavap. The crude product was purified by flash column with silica gel and dichloromethane as the eluent to obtain 370 mg of product consisting of 25% of the monosubstituted product and 56% of the disubstituted product.
Reaction SMILES: [N+](=[CH2:3])=[N-].[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]=[C:13]([C:15]([N+:18]([O-:20])=[O:19])=[N:16][OH:17])[CH2:12][N+:11]([O-:21])=[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:9]=2[CH:29]=1>CCOCC.C(Cl)Cl>[Cl:4][C:5]1[CH:6]=[CH:7][C:8]2[N:14]=[C:13]([C:15]([N+:18]([O-:20])=[O:19])=[N:16][O:17][CH3:3])[CH2:12][N+:11]([O-:21])=[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:9]=2[CH:29]=1
Reactant: O=[N+]([O-])C(=NO)C1=Nc2ccc(Cl)cc2C(c2ccccc2F)=[N+]([O-])C1
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Solvent: ClCCl
Product: CON=C(C1=Nc2ccc(Cl)cc2C(c2ccccc2F)=[N+]([O-])C1)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of diazomethane in ether was added to a suspension of 3.8 g (0.01 mol) of 7-chloro-5-(2-fluorophenyl)-N-hydroxy-α-nitro-3H-1,4-benzodiazepine-2-methanimine 4-oxide in 200 ml of methylene chloride. The mixture was stirred for 1 hr at room temperature whereby a clear solution resulted. The excess diazomethane was destroyed by addition of acetic acid. The reaction mixture was washed with aqueous sodium bicarbonate solution, dried over sodium sulfate and evaporated. Crystallization of the residue from ether yielded yellow crystals. The analytical sample was recrystallized from ether, mp 207°-209°.
Reaction SMILES: Cl.Cl.C(NNCC)C.O1CC[N:12]([CH2:15][CH:16]([N+:24]([O-:26])=[O:25])[CH2:17][N:18]2CCO[CH2:20][CH2:19]2)[CH2:11][CH2:10]1>CO.C1(C)C=CC=CC=1>[N+:24]([CH:16]1[CH2:15][N:12]([CH2:11][CH3:10])[N:18]([CH2:19][CH3:20])[CH2:17]1)([O-:26])=[O:25]
Reactant: O=[N+]([O-])C(CN1CCOCC1)CN1CCOCC1
Agent: CCNNCC
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CO
Product: CCN1CC([N+](=O)[O-])CN1CC
Yield: 54 %

Procedure:
A stirred solution of 4.03 g (0.025 moles) of 1,2-diethylhydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was resuspended in 100 ml of toluene. The solid morpholine hydrochloride was removed by filtration, leaving a solution of 4-nitro-1,2-diethyl-pyrazolidine in solution. To the toluene solution was added 60 ml anhydrous ethanol and 2 g. of Raney Nickel which had been washed three times with anhydrous ethanol. The mixture was hydrogenated at about 30 psi. hydrogen pressure. The mixture was filtered carefully under nitrogen to prevent ignition. Evaporation of solvents and distillation at reduced pressure gave colorless liquid product weighing 1.95 g. (54% yield calculated on diethylhydrazine), b.p. 113°-115° C./40 mm.
Reaction SMILES: C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19]#[CH:20])=[N:17][CH:18]=2)=[CH:9][CH:8]=1.[C:21](=[O:23])=[O:22].C(OCC)(=O)C>C1COCC1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19]#[C:20][C:21]([OH:23])=[O:22])=[N:17][CH:18]=2)=[CH:11][CH:12]=1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C(O)C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Temperature: -8 °C
Reaction time: 0.08 h

Procedure:
1.6 mL (2.46 mmol) of butyllithium solution (1.6M in hexane) are added dropwise at −10° C. to a solution of 0.5 g (2.34 mmol) of 5-(4-chlorophenyl)-2-ethynylpyridine in 30 mL of absolute THF and the mixture is stirred for five minutes at −8° C. stirred. The reaction mixture is combined with dry ice batchwise at −70° C., stirred for 1 hour at ambient temperature, and evaporated down. The residue is suspended in 5 mL of water and combined with 1.6 mL of 1N hydrochloric acid, whereupon a precipitate is formed. Then ethyl acetate is added and the suspension is filtered. The solid is dried in the vacuum drying chamber at 70° C. Yield: 0.25 g (41.5% of theory); melting point: 210° C.; C14H8ClNO2 (M=257.67); calc.: molecular ion peak (M+H)+: 258/260; found: molecular ion peak (M+H)+: 258/260.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[CH2:9]([Sn](CCCC)(CCCC)C=C)[CH2:10]CC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:9]=[CH2:10])[CH:7]=1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: Fc1cncc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: C=Cc1cncc(F)c1

Procedure:
A mixture of 7.0 g (0.04 mole) 3-fluoro-5-bromopyridine, 15.3 g (0.048 mole) tributyl(vinyl)stannane, 2.5 g (0.002 mole) tetrakis(triphenylphosphine)palladium in 70 ml toluene was boiled with reflux during 16 hours. Toluene was evaporated with a 30 cm column. The residue was fractionated twice.
Reaction SMILES: C(OC([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[C:21]([Cl:27])[CH:20]=2)=[O:16])[CH2:11][CH2:10]1)=O)(C)(C)C.Cl>CCOC(C)=O.O1CCOCC1>[NH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[C:21]([Cl:27])[CH:20]=2)=[O:16])[CH2:11][CH2:10]1
Reactant: CC(C)(C)OC(=O)NC1CCN(C(=O)OCc2cc(Cl)cc(C#N)c2)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: N#Cc1cc(Cl)cc(COC(=O)N2CCC(N)CC2)c1
Reaction time: 20 h

Procedure:
To a solution of 3-chloro-5-cyanobenzyl 4-((tert-butoxycarbonyl)amino)piperidine-1-carboxylate (1.846 g, 4.69 mmol) in EtOAc (30 ml) at RT under nitrogen was added 4M HCl in Dioxane (11.72 ml, 46.9 mmol) and the suspension stirred for 20 hours. After 3 hours a further 5 ml of 4M HCl in Dioxan was added. The solid was filtered off and dried to afford the title product as the hydrochloride salt;
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([S:13][CH:14]2[NH:17][C:16](=[O:18])[CH2:15]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].[CH3:19][O:20][C:21](=[O:24])[CH2:22]Br.C(OCC)(=O)C>CN(C=O)C>[CH3:19][O:20][C:21](=[O:24])[CH2:22][N:17]1[CH:14]([S:13][C:7]2[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:5]([O:4][CH3:3])[CH:6]=2)[CH2:15][C:16]1=[O:18]
Reactant: COC(=O)CBr
Reactant: COc1ccc(SC2CC(=O)N2)cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)CN1C(=O)CC1Sc1ccc(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 25.7 %

Procedure:
Sodium hydride (0.5 g, 12 mmol) in dry DMF (10 ml) was cooled to -5° C. and a solution of 4-(3,4-dimethoxyphenylthio)azetidin-2-one (3 g, 12 mmol) in dry DMF (20 ml) was added dropwise over 15 mins under a nitrogen atmosphere at -5° C. After 15 mins methylbromoacetate (2 g, 12 mmol) was added in one portion, and the mixture stirred for 30 mins at room temperature. The reaction mixture was carefully poured into brine/ice water and ethyl acetate (100 ml) was added. The organic layer was washed with brine (x2), dried (MgSO4) and evaporated to a yellow oil which was purified by flash column chromatography eluted with petroleum ether/ethyl acetate to give the product as a yellow oil (0.96 g, 25% yield).
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5]1([OH:11])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:18]=[O:19].[Cl-].[NH4+]>ClCCl>[OH:19][CH:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[OH:11]
Reactant: Oc1ccccc1
Reactant: O=Cc1ccccn1
Agent: [Al+3]
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: Oc1ccccc1C(O)c1ccccn1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a solution of AlCl3 (1.42 g) in dichloromethane (20 mL) at 0° C. is added a solution of phenol (1 g) in dichloromethane (20 mL) and the mixture is stirred at this temperature for 40 minutes. After addition of a solution of pyridine-2-carboxaldehyde (1.21 g) in dichloromethane (10 mL), the mixture is allowed to warm at room temperature for 4 hours, then cooled to 0° C., treated dropwise with aqueous ammonium chloride and stirred at room temperature for 30 minutes. The aqueous phase is extracted twice with dichloromethane and pooled organic extracts dried over magnesium sulfate and concentrated. The residue is purified by column chromatography over silica gel (gradient heptane/ethyl acetate from 100/0 to 70/30) to afford pure 2-(hydroxy-pyridin-2-yl-methyl)-phenol.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[CH:21]=[CH:20][C:14]3[N:15]([CH3:19])[C:16](=[O:18])[O:17][C:13]=3[CH:12]=2)=[O:10])=[C:4]([Cl:22])[CH:3]=1.[H-].[Na+].[CH3:25]I>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:25])[C:9]([C:11]2[CH:21]=[CH:20][C:14]3[N:15]([CH3:19])[C:16](=[O:18])[O:17][C:13]=3[CH:12]=2)=[O:10])=[C:4]([Cl:22])[CH:3]=1
Reactant: Cn1c(=O)oc2cc(C(=O)Cc3ccc(Br)cc3Cl)ccc21
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C(=O)c1ccc2c(c1)oc(=O)n2C)c1ccc(Br)cc1Cl
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 68.6 %

Procedure:
6-[2-(4-Bromo-2-chloro-phenyl)-acetyl]-3-methyl-3H-benzooxazol-2-one (747 mg) was dissolved in DMF (20 mL). The mixture was cooled to 0° C. To this solution was added sodium hydride (55% in mineral oil, 90 mg). The mixture was stirred for 10 minutes at 0° C. and then for 1 hour at r.t. The mixture was cooled to 0° C. and methyl iodide (292 mg) was added dropwise over a period of 10 minutes. Stirring was continued over night at r.t. The reaction mixture was poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a brown foam (531 mg, 69%). MS (neg. ion, m/e)=394.2 [M−H)−].
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[CH:15]1[CH2:20][CH2:19][C:18](=[CH:21][C:22]([O:24][CH3:25])=[O:23])[CH2:17][CH2:16]1>[Pd].C(O)C>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[CH:7][C:6]=1[C@H:15]1[CH2:16][CH2:17][C@H:18]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH2:19][CH2:20]1
Reactant: COCOc1ccc(C2CCC(=CC(=O)OC)CC2)c(OCOC)c1
Agent: [Pd]
Solvent: CCO
Product: COCOc1ccc([C@H]2CC[C@H](CC(=O)OC)CC2)c(OCOC)c1
Reaction time: 17 h

Procedure:
To a round bottomed flask equipped with magnetic stirrer was added (±)-methyl {4-[2,4-bis(methoxymethoxy)phenyl]cyclohexylidene}acetate (1.13 g, 3.23 mmol) and ethanol (50 ml). To the stirred solution was added palladium (catalytic amount, 10% on activated carbon) in one portion. The reaction vessel was evacuated and placed under an atmosphere of hydrogen. This process was repeated for 10 cycles before leaving under a hydrogen atmosphere and then stirred vigorously for 17 hr. The reaction mixture was filtered through celite, washing with ethanol and the filtrate was evaporated to dryness, furnishing the title compound (1.13 g, 99%) as a colourless oil and a mixture of diastereoisomers. δH(CD3OD) 1.53 (2H, m), 1.62-1.78 (2H, m), 1.87 (4H, m), 2.93 (1H, m), 3.47 (3H, s), 3.51 (3H, s), 3.71 and 3.72 (3H, s), 5.16 and 5.17 (2H, s), 5.22 and 5.23 (2H, s), 6.66 and 6.68 (1H, d), 6.79 and 6.80 (1H, s), 7.12 and 7.15 (1H, d).
Reaction SMILES: [CH3:1][O:2][CH:3]([CH2:27][NH:28][S:29]([CH2:32][CH2:33]OS(C)(=O)=O)(=[O:31])=[O:30])[CH2:4][O:5][C:6](=[O:26])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[I-:39].[Na+]>CC(C)=O>[I:39][CH2:33][CH2:32][S:29]([NH:28][CH2:27][CH:3]([O:2][CH3:1])[CH2:4][O:5][C:6](=[O:26])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])(=[O:31])=[O:30]
Reactant: [I-]
Reactant: CCCCCCCCCCCCCCCCCCNC(=O)OCC(CNS(=O)(=O)CCOS(C)(=O)=O)OC
Agent: [Na+]
Solvent: CC(C)=O
Product: CCCCCCCCCCCCCCCCCCNC(=O)OCC(CNS(=O)(=O)CCI)OC
Reaction time: 5 h
Yield: 89.2 %

Procedure:
To a solution of 200 mg (0.341 mM) of 2-methoxy-1-octadecylcarbamoyloxy-3-(2-methanesulfonyloxyethylsulfonylamino)propane VIa4' in 5 ml of acetone is added 200 mg (1.33 mM) of sodium iodide and the mixture is refluxed with stirring for 5 hours. After the solvent is evaporated, the residue is purified by the column chromatography on silica gel with a n-hexane-ethyl acetate (2:1) mixture as an eluent to give 188 mg (0.296 mM) of 3-(2-iodoethylsulfonylamino)-2-methoxy-1-octadecylcarbamoyloxypropane IIa4 in 87% yield.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][C:14](=O)[CH2:13][N:12]1[C:17](=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O.Cl>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[CH2:13][N:12]1[C:17](=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CN(C(=O)Cc2ccc(F)cc2)N(C(=O)OCc2ccccc2)C1
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: O=C(Cc1ccc(F)cc1)N1CC(N2CCOCC2)CN1C(=O)OCc1ccccc1
Reaction time: 12 h
Yield: 60 %

Procedure:
To a solution of 2-[2-(4-fluorophenyl)acetyl]-4-oxo-pyrazolidine-1-carboxylic acid benzyl ester, 11, (0.14 g, 0.4 mmol) and morpholine (0.038 mL, 0.43 mmol) in THF at room temperature is added Na(OAc)3BH (0.125 g, 0.6 mmol) and HOAc (0.022 mL, 0.4 mmol). The solution is stirred 12 hours then partitioned between diethyl ether and NaHCO3. The aqueous layer was extracted several times with ether and the organic layers combined, dried, and concentrated in vacuo to a clear oil which was re-dissolved in ether and one equivalent of ethereal HCl is added and a white solid forms. The solid is collected by filtration and 100 mg (60% yield) of the desired product is isolated as the HCl salt.
Reaction SMILES: [CH3:1][NH2:2].[C:3]([O:7][C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[C:27]([C:28](ON3C(=O)CCC3=O)=[O:29])=[C:26]([CH2:38][OH:39])[N:25]=[C:24]2[CH2:40][CH2:41][CH2:42][CH3:43])=[CH:18][CH:17]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O.C(Cl)Cl.CO>[CH3:1][NH:2][C:28]([C:27]1[N:23]([CH2:22][C:19]2[CH:18]=[CH:17][C:16]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[C:8]([O:7][C:3]([CH3:4])([CH3:5])[CH3:6])=[O:9])=[CH:21][CH:20]=2)[C:24]([CH2:40][CH2:41][CH2:42][CH3:43])=[N:25][C:26]=1[CH2:38][OH:39])=[O:29]
Reactant: CCCCc1nc(CO)c(C(=O)ON2C(=O)CCC2=O)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Reactant: CN
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: CCCCc1nc(CO)c(C(=O)NC)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Reaction time: 16 h

Procedure:
0.4 ml of a 40% by volume solution of methylamine in water was added at room temperature to a solution of 0.278 g of succinimido 1-[(2'-t-butoxycarbonylbiphenyl-4-yl)methyl]-2-butyl-4-hydroxymethylimidazole-5-carboxylate [prepared as described in Example 52(a)] in a mixture of 3 ml of methylene chloride and 2 ml of methanol, and the resulting mixture was allowed to stand for 16 hours at room temperature. At the end of this time, the solution was concentrated by evaporation under reduced pressure, and the concentrate was dissolved in ethyl acetate. The resulting solution was washed with an aqueous solution of potassium bisulfate and with an aqueous solution of sodium hydrogencarbonate, in that order, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using ethyl acetate as the eluent, to give 176 mg of the title compound as a glass.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:13]([O:27][C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>C(Cl)Cl>[CH2:13]([O:27][C:28]1[CH:34]=[CH:33][C:31]([N:32]=[C:2]=[O:4])=[CH:30][CH:29]=1)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CCCCCCCCCCCCCCOc1ccc(N)cc1
Solvent: ClCCl
Product: CCCCCCCCCCCCCCOc1ccc(N=C=O)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 8.74 g of triphosgene in 125 ml of methylene chloride cooled to 0° C. is added dropwise a solution of p-(tetradecyloxy)aniline, 7.95 g of 125 ml of methylene chloride over 30 minutes. Stirring at ambient temperature is continued for 4 hours. The solvent is evaporated and the residue stirred with ether and filtered. The cake is washed with additional ether and the combined filtrates evaporated to give the desired product as an oil.
Reaction SMILES: [F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:4]([C:5](F)=[O:6])[C:3]=1[C:14](F)=[O:15].FC1(F)C2C(=C(F)C(F)=C(F)C=2F)C(=O)[O:19]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C(C)=CC=CC=1>[F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:4]2[C:5](=[O:19])[O:6][C:14](=[O:15])[C:3]=12
Reactant: O=C1OC(F)(F)c2c(F)c(F)c(F)c(F)c21
Reactant: O=C(F)c1c(F)c(F)c(F)c(F)c1C(=O)F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Yield: 91.5 %

Procedure:
Into a 500 ml glass reactor equipped with a reflux condenser and a stirrer, 100 g (0.413 mol) of the mixture (1:1) of the 3,4,5,6-tetrafluorophthaloyldifluoride and the 3,3,4,5,6,7-hexafluoro-1-[3H]-isobenzofuranone of Example 2, 43.8 g (0.413 mol) of sodium carbonate and 200 g of xylene were charged, and the mixture was reacted at 130° C. for 3 hours with vigorous stirring. Then, the inorganic substance was removed by filtration, and the residue was subjected to distillation to obtain 83.1 g of tetrafluorophthalic anhydride. The yield was 91.5%.
Reaction SMILES: [NH2:1][CH:2]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[CH2:3][C:4]([OH:6])=[O:5].S1C=CC=[C:13]1C=O.Cl.O1CCOCC1.CCOCC.CC#N>CO>[NH2:1][CH:2]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[CH2:3][C:4]([O:6][CH3:13])=[O:5]
Reactant: NC(CC(=O)O)c1cccs1
Reactant: O=Cc1cccs1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Solvent: CC#N
Product: COC(=O)CC(N)c1cccs1

Procedure:
A solution of 3-amino-3-(2-thienyl)propanoic acid (0.5 g) [prepared substituting a molar equivalent amount of 2-thiophene-carboxaldehyde in Example 57, Step A] in methanol (50 ml) was treated with 4N HCl/dioxane (10 ml). After 6 hours the excess solvent was removed under reduced pressure to give a waxy solid. Treatment with Et2O/CH3CN produced methyl β-aminothiophene-2-propanoate (370 mg) as a white powder. MS and 1H-NMR were consistent with the desired product.
Reaction SMILES: [C:1]([CH:4]([CH2:9][C:10]([CH3:12])=[CH2:11])C(OC)=O)(=[O:3])[CH3:2].[OH-].[K+].[N:15]([O-])=[O:16].[Na+].S(=O)(=O)(O)O.C(=O)=O>>[CH3:12][C:10](=[CH2:11])[CH2:9][C:4](=[N:15][OH:16])[C:1](=[O:3])[CH3:2]
Reactant: C=C(C)CC(C(C)=O)C(=O)OC
Reactant: O=N[O-]
Agent: O=C=O
Agent: O=S(=O)(O)O
Agent: [K+]
Product: C=C(C)CC(=NO)C(C)=O
Temperature: 23 °C
Reaction time: 18 h

Procedure:
At 10° C., 200 g of methyl 2-acetyl-4-methylpent-4-enoate (Preparation: cf. Tetrahedron (1985) 4633) in 2000 ml of aqueous 10% strength potassium hydroxide solution were admixed with 85 g of sodium nitrite, and the mixture was stirred at 23° C. for 18 hours. With ice-cooling, 1000 ml of 10% strength sulfuric acid were subsequently added dropwise such that the internal temperature remained below 10° C. The mixture was then stirred at 10° C. until evolution of CO2 had ceased. For work-up, the mixture was extracted with methyl tert-butyl ether, the combined organic phases were extracted with 3 N aqueous sodium hydroxide solution and the alkaline phases were adjusted to pH 1 using 20% strength sulfuric acid. They were then extracted with methylene chloride, the extract was dried over sodium sulfate and the solvent was removed under reduced pressure. This gave 142 g of the title compound as a yellow oil which crystallized on standing.
Reaction SMILES: Cl[CH2:2][CH:3]1[CH:5]([C:6]([O:8]CC)=O)[C:4]1([CH3:20])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1.[CH2:21]([NH2:24])[CH:22]=[CH2:23]>>[CH2:21]([N:24]1[CH2:2][CH:3]2[CH:5]([C:4]2([CH3:20])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:6]1=[O:8])[CH:22]=[CH2:23]
Reactant: CCOC(=O)C1C(CCl)C1(C)c1cccc([N+](=O)[O-])c1
Reactant: C=CCN
Product: C=CCN1CC2C(C1=O)C2(C)c1cccc([N+](=O)[O-])c1
Yield: 100.6 %

Procedure:
Ethyl 3-(chloromethyl)-2-methyl-2-(3-nitrophenyl)cyclopropanecarboxylate (Preparation 5, 1 g, 3.36 mmol) in allylamine (1.15 g, 20.1 mmol) was heated in a sealed tube at 150° C. for 16 h. After cooling the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution. The organic extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product as a yellow oil (0.92 g, 100%).