Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([CH2:9][CH2:10][CH2:11][OH:12])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1)([O-:24])=[O:23].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:8][C:5]([Si:2]([O:1][CH2:9][CH2:10][CH2:11][O:12][S:31]([C:28]1[CH:27]=[CH:26][C:25]([N+:22]([O-:24])=[O:23])=[CH:30][CH:29]=1)(=[O:32])=[O:33])([CH3:4])[CH3:3])([CH3:6])[CH3:7]
Reactant: CC(C)(C)[Si](C)(C)OCCCO
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)[Si](C)(C)OCCCOS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 3 h

Procedure:
A solution of 3-t-butlydimethylsiloxy-1-propanol, prepared by the method of McDougal, et al. JOC, 1986, 51, 3388, which is incorporated herein by reference, (7.6 g, 40 mmol) and diisopropylethylamine (10.4 mL, 60 mmol) in methylene chloride (200 mL) at 0° C. was treated with p-nitrophenylsulfonyl chloride (9.7 g, 44 mmol), stirred for 3 h, poured into saturated NaHCO3 and extracted with diethyl ether. The extracts were washed with brine, dried (Na2SO4), and concentrated. The residue was chromatographed on silica gel with 5% ethyl acetate/hexanes to provide 6.00 g of the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:18]=[CH:17][N:16]([S:19]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)(=[O:21])=[O:20])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)=[C:4]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[C:3]=1[N+:38]([O-])=O.CO.[Cl-].[NH4+]>C(OCC)(=O)C.[Zn]>[NH2:38][C:3]1[C:4]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])=[C:5]([C:8]2[C:9]3[CH:18]=[CH:17][N:16]([S:19]([C:22]4[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=4)(=[O:20])=[O:21])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:7][C:2]=1[NH2:1]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(-c4ccc(N)c([N+](=O)[O-])c4Oc4ccc(F)cc4F)cn(C)c(=O)c32)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1ccc(S(=O)(=O)n2ccc3c(-c4ccc(N)c(N)c4Oc4ccc(F)cc4F)cn(C)c(=O)c32)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 97.6 %

Procedure:
A solution of 4-[4-amino-2-(2,4-difluorophenoxy)-3-nitrophenyl]-6-methyl-1-[(4-methylphenyl)sulfonyl]-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (108 mg, 0.191 mmol) in ethyl acetate (0.46 mL) was treated with methanol (0.46 mL) and saturated aqueous ammonium chloride solution (0.166 mL, 2.48 mmol) and cooled to 0° C. The reaction mixture was treated with zinc (99.7 mg, 1.52 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, filtered through a pad of Celite, and the solids were washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution (40 mL). The aqueous layer was separated and re-extracted with ethyl acetate (40 mL). The combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (40% EtOAc/hexanes to 100% EtOAc) gave the desired product (100 mg, 93%) as a brown oil. LCMS calculated for C27H23F2N4O4S (M+H)+: m/z=537.1. found: 537.1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:14][N:13]([CH2:15][C:16]([OH:18])=O)[C:12](=[O:19])[CH:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:10]2[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:9]1=2.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.[NH:63]1[CH2:68][CH2:67][CH:66]([CH2:69][C:70]([O:72][CH2:73][CH3:74])=[O:71])[CH2:65][CH2:64]1>CN(C)C=O>[CH2:73]([O:72][C:70](=[O:71])[CH2:69][CH:66]1[CH2:67][CH2:68][N:63]([C:16](=[O:18])[CH2:15][N:13]2[CH2:14][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Br:1])[C:9]3[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:10]=3[CH:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:12]2=[O:19])[CH2:64][CH2:65]1)[CH3:74]
Reactant: CC(C)CC1C(=O)N(CC(=O)O)CC(c2ccccc2Br)c2cc(Cl)ccc21
Reactant: CCOC(=O)CC1CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)CC1CCN(C(=O)CN2CC(c3ccccc3Br)c3cc(Cl)ccc3C(CC(C)C)C2=O)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
150 mg of the compound from Example 6 (0.32 mol) are dissolved in 2 ml of dimethylformamide, and 147 mg of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.39 mol) and 67 μl of diisopropylethylamine (50 mg, 0.39 mol) are added. After stirring at room temperature for 30 min, 80 mg of ethyl 4-piperidylacetate hydrochloride (0.39 mol) and a further 135 μl of diisopropylethylamine (100 mg, 0.77 mol) are added. The reaction mixture is stirred at room temperature overnight and then purified directly by preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 130 mg (65% of theory) of the title compound are obtained.
Reaction SMILES: C([BH3-])#[N:2].[Na+].[CH2:5]([N:7]([CH2:22][CH3:23])[CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=O)[CH2:18][CH2:19][CH3:20])=[CH:13][CH:12]=1)[CH3:6].C([O-])(=O)C.[NH4+]>CO.C(OCC)(=O)C>[CH2:5]([N:7]([CH2:22][CH3:23])[CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([NH2:2])[CH2:18][CH2:19][CH3:20])=[CH:13][CH:12]=1)[CH3:6]
Reactant: CCCC(=O)c1ccc(OCCN(CC)CC)cc1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCCC(N)c1ccc(OCCN(CC)CC)cc1
Temperature: 40 °C
Yield: 59.4 %

Procedure:
Sodium cyanoborohydride (155 mg, 3.5 mmol) was added to a suspension of 1-(4-(2-(diethylamino)ethoxy)phenyl)butan-1-one (21; 186 mg, 0.7 mmol) and ammonium acetate (1.63 g, 21.2 mmol) in methanol (2 mL). The resulting mixture was then heated at 40° C. for 72 hours. The reaction mixture was diluted with ethyl acetate, washed with sat. aqueous NaHCO3 (2×) and sat. brine, dried over sodium sulfate and concentrated to give crude 25 (110 mg, 59%) as a yellow oil: MS (ES+) m/z 265.1 (M+H)+. This material was taken to the next step without further purification.
Reaction SMILES: Br[CH2:2][CH2:3][O:4]/[N:5]=[C:6](/[C:12]1[N:13]=[C:14]([NH:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[S:15][CH:16]=1)\[C:7]([O:9][CH2:10][CH3:11])=[O:8].BrCCBr.[N-:41]=[N+:42]=[N-:43].[Na+]>CN(C=O)C>[N:41]([CH2:2][CH2:3][O:4]/[N:5]=[C:6](/[C:12]1[N:13]=[C:14]([NH:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[S:15][CH:16]=1)\[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N+:42]=[N-:43]
Reactant: CCOC(=O)/C(=N\OCCBr)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: BrCCBr
Product: CCOC(=O)/C(=N\OCCN=[N+]=[N-])c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1

Procedure:
The starting material was prepared as follows. Using the procedure of Footnote 15, ethyl 2-((Z)-2-bromoethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetate was prepared from 1,2-dibromoethane, and reacted with sodium azide in DMF solution. Purification by chromatography gave ethyl 2-((Z)-2-azidoethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetate, which was dissolved in 1,2-dimethyoxyethane and hydrogenated using 5% w/w palladium on charcoal as catalyst at ambient temperature and pressure for 16 hours. Catalyst was filtered off, and the solution was treated with bis(O-t-butyl)carbonic anhydride at ambient temperature. After 48 hours, the reaction was worked up conventionally, and the product isolated by chromatography on silica, eluting with 60:40 v/v hexane:EtOAc. The ethyl ester was saponified (see Footnote 15) to give 2-((Z)-2-t-butoxycarbonylaminoethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid, having the following n.m.r. in CDCl3 : 1.33(s, 9H); 3.37(m, 2H); 4.27(t, 2H); 5.38(br s, 1H); 6.59(s, 1H); s, 1H); 7.29(m, 16H).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].[O:9]1[CH:14]=[CH:13][CH2:12][CH2:11][CH2:10]1.CCOCC.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][O:9]1
Reactant: OCCCCCCCl
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOCC
Product: ClCCCCCCOC1CCCCO1
Temperature: 25 °C
Reaction time: 15 h
Yield: 86.6 %

Procedure:
To a mixture of 15 g of 6-chlorohexanol, 100 ml of methylenechloride and 0.2 g of p-toluenesulphonic acid were added dropwise 12 g of dihydropyrane in 40 ml of methylenechloride. The reaction mixture was stirred for 15 h at room temperature and then distributed between ether and saturated sodium bicarbonate solution. The ether phase was washed with water, dried over sodium sulphate, filtered and concentrated to dryness. Chromatography of the residue on silica using hexane/ether (3:1) gave 21 g of the product as a colourless oil.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:13]([O:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:14](=[O:21])[C:15]([CH3:20])([CH3:19])[CH2:16][CH2:17]Cl>C1(C)C=CC=CC=1>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([O:22][C:13]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[C:14]2[C:15]([CH3:20])([CH3:19])[CH2:16][CH2:17][O:21]2)=[CH:24][CH:25]=1
Reactant: CC(C)(CCCl)C(=O)C(Br)Oc1ccc(Cl)cc1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CC1(C)CCOC1=C(Oc1ccc(Cl)cc1)n1ccnc1
Temperature: 90 °C
Reaction time: 10 h
Yield: 15.9 %

Procedure:
35 g (0.5 mol) of imidazole and 70 g (0.5 mol) of potassium carbonate are dissolved in 700 ml of toluene. 93 g (0.26 mol) of 1-bromo-1-(4-chlorophenoxy)-5-chloro-3,3-dimethyl-pentan-2-one in 200 ml of toluene are added to this mixture at 80° C. The reaction mixture is stirred for a further 10 hours at 90° C., cooled and filtered off under suction from the inorganic residue. The filtrate is washed with water, dried over sodium sulphate and evaporated down. The residue is purified by column chromatography (silica gel: ethyl acetate/cyclohexane=3/1). 12.6 g (14.2% of theory) of (4-chlorophenoxy)-(imidazol-1-yl)-3,3-dimethyltetrahydrofuran-2-ylidene-methane of melting point 85°-88° C. are obtained.
Reaction SMILES: CO[C:3](=[O:20])[C:4]([C:16]([O:18][CH3:19])=[O:17])=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:6]=[CH:7][N:8]([CH3:10])C.C(N)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CCO>[CH3:19][O:18][C:16]([C:4]1[C:3](=[O:20])[N:8]([CH2:10][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:7]=[CH:6][C:5]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:17]
Reactant: CCOC(=O)C(C=CN(C)C)=C(C(=O)OC)C(=O)OC
Reactant: NCc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1ccn(Cc2ccccc2)c(=O)c1C(=O)OC
Temperature: 25 °C
Yield: 104.6 %

Procedure:
A mixture of 5-dimethylamino-3-ethoxycarbonyl-2-methoxycarbonyl-penta-2,4-dienoic acid methyl ester (5 g, 17.5 mmol) and benzylamine (2 mL, 18.4 mmol) in EtOH (30 mL) was refluxed for 5 h. The mixture was cooled to r.t., concentrated in vacuo, and taken up in ether. The solution was washed with 1M HCl and water, and then dried over MgSO4. Evaporation of the solvent in vacuo afforded 5.77 g of the title compound as a viscous orange oil. MS: (+) m/z 338.06 (M+Na).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11](=[O:13])[CH3:12].[N+:14]([O-])([O-:16])=[O:15].[K+]>C(O)(C(F)(F)F)=O.C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([N+:14]([O-:16])=[O:15])=[CH:4][C:3]=1[NH:10][C:11](=[O:13])[CH3:12]
Reactant: O=[N+]([O-])[O-]
Reactant: COc1ccc(NC(C)=O)c(C)c1
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: COc1cc(C)c(NC(C)=O)cc1[N+](=O)[O-]
Temperature: 0 °C
Yield: 46.3 %

Procedure:
N-[2-methyl-4-(methyloxy)phenyl]acetamide (1.95 g, 10.88 mmol) was dissolved in TFA (20 mL) and cooled to 0° C. in an ice bath. Potassium nitrate (1.210 g, 11.97 mmol) was added slowly. The reaction was monitored by tic and quenched by pouring into ice and diluting with EtOAc. A solution of saturated sodium bicarbonate was added until solution was a neutral pH. Organics were washed with water and saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure to afford a yellow solid. Efforts to dissolve the solid in ethyl acetate resulted in a suspension that was let sit for several hours. Hexanes were added and the solids filtered to afford N-[2-methyl-4-(methyloxy)-5-nitrophenyl]acetamide (1.13 g, 5.04 mmol) as yellow fluffy solid. The filtrate was purified via SiO2 chromatography to afford N-[2-methyl-4-(methyloxy)-5-nitrophenyl]acetamide (1.02 g, 4.55 mmol) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.00-2.11 (m, 3 H) 2.29 (s, 3 H) 3.90 (s, 3 H) 7.24 (s, H) 7.99 (s, 1 H) 9.42 (s, 1 H)
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[CH3:19][NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]1)=[O:22].C1COCC1>C(N(CC)CC)C>[CH3:19][NH:20][C:21]([C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:13]([C:11]2[S:12][C:8]([C:5]3[C:4]([CH3:16])=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:24]1)=[O:22]
Reactant: CNC(=O)[C@@H]1CCCNC1
Reactant: Cc1c(-c2ccc(C(=O)O)s2)noc1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CNC(=O)[C@@H]1CCCN(C(=O)c2ccc(-c3noc(C(F)(F)F)c3C)s2)C1
Yield: 86 %

Procedure:
Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and (3R)-N-methylpiperidine-3-carboxamide (Preparative Example 31) by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine and (3R)-N-methylpiperidine-3-carboxamide. After 3 hr the reaction mixture was evaporated in vacuo and filtered with the aid of water. The resulting solids were then washed with a 1 N aqueous HCl solution followed by water. The material was air dried to afford product as a colorless solid (157 mg, 86%). LC/MS 6.00 min, [M+1]+ 402.
Reaction SMILES: [O:1]=[CH:2][C:3](=[CH2:5])[CH3:4].[CH3:6][CH:7]([CH3:13])[CH2:8][C:9](=[CH2:12])[CH:10]=[CH2:11]>C1(C)C=CC=CC=1.[Al+3].[Cl-].[Cl-].[Cl-]>[CH2:8]([C:9]1[CH2:12][CH2:4][C:3]([CH3:5])([CH:2]=[O:1])[CH2:11][CH:10]=1)[CH:7]([CH3:13])[CH3:6]
Reactant: C=C(C)C=O
Reactant: C=CC(=C)CC(C)C
Agent: [Al+3]
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: CC(C)CC1=CCC(C)(C=O)CC1
Yield: 47.5 %

Procedure:
Anhydrous AlCl3 (0.6 g, 4.1 mmol) was suspended in toluene (250 ml) with vigorous stirring and a slow flow of nitrogen applied. Methacrolein (90% tech., 14 ml, 160 mmol) was added at room temperature over 10 min causing a slight increase in temperature. After stirring for 15 min, 5-methyl-3-methylenehex-1-ene 2 (25 g, 140 mmol) was added over 30 min causing the temperature to rise further to 31° C. The reaction mixture was stirred for 2 h and then quenched with sat. NaHCO3 solution (200 ml). After brief agitation the phases were separated and the lower aqueous phase extracted with toluene (300 ml). The combined organic phases were washed with sat. sodium potassium tartrate solution (2×200 ml) and water (300 ml), dried (Na2SO4) and concentrated in vacuo. The oil was purified by short Vigreux distillation at reduced pressure to give 3a as a colorless oil (12 g, 48% yield) containing ca. 10% GC of an isomer 3′a.
Reaction SMILES: [CH2:1]([OH:4])[CH:2]=[CH2:3].N1C=CC=CC=1.[C:11](Cl)(=[O:15])[O:12][CH2:13][CH3:14].Cl>CCCCCC.C1COCC1>[C:11](=[O:15])([O:12][CH2:13][CH3:14])[O:4][CH2:1][CH:2]=[CH2:3]
Reactant: CCOC(=O)Cl
Reactant: C=CCO
Agent: Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: CCCCCC
Product: C=CCOC(=O)OCC
Reaction time: 2 h
Yield: 81 %

Procedure:
A reactor equipped with a stirrer, thermometer and reflux condenser was charged with 469 g of allyl alcohol, 693 g of pyridine, and 1,200 g of THF. With stirring, 797 g of ethyl chlorocarbonate was added dropwise to the mixture while the internal temperature was controlled at −5° C. After the completion of dropwise addition, the reaction solution was aged at room temperature for 2 hours to complete the reaction. The reaction solution was neutralized with aqueous hydrochloric acid. This was combined with 1,000 ml of hexane and washed with water, whereupon the hexane layer was separated and dried over anhydrous sodium sulfate. The solution was precision distilled, collecting a fraction having a boiling point of 149-150° C. Allyl ethyl carbonate, 769 g, was obtained in a yield of 81%. It had a purity of 99.5% as analyzed by gas chromatography. On analysis by 1H-NMR in heavy chloroform, peaks appeared at 1.28 ppm (3H, t), 4.14 ppm (2H, q), 4.57 ppm (2H, d), 5.3 ppm (2H, m), and 5.9 ppm (1H, m). Also on analysis by 13C-NMR in heavy acetone, signals were observed at 14.4, 64.2, 68.4, 118.2, 133.2, and 155.5 ppm. On IR analysis, a strong signal of carbonyl radical was observed at 1748 cm−1. With these data, the product was identified to be allyl ethyl carbonate.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[C:11]2[C:6]([CH:7]=[C:8]([C:20]([OH:22])=O)[C:9](=[O:19])[NH:10]2)=[CH:5][CH:4]=1.[N:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][NH2:31])=[CH:25][CH:24]=1.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[N:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][NH:31][C:20]([C:8]2[C:9](=[O:19])[NH:10][C:11]3[C:6]([CH:7]=2)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:12]=3[O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:22])=[CH:25][CH:24]=1
Reactant: NCCc1ccncc1
Reactant: CCCCCOc1c(OC)ccc2cc(C(=O)O)c(=O)[nH]c12
Agent: O=C([O-])O
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCCOc1c(OC)ccc2cc(C(=O)NCCc3ccncc3)c(=O)[nH]c12
Temperature: 25 °C
Reaction time: 5 h
Yield: 87 %

Procedure:
7-Methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid (30.0 mg) obtained in Example 2-1, 2-pyridine-4-ylethylamine (36.0 mg), and 1-hydroxybenzotriazole hydrate (17.3 mg) were dissolved in dimethylformamide (2 ml), and 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride (24.5 mg) was successively added to this solution while being cooled with ice. After the reaction solution was stirred at room temperature for 5 hours, ethyl acetate (3 ml) and a saturated aqueous solution of sodium hydrogencarbonate (3 ml) were added to this solution. The organic layer was separated and dried over anhydrous sodium sulfate, filtered to remove the desiccating agent, and concentrated under reduced pressure. The resultant residue was purified through column chromatography (eluent: a mixture of chloroform and methanol at a ratio of 25:1) to obtain the title compound (35 mg) as colorless crystals (Table 8).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:11]([O:18][C:19](=[O:35])[CH2:20][N:21]=C(C1C=CC=CC=1)C1C=CC=CC=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:36]([Cl:40])(=[O:39])[CH2:37][CH3:38]>O1CCCC1>[ClH:40].[CH2:11]([O:18][C:19](=[O:35])[CH:20]([NH2:21])[C:36](=[O:39])[CH2:37][CH3:38])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CCC(=O)Cl
Reactant: O=C(CN=C(c1ccccc1)c1ccccc1)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC(=O)C(N)C(=O)OCc1ccccc1
Product: Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Lithium bis(trimethylsilyl)amide (1M in THF, 10.5 mL, 10.5 mmol) was added to N-(diphenylmethylene)glycine benzyl ester (3.28 g, 10 mmol) in tetrahydrofuran (10 mL) at −78° C. under argon. The reaction mixture was stirred at this temperature for about 1 hr. Propionyl chloride (0.913 mL, 10.5 mmol) in tetrahydrofuran (5 mL) was slowly added into the above mixture and stirred for 30 minutes. The reaction mixture was warmed up to room temperature and let stir overnight. After the completion of the above reaction, the reaction mixture was cooled to −40° C. quenched with 50 mL dilute hydrochloride acid (3N) and stirred at room temperature for 2 hr. After removal of tetrahydrofuran, the aqueous solution was extracted with ethyl acetate (3×50 mL), ether (1×50 mL) and CH2Cl2 (50 mL). The aqueous solution was concentrated in vacuo to about ½ volume and lyophilized to give 2-amino-4-methyl-3-oxo-butanoic acid benzyl ester hydrochloride salt, which was used in the next step without further purification.
Reaction SMILES: COC(=O)[C@@H]1CCCN1C(=O)CCCCCCCCCCC/C=C\CCCCCCCC.[C:33]([OH:56])(=O)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]/[CH:45]=[CH:46]\[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54].[NH2:57][C:58]1[CH:66]=[CH:65][C:64]([Cl:67])=[CH:63][C:59]=1[C:60]([OH:62])=[O:61].C(Cl)Cl>N1C=CC=CC=1>[C:33]([NH:57][C:58]1[CH:66]=[CH:65][C:64]([Cl:67])=[CH:63][C:59]=1[C:60]([OH:62])=[O:61])(=[O:56])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]/[CH:45]=[CH:46]\[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54]
Reactant: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)O
Reactant: Nc1ccc(Cl)cc1C(=O)O
Agent: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)N1CCC[C@H]1C(=O)OC
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCCCCC/C=C\CCCCCCCCCCCC(=O)Nc1ccc(Cl)cc1C(=O)O

Procedure:
In a manner similar to (i), erucic acid (1.05 g) was converted to its acid chloride, to which was added 2-amino-5-chlorobenzoic acid (530 mg). The mixture was stirred in pyridine (5 ml)-methylene chloride (2 ml) at room temperature for three hours. The solvent was concentrated and the residue was washed with 0.5N HCl and methanol. Resulting precipitates were dried, followed by recrystallization from ethanol to afford pale yellow crystals [550 mg (36%)], m.p. 159 to 162° C.
Reaction SMILES: C([O:3][C:4](=[O:27])[CH2:5][C:6]1[CH:7]=[N:8][N:9]([CH2:12][C:13]2[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:10]=1[CH3:11])C.[Li+].[OH-].O>C1COCC1.CO>[Br:19][C:17]1[CH:16]=[CH:15][C:14]([O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[C:13]([CH:18]=1)[CH2:12][N:9]1[C:10]([CH3:11])=[C:6]([CH2:5][C:4]([OH:27])=[O:3])[CH:7]=[N:8]1
Reactant: CCOC(=O)Cc1cnn(Cc2cc(Br)ccc2OCC(CC)CC)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CCC(CC)COc1ccc(Br)cc1Cn1ncc(CC(=O)O)c1C
Temperature: 100 °C
Yield: 10 %

Procedure:
To a solution of {1-[5-bromo-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-4-yl}-acetic acid ethyl ester, 3, 0.1 g (0.22 mmol) in a mixture of THF (1 mL) and methanol (0.5 ml) was added a solution of LiOH (0.12 g in 1 ml H2O). The resulting mixture was heated at 100° C. on microwave for 20 minutes. The mixture was poured into water (20 mL) and extracted with EtOAc (3×15 mL). The organic layers were combined, washed with brine (30 mL), dried (MgSO4) and the volatiles removed in vacuo. The crude product was purified on silica to yield 7.4 mg (10%) of {1-[5-Bromo-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-4-yl}-acetic acid, 4 as a white solid.
Reaction SMILES: [F-:1].[Cs+].[F:3][C:4]1([F:17])[C:10]([F:12])([F:11])[C:9]([F:14])([F:13])[C:8]([F:16])([F:15])[O:7][C:5]1=[O:6].[F:18][C:19]([F:27])([F:26])[C:20]1([F:25])[O:24][C:21]1(F)[F:22]>COCCOC>[F:25][C:20]([C:19]([F:27])([F:26])[F:18])([O:7][C:8]([F:16])([F:15])[C:9]([F:14])([F:13])[C:10]([F:12])([F:11])[C:4]([F:17])([F:3])[C:5]([F:1])=[O:6])[C:21]([F:22])=[O:24]
Reactant: FC(F)(F)C1(F)OC1(F)F
Reactant: O=C1OC(F)(F)C(F)(F)C(F)(F)C1(F)F
Reactant: [F-]
Agent: [Cs+]
Solvent: COCCOC
Product: O=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(C(=O)F)C(F)(F)F

Procedure:
In a 200 cc autoclave equipped with a mechanical stirrer, 5 g of cesium fluoride powder, 20 cc of ethyleneglycol dimethyl ether and 50 g of perfluoro-δ-valerolactone was charged. Thirty seven grams of hexafluoropropylene oxide was introduced intermittently into the reactor for about 2 hours with vigorously stirring at the temperature of 0° to 5° C. under a pressure of lower than 1.0 kg/cm2G.