Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:5][N:6]2[CH2:15][CH2:14][C@@:13]34[C:16]5[C:22]6[CH2:23][C@@H:7]2[C@@H:8]3[CH2:9][CH2:10][C:11](=[O:26])[C@@H:12]4[O:18][C:17]=5[C:19]([C:24]#[N:25])=[CH:20][CH:21]=6)[CH2:4][CH2:3][CH2:2]1.[OH-:27].[K+]>C(O)(C)(C)C>[CH:1]1([CH2:5][N:6]2[CH2:15][CH2:14][C@@:13]34[C:16]5[C:22]6[CH2:23][C@@H:7]2[C@@H:8]3[CH2:9][CH2:10][C:11](=[O:26])[C@@H:12]4[O:18][C:17]=5[C:19]([C:24]([NH2:25])=[O:27])=[CH:20][CH:21]=6)[CH2:2][CH2:3][CH2:4]1
Reactant: [OH-]
Reactant: N#Cc1ccc2c3c1O[C@H]1C(=O)CC[C@H]4[C@@H](C2)N(CC2CCC2)CC[C@]314
Agent: [K+]
Solvent: CC(C)(C)O
Product: NC(=O)c1ccc2c3c1O[C@H]1C(=O)CC[C@H]4[C@@H](C2)N(CC2CCC2)CC[C@]314
Temperature: 100 °C
Yield: 104.4 %

Procedure:
To a solution of (4R,4aR,7aR,12bS)-3-(cyclobutylmethyl)-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carbonitrile (24 g, 68.9 mmol) in tert-butanol (240 mL) was added KOH (2.1 g, 37.1 mmol). The reaction was heated to 100° C. for 15 minutes. The reaction was allowed to cool to room temperature and concentrated to 50% volume. Diluted with water and extracted with ethyl acetate twice. The organic phases were combined, washed with sodium hydrogen carbonate solution and brine and dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica chromatography eluted with 4% methanol in dichloromethane to give to give (4R,4aR,7aR,12bS)-3-(cyclobutylmethyl)-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carboxamide (14.2 g, 89% pure LCMS, 56% yield); [M+H]+367.2.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:35])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[N:14]=1)[N:11]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:10](=[O:28])[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:8]2)=[O:4].[NH2:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:21]([N:11]1[C:12]2[C:7](=[C:6]([OH:35])[C:5]([C:3]([NH:36][CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[O:4])=[N:14][C:13]=2[C:15]2[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=2)[CH:8]=[C:9]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:10]1=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: NCCC(=O)O
Reactant: COC(=O)c1nc(-c2cnn(C)c2)c2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: Cn1cc(-c2nc(C(=O)NCCC(=O)O)c(O)c3cc(-c4ccccc4)c(=O)n(Cc4ccccc4)c23)cn1
Temperature: 25 °C
Yield: 45.1 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-8-(1-methyl-1H-pyrazol-4-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (52 mg, 0.11 mmol), β-alanine (596 mg, 6.7 mmol) and NaOMe solution (10 mL, 5.0 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-100% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4, and the resulting precipitate was isolated by filtration to give 26 mg of the title compound. MS: (+) m/z 524.37 (M+1).
Reaction SMILES: [Cl:1][CH2:2][CH:3]([OH:6])[CH2:4][Cl:5].C([N-]C(C)C)(C)C.F[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22]>C1COCC1.O>[Cl:1][CH2:2][CH:3]([CH2:4][Cl:5])[O:6][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22]
Reactant: OC(CCl)CCl
Reactant: O=[N+]([O-])c1ccccc1F
Agent: CC(C)[N-]C(C)C
Solvent: O
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccccc1OC(CCl)CCl
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of 1,3-dichloro-propan-2-ol (1.29 g, 10 mmoles) in THF, under nitrogen, was cooled to 0° C., treated dropwise with llithium diisopropylamide (LDA) (5 ml, 2M solution in hexanes, 10 mmoles), while maintaining the temperature constant at 0° C., stirred at 0° C. for 15 minutes, treated with 1-fluoro-2-nitro-benzene (1.2 g ml, 8.5 mmoles) and stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with EtOAc. The extracts were combined, washed with brine, dried over Na2SO4, and concentrated under vacuum, to afford the title compound as an off-white solid (2.0 g, 8 mmoles), identified by HNMR analysis.
Reaction SMILES: [Cl:1][C:2]1([Cl:15])[C:4]([CH3:6])([CH3:5])[CH:3]1[C:7]1[CH:12]=[CH:11][C:10]([O:13]C)=[CH:9][CH:8]=1.B(Br)(Br)Br>>[Cl:1][C:2]1([Cl:15])[C:4]([CH3:6])([CH3:5])[CH:3]1[C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1
Reactant: COc1ccc(C2C(C)(C)C2(Cl)Cl)cc1
Agent: BrB(Br)Br
Product: CC1(C)C(c2ccc(O)cc2)C1(Cl)Cl

Procedure:
p-(2,2-Dichloro-3,3-dimethylcyclopropyl)phenol was prepared from 65.8 g. of p-(2,2-dichloro-3,3-dimethylcyclopropyl)anisole and 37.5 g. of boron tribromide according to the procedure described above in Example 1, part (c). There was thus obtained 23.5 g. of p-(2,2-dichloro-3,3-dimethylcyclopropyl)phenol, m.p. 111°-111.5°C. when recrystallized from a benzene-hexane mixture.
Reaction SMILES: [OH-].[Na+].[C:3]1([C:9]([CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[OH:12])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:19](Cl)[CH:20]=[CH2:21]>CS(C)=O>[CH2:21]([C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([OH:12])[C:9](=[O:10])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[CH:20]=[CH2:19]
Reactant: C=CCCl
Reactant: O=C(c1ccccc1)C(O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: C=CCC(O)(C(=O)c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 75.1 %

Procedure:
90 ml of a 10% by weight aqueous sodium hydroxide solution are added with cooling in a nitrogen atmosphere to a solution of 42.4 g (0.2 mol) benzoin in 400 ml DMSO, and 22 ml (0.27 mol) allyl chloride are added dropwise at 20°C within 15 minutes. The reaction solution is further stirred for 2 hours and then poured into ice/water. The crystalline crude product (50 g) is recrystallised from petroleum ether and gives 37.9 g (75% of theory) α-allyl-benzoin of melting point 89°- 93°C. A further 5.1 g of melting point 85°- 90°C are obtained from the mother liquor.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]([N:6]=[C:7]=[O:8])=[O:5].[C:9]([OH:13])([CH3:12])([CH3:11])[CH3:10]>ClC(Cl)C>[Cl:1][CH2:2][CH2:3][C:4]([NH:6][C:7](=[O:8])[O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:5]
Reactant: CC(C)(C)O
Reactant: O=C=NC(=O)CCCl
Solvent: CC(Cl)Cl
Product: CC(C)(C)OC(=O)NC(=O)CCCl

Procedure:
To beta-chloropropionyl isocyanate (13.3 g; 100 mmol) in dichloroethane (20 g), a solution of t-butanol (7.4 g; 100 mmol) in dichloroethane (20 g) was dropwise added under ice-cooling in 5 minutes, whereby t-butyl beta-chloropropionylcarbamate was produced. Triethylamine (9.8 g; 100 mmol) was added to the reaction mixture, and the resultant mixture was stirred for 60 minutes. Precipitated salts were eliminated by filtration, and the filtrate was concentrated under reduced pressure to give t-butyl acryloylcarbamate as crude crystals, which were recrystallized from chloroform to give colorless needles. M.P., 131°-132° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[CH2:10][C:11]([OH:13])=[O:12].[CH3:14]O>Cl>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[C:3]=1[CH2:10][C:11]([O:13][CH3:14])=[O:12]
Reactant: Cc1cc(C)c(CC(=O)O)c(C)c1
Reactant: CO
Agent: Cl
Product: COC(=O)Cc1c(C)cc(C)cc1C

Procedure:
173 g (2,4,6-trimethylphenyl)acetic acid is refluxed in 131 mL of concentrated hydrochloric acid and 1.1 L of methanol for 3 hours with stirring. The solvent is distilled off under reduced pressure and the aqueous phase extracted twice with diethyl ether. The combined organic phases are extracted twice with a saturated aqueous sodium hydrogen carbonate solution and dried with sodium sulfate and the solvent is distilled off under reduced pressure. The residue is fractionally distilled. Yield: 116 g (57%); bp15: 140° C.
Reaction SMILES: [F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[C:12]([CH3:23])[C:11]=2[F:24])=[C:6]([F:25])[CH:5]=[CH:4][C:3]=1[OH:26].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>CC(=O)CC>[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[C:12]([CH3:23])[C:11]=2[F:24])=[C:6]([F:25])[CH:5]=[CH:4][C:3]=1[O:26][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]
Reactant: Cc1cc(-c2cccc(F)c2)cc(CNc2c(F)ccc(O)c2F)c1F
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCC(C)=O
Product: CCOC(=O)COc1ccc(F)c(NCc2cc(-c3cccc(F)c3)cc(C)c2F)c1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79.8 %

Procedure:
To a stirred solution of 2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)-3-methyl-phenyl]methylamino]phenol (150 mg, 0.42 mmol, 1.0 eq) in 2-butanone (10 mL) was added Cs2CO3 (203 mg, 0.62 mmol, 1.5 eq). The resulting mixture was stirred at room temperature for 30 min then ethyl bromoacetate (83 mg, 0.50 mmol, 1.2 eq) was added. The reaction was stirred at room temperature 30 min then filtered and concentrated. The crude residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound as a gum (150 mg, 81%).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:38]/[O:39][CH:40]([C:55]([OH:57])=[O:56])[C:41]2[CH:46]=[CH:45][C:44]([O:47]C(=O)C)=[C:43]([O:51]C(=O)C)[CH:42]=2)/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15]([CH2:23][S:24][C:25]2[N:30]4[N:31]=[C:32]([C:34]([OH:36])=[O:35])[N:33]=[C:29]4[N:28]=[C:27]([CH3:37])[CH:26]=2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:6]=1.C(=O)(O)[O-].[Na+]>O>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:38]/[O:39][CH:40]([C:55]([OH:57])=[O:56])[C:41]2[CH:46]=[CH:45][C:44]([OH:47])=[C:43]([OH:51])[CH:42]=2)/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15]([CH2:23][S:24][C:25]2[N:30]4[N:31]=[C:32]([C:34]([OH:36])=[O:35])[N:33]=[C:29]4[N:28]=[C:27]([CH3:37])[CH:26]=2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:6]=1
Reactant: CC(=O)Oc1ccc(C(O/N=C(\C(=O)N[C@@H]2C(=O)N3C(C(=O)O)=C(CSc4cc(C)nc5nc(C(=O)O)nn45)CS[C@H]23)c2csc(N)n2)C(=O)O)cc1OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Cc1cc(SCC2=C(C(=O)O)N3C(=O)[C@@H](NC(=O)/C(=N\OC(C(=O)O)c4ccc(O)c(O)c4)c4csc(N)n4)[C@H]3SC2)n2nc(C(=O)O)nc2n1
Temperature: 25 °C
Reaction time: 6 h
Yield: 62.2 %

Procedure:
The product obtained in Step 3 (0.25 g) was suspended in water (10 ml), and the pH of the mixture was adjusted to 8.0 with sodium bicarbonate. After stirring at room temperature for 6 hours, the resulting solution was applied to a Diaion HP 10 column. The objective fractions eluted with water were collected and lyophilized, giving 0.14 g of the objective compound (as sodium salt).
Reaction SMILES: C(O[C:4]([N:6]1[CH2:11][C:10](=[O:12])[C:9]2[CH:13]=[CH:14][O:15][C:8]=2[CH2:7]1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH3:4][N:6]1[CH2:11][CH:10]([OH:12])[C:9]2[CH:13]=[CH:14][O:15][C:8]=2[CH2:7]1
Reactant: CCOC(=O)N1CC(=O)c2ccoc2C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CN1Cc2occc2C(O)C1
Temperature: 0 °C
Yield: 79.9 %

Procedure:
A solution of 1.76 g of 6-ethoxycarbonyl-4,5,6,7-tetrahydrofuro[2,3-c]pyridin-4-one prepared in the step 4 in 20 mL of dry THF was slowly dropped into an ice-cooled solution of 0.45 g of lithium aluminum hydride in 20 mL of dry THF. The reaction solution was gradually heated followed by heating to reflux for 30 minutes. The reaction solution was cooled, an excess of lithium aluminum hydride was decomposed by a gradual addition of ice thereto and the mixture was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated solution of sodium chloride and dried over anhydrous magnesium sulfate and the solvent was evaporated therefrom in vacuo. The residue was purified by silica gel column chromatography to give 1.03 g of the objective compound.
Reaction SMILES: [OH:1][C@@H:2]([CH3:26])[C@@H:3]([N:16]1[CH:20]=[C:19]([C:21]([O:23]CC)=O)[N:18]=[CH:17]1)[CH2:4][S:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[OH-].[NH4+:28]>COCCOC>[OH:1][C@@H:2]([CH3:26])[C@@H:3]([N:16]1[CH:20]=[C:19]([C:21]([NH2:28])=[O:23])[N:18]=[CH:17]1)[CH2:4][S:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1
Reactant: CCOC(=O)c1cn([C@@H](CSc2ccc3ccccc3c2)[C@H](C)O)cn1
Reactant: [NH4+]
Agent: [OH-]
Solvent: COCCOC
Product: C[C@H](O)[C@H](CSc1ccc2ccccc2c1)n1cnc(C(N)=O)c1

Procedure:
A mixture of ethyl 1-{(1R,2S)-2-hydroxy-1-[(2-naphthylthio)methyl]propyl}-1H-imidazole-4-carboxylate (0.18 g), 28% ammonium hydroxide (20 mL) and 1,2-dimethoxyethane (10 mL) was heated at 100° C. in the stainless steel bottle for 24 hours. After cooling, the reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (elution; 10:1 chloroform-1% ammonium hydroxide/methanol) to give the product, which was recrystallized from 3:7 n-hexane-ethyl acetate (10 mL) to give 1-{(1R,2S)-2-hydroxy-1-[(2-naphthylthio)methyl]propyl}-1H-imidazole-4-carboxamide (102) (90 mg).
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH:11][C@H:12]([C:14]3[N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18](=[O:26])[C:17]4=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]4[N:15]=3)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=1.[CH3:39][C:40]1[O:41][C:42](B2OC(C)(C)C(C)(C)O2)=[CH:43][N:44]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:30][C:27]1[CH:28]=[CH:29][N:16]2[C:17]=1[C:18](=[O:26])[N:19]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]([C@@H:12]([NH:11][C:9]1[C:10]3[C:2]([C:42]4[O:41][C:40]([CH3:39])=[N:44][CH:43]=4)=[CH:3][N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:37])[CH3:38])[C:5]=3[N:6]=[CH:7][N:8]=1)[CH3:13])=[N:15]2
Reactant: Cc1ncc(B2OC(C)(C)C(C)(C)O2)o1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc4c3c(Br)cn4COCC[Si](C)(C)C)n(-c3ccccc3)c(=O)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ncc(-c2cn(COCC[Si](C)(C)C)c3ncnc(N[C@@H](C)c4nn5ccc(C)c5c(=O)n4-c4ccccc4)c23)o1
Temperature: 100 °C
Reaction time: 2 h
Yield: 51.9 %

Procedure:
(S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (60 mg, 0.1 mmol) was treated with 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (52 mg, 0.25 mmol), tetrakistriphenylphosphine palladium (35 mg, 0.03 mmol) and aqueous solution of sodium carbonate (2M, 125 μl, 0.25 mmol) in DMF (1.5 ml). The reaction mixture was submitted at vacuum-argon cycles and stirred at 100° C. for 2 h. The reaction mixture was allowed to cool down to room temperature and poured over ice, basified with potassium carbonate and extracted with ethyl acetate (×3). The organic phase was successively washed with water and brine, dried over magnesium sulphate, filtered and the solvent evaporated under reduced pressure. The residue was purified by normal phase using SP1® Purification System (0% to 100%, hexane-diethyl ether) to obtain 31 mg (52% yield) of the title compound.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=2)[N:3]=1.[NH:16]1[C:24]2[C:19](=[C:20]([CH2:25][NH2:26])[CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17]1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[Cl:8][C:6]1[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:10]=2)[N:3]=[C:2]([NH:26][CH2:25][C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:19]=2[CH:18]=[CH:17][NH:16]3)[CH:7]=1
Reactant: NCc1cccc2[nH]ccc12
Reactant: Cc1cccc(-c2nc(Cl)cc(Cl)n2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: Cc1cccc(-c2nc(Cl)cc(NCc3cccc4[nH]ccc34)n2)n1
Temperature: 25 °C

Procedure:
A solution of 4,6-dichloro-2-(6-methyl-pyridin-2-yl)-pyrimidine (Intermediate E) (1 eq, 0.417 mmol, 0.1 g) and C-(1H-indol-4-yl)-methylamine (1 eq, 0.417 mmol, 61 mg) and K2CO3 (1 eq, 0.417 mmol, 58 mg) in NMP (1 ml) is heated using microwave radiation at 120° C. for 1 hour. After cooling to room temperature, the mixture is partitioned between DCM/water and the organic portion is separated and concentrated in vacuo. The crude brown oil is purified by flash chromatography on silica eluting with 100% DCM and the appropriate fractions are combined and concentrated in vacuo. The resulting oil is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and the residue is dissolved in DCM and concentrated in vacuo once again. The resulting solid is dried under vacuum to afford the title compound [M+H]+=350/352.
Reaction SMILES: [Br:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[CH2:10]Br)=[CH:4][CH:3]=1.[C-:18]#[N:19].[K+]>C(O)C>[Br:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH2:7][C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[CH2:10][C:18]#[N:19])=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1CCc1ccc(Br)cc1
Reactant: [C-]#N
Agent: [K+]
Solvent: CCO
Product: N#CCc1ccccc1CCc1ccc(Br)cc1
Reaction time: 2 h

Procedure:
2-(4-Bromophenethyl)-benzyl bromide, 27.0 g. (0.0764 mole) and 6.2 g. (0.0954 mole) of potassium cyanide are suspended in 180 ml. of 95% ethanol and the mixture is stirred at reflux for 2 hours. Ethanol, 70 ml. of 95%, is added and stirring at reflux is continued for 2 hours. The precipitate is removed by filtration and the ethanolic filtrate evaporated under reduced pressure. The residual brown oil is dissolved in benzene and the solution is washed thoroughly with water and dried over anhydrous sodium sulfate. Evaporation of the benzene under reduced pressure leaves the product as the residual dark yellow oil that slowly solidifies to an oily solid. Recrystallization from cyclohexane-petroleum ether gives purified material, m.p. 59°-60.5° C. Vapor phase chromatography indicates a purity of approximately 99%.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]#[C:19][CH2:20][CH3:21]>[Ni]>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH3:21]
Reactant: CCC#CCCCCCCCCCCOC1CCCCO1
Agent: [Ni]
Product: CC/C=C\CCCCCCCCCCOC1CCCCO1

Procedure:
The compounds in the composition are available commercially or can be prepared synthetically in accordance with the procedure described by S. Voerman in Agric. Ecosystems Environ. 21 31-41 (1988). The synthesis of I is shown in FIG. 1. In brief, 1,10-decanediol (III) is reacted with concentrated hydrochloric acid. Continuous extraction of the reaction mixture with petroleum ether (b.p. 100°-140° C.) gives 10-chlorodecan-1-ol (IV) free of dichloride. IV is reacted with an equimolar quantity of dihydropyran, catalysed by 1 drop of concentrated hydrochloric acid to produce 1-chloro-10-[(tetrahydro-2H-pyran-2-yl)oxy]decane (V). Butyne gas is bubbled into a solution of n-butyl lithium under nitrogen and then V is added dropwise to produce 14-[(tetrahydro-2H-pyran-2-yl)oxy]-3-tetradecyne (VI). VI is hydrogenated with a P2-nickel catalyst (H. C. Brown and V. K. Ahiya, J. Chem. Soc. Chem. Comm., pp. 553-554 (1973)) to produce the Z olefin, 14-[(tetrahydro-2H-pyran-2-yl)oxy]-(Z)-3-tetradecene (VII), with less than 1% of the E isomer. The pheromone component, I, is generated by heating VII for 15 minutes in methanol containing a few drops of hydrochloric acid. II is prepared according to the scheme shown in FIG. 2. The conversions of 1,8-octanediol (VIII) to (Z)-9-dodecen-1-ol (XIII) is carried out the same as III to I except that VIII is substituted for III. XIII is converted to the pheromone component, II, by reaction with acetic anhydride in pyridine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([F:24])=[C:16]([N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)[CH:17]=3)[C:12](=[O:25])[N:11]([O:26]CC3C=CC=CC=3)[C:10]2=[O:34])=[CH:5][CH:4]=1>[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([F:24])=[C:16]([N:19]4[CH2:20][CH2:21][CH2:22][CH2:23]4)[CH:17]=3)[C:12](=[O:25])[N:11]([OH:26])[C:10]2=[O:34])=[CH:7][CH:8]=1
Reactant: COc1ccc(-n2c(=O)n(OCc3ccccc3)c(=O)c3cc(F)c(N4CCCC4)cc32)cc1
Agent: [Pd]
Product: COc1ccc(-n2c(=O)n(O)c(=O)c3cc(F)c(N4CCCC4)cc32)cc1
Yield: 118.8 %

Procedure:
Using the General Method 6A, the reaction of 10% Pd/C (0.03 g) with 1-(4-methoxyphenyl)-6-fluoro-3-benzyloxy-7-pyrrolidin-1-yl-1H-quinazoline-2,4-dione (Example O-1, 0.09 g, 0.195 mmol) afforded 0.086 g of the title compound as a solid, mp 224-226° C.
Reaction SMILES: [OH:1][C:2]([C@H:5]1[CH2:9][CH2:8][NH:7][C@H:6]1[CH3:10])([CH3:4])[CH3:3].F[C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=1>>[OH:1][C:2]([C@H:5]1[CH2:9][CH2:8][N:7]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[C@H:6]1[CH3:10])([CH3:4])[CH3:3]
Reactant: C[C@@H]1NCC[C@@H]1C(C)(C)O
Reactant: N#Cc1ccc(F)cc1
Product: C[C@H]1[C@@H](C(C)(C)O)CCN1c1ccc(C#N)cc1

Procedure:
Using compound 1 and 4-fluorobenzonitrile as starting materials, the title compound was obtained by the same manner as shown in Example 1 (reaction temperature 90° C., reaction time 3 hr).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[H-].[Na+].[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[C:17](F)[C:14]=1[C:15]#[N:16]>CN(C)C=O>[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[C:17]([O:6][CH2:5][C:4]2[CH:7]=[CH:8][CH:9]=[C:2]([Br:1])[CH:3]=2)[C:14]=1[C:15]#[N:16]
Reactant: N#Cc1c(F)cccc1F
Reactant: OCc1cccc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1c(F)cccc1OCc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3-Bromobenzyl alcohol (1.45 mg; 7.9 mmol) in dimethylformamide was added to a cooled (0° C.) slurry of sodium hydride (316 mg; 7.9 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 30 min. The reaction mixture was then added to a cooled (0° C.) solution of 2,6-difluorobenzonitrile in dimethylformamide, stirred for 2 hours at room temperature. The reaction mixture was poured on crushed ice-water, stirred, filtered, washed with water and dried to afford 1.81 grams of 2-fluoro-6-(3-bromophenylmethoxy)benzonitrile.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:12].[CH:13]1([NH2:17])[CH2:16][CH2:15][CH2:14]1>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:17][CH:13]2[CH2:16][CH2:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:12]
Reactant: O=S(=O)(Cl)c1ccc(Br)c(F)c1
Reactant: NC1CCC1
Solvent: ClCCl
Product: O=S(=O)(NC1CCC1)c1ccc(Br)c(F)c1
Yield: 88.9 %

Procedure:
According to general procedure C, 4-Bromo-3-fluoro-benzenesulfonyl chloride (0.40 g, 1.46 mmol) and cyclobutylamine (0.31 mL, 3.65 mmol) were stirred together with dry dichloromethane (5 mL) for 16 hours. 4-bromo-N-cyclobutyl-3-fluorobenzenesulfonamide (0.40 g, 89%) was provided after purification. MS (ESI) m/z 308. HPLC purity 98.2% at 210-370 nm, 10.6 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min.