Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:9][CH2:10][CH2:11][NH:12][NH2:13]>C(O)C>[OH:9][CH2:10][CH2:11][NH:12][N:13]=[CH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccccc1
Reactant: NNCCO
Solvent: CCO
Product: OCCNN=Cc1ccccc1
Yield: 97 %

Procedure:
Benzaldehyde (2-hydroxyethyl)hydrazone is prepared by condensation of benzaldehyde with (2-hydroxyethyl)hydrazine according to the following procedure: 10-2 moles of (2-hydroxyethyl)hydrazine are added to a solution containing 10-2 moles of benzaldehyde in 20 ml of ethanol. The reaction is left under reflux for 30 minutes. The mixture is then cooled. The solvents are removed by evaporation. The product obtained is an extremely unstable oil. The crude reaction yield is 97%.
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].Br[C:6]1[N:10]([C@H:11]2[O:17][C@@H:16]([CH3:18])[C@:14](C(=O)C)([OH:15])[C@:12]2(C(=O)C)[OH:13])[C:9]2[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:8]=2[N:7]=1.C(O)C>CN(C=O)C>[CH:1]([NH:4][C:6]1[N:10]([C@H:11]2[O:17][C@@H:16]([CH3:18])[C@H:14]([OH:15])[C@@H:12]2[OH:13])[C:9]2[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:8]=2[N:7]=1)([CH3:3])[CH3:2]
Reactant: CC(=O)[C@@]1(O)[C@@H](n2c(Br)nc3cc(Cl)c(Cl)cc32)O[C@@H](C)[C@@]1(O)C(C)=O
Reactant: CC(C)N
Solvent: CCO
Solvent: CN(C)C=O
Product: CC(C)Nc1nc2cc(Cl)c(Cl)cc2n1[C@H]1O[C@@H](C)[C@H](O)[C@@H]1O
Temperature: 80 °C
Reaction time: 24 h

Procedure:
Isopropylamine (5 mL ) and 2-bromo-5,6-dichloro-1-(5-deoxy-2,3-diacetyl-beta-L-ribofuranosyl)-1H-benzimidazole (0.40 g, 0.86 mmol) were combined with absolute ethanol (20 mL) and stirred at 80° C. for 24 h. The reaction mixture was concentrated and purified by multiple cyclings on a chromatotron fitted with a 2 mm silica gel rotor, with 1:30 methanol:dichloromethane and 1:1 ethyl acetate:hexanes and 1:4 acetone:dichloromethane to give a white solid (0.18 g, 0.70, mmol, 60%); m.p. 103-105° C.; [α]20D=(+) 38.8 (c=0.5 DMF); UV λmax (ε): pH 7.0:303 nm (10,400), 276 (2,500), 260 (10,000); MS (CI): m/z (rel. intensity) 360 (14.26, M−); 1H NMR (DMSO-d6) d 7.39 (s, 1H, Ar—H), 7.31 (s, 1H, Ar—H), 6.57 (d, 1H, NH, J=7.6 Hz), 5.68 (d, 1H, H-1′, J=6.6 Hz), 5.23 (d, 1H, OH, J=4.8 Hz), 5.21 (d, 1H, OH, J=7.1 Hz), 4.31 (q, 1H, H-4′, J=6.7 Hz), 4.04-3.98 (m, 1H, isopropyl-CH), 3.95-3.87 (m, 1H), 3.81-3.76 (m, 1H), 1.36 (d, 3H, H-5′, J=6.5 Hz), 1.20 (d, 6H, cyclopentyl-CH2, J=6.6 Hz).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[F:6][C:7]([F:13])([F:12])[C:8](OC)=[O:9]>CO>[F:6][C:7]([F:13])([F:12])[C:8]([NH:1][CH2:2][CH2:3][CH2:4][OH:5])=[O:9]
Reactant: NCCCO
Reactant: COC(=O)C(F)(F)F
Solvent: CO
Product: O=C(NCCCO)C(F)(F)F
Yield: 102 %

Procedure:
3-Amino-1-propanol (10.0 mL, 0.131 mol) and methyl trifluoroacetate (65 mL, 0.646 mol) in methanol (200 mL) were refluxed for 1.5 h, cooled and concentrated to give 2,2,2-trifluoro-N-(3-hydroxypropyl)-acetamide (22.87 g, quantitative) as a light yellow oil which was used without purification. NMR CDCl3 δ 7.45 (br s, 1H), 3.77 (t, J=5.5 Hz, 2H), 3.53-3.42 (m, 2H), 2.45 (s, 1H), 1.83-1.75 (m, 2H).
Reaction SMILES: [H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2Cl>CN(C=O)C>[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Oc1ccccc1
Reactant: Clc1ncnc2ccc(I)cc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Ic1ccc2ncnc(Oc3ccccc3)c2c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 98.2 %

Procedure:
A suspension of NaH (washed free of mineral oil) in DMF (40 mL) was cooled to 0° C. and a solution of phenol (5.65 g, 60 mmol) in DMF (20 mL) was added dropwise. Upon completion of addition, 6-iodo-4-chloroquinazoline 13 (14.6 g, 50.3 mmol) was added as a solid in small portions. The cooling bath was moved and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then quenched with water (200 mL), diluted with EtOAc (300 mL) and transferred to a separatory funnel. The organic layer was washed with dilute aqueous NaOH, water and brine and dried over Na2SO4. Filtration of the solids and removal of the solvent provided 6-iodo-4-phenoxyquinazoline 14 (17.2 g, 98%) as a yellow solid. 1H NMR (400 MHz; CDCl3): δ: 8.74 (d, 1H), 8.14 (s, 1H), 8.12 (dd, 1H), 7.71 (d, 1H), 7.49 (dd, 2H), 7.32 (t, 1H), 7.22 (m, 2H).
Reaction SMILES: [CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15](I)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:33][O:34][C:35]1[N:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1>>[CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15]([C:38]3[CH:39]=[N:40][C:35]([O:34][CH3:33])=[CH:36][CH:37]=3)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: COc1ccc(B(O)O)cn1
Reactant: CCCCCCc1cccc(-c2nc(I)c(C(=O)N3CCC(N4CCCC4)CC3)n2C)c1
Product: CCCCCCc1cccc(-c2nc(-c3ccc(OC)nc3)c(C(=O)N3CCC(N4CCCC4)CC3)n2C)c1

Procedure:
In analogy to the procedure described for example 7, [2-(3-hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 2) was reacted with 6-methoxy-pyridin-3-yl-boronic acid to give the title compound as light yellow oil. MS: 530.3 (MH+).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH3:16])[C:10]([CH3:18])([CH3:17])[CH2:9]1)C1C=CC=CC=1>CO.[H][H].[OH-].[OH-].[Pd+2]>[CH2:15]([NH:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][C:10]1([CH3:17])[CH3:18])[CH3:16]
Reactant: CCNC1CCN(Cc2ccccc2)CC1(C)C
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CCNC1CCNCC1(C)C

Procedure:
A mixture of 20% Pd(OH)2 on carbon (0.4 g) and 1-benzyl-4-ethylamino-3,3-dimethylpiperidine (1.3 g, 5.3 mmol) in methanol (10 ml) was stirred in hydrogen atmosphere (1 atm.) at ambient temperature for 15 hr. The catalyst was filtered off, washed with methanol and filtrate was concentrated to dryness to afford 4-ethylamino-3,3-dimethylpiperidine. Yield 0.8 g (97%), C9H20N2, m/z 157 (M+1), PMR (CDCl3): 0.9 (s, 3H), 1.06 (s, 3H), 1.18-1.38 (m, 5H), 1.85 (bs, 2H, D2O exchangeable), 1.64-2.8 (m, 6H), 2.94 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:39])[CH:4]([N:16]1[CH2:21][CH2:20][N:19](S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH:18]([CH2:34][CH:35]2[CH2:37][CH2:36]2)[C:17]1=[O:38])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.SC1C=CC(O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[CH3:1][O:2][C:3](=[O:39])[CH:4]([N:16]1[CH2:21][CH2:20][NH:19][CH:18]([CH2:34][CH:35]2[CH2:37][CH2:36]2)[C:17]1=[O:38])[CH2:5][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: COC(=O)C(Cc1ccc2ccccc2c1)N1CCN(S(=O)(=O)c2ccccc2[N+](=O)[O-])C(CC2CC2)C1=O
Agent: O=C([O-])[O-]
Agent: Oc1ccc(S)cc1
Agent: [K+]
Solvent: CC#N
Product: COC(=O)C(Cc1ccc2ccccc2c1)N1CCNC(CC2CC2)C1=O
Reaction time: 15 h
Yield: 89 %

Procedure:
To a solution of 2-[3-cyclopropylmethyl-4-(2-nitro-benzenesulfonyl)-2-oxo-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester, 13, (3.56 g, 6.46 mmol) and 4-mercaptophenol (4.07 g, 32.3 mmol) in CH3CN (50 mL) is added potassium carbonate (8.91 g, 64.6 mmol). The reaction mixture is stirred for 15 hours, quenched with 10% NaHCO3 solution and extracted several times with EtOAc. The combined extracts are dried over Na2SO4 and concentrated in vacuo to yielding a bright yellow oil which is purified over silica gel (hexanes/EtOAc, 1:1 to EtOAc/MeOH, 10:1) to afford 2.10 g (89% yield) of the desired product. 1H NMR (300 MHz, CD3OD) δ 7.76–7.86 (m, 3H), 7.71 (s, 1H), 7.37–7.52 (m, 3H), 5.27 (dd, J=11.7, 4.8 Hz, 1H), 3.79 (s, 3H), 3.25–3.60 (m, 4H), 2.88–3.06 (m, 2H), 2.62–2.75 (m, 1H), 1.56–1.68 (m, 1H), 1.16–1.29 (m, 1H), 0.01–0.25 (m, 3H), −0.19–−0.08 (m, 2H); 13C NMR (75 MHz, MeOD) δ 171.55, 171.01 m 134.88, 133.78, 132.74, 128.15, 127.52, 127.45, 127.11, 126.11, 125.64, 59.42, 58.92, 51.78, 46.77, 41.23, 36.59, 33.97, 6.63, 3.72, 3.46; MS (ESMS) m/z 367.2 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([F:10])([F:9])[F:8])=[CH:5][C:4]([NH:11][C:12](=[O:20])OC2C=CC=CC=2)=[N:3]1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[O:33][CH3:34])[N:29]=[CH:28][N:27]=[C:26]2[S:35][C:36]1[CH:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39].C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[O:33][CH3:34])[N:29]=[CH:28][N:27]=[C:26]2[S:35][C:36]1[CH:37]=[C:38]([NH:39][C:12]([NH:11][C:4]2[CH:5]=[C:6]([C:7]([F:8])([F:9])[F:10])[N:2]([CH3:1])[N:3]=2)=[O:20])[CH:40]=[CH:41][CH:42]=1
Reactant: COc1cc2ncnc(Sc3cccc(N)c3)c2cc1OC
Reactant: Cn1nc(NC(=O)Oc2ccccc2)cc1C(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C(F)(F)F)n(C)n4)c3)c2cc1OC
Yield: 17 %

Procedure:
Using the procedure described in Example 159B, phenyl 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-ylcarbamate described in Example 165A (0.114 g, 0.4 mmol) was reacted with 3-(6,7-dimethoxyquinazolin-4-ylthio)aniline from Example 115B (0.125 g, 0.4 mmol), and N,N-diisopropylethylamine (0.5 mL) in THF (6 mL) at 50° C. for 3 hours, to afford 1-[3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl]-3-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]urea as solid (0.035 g, 17%). 1H NMR (300 MHz, CDCl3) δ 9.43 (br, 1H), 8.77 (s, 1H), 7.80 (m, 1H), 7.63 (d, 1H), 7.44 (t, 1H), 7.38 (m, 2H), 7.28 (s, 1H), 7.20 (s, 1H), 6.31 (s, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.91 (s, 3H); LC-MS (ESI) m/z 505 (M+H)+.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][CH3:10])=[N:7][CH:8]=1.[CH2:11]([O:18][C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH2:21][CH2:22][CH2:23][CH:24]2[C:29]([NH:31][C:32]1[CH:33]=[N:34][C:35]([CH:38]([CH3:40])[CH3:39])=[CH:36][CH:37]=1)=[O:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([O:18][C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH2:21][CH2:22][CH2:23][CH:24]2[C:29]([N:31]([C:32]1[CH:33]=[N:34][C:35]([CH:38]([CH3:40])[CH3:39])=[CH:36][CH:37]=1)[CH2:2][C:3]1[CH:8]=[N:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1)=[O:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)c1ccc(NC(=O)C2CCCc3c(OCc4ccccc4)cccc32)cn1
Reactant: COc1ccc(CCl)cn1
Product: COc1ccc(CN(C(=O)C2CCCc3c(OCc4ccccc4)cccc32)c2ccc(C(C)C)nc2)cn1
Yield: 108.5 %

Procedure:
By the reaction and treatment in the same manner as in Example 132 using 5-chloromethyl-2-methoxypyridine (0.63 g) and 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.87 g) as starting materials, 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-N-[(6-methoxypyridin-3-yl)methyl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide (1.23 g) was obtained.
Reaction SMILES: COC1C=CC(C[NH:8][C:9]2[N:10]=[N:11][C:12]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[CH:13][C:14]=2[C:15]([F:18])([F:17])[F:16])=CC=1.OS(O)(=O)=O>>[F:18][C:15]([F:16])([F:17])[C:14]1[CH:13]=[C:12]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[N:11]=[N:10][C:9]=1[NH2:8]
Reactant: COc1ccc(CNc2nnc(-c3ccc(C(F)(F)F)cc3)cc2C(F)(F)F)cc1
Agent: O=S(=O)(O)O
Product: Nc1nnc(-c2ccc(C(F)(F)F)cc2)cc1C(F)(F)F
Temperature: 5 °C
Reaction time: 0.08 h

Procedure:
(4-Methoxy-benzyl)-[4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyridazin-3-yl]-amine (example C.26 step 8) (6.48 g, 15 mmol) was added portionwise at 5° C. to conc. H2SO4 (d 1.83, 17.0 mL, 303 mmol).The deep purple solution was stirred for 5 min at 5° C. then the cooling bath was removed and stirring was continued for further 60 min at 23° C. The mixture was poured onto ice, made alkaline with 32% NaOH-sol., saturated with solid NaCl and extracted with THF and TBME, dried the organic layer over MgSO4. Removal of the solvent in vacuum left the title compound as a light yellow solid (4.44 g, 95%), which was used without further purification. MS (ISP) 308.1 [(M+H)+]; mp 186–190° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:14]=2)[C@H:9]([NH2:20])[CH2:8][C@@H:7]1[CH2:21][CH3:22])=[O:5])[CH3:2].C(O)(=O)C.[F:27][C:28]([F:42])([F:41])[C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH:32]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[OH-].[K+]>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:17])([F:18])[F:19])=[CH:13][CH:14]=2)[C@H:9]([NH:20][CH2:32][C:31]2[CH:34]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:36]=[C:29]([C:28]([F:27])([F:41])[F:42])[CH:30]=2)[CH2:8][C@@H:7]1[CH2:21][CH3:22])=[O:5])[CH3:2]
Reactant: CCOC(=O)N1c2ccc(C(F)(F)F)cc2[C@H](N)C[C@@H]1CC
Reactant: O=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Product: CCOC(=O)N1c2ccc(C(F)(F)F)cc2[C@H](NCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C[C@@H]1CC
Temperature: 25 °C
Reaction time: 24 h
Yield: 91.5 %

Procedure:
A solution of cis-4-amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (Example 7D) (8.8 g, 27.8 mmol) was treated sequentially with acetic acid (5.0 g, 83.5 mmol), 3,5-bis-trifluoromethyl-benzaldehyde (6.74 g, 27.8 mmol), followed by sodium triacetoxyborohydride (29.5 g, 139.2 mmol). After stirring at room temperature for 24 h, the mixture was combined with 500 mL of 1M potassium hydroxide, and the aqueous layer was extracted with dichloromethane (2×200 mL). Th combined organic phases were dried over magnesium sulfate, filtered and concentrated in vacuo to afford the crude product, which was purified by silica gel chromatography using 5-10% ethyl acetate/hexanes as eluent to afford 13.8 g of the title product. 1H NMR (CDCl3) δ 0.85 (t, 3H), 1.27 (m, 4H), 1.45 (m, 2H), 1.67 (m, 1H), 2.66 (m, 1H), 3.56 (m, 1H), 4.1-4.3 (m, 4H), 4.42 (m, 1H), 7.49 (d, 1H, J=8.5 Hz), 7.52 (d, 1H, J=8.5 Hz), 7.76 (s, 1H), 7.79 (s, 1H), 7.91 (s, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:6]=[C:5]([CH3:7])[NH:4][N:3]=1.Cl[C:9]1[CH:10]=[CH:11][C:12]([N+:17]([O-:19])=[O:18])=[C:13]([O:15][CH3:16])[CH:14]=1>>[CH3:7][C:5]1[NH:4][N:3]=[C:2]([O:1][C:9]2[CH:10]=[CH:11][C:12]([N+:17]([O-:19])=[O:18])=[C:13]([O:15][CH3:16])[CH:14]=2)[CH:6]=1
Reactant: COc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: Cc1cc(O)n[nH]1
Product: COc1cc(Oc2cc(C)[nH]n2)ccc1[N+](=O)[O-]
Yield: 13.2 %

Procedure:
Reaction of 3-hydroxy-5-methylpyrazole with 5-chloro-2-nitroanisole was carried out in the same manner as Example 3, to give a yellow viscous substance of 5-methyl-3-(3-methoxy-4-nitrophenyloxy)pyrazole (yield: 13.2%). 1H-NMR (CDCl3, TMS, ppm): δ 2.34 (s, 3H), 3.93 (s, 3H), 5.74 (s, 1H), 6.70 (dd, J=2.4 and 9.1 Hz, 1H), 6.85 (d, J=2.4 Hz, 1H), 7.95 (d, J=9.1 Hz, 1H), 9.45 (br s, 1H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH:6](Cl)[C:7]2[CH:11]=[CH:10][S:9][CH:8]=2)=[CH:2]1.[OH:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20]/[CH:21]=[CH:22]/[CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N+:31]([O-:33])=[O:32])[CH2:16][CH2:15]1>>[S:1]1[CH:5]=[CH:4][C:3]([CH:6]([C:7]2[CH:11]=[CH:10][S:9][CH:8]=2)[O:13][CH:14]2[CH2:15][CH2:16][N:17]([CH2:20]/[CH:21]=[CH:22]/[CH2:23][O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N+:31]([O-:33])=[O:32])[CH2:18][CH2:19]2)=[CH:2]1
Reactant: O=[N+]([O-])c1ccccc1OC/C=C/CN1CCC(O)CC1
Reactant: ClC(c1ccsc1)c1ccsc1
Product: O=[N+]([O-])c1ccccc1OC/C=C/CN1CCC(OC(c2ccsc2)c2ccsc2)CC1

Procedure:
The procedure of Example 39 (a) was repeated except for using di(3-thienyl)methyl chloride and 4-hydroxy-1-[4-(2-nitrophenoxy)-2(E)-butenyl]piperidine instead of phenyl-2-thienylmethyl chloride and 4-hydroxy-1-[4-(2-nitrophenoxy)-2(E)-butenyl]piperidine to give oily 4-di(3-thienyl)methoxy-1-[4-(2-nitrophenoxy)-2(E)-butenyl]piperidine.
Reaction SMILES: [Si]([O:18][C:19]1[CH:58]=[CH:57][C:22]([O:23][CH2:24][C@@H:25]([OH:56])[CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:55]=[CH:54][C:33]([NH:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([NH:43][CH2:44][CH2:45][C:46]4[CH:51]=[CH:50][CH:49]=[C:48]([O:52][CH3:53])[CH:47]=4)=[O:42])[CH2:37][CH2:36]3)=[CH:32][CH:31]=2)=[CH:21][CH:20]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)(Cl)Cl.CO>[CH3:53][O:52][C:48]1[CH:47]=[C:46]([CH2:45][CH2:44][NH:43][C:41]([N:38]2[CH2:39][CH2:40][CH:35]([NH:34][C:33]3[CH:54]=[CH:55][C:30]([CH2:29][CH2:28][NH:27][CH2:26][C@H:25]([OH:56])[CH2:24][O:23][C:22]4[CH:21]=[CH:20][C:19]([OH:18])=[CH:58][CH:57]=4)=[CH:31][CH:32]=3)[CH2:36][CH2:37]2)=[O:42])[CH:51]=[CH:50][CH:49]=1
Reactant: COc1cccc(CCNC(=O)N2CCC(Nc3ccc(CCNC[C@H](O)COc4ccc(O[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)cc4)cc3)CC2)c1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1cccc(CCNC(=O)N2CCC(Nc3ccc(CCNC[C@H](O)COc4ccc(O)cc4)cc3)CC2)c1
Yield: 31.4 %

Procedure:
4-[4-(2-{[(2S)-3-(4-{[tert-Butyl(diphenyl)silyl]oxy}phenoxy)-2-hydroxy-propyl]amino}ethyl)anilino]-N-(3-methoxyphenethyl)-1-piperidinecarboxamide (0.110 g, 0.14 mmol) was reacted according to Procedure H to yield (eluant: 5:1 chloroform-methanol) the title compound (0.025 g, 0.044 mmol).
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[C:11]2[C:6]3=[C:7]([CH2:12][N:13](C(OC(C)(C)C)=O)[CH2:14][CH2:15][N:5]3[CH2:4][CH2:3]1)[CH:8]=[CH:9][CH:10]=2.FC(F)(F)C(O)=O>ClCCl>[CH3:1][C:2]1([CH3:23])[C:11]2[C:6]3=[C:7]([CH2:12][NH:13][CH2:14][CH2:15][N:5]3[CH2:4][CH2:3]1)[CH:8]=[CH:9][CH:10]=2
Reactant: CC(C)(C)OC(=O)N1CCN2CCC(C)(C)c3cccc(c32)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(C)CCN2CCNCc3cccc1c32
Temperature: 25 °C
Yield: 72.4 %

Procedure:
287 mg (0.9 mmol) of tert-butyl 8,8-dimethyl-3,4,7,8-tetrahydro-1H-[1,4]diazepino[6,7,1-ij]quinoline-2(6H)-carboxylate of step 1.3 were dissolved in 5 mL of dichloromethane and treated with 2.5 mL of trifluoroacetic acid. The mixture was stirred over night at room temperature and then extracted once with water (10 mL). The organic phase was then extracted twice with a diluted solution of sodium hydroxide (10 mL each), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica (eluent: 10-30% methanol in dichloromethane) to yield 141 mg of the title compound as a yellow oil.
Reaction SMILES: C(O[C:6](=O)[NH:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH3:6][NH:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1
Reactant: CC(C)(C)OC(=O)NCCN1CCOCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CNCCN1CCOCC1
Yield: 103.4 %

Procedure:
To a solution of Intermediate 45a (6.0 g, 24.6 mmol) in THF (123 mL) was added lithium aluminium hydride (2.33 g, 61.5 mmol) portionwise, then the mixture was stirred at reflux for 4 h. A further portion of lithium aluminium hydride (1.28 g, 33.6 mmol) was added to the cooled solution, then the mixture was stirred at reflux for a further 8 h. Water (3.75 mL) was added dropwise, followed by 4N aqueous NaOH (11.3 mL) and water (3.75 ml). The mixture was filtered, washed with diethyl ether, dried (MgSO4) and concentrated in vacuo to give the title compound as a yellow oil (3.67 g, 99%). 1H NMR (400 MHz, CDCl3): 2.40-2.52 (9H, m), 2.67 (2H, t, J 2.7), 3.70 (4H, t, J 4.5).
Reaction SMILES: [OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C.N>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O1CCCC1.N1C=CC=CC=1>[N+:8]([C:7]1[C:2](=[O:1])[N:3]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccnc1O
Reactant: OB(O)c1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: N
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=c1c([N+](=O)[O-])cccn1-c1ccccc1
Reaction time: 8 h
Yield: 61 %

Procedure:
5 g of 2-hydroxy-3-nitropyridine, 7.14 g of phenylboronic acid, 2.6 g of copper (II) acetate, 9.9 ml of triethylamine and 5.8 ml of pyridine were added to 100 ml of tetrahydrofuran, followed by stirring overnight. The reaction mixture was poured into aqueous ammonia, and extracted with ethyl acetate. The organic layer was washed with water, dried, and concentrated. The residue was suspended into ether, and collected by filtration, to give 4.71 g of the title compound.
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11].[ClH:13]>>[Cl:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11]
Reactant: Cl
Reactant: OCCCCCCCCCCO
Product: OCCCCCCCCCCCl

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: S([O-])([O-])=O.[Na+].[Na+].[CH3:7][O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[S:17](Cl)(=[O:19])=[O:18].[OH-].[Na+]>>[CH3:7][O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[S:17]([OH:19])=[O:18]
Reactant: COc1ccc(S(=O)(=O)Cl)c(OC)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Product: COc1ccc(S(=O)O)c(OC)c1
Reaction time: 3 h

Procedure:
To an aqueous solution containing 129 g (0.974 mole) of sodium sulfite were added in small amounts and with stirring 115 g (0.487 mole) of 2,4-dimethoxy benzenesulfonyl chloride. During this operation, the pH was kept alkaline by the addition of caustic soda. After standing for 3 h, the reaction medium was filtered. The filtrate was acidified with 2N sulfuric acid until the precipitation of the sulfinic acid.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH:21]([CH3:23])[N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]2)=[O:12].C(O)(C(F)(F)F)=O>ClCCl.C(OCC)(=O)C>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH:21]([CH3:23])[NH:20][CH2:19][CH2:18]2)=[O:12]
Reactant: CC1c2c(cccc2C(=O)Nc2nc3ccccc3s2)CCN1C(=O)OC(C)(C)C
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1NCCc2cccc(C(=O)Nc3nc4ccccc4s3)c21
Temperature: 30 °C
Reaction time: 2 h

Procedure:
A solution of EXAMPLE 163B (150 mg) in dichloromethane (10 mL) was treated with TFA (1 mL). The reaction mixture was stirred for 2 hours at 30° C. The reaction mixture was diluted with ethyl acetate (100 mL), washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromotography (silica gel, dichloromethane/methanol=10/1).