Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][CH3:12])=[N:6][CH:5]=1.[H-].[Na+].BrCC1C=CC=CC=1[CH:24]([SH:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][CH2:12][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[S:31][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[N:6][CH:5]=1
Reactant: CCNc1ccc(C(=O)OC)cn1
Reactant: SC(c1ccccc1)c1ccccc1CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(NCCCc2ccccc2SCc2ccccc2)nc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70 %

Procedure:
A solution of methyl-6-ethylaminonicotinate in (59 mg, 0.332 mmol) DMF (0.8 mL) was added to sodium hydride (12 mg, 0.293 mL) in DMF (0.8 mL) at 0° C. The reaction was stirred for 1 hour and a solution of 2-(2-bromomethylphenyl sulfanylmethyl) benzene 5 (81 mg, 0.276 mmol) in 80 μL of DMF was added. The reaction was allowed to warm to ambient temperature and stirred for 18 hours. The solution was quenched with water and extracted with EtOAc (7×). The organic layers were combined, washed with water and brine twice, dried over MgSO4 and evaporated to give a white solid that was recrystallized from EtOAc/hexane. The solid was purified with 5% EtOAc/hexane by chromatography to yield 350 mg (70%) of the named compound.
Reaction SMILES: C[Si](C)(C)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12](I)=[CH:11][C:10]=2F)=[C:5](F)[C:4]=1F.C([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)CC.OCC(C)(CO)C.O>CC(O)C.CC([O-])=O.CC([O-])=O.[Pd+2].CC(C)=O>[C:6]1([C:9]2[C:10]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:8][CH:3]=[CH:4][CH:5]=1
Reactant: CCCc1ccc(B(O)O)cc1
Reactant: C[Si](C)(C)c1ccc(-c2ccc(I)cc2F)c(F)c1F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(CO)CO
Solvent: O
Solvent: CC(C)O
Solvent: CC(C)=O
Product: c1ccc(-c2ccccc2-c2ccccc2)cc1
Yield: 89 %

Procedure:
A solution of (2 mmol) of 8, (2.2 mmol) of 4-propylphenylboronic acid, 250 mg (2.40 mmol) of neopentyl glycol, 1.53 g (4.84 mmol) of Ba(OH)2. 8 H2O, 1.35 ml (0.103 mmol, 5 mol %) of a 76 mM acetone solution of Pd(OAc)2 in 20 ml of 95% i-PrOH is stirred at 80° C. for 12 hours. The solvent is subsequently removed under reduced pressure. 5 ml of 2 M HCl are added to the residue, and the mixture is extracted with dichloromethane (3×5 ml). The combined organic phases are dried over MgSO4 and filtered through SiO2. The solvent is removed under reduced pressure, and the residue is converted into 10 (yield: 89%).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.ClS([N:15]=[C:16]=O)(=O)=O>C(#N)C>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:16]#[N:15])=[CH:5][NH:6]2
Reactant: Brc1cccc2[nH]ccc12
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CC#N
Product: N#Cc1c[nH]c2cccc(Br)c12
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a 0° C. solution of 4-bromoindole (5 g, 25.5 mmol) in acetonitrile (50 ml) was added dropwise chlorsulfonylisocyanate (2.37 ml, 27.3 mmol) over a 5 minute period. The reaction mixture was stirred at 0° C. for 2 hours, and TEA (3.77 ml, 27.0) was added dropwise over a 10 minute period. The reaction mixture was allowed reach room temperature overnight, poured into ice/water mixture (200 ml), and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered, concentrated, and purified by flash chromatography to afford 4-bromo-1H-indole-3-carbonitrile LVII as an off-white solid (4.9 g, 87% yield).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][OH:42])=[O:38])([CH3:35])([CH3:34])[CH3:33].[Cl:43][C:44]1[CH:45]=[CH:46][C:47]2[O:51][N:50]=[C:49](O)[C:48]=2[CH:53]=1>O1CCCC1>[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][O:42][C:49]1[C:48]2[CH:53]=[C:44]([Cl:43])[CH:45]=[CH:46][C:47]=2[O:51][N:50]=1)=[O:38])([CH3:35])([CH3:34])[CH3:33]
Reactant: CC(C)(C)OC(=O)NCCO
Reactant: Oc1noc2ccc(Cl)cc12
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCOc1noc2ccc(Cl)cc12
Yield: 75.2 %

Procedure:
To a solution of triphenylphosphine (0.87 g) in tetrahydrofuran (10 ml), was added diethyl azodicarboxylate (0.57 g) dropwise with stirring under ice cooling. The reaction mixture was stirred at the same temperature for 10 minutes. Then, 2-(N-t-butoxycarbonylamino)ethanol (0.48 g) and 5-chloro-3-hydroxy-1,2-benzisoxazole (0.51 g) were added to the reaction mixture successively and stirred under ice cooling for 10 minutes and at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography with cyclohexane/ethyl acetate (4/1) as an eluent. The title compound (0.70 g) was obtained as colorless crystals by crystallization from isopropylether.
Reaction SMILES: NC1(C(NC2C=CC(C=CC([O-])=O)=CC=2)=O)CCCC1.CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1.[NH2:39][C:40]1[CH:45]=[CH:44][C:43](/[CH:46]=[CH:47]/[C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:42][CH:41]=1.[C:53]([O:57][C:58]([NH:60][C:61]1([C:66](O)=[O:67])[CH2:65][CH2:64][CH2:63][CH2:62]1)=[O:59])([CH3:56])([CH3:55])[CH3:54]>C1COCC1>[C:53]([O:57][C:58]([NH:60][C:61]1([C:66]([NH:39][C:40]2[CH:41]=[CH:42][C:43](/[CH:46]=[CH:47]/[C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:44][CH:45]=2)=[O:67])[CH2:65][CH2:64][CH2:63][CH2:62]1)=[O:59])([CH3:56])([CH3:55])[CH3:54]
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CCCC1
Reactant: CCOC(=O)/C=C/c1ccc(N)cc1
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Agent: NC1(C(=O)Nc2ccc(C=CC(=O)[O-])cc2)CCCC1
Solvent: C1CCOC1
Product: CCOC(=O)/C=C/c1ccc(NC(=O)C2(NC(=O)OC(C)(C)C)CCCC2)cc1
Yield: 41 %

Procedure:
(E)-ethyl (3-(4-(1-aminocyclopentanecarboxamido)phenyl)acrylate. EEDQ (593 mg, 2.4 mmol) was added to a solution of (E)-ethyl 3-(4-aminophenyl)acrylate (417 mg, 2.18 mmol) and 1-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid (500 mg, 2.18 mmol) in THF (6 mL). The solution was stirred at reflux for 3-4 hours. The mixture was concentrated and the residue partitioned between dichloromethane and water. The organic layer was washed sequentially with dilute HCl, water, and brine. The solution was dried over Na2SO4 and filtered. Dilution of the filtrate with hexanes resulted in the crystallization of (E)-ethyl 3-(4-(1-(tert-butoxycarbonylamino)cyclopentanecarboxamido)phenyl)acrylate as a pale yellow solid (360 mg, 37% yield). ESI-MS m/z 403 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:15]([O:17][C:18]([C:20]1([CH2:35]I)[CH2:24][CH2:23][N:22]([C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[O:32][CH3:33])[CH2:21]1)=[O:19])[CH3:16]>>[CH2:15]([O:17][C:18]([C:20]1([CH2:35][O:14][C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[CH2:24][CH2:23][N:22]([C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[O:32][CH3:33])[CH2:21]1)=[O:19])[CH3:16]
Reactant: Oc1ccc(-c2ccc(F)cc2)cc1
Reactant: CCOC(=O)C1(CI)CCN(C(=O)c2ccccc2OC)C1
Product: CCOC(=O)C1(COc2ccc(-c3ccc(F)cc3)cc2)CCN(C(=O)c2ccccc2OC)C1

Procedure:
The title compound was prepared according to the method described for Preparation 29 using 4′-fluoro-biphenyl-4-ol and 3-iodomethyl-1-(2-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (Preparation 15) to afford the racemate as a white solid (178 mg, 76%)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH2:13]O)[C:10]([NH:21][C:22](=[S:32])[NH:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(N(C)C)=C(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]2[C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)([N:21]=[C:22]([NH:23][C:24](=[O:31])[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[S:32][CH2:13]2)[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CC(CO)C(NC(=S)NC(=O)c2ccccc2)(c2ccccc2)C1
Agent: CC(C)=C(Cl)N(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC2CSC(NC(=O)c3ccccc3)=NC2(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of tert-butyl-3-(benzoylcarbamothioylamino)-4-(hydroxymethyl)-3-phenyl-pyrrolidine-1-carboxylate (1.6 g, 3.5 mmol) in dichloromethane (87 mL) at 0° C. is treated with 1-chloro-N,N,2-trimethylpropenylamine (0.94 mg, 7.0 mmol). The mixture is allowed to warm to room temperature and stirred for 4 hours under nitrogen. Saturated sodium bicarbonate is added and the solution extracted with dichloromethane. The combined organic layers are dried over sodium sulfate, filtered, and concentrated to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1) to give the title compound, which is used without further purification (1.6 g, 104%). ES/MS (m/e): 438 (M+H).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1/[CH:11]=N/C(C(C)C)C(C)C)[CH3:2].[OH-:20].[Na+]>C1COCC1.Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]=[O:20])[CH3:2]
Reactant: [OH-]
Reactant: CCc1cccc(OC)c1/C=N/C(C(C)C)C(C)C
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1cccc(OC)c1C=O
Temperature: 25 °C

Procedure:
A solution of 1.0 g (E)-[1-(2-ethyl-6-methoxy-phenyl)-methylidene]-(1-isopropyl-2-methyl-propyl)-amine in 1 ml THF and 0.19 ml 4N HCl was heated to reflux for 1 hour then cooled to ambient temperature and poured onto a 1N aqueous NaOH solution. The aqueous phase was extracted with ethyl acetate, the combined extracts washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by flash-chromatography on silica gel with a heptane/ethyl acetate gradient as eluent: 0.50 g 2-ethyl-6-methoxy-benzaldehyde as colourless oil: MS (EI): 261.2 (M+.), 218.2 ((M-((CH3)2CH))+., 100%).
Reaction SMILES: C[O:2][C:3]([C@@:5]1([CH3:9])[CH2:8][CH2:7][NH:6]1)=[O:4].[OH-].[Na+].[Br:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1.C(O)(=O)C>O>[Br:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([N:6]2[CH2:7][CH2:8][C@:5]2([CH3:9])[C:3]([OH:2])=[O:4])=[O:18])=[CH:15][CH:14]=1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: COC(=O)[C@@]1(C)CCN1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: C[C@]1(C(=O)O)CCN1C(=O)c1ccc(Br)cc1
Temperature: 20 °C
Reaction time: 4 h

Procedure:
To a solution of (R)-2-methyl-azetidine-2-carboxylic acid methyl ester (1 eq.) in water were added aqueous NaOH (1M) (3 eq.) then 4-bromo-benzoyl-chloride (1 eq.) dropwise. The reaction was stirred for 4 h at 20° C. The reaction was neutralised with acetic acid. The solvent was partially removed under reduced pressure and the crude was extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM/MeOH/AcOEt/AcOH/iPr2O: 95/5/98/2/300) to afford (R)-1-(4-bromo-benzoyl)-2-methyl-azetidine-2-carboxylic acid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH:10]=[O:11])[CH:9]=1)[C:5]#[N:6].B(F)(F)F.[C:16]([K])([CH3:18])=[CH2:17].C(N(CC)CC)C>CC(O)C.O.CCOCC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:10]([C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([C:16]([CH3:18])=[CH2:17])[CH:9]=1)[C:5]#[N:6])=[O:11]
Reactant: N#Cc1cc(Br)cc(C=O)c1
Reactant: C=C(C)[K]
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: FB(F)F
Solvent: CCN(CC)CC
Solvent: CC(C)O
Solvent: O
Product: C=C(C)c1cc(C#N)cc(C=O)c1

Procedure:
To 3-bromo-5-formylbenzonitrile (420 mg, 2 mmol), isopropenyl potassium trifluoroborate (296 mg, 2 mmol) and triethyl amine (0.42 ml) in 2-propanol and water (20 ml) in 2:1 ratio, PdCl2(dppf) (65 mg, 0.08 mmol) was added and the reaction mixture was refluxed for 5 h. Then the reaction mixture was cooled, diluted with ether, washed with water, brine and dried. Crude residue was column chromatographed (60% ethylacetate: 40% hexane) to yield a white solid of 3-formyl-5-(prop-1-en-2-yl)benzonitrile.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]([OH:15])[CH2:4][N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1.CCN(CC)CC.[Cl:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([C:30](Cl)=[O:31])[CH:25]=1>C(Cl)Cl>[Cl:23][C:24]1[N:29]=[CH:28][N:27]=[C:26]([C:30]([NH:1][CH2:2][C@H:3]([OH:15])[CH2:4][N:5]2[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6]2)=[O:31])[CH:25]=1
Reactant: NC[C@H](O)CN1CCc2ccccc2C1
Reactant: O=C(Cl)c1cc(Cl)ncn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NC[C@H](O)CN1CCc2ccccc2C1)c1cc(Cl)ncn1
Yield: 59.8 %

Procedure:
To a stirred and cooled (0° C.) solution of (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (7.15 g, 34.7 mmol) and Et3N (14.0 g, 138.8 mmol) in DCM (100 mL) was added 6-chloropyrimidine-4-carbonyl chloride (5.5 g, 34.7 mmol). After addition, the resulting mixture was stirred at 25° C. for 16 h, at which time LCMS showed the completion of the reaction. The solvent was evaporated and the residue purified by flash chromatography to give the (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide (7.2 g, yield: 60%). LCMS (m/z): 347.0 [M+H]+
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][N:14]=2)=[N:11][N:10]=[C:9]1[C:23]([F:40])=[C:24]([F:39])[C:25]([NH:27][NH:28][C:29](=[O:38])[C:30]1[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=1)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][N:14]=2)=[N:11][N:10]=[C:9]1[C:23]([F:40])=[C:24]([C:25]1[O:38][C:29]([C:30]2[CH:31]=[CH:32][C:33]([C:36]#[N:37])=[CH:34][CH:35]=2)=[N:28][N:27]=1)[F:39]
Reactant: CS(=O)(=O)c1ccc(-c2nnc(C(F)=C(F)C(=O)NNC(=O)c3ccc(C#N)cc3)n2-c2ccccc2Cl)nc1
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)c1ccc(-c2nnc(C(F)=C(F)c3nnc(-c4ccc(C#N)cc4)o3)n2-c2ccccc2Cl)nc1
Reaction time: 2 h

Procedure:
4-Cyano-benzoic acid N′-{3-[4-(2-chloro-phenyl)-5-(5-methanesulfonyl-pyridin-2-yl)-4H-[1,2,4]triazol-3-yl]-2,3-difluoro-acryloyl}-hydrazide 11 was dissolved into dichloromethane (10 mL) and triphenylphosphine (0.27 g, 1.02 mmol), carbon tetrabromide (0.34 g, 1.02 mmol) and triethylamine (0.18 mL, 1.30 mmol) were added. The reaction mixture was kept at ambient temperature for 2 h. The final compound was purified by column chromatography (eluting with methanol/DCM 1/99-5/95) to give 4-(5-{2-[4-(2-chloro-phenyl)-5-(5-methanesulfonyl-pyridin-2-yl)-4H-[1,2,4]triazol-3-yl]-1,2-difluoro-vinyl}-[1,3,4]oxadiazol-2-yl)-benzonitrile as a solid. Yield: 0.05 g, 13%.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]2[N:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:11]=1)[CH3:9])(C)(C)C.Cl>O1CCOCC1>[N:18]1[CH:19]=[CH:20][CH:21]=[N:22][C:17]=1[O:16][C:12]1[CH:11]=[C:10]([C@@H:8]([NH2:7])[CH3:9])[CH:15]=[CH:14][CH:13]=1
Reactant: C[C@H](NC(=O)OC(C)(C)C)c1cccc(Oc2ncccn2)c1
Agent: Cl
Solvent: C1COCCO1
Product: C[C@H](N)c1cccc(Oc2ncccn2)c1
Temperature: 50 °C
Reaction time: 5 h
Yield: 79.6 %

Procedure:
A mixture of (S)-{1-[3-(pyrimidin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.33 g, 4.2 mmol), dioxane (20 mL) and HCl (4.2 mL, 4N) was stirred at 50° C. for 5 h and concentrated in vacuo. CH2Cl2 (50 mL) was added and the reaction mixture was basified with NaOH (5N) followed by extraction with CH2Cl2 (2×50 mL). The organic layer was washed with brine (50 mL), dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated to give the title compound (0.72 g, 79% yield).
Reaction SMILES: O.NN.O=C1C2C(=CC=CC=2)C(=O)[N:6]1[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:36]=[CH:35][C:22]2[N:23]([CH2:33][CH3:34])[C:24](=[O:32])[C:25]([CH3:31])([CH3:30])[C:26](=[O:29])[N:27]([CH3:28])[C:21]=2[CH:20]=1.[OH-].[Na+]>CO>[NH2:6][CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:36]=[CH:35][C:22]2[N:23]([CH2:33][CH3:34])[C:24](=[O:32])[C:25]([CH3:30])([CH3:31])[C:26](=[O:29])[N:27]([CH3:28])[C:21]=2[CH:20]=1
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CCCCN3C(=O)c4ccccc4C3=O)ccc21
Agent: NN
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(CCCCN)ccc21
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 87.7 %

Procedure:
Hydrazine hydrate (0.5 ml) was added to a methanol solution (60 ml) of 7-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine 2,4-dione (1.93 g). The mixture was stirred for 5.5 hours while heated under reflux. After cooled to room temperature, a 1N-sodium hydroxide aqueous solution was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and condensed under reduced pressure to give the title compound (1.2 g) as a yellow solid.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]#[N:20])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH3:4].[CH2:21]([C:23]1([CH2:31][CH3:32])[CH2:29][CH2:28][C:27](=[O:30])[O:26][C:24]1=[O:25])[CH3:22]>O1CCOCC1>[CH2:1]([N:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]#[N:20])=[CH:9][CH:8]=1)[C:27](=[O:30])[CH2:28][CH2:29][C:23]([C:24]([OH:26])=[O:25])([CH2:31][CH3:32])[CH2:21][CH3:22])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCNCc1ccc(-c2ccccc2C#N)cc1
Reactant: CCC1(CC)CCC(=O)OC1=O
Solvent: C1COCCO1
Product: CCCCN(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)CCC(CC)(CC)C(=O)O

Procedure:
The starting material can be prepared, for example, as follows: A solution of 3.2 g of N-butyl-N-(2'-cyanobiphenyl-4-ylmethyl)-amine and 3.09 g of 2,2-diethylglutaric acid anhydride in 50 ml of dioxane is heated at 115° (bath temperature) for 6 hours. After concentration of the reaction mixture by evaporation, the residue is taken up in 100 ml of ethyl acetate, and the ethyl acetate phase is washed twice with 50 ml of water each time, dried over Na2SO4 and concentrated by evaporation in vacuo. Chromatography of the evaporation residue on silica gel 60 (40-63 μm) using CH2Cl2 /CH3OH (95:5) as eluant yields pure 4-carboxy-4-ethyl-hexanoic acid N-butyl-N-(2'-cyanobiphenyl-4-ylmethyl)-amide that has an Rf value of 0.72 [CH2Cl2 /CH3OH (4:1)].
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([CH2:9][CH2:10][CH2:11]C)[NH:5][C:6]=1[C:7]#[N:8].CO[C:15]1([C:22](OC)=O)[CH2:19][CH2:18][CH:17]([O:20][CH3:21])[O:16]1>>[C:7]([C:6]1[NH:5][C:4]([CH2:9][CH2:10][CH3:11])=[N:3][C:2]=1[N:1]1[CH:22]=[CH:15][CH:19]=[C:18]1[C:17]([O:20][CH3:21])=[O:16])#[N:8]
Reactant: CCCCc1nc(N)c(C#N)[nH]1
Reactant: COC(=O)C1(OC)CCC(OC)O1
Product: CCCc1nc(-n2cccc2C(=O)OC)c(C#N)[nH]1

Procedure:
Using the method of Example 5, 4-amino-5-cyano-2-propylimidazole (Example 7) was reacted with methyl 2,5-dimethoxy-tetrahydrofuran-2-carboxylate to afford the title compound. 1H-NMR 9.4 (br, 2H), 7.3 (m, 1H), 7.2 (m, 1 H), 6.4 (t, 1H), 3.8 (s, 3H), 2.7 (t, 2H), 1.8 (m, 2H), 1.0 (t, 3H).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[C:6]1([C@@H:4]2[CH2:5][C@H:3]2[CH:2]=[O:1])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: OC[C@@H]1C[C@H]1c1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: ClC(Cl)Cl
Product: O=C[C@@H]1C[C@H]1c1ccccc1
Yield: 50.7 %

Procedure:
104 mg of the alcohol was dissolved in 5 ml of chloroform and stirred with 445 mg of the Dess-Martin reagent (periodinane) at room temperature for 30 minutes. The reaction solution was poured into a mixture of saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium thiosulfate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography [hexane/ethyl acetate=10/1] to give 52 mg of the title compound as a colorless oily substance.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:18](=[O:29])[CH2:19][CH2:20][C:21]3[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=3[Cl:28])[C:10]([N+:15]([O-])=O)=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)(=O)C.[Fe]>[NH2:15][C:10]1[C:9]([C:18](=[O:29])[CH2:19][CH2:20][C:21]2[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=2[Cl:28])=[CH:8][C:7]([O:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[C:12]([O:13][CH3:14])[CH:11]=1
Reactant: COc1cc([N+](=O)[O-])c(C(=O)CCc2c(Cl)cncc2Cl)cc1OC1CCCC1
Agent: [Fe]
Solvent: CC(=O)O
Product: COc1cc(N)c(C(=O)CCc2c(Cl)cncc2Cl)cc1OC1CCCC1
Yield: 75 %

Procedure:
Operating analogously to example 31 using 1-(3-cyclopentyloxy-4-methoxy-6-nitro-phenyl)-2-(3,5-dichloro-pyridin-4-yl-methyl)-ethanone (26.75 g, 63 moles), obtained as described in example 38, and iron dust (21.1 g, 378 moles) in acetic acid (120 ml) 18.7 g of the title product were obtained (yield: 75%).
Reaction SMILES: [CH3:1][C:2]1([CH3:31])[CH:4]([C:5]([O:7][CH:8]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[C:9]#[N:10])=[O:6])[CH:3]1/[CH:24]=[C:25](\[Cl:30])/[C:26]([F:29])([F:28])[F:27].C(NC(C)C)(C)C.S(=O)(=O)(O)O>C(O)(C)C.CCCCCC.O>[CH3:1][C:2]1([CH3:31])[C@H:4]([C:5]([O:7][C@@H:8]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:16]=2)[C:9]#[N:10])=[O:6])[C@@H:3]1/[CH:24]=[C:25](\[Cl:30])/[C:26]([F:27])([F:29])[F:28]
Reactant: CC1(C)C(/C=C(\Cl)C(F)(F)F)C1C(=O)OC(C#N)c1cccc(Oc2ccccc2)c1
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: CCCCCC
Solvent: O
Product: CC1(C)[C@H](C(=O)O[C@H](C#N)c2cccc(Oc3ccccc3)c2)[C@@H]1/C=C(\Cl)C(F)(F)F
Temperature: -5 °C
Reaction time: 65 h

Procedure:
A 600 ml vacuum jacketed non-baffled split-neck reaction flask was equipped with a dual blade agitator. To the reactor, already containing a slurry of epimerisation mass as seed from a previous experiment (already˜⅔rds full), was charged the 1 R cyhalothrin (II) (166.3 g) in a mixture of isopropanol (99.9 g), water (3.09 g) and di-isopropylamine (5.22 g). The reaction mass was agitated at 100 rpm and −5° C. for 65 hr, before removing 251 g of reaction mass and transferring it to a 1 liter split-neck reaction vessel in an ice/water bath. To the 1 liter reaction vessel was charged hexane (60 ml) and sulphuric acid (47 ml of 50% w/w), and the resultant thick paste was agitated for 0.5 hr before diluting with hexane (350 ml) and water (350 ml). The mixture was heated to 55° C. for 30 min, then transferred to a separating funnel and the lower aqueous phase was separated off. The hexane solution was concentrated under reduced pressure to give the desired product as a viscous red/brown oil which solidified upon standing to give an off-white solid. The product weighed 151.2 g giving an estimated yield of 97% as gamma-cyhalothrin and a diastereomer ratio of 95:5.