Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].O1CCOCC1.C(ON=O)CC(C)C.C(N(CC)CC)C.[NH:23](C(OCC1C=CC=CC=1)=O)[C@H:24]([C:27]([NH:29][C@H:30]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][C:32](=[O:34])[NH2:33])=[O:28])[CH2:25][OH:26]>CN(C)C=O>[ClH:1].[NH2:23][C@H:24]([C:27]([NH:29][C@H:30]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][C:32](=[O:34])[NH2:33])=[O:28])[CH2:25][OH:26]
Reactant: CC(C)(C)OC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)OCc1ccccc1
Agent: CC(C)CCON=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO
Temperature: -70 °C
Reaction time: 0.58 h

Procedure:
pGlu-Ala-Lys(Xys)-Ser(Bzl)-Gln-Gly-Gly-NHNH2 (140 mg) is dissolved in dimethylformamide (5 ml). While the solution is cooled to -70° C., 6.51 N HCl-dioxane (0.05 ml) and isoamylnitrite (0.02 ml) are added. The mixture is stirred at -30° C. for 35 minutes and cooled again to -70° C., followed by addition of triethylamine (0.05 ml). HCl-H-Ser-Asn-OBut which is prepared by reducing Z-Ser-Asn-OBut (123 mg) is dissolved in dimethylformamide (2 ml) and this solution is added to the mixture, followed by addition of triethylamine (0.05 ml). The mixture is stirred between -15° C. and 5° C. for 30 hours. Insolubles are filtered off and the filtrate is distilled to evaporate the solvent. Ether is added and resulting powder is collected by filtration. Into a mixture of the powder and anisole contained in a cylinder of teflon resin, is introduced hydrogen fluoride (5 ml) and the mixture is stirred at 0° C. for one hour. Immediately the hydrogen fluoride is distilled off under reduced pressure and the residue is extracted twice-with water (10 ml each). The aqueous extract is washed three times with ether (3 ml each) and passed through a column (1.5×10 cm) of Amberlite IRA-410 (acetate form).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([OH:11])=[CH:4][CH:3]=1.[CH2:12]([O:14][C:15]([C:17]1[C:18]2[CH2:26][CH2:25][CH2:24][CH2:23][C:19]=2[S:20][C:21]=1[NH2:22])=[O:16])[CH3:13]>>[CH2:12]([O:14][C:15]([C:17]1[C:18]2[CH2:26][CH2:25][CH2:24][CH2:23][C:19]=2[S:20][C:21]=1[NH:22][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[OH:11])=[O:16])[CH3:13]
Reactant: O=C(O)c1cc(Cl)ccc1O
Reactant: CCOC(=O)c1c(N)sc2c1CCCC2
Product: CCOC(=O)c1c(NC(=O)c2cc(Cl)ccc2O)sc2c1CCCC2
Yield: 49.6 %

Procedure:
Using 5-chlorosalicylic acid and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester as the raw materials, the same operation as the example 16 gave the title compound.
Reaction SMILES: [N:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[CH:5]=[CH:4][CH:3]=[CH:2]1.C(=O)(O)[O-].[Na+].Cl[C:19]([O:21][CH2:22][CH3:23])=[O:20]>ClCCl>[CH2:22]([O:21][C:19](=[O:20])[N:6]([C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1)[N:1]1[CH:2]=[CH:3][CH:4]=[CH:5]1)[CH3:23]
Reactant: CCOC(=O)Cl
Reactant: c1ccn(Nc2ccncc2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)N(c1ccncc1)n1cccc1

Procedure:
To a solution containing 9 g of N-(1H-pyrrol-1-yl)-4-pyridinamine and 15 g of sodium bicarbonate in 350 ml of dichloromethane was added a solution containing 6.7 g of ethyl chloroformate in 50 ml of dichloromethane.
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[CH:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:20][C:21]1[CH:26]=[C:25]([N:27]=[O:28])[CH:24]=[C:23]([CH3:29])[C:22]=1[OH:30]>ClCCl>[OH:28][N:27]([C:25]1[CH:24]=[C:23]([CH3:29])[C:22]([OH:30])=[C:21]([CH3:20])[CH:26]=1)[C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Cc1cc(N=O)cc(C)c1O
Reactant: O=Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: Cc1cc(N(O)C(=O)c2ccccc2)cc(C)c1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
DBU (15 mg, 0.1 mmol) was added under argon to a solution of benzaldehyde (106 mg, 1 mmol), 2,6-dimethyl-4-nitrosophenol (151 mg, 1 mmol) and catalyst (36.4 mg, 0.1 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 60 min. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography using hexane and ethyl acetate as the eluents.
Reaction SMILES: [F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2.Br[CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=1[F:39].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:39][C:33]1[C:34]([F:38])=[CH:35][CH:36]=[CH:37][C:32]=1[O:31][CH2:30][CH2:29][N:18]1[CH2:19][CH2:20][C:15]([CH2:14][CH2:13][CH2:12][C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([O:26][CH3:27])[CH:9]=3)[N:4]=[CH:3][C:2]=2[F:1])([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16][CH2:17]1
Reactant: Fc1cccc(OCCBr)c1F
Reactant: CCOC(=O)C1(CCCc2c(F)cnc3ccc(OC)cc23)CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C1(CCCc2c(F)cnc3ccc(OC)cc23)CCN(CCOc2cccc(F)c2F)CC1
Temperature: 70 °C
Reaction time: 18 h
Yield: 75.9 %

Procedure:
A mixture of 0.4 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.3 g of 1-(2-bromoethoxy)-2,3-difluorobenzene, 0.181 g of potassium iodide and 0.74 g of potassium carbonate in 15 cm3 of acetonitrile was stirred for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a cartridge of silica gel (Bond Elut; particle size 70-200μ; mass 12 g), eluting with a mixture of ethyl acetate/40-60° C. petroleum ether (8/2 by volume). The fractions containing the product were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.43 g of ethyl 1-[2-(2,3-difluorophenoxy)ethyl]-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH:15]([F:17])[F:16])=[CH:12][CH:11]=[C:10]([CH2:18][C:19]3[CH:20]=[CH:21][C:22](F)=[N:23][CH:24]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH3:27][NH:28][CH2:29][C:30]([NH2:32])=[O:31].N12CCCN=C1CCCCC2>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH:15]([F:16])[F:17])=[CH:12][CH:11]=[C:10]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([N:28]([CH3:27])[CH2:29][C:30]([NH2:32])=[O:31])=[N:23][CH:24]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CNCC(N)=O
Reactant: Fc1ccc(Cc2ccc(OC(F)F)c(-c3cccc(Cl)c3)c2)cn1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CN(CC(N)=O)c1ccc(Cc2ccc(OC(F)F)c(-c3cccc(Cl)c3)c2)cn1
Temperature: 160 °C
Yield: 3 %

Procedure:
In an 8 mL vial equipped with a stir bar was placed 5-(3′-Chloro-6-difluoromethoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (I-153, 210 mg, 0.577 mmol), 2-methylamino-acetamide hydrochloride (216 mg, 1.73 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (488 uL, 3.46 mmol). The mixture was heated to 160° C. for 3 hours and then diluted with dichloromethane (5 mL). The organic portion was washed with 0.5M HCl (3 mL) and the aqueous washes were combined and extracted with dichloromethane (2×3 mL). The organic portions were combined, washed with brine (4 mL), dried (MgSO4) and concentrated. The crude material was purified by Teledyne CombiFlash system utilizing a 12 g RediSepRf silica gel cartridge and a gradient elution of 0-30% methanol/dichloromethane, followed by preparative TLC (20×20 cm, 1000 microns) using 5% methanol/dichloromethane as the eluent to produce 8 mg of P-621?? as a dark brown semi-solid in 3% yield. 1H NMR (400 MHz, DMSO-d6) δ 2.98 (s, 3H), 3.83 (s, 2H), 4.03 (s, 2H), 6.53 (d, J=9 Hz, 1H), 7.10 (t, J=74 Hz, 1H), 7.21 (d, J=8 Hz, 1H), 7.30 (dd, J=8, 2 Hz, 1H), 7.36 (d, J=2 Hz, 1H), 7.40-7.50 (m, 5H), 8.01 (d, J=2 Hz, 1H) ppm. MS (APCI+): 432.1 (M+1). LC/MS: 86%.
Reaction SMILES: C1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH:11]=[CH:12]C=O)=CN=1.[NH2:15][C:16]1[S:17][C:18]2[CH2:19][CH2:20][NH:21][CH2:22][CH2:23][C:24]=2[N:25]=1.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[NH2:15][C:16]1[S:17][C:18]2[CH2:19][CH2:20][N:21]([CH2:12][C:11]#[C:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH2:22][CH2:23][C:24]=2[N:25]=1
Reactant: O=CC=Cc1cncc2ccccc12
Reactant: Nc1nc2c(s1)CCNCC2
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: Nc1nc2c(s1)CCN(CC#Cc1ccccc1)CC2

Procedure:
Prepared from 3-(4-isoquinolinyl)acrolein and 2-amino-4,5,7,8-tetrahydro-6H-thiazolo[5,4-d]azepine by reductive amination with sodium cyanoborohydride (in methanol in the presence of I equivalent of glacial acetic acid). The crude product is purified by column chromatography on silica gel (acetone/methanol/conc. ammonia =50:12:0.5). At first the title compound (A) is eluted. Yield: 4% of theory, Melting point: 205°-208° C. (ether).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([N:25]([CH3:31])[N:26]=[N:27][CH2:28][CH2:29]O)([O:22][CH2:23][CH3:24])=[O:21].C(Cl)(Cl)(Cl)[Cl:33]>CCCCC>[C:20]([N:25]([CH3:31])[N:26]=[N:27][CH2:28][CH2:29][Cl:33])([O:22][CH2:23][CH3:24])=[O:21]
Reactant: ClC(Cl)(Cl)Cl
Reactant: CCOC(=O)N(C)N=NCCO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCC
Product: CCOC(=O)N(C)N=NCCCl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
6a. A solution of triphenylphosphine (2.83 g, 1.08×10-2 mol) and 3-carboethoxy-1-(2-hydroxyethyl)-3-methyltriazene, 5a. (1.89 g, 1.08×10-2 mol) in 25 mL of carbon tetrachloride (dried over 3A molecular sieves) was refluxed overnight under nitrogen. The reaction mixture was cooled to room temperature and diluted with pentane (100 mL). After standing at 10° C. for four hours, the reaction mixture was filtered through a pad of Celite to remove precipitated triphenylphosphine oxide. The filtrate was concentrated on a rotary evaporator at 22° C., redissolved in a minimum amount of ether and chromatographed on a column of 40 g of Silica Gel 60 packed in 1:10 ether-pentane and eluted with 200 mL each of 10%, 20% and 30% ether in pentane. The first 200 mL of eluent contained 1.4 g of a yellow oil. Distillation of that oil at reduced pressure with a short path distillation apparatus produced 1.22 g (6:30×10-3 mol, 58.3%) of the desired compound, 3-carboethoxy-(2-chloroethyl)-3-methyltriazene, 6a:bp 60°-62° C. (0.003 mm); IR (CCl4) 2990, 2970, 1730, 1155, 990 cm10-1 ; UV (CH3CN) λ max 2333 (log ε 4.19); 1H NMR 9CDCl3, Me4Si) δ 1.39 (0-CH2CH3,t,J=7 Hz), 3.28 (NCH3,s), 3.88 (Cl-CH2,t,J=6 Hz), 4.12 (CH2CH-N.t,J=6Hz), 4.39 (0--CH2CH3,q,J=7 Hz); proton decoupled 13C NMR (CDCl3, Me4Si) δ 14.47 (0--CH2CH3), 29.76 (N--CH3), 41.92 (Cl--CH2), 62.50 (CH2 --N), 63.17 (0--CH2CH3), 154.27 (C50 0); (1H and 13C NMR assignments made via 13C -APT and 2D-heteronuclear correlated spectrum (2D-COSY) experiments); exact mass calcd m/z for C6H12N23O2Cl 193.0618, found 193.0629 (by EI).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7](=[S:9])[NH2:8].N1C=CC=CC=1.Br[CH:17]([CH:20]=O)[CH:18]=[O:19]>O1CCCC1.CS(C)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[S:9][C:17]([CH:18]=[O:19])=[CH:20][N:8]=1
Reactant: NC(=S)c1ccccn1
Reactant: O=CC(Br)C=O
Solvent: CS(C)=O
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: O=Cc1cnc(-c2ccccn2)s1
Yield: 38.7 %

Procedure:
Pyridine-2-carbothioamide (4.5 g) was dissolved in tetrahydrofuran (40 mL). Pyridine (7.9 mL) was added and the reaction was heated to reflux. 2-Bromomalonaldehyde (7.2 g) was added in dimethylsulfoxide (15 mL) dropwise over 10 minutes and the reaction was heated for 3 hours. The reaction was concentrated in vacuo and partitioned between ethyl acetate and sodium hydrogen carbonate aqueous solution. The aqueous layer was back extracted and the combined organic phase was washed with brine and concentrated. The crude reaction was purified by silica gel column chromatography using an eluant of 2% to 4% acetone/dichloromethane to obtain the title compound (2.4 g) with the following physical data.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH:16]=[C:15]([N:17]([CH3:19])[CH3:18])[S:14][C:13]=2[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[F:31])[C:25](Cl)=[O:26]>>[F:21][C:22]1[CH:23]=[C:24]([C:25]([C:16]2[C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:20][C:13]=3[S:14][C:15]=2[N:17]([CH3:18])[CH3:19])=[O:26])[CH:28]=[CH:29][C:30]=1[F:31]
Reactant: O=C(Cl)c1ccc(F)c(F)c1
Reactant: CN(C)c1cc2ccc(OCc3ccccc3)cc2s1
Product: CN(C)c1sc2cc(OCc3ccccc3)ccc2c1C(=O)c1ccc(F)c(F)c1
Yield: 95 %

Procedure:
The title compound (oil) was prepared in 95% yield from 6-benzyloxy-2-(dimethylamino)benzo[b]thiophene and 3,4-difluorobenzoyl chloride by essentially following the procedure outlined in Example 81, Part C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:11])/[CH:7]=[CH:8]/[CH2:9]I)([CH3:4])([CH3:3])[CH3:2].[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(=O)([O-])O.[Na+].C(OCC)(=O)C>O1CCCC1>[O:15]1[CH2:16][CH2:17][N:12]([CH2:9]/[CH:8]=[CH:7]/[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:11])[CH2:13][CH2:14]1
Reactant: C1COCCN1
Reactant: CC(C)(C)OC(=O)/C=C/CI
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)/C=C/CN1CCOCC1
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a solution of 4-iodocrotonic acid tert-butyl ester (310 mg) synthesized according to the method described in Journal of Medicinal Chemistry, 2005, vol. 48, pp. 1107-1131 in tetrahydrofuran (3 mL), morpholine (200 μL) was added under ice cooling, and the mixture was stirred at room temperature for 13 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain (E)-tert-butyl 4-morpholino-2-butenoate (B14, 180 mg).
Reaction SMILES: [CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH2:17][O:18][C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.Cl.[CH2:29]([O:31][C:32](=[O:42])[C@H:33]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[NH2:34])[CH3:30].C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C.C(O)(=O)C1C=CC=CC=1>CN(C=O)C.C(P(=O)(OCC)OCC)#N>[CH3:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[C:14]([CH2:17][O:18][C:19]4[CH:27]=[CH:26][C:22]([C:23]([NH:34][C@H:33]([C:32]([O:31][CH2:29][CH3:30])=[O:42])[CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: CCOC(=O)CC[C@H](N)C(=O)OCC
Reactant: Cc1nc2ccc3ccc(COc4ccc(C(=O)O)cc4)cc3c2c(=O)[nH]1
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Agent: O=C(O)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(OCc2ccc3ccc4nc(C)[nH]c(=O)c4c3c2)cc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 64.7 %

Procedure:
To a stirred suspension of 4-((1,2-dihydro-3-methyl-1-oxobenzo[f]-quinazolin-9-yl)methoxy) benzoic acid (0.19 g, 0.53 mmol) and L-glutamic acid diethyl ester hydrochloride (0.14 g, 0.58 mmol) (Aldrich) in DMF (3 ml) Were added diethyl cyanophosphonate (0.09 ml, 0.6 mmol) (Aldrich) and triethylamine (0.15 ml, 1.1 mmol). Additional DMF (7 ml) was added but homogeneous solution was not obtained. The reaction mixture was stirred 45 minutes at room temperature and TLC analysis indicated remaining benzoic acid. Diethyl cyanophosphonate (2 drops) was added, the mixture stirred 45 minutes, and was then concentrated in vacuo. The residue was purified by chromatography on silica gel (50 g) eluting with ethanol:methylene chloride (1:9). The solid was filtered from a small volume of ethanol and dried under reduced pressure to give diethyl N-(4-((1,2-dihydro-3-methyl-1-oxo-benzo[f]quinazolin-9-yl)methoxy)benzoyl)-L-glutamate (0.187 g). 1H NMR (DMSO-d6, 300 MHz) δ: 1.16 (t, J=7 Hz, 3H, ester CH3), 1.18 (t, J=7 Hz, 3H, ester CH3), 1.90-2.18 (m, 2H, glu CH2 ), 2.43 (t, J=7 Hz, 2H, glu CH2), 2.44 (s, 3H, C3 --CH3), 4.05 (q, J=7 Hz, 2H, ester CH2), 4.10 (q, J=6 Hz, 2H, ester CH2), 4.36-4.46 (m, 1H, glu CH), 5.43 (s, 2H, CH2O), 7.17 (d, J=9 Hz, 2H, Ar), 7.65 (d, J=9 Hz, 1H, Ar), 7.74 (dd, J=8,2 Hz, 1H, Ar), 7.88 (d, J=9 Hz, 2H, Ar), 8.08 (d, J =8 Hz, 1H, Ar), 8.26 (d, J=9 Hz, 1H, Ar), 8.58 (d, J=7 Hz, 1H, glu NH), 9.94 (s, 1H, Ar), 12.59 (s, 1H, N2H). Anal. Calculated for C30H31N3O7.1/4H2O: C, 65.50; H, 5.77; N, 7.64. Found: C, 65.54; H, 5.77; N, 7.61.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]3[C:12]4[CH:24]=[CH:23][S:22][C:13]=4[C:14](=[O:21])[NH:15][C:16]=3[CH:17]=[CH:18][C:19]=2[OH:20])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(O)C>[OH:20][C:19]1[CH:18]=[CH:17][C:16]2[NH:15][C:14](=[O:21])[C:13]3[S:22][CH:23]=[CH:24][C:12]=3[C:11]=2[C:10]=1[C:7]1[CH:8]=[CH:9][C:4]([CH:1]([OH:3])[CH3:2])=[CH:5][CH:6]=1
Reactant: CC(=O)c1ccc(-c2c(O)ccc3[nH]c(=O)c4sccc4c23)cc1
Agent: [Al+3]
Agent: [BH4-]
Agent: [H-]
Solvent: CCO
Product: CC(O)c1ccc(-c2c(O)ccc3[nH]c(=O)c4sccc4c23)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 1.3 %

Procedure:
A solution of 9-(4-acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (200 mg, 0.59 mmol) in ethanol (4 mL) was cooled to 0° C. and sodium borohydride (45 mg, 1.2 mmol) was added. The reaction mixture was stirred at room temperature for 18 h however starting material was present. The reaction was cooled to 0° C. and lithium aluminum hydride (1.0 M in THF, 1.2 mL, 1.2 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The reaction was cooled to 0° C., quenched with methanol and concentrated. The residue was purified by preparatory HPLC (C18 silica, water/acetonitrile w/0.05% TFA gradient) to afford the desired product (2.6 mg, 1%) as a light brown solid: 1H NMR (300 MHz, CD3OD) δ 7.59-7.52 (m, 3H), 7.39 (d, J=8.9 Hz, 1H), 7.29-7.25 (m, 2H), 7.16 (d, J=8.9 Hz, 1H), 6.03 (d, J=5.4 Hz, 1H), 4.97 (q, J=6.4 Hz, 1H), 1.56 (d, J=6.5 Hz, 3H); ESI MS m/z 338 [C19H15NO3S+H]+; HPLC 98.6% (AUC), tR=9.78 min.
Reaction SMILES: CCOCC.[CH3:6][CH:7]([C:9]1[C:10]([O:28][Si](C)(C)C)(C#N)[CH2:11][C:12]([CH3:25])=[CH:13][CH2:14][CH2:15][C:16]([CH3:24])=[CH:17][CH2:18][CH2:19][C:20]([CH3:23])=[CH:21][CH:22]=1)[CH3:8].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:8][CH:7]([C:9]1[C:10](=[O:28])[CH2:11][C:12]([CH3:25])=[CH:13][CH2:14][CH2:15][C:16]([CH3:24])=[CH:17][CH2:18][CH2:19][C:20]([CH3:23])=[CH:21][CH:22]=1)[CH3:6]
Reactant: CC1=CC=C(C(C)C)C(C#N)(O[Si](C)(C)C)CC(C)=CCCC(C)=CCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC1=CC=C(C(C)C)C(=O)CC(C)=CCCC(C)=CCC1
Reaction time: 48 h
Yield: 84.4 %

Procedure:
The above cyanohydrine trimethylsily ether compound, 2-(1-methylethyl)-5,9,13-trimethyl-1-trimethylsiloxy-2,4,8,12-cyclotetradecatetraen-1-carbonitrile (657 mg, 1.7 mmol) was dissolved in 10% aqueous tetrahydrofuran (10 ml). To the solution on an ice-water bath was added a solution of 1M tetra n-butylammonium fluoride in tetrahydrofuran (0.02 ml), and the mixture was stirred and then allowed to stand at room temperature for 2 days. Most of the tetrahydrofuran was removed in vacuo and the residue was dissolved in ethyl ether. The ether layer was dried over MgSO4, filtered, concentrated, and subjected to silica gel column chromatography (solvent: n-hexane/ethyl acetate=30:1) to obtain the ketone compound, 2-(1-methylethyl)-5,9,13-trimethyl-2,4,8,12-cyclotetradecatetraen-1-one (411 mg, 85%).
Reaction SMILES: [NH2:1][C@@H:2]([CH2:20][C:21]1[N:22]=[CH:23][NH:24][CH:25]=1)[C:3]([NH:5][C@@H:6]([CH2:16][CH:17]([CH3:19])[CH3:18])[C@@H:7]([OH:15])[CH2:8][CH:9]([CH:12]([CH3:14])[CH3:13])[CH:10]=[CH2:11])=[O:4].C(N(C(C)C)C(C)C)C.[CH2:35]([CH:42]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:43](O)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(#N)C>[CH2:46]([CH:42]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:43]([NH:1][C@@H:2]([CH2:20][C:21]1[N:22]=[CH:23][NH:24][CH:25]=1)[C:3]([NH:5][C@@H:6]([CH2:16][CH:17]([CH3:19])[CH3:18])[C@@H:7]([OH:15])[CH2:8][C@@H:9]([CH:12]([CH3:14])[CH3:13])[CH:10]=[CH2:11])=[O:4])=[O:44])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1
Reactant: O=C(O)C(Cc1ccccc1)Cc1ccccc1
Reactant: C=CC(C[C@H](O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc1c[nH]cn1)C(C)C
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C=C[C@@H](C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)C(Cc1ccccc1)Cc1ccccc1)C(C)C
Yield: 16 %

Procedure:
0.65 g of (S)-α-amino-N-[(1S,2S,4RS)-2-hydroxy-1-isobutyl-4-isopropyl-5-hexenyl]imidazole-4-propionamide in 20 ml of acetonitrile were added together with 0.36 ml of ethyldiisopropylamine to a solution of 0.45 g of 2-benzyl-3-phenylpropionic acid (which was prepared according to the method described in J. Am. Chem. Soc. 71 1863 (1949)) and 0.8 g of BOP in 30 ml of acetonitrile and the mixture was stirred at room temperature for 20 hours. Subsequently, the reaction mixture was evaporated under reduced pressure, the residue was dissolved in 50 ml of ethyl acetate and the organic solution was washed twice with 100 ml of water each time, dried over sodium sulfate and evaporated. The residue Was separated by flash chromatography on 100 g of silica gel with a 250:15 mixture of methylene chloride and methanol as the eluting agent, to obtain there was obtained 0.17 g of (S)-α-(2,2-dibenzylacetamido)-N-[(1S,2S,4S)-2 -hydroxy-1-isobutyl-4-isopropyl-5-hexenyl]imidazole-4-propionamide as a white powder, melting point 120°. This compound corresponds to the less polar isomer and has a Rf value of 0.14.
Reaction SMILES: [CH2:1](O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CI.C/C(/[O-])=C/C(C)=O.[C:18]([OH:21])(=[O:20])C>[Ni].O.O.O.O.C([O-])(=O)C.[Ni+2].C([O-])(=O)C.[V].[O-][V]([O-])([O-])=O.[Na+].[Na+].[Na+]>[C:2]1([CH2:1][C:18]([OH:21])=[O:20])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)O
Reactant: OCc1ccccc1
Agent: O=[V]([O-])([O-])[O-]
Agent: [Ni+2]
Agent: [Ni]
Solvent: CI
Solvent: O
Product: O=C(O)Cc1ccccc1

Procedure:
Using the equipment and the procedure described for Example 1, an experiment was carried out on a charge comprising 25 ml (232 mmols) of benzyl alcohol, 15 ml of acetic acid, 161 mmols of methyl iodide, 8 mg atoms of nickel in the form of nickel acetate tetrahydrate and 40 mg atoms of vanadium in the form of vanadyl bis-acetylacetonate. The reaction temperature was 180° C.; the total pressure was maintained at 60 bars by introduction of additional amounts of pure CO. In a reaction time of 1 hour, 30 minutes at the temperature indicated, 15.8 g of phenylacetic acid were obtained (RY=48%).
Reaction SMILES: CC(C1C(S(C)=O)=C(N)N([C:13]2[C:18](Cl)=[CH:17][C:16]([C:20](F)(F)F)=[CH:15][C:14]=2Cl)N=1)=O.CC[S+]([O-])[C:28]1[C:29](C#N)=[N:30][N:31](C2C(Cl)=CC(C(F)(F)F)=CC=2Cl)C=1N.C1C(C(F)(F)F)=CC(Cl)=C(N2N=C(C#N)C([S+]([O-])C(F)(F)F)=C2N)C=1Cl.COC1C(=O)C=C/C(=C\NC2N(C3C(Cl)=CC(C(F)(F)F)=CC=3Cl)N=C(C#N)C=2SC(F)(F)F)/C=1.C1N=CC(CNC2N(C3C(Cl)=CC(C(F)(F)F)=CC=3Cl)N=C(C#N)C=2SCF)=NC=1>>[C:16]1([C:20]2[CH:28]=[CH:29][NH:30][N:31]=2)[CH:15]=[CH:14][CH:13]=[CH:18][CH:17]=1
Reactant: CC[S+]([O-])c1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Reactant: CC(=O)c1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1S(C)=O
Agent: COC1=C/C(=C/Nc2c(SC(F)(F)F)c(C#N)nn2-c2c(Cl)cc(C(F)(F)F)cc2Cl)C=CC1=O
Agent: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1[S+]([O-])C(F)(F)F
Agent: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(NCc2cnccn2)c1SCF
Product: c1ccc(-c2cc[nH]n2)cc1

Procedure:
acetoprole, ethiprole, fipronil, vaniliprole, pyripiole, and pyrafluprole.