Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:39])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][C:17]3[C:18]([CH3:38])=[N:19][C:20]([C:27]4[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=4)=[CH:21][C:22]=3[C:23]([F:26])([F:25])[F:24])[CH:13]=2)[CH:8]=[CH:7]1)C.[Li+].[OH-]>>[CH3:38][C:18]1[C:17]([CH2:16][O:15][C:12]2[CH:13]=[C:14]3[C:9]([CH:8]=[CH:7][N:6]3[CH2:5][C:4]([OH:39])=[O:3])=[CH:10][CH:11]=2)=[C:22]([C:23]([F:25])([F:26])[F:24])[CH:21]=[C:20]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:36])([F:35])[F:37])=[CH:29][CH:28]=2)[N:19]=1
Reactant: CCOC(=O)Cn1ccc2ccc(OCc3c(C(F)(F)F)cc(-c4ccc(OC(F)(F)F)cc4)nc3C)cc21
Agent: [Li+]
Agent: [OH-]
Product: Cc1nc(-c2ccc(OC(F)(F)F)cc2)cc(C(F)(F)F)c1COc1ccc2ccn(CC(=O)O)c2c1

Procedure:
In analogy to the procedure described in example 5 g], {6-[2-methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-ylmethoxy]-indol-1-yl}-acetic acid ethyl ester was treated with LiOH to obtain the title compound as colorless solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([N+:19]([O-])=O)[CH:11]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:22][P:23](=[O:27])([CH2:25]N)[CH3:24]>C1(C)C=CC=CC=1>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([O:9][C:3]2[C:2]([Cl:1])=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=2)=[CH:11][C:12]=1[NH:19][CH2:22][P:23](=[O:27])([CH3:25])[CH3:24])([O-:18])=[O:17]
Reactant: CP(C)(=O)CN
Reactant: O=[N+]([O-])c1ccc(Oc2ncc(Cl)cc2Cl)cc1[N+](=O)[O-]
Solvent: Cc1ccccc1
Product: CP(C)(=O)CNc1cc(Oc2ncc(Cl)cc2Cl)ccc1[N+](=O)[O-]
Yield: 83.7 %

Procedure:
A solution of 4.95 g (3,5-Dichloro-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added. After the initial evolution of nitrous gases has finished, the mixture is refluxed for a further 2 hours. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether. There are obtained, in the form of yellow crystals, 4.9 g (84% of theory) of N-[2-nitro-5-(3,5-dichloro-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide, m.p. 153°-155° C.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[CH2:13][O:12][C@H:11]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[C@@H:10]1/[CH:20]=[CH:21]/[C:22]([O:24][CH3:25])=[O:23])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C(O)C.[Pd]>[Si:1]([O:8][C@@H:9]1[CH2:13][O:12][C@H:11]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[C@@H:10]1[CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: COC(=O)/C=C/[C@H]1[C@@H](c2cccnc2)OC[C@H]1O[Si](C)(C)C(C)(C)C
Agent: [Pd]
Solvent: CCO
Product: COC(=O)CC[C@H]1[C@@H](c2cccnc2)OC[C@H]1O[Si](C)(C)C(C)(C)C

Procedure:
A solution of 6.7 g (0.0184 mol) of methyl (E)-(2S,3S,4S)-3-[4-(t-butyldimethylsilyloxy)-2-(3-pyridyl)tetrahydrofuran-3-yl]-2-propenoate in 94 mL of ethanol is hydrogenated over 0.7 g of 10% palladium on carbon catalyst at atmospheric pressure. The catalyst is filtered, washed with ethanol and the filtrates are evaporated to dryness to give methyl (2S,3S,4S)-3-[4-(t-butyl-dimethylsilyloxy)-2-(3-pyridyl)tetrahydrofuran-3-yl]propanoate as an oil with elemental analysis: C, 62.77; H, 8.35: N, 3.84 (theory: C, 62.43: H, 8.55: N, 3.83).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][O:12][C:13](=[O:25])[CH:14]([S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:18])=[O:17])[CH3:15].[Br:26][CH2:27][CH2:28][CH2:29]Br>O1CCCC1>[CH3:11][O:12][C:13](=[O:25])[C:14]([S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:17])=[O:18])([CH3:15])[CH2:29][CH2:28][CH2:27][Br:26]
Reactant: BrCCCBr
Reactant: COC(=O)C(C)S(=O)(=O)c1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C(C)(CCCBr)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 16.6 %

Procedure:
A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1M, 6.6 ml, 6.6 mmol) was added dropwise to a stirred solution of 2-benzenesulfonylpropionic acid methyl ester (1.38 g, 5.7 mmol) in tetrahydrofuran at −78° C. The mixture was stirred for 30 min. and 1,3-dibromopropane (3.17 ml, 31.2 mmol) was added. The mixture was slowly warmed to room temperature and stirred for 4 days. After quenching with satd. aqueous NH4Cl, the mixture was extracted into dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified on silica gel (i-hexane-ethyl acetate 5–20%) to give the title product (330 mg, 15%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.[IH:12]>>[I:12][C:4]1[N:3]=[C:2]([NH2:1])[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1
Reactant: I
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Product: Nc1nc(I)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A mixture of 2-amino-6-chloro-3-nitropyridine (5-1) (5.00 g, 28.8 mmol) and 57% HI (100 mL) was stirred for 48 hours at RT. The red-orange colored suspension was filtered to collect the precipitate which was washed with a small amount of water. The resulting yellow solid was suspended in CH2Cl2 (100 mL) and water (50 mL), and triethylamine (5.0 mL) was added while stirring. The layers were separated and the aqueous phase was reextracted with 4:1 CHCl3-isopropanol. The organic layers were combined and concentrated to yield a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[C:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=1[O:36][CH3:37].[I-].[K+]>C(O)CCC>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:9]2[CH2:14][CH2:13][N:12]([CH2:23][CH2:24][CH2:25][O:26][C:27]3[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=3[O:36][CH3:37])[CH2:11][CH2:10]2)=[CH:20][CH:19]=1
Reactant: COc1cc(C(C)=O)ccc1OCCCCl
Reactant: Clc1ccc(C(=C2CCNCC2)c2ccc(Cl)cc2)cc1
Agent: [I-]
Agent: [K+]
Solvent: CCCCO
Product: COc1cc(C(C)=O)ccc1OCCCN1CCC(=C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)CC1

Procedure:
A mixture of 3.96 g (0.01305 mole) of 4-[bis(4-chlorophenyl)methylene]piperidine, 3.16 g (0.013 mole) of 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone in 300 ml of 1-butanol containing 0.3 g of potassium iodide was heated overnight at gentle reflux. The reaction mixture was stripped to dryness and partitioned between chloroform-water and chloroform-5% sodium hydroxide. Removal of chloroform gave an oil which crystallized from isopropyl alcohol. The solid was again crystallized from isopropyl alcohol to give 4.16 g (61%) of light yellow solid, m.p. 143°-144° C.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[S:7][CH:8]=[CH:9][CH:10]=1.Cl[C:12]([CH3:15])([CH3:14])[CH3:13].[Cl-].[Al+3].[Cl-].[Cl-].O>C(Cl)Cl>[C:12]([C:5]1[S:1][C:2]([C:6]2[S:7][CH:8]=[CH:9][CH:10]=2)=[CH:3][CH:4]=1)([CH3:15])([CH3:14])[CH3:13]
Reactant: c1csc(-c2cccs2)c1
Reactant: CC(C)(C)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)c1ccc(-c2cccs2)s1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.5 %

Procedure:
2,2′-bithiophene (10 g, 60.1 mmol) was dissolved in DCM (300 mL) and 2-chloro-2-methylpropane (7.95 g, 72.2 mmol) was added. Aluminum chloride (8.82 g, 66.2 mmol) was added in one portion, and the colourless solution turned a green/brown colour immediately. The reaction mixture was stirred at room temperature for 30 minutes, then was poured into water (500 mL), mixed well and separated. The aqueous portion was extracted with DCM (200 mL) and the combined organics were washed with brine (2×400 mL), dried over MgSO4, filtered and solvent removed by rotary evaporation to afford a clear, green oil (13.3 g, 99%) that was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 7.17 (dd, J=5.1, 1.1 Hz, 1H), 7.10 (dd, J=3.6, 1.1 Hz, 1H), (dd, J=5.1, 3.6 Hz, 1H), 6.98 (d, J=3.6 Hz, 1H), 6.73 (d, J=3.7 Hz, 1H), 1.40 (s, 9H).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:12][C:13]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH2:9][CH2:10][NH:11][C:5]2=[N:4][CH:3]=1.C([N:29]1[CH2:34][CH2:33][N:32]([C:35]2[N:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][N:36]=2)[CH2:31][CH2:30]1)(OC(C)(C)C)=O>>[Cl:21][C:14]1[C:15]([F:20])=[CH:16][CH:17]=[C:18]([F:19])[C:13]=1[CH2:12][N:8]1[C:6]2=[N:7][C:2]([C:38]3[CH:37]=[N:36][C:35]([N:32]4[CH2:33][CH2:34][NH:29][CH2:30][CH2:31]4)=[N:40][CH:39]=3)=[CH:3][N:4]=[C:5]2[NH:11][CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Reactant: Fc1ccc(F)c(CN2CCNc3ncc(Br)nc32)c1Cl
Product: Fc1ccc(F)c(CN2CCNc3ncc(-c4cnc(N5CCNCC5)nc4)nc32)c1Cl

Procedure:
The entitled compound was prepared from 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine and 2-(4-Boc-piperazin-1-yl)pyrimidine-5-boronic acid pinacol ester using Suzuki coupling conditions as described in Example 1. The Suzuki coupling yielded the desired compound in its BOC protected form. The BOC protected intermediate was then treated with TFA in CH2Cl2 and purified by Silica gel column chromatography.
Reaction SMILES: [F:1][C@:2]([C:14]([F:17])([F:16])[F:15])([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:3](Cl)=[O:4].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>CCOCC>[F:1][C@:2]([C:14]([F:15])([F:16])[F:17])([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:3][OH:4]
Reactant: CCCCCCCC[C@@](F)(C(=O)Cl)C(F)(F)F
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CCCCCCCC[C@@](F)(CO)C(F)(F)F
Reaction time: 3 h
Yield: 55.4 %

Procedure:
In 10 ml of anhydrous ether was dissolved 1.4 g (5.1 mmol) of (S)-(+)-2-fluoro-2-(trifluoromethyl)decanoyl chloride, and then 0.14 g (3.5 mmol) of lithium aluminum hydride was portion-wise added to the above-obtained solution while the solution was being cooled with ice. The resulting mixture was stirred for 3 hours. Thereafter, 1N hydrochloric acid was portionwise added to the resulting reaction mixture while the mixture was being cooled with ice, and then a reaction product was extracted with ether. The resulting ether layer was dried with magnesium sulfate, the solvent was removed under reduced pressure, and then the residual product was distilled. Thus, there was obtained 0.69 g of (R)-(-)-2-fluoro-2-(trifluoromethyl)-1-decanol having the physical properties as mentioned hereinbefore, in a yield of 56%.
Reaction SMILES: [CH:1]([C:3]1[N:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH3:12])=[C:5]([C:13]#[N:14])[CH:4]=1)=O.[CH3:15][NH:16][CH3:17].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:15][N:16]([CH2:1][C:3]1[N:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH3:12])=[C:5]([C:13]#[N:14])[CH:4]=1)[CH3:17]
Reactant: Cc1cccc2c(C#N)cc(C=O)n12
Reactant: CNC
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1cccc2c(C#N)cc(CN(C)C)n12
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 3-Formyl-5-methyl-indolizine-1-carbonitrile (200 mg, 1.09 mmol) in CH2Cl2 (10 mL) and dimethylamine (2M MeOH solution) (1.09 mL, 2.17 mmol) was added NaBH(OAc)3 (460 mg, 2.17 mmol) at 0° C. Upon complete addition the cooling bath was removed and the reaction mixture was stirred at room temperature for 12 h. When the reaction was complete, the mixture was diluted with CH2Cl2 and washed with saturated NaHCO3. The layers were separated and the organic phase was dried over MgSO4, filtered and concentrated. The residue was purified by CombiFlash with 20% EtOAc in Hexane as the eluent to afford the desirable product 3-Dimethylaminomethyl-5-methyl-indolizine-1-carbonitrile, CAS: 3-Dimethylaminomethyl-5-methyl-indolizine-1-carbonitrile (150 mg, 65%) as a white solid.
Reaction SMILES: [C:1](PCC1C(CPC(C)(C)C)=CC=CC=1)(C)(C)C.CS(O)(=O)=O.[C:24]([O-:44])(=[O:43])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][C@@H:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[OH:36]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:43][C:24](=[O:44])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][C@@H:35]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[OH:36]
Reactant: CCCCCC[C@@H](O)C/C=C\CCCCCCCC(=O)[O-]
Reactant: CC(C)(C)PCc1ccccc1CPC(C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CS(=O)(=O)O
Product: CCCCCC[C@@H](O)C/C=C\CCCCCCCC(=O)OC
Temperature: 25 °C

Procedure:
Pd(OAc)2 (0.45 mg, 0.002 mmol) and α,α′-di-tert-butylphosphino-o-xylene (4 mg, 0.01 mmol) were dissolved in 4 mL of either one of the solvents of Table 5. Subsequently, methanesulfonic acid (1.3 μL, 0.02 mmol) and ricinoleate (1 mmol, 338 μL) were added. The reaction was allowed to proceed at the temperature and time as indicated in Table 5. The reaction mixtures were cooled down to room temperature and analyzed by means of GC. The results are summarized in Table 5.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=[O:15])[NH:8][CH2:7]/[C:6]/2=[CH:16]\[C:17]([O:19]CC)=[O:18].[Li+].[OH-]>CO.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9](=[O:15])[NH:8][CH2:7]/[C:6]/2=[CH:16]\[C:17]([OH:19])=[O:18]
Reactant: CCOC(=O)/C=C1\CNC(=O)c2cc(OC)c(OC)cc21
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc2c(cc1OC)/C(=C/C(=O)O)CNC2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
To a stirred solution of (Z)-ethyl 2-(6,7-dimethoxy-1-oxo-2,3-dihydroisoquinolin-4(1H)-ylidene)acetate (1.45 g, 5 mmol) in MeOH (20 mL) and THF (40 mL) was added 2N LiOH (5 mL) dropwise at room temperature and the resulting mixture was stirred at room temperature overnight. The reaction was quenched by addition of 1N HCl and the solvents were removed under reduced pressure. The mixture was diluted with water and cooled and the precipitate collected by filtration to afford (Z)-2-(6,7-dimethoxy-1-oxo-2,3-dihydroisoquinolin-4(1H)-ylidene)acetic acid (1.0 g, 77%). LC-MS (ES-API); rt 7.21 min; m/z calculated for C13H13NO5 [M−H]− 262.0, found 262.1.
Reaction SMILES: OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH2:15]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[C:16]#[CH:17].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][CH2:33][OH:34]>C(#N)C>[CH2:15]([N:18]1[CH2:23][CH2:22][N:21]([CH2:31][CH2:32][CH2:33][OH:34])[CH2:20][CH2:19]1)[C:16]#[CH:17]
Reactant: OCCCBr
Reactant: C#CCN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: C#CCN1CCN(CCCO)CC1
Temperature: 85 °C
Yield: 78.5 %

Procedure:
1-Prop-2-yn-1-ylpiperazine diTFA salt (704 mg, 2 mmol), (prepared as described for the starting material in Example 26), was dissolved in acetonitrile (5 ml). Potassium carbonate (1.38 g, 10 mmol) and 3-bromopropan-1-ol (180 μL, 2 mmol) were added and the mixture heated to 85° C. for 6.5 hours. The reaction mixture was cooled, filtered and concentrated to give an oil. This was triturated with diethyl ether to give a white solid, which was partitioned between dichloromethane and water. The organic phase was then dried (MgSO4) and concentrated to give 3-(4-prop-2-yn-1-ylpiperazin-1-yl)propan-1-ol (286 mg, 79%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:11][CH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([NH:19][OH:20])=[NH:18])=[CH:15][CH:14]=1.N1C=CC=CC=1.[C:33]1([O:39]C(Cl)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>ClCCl.C(#N)C>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:11][CH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]2[NH:18][C:33](=[O:39])[O:20][N:19]=2)=[CH:15][CH:14]=1
Reactant: CCCCN(CCc1ccc(C(=N)NO)cc1)c1nc2ccccc2o1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CC#N
Product: CCCCN(CCc1ccc(-c2noc(=O)[nH]2)cc1)c1nc2ccccc2o1
Temperature: 25 °C

Procedure:
280 mg 4-[2-(Benzooxazol-2-yl-butyl-amino)-ethyl]-N-hydroxy-benzamidine were dissolved in 5 ml dichloromethane. 78 μl pyridine and 120 μl phenylchloroformate were added and the mixture stirred at room temperature for ten minutes. The mixture was diluted by the addition of 15 ml acetonitrile and 115 μl ml 1,8-Diazabicyclo[5.4.0]undec-7-ene were added. The mixture was stirred at room temperature for 10 minutes. The mixture was evaporated in vacuo and the resulting crude material was purified by reversed phase HPLC to obtain 105 mg 3-{4-[2-(Benzooxazol-2-yl-butyl-amino)-ethyl]-phenyl}-4H-[1,2,4]oxadiazol-5-one as an amorphous lyophilisate.
Reaction SMILES: [C:1]1([N:7]([CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:8]([C:10]2[CH:11]=[CH:12][C:13]3[S:17][C:16]([CH2:18][S:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=4)=[N:15][C:14]=3[CH:28]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:36].C(O)C.C(=O)([O-])[O-].[NH4+:44].[NH4+]>C(O)(=O)C.C(Cl)Cl.C(O)C>[ClH:36].[C:1]1([N:7]([CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:8]([C:10]2[CH:11]=[CH:12][C:13]3[S:17][C:16]([CH2:18][S:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:44])[NH2:27])=[CH:22][CH:21]=4)=[N:15][C:14]=3[CH:28]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [NH4+]
Reactant: CCOC(=O)CCN(C(=O)c1ccc2sc(CSc3ccc(C#N)cc3)nc2c1)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCOC(=O)CCN(C(=O)c1ccc2sc(CSc3ccc(C(=N)N)cc3)nc2c1)c1ccccc1
Yield: 61 %

Procedure:
Prepared analogously to Example 9 from 2-[(4-cyanophenyl)thiomethyl]-benzothiazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide, ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 61% of theory, C27H26N4O3S2 (518.66) Rf value: 0.27 (silica gel; methylene chloride/ethanol=4:1+a few drops of acetic acid) EKA mass spectrum: (M+H)+ =519
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[C:13]([NH:18][C:19]2[CH:20]=[C:21]([CH3:25])[CH:22]=[CH:23][CH:24]=2)=[N:14][CH:15]=[CH:16][CH:17]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]>CC(O)=O>[C:1]([O:5][C:6](=[O:27])[NH:7][C@H:8]([C:10]1[N:18]([C:19]2[CH:20]=[C:21]([CH3:25])[CH:22]=[CH:23][CH:24]=2)[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cccc(Nc2ncccc2NC(=O)[C@H](C)NC(=O)OC(C)(C)C)c1
Solvent: CC(=O)O
Product: Cc1cccc(-n2c([C@H](C)NC(=O)OC(C)(C)C)nc3cccnc32)c1
Temperature: 25 °C

Procedure:
A solution of [(S)-1-(2-m-tolylaminopyridin-3-ylcarbamoyl)ethyl]carbamic acid tert-butyl ester (3.01 mmol) in AcOH (20 mL) was heated at 70° C. for 2 h under a nitrogen atmosphere. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with DCM (×3) and the combined organic fractions washed with water, dried (Na2SO4) and concentrated in vacuo to afford the title compound as an off-white foam (quantitative). LCMS (Method C): RT 3.23 min [M+H]+ 353.4.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:4]=[C:3]1[CH2:15][C:16]([O-:18])=O.[Na+].[I:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[F:28])[NH2:24]>>[I:20][C:21]1[CH:22]=[C:23]([NH:24][C:16](=[O:18])[CH2:15][C:3]2[N:2]([CH3:1])[C:7](=[O:8])[CH:6]=[C:5]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)[N:4]=2)[CH:25]=[CH:26][C:27]=1[F:28]
Reactant: Nc1ccc(F)c(I)c1
Reactant: Cn1c(CC(=O)[O-])nc(N2CCOCC2)cc1=O
Agent: [Na+]
Product: Cn1c(CC(=O)Nc2ccc(F)c(I)c2)nc(N2CCOCC2)cc1=O
Yield: 54.2 %

Procedure:
The product is prepared according to the procedure described in example 68, using 200 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 210 mg of 3-iodo-4-fluoroaniline. 186 mg of N-(3-iodo-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:
Reaction SMILES: [NH2:1][C:2]([CH3:7])([CH2:5][OH:6])[CH2:3][OH:4].[CH2:8]([NH:20][C:21](N1C=CN=C1)=[O:22])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>CO>[CH2:8]([NH:20][C:21]([NH:1][C:2]([CH2:5][OH:6])([CH3:7])[CH2:3][OH:4])=[O:22])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCCCCCCCCNC(=O)n1ccnc1
Reactant: CC(N)(CO)CO
Solvent: CO
Product: CCCCCCCCCCCCNC(=O)NC(C)(CO)CO

Procedure:
The preparation was carried out, according to the same process described in Example 1, from 3.5 g of 2-amino-2-methyl-1,3-propanediol of corresponding formula R2 --NH--R3, where R2 denoted H and R3 denoted: ##STR7## and 7 g of 1-N-(dodecylaminocarbonyl)imidazole of corresponding formula (III), where R1 denoted C12H25, in 100 cm3 of methanol.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:15]4[CH:16]=[C:17]5[C:21](=[C:22]([F:24])[CH:23]=4)[CH2:20][N:19]([S:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH2:18]5)[C:12]=3[CH3:14])[C:7](=[O:35])[C:6]([C:36]([O:38]CC)=[O:37])=[CH:5]2)[CH2:3][CH2:2]1.[OH-].[Na+].O1CCOCC1.Cl>C(O)C>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:15]4[CH:16]=[C:17]5[C:21](=[C:22]([F:24])[CH:23]=4)[CH2:20][N:19]([S:25]([C:28]4[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=4)(=[O:27])=[O:26])[CH2:18]5)[C:12]=3[CH3:14])[C:7](=[O:35])[C:6]([C:36]([OH:38])=[O:37])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: CCOC(=O)c1cn(C2CC2)c2c(C)c(-c3cc(F)c4c(c3)CN(S(=O)(=O)c3ccc(C)cc3)C4)ccc2c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1COCCO1
Product: Cc1ccc(S(=O)(=O)N2Cc3cc(-c4ccc5c(=O)c(C(=O)O)cn(C6CC6)c5c4C)cc(F)c3C2)cc1
Yield: 98.9 %

Procedure:
In 3.3 ml of ethanol was suspended 0.33 g of ethyl 1-cyclopropyl-7-[7-fluoro-2-(p-toluenesulfonyl)-isoindolin-5-yl)-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate, followed by adding thereto 3.3 ml of a 1N aqueous sodium hydroxide solution and 3.3 ml of dioxane, and the resulting mixture was stirred at 40° C. for 30 minutes. To the reaction mixture was added 3.3 ml of 1N hydrochloric acid and the crystals were collected by filtration to obtain 0.31 g of colorless 1-cyclopropyl-7-[7-fluoro-2-(p-toluenesulfonyl)isoindolin-5-yl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([CH2:6][C:7]([CH2:13][CH3:14])([CH3:12])[CH2:8]2)=[C:4]([CH3:15])[C:3]=1[CH:16]=O.O.[OH-].[Na+].Cl.[CH3:22][C:23]([CH3:25])=[O:24]>>[Cl:1][C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([CH2:6][C:7]([CH2:13][CH3:14])([CH3:12])[CH2:8]2)=[C:4]([CH3:15])[C:3]=1[CH:16]=[CH:22][C:23](=[O:24])[CH3:25]
Reactant: CCC1(C)Cc2c(C)c(Cl)c(C=O)c(C)c2C1
Reactant: CC(C)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCC1(C)Cc2c(C)c(Cl)c(C=CC(C)=O)c(C)c2C1
Yield: 78 %

Procedure:
To a solution of 24.35 g of the 6-chloro-2-ethyl-2,4,7-trimethylindan-5-carboxaldehyde in 73 ml of absolute acetone was added 36 ml of water and 40 g of 2% NaOH. After refluxing for 20 hours, the solution was acidified with 2N HCl and extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography to afford 22.08 g of the title compound as brown oil.
Reaction SMILES: [Li+].[OH-].C[O:4][C:5](=[O:20])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1.Cl>C1COCC1>[CH2:13]([O:12][C:9]1[CH:8]=[CH:7][C:6]([C:5]([OH:20])=[O:4])=[CH:11][CH:10]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(=O)c1ccc(OCc2ccccc2)cc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1ccc(OCc2ccccc2)cc1
Yield: 98.1 %

Procedure:
16 mL of a 2N LiOH aqueous solution were added to a solution of 3.0 g (12.5 mmol) of 4-benzyloxy-benzoic acid methyl ester in 50 mL of THF and the mixture was refluxed overnight. The reaction mixture was acidified with HCl 6N and extracted with ethyl acetate affording after filtration and removal of the solvent under reduced atmosphere, 2.8 g (93% yield) of 4-benzyloxy-benzoic acid.