Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[S:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[NH:14][C:15](=O)[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=2)[CH2:4][CH2:3]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.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[NH2:73][CH2:74][C:75]1([NH2:79])[CH2:78][O:77][CH2:76]1>CN(C)C=O.O>[NH2:79][C:75]1([CH2:74][NH:73][C:15]2[C:16]3[S:21][C:20]([CH3:22])=[CH:19][C:17]=3[N:18]=[C:13]([N:5]3[CH2:6][C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=4[S:2](=[O:1])[CH2:3][CH2:4]3)[N:14]=2)[CH2:78][O:77][CH2:76]1
Reactant: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)[nH]c(=O)c2s1
Reactant: NCC1(N)COC1
Agent: C1=NCCCN(C2CCCCCCCCCC2)CCCCC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc2nc(N3CCS(=O)c4ccccc4C3)nc(NCC3(N)COC3)c2s1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A suspension of 2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one (250 mg, 0.72 mmol), benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (415 mg, 0.94 mmol) and 1,8-diazabicycloundec-7-ene (165 mg, 1.08 mmol) in anhydrous N,N-dimethylformamide (10 mL) was stirred at r.t. for 10 min, then a solution of 3-aminomethyl-oxetan-3-ylamine (150 mg, 1.44 mmol) in N,N-dimethylformamide (5 mL) was added dropwise. After the addition was complete, the mixture was heated at 60° C. overnight, then it was diluted with water (50 mL), extracted by dichloromethane, washed by brine, dried with anhydrous sodium sulfate. The solvent was removed and the residue was purified by preparative HPLC to afford N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine as a white solid. MS obsd. (ESI+) [(M+H)+] 430, 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67-7.80 (m, 2H), 7.45 (t, J=5.8 Hz, 2H), 6.82 (s, 1H), 5.21 (d, J=15.4 Hz, 1H), 4.71 (br. s., 1H), 4.63 (d, J=6.3 Hz, 2H), 4.46-4.56 (m, 2H), 4.01 (s, 2H), 3.30-3.49 (m, 4H), 2.55 (s, 3H).
Reaction SMILES: [CH2:1]([N:4]([CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:5]([C:7]1[CH:26]=[CH:25][C:10]2[N:11]([CH3:24])[C:12]([CH2:14][NH:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=3)=[N:13][C:9]=2[CH:8]=1)=[O:6])[C:2]#[CH:3].[ClH:34].C(O)C.C(=O)([O-])[O-].[NH4+:42].[NH4+]>ClCCl.C(O)C>[ClH:34].[CH2:1]([N:4]([CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:5]([C:7]1[CH:26]=[CH:25][C:10]2[N:11]([CH3:24])[C:12]([CH2:14][NH:15][C:16]3[CH:21]=[CH:20][C:19]([C:22](=[NH:42])[NH2:23])=[CH:18][CH:17]=3)=[N:13][C:9]=2[CH:8]=1)=[O:6])[C:2]#[CH:3]
Reactant: [NH4+]
Reactant: C#CCN(CCC(=O)OCC)C(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cc1)n2C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: ClCCl
Product: C#CCN(CCC(=O)OCC)C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C
Yield: 81 %

Procedure:
Prepared analogously to Example 25d from 1-methyl-2-[N-(4-cyanophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-propargyl-N-(2-ethoxycarbonylethyl)-amide, ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 81% of theory, C25H28N6O3 (460.6) Rf value: 0.094 (silica gel; dichloromethane/ethanol=4:1) ##EQU94##
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C@H:7]2[O:8][C@H:6]2[C:5]2C=C(C#N)C=[CH:12][C:4]=2[O:3]1.[CH2:16]([O:18][C:19]([NH:21][C:22]1[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=1[NH2:24])=[O:20])[CH3:17].Cl([O-])(=O)(=O)=O.[Mg+2].Cl([O-])(=O)(=O)=O.C(#[N:42])C>C(OCC)(=O)C>[C:12]([C:4]1[O:3][C:2]([CH3:1])([CH3:15])[C@@H:7]([OH:8])[C@H:6]([NH:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[NH:21][C:19](=[O:20])[O:18][CH2:16][CH3:17])[CH:5]=1)#[N:42]
Reactant: CCOC(=O)Nc1ccccc1N
Reactant: CC#N
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H]2O[C@@H]21
Agent: [Mg+2]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCOC(C)=O
Product: CCOC(=O)Nc1ccccc1N[C@@H]1C=C(C#N)OC(C)(C)[C@H]1O
Yield: 92.8 %

Procedure:
The reaction mixture containing (1aS-cis)-1a,7b-dihydro-2,2-dimethyl-2H-oxireno-[c][1]benzopyran-6-carbonitrile, from example 2, part A (1.0 g, 5.0 mmol), 2-[(ethoxycarbonyl)amino]aniline, compound of example 1, part B (900 mg, 5.0 mmol) and magnesium perchlorate (1.12 g, 5.0 mmol) in acetonitrile (5.0 mL) was stirred under argon at room temperature for 48 hours. The reaction mixture was diluted with ethyl acetate and washed with water, saturated sodium bicarbonate solution and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated to give a colorless foam which was purified by flash chromatography (25% ethyl acetate in hexanes) to yield the title product as an amorphous solid (1.76 g, 92.8%) (shrinks at 84° C.). [a]D =+21° (c=1.1%, MeOH). Microanalysis calculated for C21H23N3O4 : C,66.13; H, 6.08; N,11.02. Found: C, 66.11 ; H, 6.15; N, 10.78.
Reaction SMILES: O1C=C(CN)N=C1.[S:8]1[CH:12]=[CH:11][N:10]=[C:9]1[CH2:13][NH2:14].[F:15][C:16]1[CH:37]=[CH:36][C:19]([CH2:20][N:21]2[CH2:25][CH2:24][N:23]([C:26]3[CH:27]=[C:28]([CH:32]=[CH:33][N:34]=3)[C:29](O)=[O:30])[C:22]2=[O:35])=[CH:18][CH:17]=1>>[F:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:20][N:21]2[CH2:25][CH2:24][N:23]([C:26]3[CH:27]=[C:28]([CH:32]=[CH:33][N:34]=3)[C:29]([NH:14][CH2:13][C:9]3[S:8][CH:12]=[CH:11][N:10]=3)=[O:30])[C:22]2=[O:35])=[CH:36][CH:37]=1
Reactant: NCc1nccs1
Reactant: O=C(O)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Agent: NCc1cocn1
Product: O=C(NCc1nccs1)c1ccnc(N2CCN(Cc3ccc(F)cc3)C2=O)c1
Yield: 88 %

Procedure:
Following the procedure as described in Example 14, making variations as required to replace oxazol-4-ylmethanamine with thiazol-2-ylmethanamine to react with 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinic acid, 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-N-(thiazol-2-ylmethyl)isonicotinamide was obtained as a colorless solid in 88% yield: mp 123-125° C.; NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.70 (d, J=2.7 Hz, 1H), 7.39-7.21 (m, 5H), 7.04-6.99 (m, 2H), 4.93 (d, J=5.7 Hz, 2H), 4.42 (s, 2H), 4.02 (t, J=8.1 Hz, 2H), 3.36 (t, J=8.1 Hz, 2H); MS (ES+) m/z 411.9 (M+1).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([CH2:33][CH3:34])=[C:17]3[N:22]([CH:23]=2)[CH:21]=[CH:20][CH:19]=[C:18]3[CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:35][C:36](=[O:39])[C:37]#[CH:38]>>[C:36]([C:37]1[CH:38]=[C:23]2[N:22]3[C:17](=[C:18]([CH2:24][O:25][Si:26]([C:29]([CH3:30])([CH3:32])[CH3:31])([CH3:27])[CH3:28])[CH:19]=[CH:20][C:21]=13)[C:16]([CH2:33][CH3:34])=[C:15]2[C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][CH:11]=1)(=[O:39])[CH3:35]
Reactant: CCc1c(-c2ccc(OCc3ccccc3)cc2)cn2cccc(CO[Si](C)(C)C(C)(C)C)c12
Reactant: C#CC(C)=O
Product: CCc1c(-c2ccc(OCc3ccccc3)cc2)c2cc(C(C)=O)c3ccc(CO[Si](C)(C)C(C)(C)C)c1n32
Yield: 70 %

Procedure:
2-(4-Benzyloxyphenyl)-8-(tert-butyldimethylsilanyloxymethyl)-1-ethylindolizine was reacted with 3-butyn-2-one by the general synthetic principles outlined in example 73, step 1, to afford 4-acetyl-2-(4-benzyloxyphenyl)-7-(tert-butyldimethylsilanyloxymethyl)-1-ethylpyrrolo[2,1,5-cd]indolizine as a brown oil in 70% yield. 1H--NMR (DMSO-d6, 200 MHz) δ: 0.13 (s, 6 H); 0.89 (s, 9 H); 1.37 (t, 3 H); 2.64 (s, 3 H); 3.18 (q, 2 H); 5.20 (s, 2 H); 5.32 (s, 2 H); 7.12-7.54 (m, 7 H); 7.73 (d, 2 H); 7.94 (d, 1 H); 8.18 (s, 1 H); 8.34 (d, 1 H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:11])[CH2:9]Br)=[CH:4][C:3]=1[S:12]([NH2:15])(=[O:14])=[O:13].[CH3:16][CH:17]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1OC1C>CC(=O)CC>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:11])[CH2:9][N:26]([CH:17]([CH3:16])[CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:4][C:3]=1[S:12]([NH2:15])(=[O:14])=[O:13]
Reactant: Nc1ccc(C(=O)CBr)cc1S(N)(=O)=O
Reactant: CC(CCc1ccccc1)NCc1ccccc1
Agent: CC1CO1
Solvent: CCC(C)=O
Product: CC(CCc1ccccc1)N(Cc1ccccc1)CC(O)c1ccc(N)c(S(N)(=O)=O)c1

Procedure:
A solution of 2-amino-5-(2-bromoacetyl)benzenesulphonamide (0.5 g), N-(1-methyl-3-phenylpropyl)-N-(phenylmethyl) amine (0.45 g) and propylene oxide (2.5 ml) in 2-butanone (30 ml) was heated under reflux for 3 hours. The solution was then concentrated to a red-brown oil (0.7 g) which was dissolved in absolute ethanol (30 ml) and treated with sodium borohydride (258 mg) at room temperature during 2 hours. Excess borohydride was then destroyed with 2N hydrochloric acid and the ethanol was removed under reduced pressure. The residue was basified with 8% sodium bicarbonate and extracted with ethyl acetate (3 × 50 ml). The extracts were washed with water (100 ml), dried and concentrated to an orange oil (0.63 g). The oil was dissolved in acetone (10 ml) and re-precipitated as an orange solid (340 mg) by addition of petroleum ether (b.p. 60°-80°). Chromatographic purification of this solid on silica plates [Merck St17; elution with chloroform: methanol (5:1 )] and conversion of the product into a hydrochloride salt gave the title compound, 0.2 g, m.p. 133°-136°.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:3]=1.[C:16](#[N:18])C.[OH2:19]>>[Cl:8][C:6]1[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16]([NH2:18])=[O:19])[N:5]=1
Reactant: Clc1nc(Cl)nc(Nc2ccccc2)n1
Reactant: CC#N
Reactant: O
Product: NC(=O)N(c1ccccc1)c1nc(Cl)nc(Cl)n1
Reaction time: 2 h

Procedure:
A solution of 30 parts of dichlorosulphonylisocyanate in 100 parts of dry acetronitrile is slowly added dropwise to a suspension of 48.22 parts of 2,4-dichloro-6-phenylamino-s-triazine in 100 parts by volume of dry acetonitrile. The mixture is warmed gently and soon a clear, slightly yellowish solution forms. The reaction is brought to completion by subsequently stirring the solution for about 2 hours at 45°-50°C and then for 2 hours at room temperature. Then 320 parts by volume of water are added in such a manner that the temperature rises initially to 70°-75°C but is then immediately lowered. The precipitate which has formed is filtered off with suction, washed neutral with water and dried in vacuo to yield 52 parts of N-(2,4-dichloro-s-triazin-6-yl)-N-phenyl-urea which melts at 151°-154°C and is pure enough for most reactions. Recrystallisation from perchloroethylene yields a white, crystalline product which melts at 155°-157°C and has the following analytical values:
Reaction SMILES: [OH:1][C:2]([CH:5]1[CH2:9][CH2:8][CH:7]([CH3:10])[CH:6]1[OH:11])([CH3:4])[CH3:3].ClCCl.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(OCC)C>[OH:1][C:2]([CH:5]1[CH2:9][CH2:8][CH:7]([CH3:10])[C:6]1=[O:11])([CH3:4])[CH3:3]
Reactant: CC1CCC(C(C)(C)O)C1O
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: CC1CCC(C(C)(C)O)C1=O
Temperature: 25 °C
Reaction time: 5 h
Yield: 84.6 %

Procedure:
7.9 g of 2-(1-hydroxyisopropyl)-5-methyl-cyclopentanol was added dropwise to 100 ml of a dichloromethane suspension containing 16.2 g pyridinium chlorochromate and the mixture was stirred for 5 hours at room temperature. The reaction solution was admixed with diethylether and stirred. Then, the chromate was filtered out and the filtrate was condensed under a vacuum. The residue was purified by means of silica gel column chromatography (eluent: hexane/ethylacetate=7/3) and 6.6 g of 2-(1-hydroxyisopropyl)-5-methyl-cyclopentanone was obtained as an oily substance (yield: 86%).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[N+:16]([C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[C:21]([C:29]([F:32])([F:31])[F:30])[CH:20]=1)([O-:18])=[O:17]>C(Cl)Cl>[CH3:8][O:9][CH:10]1[CH2:15][CH2:14][N:13]([S:25]([C:22]2[CH:23]=[CH:24][C:19]([N+:16]([O-:18])=[O:17])=[CH:20][C:21]=2[C:29]([F:30])([F:31])[F:32])(=[O:27])=[O:26])[CH2:12][CH2:11]1
Reactant: COC1CCNCC1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)c(C(F)(F)F)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1CCN(S(=O)(=O)c2ccc([N+](=O)[O-])cc2C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Triethylamine (1.0 g) and 4-methoxypiperidine (1.15 g) were added to a solution of 4-nitro-2-trifluoromethylbenzene sulphonyl chloride (2.89 g) in methylene chloride (40 ml). The mixture was stirred at 25°C. for 2 hours and then evaporated to dryness in vacuo. The residual oil was triturated with 1:1 aqueous isopropanol and the resulting solid was recrystallized from isopropanol to give 1-(4-methoxypiperidinosulphonyl)-4-nitro-2-trifluoromethyl-benzene, m.p. 141°-143°C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C:13]([C:15]([OH:17])=[O:16])=[CH:12][CH2:11][C@H:10]1[C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][Si](C=[N+]=[N-])(C)C.C(O)(=O)C>CO.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C:13]([C:15]([O:17][CH3:27])=[O:16])=[CH:12][CH2:11][C@H:10]1[C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CC(C(=O)O)=CC[C@H]1c1cc(F)c(F)cc1F
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: CC(=O)O
Solvent: ClCCl
Product: COC(=O)C1=CC[C@@H](c2cc(F)c(F)cc2F)[C@H](NC(=O)OC(C)(C)C)C1

Procedure:
A solution of Example 39A (510 mg) was dissolved in methanol (1 mL) and CH2Cl2 (1 mL). Then, (trimethylsilyl)diazomethane solution (0.4 mL, 2M in ether) was added. After ten minutes, acetic acid (0.2 mL) was added. The mixture was concentrated, filtered through a silica gel plug, and purified by chromatography (Column: Chiralcel AD, Mobile Phase: hexane/ethanol/methanol=95/2.5/2.5) to give the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.31 (s, 9H), 2.18-2.28 (m, 1H), 2.41-2.50 (m, 1H), 2.57-2.67 (m, 1H), 2.86 (d, J=16.48 Hz, 1H), 3.10-3.18 (m, 1H), 3.76 (s, 3H), 4.02 (s, 1H), 4.37 (d, J=7.63 Hz, 1H), 6.86-6.94 (m, 1H), 6.99 (s, 1H), 7.11 (s, 1H). MS (DCI) m/z 403 (M+NH4)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[CH:5]([O:16][CH2:17][CH3:18])[CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2)[CH3:2].Cl[CH2:21][C:22]1[N:23]=[C:24]([C:28]2[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=2)[O:25][C:26]=1[CH3:27].[H-].[Na+]>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:19])[CH:5]([O:16][CH2:17][CH3:18])[CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[CH:10][N:11]2[CH2:21][C:22]1[N:23]=[C:24]([C:28]2[CH:29]=[CH:30][C:31]([CH:34]([CH3:36])[CH3:35])=[CH:32][CH:33]=2)[O:25][C:26]=1[CH3:27])[CH3:2]
Reactant: CCOC(=O)C(Cc1cccc2[nH]ccc12)OCC
Reactant: Cc1oc(-c2ccc(C(C)C)cc2)nc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(Cc1cccc2c1ccn2Cc1nc(-c2ccc(C(C)C)cc2)oc1C)OCC

Procedure:
In analogy to the procedures described in examples 1 a] and 1 b], rac-2-ethoxy-3-(1H-indol-4-yl)-propionic acid ethyl ester was reacted with 4-chloromethyl-2-(4-isopropyl-phenyl)-5-methyl-oxazole in N,N-dimethylformamide in the presence of sodium hydride to yield rac-3-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-1H-indol-4-yl}-2-ethoxy-propionic acid ethyl ester, which was subsequently saponified to yield rac-3-{1-[2-(4-isopropyl-phenyl)-5-methyl-oxazol-4-ylmethyl]-1H-indol-4-yl}-2-ethoxy-propionic acid as light green solid.
Reaction SMILES: [CH:1]([C:3]([CH3:5])=O)=[CH2:2].O=[C:7]([CH:9]=[C:10]([CH3:12])[CH3:11])[CH3:8].[OH-:13].[K+]>C(O)(=O)C>[CH3:5][C:3]1[CH2:8][CH2:7][C:9](=[C:10]([CH3:12])[CH3:11])[C:2](=[O:13])[CH:1]=1
Reactant: [OH-]
Reactant: C=CC(C)=O
Reactant: CC(=O)C=C(C)C
Agent: [K+]
Solvent: CC(=O)O
Product: CC1=CC(=O)C(=C(C)C)CC1

Procedure:
70 g of methyl vinyl ketone are added dropwise in the course of 60 minutes, whilst stirring, to 1,000 g of mesityl oxide and 50 ml of 50% potassium hydroxide solution, at 70°C. Thereafter the mixture is stirred for a further 10 minutes at 70°C and neutralized with glacial acetic acid, and the organic phase is distilled. 181 g of crude piperitenone are obtained; piperitenone content 55.7%, yield therefore 67.2%.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[NH2:19][CH:20]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:21]#[N:22]>>[C:21]([CH:20]([NH:19][C:10]([C:7]1[CH:6]=[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:9][N:8]=1)=[O:12])[C:23]([CH3:26])([CH3:25])[CH3:24])#[N:22]
Reactant: CC(C)(C)C(N)C#N
Reactant: O=C(O)c1cc(OCC(F)(F)F)c(C2CC2)cn1
Product: CC(C)(C)C(C#N)NC(=O)c1cc(OCC(F)(F)F)c(C2CC2)cn1

Procedure:
The title compound was synthesized in analogy to Example 112e, using 5-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 48c) and 2-Amino-3,3-dimethyl-butyronitrile (CAN 77425-86-6) as starting materials and isolated (782 mg, 90%); MS (ESI, m/z): 356.2 (M+H+).
Reaction SMILES: [OH-:1].[Na+].[OH:3][C:4]1[C:9](=[O:10])[CH:8]=[CH:7][O:6][CH:5]=1.[CH2:11]=O>O.CO>[OH:1][CH2:11][C:5]1[O:6][CH:7]=[CH:8][C:9](=[O:10])[C:4]=1[OH:3]
Reactant: C=O
Reactant: O=c1ccocc1O
Reactant: [OH-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=c1ccoc(CO)c1O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 85.3 %

Procedure:
Sodium hydroxide (4 g, 100 mmol, 1.25 eq.) dissolved in 10 ml distalled water was added to a solution of 3-hydroxy-pyran-4(1H)-one (8.96 g, 80 mmol, 1 eq.) in 50 ml methanol and allowed to stir at room temperature for 5 minutes. 16 ml (200 mmol, 2.5 eq.) of 35% formaldehyde solution was added dropwise over 15 minutes and the solution was stirred overnight. After adjustment to pH 1 with 37% w/v hydrochloric acid, the reaction mixture was concentrated in vacuo to dryness and the resulting solid was extracted with 2×100 ml of isopropanol at 90° C. The isopropanol extracts were concentrated to yield the crude products. Recrystallisation from isopropanol afforded 9.7 g (85.4%) of the pure title product as a white crystalline solid. m.p. 154-156° C. [lit. 148-150° C. (Tate and Miller., 1964)].
Reaction SMILES: [Cl-].[Na+:2].[OH-].[Na+].[C:5]([O-:24])(=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Na+]>O>[C:5]([O-:24])(=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:5][CH2:6][CH2:7][CH3:8].[Na+:2].[C:5]([O-:24])(=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Na+:2]
Reactant: CCCCCCCCCCCCCCCCCC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCCC(=O)[O-]
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]

Procedure:
The charge consists of 450 ml. water and 150 g. of the copolymer plus surfactant and, in some cases, sodium chloride as indicated. Sodium behenate and sodium myristate are prepared by neutralization of the corresponding acids with sodium hydroxide. Sodium stearate employed is U.S.P. grade.
Reaction SMILES: [F-].[K+].[F:3][C:4]([Si](C)(C)C)([F:6])[F:5].[Br:11][C:12]1[CH:13]=[N:14][C:15](I)=[N:16][CH:17]=1.N>CN1C(=O)CCC1.CN(C)C=O>[Br:11][C:12]1[CH:13]=[N:14][C:15]([C:4]([F:6])([F:5])[F:3])=[N:16][CH:17]=1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: Brc1cnc(I)nc1
Agent: N
Agent: [F-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: CN(C)C=O
Product: FC(F)(F)c1ncc(Br)cn1

Procedure:
A mixture of potassium fluoride (1.77 g) and cuprous iodide (5.79 g) was stirred and heated together using a heat gun under vacuum (˜1 mm) for 20 min. After cooling, dimethyl formamide (20 ml) and N-methyl pyrrolidinone (20 ml) were added followed by (trifluoromethyl)trimethylsilane (4.1 ml) and 5-bromo-2-iodopyrimidine (6.5 g). The mixture was stirred at rt for 5 h and then the brown solution was poured into 6N ammonia solution. The product was extracted into ethyl acetate and the extracts were washed with sodium bicarbonate solution and brine and then dried (Na2SO4) and evaporated. Chromatography on silica gel (elution with 20-50% dichloromethane in pentane) gave the title compound (D13) as a white solid (2.4 g). 1H NMR (CDCl3): 8.97 (2H, s).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6]3=[C:7]([C:12]([O:14][C:15](=[O:16])[C:5]3=[CH:4][CH:3]=1)=O)[CH:8]=[CH:9][CH:10]=2.[CH:17]([C:20]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]([CH3:29])[CH3:28])[C:21]=1[NH2:22])([CH3:19])[CH3:18]>CN1CCCC1=O.C([O-])(=O)C.[Zn+2].C([O-])(=O)C>[Cl:1][C:2]1[C:11]2[C:6]3=[C:7]([C:12](=[O:14])[N:22]([C:21]4[C:23]([CH:27]([CH3:28])[CH3:29])=[CH:24][CH:25]=[CH:26][C:20]=4[CH:17]([CH3:19])[CH3:18])[C:15](=[O:16])[C:5]3=[CH:4][CH:3]=1)[CH:8]=[CH:9][CH:10]=2
Reactant: O=C1OC(=O)c2ccc(Cl)c3cccc1c23
Reactant: CC(C)c1cccc(C(C)C)c1N
Agent: CC(=O)[O-]
Agent: [Zn+2]
Solvent: CN1CCCC1=O
Product: CC(C)c1cccc(C(C)C)c1N1C(=O)c2cccc3c(Cl)ccc(c23)C1=O
Temperature: 200 °C

Procedure:
A mixture of 23.3 g of 4-chloronaphthalene-1,8-dicarboxylic anhydride, 19.0 g of 2,6-diisopropylaniline and 9.2 g of anhydrous zinc acetate in 65 ml of N-methylpyrrolidone was heated at 200° C. for 3 hours. After cooling, the precipitate formed was filtered off, washed and dried. This gave 22.4 g of 4-chloro-N-(2,6-diisopropylphenyl)naphthalene-1,8-dicarboximide having a melting point of 289° C.
Reaction SMILES: [Na].[CH3:2][CH2:3][O:4][C:5]([CH2:7][NH2:8])=[O:6].CN(C)[CH:11]=[C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:13]=[N+](C)C.Cl([O-])(=O)(=O)=O>O.CCO>[CH2:3]([O:4][C:5]([C:7]1[NH:8][CH:11]=[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:13]=1)=[O:6])[CH3:2]
Reactant: CCOC(=O)CN
Reactant: CN(C)C=C(C=[N+](C)C)c1ccccc1
Agent: [Na]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1cc(-c2ccccc2)c[nH]1
Reaction time: 0.5 h
Yield: 31.83 %

Procedure:
Sodium metal (119 mg, 5.1 mmol) was added to EtOH (15 mL) and stirred for 30 minutes. Glycine ethyl esater hydrochloride (345 mg, 2.47 mmol) and (3-dimethylamino-2-phenyl-allylidene)-dimethyl-ammonium; perchlorate (500 mg, 1.65 mmol) was then added. The resulting mixture was stirred and heated to reflux for 2 hrs. Evaporated the reaction mixture to get the residue. The residue was diluted with cold water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to get the residue. The residue obtained was purified by column chromatography (using silicagel of 60-120 mesh and 10% EtOAc in Hexane as eluent) to afford 113 mg (31.83% yield) of 4-phenyl-1H-pyrrole-2-carboxylic acid ethyl ester. LCMS Purity: 98.96%. 1H NMR (CDCl3): δ 9.2 (bs, 1H), 7.58 (d, 2H), 7.42 (t, 2H), 7.26 (m, 3H), 4.4 (q, 2H), 1.4 (t, 3H).