Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.[OH:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:12][C:11]=1[C:26](OCC)=[O:27]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH3:8][C:4]1[N:3]=[C:2]([NH:1][C:26]([C:11]2[C:10](=[O:9])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:12]=2)=[O:27])[CH:7]=[CH:6][CH:5]=1
Reactant: Cc1cccc(N)n1
Reactant: CCOC(=O)C1=C(O)c2ccccc2N(c2ccccc2)C1
Agent: [Mn+4]
Agent: [O-2]
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: Cc1cccc(NC(=O)c2cn(-c3ccccc3)c3ccccc3c2=O)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of 5.49 g of 2-amino-6-methylpyridine and 10 g of 1,2-dihydro-4-hydroxy-1-phenyl-3-quinolinecarboxylic acid, ethyl ester in 500 ml of toluene was refluxed for 24 hours in a soxhlet apparatus containing 10 g of 4 Å molecular sieves. The solution was filtered and evaporated. The residue was purified by means of high pressure liquid chromatography (silica gel: dichloromethane as the eluent) to afford 9.8 g of 1,2-dihydro-4-hydroxy-N-(6-methyl-2-pyridyl)-1-phenyl-3-quinolnecarboxamide which was dissolved in chloroform, treated with 35 g of activated manganese dioxide and stirred for three hours at room temperature.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[S:11]([C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1)(=[O:14])(=[O:13])[NH2:12]>N1C=CC=CC=1>[NH:9]1[C:10]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[NH:1][S:21]([C:18]2[CH:17]=[CH:16][C:15]([S:11](=[O:14])(=[O:13])[NH2:12])=[CH:20][CH:19]=2)(=[O:23])=[O:22])[CH:7]=[CH:8]1
Reactant: NS(=O)(=O)c1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1cccc2cc[nH]c12
Solvent: c1ccncc1
Product: NS(=O)(=O)c1ccc(S(=O)(=O)Nc2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Yield: 63.3 %

Procedure:
The synthesis of the present compound can be carried out according to the process disclosed in JP-A-7-165708. For example, the present compound can be synthesized as follows. After dissolving 264 mg (2 mmol) of 7-amino-1H-indole in pyridine, 767 mg (3 mmol) of 4-sulfamoylbenzenesulfonyl chloride is added thereto under stirring at room temperature. After the mixture is stirred overnight at room temperature, the solvent is evaporated under reduced pressure. Ethyl acetate and 0.2 N hydrochloric acid are added to the resulting residue. The organic layer is separated, washed with water, and dried over magnesium sulfate, followed by evaporation of the solvent. The resulting residue is purified by silica gel column chromatography to give 445 mg of N-(1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([NH:7][CH2:8][CH2:9][CH3:10])=[N:4][N:3]=1.[CH:11]1([C:15](Cl)=[O:16])[CH2:14][CH2:13][CH2:12]1.C(N(CC)CC)C>C1C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([N:7]([CH2:8][CH2:9][CH3:10])[C:15]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[O:16])=[N:4][N:3]=1
Reactant: CCCNc1nnc(C)o1
Reactant: O=C(Cl)C1CCC1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CCCN(C(=O)C1CCC1)c1nnc(C)o1

Procedure:
5-Methyl-2-n-propylamino 1,3,4-oxadiazole (6 g, 0.04 mol) prepared as in (b) above, was refluxed with cyclobutanecarboxylic acid chloride (5.5 g, 0.05 mol) in benzene (25 ml) in the presence of triethylamine (4.72 g, 0.05 mol) for 2 hours. The mixture was filtered and the filtrate washed with dilute HCl, saturated solution NaCHO3 and water; dried over magnesium sulphate, filtered, solvent evaporated off to yield a reddish brown liquid which was distilled twice in a vigreux flask to yield the title compound as a slightly pink liquid (b.p. 110°-111° C./0.27 mm Hg).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][C:20]([O:26][CH3:27])=[CH:21][CH:22]=3)[CH:17]=2)(=[O:15])=[O:14])[C:8]1=[O:28])#[N:2].[CH2:32](Br)[CH:33]=[CH:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([N:12]([CH2:32][CH:33]=[CH:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[S:13]([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][C:20]([O:26][CH3:27])=[CH:21][CH:22]=3)[CH:17]=2)(=[O:15])=[O:14])[C:8]1=[O:28])#[N:2]
Reactant: BrCC=Cc1ccccc1
Reactant: COc1ccc2ccc(S(=O)(=O)N[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)cc2c1
Product: COc1ccc2ccc(S(=O)(=O)N(CC=Cc3ccccc3)[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)cc2c1

Procedure:
The title compound is prepared as described in EXAMPLE 25, Part A using 7-methoxynaphthalene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]amide, prepared as described in EXAMPLE 43, part A, and cinnamyl bromide. The crude product is purified by column chromatography eluting with gradient of 20% EtOAc/hexanes to 30% EtOAc/hexanes to afford the title compound as a white foam.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:5]=[CH:6][C:7]([OH:19])=[C:8]([NH:10][C:11](=O)[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)[CH:9]=1.O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O.C1(C)C=CC=CC=1>[N:15]1[CH:16]=[CH:17][C:12]([C:11]2[O:19][C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:21])([F:20])[F:1])=[CH:9][C:8]=3[N:10]=2)=[CH:13][CH:14]=1
Reactant: O=C(Nc1cc(OC(F)(F)F)ccc1O)c1ccncc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Solvent: O
Product: FC(F)(F)Oc1ccc2oc(-c3ccncc3)nc2c1
Reaction time: 1 h

Procedure:
To a mixture of 1.96 g of N-[5-(trifluoromethoxy)-2-hydroxyphenyl]isonicotinamide, 35 ml of tetrahydrofuran and 1.73 g of triphenylphosphine, a mixture of 1.26 g of diethyl azodicarboxylate and 5 ml of THF was added dropwise at room temperature. The resultant mixture was stirred at room temperature for two hours. To the mixture, 1.73 g of triphenylphosphine and 3.15 g of 40% toluene solution of diethyl azodicarboxylate were added and stirred for one hour. Furthermore, to the mixture, 0.58 g of triphenylphosphine and 1.05 g of 40% toluene solution of diethyl azodicarboxylate were added and stirred for one hour. The mixture solution was poured into water, followed by extraction with ethyl acetate. The combined organic layers were washed with water and a saturated sodium chloride solution, and dried over magnesium sulfate. The reaction mixture was concentrated. The residue was subjected to silica gel column chromatography to give 2-(pyridin-4-yl)-5-(trifluoromethoxy)benzoxazole (hereinafter, referred to as “active compound 12”).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[I-].[CH2:48]([N+:52]1[N:56]=[C:55]([CH3:57])[S:54][C:53]=1[CH3:58])[CH2:49][CH2:50][CH3:51]>>[CH2:48]([N:52]1[N:56]=[C:55]([CH3:57])[S:54]/[C:53]/1=[CH:58]\[C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[O:13])[CH2:49][CH2:50][CH3:51]
Reactant: CCCC[n+]1nc(C)sc1C
Reactant: O=C(O)c1ccc2ccccc2c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [I-]
Solvent: CCN(C(C)C)C(C)C
Product: CCCCN1N=C(C)S/C1=C\C(=O)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 20 mL vial 2-naphthoic acid (0.9 mL of 0.2 M in DMA, 1.10 equiv) was added followed by the addition of HATU (76 mg in 0.7 mL of DMA, 0.2 mmol, 1.20 equiv.), DIEA (51 mg in 0.7 mL of DMA, 0.4 mmol, 2.40 equiv.), and finally 3-butyl-2,5-dimethyl-1,3,4-thiadiazol-3-ium iodide (49 mg in 0.7 mL of DMA, 0.17 mmol, 1 equiv.). The mixture was shaken overnight at room temperature and then concentrated in vacuo. The resulting residue was taken up in 1:1 DMSO/MeOH and purified by reverse phase HPLC using a method analogous to that described in Example 53 to provide the title compound. 1H NMR (500 MHz, DMSO-d6/D2O) δ ppm 0.93 (t, 3 H) 1.32-1.41 (m, 2 H) 1.75-1.83 (m, 2 H) 2.50 (s, 3 H) 4.28 (t, 2 H) 6.90 (s, 1 H) 7.93-8.00 (m, 2 H) 8.04-8.08 (m, 1 H) 8.10-8.15 (m, 1 H) 8.61 (s, 1 H); MS (ESI) m/z 325 (M+H)+.
Reaction SMILES: CO[C:3](=[O:23])[CH:4]([N:6]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[C:8]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[C:7]1[CH3:22])[CH3:5].Cl.[CH3:25][NH:26][O:27][CH3:28].C([Mg]Cl)(C)C>>[CH3:28][O:27][N:26]([CH3:25])[C:3](=[O:23])[CH:4]([N:6]1[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[C:8]([C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])=[C:7]1[CH3:22])[CH3:5]
Reactant: CNOC
Reactant: COC(=O)C(C)n1c(C)c(C(=O)OC(C)(C)C)c2cccnc21
Agent: CC(C)[Mg]Cl
Agent: Cl
Product: CON(C)C(=O)C(C)n1c(C)c(C(=O)OC(C)(C)C)c2cccnc21
Temperature: 0 °C
Yield: 60.2 %

Procedure:
To a 100 mL round-bottom flask was added (±)-tert-butyl 1-(1-methoxy-1-oxopropan-2-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (0.958 g, 3.01 mmol) and N,O-dimethylhydroxylamine hydrochloride (0.440 g, 4.51 mmol). The flask was vac/purged 3× with N2 then THF (17 mL) were added and the reaction was cooled to −40° C. isopropylmagnesium chloride (4.51 ml, 9.03 mmol) was added dropwise and the reaction was mixed at that temperature for 1 h then warmed to 0° C. for 1 h then quenched with 1N HCl, extracted with EtOAc. The org layer was washed with water then brine, dried over Na2SO4, filtered, concentrated, deposited onto silica gel with aid of DCM, and purified by CC using 25% EtOAc in Hex as eluent to provide (±)-tert-butyl 1-(1-(methoxy(methyl)amino)-1-oxopropan-2-yl)-2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (0.630 g, 60.3%). LRMS (M+H+) m/z: calcd 348.41. found 348.2.
Reaction SMILES: [H-].[Na+].[CH3:3][CH2:4][O:5][C:6]([CH:8](P(OCC)(OCC)=O)[F:9])=[O:7].[CH3:18][Si:19]([CH3:50])([CH3:49])[CH2:20][CH2:21][O:22][CH2:23][N:24]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:25]1[N:30]2[N:31]=[CH:32][CH:33]=[C:29]2[N:28]=[C:27]([CH:34]2[CH2:39][CH2:38][C:37](=O)[CH2:36][CH2:35]2)[CH:26]=1>C1COCC1.C(Cl)Cl>[CH3:46][Si:45]([CH3:48])([CH3:47])[CH2:44][CH2:43][O:42][CH2:41][N:24]([CH2:23][O:22][CH2:21][CH2:20][Si:19]([CH3:50])([CH3:49])[CH3:18])[C:25]1[N:30]2[N:31]=[CH:32][CH:33]=[C:29]2[N:28]=[C:27]([CH:34]2[CH2:39][CH2:38][C:37](=[C:8]([F:9])[C:6]([O:5][CH2:4][CH3:3])=[O:7])[CH2:36][CH2:35]2)[CH:26]=1
Reactant: CCOC(=O)C(F)P(=O)(OCC)OCC
Reactant: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(C2CCC(=O)CC2)nc2ccnn12
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCOC(=O)C(F)=C1CCC(c2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3nccc3n2)CC1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 92.1 %

Procedure:
To a 250 mL roundbottom flask containing 80 mL THF was charged sodium hydride (60% w/w in mineral oil, 12.86 mmol, 515 mg). This suspension was broken up in the sonicaid and then cooled to 0° C. in icebath. Triethyl 2-fluoro-2-phosphonoacetate (12.86 mmol, 3.12 g) was taken up in THF (10 mL) and added dropwise to stirring NaH suspension. The resulting solution was allowed to stir at 0° C. for 10 minutes. 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanone (6.43 mmol, 3.16 g) was taken up in THF (10 mL) and added dropwise to the stirring solution. The reaction was allowed to warm to room temperature and stir 18 hours. At 18 hours, the reaction was diluted with DCM (400 mL) and washed with H2O. The organic layer was collected and dried over Na2SO4. This solution was reduced in vacuo and purified via flash chromatography to yield the title compound (3.43 g, 5.92 mmol).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][NH:16][C:17](=[O:25])[C:18]3[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][N:19]=3)[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].Br[CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29]>>[CH2:28]([CH:27]([O:1][C:2]1[CH:3]=[C:4]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][NH:16][C:17](=[O:25])[C:18]3[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][N:19]=3)[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9])[CH2:30][CH3:31])[CH3:29]
Reactant: COc1ccc(-c2nc(CNC(=O)c3ncccc3C)co2)cc1O
Reactant: CCC(Br)CC
Product: CCC(CC)Oc1cc(-c2nc(CNC(=O)c3ncccc3C)co2)ccc1OC

Procedure:
Using the compound obtained in Example 17 and 3-bromopentane, white powdery N-{2-[3-(1-ethylpropoxy)-4-methoxy phenyl]oxazol-4-ylmethyl}-3-methylpicolinamide was obtained following the procedure of Example 3.
Reaction SMILES: [CH2:1]([C:4]1([CH2:22][CH:23]=C)[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]1=[O:21])[CH:2]=C>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.ClCCCl>[CH3:20][Si:17]([CH3:18])([CH3:19])[CH2:16][CH2:15][O:14][CH2:13][N:6]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:12]2[C:4]2([CH2:1][CH:2]=[CH:23][CH2:22]2)[C:5]1=[O:21]
Reactant: C=CCC1(CC=C)C(=O)N(COCC[Si](C)(C)C)c2ncccc21
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Solvent: ClCCCl
Product: C[Si](C)(C)CCOCN1C(=O)C2(CC=CC2)c2cccnc21

Procedure:
A mixture of 3,3-diallyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one from Step D (1.02 g, 2.96 mmol) and Grubbs second generation catalyst (37 mg, 0.045 mmol) in DCE (60 mL) was heated at reflux for 3.5 h. The mixture was concentrated in vacuo and purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 75:25, to give the title compound. MS: m/z=317 (M+1).
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.[NH2:12][C@@H:13]([CH2:31][O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:19][CH:18]=1)=[O:15]>>[CH2:33]([O:32][CH2:31][C@H:13]([NH:12][C:9](=[O:11])[CH2:8][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][N:2]=1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:19][CH:18]=1)=[O:15])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Reactant: O=C(O)Cc1cnccn1
Agent: Cl
Product: O=C(Cc1cnccn1)N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Yield: 46 %

Procedure:
Proceeding as in Example 1, but substituting 2-(pyrazin-2-yl)acetic acid hydrochloride and (S)-2-amino-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide, gave Compound 159, (S)-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)-2-(2-(pyrazin-2-yl)acetamido)propanamide (66 mg, 46%). 1H-NMR (400 MHz, CDCl3): σ 8.63-8.44 (m, 4H), 7.40-7.19 (m, 9H), 7.05-6.92 (m, 3H), 4.74-4.70 (m, 1H), 4.66 (d, 1H), 4.55 (d, 1H), 4.10 (dd, 1H), 3.85 (s, 2H), 3.64 (dd, 1H). MS (EI) for C28H25FN4O4. found 501.2 (MH+).
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35](Cl)=[O:36])[C:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][N:39]([CH3:48])[C:40]([N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)=[O:41]>>[CH3:38][N:39]([CH3:48])[C:40]([N:42]1[CH2:43][CH2:44][N:45]([C:35]([N:15]2[C:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=[C:14]2[C:8]2[C:9]([O:11][CH2:12][CH3:13])=[N:10][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[N:6][CH:7]=2)=[O:36])[CH2:46][CH2:47]1)=[O:41]
Reactant: CCOc1nc(C(C)(C)C)ncc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CN(C)C(=O)N1CCNCC1
Product: CCOc1nc(C(C)(C)C)ncc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(C(=O)N(C)C)CC1

Procedure:
In a manner analogous to the method described in example 3, rac-(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with piperazine-1-carboxylic acid dimethylamide (Oakwood) to give the title compound. HR-MS (ES, m/z) calculated for C35H44N7O3Cl2 [(M+H)+] 680.2877, observed 680.288.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[S:10]([NH:13][C:14]1[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=[O:19])=[CH:16][CH:15]=1)(=[O:12])=[O:11].O[Li].O>CCO.O>[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[S:10]([NH:13][C:14]1[CH:24]=[CH:23][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1)(=[O:11])=[O:12]
Reactant: CCOC(=O)c1ccc(NS(=O)(=O)c2ccc(F)c(N)c2N)cc1
Agent: [Li]O
Solvent: O
Solvent: CCO
Product: Nc1c(F)ccc(S(=O)(=O)Nc2ccc(C(=O)O)cc2)c1N
Temperature: 70 °C
Reaction time: 8 h

Procedure:
To a solution of the compound 39E (350 mg, 1 mmol) in EtOH/H2O (10 mL/3 mL) was added LiOH.H2O (200 mg, 5 mmol) and the resulting suspension was stirred at 70° C. overnight. The solvent was concentrated and the residue was partitioned between aqueous 2 N HCl and EtOAc. The organic layer was separated and washed with water and brine, dried over Na2SO4 and concentrated to give the desired crude product 39F, which was confirmed by LCMS, and used in subsequent reaction without further purification. LC-MS: m/z 326.3 (M+H)+.
Reaction SMILES: [CH2:1]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH3:26])[C:23]([OH:25])=[O:24])=[CH:18][CH:17]=1)[CH2:2][CH2:3][CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[OH:27][CH2:28][CH:29]([CH2:31]O)[OH:30].B(F)(F)F.CCOCC>C1(C)C=CC=CC=1>[CH2:1]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH3:26])[C:23]([O:25][CH2:31][CH:29]([OH:30])[CH2:28][OH:27])=[O:24])=[CH:18][CH:17]=1)[CH2:2][CH2:3][CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: OCC(O)CO
Reactant: CCCCCCCCCC=CCCCNc1ccc(C(C)C(=O)O)cc1
Agent: FB(F)F
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CCCCCCCCCC=CCCCNc1ccc(C(C)C(=O)OCC(O)CO)cc1
Reaction time: 120 h

Procedure:
A solution of 11.8 g. of 4-(4-tetradecenylamino)phenylpropionic acid, 1.00 g. of glycerol, and 5.35 ml. of boron trifluoride etherate in 200 ml. of toluene is stirred under reflux for 48 hours. The solution is treated with an additional 5.35 ml. of boron trifluoride etherate and refluxing is continued for 120 hours. Dilution with water and methylene chloride followed by filtration affords the product as a white solid.
Reaction SMILES: [I:1][C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([NH2:9])[CH:3]=1.C(=O)(O)[O-].[Na+].Cl[CH:16]([CH:22]=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18]>C(COC)OC.ClCCl>[I:1][C:2]1[C:7]([CH3:8])=[CH:6][N:5]2[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][N:9]=[C:4]2[CH:3]=1
Reactant: CCOC(=O)C(Cl)C=O
Reactant: Cc1cnc(N)cc1I
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: COCCOC
Product: CCOC(=O)c1cnc2cc(I)c(C)cn12
Temperature: 100 °C

Procedure:
To a suspension of 4-iodo-5-methylpyridin-2-amine (I-28A) (1.55 g. 6.6 mmol), sodium bicarbonate (0.67 g, 7.9 mmol) in dry dimethoxyethane (10 mL) at room temperature, ethyl 2-chloro-3-oxopropanoate (1 g, 6.41 mmol) in dimethoxyethane (1 mL) was added dropwise. The reaction mixture was heated to 100° C. for 1 h and then cooled to room temperature and diluted with dichloromethane (50 mL). The organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The brown crude oil was purified by silica gel chromatography with a gradient of 0-15% ethyl acetate/hexanes to yield ethyl 7-iodo-6-methylimidazo[1,2-a]pyridine-3-carboxylate (I-28B) as light tan solid. 1H-NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 8.41 (s, 1H), 8.22 (s, 1H), 4.36 (q, J=7.2 Hz, 2H), 2.42 (s, 3H), 1.37 (t, J=7.2 Hz, 3H). MS m/z 331.0 (M+1).
Reaction SMILES: [C:1]([C:4]1[C:5]([O:17][CH3:18])=[C:6]([O:15][CH3:16])[CH:7]=[C:8](C(=O)C)[C:9]=1[O:10][CH3:11])(=[O:3])[CH3:2].[C:19]([O:22]O)(=[O:21])[CH3:20]>>[C:19]([O:22][C:8]1[C:9]([O:10][CH3:11])=[C:4]([C:1](=[O:3])[CH3:2])[C:5]([O:17][CH3:18])=[C:6]([O:15][CH3:16])[CH:7]=1)(=[O:21])[CH3:20]
Reactant: CC(=O)OO
Reactant: COc1cc(C(C)=O)c(OC)c(C(C)=O)c1OC
Product: COc1cc(OC(C)=O)c(OC)c(C(C)=O)c1OC
Yield: 30 %

Procedure:
It is moreover known from another class of substances that re action of 3, 5-diacetyl-1,2,4-trimethoxybenzene with peracetic acid provides 5-acetoxy-3acetyl-1,2,4-trimethoxybenzene as byproduct in 30% yield (H.H. Lee et al., J. Chem. Soc. 1965, 2743-2749).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N:9]1[N:13]=[C:12]2[CH:14]=[CH:15][C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:17][C:11]2=[N:10]1.N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:34]Br>C(Cl)(Cl)(Cl)Cl>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][Br:34])=[CH:4][C:3]=1[N:9]1[N:13]=[C:12]2[CH:14]=[CH:15][C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:17][C:11]2=[N:10]1
Reactant: Cc1ccc(O)c(-n2nc3ccc(C(C)(C)C)cc3n2)c1
Reactant: BrBr
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)c1ccc2nn(-c3cc(CBr)ccc3O)nc2c1
Temperature: 25 °C

Procedure:
2-(2′-hydroxy-5′-bromomethyphenyl)-5-tert-butylbenzotriazole was prepared from the bromination of 2-(2′-hydroxy-5′-methyphenyl)-5-tert-butylbenzotriazole using azobis isobutyronitrile (AIBN) as an initiator. In a 500 ml three-necked round bottomed flask, 6.274 g (0.0223 mol) 2-(2′-hydroxy-5′-methyphenyl)-5-tert-butylbenzotriazole and 100 mg of AIBN were taken and dissolved in 150 ml of dry carbon tetrachloride. In a separate conical flask 4.18 g (1.5 ml, 0.03 mol) of bromine was dissolved in 75 ml of dry carbon tetrachloride and solution was transferred to a cylindrical funnel with pressure equalizing tube. Three-necked round-bottomed flask containing solution of 2-(2′-hydroxy-5′-methyphenyl)-5-tert-butylbenzotriazole was kept in oil-bath with temperature 50° C. Nitrogen was bubbled through the solution for creating inert atmosphere. Cylindrical funnel containing bromine solution was mounted on the three-necked round-bottomed flask. Solution in the flask was continuously stirred with the help of magnetic stirrer. Bromine solution was added, drop-by-drop, from funnel to the flask for a span of 4-5 hours till all the solution was poured out. After that heating was stopped and the final reaction mixture was allowed to cool at room temperature. Product was separated by solvent evaporation. Finally the product was purified by recrystallization from acetone. The yield of 2-(2′-hydroxy-5′-bromomethyphenyl)-5-tert-butylbenzotriazole was 6.8 g (84%)
Reaction SMILES: [CH2:1]1[CH2:14][O:13][C:8]23[O:9][CH2:10][CH2:11][O:12][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16][C:17](=O)[C@:18]5([OH:28])[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:2]1.[OH:30]/[N:31]=C1\C[C@@H]2[C@@H]([C@]3(C)C\1CC(=O)CC3)CC[C@@]1(C)[C@H]2CCC1=O>>[CH2:1]1[CH2:14][O:13][C:8]23[O:9][CH2:10][CH2:11][O:12][C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16]/[C:17](=[N:31]\[OH:30])/[C@:18]5([OH:28])[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:2]1
Reactant: C[C@]12CC[C@H]3[C@@H](CC(=O)[C@@]4(O)CCCC[C@]34C)[C@@H]1CC13OCCOC12OCCO3
Reactant: C[C@]12CCC(=O)CC1/C(=N/O)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Product: C[C@]12CC[C@H]3[C@@H](C/C(=N\O)[C@@]4(O)CCCC[C@]34C)[C@@H]1CC13OCCOC12OCCO3
Yield: 85 %

Procedure:
17,17-Bis(ethylendioxy)-5α-hydroxy-6-(E)-hydroxyiminoandrostane was prepared in 85% yield from 3,3:17,17-bis(ethylendioxy)-5α-hydroxyandrostan-6-one by the procedure described above for the preparation of 6-(E)-hydroxyiminoandrostane-3,17-dione (II-at, Prepn. 20). The crude was purified by flash chromatography (SiO2, cyclohexane/acetone/CH2Cl2 70/15/15). 1H-NMR (300 MHz, DMSO-d6, ppm from TMS: δ 10.45 (s, 1H), 4.33 (s, 1H), 3.96-3.69 (m, 8H), 2.96 (dd, 1H), 2.02-1.08 (m, 18H), 0.74 (s, 3H), 0.71 (s, 3H).