Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH:18]=2)[C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[CH:6][N:5]=[C:4]2[N:19](COCC[Si](C)(C)C)[CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:3]=12.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([CH:18]=2)[C:13]([N:15]([CH3:16])[CH3:17])=[O:14])=[CH:6][N:5]=[C:4]2[NH:19][CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[F:28])[C:3]=12
Reactant: CN(C)C(=O)c1cncc(-c2cnc3c(c(-c4ccccc4F)cn3COCC[Si](C)(C)C)c2Cl)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)C(=O)c1cncc(-c2cnc3[nH]cc(-c4ccccc4F)c3c2Cl)c1
Reaction time: 10 h
Yield: 33 %

Procedure:
5-[4-chloro-3-(2-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-nicotinamide was taken up in dichloromethane and 500 μL of trifluoroacetic acid added. The mixture was left at ambient temperature for 10 h and then evaporated. The residue was re-dissolved in 3 mL of dichloromethane and 100 μL of 1,2-ethylenediamine. After 6 h at ambient temperature the mixture was evaporated to dryness. The resulting crude was dissolved in dimethylsulfoxide and purified by mass-triggered reverse phase HPLC to afford 18.2 mg (46 μmol, 33%) of 5-[4-chloro-3-(2-fluoro-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-nicotinamide as an off-white solid. 1H-NMR [500 MHz, d6-DMSO] δ: 12.50 (s, br., 1H), 8.73 (d, 1H), 8.65 (d, 1H), 8.32 (s, 1H), 7.97 (t, 1H), 7.76 (s, 1H), 7.47 (ddd, 1H), 7.41 (, 1H), 7.28-7.21 (m, 2H), 3.01 (s, 3H), 2.97 (s, 3H); MS [MH+] m/z: 395.
Reaction SMILES: [OH:1][C:2]([C:5]1[N:6]=[C:7]([CH2:58][CH2:59][CH3:60])[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]3[N:38](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:37]=[N:36][N:35]=3)=[CH:24][CH:23]=2)[C:9]=1[C:10]([O:12][CH2:13][C:14]1[O:15][C:16](=[O:20])[O:17][C:18]=1[CH3:19])=[O:11])([CH3:4])[CH3:3]>C(O)(=O)C>[OH:1][C:2]([C:5]1[N:6]=[C:7]([CH2:58][CH2:59][CH3:60])[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]3[NH:38][N:37]=[N:36][N:35]=3)=[CH:24][CH:23]=2)[C:9]=1[C:10]([O:12][CH2:13][C:14]1[O:15][C:16](=[O:20])[O:17][C:18]=1[CH3:19])=[O:11])([CH3:4])[CH3:3]
Reactant: CCCc1nc(C(C)(C)O)c(C(=O)OCc2oc(=O)oc2C)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)O
Product: CCCc1nc(C(C)(C)O)c(C(=O)OCc2oc(=O)oc2C)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 74.8 %

Procedure:
A mixture of 1.4 g of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate [prepared as described in step (a) above] and 48 ml of 75% v/v aqueous acetic acid was stirred at 60° C. for 1 hour, after which it was concentrated by evaporation under reduced pressure. The residue was dissolved in toluene, and the resulting solution was concentrated by distillation under reduced pressure; this was repeated a further time in order to remove the remaining water and acetic acid. The residue thus obtained was purified by column chromatography through silica gel using 1:9 and 1:4 by volume mixtures of methanol and methylene chloride as the eluent, to give 0.73 g of the title compound, melting at 170°-172° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:14]1(=[O:20])[O:19][C:17](=[O:18])[CH2:16][CH2:15]1.[Cl-].[Al+3].[Cl-].[Cl-]>[N+](C1C=CC=CC=1)([O-])=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:20])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: O=C1CCC(=O)O1
Reactant: Clc1ccc(-c2ccccc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=[N+]([O-])c1ccccc1
Product: O=C(O)CCC(=O)c1ccc(-c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 13.6 %

Procedure:
A suspension of 4-chlorobiphenyl (9.43 g, 0.0500 mol), succinic anhydride (5.50 g, 0.0550 mol), and anhydrous aluminum chloride (14.8 g, 0.111 mol) in nitrobenzene (25 mL) at 5° C. under nitrogen was stirred 4 hours, then allowed to warm to room temperature. After 3 days, the mixture was heated at 95° C. to 120° C. for 1 hour, cooled to 5° C., and quenched with a mixture of ice (15 g), water (8 mL), and concentrated hydrochloric acid (HCl) solution (8 mL). Additional water (150 mL) was added, followed by ethyl acetate. The ethyl acetate layer was washed with 0.2 M HCl and extracted with saturated aqueous sodium bicarbonate solution. The bicarbonate layer was rotary evaporated briefly to remove residual ethyl acetate, then acidified by the dropwise addition of concentrated HCl solution. The resulting tan precipitate was filtered off, washed with 0.2 M HCl, and air dried. The solids were dissolved in hot toluene/acetone, and the solution was decolorized with activated carbon, and filtered hot through celite. The filtrate was concentrated, and the resulting crystals were filtered, washed, and dried in vacuo to give 1.96 g of 4-(4′-chloro-biphenyl-4-yl)-4-oxo-butyric acid as pale yellow plates; mp 184-185° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[NH:10][CH:11]1[CH2:13][CH2:12]1.[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1.OOS([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:11]1([N:10]2[C:3]3[CH:4]=[C:5]([C:6]#[N:7])[CH:8]=[CH:9][C:2]=3[N:1]=[C:14]2[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH2:12][CH2:13]1
Reactant: O=Cc1cccnc1
Reactant: N#Cc1ccc(N)c(NC2CC2)c1
Agent: O=C([O-])[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccc2nc(-c3cccnc3)n(C3CC3)c2c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4-amino-3-(cyclopropylamino) benzonitrile, (0.2 g, 0.0011 mol) and nicotinaldehyde (0.14 g, 0.0012 mol) in DMF (5 ml) and H2O (2 ml) was added OXONE® monopersulphate (0.84 g, 0.0013 mol). Reaction mass was stirred at room temperature for 3 h. The reaction mixture was basified with 10% K2CO3 solution to pH˜8-10 and extracted with EtOAc (3×20 ml). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under vacuum to afford the crude compound, which was purified by column chromatography to obtain title compound 1-cyclopropyl-2-(pyridine-3-yl)-1H-benzo[d]imidazole-6-carbonitrile. 1H NMR (400 MHz, DMSO-d6), δ: 9.21 (s, 1H), 8.77-8.76 (d, J=4.4 Hz, 1H), 8.45-8.43 (d, J=8 Hz, 1H), 8.25 (s, 1H), 7.89-7.87 (d, J=8 Hz, 1H), 7.68-7.61 (m, 2H), 3.91-3.87 (m, 1H), 1.17-1.12 (m, 2H), 0.71-0.70 (m, 2H). MS (M+1): 261.12; purity 97.77%.
Reaction SMILES: [C:1]([CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:9]=2[O:8][C:7]1=[O:16])([O:3][CH3:4])=[O:2].[Cl:17][C:18]1[CH:19]=[C:20]([C:26]([F:29])([F:28])[F:27])[CH:21]=[C:22]([F:25])[C:23]=1F.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[C:1]([CH2:5][N:6]1[C:10]2[CH:11]=[C:12]([O:15][C:23]3[C:22]([F:25])=[CH:21][C:20]([C:26]([F:27])([F:29])[F:28])=[CH:19][C:18]=3[Cl:17])[CH:13]=[CH:14][C:9]=2[O:8][C:7]1=[O:16])([O:3][CH3:4])=[O:2]
Reactant: Fc1cc(C(F)(F)F)cc(Cl)c1F
Reactant: COC(=O)Cn1c(=O)oc2ccc(O)cc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)Cn1c(=O)oc2ccc(Oc3c(F)cc(C(F)(F)F)cc3Cl)cc21
Temperature: 75 °C

Procedure:
A mixture of 1.37 grams (0.006 mole) of 3-carbomethoxymethyl-5-hydroxybenzoxazolone, 1.52 grams (0.007 mole) of 3-chloro-4,5-difluorobenzotrifluoride, 1.26 grams (0.009 mole) of potassium carbonate and 25 milliliters of dimethylsulfoxide was stirred in a water bath maintained at 75° C. until HPLC analysis indicated substantially complete consumption of starting material. The mixture was then poured into 100 milliliters of water, cooled in an ice bath and extracted twice with methylene chloride. The organic extracts were further extracted with three portions of water, dried over anhydrous magnesium sulfate and evaporated at reduced pressure. The oily residue was taken up in hexane, solidified, filtered and recrystallized from methanol affording 0.67 gram of material confirmed by NMR analysis as the desired product.
Reaction SMILES: [CH2:1]([NH:4][CH2:5][C:6]1[NH:7][C:8](=[O:16])[C:9]2[CH2:15][O:14][CH2:13][CH2:12][C:10]=2[N:11]=1)[C:2]#[CH:3].[F:17][C:18]1[CH:35]=[CH:34][C:21]([C:22]([CH:24]2[CH2:29][CH2:28][N:27]([CH2:30][C:31](O)=[O:32])[CH2:26][CH2:25]2)=[O:23])=[CH:20][CH:19]=1>>[F:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([CH:24]2[CH2:25][CH2:26][N:27]([CH2:30][C:31]([N:4]([CH2:5][C:6]3[NH:7][C:8](=[O:16])[C:9]4[CH2:15][O:14][CH2:13][CH2:12][C:10]=4[N:11]=3)[CH2:1][C:2]#[CH:3])=[O:32])[CH2:28][CH2:29]2)=[O:23])=[CH:34][CH:35]=1
Reactant: O=C(O)CN1CCC(C(=O)c2ccc(F)cc2)CC1
Reactant: C#CCNCc1nc2c(c(=O)[nH]1)COCC2
Product: C#CCN(Cc1nc2c(c(=O)[nH]1)COCC2)C(=O)CN1CCC(C(=O)c2ccc(F)cc2)CC1

Procedure:
Following the general procedure of Example 4, the title compound was prepared (44.3 mg) from 2-((prop-2-ynylamino)methyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-one and 2-(4-(4-fluorobenzoyl)piperidin-1-yl)acetic acid. Exact mass calculated for C25H27FN4O4 466.5. found 467.7 (ESI, M+H); 1H NMR (400 MHz, dichloromethane-d2) δ ppm 7.98 (dd, J=9.09, 5.56 Hz, 2H) 7.20 (t, J=8.59 Hz, 2H) 4.67 (d, J=9.60 Hz, 2H) 4.51 (d, J=15.16 Hz, 2H) 4.26-4.41 (m, 3H) 4.22 (br. s., 2H) 3.88-4.01 (m, 4H) 2.63-2.85 (m, 2H) 2.32 (br. s., 1H) 2.24 (br. s., 4H) 1.46-1.58 (s, 2H).
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[CH:16]([NH:18][C:19]1[S:20][CH:21]=[C:22]([C:24](=[N:40][O:41][CH3:42])[C:25]([NH:27][CH:28]2[C:38](=[O:39])[N:30]3[C:31]([C:35]([OH:37])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]23)=[O:26])[N:23]=1)=[O:17].[C:43]([O:53][CH2:54][CH:55]([CH2:57][O:58][C:59](=[O:68])[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH3:67])O)(=[O:52])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51].N1C=CC=CC=1>O1CCCC1>[CH:16]([NH:18][C:19]1[S:20][CH:21]=[C:22]([C:24](=[N:40][O:41][CH3:42])[C:25]([NH:27][CH:28]2[C:38](=[O:39])[N:30]3[C:31]([C:35]([O:37][CH:55]([CH2:54][O:53][C:43](=[O:52])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])[CH2:57][O:58][C:59](=[O:68])[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH3:67])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]23)=[O:26])[N:23]=1)=[O:17]
Reactant: CCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCC
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)c1csc(NC=O)n1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCCCCCCCC(=O)OCC(COC(=O)CCCCCCCC)OC(=O)C1=CCS[C@@H]2C(NC(=O)C(=NOC)c3csc(NC=O)n3)C(=O)N12
Temperature: 0 °C
Reaction time: 4 h
Yield: 28.9 %

Procedure:
Dicyclohexylcarbodiimide (6.5 g) was added to a stirred solution of 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 8.6 g) and 2-n-nonanoyloxy-1-n-nonanoyloxymethylethanol (7.8 g) in a mixture of dry pyridine (80 ml) and dry tetrahydrofuran (25 ml) at 3° C., and then stirred at 0° to 5° C. for 4 hours and allowed to stand at room temperature overnight. The resultant mixture was poured into ice water (450 ml) and extracted with ethyl acetate (450 ml). Water (50 ml) was added to the extract and adjusted to pH 2 to 3 with 20% sulfuric acid. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride (100 ml×2) and an aqueous solution of sodium bicarbonate in turn, and dried over anhydrous magnesium sulfate. After removing the solution in vacuo, the residue was subjected to column chromatography on silica gel (370 g) with a mixture of chloroform and acetone (5:1). The eluate was evaporated in vacuo to give powder (4.62 g) of 2-n-nonanoyloxy-1-n-nonanoyloxymethylethyl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer).
Reaction SMILES: [N:1]([C@@H:4]1[C:12]2[C:7](=[CH:8][C:9]([Br:13])=[CH:10][CH:11]=2)[CH2:6][CH2:5]1)=[N+]=[N-].O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[K+]>C1COCC1>[Br:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[C@@H:4]([NH2:1])[CH2:5][CH2:6]2
Reactant: [N-]=[N+]=N[C@H]1CCc2cc(Br)ccc21
Agent: [K+]
Agent: [OH-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: N[C@H]1CCc2cc(Br)ccc21
Yield: 80.6 %

Procedure:
(S)-1-Azido-5-bromo-2,3-dihydro-1H-indene (8.09 g, 34.0 mmol) was dissolved in THF (155 ml), then water (17.2 ml) was added, followed by triphenylphosphine (9.8 g, 37.4 mmol). To this mixture, potassium hydroxide (1.0 N, 34.0 ml, 34.0 mmol) was added drop by drop below 25° C. and stirring continued over night at RT. The reaction mixture was then poured into H2O (150 ml) and extracted with EtOAc (2×100 ml). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (17.34 g), which was purified by flash chromatography (silica gel, 100 g, 0% to 40% MeOH in CH2Cl2) to yield the title compound (5.81 g, 81%) as light yellow oil. MS: 211 (M+, 1Br).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[C:11]1([CH:17]([C:20]2[CH:21]=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=2)[CH2:18][NH2:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:19][CH2:18][CH:17]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:20]1[CH:21]=[N:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=1)=[O:6]
Reactant: NCC(c1ccccc1)c1ccc(C(F)(F)F)nc1
Reactant: O=C(O)c1ccccc1Cl
Product: O=C(NCC(c1ccccc1)c1ccc(C(F)(F)F)nc1)c1ccccc1Cl

Procedure:
From 2-chlorobenzoic acid and 2-phenyl-2-(6-(trifluoromethyl)pyridin-3-yl)ethanamine. LCMS (MH+): m/z=405.2, tR (minutes, Method D)=0.79
Reaction SMILES: C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:41])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:40])[CH2:12][CH2:13][C@@:14]3([C:30](=[O:39])[NH:31][CH:32]4[CH2:36][CH:35]([CH2:37][OH:38])[CH:34]=[CH:33]4)[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:43])[CH3:42])(=O)C.C1COCC1.[OH-].[Na+]>CO>[OH:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:41])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:40])[CH2:12][CH2:13][C@@:14]3([C:30]([NH:31][CH:32]4[CH2:36][CH:35]([CH2:37][OH:38])[CH:34]=[CH:33]4)=[O:39])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:43])[CH3:42]
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)NC3C=CC(CO)C3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(C)=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)NC3C=CC(CO)C3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 25 °C
Reaction time: 6 h
Yield: 68.5 %

Procedure:
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(4-(hydroxymethyl)cyclopent-2-enylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yl acetate (Example 27, 0.22 g) in MeOH:THF (8:8 ml) and cooled the contents to 0° C. then sodium hydroxide (0.05 g in 4 ml water) was added and the contents were stirred for about 6 hours at room temperature then completion of the reaction was monitored by TLC. The reaction mixture was evaporated under reduced pressure, the residue was taken in water and extracted with DCM. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 5% methanol in DCM as eluent to furnish the title compound (0.14 g) as a white solid. 1H NMR (300 MHz, CDCl3): 0.76-0.99 (m, 16H); 1.25-1.85 (m, 35H); 2.03-2.28 (m, 6H); 2.47 (s, 3H); 2.86-3.10 (m, 3H); 3.18 (s, 1H); 4.60 (s, 1H); 4.74 (s, 1H); ES Mass: 551 (100%), [M+1] 551; HPLC: 96.94%.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:4]=[C:3]1[CH3:11].[Se](=O)=[O:13]>O1CCOCC1>[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:4]=[C:3]1[CH:11]=[O:13]
Reactant: Cc1nc2cnccc2n1C
Reactant: O=[Se]=O
Solvent: C1COCCO1
Product: Cn1c(C=O)nc2cnccc21
Temperature: 130 °C
Yield: 73 %

Procedure:
To a solution of 1,2-dimethyl-1H-imidazo[4,5-c]pyridine (500 mg, 3.40 mmol) in dry 1,4-dioxane (7.5 mL) was addedhttp://newsearchch.chemexper.com/cheminfo/servlet/org.dbcreator.MainServlet?sort=%3E%7Eentry.int Value&query=structure._structureID%3D4635571 &target=entry&action=PowerSearch&onclick=1 &from=0 &history=off&forGroupNames=&style=&realQuery=rn.value%3D%22CF3COOH%22+elsor+entry.catalogID%3D%22CF3COOH%22+elsor+iupac.value%3D%22CF3COOH%22+elsor+mf.value%3D%22CF3COOH%22+elsor+%28iupac.value%3D%7E%22CF3COOH%22+ or +catalog.description%3D%7E%22CF3COOH%22%29&format=ccd&searchTemplate=rn.value%3D%3F+elsor+entry.catalogID%3D%3 selenium dioxide (665 mg, 5.10 mmol). The mixture heated by microwave at 130° C. for 5 min. Then the mixture was filtered and concentrated to give the crude product, which was purified by column chromatography (silica gel, petroleum ether:DCM 10:1 to 1:1) to give the title compound (400 mg, yield 28%). LC-MS (ESI) m/z: 162 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 3.61 (s, 3H), 5.91 (s, 1H), 7.67-7.70 (d, J=5.6 Hz, 1H), 8.39-8.41 (d, J=5.6 Hz, 1H), 8.93 (s, 1H).
Reaction SMILES: [C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])(=[O:4])[CH2:2][CH3:3].CN1CCOCC1.[F:22][CH2:23][CH2:24][CH:25]=[O:26].Cl>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[F:22][CH2:23][CH2:24][C@H:25]([OH:26])[C@@H:2]([CH3:3])[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])=[O:4]
Reactant: O=CCCF
Reactant: CCC(=O)n1c(=O)oc2ccccc21
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: Cl
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: C[C@@H](C(=O)n1c(=O)oc2ccccc21)[C@@H](O)CCF
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 74.3 %

Procedure:
Titanium tetrachloride (15.8 mL, 144 mmol) was added over 5 minutes to a vigorously stirred solution of N-propionyl-2-benzoxazolone (25.0 g, 131 mmol) in anhydrous CH2Cl2 (250 mL) cooled on ice and maintained under inert atmosphere. After 10 minutes, the yellow slurry was treated with N-methylmorpholine (15.8 mL, 144 mmol) over 5 minutes, and stirring was continued for an additional 45 minutes. A 0.48 M solution of 3-fluoropropanal (310 mL, 150 mmol) was added to the dark red solution over 30 minutes, such that the internal temperature remained below 10° C. After addition was complete, the mixture was stirred for an additional 30 minutes on ice, then at warm to ambient temperature an additional 1 hour. The reaction was treated with 250 mL of 2 N HCl with vigorous mixing, and the phases were separated, discarding the aqueous phase. The organic phase was filtered through a pad of silica gel (10 g), which was subsequently washed with 100 mL of methyl tert-butyl ether (MTBE). The combined eluates were evaporated to dryness. The resulting solid mass was triturated with MTBE, allowed to stand for 1 hour, then collected by vacuum filtration, yielding 26 gm of crystalline product. 1H-NMR: δ 8.07-8.02 (m, 1H), 7.29-7.18 (m, 3H), 4.77-4.05 (m, 2H), 4.31 (m, 1H), 3.96 (dq, J=7, 3 Hz, 1H), 2.00-1.79 (m, 2H), 1.34 (d, J=7 Hz, 3H). 13C-NMR: δ 176.1, 151.1, 142.2, 127.7, 125.6, 125.0, 116.2, 110.0, 82.0, 80.4, 68.0, 43.8, 34.7, 34.5, 10.4.
Reaction SMILES: [H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[C:15](CC(C)C)[C:14]([CH3:24])=[C:13]([CH3:25])[N:12]=1>O1CCCC1>[CH3:24][C:14]1[C:15]([NH:12][CH2:13][CH:14]([CH3:24])[CH3:15])=[C:16]([N+:17]([O-:19])=[O:18])[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:12][C:13]=1[CH3:25]
Reactant: Oc1ccccc1
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(CC(C)C)c1C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1nc(Oc2ccccc2)c([N+](=O)[O-])c(NCC(C)C)c1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 216.2 %

Procedure:
Sodium hydride (19.8 g of a 60% dispersion in mineral oil, 0.495 mol) in tetrahydrofuran (THF) (450 mL) was cooled to 0° C.; a solution of phenol (77.7 g, 0.826 mol) in THF (150 mL) was added slowly over a period of 30 minutes. The reaction was stirred at ambient temperature for 30 minutes, and a solution of 2-chloro-5,6-dimethyl-4-(2-methylpropyl)-3-nitropyridine (60.78 g, 0.236 mol) in THF (350 mL) was added. The reaction was heated to 70° C., heated at 50° C. overnight, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (800 mL). The resulting solution was washed sequentially with 1 N aqueous sodium hydroxide (1×800 mL), brine (3×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), brine (1×400 mL), 1 N aqueous sodium hydroxide (1×400 mL), and deionized water (1×400 mL); dried over magnesium sulfate; filtered through a layer of CELITE filter agent; concentrated under reduced pressure; and further dried overnight under high vacuum to provide 80.46 g of 5,6-dimethyl-N-(2-methylpropyl)-3-nitro-2-phenoxypyridin-4-amine as an orange-red solid containing some mineral oil.
Reaction SMILES: Cl[CH2:2][C:3]([CH3:5])=[CH2:4].[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH:18]=[CH2:19])(=[O:15])=[O:14])=[CH:9][CH:8]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([N:16]([CH2:4][C:3]([CH3:5])=[CH2:2])[CH2:17][CH:18]=[CH2:19])(=[O:15])=[O:14])=[CH:9][CH:8]=1
Reactant: C=C(C)CCl
Reactant: C=CCNS(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCN(CC(=C)C)S(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
3-Chloro-2-methylpropene (20 mL, 0.20 mol) is added over a period of 5 minutes to a suspension of 4-methyl-N-(prop-2-en-1-yl)benzene-1-sulphonamide (27.9 g, 0.13 mol) and potassium carbonate (28.1 g, 0.20 mol) in N,N-dimethylformamide (200 mL) cooled in an ice bath. After 20 minutes, the suspension is stirred at ambient temperature for 18 hours. The suspension is concentrated to dryness. The residue is taken up in ethyl acetate (250 mL) and water (110 mL). The aqueous phase is extracted with ethyl acetate (2×50 mL). The combined organic phases are washed successively with aqueous 3N HCl solution (50 mL), water (3×50 mL), aqueous 5% potassium bicarbonate solution (50 mL), and finally brine (50 mL). The organic phase is dried over Na2SO4, filtered and concentrated to obtain the expected compound in the form of an oil.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH2:9]Br)([O:3][CH2:4][CH3:5])=[O:2].[NH3:14]>C(#N)C>[C:1]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH2:9][NH2:14])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)c1cccc(CBr)c1
Reactant: N
Solvent: CC#N
Product: CCOC(=O)c1cccc(CN)c1
Temperature: -30 °C

Procedure:
3-Carboethoxybenzyl bromide (1 ml; Heterocycles, 1977, 6, 5) was added to a saturated solution of ammonia in acetonitrile (30 ml) which had been cooled to -30° C. The mixture was stirred and allowed to warm to laboratory temperature. The mixture was filtered and the filtrate was evaporated. The residue was purified by chromatography on a silica gel column using a 10:1 v/v mixture of ethyl acetate and methanol as eluent. There was thus obtained as an oil 3-carboethoxybenzylamine (0.4 g) which was used without further purification as the appropriate amine in the process described in Example 1.