Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[OH:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1.C(N(CC)CC)C>C(Cl)Cl>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CN1CCN(CCCO)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1

Procedure:
4-Toluenesulphonyl chloride (3.2 g) was added to a stirred mixture of 1-(3-hydroxypropyl)-4-methylpiperazine (2.4 g), triethylamine (4.6 ml) and methylene chloride (60 ml) and the resultant mixture was stirred at ambient temperature for 2 hours. The solution was washed in turn with a saturated aqueous sodium bicarbonate solution and with water and filtered through phase separating paper. The organic filtrate was evaporated to give 3-(4-methylpiperazin-1-yl)propyl 4-toluenesulphonate as an oil which crystallised on standing (3.7 g); Mass Spectrum: M+H+ 313.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].C([O-])([O-])=O.[K+].[K+].Br[C:26]([C:28]([F:31])([F:30])[F:29])=[CH2:27]>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:9][C:6]1[CH:5]=[C:4]([C:26]([C:28]([F:31])([F:30])[F:29])=[CH2:27])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH3:8]
Reactant: C=C(Br)C(F)(F)F
Reactant: Cc1c(Cl)cc(B2OC(C)(C)C(C)(C)O2)cc1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C(c1cc(Cl)c(C)c(Cl)c1)C(F)(F)F
Temperature: 80 °C
Reaction time: 3 h
Yield: 54.6 %

Procedure:
The mixture of 2-(3,5-dichloro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (160 mg, 0.56 mmol), K2CO3 (232 mg, 1.68 mmol), compound 2-bromo-3,3,3-trifluoroprop-1-ene (146 mg, 0.84 mmol) and Pd(PPh3)2Cl2 (39 mg, 0.1 mmol) in THF/H2O (2/1 mL) was stirred in a sealed tube at 80° C. for 3 h. It was partitioned between EA and H2O. The organic layer was washed with brine, dried over Na2SO4, concentrated under vacuum. The residue was purified by column chromatography to give the desired product (78 mg, 55% yield).
Reaction SMILES: C[O:2][C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]([CH3:28])=[C:15]3[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:8][CH:7]=1.[OH-].[K+]>C1COCC1.CO>[CH2:21]([N:17]1[C:18]2[C:14](=[CH:13][C:12]([C:9]3[CH:10]=[CH:11][C:6]([O:5][CH2:4][C:3]([OH:36])=[O:2])=[CH:7][CH:8]=3)=[CH:20][CH:19]=2)[C:15]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:16]1[CH3:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: COC(=O)COc1ccc(-c2ccc3c(c2)c(Cc2ccccc2)c(C)n3Cc2ccccc2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1c(Cc2ccccc2)c2cc(-c3ccc(OCC(=O)O)cc3)ccc2n1Cc1ccccc1

Procedure:
The desired product was prepared using a procedure similar to step 2 of example 4. Thus, [4-(1,3-dibenzyl-2-methyl-1H-indol-5-yl)-phenoxy]-acetic acid methyl ester (0.147 g, 0.309 mmol) was reacted with 1N KOH (0.62 ml) in THF/MeOH (3 ml/2 ml) to give the product (0.072 g, 0.156 mmol, 50%) as a tan solid, mp 180-183° C. 1H NMR (DMSO-d6), δ 2.35 (s, 3H), 4.10 (s, 2H), 4.66 (s, 2H), 5.42 (s, 2H), 6.94 (d, J=8.9 Hz, 2H), 6.99 (d, J=7.0 Hz, 2H), 7.09-7.13 (m, 1H), 7.20-7.30 (m, 8H), 7.39 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.7 Hz, 2H), 7.58 (d, J=1.5 Hz, 1H), 13.00 (broad s, 1H); IR (solid) 3010, 2905, 1730, 1520, 1480, and 1240 cm−1; [ESI(+)], m/z 462 (M+H)+; Anal. Calcd. for C31H27NO3: C, 80.67; H, 5.90; N, 3.03; Found: C, 80.60; H, 5.79; N, 2.94.
Reaction SMILES: [F:1][C:2]1[C:18]([NH:19][C:20]2[C:23](=O)[C:22](=[O:25])[C:21]=2[O:26]C)=[CH:17][CH:16]=[C:15]([F:28])[C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]([O:13][CH3:14])=[O:12])=[O:5].[CH3:29][C:30]1[O:34][C:33]([CH:35]([NH2:41])[C:36]2([CH3:40])[CH2:39][O:38][CH2:37]2)=[CH:32][CH:31]=1>CO>[F:1][C:2]1[C:18]([NH:19][C:20]2[C:21](=[O:26])[C:22](=[O:25])[C:23]=2[NH:41][CH:35]([C:33]2[O:34][C:30]([CH3:29])=[CH:31][CH:32]=2)[C:36]2([CH3:40])[CH2:37][O:38][CH2:39]2)=[CH:17][CH:16]=[C:15]([F:28])[C:3]=1[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]([O:13][CH3:14])=[O:12])=[O:5]
Reactant: COC(=O)[C@@H]1CCCN1C(=O)c1c(F)ccc(Nc2c(OC)c(=O)c2=O)c1F
Reactant: Cc1ccc(C(N)C2(C)COC2)o1
Solvent: CO
Product: COC(=O)[C@@H]1CCCN1C(=O)c1c(F)ccc(Nc2c(NC(c3ccc(C)o3)C3(C)COC3)c(=O)c2=O)c1F
Temperature: 60 °C
Reaction time: 8 h
Yield: 92.7 %

Procedure:
A mixture of 500 mg (1.27 mmol) of methyl (S)-1-[2,6-difluoro-3-(2-methoxy-3,4-dioxocyclobut-1-enylamino)benzoyl]-pyrrolidine-2-carboxylate and 344 mg (1.90 mmol, 1.5 eq) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine in 25 ml of methanol was heated at 60° C. and was then stirred at ambient temperature overnight. The reaction medium was concentrated. The residue was taken up with ethyl acetate and was washed twice with a 1 M aqueous sodium dihydrogen phosphate solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. 0.64 g of methyl (S)-1-[2,6-difluoro-3-(2-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}-3,4-dioxocyclobut-1-enylamino)benzoyl]pyrrolidine-2-carboxylate was obtained. Yield=93%, Mp=122° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH3:11]N(C=O)C.C(Cl)(=O)C(Cl)=O.CO>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)c1cccc(Cl)n1
Reactant: CN(C)C=O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1cccc(Cl)n1
Reaction time: 1 h
Yield: 100 %

Procedure:
6-Chloropyridine-2-carboxylic acid (15.0 g, 0.11 mol) was dissolved in DCM (300 mL) and DMF (1.5 mL) and oxalyl chloride (27.4 g, 0.22 mol) was added dropwise over 10 min. The reaction mixture was stirred for 1 h, MeOH (50 mL) was added dropwise over 5 min and the reaction mixture was stirred for 1.5 h. The solvents were removed in vacuo and the residue azeotroped with DCM (2×150 mL) to give the crude title compound (16.5 g, 100%) as a green solid. LCMS (ES+): 154.5 [MH]+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=1[Cl:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)(=O)C.[Fe]>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=1[Cl:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1ccc(OCc2ccccc2)c(Cl)c1
Agent: [Fe]
Solvent: CC(=O)O
Product: Nc1ccc(OCc2ccccc2)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88.1 %

Procedure:
1-Benzyloxy-2-chloro-4-nitrobenzene (10.0 g, 37.9 mmol) and iron powder (10.6 g, 189.6 mmol) were mixed in 250 mL acetic acid and were stirred at rt overnight. The reaction mixture was filtered through a pad of Celite®, and washed with EtOAc. The filtrate was concentrated in vacuo and neutralized with saturated Na2CO3 solution. The contents were extracted with EtOAc (6×300 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was triturated with Hex/EtOAc (2:1) to furnish 4-Benzyloxy-3-chloro-phenylamine (7.8 g, 88%) as a white solid. 1H-NMR (DMSO-d6) δ 7.43-7.30 (m, 5H), 6.90 (d, 1H), 6.63 (d, 1H), 6.46 (dd, 1H), 4.99 (s, 2H), 4.92 (s, 2H); LCMS RT=2.09 min; [M+H]+=234.5.
Reaction SMILES: [C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O>>[C:1]([O:9][CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]
Reactant: O=C(O)c1ccccc1
Product: COC(=O)c1ccccc1
Reaction time: 15 h

Procedure:
A 0.5 mM solution of benzoic acid containing 0.2 mM chloromethane and buffered at pH 4.0 with 20 mM citrate buffer was incubated with 0.035 g of fungal mycelium (Phellinus ribis NCWRF. FPRL 42 or CBS 175.29) for a period of 15 hours at a temperature of 25° C. Methyl benzoate was formed at a rate of 77 nanomoles/g fungal mycelium/hour.
Reaction SMILES: C([O:4][C@@H:5]1[CH:24]=[CH:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[C:20](=[O:26])[CH2:19][C@@:18]2([CH3:27])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=O)C.[OH-].[K+].O>CO>[OH:4][C@@H:5]1[CH:24]=[CH:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[C:20](=[O:26])[CH2:19][C@@:18]2([CH3:27])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1
Reactant: CC(=O)O[C@@H]1C=C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2C(=O)C[C@]2(C)[C@@H](C(C)=O)CC[C@@H]32)C1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)C=C[C@]4(C)[C@H]3C(=O)C[C@]12C
Temperature: 25 °C
Reaction time: 2 h
Yield: 52 %

Procedure:
A solution of crude 3α-acetoxy-5α-pregn-1-ene-11,20-dione (3.6 g.) in dry methanol (96 ml.) was treated with a solution of potassium hydroxide (650 mg.) in methanol (72 ml.), and the mixture stirred under nitrogen at room temperature for 2 hr. The reaction mixture was poured into water, and the product extracted with methylene chloride. The extract was washed with water, dried (MgSO4), and evaporated in vacuo. The residue (3.1 g.) was subjected to preparative t.l.c. The more polar product afforded the title compound (1.66 g.), with an RF identical on t.l.c. to that of the product of (a).
Reaction SMILES: O.S[C@@H:3]1[O:11][C@H:10]([CH2:12][OH:13])[C@@H:8]([OH:9])[C@H:6]([OH:7])[C@H:4]1[OH:5].C([O-])([O-])=[O:15].[K+].[K+]>CN(C=O)C>[O:11]=[CH:3][C@@H:4]([C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:15])[OH:9])[OH:7])[OH:5]
Reactant: O=C([O-])[O-]
Reactant: OC[C@H]1O[C@@H](S)[C@H](O)[C@@H](O)[C@@H]1O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 25 °C
Reaction time: 30 h

Procedure:
0.2 g of Polymer 2 was dissolved in 8 ml of DMF in 25 mL single-neck round bottom flask. 0.2 g of 1-thio-β-D-glucose was added, following by 0.5 g of anhydrous K2CO3. The reaction mixture was stirred at room temperature for 30 hrs, and then transferred into a dialysis tube for dialysis against water for 2 days (8 water changes). The solution obtained in dialysis tube was then transferred into a single-neck round bottom flask. After removal of water, Glucose-functionalized Polymer 2 was obtained as a black solid.
Reaction SMILES: C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.C([N:20](CC1C=CC=CC=1)[C:21]1[C:26]([NH2:27])=[C:25]([NH:28][CH2:29][C:30]2[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=2)[CH:24]=[C:23]([C:37]2[O:38][CH:39]=[CH:40][N:41]=2)[N:22]=1)C1C=CC=CC=1>C1COCC1>[NH2:20][C:21]1[C:26]2[NH:27][C:6](=[O:7])[N:28]([CH2:29][C:30]3[CH:31]=[N:32][C:33]([CH3:36])=[CH:34][CH:35]=3)[C:25]=2[CH:24]=[C:23]([C:37]2[O:38][CH:39]=[CH:40][N:41]=2)[N:22]=1
Reactant: Cc1ccc(CNc2cc(-c3ncco3)nc(N(Cc3ccccc3)Cc3ccccc3)c2N)cn1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: Cc1ccc(Cn2c(=O)[nH]c3c(N)nc(-c4ncco4)cc32)cn1
Temperature: 60 °C
Reaction time: 5 h
Yield: 11.1 %

Procedure:
CDI (272 mg) was added to a solution of N2,N2-dibenzyl-N4-(6-methyl-pyridin-3-ylmethyl)-6-oxazol-2-yl-pyridine-2,3,4-triamine (400 mg) in THF (10 ml). The solution was left to stir under N2 at 60° C. for 5 h. A further 3 equivalents of CDI (408 mg) were added and the reaction heated at reflux for 16 h. The reaction mixture was allowed to cool then concentrated in vacuo. The crude mixture was then dissolved in concentrated H2SO4 (5 ml) and left for 30 minutes at RT. The dark brown solution was added drop-wise onto crushed ice. The pH was adjusted to ˜8 by addition of a saturated solution of K2CO3 then the mixture was filtered. The solid obtained was washed with EtOAc (50 ml) then the organic and aqueous filtrates were transferred to a separating funnel. The layers were separated and the aqueous was re-extracted with EtOAc (50 ml). The organics were combined, dried (MgSO4) and evaporated to provide a gummy solid. This was triturated with Et2O and the solid collected by filtration and washed with Et2O, giving the title compound as an off-white solid (30 mg). 1H NMR (CDCl3, 400 MHz) □ 2.45 (s, 3H), 5.09 (s, 2H), 7.21-7.28 (m, 2H), 7.30 (s, 1H), 7.70 (dd, 1H), 7.95 (s, 1H), 8.42 (d, 1H). LCMS rt=2.29 m/z 323 [MH]+
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[CH2:14](O)[CH3:15]>S(=O)(=O)(O)O>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH2:14][CH3:15])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc(F)c([N+](=O)[O-])c1
Yield: 93 %

Procedure:
To a suspension of 4-fluoro-3-nitrobenzoic acid (150 g, 0.810 mol) in ethanol (1000 ml), concentrated sulfuric acid (25 ml) was added dropwise, and the mixture was heated under reflux for 8 hours. After being allowed to cool, the mixture was concentrated under a reduced pressure, and water was added thereto under stirring. The precipitate was separated by filtration, washed with water and then subjected to through circulation drying to give the title compound (160 g, 93%) as a yellow solid.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][C:4]1[C:9]([OH:10])=[C:8]([C:11]([CH3:13])=[O:12])[CH:7]=[CH:6][C:5]=1[OH:14].Cl[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(C(C)=O)C>[C:11]([C:8]1[CH:7]=[CH:6][C:5]([O:14][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]#[N:22])=[C:4]([CH2:3][CH2:2][CH3:1])[C:9]=1[OH:10])(=[O:12])[CH3:13]
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Reactant: N#CCCCCCCl
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCc1c(OCCCCCC#N)ccc(C(C)=O)c1O

Procedure:
A solution of 44.4 g. of 2,4-dihydroxy-3-propylacetophenone, 42.2 g. of 6-chlorocapronitrile, 33.2 g. of potassium carbonate and 4.0 g. of potassium iodide in one liter of methyl ethyl ketone was allowed to reflux for three days. The reaction mixture was filtered and the filtrate was evaporated in vacuo. Chromatography of the residue over silica gel (0-30% ethyl acetate gradient in hexane) gave 53.6 g. of the title product as an oil.
Reaction SMILES: [CH3:1][N:2]([CH3:22])/[CH:3]=[N:4]/[S:5]([C:8]1[C:13]([OH:14])=[CH:12][CH:11]=[CH:10][C:9]=1[NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:7])=[O:6].[CH2:23](Br)[CH:24]=[CH2:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:25]([O:14][C:13]1[C:8]([S:5](=[O:7])(=[O:6])/[N:4]=[CH:3]/[N:2]([CH3:1])[CH3:22])=[C:9]([NH:15][C:16](=[O:21])[C:17]([CH3:19])([CH3:18])[CH3:20])[CH:10]=[CH:11][CH:12]=1)[CH:24]=[CH2:23]
Reactant: CN(C)/C=N/S(=O)(=O)c1c(O)cccc1NC(=O)C(C)(C)C
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCOc1cccc(NC(=O)C(C)(C)C)c1S(=O)(=O)/N=C/N(C)C

Procedure:
A solution of N-(2-{[1-dimethylamino-meth-(E)-ylidene]-sulfamoyl}-3-hydroxy-phenyl)-2,2-dimethyl-propionamide (600 mg, 1.84 mmol) in DMF (4 ml) is treated at 70° C. with allyl bromide (217 μl, 2.57 mmol) and K2CO3 (380 mg) for 45 min with stirring. After evaporation of the solvent, the residue is partitioned between water and EtOAc. The organic layer is dried (Na2SO4) and evaporated yielding N-(3-allyloxy-2-{[1-dimethylamino-meth-(E)-ylidene]-sulfamoyl}-phenyl)-2,2-dimethyl-propionamide.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]2[CH:14]=[CH:15][C:16](=[O:19])[NH:17][CH:18]=2)=[C:4]([C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)[N:3]=1.[CH2:25](I)[CH2:26][CH3:27]>>[NH2:1][C:2]1[N:3]=[C:4]([C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)[C:5]([C:13]2[CH:14]=[CH:15][C:16](=[O:19])[N:17]([CH2:25][CH2:26][CH3:27])[CH:18]=2)=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1
Reactant: Nc1nc(-c2ccco2)c(-c2ccc(=O)[nH]c2)c(-c2ccco2)n1
Reactant: CCCI
Product: CCCn1cc(-c2c(-c3ccco3)nc(N)nc2-c2ccco2)ccc1=O

Procedure:
The title compound was synthesized in a similar manner to Example 66 using 5-[2-amino-4,6-di(2-furyl)-5-pyrimidinyl]-1,2-dihydro-2-pyridinone and propyl iodide.
Reaction SMILES: C(O[C:6]([N:8](C)[C@H:9]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:10][CH2:11][C:12](OC)=[O:13])=O)(C)(C)C.N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(Cl)Cl>[Si:18]([O:17][CH2:16][C@@H:9]([NH:8][CH3:6])[CH2:10][CH2:11][CH2:12][OH:13])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]
Reactant: COC(=O)CC[C@@H](CO[Si](C)(C)C(C)(C)C)N(C)C(=O)OC(C)(C)C
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CN[C@@H](CCCO)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (S)-methyl 4-(tert-butoxycarbonyl(methyl)amino)-5-(tert-butyldimethylsilyloxy)pentanoate (37.9 g, 109.2 mmol) in DCM (200 mL) was added 2,6-lutidine (25.3 mL, 218.4 mmol) followed by TMSOTf (29.6 mL, 163.8 mmol). The resulting solution was stirred at RT for 1 h. The solvent was removed and the remaining residue was diluted with EtOAc. The organic mixture was washed with water and brine, dried over Na2SO4, filtered, and concentrated to give (S)-5-(tert-butyldimethylsilyloxy)-4-(methylamino)pentan-1-ol, which was used without further purification. LRMS (M+H+) m/z 248.2.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]([C:27]([OH:29])=[O:28])[NH:4][C:5](=[O:26])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH:18]=[CH:19][NH:20]3)=[O:13])=[CH:8][C:7]=1[Cl:25].C1C=NC2N(O)N=NC=2C=1.C(N=C=NC(C)C)(C)C.[S:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54](O)=[O:55]>CN1CCCC1=O>[S:49]1[CH:53]=[CH:52][CH:51]=[C:50]1[C:54]([NH:1][CH2:2][C@@H:3]([C:27]([OH:29])=[O:28])[NH:4][C:5](=[O:26])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([NH:14][CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=2[CH2:18][CH2:19][NH:20]3)=[O:13])=[CH:8][C:7]=1[Cl:25])=[O:55]
Reactant: NC[C@H](NC(=O)c1ccc(C(=O)NCc2cccc3[nH]ccc23)cc1Cl)C(=O)O
Reactant: O=C(O)c1cccs1
Agent: CC(C)N=C=NC(C)C
Agent: On1nnc2cccnc21
Solvent: CN1CCCC1=O
Product: O=C(NCc1cccc2c1CCN2)c1ccc(C(=O)N[C@@H](CNC(=O)c2cccs2)C(=O)O)c(Cl)c1
Reaction time: 2 h

Procedure:
To 3-amino-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine on Wang resin (Example 69; 100 mg) was added a solution of HOAT (70 mg, 0.51 mmol), diisopropylcarbodiimide (80 μL, 0.51 mmol), and thiophene-2-carboxylic acid (70 mg, 0.55 mmol) in 1-methyl-2-pyrrolidinone (1 mL). The mixture was agitated for 2 h and then the resin was filtered and washed extensively with dichloromethane and methanol. Cleavage of the product was effected with triethylsilane/trifluoroacetic acid/dichloromethane (2:1:1; 1 mL) at room temperature for 30 min. The solvent was evaporated and the residue was purified by HPLC to give 3-(thiophene-2-carbonyl)amino-N-[2-chloro-4-[[(2,3-dihydro-1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-L-alanine (10.7 mg).
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[O:5][N:4]=1.[CH3:15][C:16]1[S:17][C:18]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C@@H:27]([OH:35])[CH2:28][N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[CH:21][C:19]=2[N:20]=1.CCN(CC)CC>CCO>[F:14][C:10]1[CH:9]=[C:8]([C:6]2[O:5][N:4]=[C:3]([CH2:2][N:32]3[CH2:33][CH2:34][N:29]([CH2:28][CH:27]([OH:35])[CH2:26][O:25][C:22]4[CH:23]=[CH:24][C:18]5[S:17][C:16]([CH3:15])=[N:20][C:19]=5[CH:21]=4)[CH2:30][CH2:31]3)[N:7]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: Fc1cccc(-c2nc(CCl)no2)c1
Reactant: Cc1nc2cc(OC[C@@H](O)CN3CCNCC3)ccc2s1
Solvent: CCN(CC)CC
Solvent: CCO
Product: Cc1nc2cc(OCC(O)CN3CCN(Cc4noc(-c5cccc(F)c5)n4)CC3)ccc2s1
Temperature: 90 °C

Procedure:
3-(Chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole (242 mg, 1.02 mmol) and (2S)-1-(2-methylbenzothiazol-5-yloxy)-3-piperazine-1-yl-propan-2-ol, a compound of formula (6) (309 mg, 1.0 mmol) in EtOH (8 mL) were treated with Et3N (0.5 mL, 3.57 mmol) and refluxed at 90° C. on a J-Kem™ block for 48 hours. The reaction product was concentrated and the product purified by flash chromatography (90:10 EtOAc-MeOH) to yield 3-(4-{[5-(3-fluorophenyl)(1,2,4-oxadiazol-3-yl)]methyl}piperazinyl)-1-(2-methylbenzothiazol-5-yloxy)propan-2-ol, a compound of Formula I.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]=[C:13]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=4)[CH:12]=[C:11]([C:25]([O:27][CH3:28])=[O:26])[C:7]=3[NH:8][C:9]=2[CH:10]=1.[F:29][C:30]([F:45])([F:44])[S:31](OC1C=CC([N+]([O-])=O)=CC=1)(=[O:33])=[O:32].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:22][C:21]([F:24])([F:23])[C:17]1[CH:16]=[C:15]([C:13]2[CH:12]=[C:11]([C:25]([O:27][CH3:28])=[O:26])[C:7]3[NH:8][C:9]4[CH:10]=[C:2]([O:1][S:31]([C:30]([F:45])([F:44])[F:29])(=[O:33])=[O:32])[CH:3]=[CH:4][C:5]=4[C:6]=3[N:14]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: COC(=O)c1cc(-c2cccc(C(F)(F)F)c2)nc2c1[nH]c1cc(O)ccc12
Reactant: O=[N+]([O-])c1ccc(OS(=O)(=O)C(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc(-c2cccc(C(F)(F)F)c2)nc2c1[nH]c1cc(OS(=O)(=O)C(F)(F)F)ccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 51.2 %

Procedure:
A suspension of methyl 7-hydroxy-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (800 mg, 2.07 mmol), 4-nitrophenyl trifluoromethanesulfonate (842 mg, 3.11 mmol), and potassium carbonate (859 mg, 6.21 mmol) in DMF (12 ml) was stirred at RT for 3 hr. The reaction was partitioned between water and EtOAc. The organic phase was separated and washed with water (5×) and brine. It was dried with sodium sulfate and the solvent was removed. Column chromatography (step gradient elution with hexane containing 20 to 80% DCM) afforded methyl 2-(3-(trifluoromethyl)phenyl)-7-(trifluoromethylsulfonyloxy)-5H-pyrido[3,2-b]indole-4-carboxylate (548 mg, 1.06 mmol, 51% yield) as a light yellow solid. MS (ESI) m/z 587.09 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.76 (1H, s), 8.51 (1H, d, J=8.55 Hz), 8.44 (1H, s), 8.31-8.38 (2H, m), 7.60-7.72 (2H, m), 7.51 (1H, d, J=2.14 Hz), 7.29 (1H, dd, J=8.55, 2.14 Hz), 4.13 (3H, s).
Reaction SMILES: [CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=3)[C:17]([NH:19][C:20]3[C:21](O)=[C:22]([CH:27]=[CH:28][CH:29]=3)[C:23]([O:25][CH3:26])=[O:24])=[O:18])=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.O.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:15]=[C:16]([C:17]4[O:18][C:21]5[C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:27][CH:28]=[CH:29][C:20]=5[N:19]=4)[CH:31]=[CH:32][CH:33]=3)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1
Reactant: COC(=O)c1cccc(NC(=O)c2cccc(C(=O)N3CCN(C(=O)C4CC4)CC3)c2)c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: COC(=O)c1cccc2nc(-c3cccc(C(=O)N4CCN(C(=O)C5CC5)CC4)c3)oc12
Yield: 85.7 %

Procedure:
Methyl 3-(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)benzamido)-2-hydroxybenzoate (160 mg, 0.35 mmol) and 4-methylbenzenesulfonic acid monohydrate (200 mg, 1 mmol) were added to toluene (10 mL) and the mixture was stirred at reflux for 16 hr. The resulting mixture was extracted with ethyl acetate (100 mL×4) and concentrated to yield methyl 2-(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)benzo[d]oxazole-7-carboxylate as a solid (130 mg, yield: 85%). LC-MS (ESI) m/z: 434 (M+1)+.