Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:27])[C:3]([C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[C:15]3[CH2:16][C:17]([CH3:20])([CH3:19])[O:18][C:14]=3[CH:13]=[C:12]([C:21]([OH:23])=O)[CH:11]=2)=[CH:7][C:6]=1[F:26])=[O:4].C([SiH2][O:33][C:34](C)(C)[C:35]1[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=1)(C)(C)C.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:33][CH2:34][C:35]1[CH:36]=[CH:37][C:38]([NH:41][C:21]([C:12]2[CH:11]=[C:10]([O:9][C:8]3[CH:24]=[CH:25][C:5]([C:3](=[O:4])[N:2]([CH3:27])[CH3:1])=[C:6]([F:26])[CH:7]=3)[C:15]3[CH2:16][C:17]([CH3:19])([CH3:20])[O:18][C:14]=3[CH:13]=2)=[O:23])=[N:39][CH:40]=1
Reactant: CN(C)C(=O)c1ccc(Oc2cc(C(=O)O)cc3c2CC(C)(C)O3)cc1F
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1ccc(N)nc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(C)C(=O)c1ccc(Oc2cc(C(=O)Nc3ccc(CO)cn3)cc3c2CC(C)(C)O3)cc1F
Temperature: 50 °C
Reaction time: 8 h
Yield: 24.5 %

Procedure:
To a solution of 4-(4-dimethylcarbamoyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (143a) (381 mg, 1.02 mmol), 5-(tert-butyl-dimethyl-silanyloxymethyl)-pyridin-2-ylamine (22a) (365 mg, 1.53 mmol) and triethylamine (0.284 mL, 2.04 mmol) in 5 mL of DMF was added HATU (776 mg, 2.04 mmol). The mixture was stirred at 50° C. overnight, quenched with water, extracted with 3×EtOAc. The combined organic layer was washed with 2×H2O, dried with Na2SO4, concentrated and the resulting oil was purified by Biotage column chromatography with 50-100% EtOAc in hexanes to give a yellow solid (120 mg, 25% yield). 1H NMR (400 MHz, CDCl3) δ 8.76 (br. s., 1 H) 8.29 (d, J=8.59 Hz, 1 H) 8.21 (d, J=1.77 Hz, 1 H) 7.74 (dd, J=8.59, 2.27 Hz, 1 H) 7.35 (t, J=8.08 Hz, 1 H) 7.27 (s, 1 H) 7.11 (d, J=5.81 Hz, 1 H) 6.78 (dd, J=8.46, 2.40 Hz, 1 H) 6.68 (dd, J=10.61, 2.27 Hz, 1 H) 4.66 (s, 2 H) 3.11 (s, 3 H) 2.96 (s, 3 H) 2.88 (s, 2 H) 1.48 (s, 6 H); LCMS for C26H26FN3O5 m/z 480.20 (M+H).
Reaction SMILES: OC1C2C(=CC=CC=2)C(NS(C2SC=CC=2)(=O)=O)=CC=1[S:21][CH2:22][C:23]([OH:25])=[O:24].[Cl:26][C:27]1[CH:28]=[C:29]([S:33]([N:36]=[C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40](=[O:47])[C:39](Cl)=[CH:38]2)(=[O:35])=[O:34])[S:30][C:31]=1[Cl:32]>>[Cl:26][C:27]1[CH:28]=[C:29]([S:33]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]([OH:47])=[C:39]([S:21][CH2:22][C:23]([OH:25])=[O:24])[CH:38]=2)(=[O:35])=[O:34])[S:30][C:31]=1[Cl:32]
Reactant: O=C1C(Cl)=CC(=NS(=O)(=O)c2cc(Cl)c(Cl)s2)c2ccccc21
Reactant: O=C(O)CSc1cc(NS(=O)(=O)c2cccs2)c2ccccc2c1O
Product: O=C(O)CSc1cc(NS(=O)(=O)c2cc(Cl)c(Cl)s2)c2ccccc2c1O

Procedure:
5.2.56 2-(4-(4,5-dichlorothiophene-2-sulfonamido)-1-hydroxynaphthalen-2-ylthio)acetic acid (14n) was prepared according to the procedure of procedure B for 10a except using 4,5-dichloro-N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)thiophenesulfonamide (12c), which afforded the title compound 17.8 mg (39%) as a white solid, m.p.: ° C.
Reaction SMILES: [CH2:1]=[CH:2][CH3:3].[O:4]=[O:5].C[C:7]1[C:12]2[CH2:13][O:14][C:15](=[O:16])[C:11]=2C(O[C@@H]2O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]2O)=C(C/C=C(/CCC(O)=O)\C)C=1OC>C(O)(=O)C.O>[C:15]([O:14][CH2:13][CH:12]=[CH2:7])(=[O:16])[CH3:11].[CH2:1]=[CH:2][CH3:3].[O:4]=[O:5]
Reactant: COc1c(C)c2c(c(O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3O)c1C/C=C(\C)CCC(=O)O)C(=O)OC2
Agent: O=O
Solvent: CC(=O)O
Solvent: O
Solvent: C=CC
Product: C=CCOC(C)=O

Procedure:
After uniformly diluting 14.0 ml of each of catalysts B and G-I obtained in Examples 2, 5 and 6 and Comparative Example 3 with 42.0 ml of silica carrier, it was packed into a reaction tube (SUS316 L, inner diameter: 25 mm). Gas with a gas composition of propylene:oxygen:acetic acid:water in a volume ratio of 29:6:7.1:19:38.9 was introduced at a space velocity of 2070 h−1 with a reaction temperature of 135° C. and a reaction pressure of 0.8 MPaG (gauge pressure), for reaction to obtain allyl acetate from propylene, oxygen and acetic acid.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:7][C:8]([Cl:12])=[N:9]2)=[CH:4][CH:3]=1.[CH:19]([C:21]1[O:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20].C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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.O.CCO>[Cl:12][C:8]1[N:7]=[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[C:10](=[CH:11][C:2]([C:24]3[O:25][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)=[CH:3][CH:4]=2)[N:9]=1
Reactant: O=Cc1ccc(B(O)O)o1
Reactant: Clc1nc(N2CCOCC2)c2ccc(Br)cc2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=Cc1ccc(-c2ccc3c(N4CCOCC4)nc(Cl)nc3c2)o1
Temperature: 75 °C
Reaction time: 2.5 h
Yield: 69 %

Procedure:
To a 50 mL round bottom flask, 7-bromo-2-chloro-4-morpholin-4-yl-quinazoline (Example 1; 1.0 g, 0.00304 mol) and 5-formyl-2-furanylboronic acid (0.384 g, 0.00274 mol), sodium carbonate (0.806 g, 0.0076 mol), toluene (15 mL), EtOH (15 mL) and water (5 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (0.105 g, 0.000152 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 75° C. for 2.5 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified; using column chromatography (60-120 silica gel, 75% ethyl acetate in hexane) to yield the desired product [0.65 g, 62%]. 1H NMR (300 MHz, CDCl3): δ 9.73 (s, 1H), 8.20 (s, 1H), 7.90 (s, 2H), 7.38 (d, J=3.6 Hz, 1H), 7.06 (d, J=3.6 Hz, 1H), 3.91 (s, 4H), 3.90 (s, 4H). LC-MS (ESI): Calculated mass: 343.0; Observed mass: 344.3 (RT: 1.21 min).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:16]=2[C:22]2[O:23][C:24]3[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:25]=3[CH:26]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C1CCC=CC=1>CO.[Pd]>[OH:31][C:28]1[CH:29]=[CH:30][C:24]2[O:23][C:22]([C:16]3[C:15]([C:12]4[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=4)=[CH:20][C:19]([OH:21])=[CH:18][CH:17]=3)=[CH:26][C:25]=2[CH:27]=1
Reactant: Oc1ccc(-c2cc3cc(O)ccc3o2)c(-c2ccc(OCc3ccccc3)cc2)c1
Agent: [Pd]
Solvent: C1=CCCC=C1
Solvent: CO
Product: Oc1ccc(-c2cc(O)ccc2-c2cc3cc(O)ccc3o2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 47.1 %

Procedure:
A solution of 104 (0.13 g, 0.32 mmol) in MeOH (10 mL) was treated with 0.2 g 10% Pd/C and cyclohexadiene (1 mL) and stirred at rt for 24 h. The reaction was filtered through a bed of Celite, concentrated and chromatographed on silica gel (1:1 EtOAc/hexanes) and the product was obtained as an oil which crystallized upon addition of CH2Cl2 to yield 48 mg of yellowish needles: Mp=238-239° C.; 1H NMR (DMSO-d6) δ 9.87 (brs, 1 H), 9.54 (brs, 1 H), 9.08 (br s, 1 H), 7.64 (d, 1 H, J=8.5 Hz), 7.21 (d, 1H, J=8.7 Hz), 7.05 (d, 2 H, J=8.4 Hz), 6.84 (dd, 1 H, J=8.5 Hz, 2.5 Hz), 6.76 (d, 2 H, J=8.5 Hz), 6.69 (dd, 2 H, J=6.6 Hz, 2.4 Hz), 6.63 (dd, 1 H, J=8.7 Hz, 2.4 Hz), 5.84 (s, 1H); MS 317 (M−H)−.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21](=[O:32])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24](CC(=O)C)[CH:23]=3)[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH:35](C1C=C(C=CC=1)C(O)=O)=[O:36]>>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21](=[O:32])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH:35]=[O:36])[CH:23]=3)[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(CC(C)=O)c1
Reactant: O=Cc1cccc(C(=O)O)c1
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C=O)c1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 29, using 3-formylbenzoic acid in place of 3-(2-oxopropyl)benzoic acid. ES/MS calcd. for C24H30N5O3+ 436.2. found m/z=436.2 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[C:5]([CH3:13])[CH:4]=1.[N+:14]([O-])([OH:16])=[O:15]>C(O)(=O)C>[CH3:1][O:2][C:3]1[C:8]([N+:14]([O-:16])=[O:15])=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[C:5]([CH3:13])[CH:4]=1
Reactant: COc1ccc(NC(C)=O)c(C)c1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: COc1cc(C)c(NC(C)=O)cc1[N+](=O)[O-]
Yield: 53 %

Procedure:
34 g(0.19 mol) of N-(4-methoxy-2-methylphenyl)acetamide were added in small portions to a mixture of 40 ml of glacial acetic acid and 70 ml of fuming nitric acid at −10 to −15° C. These portions were such that the temperature did not rise above −10° C. The reaction mixture was then poured onto ice. The resulting precipitate was filtered off with suction and washed with water, ethanol and diethyl ether. 22.5 g (53%) of the desired product were obtained.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:41]=[CH:42][CH:43]=1)[C:8]([NH:10][C:11]1[S:12][C:13]2[CH2:40][CH2:39][CH2:38][CH2:37][C:14]=2[C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)=[O:17])=[O:9])(=[O:4])=[O:3].[CH:44]1([NH:47][CH:48]2[CH2:53][CH2:52][CH:51]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[CH2:50][CH2:49]2)[CH2:46][CH2:45]1>ClCCl>[CH:44]1([N:47]([CH:48]2[CH2:53][CH2:52][CH:51]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[CH2:50][CH2:49]2)[S:2]([C:5]2[CH:6]=[C:7]([CH:41]=[CH:42][CH:43]=2)[C:8]([NH:10][C:11]2[S:12][C:13]3[CH2:40][CH2:39][CH2:38][CH2:37][C:14]=3[C:15]=2[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]3[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=3)=[CH:21][CH:20]=2)=[O:17])=[O:9])(=[O:4])=[O:3])[CH2:45][CH2:46]1
Reactant: COC(=O)c1ccc(CCc2ccc(NC(=O)c3c(NC(=O)c4cccc(S(=O)(=O)Cl)c4)sc4c3CCCC4)cc2)cc1
Reactant: CCOC(=O)C1CCC(NC2CC2)CC1
Solvent: ClCCl
Product: CCOC(=O)C1CCC(N(C2CC2)S(=O)(=O)c2cccc(C(=O)Nc3sc4c(c3C(=O)Nc3ccc(CCc5ccc(C(=O)OC)cc5)cc3)CCCC4)c2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.1 %

Procedure:
A mixture of 300 mg of methyl 4-[2-(4-{[(2-{[3-(chlorosulfonyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, 298 mg of ethyl 4-(cyclopropylamino)cyclohexane carboxylate, and 3.0 mL of dichloromethane was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (chloroform only) to obtain 314 mg of methyl 4-(2-{4-[({2-[(3-{cyclopropyl[4-(ethoxycarbonyl)cyclohexyl]sulfamoyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoate as a yellow powder solid.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]([CH2:15][CH2:16][NH:17][C:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[CH:8]=[CH:9][C:10]=1[O:11][C:12](=[O:14])[CH3:13])(=[O:3])[CH3:2].[CH3:26][I:27]>CO>[I-:27].[CH3:26][N+:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:18](=[O:19])[NH:17][CH2:16][CH2:15][C:7]2[CH:8]=[CH:9][C:10]([O:11][C:12](=[O:14])[CH3:13])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[CH:6]=2)[CH:21]=1
Reactant: CI
Reactant: CC(=O)Oc1ccc(CCNC(=O)c2cccnc2)cc1OC(C)=O
Solvent: CO
Product: CC(=O)Oc1ccc(CCNC(=O)c2ccc[n+](C)c2)cc1OC(C)=O
Product: [I-]

Procedure:
To a solution of 1.71 g (5 mmol) of 3-{N-[β-(3,4-diacetoxyphenyl)ethyl]}carbamoylpyridine (prepared like compound 8c), 1.41 g (10 mmol) of methyl iodide were added and the mixture was refluxed overnight under stirring. The acetone solution was then decanted from the insoluble oily residue. Ether was added to the acetone solution and the solid which separated was crystallized from acetone/ether. Yield, 1.9 g (78%) of yellow crystalline needles, m.p. 171°-173° C. U.V. (methanol) 215, 265 nm; NMR (D2O) δ 8.86-7.63 (ms, 4H, C5H4N+), 6.66 (bs, 3H, C6H3), 4.4 (s, 3H, --N+ --CH3), 3.50 (t, 2H, --N--CH2), 3.03 (t, 2H, CH2), 2.21 (bs, 6H, 2 COCH3). Anal. Calcd for C19H21IN2O5 : C, 47.12; H, 4.37; N, 5.78. Found: C, 47.23; H, 4.38; N, 5.78.
Reaction SMILES: [C:1]([C:9]1[C:17]2[C:16]([NH:18][C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=3)C(O)=O)=[N:15][CH:14]=[N:13][C:12]=2[NH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN([C:40]([O:44]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>CN(C=O)C>[C:1]([C:9]1[C:17]2[C:16]([NH:18][C:19]3[CH:27]=[CH:26][CH:25]=[CH:21][C:20]=3[C:40]([NH:61][C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)=[O:44])=[N:15][CH:14]=[N:13][C:12]=2[NH:11][CH:10]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cccc(Nc2ncnc3[nH]cc(C(=O)c4ccccc4)c23)c1
Reactant: Nc1ccccc1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1ccccc1)c1ccccc1Nc1ncnc2[nH]cc(C(=O)c3ccccc3)c12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 3-((5-benzoyl-7H-pyrrolo[2,3-d]pyrimidine-4-yl)amino)benzoic acid (25 mg, 0.07 mmol) in DMF (1 mL) was added DIPEA (18 μL, 0.105 mmol), HBTU (32 mg, 0.084 mmol), and aniline (7.6 μL, 0.084 mmol). The reaction was stirred at room temperature for 18 hours. The crude was purified by reverse phase preparative HPLC. M.p.>300° C.; 400 MHz 1HNMR (DMSO-d6) δ 13.04 (s, 1H), 11.50 (s, 1H), 10.34 (s, 1H), 8.50 (s, 1H), 8.33 (t, J=1.6 Hz, 1H), 8.26-8.23 (d, J=8.0 Hz, 1H), 7.99 (d, J=2.4 Hz, 1H), 7.88 (d, J=6.8 Hz, 2H), 7.79 (d, J=7.6 Hz, 1H), 7.69-7.53 (m, 5H), 7.37 (t, J=7.6 Hz, 2H), 7.11 (t, J=6.8 Hz, 1H); LCMS [M+H] 434.
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:34]=[CH:33][N:32]([CH2:35][C:36]([CH3:39])([OH:38])[CH3:37])[N:31]=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C)C=O>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([CH3:22])[CH3:21])(=[O:18])=[O:19])=[CH:13][CH:12]=2)[C:8]([NH:29][C:30]2[CH:34]=[CH:33][N:32]([CH2:35][C:36]([OH:38])([CH3:37])[CH3:39])[N:31]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC(C)(O)Cn1ccc(N)n1
Reactant: CC(C)S(=O)(=O)c1ccc([C@@H](CC2CCCC2)C(=O)O)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: Cc1cccc(C)n1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)S(=O)(=O)c1ccc([C@@H](CC2CCCC2)C(=O)Nc2ccn(CC(C)(C)O)n2)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 58 %

Procedure:
(R)-3-cyclopentyl-2-[4-(propane-2-sulfonyl)-phenyl]-propionic acid (100 mg, 0.31 mmol) was dissolved in methylene chloride (3 mL) and N,N-dimethylformamide (three drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 180 μL, 0.33 mmol) which produced gas evolution and it was then stirred at 25° C. for 15 minutes after which time it was concentrated in vacuo. The residue was then dissolved in methylene chloride (3 mL) and added dropwise into a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 50 mg, 0.31 mmol), 2,6-lutidine (100 μL, 0.62 mmol) and methylene chloride (3 mL) at 0° C. It was then allowed to warm to 25° C. and stirred for 3 h. After this time, the reaction was quenched with a small amount of methanol and diluted with methylene chloride. It was then washed with 1 N aqueous hydrochloric acid solution and saturated aqueous brine solution dried over sodium sulfate and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 60% ethyl acetate/hexanes to 100% ethyl acetate) to afford (R)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(propane-2-sulfonyl)-phenyl]-propionamide (83 mg, 58%) as a white foam: [α]30589=−8.3° (c=0.18, methanol); ES-HRMS m/e calcd for C24H35N3O4S (M+H)+ 462.2421, observed 462.2421; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.03 (s, 3H, CH3), 1.04 (s, 3 H, CH3), 1.11 (m, 2H, CH2), 1.13 (d, J=6.9 Hz, 6H, 2×CH3), 1.35-1.80 (m, 8H, 4×CH2), 2.10 (m, 1H, CH), 3.36 (m, 1H, SO2CH), 3.86 (s, 2H, NCH2), 3.93 (m, 1H, ArCHCO), 4.65 (s, 1H, OH), 6.46 (d, J=2.4 Hz, 1H, Ar), 7.50 (d, J=2.4 Hz, 1H, Ar), 7.64 (d, J=8.4 Hz, 2H, Ar), 7.80 (d, J=8.4 Hz, 2H, Ar), 10.79 (s, 1H, NH).
Reaction SMILES: [CH2:1]([NH:13][CH:14]1[CH2:19][C:18]([CH3:21])([CH3:20])[N:17]([O:22][CH:23]([CH3:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:16]([CH3:32])([CH3:31])[CH2:15]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])C.Cl[P:41]1[O:46][CH2:45][C:44]2([CH2:51][O:50][P:49](Cl)[O:48][CH2:47]2)[CH2:43][O:42]1>O1CCCC1>[CH3:30][CH:23]([O:22][N:17]1[C:18]([CH3:20])([CH3:21])[CH2:19][CH:14]([N:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[P:41]2[O:46][CH2:45][C:44]3([CH2:51][O:50][P:49]([N:35]([CH2:36][CH2:37][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH:38]4[CH2:39][C:18]([CH3:19])([CH3:20])[N:17]([O:22][CH:23]([CH3:30])[C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[C:16]([CH3:15])([CH3:31])[CH2:32]4)[O:48][CH2:47]3)[CH2:43][O:42]2)[CH2:15][C:16]1([CH3:31])[CH3:32])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCN(CC)CC
Reactant: ClP1OCC2(CO1)COP(Cl)OC2
Reactant: CCCCCCCCCCCCNC1CC(C)(C)N(OC(C)c2ccccc2)C(C)(C)C1
Solvent: C1CCOC1
Product: CCCCCCCCCCCCN(C1CC(C)(C)N(OC(C)c2ccccc2)C(C)(C)C1)P1OCC2(CO1)COP(N(CCCCCCCCCCCC)C1CC(C)(C)N(OC(C)c3ccccc3)C(C)(C)C1)OC2
Temperature: 25 °C
Reaction time: 4 h
Yield: 99.3 %

Procedure:
A solution of 8.2 grams (18.4 mmol) of 4-dodecylamino 1-alpha-methylbenzyloxy-2,2,6,6-tetramethylpiperidine (made in Example 11B), 1.86 gram (18.4 mmol) of triethylamine, and 30 ml of tetrahydrofuran is added dropwise over a fifteen minute period to a solution of 2.44 grams (9.2 mmol) of 3,9-dichloro 2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane in 20 ml of tetrahydrofuran. The reaction mixture is then stirred at ambient temperature for four hours. Triethylamine hydrochloride is removed by filtration, and the filtrate is evaporated at reduced pressure to afford 9.88 grams of the title compound as a colorless syrup.
Reaction SMILES: [I:1][C:2]1[C:3]2[C:4](=[CH:8][NH:9][N:10]=2)[N:5]=[CH:6][CH:7]=1.Br[CH2:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[I:1][C:2]1[C:3]2[C:4](=[CH:8][N:9]([CH2:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15])[N:10]=2)[N:5]=[CH:6][CH:7]=1.[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[N:9][N:10]([CH2:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15])[C:3]=12
Reactant: CC(C)(O)CCBr
Reactant: Ic1ccnc2c[nH]nc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(O)CCn1cc2nccc(I)c2n1
Product: CC(C)(O)CCn1ncc2nccc(I)c21
Temperature: 120 °C

Procedure:
7-Iodo-2H-pyrazolo[4,3-b]pyridine (342 mg, 1.396 mmol), 4-bromo-2-methylbutan-2-ol (233 mg, 1.396 mmol) and Cs2CO3 (455 mg, 1.396 mmol) were combined in DMF (5 mL) and heated in a microwave at 120° C. for 60 minutes. The reaction was cooled, filtered, and concentrated to give a residue which purified on a silica column and eluted using a step gradient of EtOAc (0-90%) in hexanes to give 4-(7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)-2-methylbutan-2-ol and 4-(7-iodo-1H-pyrazolo[4,3-b]pyridin-1-yl)-2-methylbutan-2-ol.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:11][CH:10]=[N:9][CH:8]=1.[CH2:12]([O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][C:28](O)=[O:29])[CH:23]=[CH:24][CH:25]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[O:29]=[C:28]([C:10]1[O:11][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[CH:8][N:9]=1)[CH2:27][CH2:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:21]=1
Reactant: O=C(O)CCc1cccc(OCc2ccccc2)c1
Reactant: c1ccc(-c2cnco2)nc1
Product: O=C(CCc1cccc(OCc2ccccc2)c1)c1ncc(-c2ccccn2)o1
Yield: 18 %

Procedure:
The title compound was prepared from 5-(2-pyridyl)oxazole and 3-(3-(benzyloxy)phenyl)propanoic acid (Bänteli, R.; Brun, I.; et al. Tetrahedron Lett. 1999, 40, 2109-2112) using General Procedure B. Column chromatography (SiO2, 2.5×6 cm, 10-20% EtOAc-hexanes gradient) followed by PTLC (SiO2, 50% EtOAc-hexanes) afforded 11c (46 mg, 0.12 mmol, 18%) as a yellow solid: 1H NMR (CDCl3, 400 MHz) 8.67 (m, 1H), 7.88 (s, 1H), 7.87-7.85 (m, 1H), 7.81 (td, 1H, J=7.8, 1.8 Hz), 7.45 (d, 2H, J=8.5 Hz), 7.38 (t, 2H, J=7.3 Hz), 7.32 (t, 2H, J=6.8 Hz), 7.22 (t, 2H, J=7.9 Hz), 6.92 (d, 2H, J=2.1 Hz), 6.88 (d, 2H, J=7.6 Hz), 6.83 (dd, 2H, J=7.9, 2.4 Hz), 5.06 (s, 2H), 3.47 (t, 2H, J=7.4 Hz), 3.10 (t, 2H, J=7.4 Hz); 13C NMR (CDCl3, 100 MHz) 187.2, 158.9, 157.2, 153.4, 150.1, 146.2, 142.0, 137.1, 137.0, 129.5, 128.5, 127.9, 127.5, 127.0, 124.2, 121.0, 120.4, 115.1, 112.5, 69.9, 40.5, 29.7; IR (film) νmax 3073, 3032, 2929, 1697, 1601, 1582, 1499, 1468, 1452, 1425, 1380, 1256, 1154, 1027, 784, 737, 695 cm−1; ESI-TOF m/z 385.1549 (C24H20N2O3+H+ requires 385.1547).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:13]2[CH2:17][C@H:16]([CH2:18][N:19]3[CH:23]=[CH:22][N:21]=[N:20]3)[O:15][C:14]2=[O:24])[CH:5]=[CH:6][C:7]=1[C:8]1[N:9]=[N:10][NH:11][CH:12]=1.[H-].[Na+].Br[CH2:28][C:29]#[N:30]>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[C:4]([N:13]2[CH2:17][C@H:16]([CH2:18][N:19]3[CH:23]=[CH:22][N:21]=[N:20]3)[O:15][C:14]2=[O:24])[CH:5]=[CH:6][C:7]=1[C:8]1[N:9]=[N:10][N:11]([CH2:28][C:29]#[N:30])[CH:12]=1
Reactant: N#CCBr
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(-c2c[nH]nn2)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: N#CCn1cc(-c2ccc(N3C[C@H](Cn4ccnn4)OC3=O)cc2F)nn1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 108.6 %

Procedure:
(5R)-3-[3-Fluoro-4-(1H-1,2,3-triazol4-yl)phenyl]-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 7, 1.5 g, 4.6 mmol) was stirred in N,N-dimethylformamide at 0° C. Sodium hydride (0.35 g, 9.2 mmol) was added and the mixture was stirred 30 minutes. Bromoacetonitrile (0.66 g, 5.5 mmol) was added and the reaction was stirred overnight, slowly warming to room temperature. Starting material was present so additional bromoacetonitrile (0.33 g, 2.8 mmol) was added and the reaction was stirred for two additional days. The mixture was diluted with water and extracted using ethyl acetate. The organic layer was washed with water, dried (magnesium sulfate) and concentrated under vacuum to give a yellow solid (1.84 g). The solid was dissolved in dimethylsulfoxide (18 ml) and water (5 ml) and the isomers were separated using Gilson HPLC. Peaks 1 and 2 were collected, concentrated and lyophilized to give a light yellow solid (Example 10, peak 1, 36 mg; Example 11, peak 2, 182 mg). NOE experiments were used to distinguish the two isomers with the cyano group of peaks 1 and 2 corresponding to the 1 and 2 positions of the nitrogen, respectively.