Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].C(O)(=O)C(O)=O.[NH2:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][NH:22][C:23]([C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH:34]([CH3:36])[CH3:35])[N:26]=2)=[O:24])[CH2:16][CH2:15]1.C(N(CC)CC)C.[C:44](Cl)(=[O:48])[CH:45]([CH3:47])[CH3:46]>O1CCCC1>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:44]([NH:13][CH:14]1[CH2:15][CH2:16][N:17]([CH2:20][CH2:21][NH:22][C:23]([C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]([CH:34]([CH3:36])[CH3:35])[N:26]=2)=[O:24])[CH2:18][CH2:19]1)(=[O:48])[CH:45]([CH3:47])[CH3:46]
Reactant: CC(C)n1nc(C(=O)NCCN2CCC(N)CC2)c2ccccc21
Reactant: CC(C)C(=O)Cl
Agent: O=C(O)C(=O)O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)C(=O)NC1CCN(CCNC(=O)c2nn(C(C)C)c3ccccc23)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
The product from Example 23, as the free base (0.330 g, 1 mmol) and triethylamine (0.15 mL, 1.05 mmol) were stirred in 10.0 mL tetrahydrofuran and cooled briefly in an ice bath. To the mixture was added dropwise isobutyryl chloride (0.10 mL, 1 mmol) and the resulting mixture was stirred 18 h at room temperature and filtered, and the filtrate was evaporated to 0.417 g oil. Crystallization as the oxalate salt from 2-propanol provided 0.194 g colorless crystals. Mp 193° C. Mass spectrum, m+ =399. Anal (C24H35N506) theory C, 58.88; H, 7.21; N, 14.30; found C, 58.60; H, 6.95; N, 14.11.
Reaction SMILES: [C:1]([Si:5]([O:18][C@@H:19]1[C@H:26]2[C@H:22]([O:23][C:24]([CH3:28])([CH3:27])[O:25]2)[C:21]([CH2:29][O:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:20]1I)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:51][C:52]1([CH3:59])[C:56]([CH3:58])([CH3:57])[O:55][BH:54][O:53]1>C1COCC1>[CH3:28][C:24]1([CH3:27])[O:25][C@H:26]2[C@@H:19]([O:18][Si:5]([C:1]([CH3:2])([CH3:4])[CH3:3])([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:20]([B:54]3[O:55][C:56]([CH3:58])([CH3:57])[C:52]([CH3:59])([CH3:51])[O:53]3)=[C:21]([CH2:29][O:30][C:31]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C@H:22]2[O:23]1
Reactant: CC1(C)O[C@@H]2[C@H](O1)C(COC(c1ccccc1)(c1ccccc1)c1ccccc1)=C(I)[C@@H]2O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: CC1(C)OBOC1(C)C
Solvent: C1CCOC1
Product: CC1(C)O[C@@H]2[C@H](O1)C(COC(c1ccccc1)(c1ccccc1)c1ccccc1)=C(B1OC(C)(C)C(C)(C)O1)[C@@H]2O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 35 %

Procedure:
To a 25 mL round-bottom 3-neck flask equipped with nitrogen inlet/outlet, stir bar, and thermocouple with temperature controller was charged 0.2806 g of compound 8 (0.353 mmol, 1.0 eq) and 3 mL tetrahydrofuran (10 V). The reaction was cooled to 0° C. To this solution was added 0.653 mL (0.847 mmol, 2.4 eq) of isopropylmagnesium chloride lithium chloride complex, 1.3 M in THF slowly over 15 minutes. The reaction was stirred at 0° C. for 1 hour. HPLC assay indicated formation of intermediate. 0.128 mL of 4,4,5,5 tetramethyl-1,3,2 dioxaborolane (0.884 mmol, 2.5 eq) was added to the reaction. An HPLC assay after 1 hour at 0° C. indicated that the reaction was completed. The reaction was quenched with saturated aqueous ammonium chloride solution (3V). The ice bath was removed and the reaction warmed to room temperature. The reaction was charged with DI water (3V) and ethyl acetate (6V). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (6V). The organic phases were combined and washed with brine (3V) and dried over MgSO4. The resulting mixture was filtered. The filtrate was concentrated to dryness by the rotary evaporator. Obtained 0.098 grams as a white solid, (35% yield), 80 A % purity of [(3aR,6S,6aR)-2,2-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trityloxymethyl)-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]oxy-tert-butyl-diphenyl-silane (compound 9c-2).
Reaction SMILES: Br[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[F:10][C:11]([F:23])([F:22])[C:12]1[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][N:13]=1.C(=O)(O)[O-].[Na+]>ClCCl>[C:6]([O:5][C:3](=[O:4])[CH2:2][N:14]1[CH:15]=[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([C:11]([F:10])([F:22])[F:23])=[N:13]1)([CH3:9])([CH3:8])[CH3:7]
Reactant: CCOC(=O)c1c[nH]nc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)c1cn(CC(=O)OC(C)(C)C)nc1C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h

Procedure:
404 mg of Hünig-base and 469 mg of tert-butyl bromoacetate, dissolved in 2 ml of dichloromethane, are added to a solution of 50 mg of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate in 10 ml of dichloromethane. The mixture is stirred at room temperature for 16 hours. After addition of saturated sodium bicarbonate solution, the mixture is extracted with ethyl acetate, the organic phase is separated off and dried over sodium sulphate and the solvent is removed under reduced pressure. This gives 742 mg of ethyl 1-(2-tert-butoxy-2-oxoethyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Va-10) in a purity of about 78% (LCMS).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]2[CH2:11][CH:10]([CH2:12][CH2:13][F:14])[CH2:9]2)[CH:3]=1.[CH:15]([Si:18]([C:25]#[CH:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])([CH3:17])[CH3:16].C(N(CC)CC)C>[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:14][CH2:13][CH2:12][CH:10]1[CH2:11][CH:8]([C:4]2[CH:3]=[C:2]([C:26]#[C:25][Si:18]([CH:15]([CH3:17])[CH3:16])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])[CH:7]=[CH:6][CH:5]=2)[CH2:9]1
Reactant: C#C[Si](C(C)C)(C(C)C)C(C)C
Reactant: FCCC1CC(c2cccc(Br)c2)C1
Agent: I[Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: CC(C)[Si](C#Cc1cccc(C2CC(CCF)C2)c1)(C(C)C)C(C)C
Yield: 80.4 %

Procedure:
In a CEM snap top microwave vial were combined 1-Bromo-3-[3-(2-fluoro-ethyl)-cyclobutyl]-benzene (0.250 gm 9.72 mmol), triisopropylsilylacetylene (0.22 gm, 1.21 mmol), copper iodide (7 mg, 0.178 mmol), tetrakis(triphenylphosphine)palladium (22 mg, 0.088 mmol) and triethylamine (0.600 g, 5.93 mmol). The vial was quickly agitated then irradiated in a CEM Explorer™ microwave instrument for 30 minutes at 80° C. Purification by column chromatography (hexanes) afforded an oil 349 mg. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06 (s, 21H) 1.62-1.81 (m, 2H) 1.82-1.97 (m, 1H) 2.00-2.45 (m, 4H) NMR (400 MHz, DMSO-d6) δ ppm 3.31-3.62 (m, 1H) 4.30-4.51 (m, 2H) 7.17-7.41 (m, 4H); MS (EI) m/z 256 [M+·].
Reaction SMILES: C(O[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)[CH:9]=[C:8]([CH3:20])[N:7]=1)=[O:5])C.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1>>[CH3:28][C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:4]([C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]([F:19])[CH:15]=[C:16]([F:18])[CH:17]=3)[CH:9]=[C:8]([CH3:20])[N:7]=2)=[O:5])=[N:23][CH:24]=1
Reactant: Cc1ccc(N)nc1
Reactant: CCOC(=O)c1cc(-c2cc(F)cc(F)c2)cc(C)n1
Product: Cc1ccc(NC(=O)c2cc(-c3cc(F)cc(F)c3)cc(C)n2)nc1

Procedure:
The title compound, was prepared from 4-(3,5-Difluorophenyl)-6-methyl-pyridine-2-carboxylic acid ethyl ester in accordance with the general method of example 26, step 6 using 2-Amino-5-methylpyridine instead of 3-chloroaniline to yield the final compound as a white crystalline, MS (ISP): m/e=340.2 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:33]=[C:34]([CH:36]=[CH:37][CH:38]=2)[NH2:35])[CH2:28][CH2:27]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:23][N:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:35][C:34]3[CH:36]=[CH:37][CH:38]=[C:32]([N:29]4[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]4)[CH:33]=3)[N:24]=2)[CH:9]=[CH:8][CH:7]=1)[S:19]([CH3:22])(=[O:21])=[O:20]
Reactant: CN(c1ccccc1CNc1cccn2nc(Cl)nc12)S(C)(=O)=O
Reactant: CN1CCN(c2cccc(N)c2)CC1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2cccc(Nc3nc4c(NCc5ccccc5N(C)S(C)(=O)=O)cccn4n3)c2)CC1

Procedure:
N-Methyl-N-[2-({2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-phenyl]-methanesulfonamide was prepared from N-{2-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-phenyl}-N-methyl-methanesulfonamide (75.0 mg, 0.205 mmol) and 3-(4-methylpiperazin-1-yl)aniline (44.0 mg, 0.230 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (23.0 mg, 0.0421 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.054 g, 50%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.81 (d, J=6.6 Hz, 1H), 7.55-7.51 (m, 1H), 7.38-7.28 (m, 3H), 7.24-7.18 (m, 2H), 7.04 (d, J=8.1 Hz, 1H), 6.71-6.64 (m, 2H), 6.56 (d, J=8.2 Hz, 1H), 6.37 (d, J=7.7 Hz, 1H), 5.22 (t, J=6.1 Hz, 1H), 4.72 (d, J=6.0 Hz, 2H), 3.31 (s, 3H), 3.28-3.23 (m, 4H), 3.00 (s, 3H), 2.61-2.56 (m, 4H), 2.36 (s, 3H). MS=521 (MH)+.
Reaction SMILES: [C:1]([CH:4]([C:14]1[N:22]2[C:17]([C:18](=[O:32])[NH:19][C:20]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)=[N:21]2)=[C:16]([CH3:33])[N:15]=1)[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>>[OH:3][CH:1]([CH:4]([C:14]1[N:22]2[C:17]([C:18](=[O:32])[NH:19][C:20]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)=[N:21]2)=[C:16]([CH3:33])[N:15]=1)[CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH3:2]
Reactant: COc1ccc(Cc2nn3c(C(CCCc4ccccc4)C(C)=O)nc(C)c3c(=O)[nH]2)cc1
Agent: [BH4-]
Agent: [Na+]
Product: COc1ccc(Cc2nn3c(C(CCCc4ccccc4)C(C)O)nc(C)c3c(=O)[nH]2)cc1

Procedure:
80 mg (0.19 mmol) of 7-(1-acetyl-4-phenylbutyl)-2-(4-methoxybenzyl)-5-methyl-imidazo[5,1-f][1,2,4]triazin-4(3H)-one are reacted analogously to Example 12 with 9 mg (0.19 mmol) of sodium borohydride to give 7-[1-(1-hydroxyethyl)-4-phenyl-butyl]-2-(4-methoxybenzyl)-5-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one.
Reaction SMILES: [Si:1]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([CH2:15][C:16]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)[N:13]([CH2:25][CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=2)[C:12]1=[O:38])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].P(OCC)(OCC)(OCC)=[O:40]>C1(C)C=CC=CC=1>[Si:1]([O:8][C@@H:9]([C@H:11]1[C:12](=[O:38])[N:13]2[C:25]([C:26]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]([N+:35]([O-:37])=[O:36])=[CH:33][CH:34]=3)=[O:40])=[C:16]([S:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:15][C@H:14]12)[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCOP(=O)(OCC)OCC
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N(CCOCc2ccc([N+](=O)[O-])cc2)[C@@H]1CC(=O)Sc1ccccc1
Solvent: Cc1ccccc1
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Sc3ccccc3)C[C@H]12
Temperature: 100 °C
Reaction time: 18 h
Yield: 88.3 %

Procedure:
A mixture of 114 mg (0.194 mmole) of (3S, 4R)-3-[(R)-1-t-butyldimethylsilyloxyethyl]-1-(p-nitrobenzyloxyethyl)-4-[(phenylthio)carbonylmethyl]-2-azetidinone, 258 mg (1.55 mmole) of triethyl phosphate and 10 ml of toluene was stirred at 100° C. for 18 hours under a nitrogen atmosphere. The solvent was distilled off, and the residue was purified by the procedure described in Example 5, to give 95 mg (yield 88%) of the title product , in the form of crystals.
Reaction SMILES: C(O)(C(F)(F)F)=O.C(OC([N:15]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](=[O:39])[N:24]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])=O)(C)(C)C.Cl.ON(C(=O)CCCCN(O)C(=O)CCCCN(O)C(=O)CCCCCCCCC)CCCCCN.CO.C(Cl)(Cl)Cl>C(Cl)Cl>[CH2:32]([O:31][N:24]([C:23](=[O:39])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][NH:15][O:40][CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[CH2:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: CC(C)(C)OC(=O)N(CCCCCCCC(=O)N(CCCCC#N)OCc1ccccc1)OCc1ccccc1
Agent: CCCCCCCCCC(=O)N(O)CCCCC(=O)N(O)CCCCC(=O)N(O)CCCCCN
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#CCCCCN(OCc1ccccc1)C(=O)CCCCCCCNOCc1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Excess TFA was added to [II] (2.00 g, 3.63 mmol) in CH2Cl2 at 0° C. The solution was stirred at 0° C. for 30 minutes and at room temperature for 15 minutes, and then the reaction was worked up by the method used for (5). Silica gel column chromatography with 2% MeOH/CHCl3 provided 1.51 g (92%) of [III] as an oil: NMR δ 1.17-1.90 (m, 14H), 2.23-2.50 (m, 4H), 2.90 (t, 2H, J=6), 3.40 (s, 1H), 3.63 (t, 2H, J=6), 4.67 (s, 2H), 4.77 (s, 2H), 7.30 (s, 5H), 7.33 (s, 5H). Anal. (C27H37N3O3) C, H, N.
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15](OB(O)O)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25](Cl)[N:24]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1(C)C=CC=CC=1.CCCCCC.O.CCCCCC>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([Cl:22])[N:24]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[C@H]1CC[C@H](c2ccc(OB(O)O)cc2)CC1
Reactant: Clc1cccc(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: CCCCC[C@H]1CC[C@H](c2ccc(-c3cccc(Cl)n3)cc2)CC1

Procedure:
A mixture of 0.23 mol of 4-(trans-4-pentylcyclohexyl)phenylboric acid, 0.23 mol of 2,6-dichloropyridine, 5 mmol of TPP, 230 ml of a 2 molar sodium carbonate solution and 400 ml of toluene are heated at the boil for 1 hour. The reaction mixture is cooled, and 200 ml of hexane and 200 ml of water are added. The organic phase is separated off, the solvent is removed by evaporation, and the pure product is obtained by chromatography on silica gel using toluene/hexane 3:1 as the eluent.
Reaction SMILES: [CH:1]1([C:7]2[N:8]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([CH3:12])=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([SiH](CC)CC)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[N:38]1([S:43]([C:46]2[CH:53]=[CH:52][CH:51]=[CH:50][C:47]=2[CH:48]=O)(=[O:45])=[O:44])[CH2:42][CH2:41][CH2:40][CH2:39]1>>[CH:1]1([C:7]2[N:8]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([CH3:12])=[C:10]([CH2:48][C:47]3[CH:50]=[CH:51][CH:52]=[CH:53][C:46]=3[S:43]([N:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)(=[O:44])=[O:45])[CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=Cc1ccccc1S(=O)(=O)N1CCCC1
Reactant: CCOC(=O)Cn1c(C)ccc1C1CCCCC1
Agent: CC[SiH](CC)CC
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Product: CCOC(=O)Cn1c(C2CCCCC2)cc(Cc2ccccc2S(=O)(=O)N2CCCC2)c1C
Yield: 33.9 %

Procedure:
was followed using ethyl 2-(2-cyclohexyl-5-methyl-1H-pyrrol-1-yl)acetate (1.00 g, 4.01 mmol), triethylsilane (1.92 mL, 12.0 mmol), trimethylsilyl trifluoromethanesulfonate (1.45 mL, 8.02 mmol) and 2-(pyrrolidin-1-ylsulfonyl)benzaldehyde (0.960 g, 4.01 mmol) to afford ethyl 2-(5-cyclohexyl-2-methyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (642 mg, 1.36 mmol, 34% yield).
Reaction SMILES: [F:1][C:2]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:3]=1[NH:4][C:5]1[C:6]([C:13]([OH:15])=O)=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:33][C:34]([CH2:39][OH:40])([CH2:37][OH:38])[CH2:35][OH:36].CCCCCC>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:33][C:34]([CH2:39][OH:40])([CH2:37][OH:38])[CH2:35][OH:36])=[O:15])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1
Reactant: NC(CO)(CO)CO
Reactant: Cn1cc(C(=O)O)c(Nc2ccc(I)cc2F)cc1=O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCCCCC
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cn1cc(C(=O)NC(CO)(CO)CO)c(Nc2ccc(I)cc2F)cc1=O
Yield: 22 %

Procedure:
4-(2-Fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid and CDI were dissolved in anhydrous THF/DMF (4:1) and treated with 2-amino-2-[hydroxymethyl]-1,3-propandiol as for example 34. After the standard workup, trituration with hexane gave 4-(2-fluoro-4-iodoanilino)-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (22%) as a yellow/cream solid; m.p. (EtOAc/Hexane) 100-105° C. (glue-liquid). 1H NMR [400 MHz, (CD3)2SO] δ 9.62 (br s, 1H), 8.15 (s, 1H), 7.73 (dd, J=10.2, 1.7 Hz, 1H), 7.57 (d, J=8.5 Hz, 1H), 7.32 (s, 1H), 7.26 (t, J=8.5 Hz, 1H), 5.54 (s, 1H), 4.59 (t, J=5.7 Hz, 3H), 3.68 (d, J=5.7 Hz, 6H), 3.37 (s, 3H). HPLC 78.1% (254 nm). HRMS (FAB+) cald for C17H20FIN3O5 492.043 (M+), found 492.0425.
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([OH:30])=[C:11]([CH2:13][N:14]2[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[O:16][C:15]2=[O:29])[CH:12]=1.N1C=CC=CC=1>ClCCl>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([O:30][C:3]([CH2:2][Cl:1])=[O:4])=[C:11]([CH2:13][N:14]2[N:18]=[C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:23][CH:24]=3)[O:16][C:15]2=[O:29])[CH:12]=1
Reactant: O=C(Cl)CCl
Reactant: O=c1oc(-c2ccc(C(F)(F)F)cc2)nn1Cc1cc(Cl)ccc1O
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(CCl)Oc1ccc(Cl)cc1Cn1nc(-c2ccc(C(F)(F)F)cc2)oc1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 100.4 %

Procedure:
Neat chloroacetyl chloride (0.45 g, 5.6 mmol) was added dropwise to a stirred cold (0° C.) solution of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one (1.8 g, 4.9 mmol) and anhydrous pyridine (0.45 g, 5.5 mmol) in anhydrous dichloromethane (30 mL). The resulting mixture was allowed to warm to room temperature and stirred for 4 hr. The dichloromethane was rotary evaporated and the residue was partitioned between diethylether-ethyl acetate and dilute HCl. The organic layer was washed with saturated sodium bicarbonate, water and brine and then dried (MgSO4). Evaporation of the solvents followed by recrystallization of the residue from acetone/hexanes afforded the title compound as off-white crystals (2.2 g, 98%). MS m/e 447 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:12]([OH:14])=O)[NH:7]2.[CH3:15][O:16][C:17]1[CH:23]=[C:22]([B:24]2[O:28][C:27]([CH3:30])([CH3:29])[C:26]([CH3:32])([CH3:31])[O:25]2)[CH:21]=[CH:20][C:18]=1[NH2:19].C(N=C=NCCCN(C)C)C.Cl.ON1C2N=CC=CC=2N=N1>ClCCl.O>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:12]([NH:19][C:18]1[CH:20]=[CH:21][C:22]([B:24]3[O:25][C:26]([CH3:31])([CH3:32])[C:27]([CH3:30])([CH3:29])[O:28]3)=[CH:23][C:17]=1[O:16][CH3:15])=[O:14])[NH:7]2
Reactant: COc1cccc2[nH]c(C(=O)O)cc12
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: O
Solvent: ClCCl
Product: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1NC(=O)c1cc2c(OC)cccc2[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 65 %

Procedure:
To 4-methoxy-1H-indole-2-carboxylic acid (0.844 g, 4.42 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1 g, 4.01 mmol) in dichloromethane (20 ml) at 0° C. under a nitrogen atmosphere were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) hydrochloride (0.846 g, 4.42 mmol) and 1-hydroxy-7-azabenzotriazole (0.546 g, 4.01 mmol). The resulting brown solution was stirred at room temperature overnight. The reaction mixture was poured in water, the solids were collected by filtration and washed with some water. The solid was dried in a vacuum oven at 40° C. The solids were suspended in acetonitril (50 ml) and methanol (10 ml) and heated at 60° C. for 1 hour. The solids were collected by filtration and washed with hot acetonitril. Then the solids were stirred over night in dichloromethane. The mixture was filtered over a filter. The filtrate was concentrated in vacuo and gave 4-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-indole-2-carboxamide (1.1 g).
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[Cl:6][C:7]1[S:8][C:9]([S:13](Cl)(=[O:15])=[O:14])=[C:10]([CH3:12])[N:11]=1>C([O-])(O)=O.[Na+].C(OCC)(=O)C>[C:1]([NH:5][S:13]([C:9]1[S:8][C:7]([Cl:6])=[N:11][C:10]=1[CH3:12])(=[O:15])=[O:14])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1nc(Cl)sc1S(=O)(=O)Cl
Reactant: CC(C)(C)N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: Cc1nc(Cl)sc1S(=O)(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 79.1 %

Procedure:
To a stirred solution of commercially available tert-butylamine (3.76 mL, 35.5 mmol) in saturated NaHCO3 solution (30 mL) and ethyl acetate (50 mL) was added at 0° C. (ice water bath) a solution of commercially available 2-chloro-4-methyl-thiazole-5-sulfonyl chloride [CAS-No. 292138-59-1] (5.0 g, 21.5 mmol). The reaction mixture was stirred at room temperature for 16 h, ethyl acetate (50 mL) was added followed by extraction. The water layer was again extracted with ethyl acetate (50 mL). The combined organic layers were washed with 2N HCl solution (40 mL) and brine (40 mL), dried (MgSO4) and evaporated to yield the title compound (4.57 g, 79%) as a yellow solid. MS (ISN) 267.3 [(M−H)−].
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.C([O-])([O-])=O.[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CO>[CH2:18]([N:1]([CH2:2][C@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([OH:11])=[O:10])[CH2:7][CH2:8]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: NC[C@H]1CC[C@H](C(=O)O)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: O=C(O)[C@H]1CC[C@H](CN(Cc2ccccc2)Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred slurry of trans-4-aminomethyl-cyclohexanecarboxylic acid (5.00 g, 31.8 mmol) and K2CO3 (4.40 g, 127.2 mmol) in MeOH (100 mL) cooled to 0° C. was added benzyl bromide (7.94 mL, 66.8 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight. Most of the volatiles were removed in vacuo before addition of water (100 mL). The aqueous mixture was extracted with Et2O (2×200 mL) before adjusting to pH 5-6 by addition of 2 N HCl. The aqueous phase was extracted with DCM (3×200 mL) and the combined DCM extracts dried over Na2SO4 before concentrating in vacuo to afford trans-4-[(dibenzylamino)-methyl]-cyclohexanecarboxylic acid (3.22 g, 43%) as an off-white solid, m/z 338 [M+1]+.