Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[C:29]([CH3:30])=[CH:28][C:8]([O:9][C:10]2[CH:11]=[CH:12][C:13]([N+:25]([O-])=O)=[C:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:15]=2)=[CH:7][C:6]=1[CH3:31]>[Pd].CO>[NH2:25][C:13]1[CH:12]=[CH:11][C:10]([O:9][C:8]2[CH:7]=[C:6]([CH3:31])[C:5]([O:4][CH2:3][O:2][CH3:1])=[C:29]([CH3:30])[CH:28]=2)=[CH:15][C:14]=1[N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22]
Reactant: COCOc1c(C)cc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc1C
Agent: [Pd]
Solvent: CO
Product: COCOc1c(C)cc(Oc2ccc(N)c(N(C)C(=O)OC(C)(C)C)c2)cc1C
Yield: 93.7 %

Procedure:
By using 3.12 g of t-butyl N-[5-(4-methoxymethoxy-3,5-dimethylphenoxy)-2-nitrophenyl]-N-methylcarbamate, 0.33 g of 10% palladium on carbon and 30 ml of methanol, reaction and purification were carried out in a similar manner to that described in Reference Example 7, whereby 2.72 g of the title compound were obtained.
Reaction SMILES: [F-].[Cs+].Br[C:4]1[CH:17]=[CH:16][C:15]2[C:6](=[CH:7][C:8]3[C:13]([CH:14]=2)=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:5]=1.C([Sn](CCCC)(CCCC)[C:23]1[S:27][C:26]([C:28]2[S:29][C:30]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[CH:31][CH:32]=2)=[CH:25][CH:24]=1)CCC.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:5]1[C:6]2[C:15](=[CH:14][C:13]3[C:8]([CH:7]=2)=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:16]=[CH:17][C:4]=1[C:23]1[S:27][C:26]([C:28]2[S:29][C:30]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[CH:31][CH:32]=2)=[CH:25][CH:24]=1
Reactant: CCCCCCc1ccc(-c2ccc([Sn](CCCC)(CCCC)CCCC)s2)s1
Reactant: Brc1ccc2cc3ccccc3cc2c1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CCCCCCc1ccc(-c2ccc(-c3ccc4cc5ccccc5cc4c3)s2)s1
Temperature: 95 °C
Yield: 75 %

Procedure:
A vessel was charged with Pd2(dba)3 (77 mg, 84 μmol, 2 mol %), CsF (1.41 g, 9.29 mmol), 2-bromoanthracene (1.09 g, 4.22 mmol), 1,4-dioxane (20 mL), 5-(tri-n-butylstannyl)-5′-hexyl-2,2′-bithiophene (2.28 g, 4.22 mmol), and P(t-Bu)3 (0.74 mL of a 10 wt % solution in hexanes, 0.25 mmol). The mixture was heated at 95° C. for 36 h and then the volatile materials were removed under reduced pressure. The residue was extracted with 450 mL methylene chloride and the filtered extract was washed with 2×150 mL of brine. After drying with MgSO4, the bright orange solution was filtered, concentrated, and then cooled overnight at −35° C. Bright orange product (1.35 g, 75%) was isolated by filtration and dried under vacuum. The material may be purified further by gradient sublimation at a source temperature of 175-200° C. 1H NMR was consistent with the desired structure. UV-vis spectrum in CHCl3, 17.3 μg/mL: λmax (ε), 246 (53,500), 259 (54,700), 342 (40,200), 356 (42,900), 397 (27,600). ΔEopt˜2.8 eV. Fluorescence spectrum in CHCl3, excitation at 400 nm: λmax=464 (1.4×106 CPS). DSC (20° C./min): 204° C., (mp, ΔH=36 Jg−1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[CH2:48][CH2:47][N:46]3[C:39](=[CH:40][C:41]4[CH2:42][C:43]([CH3:50])([CH3:49])[CH2:44][C:45]=43)[C:38]2=[O:51])=[N:24][CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1)(=[O:19])[CH3:18]>>[C:17]([O:20][CH2:21][C:22]1[C:23]([N:37]2[CH2:48][CH2:47][N:46]3[C:39](=[CH:40][C:41]4[CH2:42][C:43]([CH3:50])([CH3:49])[CH2:44][C:45]=43)[C:38]2=[O:51])=[N:24][CH:25]=[CH:26][C:27]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:19])[CH3:18]
Reactant: Cn1cc(Nc2cc(Br)cn(C)c2=O)nn1
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Product: CC(=O)OCc1c(-c2cc(Nc3cn(C)nn3)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Yield: 37.3 %

Procedure:
Following the procedure in Example 283b, and starting with 293c (150 mg, 0.53 mmol, 1.0 eq.) and {3-[(acetoxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (629 mg, 1.59 mmol, 3.0 eq.) afforded 293d as a yellow solid (110 mg, 37%). MS-ESI: [M+H]+ 557.4.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:5][C:6](=[O:20])[CH:7]=[C:8]1[C:18]2=[C:19]3[C:14](=[CH:15][CH:16]=[CH:17]2)[CH:13]=[CH:12][CH:11]=[C:10]3[CH2:9]1)[CH3:4]>CO.Cl[Pd]Cl>[CH2:3]([O:5][C:6](=[O:20])[CH2:7][CH:8]1[C:18]2=[C:19]3[C:14](=[CH:15][CH:16]=[CH:17]2)[CH:13]=[CH:12][CH:11]=[C:10]3[CH2:9]1)[CH3:4]
Reactant: CCOC(=O)C=C1Cc2cccc3cccc1c23
Agent: Cl[Pd]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCOC(=O)CC1Cc2cccc3cccc1c23
Reaction time: 0.25 h

Procedure:
55 mg of PdCl2 in 5 ml of methanol are treated with 25 mg of sodium borohydride. After 15 minutes' stirring, the compound obtained in Step B (1 g, 4.20.10−3 mol), diluted with methanol (25 ml), is added. The mixture is purged with argon and placed under a hydrogen atmosphere. After 2 hours 30 minutes' hydrogenation, the reaction mixture is filtered over Celite, rinsed and then evaporated under reduced pressure.
Reaction SMILES: [C:1]([C:4]1[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])=[C:6]([C:17]([O:19][CH3:20])=[O:18])[C:7]([CH:14]([F:16])[F:15])=[N:8][C:9]=1[C:10]([F:13])([F:12])[F:11])(=[O:3])[CH3:2].[CH:25](OC)=[O:26].C[O-].[Na+].Cl>CCOCC.CO.O.CC(C)=O.N1C=CC=CC=1>[F:15][CH:14]([F:16])[C:7]1[C:6]([C:17]([O:19][CH3:20])=[O:18])=[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:4]([C:1](=[O:3])/[CH:2]=[CH:25]\[OH:26])=[C:9]([C:10]([F:12])([F:13])[F:11])[N:8]=1
Reactant: COC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C(C)=O)c1CC(C)C
Reactant: COC=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CC(C)=O
Product: COC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C(=O)/C=C\O)c1CC(C)C
Reaction time: 8 h
Yield: 52.5 %

Procedure:
This example illustrates the preparation of Compound Numbers 23 and 24, an example of the acylation of a pyridine methyl ketone, followed by further derivation to compounds of the present invention. To methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 4, prepared as in Example A) (10.8 g, 30 mmol) in anhydrous ether (100 mL) were added methyl formate (3 g) and 25% sodium methoxide in methanol (10 g) (Aldrich), and the resulting mixture was stirred overnight. It was then poured into iced water, acidified with conc. HCl, and extracted with methylene chloride. The organic extract was washed with water and brine, dried (MgSO4), and conc. in vacuo. The residue was purified by flash chromatography with 20% ethyl acetate/cyclohexane to yield 6 g methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 23) as a viscous red oil, a yield of 52.6%. nD25 1.4857.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1)[C:6](N(OC)C)=[O:7])#[N:2].[CH3:19][Mg]Br.Cl>O1CCCC1>[C:6]([C:5]1[CH:4]=[C:3]([CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=1)[C:1]#[N:2])(=[O:7])[CH3:19]
Reactant: CON(C)C(=O)c1cc(C#N)cc(C(F)(F)F)c1
Reactant: C[Mg]Br
Agent: Cl
Solvent: C1CCOC1
Product: CC(=O)c1cc(C#N)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 100 %

Procedure:
To a solution of 3-cyano-N-methoxy-N-methyl-5-(trifluoromethyl)benzamide (196 mg, 0.76 mmol) in anhydrous tetrahydrofuran (2 mL) stirred on an ice bath was added methylmagnesium bromide (0.96 M solution in ether, 0.95 mL, 0.91 mmol), and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was added with 1 M hydrochloric acid, and extracted with ethyl acetate, and then the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 3-acetyl-5-(trifluoromethyl)benzonitrile (162 mg, 100%) as a pale yellow oil.
Reaction SMILES: [Na].[NH:2]1[CH:6]=[N:5][CH:4]=[N:3]1.[OH-].[Na+].[C:9]([C:11]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[Cl:29])([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:12]Br)#[N:10].Cl>CS(C)=O.CCOCC.O>[C:9]([C:11]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[Cl:29])([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:12][N:2]1[CH:6]=[N:5][CH:4]=[N:3]1)#[N:10]
Reactant: CCCCCCCCC(C#N)(CBr)c1ccc(Cl)cc1Cl
Reactant: c1nc[nH]n1
Agent: Cl
Agent: [Na+]
Agent: [Na]
Solvent: CS(C)=O
Solvent: CCOCC
Solvent: O
Product: CCCCCCCCC(C#N)(Cn1cncn1)c1ccc(Cl)cc1Cl
Reaction time: 20 h
Yield: 28.2 %

Procedure:
To 7.0 g (0.07697 mole) of the sodium salt of 1H-1,2,4-triazole, generated from 5.3 g; (0.07697 mole) of 1H-1,2,4-triazole and 3.1 g (0.759 mole) of NaOH, in 50 ml of DMSO, is added 30.0 g (0.0767 mole) of 2-cyano-2-(2,4-dichlorophenyl) decyl bromide (prepared by the usual route); and the reaction is stirred at 130° for 20 hours. The mixture is then cooled and mixed with 200 ml of water. The organic material which separates is extracted 2×100 ml of ether, and the extract is washed 2×50 ml of water, dried over anhydrous magnesium sulfate and concentrated to give 24.0 g (82.5%) of the crude product. This material is dissolved in ether, and it is treated with hydrogen chloride gas until it is acidic to litmus. The solid which precipitates is separated by filtration to give 9.0 g (28.2%) of the hydrochloric salt, mp 125°-31°. To 6.7 g (0.0161 mole) of the hydrochloride salt in 200 ml of water is stirred. The organic soluble material is extracted 2×200 ml of ether, and the extract is washed 2×50 ml of water, dried over anhydrous magnesium sulfate, and concentrated to give 4.9 g (80.2%) of the oil product.
Reaction SMILES: CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:8]=[C:9]2[C:20](=[CH:21][CH:22]=1)[C:12]1[N:13]([CH2:16][CH:17](O)[CH3:18])[CH:14]=[CH:15][C:11]=1[CH2:10]2.C(N(CC)CC)C.[N-:30]=[N+:31]=[N-:32].[Na+]>ClCCl.CN(C)C=O.O>[N:30]([CH:17]([CH3:18])[CH2:16][N:13]1[CH:14]=[CH:15][C:11]2[CH2:10][C:9]3[C:20]([C:12]1=2)=[CH:21][CH:22]=[C:7]([Cl:6])[CH:8]=3)=[N+:31]=[N-:32]
Reactant: CC(O)Cn1ccc2c1-c1ccc(Cl)cc1C2
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(Cn1ccc2c1-c1ccc(Cl)cc1C2)N=[N+]=[N-]
Yield: 38.2 %

Procedure:
1.2 ml of methanesulfonyl chloride were added dropwise while stirring to a solution, cooled to 0°, of 1.9 g of (RS)-1-(6-chloro-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 4.3 ml of triethyl-amine in 60 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 150 ml of dichloromethane, washed twice with 70 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases were washed with 70 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 40 ml of anhydrous dimethylformamide, treated with 1.0 g of sodium azide and the reaction mixture was heated to 50° for 17 hours while stirring. After cooling, the solution was poured into 140 ml of water and extracted twice with 140 ml of diethyl ether each time and once with 140 ml of ethyl acetate. The combined organic phases were washed once with 140 ml of water and once with 140 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (toluene). 0.8 g (38%) of (RS)-1-(2-azido-propyl)-6-chloro-1,4-dihydro-indeno[1,2-b]pyrrole was obtained as a yellowish oil.
Reaction SMILES: C[N:2]1[CH2:7][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:5][CH2:4][CH2:3]1.ClC(OC(Cl)C)=O>C1(C)C=CC=CC=1>[NH:2]1[CH2:3][CH2:4][CH:5]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:7]1
Reactant: COC(=O)C1=CCCN(C)C1
Agent: CC(Cl)OC(=O)Cl
Solvent: Cc1ccccc1
Product: COC(=O)C1=CCCNC1
Temperature: 80 °C
Yield: 86.4 %

Procedure:
Arecoline (39.5 g, 0.25 mol) was dissolved in dry toluene (20 ml). 1-Chloroethyl chloroformate (30.5 ml) was added slowly at 0-5° C. The mixture was heated at 80° C. for 2 h, cooled to room temperature, filtered and evaporated to dryness in vacuo. The residue was dissolved in methylene chloride (400 ml) and extracted with 10% aqueous sodium carbonate. The organic layer was dried over magnesium sulfate, filtered and evaporated to dryness to give methyl 1,2,5,6-tetrahydropyridine-3-carboxylate (Yield: 30.5 g, 85%). Methyl 1,2,5,6-tetrahydropyridine-3-carboxylate (1.1 g, 7.8 mmol) was dissolved in methylene chloride (20 ml) and cooled to -15° C. Triethyl amine (2.2 ml, 15,8 mmol) and a solution of benzyl chloroformate (1.2 ml, 8,4 mmol) in methylene chloride (10 ml) were added. Stirring at room temperature for 1.5 h followed by evaporation to dryness. The residue was dissolved in methylene chloride and extracted with water two times. The organic layer separated, dried and evaporated to dryness in vacuo to give methyl 1-benzyloxycarbonyl-1,2,5,6-tetrahydropyridine-3-carboxylate as an oil (Yield: 2.0 g, 92%).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:41][C:42]#[C:43][C:44]([CH2:55][CH3:56])([O:47][Si:48]([CH2:53][CH3:54])([CH2:51][CH3:52])[CH2:49][CH3:50])[CH2:45][CH3:46].[H-].[Na+].C1OCCOCCOCCOCCOC1>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([O:24][CH2:41][C:42]#[C:43][C:44]([CH2:55][CH3:56])([O:47][Si:48]([CH2:53][CH3:54])([CH2:49][CH3:50])[CH2:51][CH3:52])[CH2:45][CH3:46])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCC(C#CCBr)(CC)O[Si](CC)(CC)CC
Reactant: CC(C)(O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(C#CCOC(C)(C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)(CC)O[Si](CC)(CC)CC
Yield: 37.7 %

Procedure:
1α,3β-Bis(tert-butyldimethylsilyloxy)-20-hydroxy-20-methylpregna-5,7,16-triene (100 mg, 0.17 mmol), 1-bromo-4-ethyl-4-triethylsilyloxy-2-hexyne (150 mg, 0.47 mmol), sodium hydride (60% in oil, 41 mg, 1.02 mmol), 15-crown-5 (37 mg, 0.17 mmol) and tetrahydrofuran (3 ml) were subjected to reaction using a procedure similar to that of Example 5(1) (at room temperature for 17 hours), worked up and purified by preparative thin layer chromatography (3 sheets (each 1.0 mm thickness), hexane:toluene=1:1) to give the titled compound (52 mg, 37.7%) as a yellow oil.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([NH2:21])[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](Cl)(=[O:25])[CH3:24].C(N(CC)C(C)C)(C)C>O1CCCC1>[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([NH:21][C:23](=[O:25])[CH3:24])[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)Cl
Reactant: Cc1cc2c(cc(N)c3nnc(C)n32)n1Cc1ccccc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1cc2c(cc(C)n2Cc2ccccc2)n2c(C)nnc12
Reaction time: 3.5 h

Procedure:
To a suspension of 6-benzyl-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-4-amine (32.0 mg, 0.110 mmol, from Step 3) in tetrahydrofuran (1 mL) was added acetyl chloride (15.1 μL, 0.213 mmol, Aldrich) and N,N-diisopropylethylamine (76 μL, 0.44 mmol). After 3.5 hours, the product was purified by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: (19 mg, 52%).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:8])[CH2:4][CH2:5][CH2:6][OH:7].BrC[CH2:11][C:12]([O:14][CH3:15])=[O:13].O>C1COCC1>[CH3:15][O:14][C:12](=[O:13])[CH2:11][O:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:8]
Reactant: OCCCCO
Reactant: COC(=O)CCBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)COCCCCO
Temperature: 25 °C
Reaction time: 1 h
Yield: 16 %

Procedure:
Sodium hydride (4.44 g, 60% dispersion in oil, 111 mmol) was added to a solution of 1,4-butanediol (10.0 g, 111 mmol) in THF (200 mL). After stirring 1 h at rt, the mixture was cooled to 0° C. and methyl bromomethylacetate (10.82 mL, 114 mmol) was added and the reaction was allowed to warm to room temperature. After 16 h, water (100 mL) was added and the mixture was extracted with EtOAc (3×100 mL). The combined organic phase was washed with brine (2×100 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (20%→30% EtOAc/Hexane) to afford 2.88 g (16%) of (4-hydroxy-butoxy)-acetic acid methyl ester as a colorless oil.
Reaction SMILES: C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([C:10]2[S:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=3)[N:14]=2)[CH:7]=[CH:6][C:5]=1Br.[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O)#[N:26]>>[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:5]1[C:4]([C:3]([OH:2])=[O:24])=[CH:9][C:8]([C:10]2[S:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=3)[N:14]=2)=[CH:7][CH:6]=1)#[N:26]
Reactant: N#Cc1ccccc1B(O)O
Reactant: COC(=O)c1cc(-c2nc(-c3ccc(Cl)c(Cl)c3)cs2)ccc1Br
Product: N#Cc1ccccc1-c1ccc(-c2nc(-c3ccc(Cl)c(Cl)c3)cs2)cc1C(=O)O
Yield: 2.2 %

Procedure:
Using the conditions of General Procedure B for Suzuki Coupling and Hydrolysis in Parallel Mode, 2-bromo-5-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-benzoic acid methyl ester (which may be prepared as described for Intermediate 6; 89 mg, 0.2 mmol) was reacted with 2-cyanophenylboronic acid (available from Aldrich Chemical Company, Inc.; 59 mg, 0.4 mmol). The resulting ester was hydrolyzed and the acid was purified to give 2′-cyano-4-[4-(3,4-dichloro-phenyl)-thiazol-2-yl]-biphenyl-2-carboxylic acid (2 mg, 1%). The compound of Example 111 has the same formula as the compound of Example 112. LCMS analysis indicated that the material was ˜94% pure, as measured by UV at 214 nm. LRMS m/z 450.8 (M+H+).
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH2:11])=[CH:8][C:7]([CH3:12])=[N:6][C:5]=2[S:4][C:3]=1[CH3:13].O.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]([N:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)[CH:26]=[CH:27][CH:28]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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.C(OCC)(=O)C>[NH2:11][C:9]1[CH:8]=[C:7]([CH3:12])[N:6]=[C:5]2[S:4][C:3]([CH3:13])=[C:2]([C:23]3[CH:24]=[C:25]([N:29]4[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]4)[CH:26]=[CH:27][CH:28]=3)[C:10]=12
Reactant: Cc1cc(N)c2c(Br)c(C)sc2n1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1cc(N)c2c(-c3cccc(N4CCN(C(=O)OC(C)(C)C)CC4)c3)c(C)sc2n1
Temperature: 120 °C
Yield: 88.8 %

Procedure:
Under nitrogen, 3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-amine (130 mg, 0.506 mmol) (Description 8) was dissolved in 1,4-dioxane (3 mL) and water (1 mL) and 1,1-dimethylethyl 4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-piperazinecarboxylate (294 mg, 0.758 mmol), tetrakis(triphenylphosphine)palladium(0) (58.4 mg, 0.051 mmol) and potassium carbonate (210 mg, 1.517 mmol) were added. The mixture was then heated in a microwave at 120° C. for 30 min. Ethyl acetate (10 mL) was added and the mixture washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo. Purification by chromatography on silica gel, eluting with a gradient of 0-70% ethyl acetate in cyclohexane, afforded the title compound (197 mg). LCMS (A) m/z: 439 [M+1]+, Rt 0.99 min (acidic).
Reaction SMILES: [S:1]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C@H:2]1[O:10][C@@H:9]([CH3:11])[C@@H:7]([OH:8])[C@@H:5]([OH:6])[C@@H:3]1[OH:4].[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:18]([O:4][C@H:3]1[C@H:5]([O:6][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C@H:7]([O:8][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C@H:9]([CH3:11])[O:10][C@@H:2]1[S:1][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]
Reactant: C[C@@H]1O[C@H](Sc2ccccc2)[C@@H](O)[C@H](O)[C@@H]1O
Reactant: CC(C)(C)C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: C[C@@H]1O[C@H](Sc2ccccc2)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Temperature: 100 °C

Procedure:
To a solution of crude phenyl 6-deoxy-1-thio-β-L-galactopyranoside 3 in 15 mL of pyridine is added pivaloyl chloride (4.0 mL, 3.90 g, 32.5 mmol) and DMAP (0.33 g, 2.71 mmol). The reaction mixture is heated at 100° C. for 12 h, cooled, diluted with 50 mL of CH2Cl2, washed with H2O (100 mL) and saturated NaCl (100 mL), dried over Na2SO4, filtered and concentrated to afford 3.25 g of phenyl 6-deoxy-2,3,4-tri-O-pivaloyl-1-thio-β-L-galactopyranoside 4 as a brown oil. This oil is purified by flash chromatography (15% EtOAc/petroleum ether) to afford 0.53 g (48%) of the pure compound. An additional 0.81 g of a brown oil, which that appeared to be a mixture of incompletely acylated products, is also isolated. This material is resubjected to the reaction conditions for 48 h and provided an additional 0.21 g (19%, total yield 67% for 2 steps): Rf 0.48 (15% EtOAc/petroleum ether); 1H NMR (CDCl3, 270 MHz) δ 7.50-7.59 (m, 2H), 7.23-7.35 (m, 3H), 5.16-5.30 (m, 2H), 5.08 (dd, J=9.9, 3.0 Hz, 1H, H-3), 4.66 (d, J=9.6 Hz, 1H, H-1), 3.90 (q, J=6.3 Hz, 1H, H-5), 1.21 (s, 9H), 1.18 (s, 9H), 1.21 (s, 9H), 1.21 (d, J=6.6 Hz, 3H, H-6); 13C NMR (CDCl3, 68 MHz) δ 177.2, 177.4, 177.1, 133.5, 131.1, 128.6, 128.4, 128.1, 127.7, 85.1, 73.3, 72.6, 69.9, 66.3, 38.9, 38.6, 26.9, 27.0, 16.4; FABMS C27H39O7S (MNa+) calcd 531.2392, found 531.2404.