Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.[NH2:14][C:15]1[N:19]=[C:18]([NH2:20])[NH:17][N:16]=1>O1CCCC1>[NH2:20][C:18]1[N:19]=[C:15]([NH:14][C:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)=[O:13])[NH:16][N:17]=1
Reactant: O=C(O)c1ccc2ccccc2c1
Reactant: Nc1n[nH]c(N)n1
Solvent: C1CCOC1
Product: Nc1n[nH]c(NC(=O)c2ccc3ccccc3c2)n1
Yield: 32.3 %

Procedure:
A mixture of 2-naphthyl carboxylic acid (2.0 g, 11.6 mmol) and N,N'-carbonyldimidazole (2.07 g, 12.8 mmol) in dry tetrahydrofuran (50 ml) was stirred at reflux temperature for 1 h. To the cooled reaction mixture was added 3,5-diamino-1,2,4-triazole (1.15 g, 11.6 mmol) and the resulting mixture was refluxed for 3 h. The cooled reaction mixture was quenched with water (75 ml) and extracted with diethyl ether (2×75 ml). The combined organic extracts were washed with saturated aqueous sodium chloride (2×50 ml), dried (MgSO4), filtered and evaporated in vacuo. The residue was crystallised from diethyl ether (20 ml), filtered off and washed with diethyl ether (2×10 ml), dried in vacuo afforded 0.95 g (32%) of the title compound as a solid.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].CN(C)C=O.[S:10]1(=[O:19])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1.[C:20](Cl)(=[O:22])[CH3:21]>>[C:20]([C:16]1[CH:17]=[CH:18][C:13]2[N:12]=[CH:11][S:10](=[O:19])[C:14]=2[CH:15]=1)(=[O:22])[CH3:21]
Reactant: CC(=O)Cl
Reactant: O=S1C=Nc2ccccc21
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: CC(=O)c1ccc2c(c1)S(=O)C=N2

Procedure:
To a solution containing 0.5 mol of anhydrous aluminium chloride in 0.20 mol of dimethylformamide is added 0.05 mol of benzothiazolinone, then, slowly and with agitation, 0.06 mol of acetyl chloride.
Reaction SMILES: Cl.[CH3:2][O:3][NH2:4].[CH2:5]([O:12][C@:13]1([CH3:36])[C@H:17]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@@H:16]([CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:15][C@@H:14]1O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CO>C(N(CC)CC)C>[CH2:28]([O:27][CH2:26][C@@H:16]([OH:15])[C@@H:17]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C@@:13]([O:12][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH:36]=[N:4][O:3][CH3:2])[CH3:14])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: C[C@@]1(OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H](COCc2ccccc2)O[C@@H]1O
Reactant: CON
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: CON=C[C@](C)(OCc1ccccc1)[C@H](OCc1ccccc1)[C@H](O)COCc1ccccc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 93.7 %

Procedure:
0.69 g of O-methylhydroxylamine hydrochloride was added to a mixture of 2.0 g of (2S,3R,4R,5R)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)-3-methyloxolan-2-ol and 10 mL of methanol, and thereafter, 0.56 g of triethylamine was added dropwise to the mixture. The obtained mixture was stirred at room temperature for 6 hours. Thereafter, the solvent was distilled away under reduced pressure, and 20 mL of ethyl acetate and 20 mL of water were then added to the obtained residue. The organic layer was fractionated, and was then washed with water twice. The solvent was distilled away under reduced pressure, so as to obtain 2.0 g of (2R,3R,4S)-1,3,4-tris(benzyloxy)-4-((methoxyimino)methyl)pentan-2-ol in the form of a colorless oily product.
Reaction SMILES: C(N(CC)CC)C.[CH2:8]([O:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[C:9]#[C:10][CH3:11].[NH2:23][CH2:24][C:25]([N:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1)([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27]>ClCCl>[C:43]([O:42][C:40]([N:37]1[CH2:38][CH2:39][N:34]([C:25]([CH2:24][NH:23][S:19]([C:16]2[CH:17]=[CH:18][C:13]([O:12][CH2:8][C:9]#[C:10][CH3:11])=[CH:14][CH:15]=2)(=[O:21])=[O:20])([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27])[CH2:35][CH2:36]1)=[O:41])([CH3:45])([CH3:46])[CH3:44]
Reactant: COC(=O)C(CN)(C(=O)OC)N1CCN(C(=O)OC(C)(C)C)CC1
Reactant: CC#CCOc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC#CCOc1ccc(S(=O)(=O)NCC(C(=O)OC)(C(=O)OC)N2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 54.2 %

Procedure:
1.1 ml (8 mmol) of triethylamine and then 1.8 ml (7 mmol) of 4-but-2-ynyloxybenzenesulfonyl chloride are added to a solution of 2.5 g (7 mmol) of dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonate in 30 ml of dichloromethane. The reaction medium is stirred at ambient temperature for 2 hours and then concentrated under vacuum. The crude product obtained is purified by chromatography on silica gel, elution being carried out with a 70/30 heptane/ethyl acetate mixture. 2.1 g (51%) of dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-[(4-but-2-ynyloxybenzenesulfonylamino)methyl]malonate are obtained in the form of a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:9])=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[CH2:10]([O:12][C:13](=[O:17])[C:14]#[C:15][CH3:16])[CH3:11].N12CCCN=C1CCCCC2>O1CCCC1>[CH2:10]([O:12][C:13](=[O:17])[CH:14]=[C:15]([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[F:9])[CH3:16])[CH3:11]
Reactant: CC#CC(=O)OCC
Reactant: Oc1cccc(Cl)c1F
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: CCOC(=O)C=C(C)Oc1cccc(Cl)c1F
Temperature: 130 °C
Reaction time: 8 h
Yield: 61 %

Procedure:
A mixture of 3-chloro-2-fluoro-phenol (1.31 g, 8.93 mmol) and ethyl-2-butynoate (2.0 g, 17.83 mmol) in tetrahydrofuran (14 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.37 mmol). The reaction was then heated at 130° C. for 2 h. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. overnight. At this time, the reaction was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 1N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over magnesium sulfate, filtered, rinsed with dichloromethane, and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 1-10% ethyl acetate/hexanes) afforded 3-(3-chloro-2-fluoro-phenoxy)-but-2-enoic acid ethyl ester (1.41 g, 61%) as a white solid: HR-ES-MS m/z calculated for C12H12O3FCl [M+H]+ 259.0532, observed 259.0531; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.1 Hz, 3H), 2.45 (s, 3H), 4.03 (q, J=7.1 Hz, 2H), 4.76 (s, 1H), 7.27-7.39 (m, 2H), 7.50-7.61 (m, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[C:12]2[CH2:15][CH2:16][CH2:17][CH2:18][C:11]=2[C:10]1=[O:19].[CH2:20]([NH:22][CH2:23][CH3:24])[CH3:21]>CC(C)=O>[CH2:20]([N:22]([CH2:23][CH3:24])[C:10](=[O:19])[C:11]1[CH2:18][CH2:17][CH2:16][CH2:15][C:12]=1[C:13]([NH:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[F:1])=[O:14])[CH3:21]
Reactant: O=C1C2=C(CCCC2)C(=O)N1c1ccc(Cl)cc1F
Reactant: CCNCC
Solvent: CC(C)=O
Product: CCN(CC)C(=O)C1=C(C(=O)Nc2ccc(Cl)cc2F)CCCC1
Temperature: 25 °C
Yield: 56.6 %

Procedure:
In 50 ml of acetone is dissolved 2.8 g of N-(2-fluoro-4-chlorophenyl)-3,4,5,6-tetrahydrophthalimide. To the solution is added 0.8 g of diethylamine under stirring at room temperature. After further stirring for 30 minutes, the solution is concentrated to dryness under reduced pressure, followed by adding 50 ml of n-hexane to cool. The resultant crystals are recovered by filtration and recrystallized from n-hexane, to yield 2.0 g of the subject compound. Melting point: 105° C.-106° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7](=[O:15])[CH2:8]2.Br[CH2:17][C:18]([O:20]CC)=[O:19]>C1(C)C=CC=CC=1.C1C=CC=CC=1.[Zn]>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7]([OH:15])([CH2:17][C:18]([OH:20])=[O:19])[CH2:8]2
Reactant: COc1ccc(OC)c2c1CCC(=O)C2
Reactant: CCOC(=O)CBr
Agent: [Zn]
Solvent: Cc1ccccc1
Solvent: c1ccccc1
Product: COc1ccc(OC)c2c1CCC(O)(CC(=O)O)C2

Procedure:
A fifth of a solution of 20.6 g of 3,4-dihydro-5,8-dimethoxy-2(1H)-naphthalenone and 18.4 g of ethyl bromoacetate in 100 ml of toluene/benzene (1:1) was added to 7.4 g of activated zinc dust. An exothermic reaction set in after heating to reflux for a few minutes. The remainder of the solution was then added dropwise within 10 minutes. The reaction mixture was then heated to reflux for 11/2 hours, cooled and partitioned between 300 ml of benzene and 300 ml of 3N aqueous sulfuric acid. The organic phase was washed with water and saturated aqueous sodium bicarbonate solution and evaporated. The residue was dissolved in 200 ml of methanol, treated with a solution of 10 g of sodium hydroxide in 100 ml of water and the mixture was heated to reflux for 3 hours. The solution was concentrated to half of the volume, treated with 500 ml of water and the neutral constituents were extracted with 500 ml of chloroform. The aqueous phase was made acid with sulfuric acid and the product was extracted in 900 ml of ether. The extract was dried over magnesium sulfate and evaporated. Recrystallization of the residue yielded 5,8-dimethoxy-1,2,3,4-tetrahydro-2-hydroxy-2-naphthaleneacetic acid, m.p. 112°-114°.
Reaction SMILES: [Li]CCCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](C(C3C(C)=NC(C)=CC=3)O)[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.[CH3:40][N:41]1[C:45]([C:46]([C:48]2[CH:49]=[N:50][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:53]=2)=[O:47])=[CH:44][N:43]=[CH:42]1>C1COCC1>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:46]([C:45]3[N:41]([CH3:40])[CH:42]=[N:43][CH:44]=3)([C:48]3[CH:49]=[N:50][C:51]([C:54]([F:57])([F:55])[F:56])=[CH:52][CH:53]=3)[OH:47])[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:37])[F:38])=[CH:32][CH:31]=1
Reactant: Cn1cncc1C(=O)c1ccc(C(F)(F)F)nc1
Reactant: COc1nc2ccc(C(O)c3ccc(C)nc3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1nc2ccc(C(O)(c3ccc(C(F)(F)F)nc3)c3cncn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.03 h

Procedure:
A solution of n-BuLi (2.5 M in hexanes, 1.85 mL, 4.62 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.00 g, 4.65 mmol, Intermediate 47: step d) in dry THF (30 mL) in a dry ice-acetone bath. After 1.5 minutes, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (1.26 g, 4.92 mmol, Intermediate 36: step c) in dry THF (5 mL) was added dropwise. The reaction mixture was stirred for 2 minutes in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 10 minutes, the mixture was warmed to room temperature and the reaction was quenched with saturated ammonium chloride. The mixture was partitioned between water and DCM. The separated aqueous phase was further extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated to provide the title compound as crude white solid. MS m/e 607.2 [M+H]+ Example 62A was purified by chiral HPLC (ChiralPak AD, 50:50 methanol/ethanol) to provide two enantiomers, Example 62B and Example 62C. The first eluting enantiomer was Example 62B: 1H NMR (500 MHz, CDCl3) δ ppm 8.80 (d, J=1.8 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.85 (dd, J=8.2, 1.9 Hz, 1H), 7.79 (d, J=8.5 Hz, 1H), 7.61 (d, J=8.5 Hz, 1H), 7.52 (dd, J=8.8, 2.1 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.36 (d, J=8.1 Hz, 2H), 7.05 (s, 1H), 6.15 (s, 1H), 4.30 (s, 2H), 4.07 (s, 3H), 3.29 (s, 3H); MS m/e 607.2 [M+H]+ and the second eluting enantiomer was Example 62C: 1H NMR (500 MHz, CDCl3) δ ppm 8.80 (d, J=1.7 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.99 (s, 1H), 7.86 (dd, J=8.2, 1.8 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.3 Hz, 1H), 7.53 (dd, J=8.8, 2.1 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 7.06 (s, 1H), 6.16 (s, 1H), 4.30 (s, 2H), 4.07 (s, 3H), 3.30 (s, 3H); MS m/e 607.2 [M+H]+.
Reaction SMILES: C([O:5][C:6](=[O:35])[C@@H:7]([NH:25][S:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH2:8][NH:9][C:10](=[O:24])[CH2:11][NH:12][C:13](=[O:23])[CH2:14][CH2:15][CH2:16][C:17]1[N:18]=[C:19]([NH2:22])[S:20][CH:21]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:22][C:19]1[S:20][CH:21]=[C:17]([CH2:16][CH2:15][CH2:14][C:13]([NH:12][CH2:11][C:10]([NH:9][CH2:8][C@H:7]([NH:25][S:26]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)(=[O:28])=[O:27])[C:6]([OH:35])=[O:5])=[O:24])=[O:23])[N:18]=1
Reactant: CC(C)(C)OC(=O)[C@H](CNC(=O)CNC(=O)CCCc1csc(N)n1)NS(=O)(=O)c1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1nc(CCCC(=O)NCC(=O)NC[C@H](NS(=O)(=O)c2ccccc2)C(=O)O)cs1

Procedure:
Ester 1-8 (365 mg, 0.69 mmol) was dissolved in CH2Cl2 (3.5 mL), then TFA (3.5 mL) was added. After 5 h the reaction mixture was concentrated, azeotroped with toluene, then purified by sequential flash chromatography (silica, 22:20:1:1 EtOAc/EtOH/H2O/NH4OH, then silica, 4:1:1 CH2Cl2/MeOH/HOAc, then 7:1:1 CH2Cl2/MeOH/HOAc), providing 1-9 as a white solid.
Reaction SMILES: [H-].[Na+].[C:3]1([SH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:10]1(=[O:15])[O:14][CH2:13][CH2:12][CH2:11]1.[OH-].[Na+]>C1COCC1.O>[C:3]1([S:9][CH2:13][CH2:12][CH2:11][C:10]([OH:15])=[O:14])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Sc1ccccc1
Reactant: O=C1CCCO1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CCCSc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.1 %

Procedure:
To a suspension of sodium hydride (60% in mineral oil, 10.4 g, 0.26 mol) in anhydrous THF (400 mL) at ambient temperature is added thiophenol (26 g, 0.23 mol) dropwise via syringe. The resulting white suspension is stirred for 30 minutes under a nitrogen atmosphere then γ-butyrolactone (22.4 g, 0.26 mol) is added. The mixture is warmed to gentle reflux and stirred for 6 hours after which it became a solid mass and is allowed to cool to room temperature and stand overnight. The mixture is dissolved in water (1200 mL) containing 1 N NaOH (100 mL) and is extracted with diethyl ether (2×500 mL). The aqueous layer is acidified with 1N HCl and extracted with diethyl ether (3×500 mL). The organic extracts are washed with brine (300 mL) then dried over MgSO4, filtered and concentrated to afford a white solid which is chromatographed on silica gel (pet-ether/EtOAc, 19:1→9:1) to afford 4-phenylsulfanylbutanoic acid (36.6 g, 79%) as a white solid. TLC analysis [pet-ether/EtOAc, 1:1, Rf (thiophenol)=0.90, Rf (acid)=0.50]. m.p. 73-74° C.; 1H NMR (300 MHz, CDCl3) δ 1.95 (quint, J=7.1 Hz, 2H), 2.52 (t, J=7.2 Hz, 2H), 2.97 (t, J=7.1 Hz, 2H), 7.1-7.3 (m, 5H) ppm. Mass spectrum (EI) m/z 196 (M)+.
Reaction SMILES: Br[C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[NH:21][N:20]=[N:19][N:18]=3)[CH:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1B(O)O>>[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[C:2]1[S:6][C:5]([S:7]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]3[NH:21][N:20]=[N:19][N:18]=3)[CH:12]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)cc1F
Reactant: O=S(=O)(Nc1cccc(-c2nnn[nH]2)c1)c1ccc(Br)s1
Product: O=S(=O)(Nc1cccc(-c2nnn[nH]2)c1)c1ccc(-c2ccc(F)cc2F)s1
Yield: 33 %

Procedure:
The product was prepared according to General Procedure 3, described in Example 22, using 5-bromo-N-[3-(1H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide (Intermediate 17) (19 mg, 0.055 mmol) and 2,4-difluorophenylboronic acid (9 mg, 0.06 mmol). The title compound was obtained in 33% yield (6.9 mg). MS (ESI+) calcd mass for C17H11F2N5O2S2 419.032222, found 419.032372.
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:33])[N:10]([CH2:31][CH3:32])[CH2:11][C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1B1OC(C)(C)C(C)(C)O1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:34][O:35][C:36](=[O:56])[CH2:37][C:38]1[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[C:40](OS(C(F)(F)F)(=O)=O)[CH:39]=1>>[CH3:34][O:35][C:36](=[O:56])[CH2:37][C:38]1[CH:39]=[C:40]([C:13]2[CH:14]=[CH:15][C:16]([C:18]([F:20])([F:19])[F:21])=[CH:17][C:12]=2[CH2:11][N:10]([CH2:31][CH3:32])[C:9]([NH:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:33])[CH:41]=[C:42]([C:44]([F:46])([F:45])[F:47])[CH:43]=1
Reactant: CCN(Cc1cc(C(F)(F)F)ccc1B1OC(C)(C)C(C)(C)O1)C(=O)NCc1ccccc1
Reactant: COC(=O)Cc1cc(OS(=O)(=O)C(F)(F)F)cc(C(F)(F)F)c1
Product: CCN(Cc1cc(C(F)(F)F)ccc1-c1cc(CC(=O)OC)cc(C(F)(F)F)c1)C(=O)NCc1ccccc1

Procedure:
Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: 3-benzyl-1-ethyl-1-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-urea and (3-trifluoromethanesulfonyloxy-5-trifluoromethyl-phenyl)-acetic acid methyl ester.
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=3)=[O:7])=[CH:4][CH:3]=1.[Cl:24][C:25]1[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:26]=1[C:27](Cl)=[O:28].Cl>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Cl:24][C:25]1[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:26]=1[C:27]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=3)=[O:7])=[CH:22][CH:23]=1)=[O:28]
Reactant: O=C(Cl)c1c(Cl)cccc1Cl
Reactant: Nc1ccc(C(=O)N2Cc3ccccc3-c3ccccc32)cc1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: O=C(Nc1ccc(C(=O)N2Cc3ccccc3-c3ccccc32)cc1)c1c(Cl)cccc1Cl
Temperature: 100 °C
Reaction time: 144 h
Yield: 240.8 %

Procedure:
A mixture of 300 mg (0.5 mmol) of 5-(4-aminobenzoyl)-5,6-dihydrophenanthridine and 230 mg of (0.55 mmol) of 2,6-dichlorobenzoyl chloride in 1.2 ml of pyridine is heated (100° C.) for 3 hr and then stirred at room temperature for 6 days. To the mixture is added 10 mg of 4-(dimethylamino)pyridine and the mixture stirred for 22 days. To the mixture is added 6 ml of 2N HCl and the solid filtered and washed with 2N HCl, 1N NaOH, H2O to give 0.57 g of solid. The solid is chromatographed on thick layer silica gel plates with hexane ethyl-acetate (1:1) to give 110 mg of solid. Recrystallization from CH2Cl2 -diisopropyl ether to give 73 mg of white crystals, m.p. 230°-235° C.
Reaction SMILES: [OH-:1].[K+:2].O=C[C@@H:5]([C@H:7]([C@H:9]([C@@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8])[OH:6]>CO.O>[O:1]=[C:5]([O-:6])[C@H:7]([C@H:9]([C@@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8].[K+:2]
Reactant: [OH-]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Agent: [K+]
Solvent: O
Solvent: CO
Product: O=C([O-])[C@@H](O)[C@@H](O)[C@H](O)CO
Yield: 573.9 %

Procedure:
Air was sparged at 100 mL/min through a rapidly stirred solution of potassium hydroxide (41.9 g, 65.5 mmol) and D-galactose (45.0 g, 25.0 mmol) in a mixture of methanol/water (375 mL/180 mL) at 60 psi in a Parr bomb (1 L). The temperature was maintained at 35°-36° C. throughout the reaction. After sparging for 24 hours (h), methanol (50 mL) was added and sparging continued for a total of 45 h. The reaction mixture was cooled and vented. The bomb was opened and the light yellow mixture was filtered to remove a small amount of solids. The bomb and filter were rinsed with water (5 mL) in which most of the solids dissolved. The filtrate was stirred and diluted with methanol (850 mL). Crystallization occurred after approximately 500 mL of methanol had been added. After stirring for 4 h, the crystals were collected by filtration and vacuum dried to provide 29.3 g (57% yield) of potassium D-lyxonate 1 as a white solid: DISC mp 171.25° C.; Analysis calculated for C5H9O6K: C, 29.41; H, 4.44. Found: C, 28.86; H, 4.16. This white solid material was used in Example 2 without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=O)[C:10]([OH:12])=O)=[CH:4][CH:3]=1.[CH2:14]([C:21]1[C:22]([NH2:33])=[N:23][CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH2:14]([C:21]1[NH:26][C:25]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:24][N:23]2[C:10](=[O:12])[C:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=3)=[N:33][C:22]=12)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=C(O)C(=O)Cc1ccc(O)cc1
Reactant: Nc1ncc(-c2ccccc2)nc1Cc1ccccc1
Product: O=c1c(Cc2ccc(O)cc2)nc2c(Cc3ccccc3)[nH]c(-c3ccccc3)cn1-2

Procedure:
Synthesized using method A with 3-(4-hydroxyphenyl)-2-oxopropanoic acid and 3-benzyl-5-phenylpyrazin-2-amine as starting materials. Exact mass calculated for C26H22N3O2+ m/z+ 408.17, found m/z+ 408.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH2:20])[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Br[C:22]1[CH:34]=[CH:33][C:25]([CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[CH:24][CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH:20][C:22]4[CH:23]=[CH:24][C:25]([CH2:26][N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)=[CH:33][CH:34]=4)[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]
Reactant: Brc1ccc(CN2CCOCC2)cc1
Reactant: CS(=O)(=O)c1ccc(-c2cccn3nc(N)nc23)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CS(=O)(=O)c1ccc(-c2cccn3nc(Nc4ccc(CN5CCOCC5)cc4)nc23)cc1

Procedure:
[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-morpholin-4-ylmethyl-phenyl)-amine was prepared from 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (50.0 mg, 0.173 mmol) and 4-(4-bromo-benzyl)-morpholine (55.0 mg, 0.215 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (20.0 mg, 0.0366 mmol) as the ligand in a manner analogous to Step 2d and was isolated as a yellow foam (0.006 g, 7%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.50 (d, J=6.6 Hz, 1H), 8.23 (d, J=8.3 Hz, 2H), 8.09 (d, J=8.3 Hz, 2H), 7.66 (d, J=7.4 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.2 Hz, 2H), 7.03 (t, J=6.7 Hz, 1H), 6.86 (s, 1H), 3.74-3.69 (m, 4H), 3.48 (s, 2H), 3.11 (s, 3H), 2.48-2.43 (m, 4H). MS=464 (MH)+.
Reaction SMILES: [NH2:1][C:2]1[C:11]([Cl:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1.C(N(C(C)C)CC)(C)C.[C:24](Cl)(=[O:27])[CH:25]=[CH2:26].C(=O)(O)[O-].[Na+]>ClCCl>[C:24]([NH:1][C:2]1[C:11]([Cl:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:13][CH3:14])[CH:3]=1)(=[O:27])[CH:25]=[CH2:26]
Reactant: COC(=O)c1cc(Cl)c(N)cc1OC
Reactant: C=CC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: C=CC(=O)Nc1cc(OC)c(C(=O)OC)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66.7 %

Procedure:
To a 1-liter three-necked round-bottom flask equipped with overhead stirrer, temperature control and addition funnel was added methyl 4-amino-5-chloro-2-methoxybenzoate (44.2 g, 200 mmol), dichloromethane (500 mL) and diisopropylethylamine (104.5 mL, 600 mmol). The resulting mixture was stirred at room temperature until the ingredients dissolved and then the mixture was cooled to 0° C. Acryloyl chloride (16.25 mL, 200 mmol) was then added dropwise while maintaining the internal reaction mixture temperature below 10° C. The total time for addition was about 30 min. The reaction mixture was then slowly warmed from 0° C. to room temperature over a period of about 2 hours. Aqueous saturated sodium bicarbonate solution (200 mL) and dichloromethane (200 mL) were then added and this mixture was stirred for 15 min. and then the layers were separated. The dichloromethane layer was washed with 1 M hydrochloric acid (200 mL) and then concentrated under reduced pressure to about one-third its original volume resulting in a thick slurry. The slurry was filtered and the filter cake was washed with dichloromethane (100 mL) and dried to provide the title compound as an off-white solid (36 g, 67% yield, >98% purity by HPLC).