Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].Cl.N1C=CC=C[CH:20]=1.[NH2:25][C:26]1[C:31](C)=[CH:30][C:29]([OH:33])=[C:28]([CH3:34])[CH:27]=1>C(OCCO)C>[OH:33][C:29]1[C:28]([CH3:34])=[CH:27][C:26]([NH:25][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:16]#[N:17])=[CH:31][C:30]=1[CH3:20]
Reactant: c1ccncc1
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1OC
Reactant: Cc1cc(O)c(C)cc1N
Agent: Cl
Solvent: CCOCCO
Product: COc1cc2ncc(C#N)c(Nc3cc(C)c(O)c(C)c3)c2cc1OC
Yield: 66.7 %

Procedure:
Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 10 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 164.6 mg (1.2 mmol) of 4-amino-2,5-dimethylphenol to give 232.9 mg (66.7%) of the product as a light brown solid, m.p. 234-236° C., mass (electrospray, m/e): M+H 349.9.
Reaction SMILES: [CH3:1][C:2]1=[C:3]([CH3:9])[C:4]([O:6][C:7]1=[O:8])=O.[NH2:10][CH:11]1[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]1>C(Cl)Cl>[OH:17][CH:14]1[CH2:15][CH2:16][CH:11]([N:10]2[C:4](=[O:6])[C:3]([CH3:9])=[C:2]([CH3:1])[C:7]2=[O:8])[CH2:12][CH2:13]1
Reactant: CC1=C(C)C(=O)OC1=O
Reactant: NC1CCC(O)CC1
Solvent: ClCCl
Product: CC1=C(C)C(=O)N(C2CCC(O)CC2)C1=O
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 69.4 %

Procedure:
126 g (1 mol) of dimethylmaleic anhydride and 115 g (1 mol) of 4-aminocyclohexanol are warmed, in an oil bath whilst stirring, to 120° to 125° C. (internal temperature) for 30 minutes. After cooling to 20° C., the reaction product is dissolved in 500 ml of methylene chloride and extracted once with 100 ml of 1 N NaOH, whilst cooling with ice. The reaction product is then washed twice with water and dried over sodium sulphate. The solvent is evaporated and the residue is recrystallised from a 1:1 mixture by volume of ethyl acetate and petroleum ether. 155 g (70% of theory) of N-(4-hydroxycyclohexyl)-dimethylmaleimide are obtained; melting point 109° to 111° C.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:20]1[CH:25]=[N:24][CH:23]=[CH:22][N:21]=1)CCC.CN(C=O)C>C(OCC)(=O)C.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>[N:21]1[CH:22]=[CH:23][N:24]=[CH:25][C:20]=1[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cn1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cnccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)c1ccc(-c2cnccn2)cn1
Temperature: 120 °C
Reaction time: 10 h

Procedure:
To a flask containing tert-butyl 5-bromopicolinate 41-1 (1.55 g, 6.0 mmol), 2-(tributylstannyl)pyrazine 41-2 (2.21 g, 6.0 mmol) and Pd(PPh3)4 (426 mg, 0.6 mmol) under argon was added DMF (15 mL). The mixture was stirred at 120° C. for 10 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, eluted with 5% methanol in dichloromethane to give tert-butyl 5-(pyrazin-2-yl)picolinate 41-3 as a pale yellow solid. MS m/z 258.1 (M+1)
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]([CH3:13])[CH3:12])=[CH:7][C:3]=1[C:4](O)=[O:5].C1N=C[N:16](C(N2C=NC=C2)=O)C=1.C(=O)([O-])[O-].[NH4+].[NH4+].O>CN(C=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([N:11]([CH3:13])[CH3:12])=[CH:7][C:3]=1[C:4]([NH2:16])=[O:5]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CN(C)c1ccc(Br)c(C(=O)O)c1
Agent: O=C([O-])[O-]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)c1ccc(Br)c(C(N)=O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 27.3 %

Procedure:
To a solution of give 2-bromo-5-(dimethylamino)benzoic acid (7.89 g, 32.3 mmol) in DMF (25 mL) was added N,N-carbonyldiimidazole (13.1 g, 80.8 mmol). The reaction mixture was allowed to stir at rt for 30 min and then ammonium carbonate (14.0 g, 145 mmol) was added. The reaction mixture was allowed to stir at rt overnight and then poured into water. The mixture was extracted with EtOAc. The organic solutions were combined, washed with water and brine, dried over Na2SO4, filtered and concentrated to give 2-bromo-5-(dimethylamino)benzamide (2.14 g, 27%). The product could be further purified by recrystallization from MeOH.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[N:3]=[C:4]([CH3:6])[CH3:5].C([N-]C(C)C)(C)C.[Li+].[F:16][C:17]([F:37])([F:36])[C:18]1[CH:35]=[CH:34][C:21]([O:22][C:23]2[CH:33]=[CH:32][C:26]([O:27][CH:28]([CH3:31])[CH:29]=[O:30])=[CH:25][CH:24]=2)=[CH:20][CH:19]=1.O.C(Cl)Cl>O1CCCC1>[CH3:1][N:2]([CH3:7])[N:3]=[C:4]([CH2:6][CH:29]([OH:30])[CH:28]([O:27][C:26]1[CH:25]=[CH:24][C:23]([O:22][C:21]2[CH:34]=[CH:35][C:18]([C:17]([F:37])([F:16])[F:36])=[CH:19][CH:20]=2)=[CH:33][CH:32]=1)[CH3:31])[CH3:5]
Reactant: CC(C=O)Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1
Reactant: CC(C)=NN(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: O
Product: CC(CC(O)C(C)Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1)=NN(C)C
Reaction time: 1 h

Procedure:
To a solution of acetone N,N-dimethylhydrazone (6.5 mmol) in tetrahydrofuran (THF; 15 ml) under nitrogen is added lithium diisopropylamide (LDA; 7.2 mmol) in THF (15 ml) at 0° for 5 hours. The resulting solution is cooled to -78°, and to it is added 2-[4-(4-trifluoromethylphenoxy)phenoxy]propanal (7.2 mmol). After 1 hour at -78°, the reaction mixture is allowed to warm to 0° and is poured into water/methylene chloride (3:1). The organic phase is separated (3X), and the combined organic extracts are dried over sodium sulfate and concentrated to give 4-hydroxy-5-[4-(4-trifluoromethylphenoxy)-phenoxy]-2-hexanone N,N-dimethylhydrazone (cpd. 1, Table A).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([Cl:16])[N:13]=[C:12]([F:17])[C:11]=2[OH:18])=[O:9])[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:18][C:11]1[C:12]([F:17])=[N:13][C:14]([Cl:16])=[CH:15][C:10]=1[C:8]2=[O:9]
Reactant: O=C(c1cc(Br)ccc1F)c1cc(Cl)nc(F)c1O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: O=c1c2cc(Br)ccc2oc2c(F)nc(Cl)cc12
Temperature: 100 °C
Yield: 87.3 %

Procedure:
A solution of (5-bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-hydroxypyridin-4-yl)methanone (730 g, 2.10 mol) in dioxane (6 L) was treated with Cs2CO3 (1024 g, 3.14 mol). The reaction mixture was heated to 100° C. for 5 hours and then cooled to RT. Water (9 L) was added and the mixture was stirred vigorously. The resulting solids were filtered, washed with water (1 L×2), hexanes (1 L×1), and EtOAc (700 mL) to provide 602 g of 7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one as a light yellow solid.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH2:5])=[O:4].[C:6]1([P:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[N+](C)([O-])=O>O>[Cl-:1].[C:3]([CH2:2][P+:12]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)(=[O:4])[NH2:5]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: NC(=O)CCl
Solvent: C[N+](=O)[O-]
Solvent: O
Product: NC(=O)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Cl-]

Procedure:
Benzhydryl 3-[prop-1′E-ene-3′-amide)]-7Z-[(2″-pyridyl)methylidene]-2-cephem-4-carboxylate (11d). Using a procedure similar to that described by S. Trippet, and D. M. Walker, J. Chem. Soc. 3874, 1959, the requisite ylide (carbamoylmethylenetriphenyl-phosphorane) was obtained as follows: A solution of carbamoylmethyltriphenyl-phosphonium chloride (5 g, 14.0 mmol), (itself obtained from chloroacetamide and triphenylphosphine in refluxing nitromethane) in H2O (75 mL) was cooled to 0° C. and a cold (0-5° C.) solution of NaOH (0.56 g in 5 mL H2O) was added in one portion. The resultant mixture was immediately filtered and washed with cold water (75 mL). The collected precipitate was dried under high vacuum to provide carbamoylmethylenetriphenylphosphorane. This ylide was reacted with aldehyde 10 according to the general procedure above to give the title compound; yield: 78%; 1H NMR (CDCl3): δ 5.41 (s, 1H), 5.70 (d, J=15.5 Hz, 1H), 5.95 (s, 1H), 6.84 (s, 1H), 6.87 (s, 1H), 6.96 (s, 1H), 7.23-7.36 (m, 13H), 7.69-7.72 (m, 2H), 8.60 (d, J=4.12 Hz, 1H).
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH3:6].[C:9](Cl)(=O)C(Cl)=O.CN(C)C=O.CO>O1CCCC1>[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH3:6]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCC/C=C/C(=O)O
Solvent: CO
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCC/C=C/C(=O)OC
Reaction time: 0.5 h
Yield: 100 %

Procedure:
To a solution (100 mL) of (2E)-hex-2-enoic acid (5.0 g) in tetrahydrofuran were added dropwise under ice-cooling oxalyl chloride (3.76 mL) and N,N-dimethylformamide (1 mL). The mixture was stirred at the same temperature for 30 min, methanol (10 mL) was gradually added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure, and the residue was treated with 6% aqueous sodium hydrogencarbonate solution, and extracted with diethyl ether. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure (50 Torr, water bath 10° C.) to give the title compound as a colorless oil (yield 5.67 g, about 100%).
Reaction SMILES: [C:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH2:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ccccc1)N1CCc2[nH]c3cccc(Oc4ccccc4)c3c2CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: c1ccc(CN2CCc3[nH]c4cccc(Oc5ccccc5)c4c3CC2)cc1

Procedure:
A solution of 3-benzoyl-10-phenoxy-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.55 g, 1.45 mmol) in tetrahydrofuran (30.0 mL) and lithium aluminum hydride (0.56 g, 14.5 mmol) was reacted in a manner similar to Preparation 11 to afford 0.47 g (87%) of colorless solid as the desired product: mp 168-170° C.(CH2Cl2/hexane); 1H NMR (400 MHz, DMSO-d6) δ 11.0; 7.34-7.21, 7.10, 7.01, 6.94, 6.84, 6.47, 3.69, 2.89-2.87, 2.84-2.81, 2.78-2.75, 2.65-2.62; 13C NMR (100.6 MHz, DMSO-d6) δ 158.5, 147.8, 139.2, 137.4, 136.9, 129.6, 128.4, 128.1, 126.7, 121.8, 120.5, 120.3, 116.4, 110.2, 109.3, 107.4, 60.2, 55.4, 53.3, 27.6, 24.8; MS (EI) m/z 368 (M+); HRMS cacld for C25H24N2O+H: 369.1967, found: 369.1961; Anal. Calcd. for C25H24N2O: C, 81.49; H, 6.57; N. 7.60. Found: C, 81.12; H, 6.70; N, 7.53.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:37])[CH2:16][NH:17][CH2:18][CH2:19][O:20][C:21]2(C(OC)=O)[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:23][CH2:22]2)=[CH:11][C:10]=1[NH:38][S:39]([CH3:42])(=[O:41])=[O:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:43].[Na+].[CH2:45]([OH:47])C.Cl>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:37])[CH2:16][NH:17][CH2:18][CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:45]([OH:47])=[O:43])=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)=[CH:11][C:10]=1[NH:38][S:39]([CH3:42])(=[O:41])=[O:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)C1(OCCNC[C@H](O)c2ccc(OCc3ccccc3)c(NS(C)(=O)=O)c2)C=CC(c2ccccc2)=CC1
Reactant: [OH-]
Reactant: CCO
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CS(=O)(=O)Nc1cc([C@@H](O)CNCCOc2ccc(-c3ccc(C(=O)O)cc3)cc2)ccc1OCc1ccccc1
Temperature: 0 °C

Procedure:
A mixture of methyl 4-{2-[(R)-2-(4-benzyloxy-3-methanesulfonylaminophenyl)-2-hydroxyethylamino]ethoxy}biphenyl-4-carboxylate (0.064 g), a 2 mol/L aqueous solution of sodium hydroxide (0.162 mL), ethanol (2 mL) and tetrahydrofuran (2 mL) was heated under reflux overnight. To the ice-cooled reaction mixture was added 2 mol/L hydrochloric acid (0.162 mL), and the solvent was evaporated under reduced pressure. The residue was washed with water to afford 4′-{2-[(R)-2-(4-benzyloxy-3-methanesulfonylaminophenyl)-2-hydroxyethylamino]ethoxy}biphenyl-4-carboxylic acid (0.06 g) as a crude product.
Reaction SMILES: [C:1]1([CH2:11][N:12]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:17]=2)[CH2:13][CH2:14][OH:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C(Cl)Cl>[C:1]1([CH2:11][N:12]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:17]=2)[CH2:13][CH2:14][O:15][S:35]([CH3:34])(=[O:37])=[O:36])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: OCCN(Cc1cccc2ccccc12)c1cc(-c2ccccc2)no1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCN(Cc1cccc2ccccc12)c1cc(-c2ccccc2)no1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
2-[Naphthalen-1-ylmethyl-(3-phenylisoxazol-5-yl)amino]ethanol (820 mg, 2.38 mmol) was dissolved in methylene chloride (15 ml), treated with triethylamine (592 μl, 4.25 mmol) followed by methanesulfonyl-chloride (265 μl, 3.42 mnmol) and the solution stirred at rt for 1.5 hr. The reaction was washed with 50% sodium bicarbonate (aq, 2×), water (1×), and brine (1×), dried over sodium sulfate, filtered and stripped to dryness in vacuo to give the product as a sticky, foam (1.07 gm, quantitative).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.[CH2:20]([O:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1)[CH3:21].[Al+3].[Cl-].[Cl-].[Cl-].O>C(Cl)Cl.CCOC(C)=O>[CH2:20]([O:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([C:10]2[C:11]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=3[S:13][C:9]=2[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[O:28])=[CH:25][CH:24]=1)[CH3:21]
Reactant: CCOc1ccc(C(=O)Cl)cc1
Reactant: COc1ccc(-c2cc3ccc(OC)cc3s2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCOc1ccc(C(=O)c2c(-c3ccc(OC)cc3)sc3cc(OC)ccc23)cc1
Reaction time: 0.75 h
Yield: 83.8 %

Procedure:
To a well stirred solution of 2-(4'-methoxyphenyl)-6-methoxybenzo[b]thiophene (0.300 g, 1.11 mmol) and 4-ethoxybenzoyl chloride (0.555 g, 3.01 mmol) in CH2Cl2 (45 ml) was added AlCl3 (0.502 g, 3.76 mmol) portion-wise over a 15 minute period. After 45 minutes, water was added, and the product was isolated initially by extraction with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed with brine and then combined and dried over MgSO4. Purification by flash chromatography (silica gel, 70:30 EtOAc/hexanes) afforded the title compound (0.389 g, 0.93 mmol, 84%) as a white solid. Recrystallization (EtOAc/hexanes) afforded a highly pure, crystalline sample with mp 124°-125° C. 1H-NMR (CDCl3, 360 MHz): δ=7.77 (d,J=8.9 Hz, 2H, ArH), 7.52 (d,J=8.9 Hz, 1H, 8.8 Hz, 2H, ArH), 7.31 (d,J =2.4 Hz, 1H, ArH), 6.95 (dd,J=8.9,2.4 Hz, 1H, ArH), 6.76 (d,J=8.8 Hz, 2H, ArH), 6.75 (d,J=8.9 Hz, 2H, ArH), 4.01 (q,J=7.0 Hz, 2H, CH2), 3.88 (s,3H, --OCH3), 3.74 (s,3H, --OCH3), 1.39 (t,J=7.0, 3H, CH3); 13C-NMR (CDCl3, 90 Mhz): δ=193.1, 163.1, 159.7, 157.6, 142.3, 140.0, 134.0, 132.3, 130.6, 130.2, 126, 124.0, 114.7, 114.0, 114.0, 104.3, 63.7, 55.6, 55.2, 14.6. HRMS (EI) M+ calcd for C25H22O4S 418.1239, found 418.1241. Anal. Calcd for C25H22O4S: C, 71.75; H, 5.30; S, 7.66. Found: C, 71.68; H, 5.30; S, 7.61.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:14]=1OS(C(F)(F)F)(=O)=O)[C:8]([O:10][CH3:11])=[O:9])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([O:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)[CH3:24].C(=O)([O-])[O-].[K+].[K+]>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>[CH3:2][C:1]([C:5]1[CH:6]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[CH:12]=[CH:13][C:14]=1[C:30]1[CH:29]=[CH:28][CH:27]=[C:26]([O:25][CH2:23][CH3:24])[CH:31]=1)([CH3:4])[CH3:3]
Reactant: COC(=O)c1ccc(OS(=O)(=O)C(F)(F)F)c(C(C)(C)C)c1
Reactant: CCOc1cccc(B(O)O)c1
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+]
Product: CCOc1cccc(-c2ccc(C(=O)OC)cc2C(C)(C)C)c1
Temperature: 80 °C
Reaction time: 20 h
Yield: 84 %

Procedure:
A dry round bottom flask containing 8.7 (1.13 g, 3.31 mmol), 3-ethoxyphenylboronic acid (available from Aldrich) (1.10 g, 6.63 mmol), tetrakis(triphenylphosphine)palladium (0.39 g, 0.340 mmol), and potassium carbonate (1.41 g, 10.20 mmol) was evacuated and backfilled three times with argon. Dry DMF (10.000 mL) was then added via syringe under argon. The mixture was then heated at 80° C. and monitored with TLC. After 20 hours, the reaction was cooled to room temperature and diluted with water. The mixture was extracted three times with EtOAc and then concentrated under reduced pressure. The residue was then purified by flash chromatography (SiO2 gel 60, eluted with 0%-25% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to provide 41.1 as a colorless oil (0.87, 84%). MS ESI (pos.) m/e: 313.1 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH:12]=[C:11]([Si](C)(C)C)[N:10]=[N:9]2)[N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[N:9]2)[N:3]=1
Reactant: C[Si](C)(C)c1cn(-c2cccc(Cl)n2)nn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: Clc1cccc(-n2ccnn2)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-chloro-6-[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]pyridine (675 mg, 2.67 mmol) in THF (10 mL) was added TBAF (1.0 M in THF, 8.01 mL, 8.01 mmol). The reaction was stirred at room temperature for 2 h. It was subsequently diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and evaporated. The crude residue was purified by flash chromatography (10-60% EtOAc/hexanes) to afford the title compound as a colorless solid.
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:15])([F:14])[C@@H:5]([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)[OH:6].[F:16][C:17]([F:23])([F:22])[S:18](Cl)(=[O:20])=[O:19]>CCOCC>[F:15][C:4]([F:3])([F:14])[C@H:5]([O:6][S:18]([C:17]([F:23])([F:22])[F:16])(=[O:20])=[O:19])[C:7]1[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=1
Reactant: O=S(=O)(Cl)C(F)(F)F
Reactant: O[C@H](c1ccc(F)cc1)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Product: O=S(=O)(O[C@H](c1ccc(F)cc1)C(F)(F)F)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 94 %

Procedure:
NaH (11.87 g, 296.7 mmol) was added to Et2O (700 mL) at 0° C. under N2 followed by addition of an Et2O solution of 2,2,2-trifluoro-1(R)-(4-fluorophenyl)ethanol (44.3g, 228.2 mmol). The reaction mixture was stirred for 10 min at 0° C. then 1 h at room temperature. Trifluoromethanesulfonyl chloride (50 g, 296.7 mmol) in Et2O was added at 0° C. under N2 and the reaction mixture was stirred 10 min at 0° C. then 3 h at room temperature. The solvent was removed under the reduced pressure and H2O (100 mL) was added slowly. The aqueous layer was extracted by hexane and the combined organic layer was dried over MgSO4. The solvent was removed under the reduced pressure to give trifluoromethanesulfonic acid 2,2,2-trifluoro-1(R)-(4-fluorophenyl)ethyl ester (70 g) as colorless oil.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:11])[CH:9]=2)[N:4]([N:12]([CH2:19][CH2:20][CH3:21])[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:28][N:29]=[C:30]=[O:31]>O1CCCC1>[CH3:28][NH:29][C:30](=[O:31])[O:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([N:12]([CH2:19][CH2:20][CH3:21])[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[CH:3]=[C:2]2[CH3:1]
Reactant: CN=C=O
Reactant: CCCN(c1ccncc1)n1cc(C)c2cc(O)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCCN(c1ccncc1)n1cc(C)c2cc(OC(=O)NC)ccc21
Reaction time: 2.3 h

Procedure:
To a stirred solution consisting of 3-methyl-1-(propyl-4-pyridinylamino)-1H-indol-5-ol (2.06 g) and tetrahydrofuran (49 ml) was added milled K2CO3 (1.06 g) followed by dropwise addition of methyl isocyanate (0.48 ml) at room temperature under nitrogen. Stirring was continued for 2.3 hours at which time the reaction mixture was filtered through a pad of celite and the solids washed with EtOAc. Concentration afforded the crude product. Purification via flash column chromatography (silica gel, 2% Et3N/EtOAc) afforded 2.30 g of the desired carbamate as an oil. The product was crystallized from ether, m.p. 147°-149° C.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:14])[CH3:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[Na+].[I-:16].Cl>CC#N>[I:16][C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:14])[CH3:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: [I-]
Reactant: CC(=O)NC(C)(C)c1ccc(Cl)nc1
Agent: Cl
Agent: [Na+]
Solvent: CC#N
Product: CC(=O)NC(C)(C)c1ccc(I)nc1

Procedure:
To a solution of N-(2-(6-chloropyridin-3-yl)propan-2-yl)acetamide, 33-c, (25 g, 0.12 mol) in MeCN (400 ml) was added NaI (353 g, 2.35 mol) and concentrated HCl (48 ml, 0.59 mol). The reaction mixture was then refluxed for 60 hours. Product conversion was monitored by LC-MS. The reaction mixture was filtered and the cake was washed with MeCN. The filtrate was concentrated under vacuo and the residue was diluted with ethyl acetate, washed with saturated aqueous Na2S203 and brine, dried and concentrated to give the product, 33-d, as a white solid (22 g, 61%).
Reaction SMILES: F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2N=N1.ON1C2C=CC=CC=2N=N1.NC1C=CC=CC=1.[N:45]1([C:51]2[N:52]=[C:53]([CH2:58][C:59]([O-])=[O:60])[NH:54][C:55](=[O:57])[CH:56]=2)[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.[Na+]>CN(C)C=O>[N:45]1([C:51]2[N:52]=[C:53]([CH2:58][C:59]([NH:8][C:12]3[CH:11]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:60])[NH:54][C:55](=[O:57])[CH:56]=2)[CH2:46][CH2:47][O:48][CH2:49][CH2:50]1
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: Nc1ccccc1
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)Nc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 66.9 %

Procedure:
370 mg of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, 113 mg of 1-hydroxybenzotriazole and 0.140 ml of aniline are added to a solution of 200 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate prepared in stage 2 of Example 1 in 3 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 3 hours, and then concentrated under reduced pressure. Water and ethyl acetate are added and the resulting mixture is thus stirred for 30 minutes. The precipitate formed is filtered off and dried in a rotary evaporator. After purification by silica column chromatography, eluent: dichloromethane/methanol 90/10, 161 mg of 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-phenylacetamide are obtained in the form of a white solid, the characteristics of which are the following: