Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][OH:9])=[CH:4][CH:3]=1.[H-].[Na+].CS([C:18]1[N:28]=[C:21]2[N:22]=[C:23]([CH3:27])[CH:24]=[C:25]([CH3:26])[N:20]2[N:19]=1)(=O)=O>O1CCCC1>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][CH2:8][O:9][C:18]2[N:28]=[C:21]3[N:22]=[C:23]([CH3:27])[CH:24]=[C:25]([CH3:26])[N:20]3[N:19]=2)=[CH:4][CH:3]=1
Reactant: OCCOc1ccc(Cl)cc1
Reactant: Cc1cc(C)n2nc(S(C)(=O)=O)nc2n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cc(C)n2nc(OCCOc3ccc(Cl)cc3)nc2n1

Procedure:
A mixture of 2-(4-chlorophenoxy)ethan-1-ol (4.0 g, 23.19 mmol) and tetrahydrofuran (40 mL) was added to a 200 mL RBF under a nitrogen atmosphere with a magnetic stirring bar. Sodium hydride (60% dispersion in mineral oil) (1.26 g, 31.62 mmol) was added portion-wise (4×˜315 mg) over 10 minutes (Effervescence). The reaction was stirred for 10 minutes before 2-methanesulfonyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine (4.76 g, 21.08 mmol) was added portion-wise (5×˜0.95 g) (Effervescence). Progress of the reaction was monitored by analytical HPLC with UV detection at 215 nm. 2-Methanesulfonyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine elutes with retention time of 1.3 min, 2-(4-chlorophenoxy)ethan-1-ol elutes with retention time of 4.5 min, and the title compound elutes with retention time of 5.7 min. A precipitate is visible after 5 minutes of reaction. An additional portion of tetrahydrofuran (10 mL) was added to aid stirring. After 30 minutes the reaction was concentrated and then partitioned between dichloromethane (100 mL) and water (50 mL). The aqueous layer was extracted once more with dichloromethane (100 mL), and the combined organic layer was dried (Na2SO4), filtered, and concentrated. To a mixture of the crude material in 1% methanol in dichloromethane (60 mL), silica gel (10 g) was added, and the mixture swirled for 10 minutes. The silica gel was removed by filtration, rinsed with dichloromethane (100 mL), and the organic solvent was concentrated under reduced pressure. The solid was dissolved in warm ethanol (125 mL) and water (13 mL), and allowed to cool overnight. Crystalline material was isolated by filtration, rinsed with ethanol:water (10:1) (110 mL) and allowed to dry. A light pink color remained. The solid was then dissolved in 2% methanol in dichloromethane (30 mL), and to this mixture, silica gel (5 g) was added and swirled for 20 minutes. The silica gel was removed by filtration through a plug of fresh silica gel (2 g), rinsed with 2% methanol in dichloromethane (50 mL), and the organic solvent was concentrated under reduced pressure. The solid was dissolved in warm ethanol (95 mL) and allowed to cool overnight. An off-white crystalline material was isolated by filtration, rinsed with ethanol (75 mL), and dried to afford the title compound as an off white solid (4.22 g, 62% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.34 (d, 2H), 7.09 (s, 1H), 7.02 (d, 2H), 4.67 (t, 2H), 4.36 (t, 2H), 2.63 (s, 3H), 2.52 (s, 3H). EM (calc.): 318.1; MS (ESI) m/e: 319.2 (M+H)+.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[N:4]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=1.[N:30]1([C:35]2[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=2)[CH2:34][CH2:33][CH2:32][CH2:31]1.[F-].[Cs+].B(O)O>COCCOC>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[CH:7][N:6]=[C:5]3[N:4]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=[C:2]([C:37]4[CH:38]=[CH:39][CH:40]=[C:35]([N:30]5[CH2:31][CH2:32][CH2:33][CH2:34]5)[CH:36]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1
Reactant: C[Si](C)(C)CCOCn1cc(Br)c2c(NS(=O)(=O)c3cccc(Cl)c3)ccnc21
Reactant: OB(O)c1cccc(N2CCCC2)c1
Agent: OBO
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Product: C[Si](C)(C)CCOCn1cc(-c2cccc(N3CCCC3)c2)c2c(NS(=O)(=O)c3cccc(Cl)c3)ccnc21
Temperature: 120 °C
Yield: 48.7 %

Procedure:
A mixture of N-[3-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide (D4) (233 mg, 0.451 mmol), [3-(1-pyrrolidinyl)phenyl]boronic acid (129 mg, 0.676 mmol), cesium fluoride (205 mg, 1.352 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (36.8 mg, 0.045 mmol) in DME (5.706 mL) was heated in a microwave at 120° C. for 30 minutes. Additional 3-(1-pyrrolidinyl)phenyl]boronic acid (129 mg, 0.676 mmol), cesium fluoride (68.3 mg) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (36.8 mg, 0.045 mmol) were added into the reaction mixture and heated in a microwave at 120° C. for 1 hour. The reaction mixture was partitioned between aqueous saturated NaHCO3 solution and ethyl acetate. The aqueous phase was separated and extracted with ethyl acetate (thrice). The organic extracts were combined, dried over phase separator. The residue was purified on silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane). The appropriate fractions were combined and evaporated to dryness to afford the title compound (128.1 mg). LCMS (A): m/z (M+H)+ 583, C29H35ClN4O3SSi requires 582 (acidic).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([CH2:16][NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:19])([C:12]([F:15])([F:14])[F:13])[C:6]=2[CH:28]=1.CCCCCC>CC(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C@@:7]([CH2:16][NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:19])([C:12]([F:14])([F:15])[F:13])[C:6]=2[CH:28]=1
Reactant: O=C(NCC1(C(F)(F)F)OC(=O)Nc2ccc(Cl)cc21)Nc1ccc(F)cc1
Solvent: CC(C)O
Solvent: CCCCCC
Product: O=C(NC[C@@]1(C(F)(F)F)OC(=O)Nc2ccc(Cl)cc21)Nc1ccc(F)cc1

Procedure:
N-{[6-chloro-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-N′-(4-fluorophenyl)urea was subjected to optical resolution by HPLC (Chiralpack AD-H, n-hexane:2-propanol=3:1), and a fraction eluted at a later time was concentrated, whereby the objective compound was obtained.
Reaction SMILES: Br[C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:15]1[O:26][CH:18]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[CH:20]=2)[O:17][CH2:16]1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:17]1[CH2:16][CH2:15][O:26][CH:18]1[C:19]1[CH:20]=[C:21]([NH:25][C:2]2[C:7]3[S:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH:22]=[CH:23][CH:24]=1
Reactant: Nc1cccc(C2OCCO2)c1
Reactant: Brc1cccc2c1sc1ccccc12
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Product: c1cc(Nc2cccc3c2sc2ccccc23)cc(C2OCCO2)c1
Temperature: 25 °C

Procedure:
A clean and dry 1000 ml round bottom flask equipped with a reflux condenser, magnetic stir bar, and thermometer with adapter was prepared and purged with nitrogen. A solution of 4-bromodibenzo[b,d]thiophene (RS-1-170, 10.7 g, 0.0407 mol) in anhydrous toluene (500.0 ml) was then prepared and transferred to the reaction flask via cannula. 3-aminobenzaldehyde ethylene acetal (8.1 g, 0.0488 mol) was added by syringe. The reaction solution was purged with a strong nitrogen flow for 20 minutes. Sodium tert-butoxide (5.86 g, 0.0610 mol) and Pd2dba3 (1.10 g, 0.0012 mol) were then added manually, followed by the addition of tri-tert-butylphosphine (0.65 g, 0.0032 mol) in toluene (−10 ml) via syringe. The vessel was heated to reflux for approximately 2 hours. The reaction was then cooled to room temperature and filtered through a Celite and silica gel pad. Solvent was removed by rotary evaporation. The crude material was dissolved in a 2:1 hexane/ethyl acetate solution purified by flash column chromatography using a gradient elution system of ethyl acetate/hexane. This provided pure product confirmed by NMR.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[CH3:22])[N:12]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])[N:10]=1.[CH2:31]([O:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH:32]1[O:34][CH2:33]1.CN(C)CC1C=CC=CC=1>C1(C)C(C)=CC=CC=1>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:33][CH:32]([OH:34])[CH2:31][O:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=2[CH3:30])[N:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=2[CH3:22])[N:14]=1
Reactant: CCCCOCC1CO1
Reactant: Cc1ccc(-c2nc(-c3ccc(C)cc3C)nc(-c3ccc(O)cc3O)n2)c(C)c1
Agent: CN(C)Cc1ccccc1
Solvent: Cc1ccccc1C
Product: CCCCOCC(O)COc1ccc(-c2nc(-c3ccc(C)cc3C)nc(-c3ccc(C)cc3C)n2)c(O)c1
Yield: 86 %

Procedure:
23.8 g (0.06 mol) of 2-(2,4-dihydroxyphenyl)-4,6-bis-(2,4-dimethylphenyl)-1,3,5-triazine (prepared as described in U.S. Pat. No. 3,244,708 Example 16) are suspended in 300 ml of xylene. 12.1 g (0.09 mol) of 97% butyl glycidyl ether and 0.75 g (0.006 mol) of dimethylbenzylamine are added to this suspension, and the mixture is heated to reflux temperature. After a reaction time of 5 hours the clear, brownish solution is cooled and clarified by filtration through 100 g of silica gel. The yellow solution is evaporated and the residue is recrystallized from hexane/toluene. This gives 27.3 g of pale yellow crystals of 2-[2-hydroxy-4(3-butoxy-2-hydroxypropyloxy)-phenyl]-4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin (=86% yield). Melting point: 80°-83° C. (Compound 1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:4]=1[N:15]=[N:16][C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18].ClC1C=CC=C(C(OO)=[O:31])C=1>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:4]=1[N+:15]([O-:31])=[N:16][C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc(-c2ccccc2)cc1N=NC(=O)OC(C)C
Solvent: ClCCl
Product: COc1ccc(-c2ccccc2)cc1[N+]([O-])=NC(=O)OC(C)C
Yield: 90.6 %

Procedure:
A solution of 1-methylethyl (4-methoxy-[1,1′-biphenyl]-3-yl)diazenecarboxylate (10.25 g) in dichloromethane (160 mL) was cooled in an ice bath and meta-chloroperbenzoic acid (14.8 g) was added in portions with stirring. Additional dichloromethane (90 mL) was added and the solution left to stir at room temperature for 3 days. To the mixture, dichloromethane (200 mL) was added and washed with saturated potassium bicarbonate (300 mL), followed by saturated sodium sulfite (2×200 mL) and finally saturated potassium bicarbonate (200 mL). The organic phase was dried with sodium sulfate and evaporated to give the product as a brown-orange solid (9.78 g). The product was purified using silica gel chromatography (1:5 ethyl acetate:hexane). Evaporation of the desired fractions gave purified product as an orange solid (6.19 g), with melting point 102-106° C. The product was analyzed by NMR (CDCl3) which showed 1.4 d (6H), 3.9 s (3H), 5.2 m (1H), 7.1-7.9 m (8H), where d signifies doublet, s signifies singlet, and m signifies multiplet; and by LC/MS which showed m/z: 315.8 (M+H)+, (M)+ 314.7.
Reaction SMILES: C(OC([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:18]=1)C(=O)OC(C)(C)C)=O)(C)(C)C.[ClH:28]>C(OCC)(=O)C>[ClH:28].[CH:23]1([C:19]2[CH:18]=[C:17]([CH2:16][NH2:8])[CH:22]=[CH:21][CH:20]=2)[CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: CC(C)(C)OC(=O)N(Cc1cccc(C2CCCC2)c1)C(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: NCc1cccc(C2CCCC2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To tert-butyl N-tert-butoxycarbonyl-N-[(3-cyclopentylphenyl)methyl]carbamate (4.70 g), a solution of hydrogen chloride in ethyl acetate (4 M, 50 mL) was added, and the mixture was then stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and ether (200 mL) was added to the residue. The resulting suspension was filtered, and the product collected by filtration was dried under reduced pressure to obtain the title compound (2.64 g).
Reaction SMILES: Br[C:2]1[C:3]([Cl:10])=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH3:11][N:12]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[N:13]1>>[Cl:10][C:3]1[C:2]([C:15]2[CH:14]=[N:13][N:12]([CH3:11])[CH:16]=2)=[CH:7][N:6]=[C:5]([O:8][CH3:9])[CH:4]=1
Reactant: COc1cc(Cl)c(Br)cn1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Product: COc1cc(Cl)c(-c2cnn(C)c2)cn1

Procedure:
Alternative way to prepare Compound 543: first, 5-bromo-4-chloro-2-methoxypyridine was reacted with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole under the standard Suzuki-Coupling condition to form 4-chloro-2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridine; then it was subject to HBr hydrolysis, followed by a second Suzuki-Coupling with (4-ethoxy-2-methylphenyl)boronic acid, then reaction with BnNH2 as described herein. Hydrogen chloride salt: 1H NMR (DMSO-d6, 400 MHz) 1H NMR (DMSO-d6, 400 MHz) δ 8.01 (s, 1H), 7.64 (s, 1H), 7.46 (s, 1H), 7.41-7.35 (m, 5H), 7.28 (m, 1H), 7.18 (d, J=8.8 Hz, 1H), 6.93 (s, 1H), 6.83 (d, J=8.8 Hz, 1H), 5.87 (s, 1H), 4.45 (s, 2H), 4.04 (q, J=6.8 Hz, 2H), 3.89 (s, 3H), 2.00 (s, 3H), 1.32 (t, J=6.8 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[C:7]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:8]([O:15][CH2:16][CH:17]([O:24]C(=O)C)[CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:9]([O:13][CH3:14])[C:10]=2[OH:12])[N:5]=[C:4]([F:35])[N:3]=1.N>CO>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([NH:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:8]([O:15][CH2:16][CH:17]([OH:24])[CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:9]([O:13][CH3:14])[C:10]=2[OH:12])[N:5]=[C:4]([F:35])[N:3]=1
Reactant: COc1c(OCC(CN2CCCC2)OC(C)=O)c(Nc2ccccc2)c2nc(F)nc(Cl)c2c1O
Agent: N
Solvent: CO
Product: COc1c(OCC(O)CN2CCCC2)c(Nc2ccccc2)c2nc(F)nc(Cl)c2c1O
Temperature: 25 °C
Reaction time: 2 h
Yield: 12.8 %

Procedure:
A suspension of 4-chloro-2-fluoro-5-hydroxyphenylamino-7-[2-acetoxy-3-(pyrrolidin-1-yl)propoxy]-6-methoxyquinazoline (170 mg) in methanol saturated with ammonia (6 ml) was stirred at ambient temperature for 2 hours. The volatiles were removed under vacuum. The residue was partitioned between ethyl acetate and water. The pH of the aqueous layer was adjusted to 6.5. The organic layer was separated, washed with water, dried (MgSO4) and evaporated. The residue was triturated under diethyl ether, filtered, washed with ether and dried under vacuum to give 4-chloro-2-fluoro-5-hydroxyphenylamino-7-[2-hydroxy-3-(pyrrolidin-1-yl)propoxy]-6-methoxyquinazoline (20 mg).
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16]#[N:17])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[OH:18][CH2:19][CH2:20][NH:21][C:22](=[O:25])[O:23][CH3:24]>>[CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:17])[O:18][CH2:19][CH2:20][NH:21][C:22]([O:23][CH3:24])=[O:25])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)NCCO
Reactant: N#CN1Cc2ccccc2-c2ccccc2C1
Product: COC(=O)NCCOC(=N)N1Cc2ccccc2-c2ccccc2C1

Procedure:
starting from 5,7-dihydro-6H-dibenz[c,e]azepine-6-carbonitrile and methyl 2-hydroxyethylcarbamate, there is obtained 2-methoxycarbonylamino-ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a resin, mass spectrum m/e: M+ 339 (5), 308 (2), 237 (22), 194 (56), 102 (100);
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].[N:19]1([NH2:24])[CH:23]=[CH:22][CH:21]=[CH:20]1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.O>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][N:6]1[CH:5]=[N:4][C:3]2[C:7]1=[N:8][CH:9]=[N:10][C:2]=2[NH:24][N:19]1[CH:23]=[CH:22][CH:21]=[CH:20]1
Reactant: Fc1ccccc1Cn1cnc2c(Cl)ncnc21
Reactant: Nn1cccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: Fc1ccccc1Cn1cnc2c(Nn3cccc3)ncnc21
Yield: 91.2 %

Procedure:
A solution of 6-chloro-9-(2-fluorobenzyl)-9H-purine (4.2 g, 16 mmole) and 1H-pyrrol-1-amine (3 g, 36 mmole) in 25 ml isopropanol was stirred at reflux for thirty minutes then was cooled, diluted with water, basified with sodium carbonate and extracted with dichloromethane. The organic extract was washed with water and saturated sodium chloride, was dried (anhydrous MgSO4), filtered and evaporated to 6 g of a solid. The solid was purified by flash chromatography (silica, 15% ethyl acetate in dichloromethane) to give 4.5 g of 9-(2-fluorobenzyl)-N-(1-H-pyrrol-1-yl)-9H-purin-6-amine, m.p. 204°-206° C.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)([CH3:3])[CH3:2].C([Li])CCC.[C:15]1(=O)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16]1.Cl>O1CCCC1>[CH2:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([C:1]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=2)([CH3:3])[CH3:2])=[CH:16]1
Reactant: O=C1CCc2ccccc21
Reactant: CC(C)c1ccccn1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C1=CCc2ccccc21)c1ccccn1

Procedure:
A solution of 10.8 g (0.09 mol) of 2-isopropylpyridine in 47 ml of tetrahydrofuran was cooled to −20° C. and 62.5 ml of n-butyllithium (1.6M in hexane, 0.11 mol) were subsequently added while stirring. The mixture was allowed to come to room temperature and was stirred for a further one hour. A solution of 15.84 g (0.12 mol) of 1-indanone in 12 ml of tetrahydrofuran was then added at such a rate that the temperature remained at 25° C. The mixture was stirred for a further 12 hours and hydrolyzed with 200 ml of dilute hydrochloric acid. The organic phase was separated off, the aqueous phase was extracted once with diethyl ether, the aqueous phase was subsequently neutralized with aqueous ammonia solution and was extracted three times with 100 ml each time of chloroform. The organic phases were combined, dried over magnesium sulfate, the magnesium sulfate was filtered off and the solvent was distilled off. This gave 16.6 g (77%) of 2-[1-(1H-inden-3-yl)-1-methylethyl]pyridine.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][C:20]([O:26][CH3:27])=[CH:21][CH:22]=3)[CH:17]=2)(=[O:15])=[O:14])[C:8]1=[O:28])#[N:2].[F:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH2:36]Br>>[C:1]([C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([N:12]([CH2:36][C:35]2[CH:38]=[CH:39][CH:40]=[C:33]([F:32])[CH:34]=2)[S:13]([C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][C:20]([O:26][CH3:27])=[CH:21][CH:22]=3)[CH:17]=2)(=[O:15])=[O:14])[C:8]1=[O:28])#[N:2]
Reactant: COc1ccc2ccc(S(=O)(=O)N[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)cc2c1
Reactant: Fc1cccc(CBr)c1
Product: COc1ccc2ccc(S(=O)(=O)N(Cc3cccc(F)c3)[C@H]3CCN(Cc4cccc(C#N)c4)C3=O)cc2c1

Procedure:
The title compound is prepared as described in EXAMPLE 25, Part A using 7-methoxynaphthalene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]amide, prepared as described in EXAMPLE 43, part A, and 3-fluorobenzyl bromide. The crude product is purified by column chromatography eluting with gradient of 40% EtOAc/hexanes to 50% EtOAc/hexanes to afford the title compound as a white foam.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1.[N:9]([CH2:12][C:13](OCC)=[O:14])=[C:10]=[S:11]>C(#N)C>[NH:6]1[CH:5]=[C:4]([CH2:3][CH2:2][N:1]2[C:13](=[O:14])[CH2:12][NH:9][C:10]2=[S:11])[N:8]=[CH:7]1
Reactant: CCOC(=O)CN=C=S
Reactant: NCCc1c[nH]cn1
Solvent: CC#N
Product: O=C1CNC(=S)N1CCc1c[nH]cn1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 79.5 %

Procedure:
Histamine (111 mg, 1 mmol) and ethyl isothiocyanatoacetate (145 mg, 1 mmol) were dissolved in acetonitrile (6 mL), and the mixture was stirred at room temperature (25° C.) for 10 minutes. After the reaction was completed the solvent was removed by evaporation under reduced pressure, and the residue was subjected to silica gel column chromatography using chloroform/methanol (4/1 (volume ratio)) as an eluent, to give 3-(2-(1H-imidazol-4-yl)ethyl)-2-thioxoimidazolidin-4-one in a yield of 167 mg (yield 79.5%).
Reaction SMILES: [O:1]([CH3:12])[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].[CH:13]1[CH:18]=[CH:17][C:16]([CH2:19]Br)=[CH:15][CH:14]=1.[H-].[Na+]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].C1COCC1>[O:1]([C:12]([CH2:19][C:16]1[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=1)([CH2:19][C:16]1[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=1)[CH2:19][C:16]1[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=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]
Reactant: CO[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O
Reactant: BrCc1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [H-]
Agent: [I-]
Solvent: C1CCOC1
Product: C[C@@H]1O[C@@H](OC(Cc2ccccc2)(Cc2ccccc2)Cc2ccccc2)[C@@H](O)[C@H](O)[C@@H]1O
Reaction time: 24 h

Procedure:
To a solution of methyl α-L-fucopyranoside (1.96 g, 9.61 mmol; Aldrich, Sigma), BnBr (8 mL, 67.3 mmol; benzyl bromide), and TBAI (177 mg, 048 mmol; tetrabutylammonium iodide; Aldrich) in THF (20 mL; tetrahydrofuran) at 0° C. was added NaH (2.35 g, 57.6 mmol). The cooling bath was removed and the reaction mixture was allowed to stir for 24 h. The reaction was diluted with EtOAc (50 mL; ethyl acetate) and poured into a saturated NH4Cl solution (50 mL). The aqueous phase was extracted with EtOAc (2×30 mL) and the combined organic phases were dried (MgSO4) and concentrated under reduced pressure providing the crude oil. Purification by silica gel flash chromatography (hexane:EtOAc, 100% to 9:1 to 1:1) gave the desired product in excellent yield (5.0 g, 92%).
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([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)[CH2:8][CH2:7]1.Cl[CH2:32][C:33](=[O:40])[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36].Cl>O1CCCC1.C(O)(C)C>[CH2:38]([O:37][C:35]([CH2:34][C:33]([CH2:32][O:3][CH2:4][CH2:5][N:6]1[CH2:7][CH2:8][N:9]([C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:10][CH2:11]1)=[O:40])=[O:36])[CH3:39]
Reactant: OCCN1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Reactant: CCOC(=O)CC(=O)CCl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)COCCN1CCN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
0.9 g of Sodium hydride was added to 15 ml of dry tetrahydrofuran stirring at room temperature under nitrogen. A solution of 1-(2-hydroxyethyl)-4-triphenylmethylpiperazine in 5 ml of dry tetrahydrofuran was added dropwise and then stirred a further 1 hour after the addition was complete. Finally, a solution of 1.8 g of ethyl 4-chloroacetoacetate in 5 ml of dry tetrahydrofuran was added over 1 hour and the mixture stirred at room temperature for 18 hours. 5 Drops of isopropanol were added to the mixture which was then poured onto 100 g of ice and carefully neutralised with concentrated hydrochloric acid. After extraction with ethyl acetate, the residual oil was dissolved in acetonitrile, washed three times with petroleum ether (40°-60°) and evaporated to give 2.6 g of 1-[2-(ethoxycarbonylacetylmethoxy)ethyl]-4-triphenylmethylpiperazine as an orange-red oil, used directly.