Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]([NH:17][C:18]2[N:19]=[C:20]([C:24]([O:26]C)=[O:25])[N:21]([CH3:23])[CH:22]=2)=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>CC(N(C)C)=O.O>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]([NH:17][C:18]2[N:19]=[C:20]([C:24]([OH:26])=[O:25])[N:21]([CH3:23])[CH:22]=2)=[O:16])[N:12]([CH3:14])[CH:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1nc(NC(=O)c2cc(NC(=O)OC(C)(C)C)cn2C)cn1C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cn1cc(NC(=O)OC(C)(C)C)cc1C(=O)Nc1cn(C)c(C(=O)O)n1
Reaction time: 8 h
Yield: 74.8 %

Procedure:
Methyl 4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate (2.0 g, 5.30 mmol) in 50 ml of DMA was added 2 g of LiOH in 30 ml of water. The mixture was stirred overnight, concentrated, diluted with water, extracted with EtAc/Hexane (1:1). The aqueous solution was adjusted to pH 4.0 with 20% H3PO4 to form precipitates. The precipitates were filtered, washed with water and dried over P2O5 with vaccum to afford 1.44 g (75%) of the title product. 1H NMR (DMSO) 10.41 (br, 1H), 9.07 (s, 1H), 7.48 (s, 1H), 6.97 (s, 1H), 6.88 (s, 1H), 3.92 (s, 1H), 3.81 (s, 1H), 1.47 (s, 9H); 13C NMR 160.46, 158.42, 152.85, 145.21, 135.81, 129.11, 127.77, 122.39, 121.57, 113.58, 79.81, 36.06, 35.25, 28.17; MS m/z− 362.1 (M−H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8](=[O:11])[CH2:9][CH3:10])[CH:5]=[CH:6][CH:7]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(OC(C)(C)C)(C)(C)C.[Na]>ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:12]1([C:2]2[CH:3]=[C:4]([C:8](=[O:11])[CH2:9][CH3:10])[CH:5]=[CH:6][CH:7]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1
Reactant: C1COCCN1
Reactant: CCC(=O)c1cccc(Br)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)OC(C)(C)C
Solvent: ClCCl
Product: CCC(=O)c1cccc(N2CCOCC2)c1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
A mixture of 3′-bromopropiophenone (11.4 g, 53 mmol), morpholine (60 mL), palladium acetate (300 mg, 2.5 mol %), di-t-butyl-biphenylphosphine (800 mg, 5 mol %), sodium t-butyloxide (6.1 g, 64 mmol) was stirred at 80° C. in a sealed tube for 24 hours. After cooling down, the reaction mixture was diluted with dichloromethane (150 mL) and washed with water (50 mL). The aqueous layer was extracted with dichloromethane (2×75 mL) and the combined organic layer was dried over magnesium sulfate and concentrated under vacuum. The crude product was purified by flash chromatography of Biotage with 25% ethyl acetate/hexanes to provide the title compound as pale yellow clear oil (4.23 g,).
Reaction SMILES: [C:1]1([S:7]([C:10]2[C:11]([S:23][CH3:24])=[N:12][N:13]3[C:18](Cl)=[CH:17][C:16]([CH:20]([CH3:22])[CH3:21])=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH3:25]>CO>[C:1]1([S:7]([C:10]2[C:11]([S:23][CH3:24])=[N:12][N:13]3[C:18]([NH2:25])=[CH:17][C:16]([CH:20]([CH3:22])[CH3:21])=[N:15][C:14]=23)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N
Reactant: CSc1nn2c(Cl)cc(C(C)C)nc2c1S(=O)(=O)c1ccccc1
Solvent: CO
Product: CSc1nn2c(N)cc(C(C)C)nc2c1S(=O)(=O)c1ccccc1

Procedure:
In an analogous manner to that described in Example 4, from 3-benzenesulphonyl-7-chloro-5-isopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidine and NH3 in MeOH there was obtained 3-benzenesulphonyl-5-isopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-ylamine as colorless crystals, m.p. 210-211°.
Reaction SMILES: N[C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([C:8]2[C:9]([C:15]#[N:16])=[C:10]([F:14])[CH:11]=[CH:12][CH:13]=2)[CH:7]=1.N([O-])=O.[Na+].[BrH:22]>O1CCOCC1.O.[Cu]Br>[Br:22][C:2]1[CH:3]=[CH:4][C:5]([F:17])=[C:6]([C:8]2[C:9]([C:15]#[N:16])=[C:10]([F:14])[CH:11]=[CH:12][CH:13]=2)[CH:7]=1
Reactant: Br
Reactant: N#Cc1c(F)cccc1-c1cc(N)ccc1F
Agent: [Cu]Br
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: N#Cc1c(F)cccc1-c1cc(Br)ccc1F
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 68 %

Procedure:
5′-Amino-3,2′-difluorobiphenyl-2-carbonitrile (2.87 g, 12.5 mmol) was dissolved in hot 1,4-dioxane (4 mL), 48% aqueous hydrobromic acid (40 mL) was added and the mixture cooled to 0° C. before dropwise addition of sodium nitrite (0.86 g, 12.5 mmol) in water (1.5 mL) over 20 min. The resulting mixture was stirred at 0° C. for 1.5 h then poured onto a cooled (0° C.) solution of copper(I) bromide (5.38 g, 37.5 mmol) in 48% hydrobromic acid (10 mL). The solution was stirred at 0° C. for 15 min then heated at 50° C. for 20 min. The mixture was cooled to ambient temperature, diluted with water (500 mL) and extracted with ethyl acetate (2×300 ml). The combined organics were washed with 10% aqueous ammonia solution (200 mL), water (200 mL) and brine (200 mL), dried over anhydrous magnesium sulfate, filtered and evaporated to give a black solid. Purification by chromatography on silica gel eluting with isohexane (containing 0.5% methanol) on a gradient of ethyl acetate (2-6%) gave 5′-bromo-3,2′-difluoro-biphenyl-2-carbonitrile (2.48 g, 68%) as a yellow solid: δH (400 MHz, CDCl3) 7.13 (1H, dd, J 9 and 9), 7.27-7.30 (2H, m), 7.53-7.59 (2H, m), 7.64-7.69 (1H, m).
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[NH:6][C:5]=1[Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19].[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C=O)C>[N:24]([CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[NH:6][C:5]=1[Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19])=[N+:25]=[N-:26]
Reactant: CC[Si](CC)(CC)c1[nH]c2ccc(C(F)(F)F)cc2c1CCBr
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC[Si](CC)(CC)c1[nH]c2ccc(C(F)(F)F)cc2c1CCN=[N+]=[N-]
Temperature: 70 °C
Reaction time: 4 h
Yield: 99.2 %

Procedure:
A mixture of 3-(2-bromoethyl)-2-(triethylsilyl)-5-(trifluoromethyl)-1H-indole (0.448 g; 1.10 mmol) and sodium azide (0.215 g; 3.31 mmol) in DMF (10 mL) was stirred at 70° C. for 4 hours and concentrated under reduced pressure. The residue was diluted in ethyl acetate, washed with brine, dried and concentrated under reduced pressure to give 0.402 g (99%) of the title compound as a brown oil.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:35]=[CH:34][C:7]([C:8]([NH:10][C:11](C(OCC)=O)([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][C:20](=[O:28])[CH:19]=2)[C:12]([O:14]CC)=[O:13])=[O:9])=[CH:6][CH:5]=1>>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][CH:11]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][C:20](=[O:28])[CH:19]=2)[C:12]([OH:14])=[O:13])=[O:9])=[CH:34][CH:35]=1
Reactant: CCOC(=O)C(Cc1cc(=O)[nH]c2ccccc12)(NC(=O)c1ccc(Cl)cc1)C(=O)OCC
Agent: [Na+]
Agent: [OH-]
Product: O=C(NC(Cc1cc(=O)[nH]c2ccccc12)C(=O)O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.78 %

Procedure:
100 ml of anhydrous ethyl alcohol and 2.23 g of sodium ethoxide (96%) were added to a 500 ml flask, and the mixture was cooled down to below 5° C. After adding 7.91 g of diethyl 4-chlorobenzamidomalonate, the resulting solution was stirred at below 5° C. for one hour. 5.00 g of 4-bromomethylquinolinon was added to the mixture and the resulting solution was stirred at the room temperature for 16 hours to produce an intermediate, ethyl 2-(4-chlorobenzoylamino)-2-ethoxycarbonyl-3-[2(1H)-quinolinon-4-yl]propionate. After the completion of the reaction, 2.71 g of sodium hydroxide (93%) was added to the above solution, which was then stirred at the room temperature for about 2 hours. Subsequently, the resulting solution was warmed to about 60° C. and stirred for 4 hours to complete the reaction. The concentrated hydrochloric acid were added to the residue for crystallization. The crystal thus obtained was filtered and then subjected to recrystallization with DMF and water to yield 7.15 g (91.78%) of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid.
Reaction SMILES: Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][C:11]3[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=3[CH2:13][N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[N:25]1([CH2:30][CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:19][N:14]([CH2:13][C:12]1[CH:20]=[CH:21][CH:22]=[CH:23][C:11]=1[NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:39][C:36]3[CH:37]=[CH:38][C:33]([O:32][CH2:31][CH2:30][N:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:34][CH:35]=3)[N:24]=2)[CH:9]=[CH:8][CH:7]=1)[S:15]([CH3:18])(=[O:17])=[O:16]
Reactant: CN(Cc1ccccc1Nc1cccn2nc(Cl)nc12)S(C)(=O)=O
Reactant: Nc1ccc(OCCN2CCCC2)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN(Cc1ccccc1Nc1cccn2nc(Nc3ccc(OCCN4CCCC4)cc3)nc12)S(C)(=O)=O

Procedure:
N-Methyl-N-(2-{2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-benzyl)-methanesulfonamide was prepared from N-[2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-benzyl]-N-methyl-methanesulfonamide (75.0 mg, 0.205 mmol) and 4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (47.0 mg, 0.228 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.017 g, 15%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.95 (d, J=6.7 Hz, 1H), 7.51 (d, J=8.9 Hz, 2H), 7.46-7.31 (m, 3H), 7.13 (t, J=7.4 Hz, 1H), 6.99 (s, 1H), 6.94 (d, J=8.9 Hz, 2H), 6.83 (d, J=7.7 Hz, 1H), 6.69 (t, J=7.1 Hz, 1H), 6.62 (s, 1H), 4.36 (s, 2H), 4.11 (t, J=6.0 Hz, 2H), 2.93-2.87 (m, 5H), 2.78 (s, 3H), 2.68-2.58 (m, 4H), 1.85-1.78 (m, 4H). MS=536 (MH)+.
Reaction SMILES: [K+:1].[C:2]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10][C:11](=[CH2:15])[C:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.C(OC(C)C)(=O)C.[H][H]>[Pt]>[K+:1].[C:2]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:3]=[CH:4][C:5]([CH2:8][C@@H:9]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH2:10][C@@H:11]([CH3:15])[C:12]([O-:14])=[O:13])=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: C=C(C[C@@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)[O-]
Agent: [Pt]
Agent: [K+]
Solvent: CC(=O)OC(C)C
Product: C[C@H](C[C@@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)[O-]
Temperature: 25 °C

Procedure:
100 mg (R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid potassium salt (2-a, R1=Boc, R2=H, R3=CO2K) (prepared according to procedure in Example 42) is added to isopropyl acetate (1 ml). 10% Platinum on carbon (10 mg) is then added. Hydrogen gas at ambient pressure is applied to the mixture. The mixture is stirred at ambient temperature and pressure overnight. The mixture is then filtered over Celite and washed with isopropyl acetate (2×1 ml). The mixture is then concentrated in vacuo to give (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid potassium salt (1-a, R1=Boc, R2=H, R3=CO2K) and (2S,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid potassium salt (1-b, R1=Boc, R2=H, R3=CO2K). Spectroscopic data as in Example 42, Method 1.
Reaction SMILES: [CH3:1][S:2]([NH:5][CH2:6][C@@H:7]([NH:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=[CH:22][C:21]=1[N+:30]([O-])=O)[CH2:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:4])=[O:3]>C(#N)C.[Pt]>[NH2:30][C:21]1[CH:22]=[N:23][C:24]2[C:29]([C:20]=1[NH:19][C@H:7]([CH2:6][NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:8][CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[CH:28][CH:27]=[CH:26][CH:25]=2
Reactant: CC(C)(C)OC(=O)NCCC[C@@H](CNS(C)(=O)=O)Nc1c([N+](=O)[O-])cnc2ccccc12
Agent: [Pt]
Solvent: CC#N
Product: CC(C)(C)OC(=O)NCCC[C@@H](CNS(C)(=O)=O)Nc1c(N)cnc2ccccc12
Reaction time: 2 h
Yield: 95.3 %

Procedure:
tert-Butyl (4S)-5-[(methylsulfonyl)amino]-4-[(3-nitroquinolin-4-yl)amino]pentylcarbamate (8.00 g, 17.1 mmol) was dissolved in 150 mL of acetonitrile and the solution was placed in a pressure bottle. Platinum on carbon (5%, 2.0 g) was then added and the reaction mixture was shaken under H2 at 50 PSI (3.4×105 Pa). After 2 hours, the reaction mixture was then filtered through a pad of CELITE filter agent. The pad was rinsed with acetonitrile and the combined filtrates were concentrated under reduced pressure to give tert-butyl (4S)-4-[(3-aminoquinolin-4-yl)amino]-5-[(methylsulfonyl)amino]pentylcarbamate (7.13 g) as an orange foam.
Reaction SMILES: [OH-].[Na+].[OH:3][C:4]1[CH:5]=[CH:6][C:7]2[C:8]([CH:12]=1)=[N:9][O:10][N:11]=2.[Br:13][CH2:14][CH2:15]Br>C(O)C>[Br:13][CH2:14][CH2:15][O:3][C:4]1[CH:5]=[CH:6][C:7]2[C:8]([CH:12]=1)=[N:9][O:10][N:11]=2
Reactant: Oc1ccc2nonc2c1
Reactant: BrCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: BrCCOc1ccc2nonc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 40.7 %

Procedure:
Sodium hydroxide (40 mg, 1 mmol) was added to a solution of 5-hydroxybenzofurazan (136 mg, 1 mmol) in ethanol (2 ml) and the mixture was stirred at room temperature for 30 min. 1,2-dibromoethane (0.26 ml, 0.56 g, 3 mmol) was added and the mixture was heated under reflux for 20 hr., cooled and the solvent was evaporated under reduced pressure. Aqueous sodium bicarbonate (saturated, 10 ml) was added and the mixture was extracted with dichloromethane (3×10 ml). The combined organic fractions were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/10% EtOAc to give the benzofurazan as a pale yellow oil (99 mg, 41%).
Reaction SMILES: C([O:8][CH2:9][C@@H:10]1[C@H:13]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][CH:17]=[N:18][C:19]=3[NH2:23])[CH2:12][CH2:11]1)C1C=CC=CC=1.C1(OC)C=CC=CC=1.[Al+3].[Cl-].[Cl-].[Cl-]>CO>[OH:8][CH2:9][C@@H:10]1[C@H:13]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][CH:17]=[N:18][C:19]=3[NH2:23])[CH2:12][CH2:11]1
Reactant: Nc1ncnc2c1ncn2[C@@H]1CC[C@@H]1COCc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: COc1ccccc1
Solvent: CO
Product: Nc1ncnc2c1ncn2[C@@H]1CC[C@@H]1CO
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a 50 mL flask with 9-[cis-4-(benzyloxymethyl)-cyclobutyl]adenine (63.2 mg, 0.2 mmol) inside, dry anisole 5 mL was added to give a light yellow solution under argon. In another 10 mL flask with AlCl3 inside, dry anisole 2 mL was added under argon to give a totally clear red solution. This solution was added drop by drop to the first flask to give a red solution. After stirring at ambient temperature for 1 hr, TLC showed no starting material. The reaction mixture was cooled to 0° C. and dry MeOH was added drop by drop until the red color disappeared. The solvents were removed by rotovap to give an off-white solid and this was purified by silica gel flash chromatography (CH2Cl2:MeOH=15:1) to yield a white solid (33 mg, 72.4%, Rf=0.15 (CH2Cl2:MeOH=15:1)).
Reaction SMILES: C([Li])CCC.[CH2:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.[CH2:15]([O:17][CH:18]([O:21][CH2:22][CH3:23])[CH2:19]Br)[CH3:16].C(Cl)Cl>C(OCC)C>[CH2:15]([O:17][CH:18]([O:21][CH2:22][CH3:23])[CH2:19][CH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:16]
Reactant: C1=Cc2ccccc2C1
Reactant: CCOC(CBr)OCC
Agent: [Li]CCCC
Solvent: ClCCl
Solvent: CCOCC
Product: CCOC(CC1C=Cc2ccccc21)OCC
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of n-butyllithium (20.0 mL, 1.6 M, 32.2 mmol) in hexanes was added dropwise to a cooled (0° C.) solution of indene (5.35 g, 32.2 mmol) in 50 mL of diethyl ether. The reaction solution turned yellow and was warmed to 25° C. for 30 minutes. This yellow solution was added dropwise to a cooled (0° C.) solution of bromoacetaldehyde diethylacetal (5.00 mL, 32.2 mmol) in 50 mL of diethyl ether. The reaction mixture turned bright red after warming to 25° C. and was stirred for 12 hours, during which time it darkened to brown. The solvent was then removed in vacuo leaving brown oil. Methylene chloride (100 mL) was added to give a cloudy white mixture which was extracted with deionized water (3×100 mL). The brown organic layer was dried over Na2SO4 and then solids were separated by filtration. Solvent was removed from the filtrate in vacuo resulting in brown oil. Yield: 5.48 g, 23.5 mmol (85%). 1H NMR (CDCl3, 600 MHz): δ 7.43 (d, 3JHH=7.2 Hz, 1H, H4), 7.35 (d, 3JHH=7.8 Hz, 1H, H7), 7.25 (t, 3JHH=7.2 Hz, 1H, H5), 7.19 (t, 3JHH=7.2 Hz, 1H, H6), 6.80 (dd, 1H, H2), 6.61 (dd, 1H, H3), 4.68 (m, 1H, CH), 3.69 (dm, 2H, OCH2CH3), 3.56 (m, 1H, H1), 3.52 (dm, 2H, OCH2CH3), 2.22 (m, 1H, CH2), 1.71 (m, 1H, CH2), 1.24 (t, 3JHH=7.2 Hz, 3H, OCH2CH3), 1.19 (t, 3JHH=7.2 Hz, 3H, OCH2CH3). 13C{1H} NMR (CDCl3, 150.8 MHz): 147.51 (s, C7a), 144.13 (s, C3a), 139.13 (s, C3), 130.79 (s, C2), 126.56 (s, C5), 124.73 (s, C6), 123.00 (s, C4), 121.05 (s, C7), 102.10 (s, CH), 61.44 (s, OCH2CH3), 61.23 (s, OCH2CH3), 46.66 (s, C1), 35.51 (s, CH2), 15.38 (s, OCH2CH3). MS (ES) m/z (assignment, relative intensity): 255.2 (C15H20O2Na, [M+Na]+, 100%). Anal. Calcd. for C15H20O2: C, 77.54; H, 8.68. Found: C, 77.34; H, 8.76.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:46])[N:14]([CH2:25][C:26]([NH:28][CH:29]([CH:43]([CH3:45])[CH3:44])[CH:30]([O:35][Si](C(C)(C)C)(C)C)[C:31]([F:34])([F:33])[F:32])=[O:27])[C:15]([CH3:24])=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(NC1C(=O)N(CC(NC(C(C)C)C(O)C(F)(F)F)=O)C(C)=C(C2C=CC=CC=2)C=1)=O)C1C=CC=CC=1.C(Cl)(Cl)Cl.CO>C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:46])[N:14]([CH2:25][C:26]([NH:28][CH:29]([CH:43]([CH3:44])[CH3:45])[C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])=[O:27])[C:15]([CH3:24])=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:17]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1c(-c2ccccc2)cc(NC(=O)OCc2ccccc2)c(=O)n1CC(=O)NC(C(C)C)C(O[Si](C)(C)C(C)(C)C)C(F)(F)F
Agent: Cc1c(-c2ccccc2)cc(NC(=O)OCc2ccccc2)c(=O)n1CC(=O)NC(C(C)C)C(O)C(F)(F)F
Solvent: CO
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: Cc1c(-c2ccccc2)cc(NC(=O)OCc2ccccc2)c(=O)n1CC(=O)NC(C(=O)C(F)(F)F)C(C)C

Procedure:
Using a similar procedure to that described in Example 1.e., 2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-5-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide was converted into 2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-5-phenyl-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide; chromatography solvent: chloroform:methanol (40:1); TLC: Rf =O.14, chloroform:ethyl acetate (20:1); MS: m/z=546(M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[CH:20]=[CH:19][N:18]=[C:17]2[CH2:21][N:22]2[C:26](=O)[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3C2=O)=[C:6]([CH:15]=1)C(C1C=CC=CC=1)=O.NN>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:16]3[CH:20]=[CH:19][N:18]=[C:17]3[CH2:21][N:22]=[C:26]([C:25]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:24]=3)[C:6]=2[CH:15]=1
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1-n1ccnc1CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CCO
Product: Clc1ccc2c(c1)C(c1ccccc1)=NCc1nccn1-2
Reaction time: 2 h

Procedure:
5-Chloro-2-[2-(phthalimidomethyl)imidazol-1-yl]benzophenone (0.883 g., 2.00 mmol) is suspended in 12 ml. of absolute ethanol, treated with hydrazine and heated to 72°-74° C. Within 10 minutes all of the solid dissolves. After 2 hours the reaction is stopped and white solid is removed by filtration. The mother liquor is concentrated in vacuo to an oil which is crystallized from ethyl acetate-hexane-mixtures to give 8-chloro-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepine of melting point 143°-148° C.
Reaction SMILES: CC([Si](C)(C)[O:6][C@H:7]1[CH2:12][C@@H:11]([CH2:13][N:14]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:24])[CH2:10][N:9]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:8]1)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[O:24]=[C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:22](=[O:23])[N:14]1[CH2:13][C@H:11]1[CH2:12][C@@H:7]([OH:6])[CH2:8][N:9]([C:25]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[O:26])[CH2:10]1
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1C[C@@H](CN2C(=O)c3ccccc3C2=O)CN(C(=O)OCc2ccccc2)C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)N1C[C@H](O)C[C@H](CN2C(=O)c3ccccc3C2=O)C1
Temperature: 25 °C
Yield: 54 %

Procedure:
To cis-phenylmethyl (3RS,5SR)-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-piperidinecarboxylate (for a preparation, see Example 134(e)) (0.92 g, 1.8 mmol) in 10 mL of THF at 0° C. was added a 1N solution of tetrabutyl ammonium fluoride in THF (4 mL, 4.0 mmol). The reaction was allowed to stir under nitrogen while warming to room temperature over 2 h. The reaction was partitioned between EtOAc and saturated aqueous NH4Cl. The organic phase was separated and washed with saturated aqueous NaHCO3, and brine, dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by chromatography on silica gel using a 5-100% EtOAc/hexanes gradient to provide the desired compound (380 mg; 54%) as a colorless oil.
Reaction SMILES: [CH2:1]([N:3]([CH2:24][CH3:25])[CH2:4][CH2:5][NH:6][C:7]1[C:20]2[C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:22][CH3:23])[CH:17]=3)[S:12][C:11]=2[CH:10]=[CH:9][CH:8]=1)[CH3:2].[C:26](O)(=[O:28])C.[OH-].[Na+].C(Cl)(Cl)Cl.CO>C=O.C(Cl)(Cl)Cl>[CH2:24]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][NH:6][C:7]1[C:20]2[C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:22][CH3:23])[CH:17]=3)[S:12][C:11]=2[C:10]([CH2:26][OH:28])=[CH:9][CH:8]=1)[CH3:25]
Reactant: CC(=O)O
Reactant: CCN(CC)CCNc1cccc2sc3ccc(OC)cc3c(=O)c12
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CCN(CC)CCNc1ccc(CO)c2sc3ccc(OC)cc3c(=O)c12
Yield: 44.5 %

Procedure:
A solution of 2.70 g (7.5 mmol) of 1-[[2-(Diethylamino)ethyl]amino]-7-methoxy-9H-thioxanthen-9-one in 135 ml of 37% formalin containing 2.7 ml of N acetic acid was heated on the steam bath for 4 hr, cooled and made alkaline with 10N NaOH solution. The suspension was taken up in CHCl3. The extract was evaporated to dryness and covered with CHCl3. The extract was evaporated to dryness and covered with C2H5OH. The "dimer" separated: yield 400 mg. It was recrystallized from 2-methoxy-ethanol. The filtrate was evaporated to dryness to leave an oil, which, after chromatography on silica gel with CHCl3 -CH3OH as the eluant, furnished 1.30 g (44.5%) of the desired product, mp 103°-105° C. after crystallization from ethyl acetate-petroleum ether.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1S(C)=O.[OH:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Cl
Reactant: OCc1ccccn1
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: Nc1nc(OCc2ccccn2)c(Cl)c(-c2ccco2)n1

Procedure:
From 5-chloro-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-yl-amine, 2-(hydroxymethyl)pyridine and DBU in DME. ES-MS m/e (%): 305 (M{37Cl}+H+, 45), 303 (M{35Cl}+H+, 100).