Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO.[C:3](=[O:6])([O-:5])[O-:4].[Na+].[Na+].[OH:9][CH2:10][CH:11]([CH2:13][OH:14])[OH:12]>>[C:3](=[O:4])([OH:6])[OH:5].[OH:9][CH2:10][CH:11]([CH2:13][OH:14])[OH:12]
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: OCC(O)CO
Solvent: CO
Product: O=C(O)O

Procedure:
In one embodiment, the DMC/methanol mixture is reacted with glycerine in the presence of a base catalyst such as sodium carbonate in a reactor connected to a distillation column. The reactor and column do not have to be physically connected, but it is more efficient to do so. The reaction is allowed to proceed to equilibrium. Some of the DMC reacts with the glycerine to form glycerine carbonate. However, some of the DMC and glycerine remain unreacted. The lighter components, including DMC and methanol, are removed by distillation, flash distillation, stripping, or any known suitable method. The bottom product mixture includes the desired glycerine carbonate, unreacted glycerine, and some methanol and DMC. For example, the glycerine carbonate may be present in the bottom product mixture in an amount between 10% and 65% by weight or between 20% and 35% by weight. After stripping, the bottom product mixture includes 10% or less by weight of DMC or methanol; preferably, 5% or less by weight of DMC or methanol; and more preferably, 2% or less by weight of DMC or methanol.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH2:24][C:25](O)=[O:26])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21]([CH3:23])[CH3:22])[CH:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:28]([NH:35][CH2:36][CH2:37][OH:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:28]([N:35]([CH2:36][CH2:37][OH:38])[C:25](=[O:26])[CH2:24][N:14]([S:11]([C:8]1[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:10][CH:9]=1)(=[O:12])=[O:13])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]([CH3:23])[CH3:22])[CH:16]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: OCCNCc1ccccc1
Reactant: CN(C)c1cccc(N(CC(=O)O)S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1
Product: CN(C)c1cccc(N(CC(=O)N(CCO)Cc2ccccc2)S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1

Procedure:
prepared by reaction of [(4-tert-butyl-benzenesulfonyl)-(3-dimethylamino-phenyl)-amino]-acetic acid with 2-benzylamino-ethanol
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[C:21]([C:22]([OH:24])=[O:23])=[C:20]2[C:15]([CH:16]3[CH2:25][CH:17]3[CH2:18][O:19]2)=[CH:14][CH:13]=1)(=[O:10])=[O:9].[CH3:26][N:27]([CH3:34])[CH2:28][CH2:29][CH2:30][CH2:31][NH:32][CH3:33].C(N(CC)CC)C>CN1C(=O)CCC1>[CH3:26][N:27]([CH3:34])[CH2:28][CH2:29][CH2:30][CH2:31][N:32]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[C:21]([C:22]([OH:24])=[O:23])=[C:20]2[C:15]([CH:16]3[CH2:25][CH:17]3[CH2:18][O:19]2)=[CH:14][CH:13]=1)(=[O:10])=[O:9])[CH3:33]
Reactant: CNCCCCN(C)C
Reactant: O=C(O)c1c(NS(=O)(=O)c2ccccc2F)ccc2c1OCC1CC21
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Product: CN(C)CCCCN(C)c1ccccc1S(=O)(=O)Nc1ccc2c(c1C(=O)O)OCC1CC21
Temperature: 150 °C
Yield: 23 %

Procedure:
A mixture of (1aRS,7bSR)-5-(2-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid (Intermediate 67, 0.1 g), N-(4-dimethylaminobutyl)-N-methylamine (Intermediate 78, 1.07 g) and triethylamine (0.42 g) in NMP (6 mL) was stirred and heated in a sealed tube at 150° C. for 3 days. After cooling, the mixture was concentrated under vacuum and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM (10%) followed by repurification by HPLC (C18) to give (1aRS,7bSR)-5-{2-[N-(4-dimethylaminobutyl)-N-methylamino]-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid (0.03 g) as a white solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:24][C:25]#[N:26].[I-].[K+]>CC(C)=O.CN(C)C=O>[C:25]([CH2:24][O:15][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)#[N:26]
Reactant: N#CCCl
Reactant: O=C(O)CCCCc1c[nH]c2ccccc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: N#CCOC(=O)CCCCc1c[nH]c2ccccc12
Reaction time: 6.5 h
Yield: 77 %

Procedure:
5-(1H-Indol-3-yl)pentanoic acid (5 g, 23 mmol) was dissolved in a mixture of acetone (25 ml) and dimethylformamide (25 ml), and caesium carbonate (3.75 g, 11.5 mmol), chloroacetonitrile (2.16 ml, 34.5 mmol) and potassium iodide (20 mg) were added in succession. After 6.5 h at 60° C. and 16 h at RT, the solid residues were filtered off and washed with acetone (2×30 ml) and the filtrate was concentrated. The crude product was purified by chromatography on silica gel (130 g) with EA/cyclohexane (1:3). The product was obtained as a colourless solid with an m.p. of 76° C. in a yield of 77% (4.53 g).
Reaction SMILES: [CH2:1]([N:3]([CH2:30][CH3:31])[C:4]([C:6]1[N:7]([CH2:25][CH2:26][CH2:27][C:28]#[N:29])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:24])=[CH:10][CH:9]=2)=[O:5])[CH3:2].[N:32]([Si](C)(C)C)=[N+:33]=[N-:34].C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[CH2:30]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[N:7]([CH2:25][CH2:26][CH2:27][C:28]2[NH:34][N:33]=[N:32][N:29]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[C:18]([Cl:24])=[CH:19][CH:20]=[CH:21][C:22]=1[Cl:23])=[CH:10][CH:9]=2)=[O:5])[CH3:31]
Reactant: CCN(CC)C(=O)c1cc2cc(OCc3c(Cl)cccc3Cl)ccc2n1CCCC#N
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: CCN(CC)C(=O)c1cc2cc(OCc3c(Cl)cccc3Cl)ccc2n1CCCc1nnn[nH]1
Yield: 46.9 %

Procedure:
To a solution of 1-(3-cyanopropyl)-5-(2,6-dichlorobenzyloxy)-1H-indole-2-carboxylic acid diethylamide (0.078 g, 0.17 mmol) in toluene (10 mL) was added azidotrimethylsilane (0.066 mL, 0.50 mmol) and dibutyltin oxide (0.012 g, 0.050 mmol). The reaction mixture was heated to reflux and stirred under argon at reflux temperature for 40 h. The solution was cooled and the toluene removed under reduced pressure. Methanol was then added and removed under reduced pressure. Ethyl acetate was added and the reaction mixture was washed with water and brine. The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. Purification by flash chromatography (silica gel, 10% methanol/dichloromethane) yielded a white solid (0.040 g, 47%). MS(ES) m/e 501.2 [M +H]+.
Reaction SMILES: [Cl-].[Li+].[CH3:3][C:4]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][C:6](=[O:16])[CH:5]=1.[CH3:17][Mg]Br.[Cl-].[NH4+]>O1CCCC1.[Cu](I)I>[CH3:3][C:4]1([CH3:17])[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][C:6](=[O:16])[CH2:5]1
Reactant: C[Mg]Br
Reactant: CC1=CC(=O)CCC1c1ccccc1
Agent: I[Cu]I
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC1(C)CC(=O)CCC1c1ccccc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
Lithium chloride (0.6 mmol) and copper iodide (0.3 mmol) are introduced first under argon in dry tetrahydrofuran (18 ml). At 0° C. 3-methyl-4-phenylcyclohex-2-enone (3 mmol) is added and stirring continues for another 10 min at this temperature. Then a solution of methylmagnesium bromide (3.6 mmol) is slowly added dropwise and the reaction mixture is maintained at 0° C. for 3 hours accompanied by stirring. The reaction is stopped by adding saturated aqueous ammonium chloride solution. The mixture is extracted with diethyl ether. The title compound is obtained from the combined organic phases after drying over sodium sulphate and evaporating-off of the solvent in a vacuum (J. Organom. Chem. 1995, 502, C5-C7): tR 2.36 min (LC-2); ESI-MS (+): m/z 203.35 [M+H]+.
Reaction SMILES: C([N:8]1[C:12]([NH:13][CH:14]2[CH2:23][CH2:22][C:17]3([O:21][CH2:20][CH2:19][O:18]3)[CH2:16][CH2:15]2)=[CH:11][CH:10]=[N:9]1)C1C=CC=CC=1.C(O)(=O)C.C([O-])=O.[NH4+].C(OCC)(=O)C>C(O)C.[OH-].[Pd+2].[OH-]>[O:18]1[C:17]2([CH2:16][CH2:15][CH:14]([NH:13][C:12]3[NH:8][N:9]=[CH:10][CH:11]=3)[CH2:23][CH2:22]2)[O:21][CH2:20][CH2:19]1
Reactant: c1ccc(Cn2nccc2NC2CCC3(CC2)OCCO3)cc1
Agent: [Pd+2]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Solvent: CCO
Solvent: CCOC(C)=O
Product: c1cc(NC2CCC3(CC2)OCCO3)[nH]n1
Temperature: 80 °C
Reaction time: 4 h
Yield: 81.3 %

Procedure:
To a suspension of 1-benzyl-N-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazol-5-amine (38 g) and palladium hydroxide (10 wt %, 11.4 g) in ethanol (200 mL)-acetic acid (40 mL) was added ammonium formate (32 g) by small portions at 80° C. After stirring at 80° C. for 4 hr, the mixture was allowed to cool to room temperature, ethyl acetate was added, and the insoluble material was filtered off. Saturated aqueous sodium hydrogen carbonate was added to the filtrate, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was crystallized using ethyl acetate, and the resulting solid was collected by filtration, washed with diisopropyl ether, and dried under reduced pressure to give the title compound as a pale-yellow solid (22 g, 81%).
Reaction SMILES: [CH:1]([C:3]1[CH:16]=[CH:15][C:6]([C:7]([NH:9][C:10]2[N:11]=[N:12][NH:13][N:14]=2)=[O:8])=[CH:5][CH:4]=1)=O.[C:17]([C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18].C(O)(=O)C.C([BH3-])#N.[Na+]>CN(C=O)C.COC(OC)OC.CO>[C:17]([C:21]1[CH:22]=[CH:23][C:24]([NH:25][CH2:1][C:3]2[CH:16]=[CH:15][C:6]([C:7]([NH:9][C:10]3[N:11]=[N:12][NH:13][N:14]=3)=[O:8])=[CH:5][CH:4]=2)=[CH:26][CH:27]=1)([CH3:20])([CH3:18])[CH3:19]
Reactant: CC(C)(C)c1ccc(N)cc1
Reactant: O=Cc1ccc(C(=O)Nc2nn[nH]n2)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: COC(OC)OC
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: CC(C)(C)c1ccc(NCc2ccc(C(=O)Nc3nn[nH]n3)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
The above resin bound 4-formyl-N-(2H-tetrazol-5-yl)benzamide (500 mg) was treated with a 0.5 M solution of 4-tert-butylaniline (2.5 mmol, 412.5 mg) in a mixture of DMF and trimethylorthoformate (1:1, 5 mL) and glacial acetic acid (500 μL) for 1 hour at 25° C. followed by sodium cyanoborohydride (2.5 mmol, 160 mg) dissolved in a mixture of DMF and methanol (1:1, 2.5 mL). Shaking at 25° C. for 4 hours followed by filtration and washing with a mixture of methanol and DMF (1:1, 2×10 mL), DMF(3×10 mL) and dichloromethane (2×10 mL) afforded the desired product.
Reaction SMILES: I[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[Sn:15](Cl)([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH2:18][CH3:19]>C1COCC1>[CH2:24]([Sn:15]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:20][CH2:21][CH2:22][CH3:23])[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)[CH2:25][CH2:26][CH3:27]
Reactant: N#Cc1ccc(I)cc1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1ccc(C#N)cc1
Temperature: -40 °C
Reaction time: 1 h
Yield: 80.1 %

Procedure:
To 4-iodobenzonitrile (2.29 g, 10.0 mmol, 1.00 equiv) in THF (30 mL) at −40° C. was added iPrMgCl (2.0 M in Et2O, 5.50 mL, 11 mmol, 1.1 equiv). The reaction mixture was stirred for 1.0 hr at −40° C. before the addition of nBu3SnCl (3.91 g, 12.0 mmol, 1.20 equiv). After stirring for 1.0 hr at −40° C., the reaction mixture was warmed to 23° C. and quenched with saturated aqueous NH4Cl (30 mL), and Et2O (20 mL) was added. The phases were separated and the aqueous phase was extracted with Et2O (2×20 mL). The combined organic phases were washed with brine (50 mL) and dried (Na2SO4). The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica gel eluting with hexanes to afford 3.14 g of the title compound as a colorless oil (80% yield).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:14]([O:15][CH3:16])=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][C:6]=1[O:17][CH3:18])=[O:4].[N-:19]=[N+:20]=[N-:21].[Na+].O>CN(C=O)C>[N:19]([CH2:2][C:3]([C:5]1[C:14]([O:15][CH3:16])=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[CH:7][C:6]=1[O:17][CH3:18])=[O:4])=[N+:20]=[N-:21]
Reactant: COC(=O)c1cc(OC)c(C(=O)CBr)c(OC)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc(OC)c(C(=O)CN=[N+]=[N-])c(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Methyl 4-(bromoacetyl)-3,5-dimethoxybenzoate was dissolved in DMF, sodium azide (96 mg) was added to it, and stirred at room temperature for 1 hour. The reaction liquid was poured into water, extracted with ethyl acetate, the organic layer was washed with water and saturated saline water, and dried with sodium sulfate. Sodium sulfate was removed through filtration, and the filtrate was concentrated under reduced pressure. The residue was purified through silica gel column chromatography (hexane/ethyl acetate=100/0 to 60/40) to obtain the title compound.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:19][C:20]1[C:39]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([C:46](=[O:57])[NH:47][C:48]3([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[CH2:50][CH2:49]3)[CH:41]=2)=[CH:38][C:23]2[C:24]([C:34]([NH:36][CH3:37])=[O:35])=[C:25]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[O:26][C:22]=2[CH:21]=1.N12CCCN=C1CCCCC2>C1COCC1.CO>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([NH:19][C:4](=[O:6])[CH2:3][O:2][CH3:1])[C:39]([C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([C:46](=[O:57])[NH:47][C:48]5([C:51]6[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=6)[CH2:50][CH2:49]5)[CH:41]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:28][CH:29]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N)c(-c3cccc(C(=O)NC4(c5ccccc5)CC4)c3)cc12
Reactant: COCC(=O)O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CO
Solvent: C1CCOC1
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(NC(=O)COC)c(-c3cccc(C(=O)NC4(c5ccccc5)CC4)c3)cc12
Temperature: 55 °C
Reaction time: 1 h

Procedure:
To a mixture of 2-methoxyacetic acid (10.40 mg, 0.115 mmol) in THF (3 mL) at r.t. under N2 was added 1,1′-carbonyldiimidazole (CDI) (28.1 mg, 0.173 mmol). The mixture was stirred at 55° C. for 1 hr. The mixture was then transferred to a flask containing 6-amino-2-(4-fluorophenyl)-N-methyl-5-(3-(1-phenylcyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide (30 mg, 0.058 mmol) at r.t. under N2. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (0.035 mL, 0.231 mmol) was then added and the mixture was stirred at 55° C. for 2 hr 35 min. The mixture was then left standing at r.t. overnight. The mixture was re-stirred at 55° C. for 3 hr. The mixture was cooled to r.t., diluted with MeOH and purified by Shimadzu-VP preparative reverse phase HPLC using the separation method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=50, Final % B=100, Gradient time=10 min, Stop time=12 min, Flow Rate=25 mL/min, Column: Waters-Sunfire 19×100 mm S5, Fraction Collection: 7.28-7.84 min. (UV detection at 220 nm). 1H NMR (500 MHz, DMSO-d6) δ 9.29 (s, 1H), 9.04 (s, 1H), 8.49 (q, J=4.58, 1H), 8.31 (s, 1H), 8.03-8.00 (overlapping m, 3H), 7.98 (m, 1H), 7.59 (s, 1H), 7.63 (s, 1H), 7.625 (d, J=2.44, 1H), 7.40 (t, J=9.00, 2H), 7.28 (apparent t, J=7.63, 2H,), 7.23 (apparent d, 2H,), 7.17 (t, J=7.17, 1H,), 3.90 (s, 2H), 3.18 (s, 3H), 2.83 (appeared as d, J=4.58, 3H), 1.28 (s, 4H). LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=4 ml/min, Column: XTERRA® MS 7 um, C18, 3.0×50 mm; (ES+) m/z (M+H)+=592.49, HPLC Rt=1.652 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N+:9]([O-])=O.Cl.C([O-])(O)=O.[Na+]>CO.O.[Fe]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH2:9]
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: [Fe]
Agent: Cl
Agent: O=C([O-])O
Solvent: CO
Solvent: O
Product: Cc1ccc(Cl)c(N)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 60.9 %

Procedure:
To a solution of 1-chloro-4-methyl-2-nitrobenzene (10.0 g, 0.058 mol) in methanol (50 mL), iron powder (3.0 g, 0.055 mol) and conc. HCl (10 mL) were added. The reaction mixture was stirred at RT for 2 h. The reaction mixture was diluted with water and basified with NaHCO3 solution and extracted with DCM. The organic layer was separated and dried over anhydrous sodium sulphate and concentrated to afford 5.0 g of the desired compound. 1HNMR (CDCl3): δ 2.23 (s, 3H), 3.94 (s, 2H), 6.50 (d, J=7.8 Hz, 1H), 6.57 (s, 1H), 7.10 (d, J=7.8 Hz, 1H); MS [M+H]+: 142.25.
Reaction SMILES: Br[C:2]1[C:7]2[N:8]3[C:21]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[C:15]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:14]4[C:9]3=[C:10]([CH:11]=[CH:12][CH:13]=4)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[B:39]([O:44]C)(OC)[O:40]C>C1COCC1.C1CCCCC1>[C:28]1([C:15]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:14]3[C:9]4=[C:10]([C:6]5[CH:5]=[CH:4][CH:3]=[CH:2][C:7]=5[N:8]4[C:21]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]2=4)[CH:11]=[C:12]([B:39]([OH:44])[OH:40])[CH:13]=3)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: COB(OC)OC
Reactant: Brc1cccc2c3cccc4c3n(c12)-c1ccccc1C4(c1ccccc1)c1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: OB(O)c1cc2c3c(c1)c1ccccc1n3-c1ccccc1C2(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
125.9 g (259 mmol) of bromo-8,8-diphenyl-8H-indolo[3,2,1-de]acridine are dissolved in 1500 ml of dry THF. 135 ml (337 mmol) of a 2.5 M solution of n-butyllithium in cyclohexane are added dropwise at −70° C., and, after 1 h, 37 ml of trimethyl borate (336 mmol) are added dropwise. The mixture is warmed to room temperature over the course of 1 h, the solvent is removed, and the residue, which is uniform according to 1H-NMR, is employed in the subsequent reaction without further purification.
Reaction SMILES: [F:1][CH:2]([F:9])[N:3]1[N:7]=[C:6]([NH2:8])[CH:5]=[N:4]1.Br[C:11]1[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=[C:15]([Br:17])[CH:16]=1>>[Br:17][C:15]1[CH:16]=[C:11]([NH:8][C:6]2[CH:5]=[N:4][N:3]([CH:2]([F:9])[F:1])[N:7]=2)[C:12](=[O:19])[N:13]([CH3:18])[CH:14]=1
Reactant: Cn1cc(Br)cc(Br)c1=O
Reactant: Nc1cnn(C(F)F)n1
Product: Cn1cc(Br)cc(Nc2cnn(C(F)F)n2)c1=O
Yield: 70 %

Procedure:
Following the procedure of Example 151f, and starting with 159b (170 mg, 1.25 mmol, 1.0 eq.) and 3,5-dibromo-1-methylpyridin-2(1H)-one (504 g, 1.89 mmol, 1.5 eq.) afforded 159c as a light yellow solid (280 mg, 70%). MS-ESI:[M+H]+ 320.1.
Reaction SMILES: [Cl:1][CH2:2][C:3]([O:11][Si:12]([CH3:15])([CH3:14])[CH3:13])([CH2:7][CH2:8][CH2:9][CH3:10])[CH2:4][C:5]#[CH:6].[CH2:16]([SnH:20]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:18][CH3:19]>>[CH2:25]([Sn:20]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:21][CH2:22][CH2:23][CH3:24])/[CH:6]=[CH:5]/[CH2:4][C:3]([CH2:2][Cl:1])([O:11][Si:12]([CH3:15])([CH3:13])[CH3:14])[CH2:7][CH2:8][CH2:9][CH3:10])[CH2:26][CH2:27][CH3:28]
Reactant: C#CCC(CCl)(CCCC)O[Si](C)(C)C
Reactant: CCCC[SnH](CCCC)CCCC
Product: CCCCC(CCl)(C/C=C/[Sn](CCCC)(CCCC)CCCC)O[Si](C)(C)C
Temperature: 125 °C
Reaction time: 1.5 h

Procedure:
A mixture of 9.27 g. of 4-chloromethyl-4-trimethylsilyloxy-1-octyne, 40 mg. of azoisobutyronitrile, and 10.0 ml. of tri-n-butyltin hydride is heated and stirred at 125° C. for 1.5 hours, then vacuum distilled through a short path to give, after a forerun, 19.5 g. of product as a colorless liquid at b.p. 140-160° C./0.1-0.2 mm.; PMR δ 5.98 (m, olefin), 3.40 (s, CH2Cl), 2.40 (m, C=C--CH2), 0.14 (s, OTMS).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.C(#N)C.Cl[C:34]1[N:39]=[C:38]([NH:40][C@H:41]2[CH2:46][CH2:45][CH2:44][C@@H:43]([O:47][CH3:48])[C@@H:42]2[OH:49])[C:37]([F:50])=[CH:36][N:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:34]3[N:39]=[C:38]([NH:40][C@H:41]4[CH2:46][CH2:45][CH2:44][C@@H:43]([O:47][CH3:48])[C@@H:42]4[OH:49])[C:37]([F:50])=[CH:36][N:35]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:21])=[O:22])[C:5]2=[N:6][CH:7]=1
Reactant: CO[C@@H]1CCC[C@H](Nc2nc(Cl)ncc2F)[C@H]1O
Reactant: Cc1ccc(S(=O)(=O)n2cc(B3OC(C)(C)C(C)(C)O3)c3cc(Cl)cnc32)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CO[C@@H]1CCC[C@H](Nc2nc(-c3cn(S(=O)(=O)c4ccc(C)cc4)c4ncc(Cl)cc34)ncc2F)[C@H]1O
Temperature: 120 °C

Procedure:
In a microwave tube was placed 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.10 g, 0.23 mmol). To this was added acetonitrile (0.61 mL) and the solution was deoxygenated with nitrogen. To the reaction was added (1R,2S,6R)-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-6-methoxy-cyclohexanol, 51j, (0.04 g, 0.14 mmol) and palladium catalyst (24 mg), and then aqueous sodium carbonate (0.21 mL of 2 M solution, 0.41 mmol). The reaction was sealed and heated to 120° C. in the microwave reactor for 15 min. The reaction was diluted with ethyl acetate (40 mL), filtered thru florisil, and concentrated in vacuo to give crude as a green solid. This was purified by silica gel chromatography (20-75% EtOAc/hexanes gradient). Used resulting product directly in the next step.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[C:6]([O:8]CC)=[O:7].O.O1CCOCC1>C(N(CC)CC)C>[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:11])[C:6]([OH:8])=[O:7]
Reactant: CCOC(=O)C(=O)NCCO
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)C(=O)NCCO

Procedure:
To 730.7 g (5 moles) of diethyl oxalate was added dropwise at room temperature a solution of 61.1 g (1 mole) of ethanolamine in 500 ml of acetone and, after the addition finished, treatment of the mixture by distillation under reduced pressure to remove the formed ethanol and the acetone and an excess amount of diethyl oxalate yielded ethyl 2-hydroxyethyloxamate. A mixture of 80.5 g (0.5 moles) of this ethyl 2-hydroxyethyloxamate, 50.6 g (0.5 moles) of triethylamine (hereinafter, referred to as TEA), 20.0 g of water, and 1000 ml of dioxane was warmed under reflux for 8 hours and treated with solvent removal followed by dehydration yielded a triethylamine salt of 2-hydroxyethyloxamic acid. A mixture of 11.7 g (0.05 moles) of this triethylamine salt of 2-hydroxyethyloxamic acid and 5.1 g (0.05 moles) of TEA was treated with dehydration by molecular sieve and then, dissolved with warming into 300 ml of THF. To this THF solution was added dropwise under a refluxing condition during 0.5 hours a solution of 5.2 g (0.05 moles) of methacrylic acid chloride in 30 ml of THF and, after the addition finished, the mixture was further stirred under the condition for 6 hours and treated with fractional extraction to get methacryloyloxyet hyloxamic acid of the following structure: ##STR17## Besides, identification of the methacrylolyloxyethyloxamic acid 1 was carried out with 13C-NMR spectra analysis (ppm, in CDCL3) and the results were 17.93 for (2), 38.86 for (6); 62.35 for (5), 120.59 for (1), 138.86 for (3), 158.01 for (7), 160.56 for (8), and 167.06 for (4).
Reaction SMILES: [C:1]1([N-:7][C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:17][CH2:18][CH2:19][C:20](Cl)=O.B.C1(N(CCCBr)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:1]1([N:7]([CH2:20][CH2:19][CH2:18][Br:17])[C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc([N-]c2ccccc2)cc1
Reactant: O=C(Cl)CCBr
Agent: B
Agent: BrCCCN(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(N(CCCBr)c2ccccc2)cc1

Procedure:
3-[N-phenyl-N-(4-nitrophenyl)amino]-1-bromopropane is prepared from N-phenyl-N-(4-nitrophenyl)amide with 3-bromopropionyl chloride, followed by reduction with borane in tetrahydrofuran, by a procedure analogous to the preparation of 3-[N,N-diphenylamino]-1-bromopropane in Example 2.