Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([CH2:17][C:18]2[N:22]4[N:23]=[C:24]([CH:27]=[CH2:28])[CH:25]=[CH:26][C:21]4=[N:20][N:19]=2)=[CH:12][CH:11]=3)[CH:4]=[N:3]1>ClCCl.CO.[Pd]>[CH2:27]([C:24]1[CH:25]=[CH:26][C:21]2[N:22]([C:18]([CH2:17][C:13]3[CH:14]=[C:15]4[C:10](=[CH:11][CH:12]=3)[N:9]=[CH:8][C:7]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)=[CH:16]4)=[N:19][N:20]=2)[N:23]=1)[CH3:28]
Reactant: C=Cc1ccc2nnc(Cc3ccc4ncc(-c5cnn(C)c5)cc4c3)n2n1
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Product: CCc1ccc2nnc(Cc3ccc4ncc(-c5cnn(C)c5)cc4c3)n2n1
Reaction time: 3 h

Procedure:
To a solution of 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-vinyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (22 mg, 0.06 mmol) in dichloromethane (5 mL) and methanol (0.5 mL) under an atmosphere of N2(g) was added 10% palladium on carbon (20 mg) and the atmosphere replaced with H2(g). After stirring vigorously for 3 hours the mixture was filtered through a pad of celite and purified via flash column chromatography (SiO2, CH2Cl2, methanol 0-10%) to return the title compound as a white solid (17 mg, 77%). Analytical data presented in Table 2.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[S:10][C:6]=2[CH:5]=[CH:4][C:3]=1[NH2:12].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22](Cl)=[O:23])=[CH:17][CH:16]=1.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[S:10][C:6]=2[CH:5]=[CH:4][C:3]=1[NH:12][C:22](=[O:23])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=1
Reactant: Cc1nc2c(Cl)c(N)ccc2s1
Reactant: COc1ccc(CC(=O)Cl)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc(CC(=O)Nc2ccc3sc(C)nc3c2Cl)cc1
Yield: 56 %

Procedure:
Reaction of 4-chloro-2-methyl-benzothiazol-5-ylamine (50 mg, 0.25 mmol) in THF (1.5 mL) with 4-methoxyphenylacetyl chloride (46 μL, 0.30 mmol) in presence of triethylamine (42 μL, 0.30 mmol) according to method A gave N-(4-chloro-2methyl-benzothiazol-5-yl)-2-(4-methoxy-phenyl)-acetamide (50 mg, 0.14 mmol, 56% yield) as a white powder after crystallisation in hexane/DCM.
Reaction SMILES: [CH:1]#[CH:2].[N+:3]([C:6]1[CH:19]=[CH:18][C:9]([C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:11])=[CH:8][CH:7]=1)([O-:5])=[O:4].Cl>O1CCCC1>[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([C:10]([C:1]#[CH:2])([OH:11])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:18][CH:19]=1)([O-:5])=[O:4]
Reactant: O=C(c1ccccc1)c1ccc([N+](=O)[O-])cc1
Reactant: C#C
Agent: Cl
Solvent: C1CCOC1
Product: C#CC(O)(c1ccccc1)c1ccc([N+](=O)[O-])cc1
Yield: 91 %

Procedure:
Acetylene is introduced for 30 minutes into a 20°-22 °C mixture of 118 ml. of tetrahydrofuran and 16.8 g. of potassium-tert.butylate, and thereafter 22.7 g. of 4-nitro-benzophenone are added to the mixture. The introduction of acetylene is continued at 20° to 22 °C for additional 30 minutes, then the mixture is neutralized with 5 n hydrochloric acid under a nitrogen atmosphere. The organic phase is separated, dried over anhydrous sodium sulfate, and the solvent is distilled off in vacuo. 23.1 g. (91 %) of 4-nitro-α-ethynyl-benzhydrol are obtained; m.p.: 88°-89 °C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:31]([CH:32]=[CH2:33])=[N:30][N:29]([CH:34]4[CH2:39][CH2:38][CH2:37][CH2:36][O:35]4)[C:18]=3[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[CH:21]=2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[C:45]([Si:49](Cl)([CH3:51])[CH3:50])([CH3:48])([CH3:47])[CH3:46].O>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]([C:16]2[C:17]3[C:31]([CH:32]=[CH2:33])=[N:30][N:29]([CH:34]4[CH2:39][CH2:38][CH2:37][CH2:36][O:35]4)[C:18]=3[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][Si:49]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:51])[CH3:50])=[CH:24][CH:23]=3)[CH:21]=2)=[O:15])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C=Cc1nn(C2CCCCO2)c2nc(-c3ccc(O)cc3)cc(C(=O)N3CCN(C(=O)OC(C)(C)C)CC3)c12
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: ClCCl
Product: C=Cc1nn(C2CCCCO2)c2nc(-c3ccc(O[Si](C)(C)C(C)(C)C)cc3)cc(C(=O)N3CCN(C(=O)OC(C)(C)C)CC3)c12
Temperature: 25 °C
Reaction time: 5 h
Yield: 53.6 %

Procedure:
To a solution of 4-[6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (3.15 g, 5.90 mmol) in dichloromethane (22 ml) were added imidazole (0.96 g, 14.17 mmol) and tert-butyl(chloro)dimethylsilane (1.07 g, 7.08 mmol). The reaction mixture was stirred at room temperature for 5 hours, water and dichloromethane were then added. The aqueous layer was separated and the organic layer was washed with water, brine, dried (Na2SO4), filtered, concentrated under vacuum. The crude residue was purified on a silica gel column chromatography using a gradient of EtOAc (0-30%) in cyclohexane to yield the title compound as a yellow foam (2.05 g, 53%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[OH:13].[H-].[Na+].[CH3:17]I>CN(C)C=O>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[O:13][CH3:17]
Reactant: CI
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc([N+](=O)[O-])cc1OC
Temperature: 25 °C
Yield: 47.4 %

Procedure:
788 mg (4 mmol) of 2-hydroxy-4-nitro-benzoic acid methyl ester is mixed in 20 ml of absolute dimethylformamide with 177 mg of sodium hydride (60%; 4.4 mmol), and it is heated for 1 hour to 50° C. After cooling to room temperature, it is mixed with 625 mg (4.4 mmol) of methyl iodide and heated for 4 hours to a bath temperature of 80° C. After concentration by evaporation, it is taken up in 50 ml of water and extracted three times with 25 ml each of ethyl acetate. The ethyl acetate phase is washed with water, dried, filtered and concentrated by evaporation. The residue is chromatographed on 5 g of Isolute SI. (50 μm) with a gradient from cyclohexane to cyclohexane:ethyl acetate=80:20 as an eluant, and 400 mg (47% of theory) of 2-methoxy-4-nitro-benzoic acid methyl ester is obtained as an oil.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:9][C:10]1[CH:26]=[CH:25][C:13]([C:14]([NH:16][CH:17]([N:22]=[C:23]=[O:24])[C:18]([Cl:21])([Cl:20])[Cl:19])=[O:15])=[CH:12][CH:11]=1>C1COCC1>[CH3:9][C:10]1[CH:11]=[CH:12][C:13]([C:14]([NH:16][CH:17]([NH:22][C:23]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[F:1])=[O:24])[C:18]([Cl:21])([Cl:20])[Cl:19])=[O:15])=[CH:25][CH:26]=1
Reactant: Nc1ccccc1F
Reactant: Cc1ccc(C(=O)NC(N=C=O)C(Cl)(Cl)Cl)cc1
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)NC(NC(=O)Nc2ccccc2F)C(Cl)(Cl)Cl)cc1
Reaction time: 2 h

Procedure:
A solution of 2-fluoroaniline (132 mg, 1.40 mmol) in THF (8 mL) at ambient temperature was treated with a solution of Example 43A (386 mg, 1.26 mmol) in THF (1.5 mL). The reaction mixture was stirred for 2 hours and concentrated to a nominal volume. The white solids which precipitated from solution were collected by filtration and washed with diethyl ether. Recrystallization from 25% ethyl acetate/hexanes provided the desired product as a white solid.
Reaction SMILES: [CH3:1][O:2][N:3]([CH3:28])[C:4]([C:6]1[C:11]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=2)(=[O:15])=[O:14])=[CH:10][C:9]([CH3:27])=[CH:8][N:7]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH3:35][O:36][CH2:37]Cl.CON(C)C(C1C(N(COC)S(C2C=CC(Cl)=C(C(F)(F)F)C=2)(=O)=O)=CC(Cl)=CN=1)=O>C1COCC1>[CH3:1][O:2][N:3]([CH3:28])[C:4]([C:6]1[C:11]([N:12]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:24])[F:25])[CH:17]=2)(=[O:15])=[O:14])[CH2:35][O:36][CH3:37])=[CH:10][C:9]([CH3:27])=[CH:8][N:7]=1)=[O:5]
Reactant: CON(C)C(=O)c1ncc(C)cc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: COCCl
Agent: COCN(c1cc(Cl)cnc1C(=O)N(C)OC)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COCN(c1cc(C)cnc1C(=O)N(C)OC)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1

Procedure:
Prepared from 223 mg (0.51 mmol) of 3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-5-methyl-pyridine-2-carboxylic acid methoxy-methyl-amide, 352 mg of potassium carbonate and 116 μL of methoxymethyl chloride in 1 mL THF using the procedure used to prepare Intermediate 12. Yield: 200 mg of a white solid. LC-MSD, m/z for C18H19ClF3N3O5S [M+H]+=482.0, 484.0; HPLC retention time: 2.5 minutes.
Reaction SMILES: [NH2:1][C:2]1[CH:26]=[C:25]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:23][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[C:9]([O:21][CH3:22])[CH:8]=1)=[O:5].[C:34](C1NC=CN=1)(C1NC=CN=1)=[O:35].C1CCN2C(=NCCC2)CC1>ClCCl>[CH3:22][O:21][C:9]1[CH:8]=[C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:26][C:25]([O:27][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:24][CH:23]=3)[NH:1][C:34]2=[O:35])[CH:12]=[CH:11][C:10]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:17][CH2:18][CH2:19][CH2:20]1
Reactant: COc1cc(NC(=O)c2ccc(Oc3ccccc3)cc2N)ccc1OCCN1CCCC1
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: COc1cc(-n2c(=O)[nH]c3cc(Oc4ccccc4)ccc3c2=O)ccc1OCCN1CCCC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
2-Amino-N-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-4-phenoxy-benzamide [Example C1] (62 mg, 0.14 mmol) was dissolved in dichloromethane (5 ml) and treated with carbonyl diimidazole (50 mg, 0.31 mmol) and DBU (0.1 ml). The mixture was stirred for 4 h at RT then the solvent removed and the residue purified by flash chromatography on silica gel (eluting with ammonia-methanol-dichloromethane) to obtain the title compound;
Reaction SMILES: [F:1][C:2]1([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([NH2:19])(=[O:18])=[O:17])=[CH:12][C:11]=2[N+:20]([O-:22])=[O:21])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.C([BH3-])#N>O1CCCC1.C(O)(=O)C>[F:1][C:2]1([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([NH2:19])(=[O:18])=[O:17])=[CH:12][C:11]=2[N+:20]([O-:22])=[O:21])[CH2:7][CH2:6][N:5]([CH:25]2[CH2:26][O:23][CH2:24]2)[CH2:4][CH2:3]1
Reactant: O=C1COC1
Reactant: NS(=O)(=O)c1ccc(OCC2(F)CCNCC2)c([N+](=O)[O-])c1
Agent: [BH3-]C#N
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccc(OCC2(F)CCN(C3COC3)CC2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of EXAMPLE 341C (72 mg) in tetrahydrofuran (1.5 mL) and acetic acid (0.5 mL) was added oxetan-3-one (14 mg) and MP-cyanoborohydride (2.38 mmol/g, 162 mg). The mixture was stirred at room temperature overnight. The reaction was then filtered and the filtrate was concentrated under vacuum. The residue was slurried in ether and the product was collected by filtration.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[Br:11]N1C(=O)CCC1=O>C1(C)C=CC=CC=1>[CH3:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([Br:11])[CH:4]=1)=[O:10]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(=O)c1ccc(N)cc1
Solvent: Cc1ccccc1
Product: CC(=O)c1ccc(N)c(Br)c1
Reaction time: 0.25 h
Yield: 91.1 %

Procedure:
A mixture containing 48.86 g of p-aminoacetophenone in 490 ml of toluene is stirred while 64.5 g of N-bromosuccinimide is added in portions over 0.5 hours at below 40° C. After 15 minutes, the mixture is washed with H2O (4×100 ml). The solution is dried (MgSO4) and evaporated to dryness to afford 70.53 g of 4-amino-3-bromoacetophenone, mp 59°-62° C. A 35 g sample of this material in 180 ml of dry dimethylformamide is stirred and heated at reflux with 17.57 g of Cu2 (CN)2 for 6 hours under N2 atmosphere. Subsequently, 180 ml of FeCl3 /HCl solution (40 g FeCl3.6H2O/10 ml concentrated HCl/60 ml H2) is added and the mixture is heated for 20 minutes at 60°-70° C. and poured into 350 ml of H2O. The aqueous mixture is extracted with CH2Cl2 and the extracts are washed with H2O, saturated NaHCO3 solution and H2O, respectively. The CH2Cl2 solution is evaporated to dryness in vacuo and the residue is recrystallized from 95% EtOH to afford 14.25 g, mp 155°-159° C., of 4-amino-3-cyanoacetophenone. A 4.8 g sample of this product in 100 ml of EtOAc and 100 ml of CHCl3 containing 13.32 g of CuBr2 is heated at reflux temperature for 20 minutes. The mixture is further heated after 20 ml of EtOH is added and then filtered while still hot. The filter cake is washed with 50 ml of hot 20% MeOH/CH2Cl2 and the combined organic solutions are evaporated to dryness in vacuo. The residue is stirred in 25 ml of CH2Cl2 and the solid is collected and washed with CH2CL2 to give 8.08 g of the phenacyl bromide. This material is added to 50 ml of t-BuNH2 in 100 ml of EtOH at 5° under N2 atmosphere. After 10 minutes of stirring, the mixture is allowed to warm to 30° C. to give a solution. This solution is cooled to 10° and 4 g of NaBH4 is added in portions. After 45 minutes, the mixture is allowed to warm (42° C.) and kept at 20° C. until the exotherm subsides. The mixture is then evaporated to dryness and the residue is washed with H2O. The residue is dried and treated with 200 ml of boiling MeOH and the hot MeOH solution is filtered. The filter cake is further washed with hot MeOH and the combined filtrates are concentrated to afford crystals. This solid is recrystallized from MeOH/2-PrOH to afford 2.08 g, mp 184°-186° C., of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][C:3]=1[CH:11]([CH3:13])[CH3:12].[N:14]1[CH:19]=[CH:18][CH:17]=[C:16]([N:20]=[C:21]=[O:22])[CH:15]=1>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:21](=[O:22])[NH:20][C:16]2[CH:15]=[N:14][CH:19]=[CH:18][CH:17]=2)=[CH:4][C:3]=1[CH:11]([CH3:13])[CH3:12]
Reactant: CC(C)c1cc2c(cc1Cl)NCC2
Reactant: O=C=Nc1cccnc1
Product: CC(C)c1cc2c(cc1Cl)N(C(=O)Nc1cccnc1)CC2
Yield: 57 %

Procedure:
6-Chloro-5-isopropylindoline (D58) (0.4 g, 2.05 mmol) was treated with 3-pyridylisocyanate as in the procedure described in Example 1. The product was recrystallised from ethanol/diethyl ether to give the title compound (0.36 g, 57%) as a white crystalline solid m.p.=183°-185° C.
Reaction SMILES: C[O:2][C:3]1[C:4]2[C:9]([C:10]([C:17]3[C:19](=[O:20])[C:18]=3[C:21]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]([O:35]C)=[C:27]4[C:22]=3[CH:23]=[CH:24][CH:25]=[CH:26]4)=[C:11]3[C:16]=1[CH:15]=[CH:14][CH:13]=[CH:12]3)=[CH:8][CH:7]=[CH:6][CH:5]=2.[Al+3].[Cl-].[Cl-].[Cl-].C(N(CC)CC)C>ClC1C=CC=CC=1>[OH:2][C:3]1[C:16]2[C:11]([C:10]([C:17]3[C:19](=[O:20])[C:18]=3[C:21]3[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:28]([OH:35])=[C:29]4[C:34]=3[CH:33]=[CH:32][CH:31]=[CH:30]4)=[C:9]3[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]3)=[CH:12][CH:13]=[CH:14][CH:15]=2
Reactant: COc1c2ccccc2c(-c2c(-c3c4ccccc4c(OC)c4ccccc34)c2=O)c2ccccc12
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Solvent: CCN(CC)CC
Product: O=c1c(-c2c3ccccc3c(O)c3ccccc23)c1-c1c2ccccc2c(O)c2ccccc12
Temperature: 0 °C
Yield: 83.7 %

Procedure:
1.17 g of bis(9-methoxy-10-anthracenyl)cyclopropenone was dissolved in chlorobenzene, and refluxed for 12 hours with 250 mg of AlCl3. When disappearance of starting materials was complete, the cooled mixture was poured into ice water with a small amount of triethylamine therein, and the organic layer separated. The water layer was washed twice with CHCl3, and the combined organics washed with water, dried with CaCl2, and evaporated to give 0.92 g bis(9-hydroxy-10-anthracenyl)cyclopropenone as a maroon solid, i.r. 1810, 1600 cm. ##STR7##
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[F:10][C:11]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:12]=1[C:13](Cl)=[O:14]>>[OH:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[NH:1][C:13](=[O:14])[C:12]1[CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=[CH:19][C:11]=1[F:10]
Reactant: Nc1ccc(F)cc1O
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1F
Product: O=C(Nc1ccc(F)cc1O)c1cc([N+](=O)[O-])ccc1F

Procedure:
Prepared by the method of Example 15a), from 2-amino-5-fluorophenol (508 mg, 4.0 mmol) and 2-fluoro-5-nitrobenzoyl chloride (814 g, 4.0 mmol) the subtitle compound was obtained. The product was used directly in the next step without purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([O:14][Si](C)(C)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)[F:20].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C(OCC)(=O)C>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([F:20])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CC=C(O[Si](C)(C)C)CC1
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(=O)C(F)C1
Reaction time: 1.25 h
Yield: 91 %

Procedure:
To a stirred solution of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydro-4-(trimethylsilyloxy)pyridine (400 g, 14.7 mmol) in anhydrous acetonitrile (160 mL) under nitrogen was added Selectfluor™ reagent (5.74 g, 16.2 mmol) and the mixture was stirred for 75 min. The mixture was poured into ethyl acetate (600 mL), washed with diluted brine (300 mL), then saturated NaCl solution (100 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by flash chromatography (alumina, 0-5% MeOH/EtOAc) to afford 2.91 g (91%) of the title compound as a colourless oil. δH (250 MHz, CDCl3) 1.50 (9H, s), 2.52-2.64 (2H, m), 3.22-3.38 (2H, m), 4.18 (1H, m), 4.45 (1H, m), 4.83 (1H, m).
Reaction SMILES: Br[C:2]1[C:3]([Cl:10])=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.C([Li])CCC.CN([CH:19]=[O:20])C.O.[Cl-].[NH4+]>C1(C)C=CC=CC=1>[Cl:10][C:3]1[C:2]([CH:19]=[O:20])=[CH:7][CH:6]=[C:5]([O:8][CH3:9])[N:4]=1
Reactant: COc1ccc(Br)c(Cl)n1
Reactant: CN(C)C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc(C=O)c(Cl)n1
Temperature: 25 °C

Procedure:
The 3-bromo-2-chloro-6-methoxy-pyridine (0.50 g, 2.26 mmol) obtained in (19-1) above was dissolved in toluene (dehydrated) (11 mL), and thereafter, n-butyllithium (1.46 mL, 2.3 mmol, 1.57 mmol/L hexane solution) was added dropwise to the solution at −78° C. in an argon atmosphere. The obtained mixture was stirred at the same temperature as described above for 30 minutes, and DMF (1.0 mL) was then added to the reaction solution. The obtained mixture was further stirred for 30 minutes. Thereafter, a saturated ammonium chloride water (20 mL) was slowly added to the reaction solution, and the temperature of the mixture was then increased to room temperature. The mixture was extracted with diethyl ether (20 mL) twice, and organic layers were gathered. The resultant was dried over anhydrous sodium sulfate and was then filtrated, followed by vacuum concentration. The obtained residue was purified by silica gel column chromatography (SiO2 30 g, hexane:ethyl acetate=95:5 to 80:20), so as to obtain 180 mg of 2-chloro-6-methoxy-3-pyridinecarboxaldehyde.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6](Cl)=[O:7])([O-])=O.BrC1C2C(Cl)=NC=NC=2N(C2CCCC2)C=1.[NH2:29][C:30]1[C:31]2[C:38](C(C3C=CC=C(N)C=3)=O)=[CH:37][N:36]([CH:48]3[CH2:52][CH2:51][CH2:50][CH2:49]3)[C:32]=2[N:33]=[CH:34][N:35]=1>>[NH2:29][C:30]1[C:31]2[C:38]([C:6]([C:5]3[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=3[NH2:1])=[O:7])=[CH:37][N:36]([CH:48]3[CH2:52][CH2:51][CH2:50][CH2:49]3)[C:32]=2[N:33]=[CH:34][N:35]=1
Reactant: Nc1cccc(C(=O)c2cn(C3CCCC3)c3ncnc(N)c23)c1
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Agent: Clc1ncnc2c1c(Br)cn2C1CCCC1
Product: Nc1ccccc1C(=O)c1cn(C2CCCC2)c2ncnc(N)c12

Procedure:
The title compound was prepared from 2-Nitrobenzoyl chloride and 5-Bromo-4-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine by procedures analogous to those described for the preparation of (4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(3-amino-phenyl)-methanone. MS: 322.3 (MH+); HPLC Rf: 5.52 min. (HPLC method 4).
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[CH:9]=[C:10]([C:15](=O)[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH:11]=[CH:12][C:13]=1[Cl:14]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.O>[Cl:14][C:13]1[CH:12]=[CH:11][C:10]([C:15]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH2:1])=[CH:9][C:8]=1[Cl:7]
Reactant: CC(C)(C)[O-]
Reactant: COc1ccc(OCC(=O)c2ccc(Cl)c(Cl)c2)cc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C(COc1ccc(OC)cc1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.7 %

Procedure:
To a solution of methyltriphenylphosphonium bromide (60.3 g) in THF (800 mL) was added potassium tert-butoxide (20.7 g), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added dropwise a solution of 1-(3,4-dichlorophenyl)-2-(4-methoxyphenoxy)ethanone (48 g) in THF (400 ml), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The obtained extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (15.1 g).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O:15]=[C:16]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[O:20][C:19]2[CH:27]=[CH:28][C:29]([CH:31]=[O:32])=[CH:30][C:18]=2[NH:17]1>C(#N)C.C(OCC)(=O)C>[CH2:7]([N:17]1[C:16](=[O:15])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[O:20][C:19]2[CH:27]=[CH:28][C:29]([CH:31]=[O:32])=[CH:30][C:18]1=2)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: BrCc1ccccc1
Reactant: O=Cc1ccc2c(c1)NC(=O)c1ccccc1O2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=Cc1ccc2c(c1)N(Cc1ccccc1)C(=O)c1ccccc1O2
Temperature: 25 °C
Yield: 63 %

Procedure:
Potassium carbonate anhydrous (0.207 g, 1.5 mmole) and benzyl bromide (0.205 g, 1.2 mmole) were added to a solution of the 11-oxo-10,11 dihydrodibenzo[b,f][1,4]oxazepine-8-carbaldehyde (0.240 g, 1 mmole) in acetonitrile under N2 at room temperature. The reaction mixture then was refluxed for 4 hours, and cooled to room temperature. Diluted the reaction mixture with ethyl acetate and filtered through a magnesol pad and concentrated. Purified with silica gel column and 50% ethyl acetate in hexane. Obtained the desired compound (light yellow oil) in 63% yield.
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][OH:9])[NH:5][C:4](=[O:6])[CH2:3]1.CO[C:12](OC)([CH3:14])[CH3:13].B(F)(F)F.CCOCC>C(Cl)Cl>[O:6]=[C:4]1[N:5]2[C:2]([CH3:1])([CH2:7][CH2:8][O:9][C:12]2([CH3:14])[CH3:13])[CH2:3]1
Reactant: COC(C)(C)OC
Reactant: CC1(CCO)CC(=O)N1
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: CC12CCOC(C)(C)N1C(=O)C2

Procedure:
A solution of 4-methyl-4-(2-hydroxyethyl)-2-azetidinone (0.016 mole) and 2,2-dimethoxypropane (1.69 g, 0.016 mole) in 25 ml anhydrous methylene chloride is treated with boron trifluoride etherate (0.201 ml, 0.002 mole) at 25° C. The resulting solution is stirred for ten minutes. After removal of the solvent under reduced pressure, chromatography of the crude product on silica gel gives 8-oxo-2,2,6-trimethyl-3-oxa-1-azabicyclo[4.2.0]octane.