Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(=O)(O)[O-].[Na+].[CH:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[C-:16]#[N:17].[Na+].COC(C)(C)C>O>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH:6]([OH:15])[C:16]#[N:17])=[CH:8][CH:9]=1
Reactant: [C-]#N
Reactant: COc1ccc(C=O)cc1
Agent: O=S([O-])O
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: O
Product: COc1ccc(C(O)C#N)cc1
Temperature: 40 °C
Reaction time: 3 h

Procedure:
Water (720 ml), sodium bisulfite (81 g, 0.775 mol, 1.2 equiv) and p-anisaldehyde (88 g, 0.646 mol, 1.0 equiv) are combined, warmed to 40° C. and stirred for 3 hrs. The slurry is cooled to 5° C., and sodium cyanide (35 g, 0.711 mol, 1.1 equiv) in 140 ml water is added. The reaction is stirred for 2 hrs. at 5° C., then warmed to room temperature, and methyl-t-butyl ether (MTBE) (400 ml) added. The layers are separated after a brief stir, and the aqueous phase re-extracted with MTBE (100 ml). The combined organic layers were dried (MgSO4), and concentrated to an oil, which was seeded to afford product: 69.5 g, 65.9%. The material can be recrystallized from toluene (3 ml per g substrate, heat to 35° C., cool to 5° C., 90% recovery).
Reaction SMILES: [CH3:1][NH:2][C@H:3]1[C@H:12]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:11][CH2:10][CH2:9][C:4]21[O:8][CH2:7][CH2:6][O:5]2.C(N(CC)CC)C.[Cl:25][C:26]1[CH:27]=[C:28]([CH2:33][C:34](Cl)=[O:35])[CH:29]=[CH:30][C:31]=1[Cl:32]>C(OCC)C>[ClH:25].[Cl:25][C:26]1[CH:27]=[C:28]([CH2:33][C:34]([N:2]([CH3:1])[C@H:3]2[C@H:12]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:11][CH2:10][CH2:9][C:4]32[O:5][CH2:6][CH2:7][O:8]3)=[O:35])[CH:29]=[CH:30][C:31]=1[Cl:32]
Reactant: CN[C@H]1[C@H](N2CCCC2)CCCC12OCCO2
Reactant: O=C(Cl)Cc1ccc(Cl)c(Cl)c1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CN(C(=O)Cc1ccc(Cl)c(Cl)c1)[C@H]1[C@H](N2CCCC2)CCCC12OCCO2
Product: Cl

Procedure:
To a stirred solution of 0.03 mole of trans-(±)-1-[6-methylamino-1,4-dioxaspiro[4.5]dec-7-yl]pyrrolidine in 200 ml of diethyl ether and 0.036 mole of triethylamine, there is added a solution of 0.036 mole of 3,4-dichlorophenylacetyl chloride in 300 ml of diethyl ether over 30 minutes under nitrogen. After two hours the mixture is filtered and the solid washed with diethyl ether. The combined ethereal layers were washed with water, 10% sodium hydroxide in water solution, water, brine, dried over magnesium sulfate and concentrated in vacuo. The residue is treated with a diethyl ether solution of hydrogen chloride and the resultant precipitate is recrystallized from a methanol/ethyl acetate mixture to give trans-(±)-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)-1,4-dioxaspiro[4.5]-dec-6-y]benzeneacetamide, monohydrochloride.
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[N:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11].C1([CH:24](C)[C:25](OCC)=[O:26])C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-].S(=O)(=O)(O)O.[C:40]1([CH3:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>>[Cl:1][C:2]1[C:25](=[O:26])[CH:24]=[C:46]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[N:4]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[Cl:11])[C:3]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Cc1ccccc1
Reactant: CCOC(=O)C(C)c1ccccc1
Reactant: ClCC(=Nc1ccccc1Cl)c1ccccc1
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [Cl-]
Product: O=c1cc(-c2ccccc2)n(-c2ccccc2Cl)c(-c2ccccc2)c1Cl

Procedure:
To 300 ml of toluene were added 7.4 g (0.030 mole) of 2-chloro-N-(2-chlorophenyl)-1-phenylethaneimine, 5.2 g (0.030 mole) of ethyl phenylpropionate and 6.7 g (0.050 mole) of aluminum chloride. The reaction mixture was then heated under reflux for 20 hours under nitrogen atmosphere. After cooling, the reaction mixture was poured into 500 ml of 2N sulfuric acid, followed by extraction with chloroform. After washing the organic layer with 50 ml of a 10% aqueous solution of sodium hydroxide and then with water, it was dried with anhydrous sodium sulfate. Subsequent to removal of the sodium sulfate, the solvent was distilled off and the residue was purified by chromatography on a silica gel column (eluent: ethyl acetate) to yield 3-chloro-1-(2-chlorophenyl)-2,6-diphenyl-4(1H)-pyridinone having a melting point of 230°-233° C.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12](=[O:20])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:23]I>O1CCCC1>[CH3:23][N:1]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12](=[O:20])[NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: CCCCCCNC(=O)Oc1ccc2c(c1)CCCN2
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCNC(=O)Oc1ccc2c(c1)CCCN2C
Reaction time: 0.33 h

Procedure:
A solution of hexyl-carbamic acid-1, 2, 3, 4-tetrahydro-quinolin-6-yl ester (0.276 g., 1 mmol) in dry tetrahydrofuran (5 ml) was added to a stirred suspension of sodium hydride (0.024 g., 1 mmol) in dry tetrahydrofuran (5 ml) at −10° C. during 5 min. The reaction mixture was stirred for 20 min. Then methyl iodide (0.224 ml, 3.6 mmol) was added to the stirring reaction mixture. Stirring was continued for additional 1.25 hours during which the temperature was allowed to rise to room temperature (34° C.). The reaction mixture was quenched with water (0.2 ml), concentrated under vaccum, diluted with water (5 ml), extracted with chloroform (2×5 ml) and dried over sodium sulphate. The combined fractions of chloroform were concentrated under vaccum. The residue was chromatographed on silica gel using chloroform: hexane (30:70) as eluant to give 2m; yield: 0.15 g. (51.7%).
Reaction SMILES: N[C:2]1[C:3](=[O:20])[NH:4][C:5]([CH3:19])=[C:6]([CH2:17][CH3:18])[C:7]=1[CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[C:11]([CH3:16])[CH:10]=1.C=O.[C:23]([BH3-])#[N:24].[Na+].[C:27](O)(=O)C>C(#N)C>[CH3:27][N:24]([CH3:23])[C:2]1[C:3](=[O:20])[NH:4][C:5]([CH3:19])=[C:6]([CH2:17][CH3:18])[C:7]=1[CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[C:11]([CH3:16])[CH:10]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)O
Reactant: CCc1c(C)[nH]c(=O)c(N)c1Cc1cc(C)cc(C)c1
Agent: C=O
Agent: [Na+]
Solvent: CC#N
Product: CCc1c(C)[nH]c(=O)c(N(C)C)c1Cc1cc(C)cc(C)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91 %

Procedure:
To a stirred solution of 3-amino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one (200 mg) and 37% of aqueous formaldehyde (0.60 mL) in 5 mL of acetonitrile was added 139 mg of sodium cyanoborohydride. Glacial acetic acid (0.07 mL) was added dropwise and the reaction mixture was stirred at room temperature for 2 hours. An additional 0.07 mL of glacial acetic acid was added, and stirring was continued for 30 minutes. The solvent was evaporated and 15 mL ether were added to the resulting residue. The organic layer was washed with 3×30 mL 1N aqueous potassium hydroxide and 3 mL brine, dried over magnesium sulfate and concentrated under reduced pressure to give 3-dimethylamino4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one (200 mg, 91%) mp 229-230° C.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:5][N:4]=1.Cl>>[N:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3](=[O:2])[NH:4][CH:5]=1
Reactant: COc1ccc(-c2ccccn2)cn1
Agent: Cl
Product: O=c1ccc(-c2ccccn2)c[nH]1
Yield: 37 %

Procedure:
A mixture of 2-methoxy-5-pyridin-2-yl-pyridine (550 g) and a 4 mol/L aqueous solution of hydrochloric acid (2.4 L) was heated under reflux for 3 hours. After cooling the reaction solution, and washed with tert-butylmethyl ether (2.2 L). To the aqueous layer was added 8 mol/L aqueous solution of sodium hydroxide (1.1 L) under cooling with ice-water, and then the mixture was washed twice with tert-butylmethyl ether (2.2 L). Then, it was adjusted to pH 8 with concentrated hydrochloric acid (310 ml) and 8 mol/L aqueous solution of sodium hydroxide (100 ml), followed by partitioning between 1-butanol (4.5 L) and brine (1.8 L). The aqueous layer was extracted again with 1-butanol (4.5 L), and the combined organic layer was evaporated at 45-50° C. To the resulting residue was added tert-butylmethyl ether (2.2 L), to give crystals. The resulting crystals were collected by filtration under reduced pressure and air-dried at 60° C. Then, water (1.6 L) was added thereto to dissolve under heating. Then the mixture was water-cooled, and recrystallized. The resulting crystals were collected by filtration under reduced pressure and air-dried at 60° C., to give 188 g (66%) of the title compound as grayish white crystals.
Reaction SMILES: C(O)(=O)C.C(=O)([O-])[O-].[K+:9].[K+].[C:11]([O:22]C1C=CC=CC=1)(=[O:21])[C:12]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:13]>CC(C)=O.O>[C:12]([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:13])[C:11]([O-:22])=[O:21].[K+:9]
Reactant: O=C(Oc1ccccc1)C(=O)Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: O=C([O-])C(=O)Oc1ccccc1
Reaction time: 4 h
Yield: 173.3 %

Procedure:
In a 1,000 mL-volume three-necked flask, 27.3 g of diphenyl oxalate was dissolved in 600 mL of acetone. In the solution, an aqueous solution of 6.76 g of acetic acid and 7.77 g of potassium carbonate in 25 mL of water was dropwise added under stirring for 4 hours. The mixture was then stirred for 2 hours, and the produced precipitate was collected on a filter by suction. The collected precipitate was washed with acetone and dried under reduced pressure to give 19.9 g of potassium phenyl oxalate. These procedures were performed at room temperature.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[ClH:16].[N:17]1(C(=N)N)[CH:21]=[N:20]C=N1.CCOCC>CN(C)C=O>[ClH:16].[N:1]1([C:21](=[NH:17])[NH2:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1CCNCC1
Reactant: N=C(N)n1cncn1
Agent: Cl
Solvent: CCOCC
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: N=C(N)N1CCCCC1
Temperature: 25 °C
Yield: 43.4 %

Procedure:
A mixture of piperidine (4.95 ml, 50 mmol), diisopropylethylamine (8.73 ml, 50.0 mmol) and 1H-1,2,4-triazole-1-carboximidamide hydrochloride (6.11 g, 55.0 mmol) in N,N-dimethylformamide (20 ml) was stirred at room temperature over the weekend. Ether (50 ml) was added to the reaction mixture and the mixture was stirred at room temperature for 10 minutes. The ether layer was separated and DMF layer was stirred with ether (50 ml) at 5° C. (ice water bath) for 10 minutes and the ether layer was separated from the residue. Ether (30 ml) was added to the residue and the mixture was stirred at 5° C. The resulting solid was triturated with ether, collected, washed with ether and dried to give the title compound as a colourless solid (3.55 g, 43%). LC/MS [M+H]+=128.
Reaction SMILES: CCN(C1C=C[C:9]2[C:12]([C:25]3C(C(O)=O)=CC=CC=3)=[C:13]3[C:23]([O:24][C:8]=2C=1)=[CH:22][C:16](=[N+](CC)CC)[CH:15]=[CH:14]3)CC.[Cl-].[OH:35][CH2:36][CH:37](CO)[OH:38].[CH2:41](O)COCCO>O>[CH2:23]([O:24][CH2:8][CH2:9][O:35][CH2:36][CH2:37][OH:38])[CH2:13][CH2:14][CH3:15].[CH3:25][CH:12]([CH2:13][C:23]([OH:24])([C:22]#[CH:16])[CH3:41])[CH3:9]
Reactant: CCN(CC)c1ccc2c(-c3ccccc3C(=O)O)c3ccc(=[N+](CC)CC)cc-3oc2c1
Reactant: OCCOCCO
Reactant: OCC(O)CO
Agent: [Cl-]
Solvent: O
Product: C#CC(C)(O)CC(C)C
Product: CCCCOCCOCCO
Reaction time: 2 h

Procedure:
A solution containing 2.50 g Kayacryl Rhodamine FB (Product Name, Nippon Kayaku, C.I. Acid Red 52), 0.06 g LM pectin (Product Name: LM-104AS, The Copenhagen Pectin Factory Ltd.), 5.00 g of glycerol, 5.00 g of diethylene glycol, 8.00 g diethylene glycol mono-n-butyl ether, 0.80 g of Surfynol 465, and 78.64 g of ultrapure water was prepared. The solution was stirred for 2 hours and then filtered through a 5 μm stainless steel mesh.
Reaction SMILES: [N:1]1[C:6]2[O:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[C:5]=2[CH:4]=[CH:3][N:2]=1.[H-].[Na+].[CH2:16]([CH:18]1[O:20][CH2:19]1)Br.[OH-].[Na+].CN(C)[CH:25]=[O:26]>O.CO>[O:20]1[CH2:19][CH:18]1[CH2:16][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:5]1[CH:4]=[CH:3][N:2]=[N:1][C:6]=1[O:26][CH3:25]
Reactant: c1ccc2c(c1)oc1nnccc12
Reactant: CN(C)C=O
Reactant: BrCC1CO1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1nnccc1-c1ccccc1OCC1CO1
Temperature: 70 °C
Reaction time: 2.5 h

Procedure:
To a stirred solution of benzofuro[2,3-c]pyridazine (5.09 g) in dimethylformamide (40 ml) containing a suspension of sodium hydride (1.68 g, 50% oil) was added dry methanol (1.5 ml). The mixture was heated to 70° C. for 30 minutes and treated with epibromohydrin (10.2 ml) and stirring was continued at room temperature for 150 minutes. The mixture was poured into water (300 ml), taken to pH 10 with sodium hydroxide, extracted into dichloromethane and the organic extract was evaporated under reduced pressure to afford an oil that was purified by column chromatography (silica, chloroformpetrol, chloroform, chloroform-methanol) to afford 4-[2-(2,3-epoxypropoxy)phenyl]-3-methoxypyridazine as an oil. This was heated under reflux for 60 minutes with t-butylamine (20 ml) in methanol (50 ml) and the mixture was allowed to stand overnight. Evaporation under reduced pressure afford an oil which on treat ment with diethyl ether-petrol gave 4-(2-[3-t-butylamino-2-hydroxypropoxy)phenyl]-3-methoxypyridazine, m.p. 109.5°-110.5° C. from cyclohexane.
Reaction SMILES: [CH:1](=O)[CH3:2].[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:35])[C:11]2[O:17][C:16]3[C:18]([Cl:31])=[CH:19][C:20]([NH:22][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:21][C:15]=3[CH2:14][S:13](=[O:33])(=[O:32])[C:12]=2[CH:34]=1)=[O:7].FC(F)(F)C(O)=O.C([BH3-])#N.[Na+]>CO>[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:35])[C:11]2[O:17][C:16]3[C:18]([Cl:31])=[CH:19][C:20]([N:22]([CH2:1][CH3:2])[CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:21][C:15]=3[CH2:14][S:13](=[O:33])(=[O:32])[C:12]=2[CH:34]=1)=[O:7]
Reactant: CC=O
Reactant: COC(=O)c1cc(C)c2c(c1)S(=O)(=O)Cc1cc(NCCN3CCOCC3)cc(Cl)c1O2
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: CCN(CCN1CCOCC1)c1cc(Cl)c2c(c1)CS(=O)(=O)c1cc(C(=O)OC)cc(C)c1O2
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Acetaldehyde (0.21 mL, 3.80 mmole) was added to a solution of Example 66k (0.370 gm, 0.76 mmol) in dry methanol (15 mL) followed by the addition of trifluoro-acetic acid (0.06 mL, 0.76 mmol). The reaction mixture was stirred at 0° C. for 2 h, allowed to come to room temperature, treated with sodium cyanoborohydride (0.119 g, 1.9 mmol), and stirred overnight. It was concentrated, treated with 10% aqueous sodium bicarbonate solution, water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, methanol/chloroform) to obtain the title compound as a white solid. Yield: 0.3 g, (76.72%); 1H NMR (CDCl3): δ 2.15 (t, 3H, CH3), 2.45-2.55 (m, 6H, 3CH2), 2.70 (s, 3H, CH3), 3.40 (q, 2H, CH2), 3.50 (t, 2H, CH2), 3.70-3.80 (m, 4H, CH2), 3.95 (s, 3H, OCH3), 4.70 (s, 2H, CH2), 6.55 (s, 1H, Ar), 6.70 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.45 (s, 1H, Ar); MS: m/e (CI+) 511 (M−CH3).
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12](=[O:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:17])[C:4]=2[CH:3]=1.[H-].[Na+].[CH2:20]([CH:22]1[O:24][CH2:23]1)Cl.O>CN1CCCC1=O>[CH2:20]([O:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12](=[O:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:17])[C:4]=2[CH:3]=1)[CH:22]1[O:24][CH2:23]1
Reactant: O=C1c2ccccc2C(=O)c2cc(O)ccc21
Reactant: ClCC1CO1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: O=C1c2ccccc2C(=O)c2cc(OCC3CO3)ccc21
Temperature: 0 °C
Reaction time: 8 h
Yield: 49.6 %

Procedure:
112.1 g (0.5 mole) of 2-hydroxyanthraquinone are dissolved in 500 ml of N-methylpyrrolidone, and 12 g (0.5 mole) of sodium hydride are added in portions. When the evolution of gas has ended, 46.37 ml (0.5 mole) of epichlorohydrin are added dropwise at 70° C. and stirring is continued at 70° C. for a further 8 hours. 1.5 liters of water are then added, the mixture is filtered and the filter cake is dried in vacuo. After drying, the product is boiled up again in 1 liter of N,N-dimethylformamide with 10 g of active charcoal and filtered hot. The crystals which precipitate on cooling to 0° C. are separated off by filtration and dried under a high vacuum. 69.45 g (50.57% of theory) of 2-anthraquinonyl glycidyl ether are obtained;
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[CH3:13][NH:14][O:15][CH3:16].OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([N:14]([O:15][CH3:16])[CH3:13])=[O:5]
Reactant: CNOC
Reactant: O=C(O)c1cc(F)ccc1Br
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)c1cc(F)ccc1Br
Temperature: 25 °C
Reaction time: 5.5 h

Procedure:
To a suspension of 2-bromo-5-fluorobenzoic acid (2.0 g, 9.13 mmol) in DCM (90 mL) at room temperature was added N,O-dimethylhydroxylamine hydrochloride (1.069 g, 10.96 mmol), N-(3-dimethylaminopropyl)-K-ethylcarbodiimide hydrochloride (2.276 g, 11.87 mmol), hydroxybenzotriazole (1.818 g, 11.87 mmol) and triethylamine (2.55 mL, 18.26 mmol). The resulting mixture was stirred at room temperature for 5.5 h after which time the reaction was quenched by addition of sat. aq. NaHCO3 solution and the layers separated. The organic layer was then washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography (SiO2, 0-40% EtOAc/Hexanes) to afford 2-bromo-5-fluoro-N-methoxy-N-methylbenzamide as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (dd, J=8.8, 4.9 Hz, 1H), 7.05 (dd, J=8.2, 3.0 Hz, 1H), 7.00 (td, J=8.4, 3.0 Hz, 1H), 3.50 (s, 2H), 3.38 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:18])[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[CH2:11].[NH:19]1[CH:23]=[CH:22][N:21]=[CH:20]1.CN(C)C(=N)N(C)C>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:18])[CH:10]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:11][N:19]1[CH:23]=[CH:22][N:21]=[CH:20]1
Reactant: c1c[nH]cn1
Reactant: C=C(C(=O)c1ccc(Cl)cc1Cl)c1ccccc1
Agent: CN(C)C(=N)N(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C(c1ccc(Cl)cc1Cl)C(Cn1ccnc1)c1ccccc1
Yield: 12 %

Procedure:
A solution of 1-(2,4-dichlorophenyl)-2-phenylpropen-1-one (4 g), imidazole (1.36 g) and tetramethylguanidine (0.5 ml) in tetrahydrofuran (100 ml) was heated at reflux for 12 hours. The reaction mixture was cooled and concentrated under reduced pressure to yield a gum. The gum was dissolved in ethyl acetate, washed with distilled water, and acidified with 4N hydrochloric acid. The resulting aqueous phase was basified with sodium hydrogen carbonate and extracted with ethyl acetate. The organic phase was separated, washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to yield an oil which was chromatographed on silica gel in methanol/dichloromethane (1:9) to yield 1-(2,4-dichlorophenyl)-3-(imidazol-1-yl)-2-phenylpropan-1-one (600 mg), which was treated with ethereal hydrogen chloride to yield the hydrochloride salt of 1-(2,4-dichlorophenyl)-3-(imidazol-1-yl)-2-phenylpropan-1-one, m.p. 110° C., (Found: C, 55.38; H, 4.37; N, 7.40; C18H15Cl3N2O.1/2H2O requires C, 55.34; H, 4.13; N, 7.17) having the formula: ##STR12##
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[Cl-].[CH3:12][C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][CH:22]=1)[CH:16]=[N+:17]([CH3:19])[CH3:18].CC1C=C(C=CC=1)C=O.CNC>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:16]([N:17]([CH3:18])[CH3:19])[C:15]1[CH:14]=[C:13]([CH3:12])[CH:22]=[CH:21][CH:20]=1
Reactant: Clc1ccc2[nH]ccc2c1
Reactant: Cc1cccc(C=[N+](C)C)c1
Agent: CNC
Agent: Cc1cccc(C=O)c1
Agent: [Cl-]
Product: Cc1cccc(C(c2c[nH]c3ccc(Cl)cc23)N(C)C)c1

Procedure:
The preparation was carried out in accordance with general synthesis instructions 4 from 5-chloro-1H-indole and (3-methyl-benzylidene)-dimethylammonium chloride, which had been prepared in accordance with example 44 from 3-methyl-benzaldehyde and dimethylamine.
Reaction SMILES: C[N:2](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:27][CH:28]1[C:36]2[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:34][CH:33]=[N:32][C:31]=2[CH2:30][S:29]1.C(OC([C:50]1([CH2:53][CH:54]([C:58]2[CH:63]=[CH:62][C:61]([Cl:64])=[CH:60][CH:59]=2)[C:55](O)=[O:56])[CH2:52][CH2:51]1)=O)(C)(C)C>C(Cl)Cl>[NH2:2][C:50]1([CH2:53][CH:54]([C:58]2[CH:63]=[CH:62][C:61]([Cl:64])=[CH:60][CH:59]=2)[C:55]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[C:36]4[CH:28]([CH3:27])[S:29][CH2:30][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38][CH2:39]2)=[O:56])[CH2:52][CH2:51]1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CC(C)(C)OC(=O)C1(CC(C(=O)O)c2ccc(Cl)cc2)CC1
Reactant: CC1SCc2ncnc(N3CCNCC3)c21
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Product: CC1SCc2ncnc(N3CCN(C(=O)C(CC4(N)CC4)c4ccc(Cl)cc4)CC3)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 80.9 %

Procedure:
HBTU (0.031 g, 0.081 mmol) was added to a solution of 5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (0.025 g, 0.081 mmol) and 3-(1-(tert-butoxycarbonyl)cyclopropyl)-2-(4-chlorophenyl)propanoic acid (0.027 g, 0.081 mmol) in DCM (5 mL) and TEA (1 mL). The mixture was stirred at room temperature for 1 hour. The solvent was removed, and the residue was subject to column chromatography, eluted by DCM/MeOH (50:1) to give 3-(1-aminocyclopropyl)-2-(4-chlorophenyl)-1-(4-(5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one (30 mg, 81%). LCMS (APCI+) [M+H]+ 558.1; Rf: 3.35 min.
Reaction SMILES: Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=1.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([N:48]([CH3:50])[CH3:49])=[C:44]([NH2:47])[CH:45]=2)[CH2:40][CH2:39]1)=[O:37])[CH3:34].[OH-].[NH4+:52]>>[CH3:49][N:48]([CH3:50])[C:43]1[CH:42]=[C:41]2[C:46](=[CH:45][C:44]=1[NH:47][C:3]1[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]3=[C:7]([NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=3[C:15]([NH2:52])=[O:17])[N:16]=1)[N:38]([C:36](=[O:37])[CH2:35][N:33]([CH3:32])[CH3:34])[CH2:39][CH2:40]2
Reactant: [NH4+]
Reactant: CN(C)CC(=O)N1CCc2cc(N(C)C)c(N)cc21
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c2nc(Cl)n2c(=O)c4c(F)cccc4nc32)cc1
Agent: Cl
Agent: [OH-]
Product: CN(C)CC(=O)N1CCc2cc(N(C)C)c(Nc3nc(Nc4cccc(F)c4C(N)=O)c4ccnc-4[nH]3)cc21
Yield: 45 %

Procedure:
In a manner analogous to a procedure outlined previously , 2-[(2-{[5-(dimethylamino)-1-(N,N-dimethylglycyl)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide was prepared from 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrochloride, 1-[(dimethylamino)acetyl]-N5,N5-dimethyl-2,3-dihydro-1H-indole-5,6-diamine, and ammonium hydroxide to afford the title compound (0.20 g, 45% over 3 steps). ESIMS (M+H)+=532. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.21-2.28 (m, 6 H) 2.54-2.62 (m, 6 H) 3.03-3.12 (m, 2 H) 3.18 (s, 2 H) 4.17 (t, J=8.33 Hz, 2 H) 6.24-6.27 (m, 1 H) 6.85-6.90 (m, 1 H) 6.96-6.99 (m, 1 H) 7.06 (s, 1 H) 7.31-7.40 (m, 1 H) 7.67 (s, 1 H) 8.03 (br. s., 1 H) 8.11 (s, 1 H) 8.51 (d, J=8.23 Hz, 1 H) 8.77 (s, 1 H) 10.54 (s, 1 H) 11.32 (s, 1 H).