Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:4]1[N:5]([NH:17]C(=O)OC(C)(C)C)[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].Cl>C(O)C.C(OCC)C>[CH2:1]([C:4]1[N:5]([NH2:17])[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc2cnc3ccccc3c2n1NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOCC
Solvent: CCO
Product: CCCc1nc2cnc3ccccc3c2n1N
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.4 %

Procedure:
A solution of tert-butyl (2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)carbamate (7.23 g, 22.2 mmol) in 40 mL of ethanol was treated with HCl (37 mL, 111 mmol, 3 M in ethanol) and heated to reflux. After 1 h, the reaction mixture was cooled to ambient temperature, diluted with 80 mL of diethyl ether, and cooled in an ice water bath. The HCl salt of the product was collected by vacuum filtration and rinsed with diethyl ether until the filtrate ran clear. The dried HCl salt was dissolved in 75 mL of water and treated with 50% NaOH solution until the pH of the water was 12–13. The free base of the product precipitated out and was triturated in the basic water for 30 min while being cooled in an ice water bath. The solid was collected by vacuum filtration and dried under vacuum to give 4.64 g of 2-propyl-1H-imidazo[4,5-c]quinolin-1-amine as a tan granular solid.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:3]=1[C:4]#[N:5].[Cl:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1>>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:11])[CH:17]=2)=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: OB(O)c1cccc(Cl)c1
Reactant: N#Cc1cc(Br)ccc1N
Product: N#Cc1cc(-c2cccc(Cl)c2)ccc1N

Procedure:
Prepared from 2-amino-5-bromobenzonitrile and 3-chlorophenyl boronic acid according to procedure A. Off-white solid: mp 118-119° C.; 1H-NMR (DMSO-d6) δ7.80 (d, 1H, J=2.3 Hz), 7.65-7.72 (m, 2H), 7.57 (d, 1H, J=8.0 Hz), 7.42 (t, 1H, J=7.9 Hz), 7.31 (m, 1H), 6.87 (d, 1H, J=8.7 Hz), 6.29 (br, 2H); Anal. Calc. For C13H9ClN2: C, 68.28, H, 3.97, N, 12.25. Found: C, 67.68, H, 4.06, N, 11.89.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(OCC)(=O)C.CCCCCC>[CH3:1][N:2]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CNc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CN(CCc1ccccc1)c1ccccc1
Yield: 53 %

Procedure:
According to GWM, 0.011 mol (=1.20 ml) of N-methylaniline and 0.011 mol (=1.00 ml) of styrene are reacted with one another. The product is isolated by column chromatography using ethyl acetate/n-hexane (1:3) as eluent, the product N-methyl-N-phenylethylaniline being obtained as a yellow liquid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1.Cl[CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17].CC(C)([O-])C.[K+]>CS(C)=O>[CH3:1][O:2][C:3]1[N:4]=[C:5]([CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]
Reactant: COc1ncccc1[N+](=O)[O-]
Reactant: CCOP(=O)(CCl)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCOP(=O)(Cc1ccc([N+](=O)[O-])c(OC)n1)OCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 5.5 %

Procedure:
A solution of 2-methoxy-3-nitropyridine (6.92 g, 44.9 mmol) and diethyl chloromethylphosphonate (7.00 mL, 44.9 mmol) in 40 mL DMSO was added drop wise to a stirred mixture of potassium tert-butoxide (15.1 g, 134.6 mmol) and 40 mL DMSO. The mixture was stirred at room temperature for 30 minutes, after which, it was poured into a 1N HCl/ice mixture and extracted with methylene chloride. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (DCM:EtOAc1:1). The slower eluting regioisomer was collected and confirmed to be the desired product (750 mg, 5.5% yield). MS (ES+): m/z 305.16 (100) [MH+]; HPLC: tR=1.16 min (UPLC, Analytical).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][CH:10]2[C:13]([OH:15])=O)=[CH:5][CH:4]=1.[CH:16]([C:19]1[CH:24]=[CH:23][C:22]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)([CH3:18])[CH3:17]>>[CH:16]([C:19]1[CH:24]=[CH:23][C:22]([N:25]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=2)[C:13]([CH:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[CH2:7][CH2:8][CH2:9]2)=[O:15])=[CH:21][CH:20]=1)([CH3:18])[CH3:17]
Reactant: COc1ccc2c(c1)C(C(=O)O)CCC2
Reactant: CC(C)c1ccc(NCc2ccc(N3CCCC3)cc2)cc1
Product: COc1ccc2c(c1)C(C(=O)N(Cc1ccc(N3CCCC3)cc1)c1ccc(C(C)C)cc1)CCC2
Yield: 32.9 %

Procedure:
By the reaction and treatment in the same manner as in Example 12 using 7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (0.39 g) and (4-isopropylphenyl) [(4-pyrrolidinophenyl)methyl]amine (0.56 g) as starting materials, N-(4-isopropylphenyl)-7-methoxy-N-[(4-pyrrolidinophenyl)methyl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.3 g) was obtained.
Reaction SMILES: [C:1]1([C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:22]([CH2:24][NH2:25])[OH:23].O>N1C=CC=CC=1>[C:1]1([C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:23][CH2:22][CH2:24][NH2:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: NCCO
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: NCCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 28.5 %

Procedure:
Triphenylchloromethane (1.00 g, 3.58 mmol) (Wako Pure Chemical Industries, Ltd.) and ethanolamine hydrochloride (1.00 g, 10.3 mmol) (Wako Pure Chemical Industries, Ltd.) were dissolved in pyridine (4 mL), and the solution was stirred at room temperature for 3 days. Water (200 mL) was poured into the reaction solution, and the precipitates were suction-filtered. The solid matters were suspended in diethyl ether, and 3 (N) hydrochloric acid (Wako Pure Chemical Industries, Ltd.) was added thereto, followed by stirring at room temperature for 15 minutes. The insoluble matters were suction-filtered. The insoluble matters were dissolved in a mixed solution of ethyl acetate (Wako Pure Chemical Industries, Ltd.) and a saturated aqueous solution of sodium hydrogen carbonate (Wako Pure Chemical Industries, Ltd.), and the mixture was shaken, followed by the separation of the organic layer. The organic layer was dried with anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.), and then suction-filtered and concentrated under reduced pressure, to thereby obtain the title compound (0.31 g, 28% yield).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:13]I>O1CCCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([CH3:13])[C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CI
Reactant: N#CCc1cccc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C#N)c1cccc(Br)c1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 54.9 %

Procedure:
To a solution of 3-bromophenylacetonitrile (12 g, 61.2 mmol) in tetrahydrofuran (150 ml) cooled down to 0° C., was added 60% sodium hydride in mineral oil (2.25 g, 56.3 mmol) portionwise over 10 minutes. The reaction mixture was stirred at 0° C. for 40 minutes. Methyl iodide (5.71 ml, 91.8 mmol) was added dropwise at 0° C. and the reaction mixture was stirred at 0° C. for a further 1 hour. The reaction mixture was diluted with ethyl acetate (250 ml), washed with water and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion, 330 g column, 0-20% EtOAc/Petrol) to afford the title compound as a colourless oil (7.06 g, 55% yield).
Reaction SMILES: O=[CH:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[C:17]1([C@@H:23]2[CH2:25][C@H:24]2[NH2:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:17]1([C@@H:23]2[CH2:25][C@H:24]2[NH:26][CH2:2][CH2:3][CH:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(C)(C)OC(=O)N1CCC(CC=O)CC1
Reactant: N[C@@H]1C[C@H]1c1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(CCN[C@@H]2C[C@H]2c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.5 %

Procedure:
To a solution of tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (1 g, 4.40 mmol) in methanol (15 mL) were added (trans)-2-phenylcyclopropanamine (0.762 g, 5.72 mmol) and acetic acid (0.252 mL, 4.40 mmol), and the mixture was stirred at room temperature for 1 h. Sodium cyanoborohydride (0.415 g, 6.60 mmol) was added and the mixture was stirred at room temperature for 18 h. The reaction was quenched with water (10 mL) and the mixture was concentrated to remove methanol. The resulting aqueous layer was extracted with DCM (3×). The DCM extract was washed with 10% HOAc aqueous solution, dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 100% EtOAc/hexanes) to give 720 mg of product as pale yellow oil. MS: (M+H)+=345.4. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.94-1.75 (m, 18H), 1.86-1.95 (m, 1H), 2.35 (dt, J=7.01, 3.69 Hz, 1H), 2.60-2.86 (m, 4H), 4.08 (br. s., 2H), 6.91-7.38 (m, 5H).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27].[CH2:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][NH:29]1>CN(C=O)C>[CH2:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][N:29]1[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27]
Reactant: c1ccc2c(c1)CNC2
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCBr)c(C)c3)nc2c1
Solvent: CN(C)C=O
Product: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCN4Cc5ccccc5C4)c(C)c3)nc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a suspension of 2-[4-(2-bromoethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.50 g, 1.15 mmol) in anhydrous DMF (9 mL) was added isoindoline (0.41 mL, 3.46 mmol) and the reaction mixture was stirred at room temperature for 16 hours under nitrogen. The solvent was removed under reduced pressure and the residue was triturated with water (50 mL). The separated solid was filtered, washed with water and ether, and dried under vacuum to give the title compound as a white solid. Yield: 0.45 g (83%). MP 202-202.5° C. 1H NMR (400 MHz, CDCl3): δ 10.09 (br s, 1H), 7.77 (s, 2H), 7.22 (br s, 4H), 6.83 (d, J=2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 4.11 (s, 4H), 4.03 (t, J=6.0 Hz, 2H), 3.96 (s, 3H), 3.93 (s, 3H), 3.22 (t, J=6.0 Hz, 2H), 2.42 (s, 6H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[ClH:10].[Cl:11]N1C(=O)CCC1=O>C(OCC)C.C(O)(=O)C>[ClH:11].[Cl:10][CH2:2][C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)=[O:3]
Reactant: CC(=O)c1cccnc1
Reactant: O=C1CCC(=O)N1Cl
Agent: Cl
Solvent: CC(=O)O
Solvent: CCOCC
Product: O=C(CCl)c1cccnc1

Procedure:
To a solution of 100 g (0.83 moles) of 3-acetylpyridine in diethyl ether (1 L) was added of 1 M hydrogen chloride in ether (950 mL) with rapid stirring. The precipitated solids were filtered, washed with ether and dried. The hydrochloride salt (129 g, 0.83 moles) was added to a 5 L reactor equipped with a mechanical stirrer and dissolved with 1 M hydrogen chloride in acetic acid (830 mL). The mixture was stirred until a clear solution was obtained. N-chlorosuccinimide (111 g, 0.83 moles) was added, and a yellow mixture resulted. The solution was stirred at room temperature for 18 hours, gradually becoming a colorless suspension. The solids were collected by filtration and washed with ether. The filtrate was treated overnight with 80 g of N-chlorosuccinimide and additional product was collected to give a combined yield of 152 g. 1H NMR (DMSO-d6) δ 10.3 (br s, 1 H), 9.27 (s, 1 H), 8.96 (d, J=5.1 Hz, 1 H), 8.62 (d, J=9.9 Hz, 1 H), 7.89 (m, 1 H), 5.30 (s, 2 H); MS (EI) m/z 155 (M+).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.[NH:37]1[CH2:43][CH2:42][CH2:41][C@H:38]1[CH2:39][OH:40]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([N:37]1[CH2:43][CH2:42][CH2:41][C@H:38]1[CH:39]=[O:40])=[O:13])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: OC[C@@H]1CCCN1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1CCC(=O)N1O
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C=O
Temperature: 4 °C
Reaction time: 21 h

Procedure:
In 200 ml of THF was dissolved 22.1 g of t-butyloxycarbonylalanine. To this solution were added under cooling with edible salt and ice 11.5 g of HOSu and 20.6 g of DCC, and the mixture was stirred for 21 hours at 4° C. The reaction liquid was filtered and the filtrate was evaporated whereby a semi-solid substance was obtained. This substance was recrystallized from chloroform to obtain a white solid substance which was then dissolved in 400 ml of THF. To this solution was added 7.5 g of L-prolinol, and the mixture was stirred for 72 hours at room temperature. After removal of THF by distillation, the residue was dissolved in 300 ml of ethyl acetate and the solution was washed with 100 ml of 1-M Na2CO3, dehydrated with anhydrous Na2SO4 and evaporated until dryness. To the resultant oily substance were added 32.5 g of WSCD.HCl and 130 ml of redistilled DMSO, and the mixture was stirred for 10 minutes. Subsequently, 6 ml of DMSO solution of 2-M anhydrous H3PO4 was added and the mixture was stirred for further 2 hours. The reaction was stopped with 300 ml of a buffer solution of 1-M potassium phosphate of pH 7.5. The reaction mixture was extracted with 250 ml of ethyl acetate, and the extract was dried over anhydrous Na2SO4. The ethyl acetate was distilled off and the residue was dissolved in 250 ml of ethanol. To this solution was added 200 g of NaHSO3 in 350 ml of water, and the mixture was stirred vigorously for 10 minutes. After concentration of the ethanol up to about 350 ml, unreacted materials were eliminated twice with 100 ml of ether, and solid Na2CO3 was added until the pH value of the liquid became 9. After 5 minutes, the reaction liquid was extracted twice with 100 ml of ether, and the ether was then distilled off to leave an oily substance. Yield 1.2 g (4.5%).
Reaction SMILES: [C:1]([S:14]([NH2:17])(=[O:16])=[O:15])([C:4]([C:7]([C:10]([F:13])([F:12])[F:11])([F:9])[F:8])([F:6])[F:5])([F:3])[F:2].[OH-].[Na+].Cl[CH2:21][C:22]([O:24][Na:25])=[O:23]>O>[C:1]([S:14]([NH:17][CH2:21][C:22]([O:24][Na:25])=[O:23])(=[O:16])=[O:15])([C:4]([C:7]([C:10]([F:13])([F:11])[F:12])([F:9])[F:8])([F:6])[F:5])([F:3])[F:2]
Reactant: O=C(CCl)O[Na]
Reactant: NS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(CNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)O[Na]
Temperature: 98 °C
Yield: 70 %

Procedure:
A 1 L 3-necked round bottom flask equipped with a mechanical stirrer, thermocouple, reflux condenser and heating mantle was charged with C4F9SO2NH2 (58 g; 0.20 moles; as prepared above), NaOH (8.7 g; 0.22 moles; pellets) and water (60 mL) and heated at 98° C. for 45 minutes. Upon cooling to 76° C., ClCH2CO2Na (25 g; 0.22 moles, Sigma-Aldrich) was added and the temperature was then increased to 100° C. and maintained for 18 hours. Water was then added (200 mL) and a white solid appeared. The upper liquid phase was decanted off and discarded leaving the white solid, to which water (250 mL) was added. Water was removed to yield C4F9SO2N(H)CH2CO2Na (53.1 g ; 74% yield).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:10])[C:6]=1[C:7](=[O:9])[CH3:8].[CH3:11][C:12]([CH3:14])=O.O>Br.C(O)(=O)C>[CH3:1][C:2]1[NH:3][C:4]([CH:12]([CH3:14])[CH3:11])=[C:5]([CH3:10])[C:6]=1[C:7](=[O:9])[CH3:8]
Reactant: CC(=O)c1c(C)c[nH]c1C
Reactant: CC(C)=O
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: CC(=O)c1c(C)[nH]c(C(C)C)c1C
Temperature: 30 °C
Reaction time: 2 h

Procedure:
Anhydrous stannous bromide (5g) was stirred to solution in 20 ml of hydrogen bromide in acetic acid (30-32 %). 2,4-Dimethyl-3-acetyl-pyrrole (548 mg) was added and the mixture was warmed to dissolve this, then cooled to 30° C. Acetone(0.6 ml) was added and the solution was stirred at 35° C. for 21/2 hrs then poured into water at 10° C. The product was separated and washed with dilute hydrochloric acid then with water. It formed colourless micro-prisms (549 mg. 77%), m.p. 166°-167° C. or 173-174.5° C. after changing to cubes at about 136° C. For analysis it was recrystallized from aqueous ethanol as prismatic rods, m.p. 172° C.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:15]=[C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:17]=1[OH:18])[C:8]([C:10]1[CH:14]=[CH:13][NH:12][CH:11]=1)=[O:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:25](Br)[CH2:26][CH2:27][CH3:28]>CN(C)C=O>[CH2:25]([N:12]1[CH:13]=[CH:14][C:10]([C:8](=[O:9])[C:7]2[CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:17]([OH:18])=[C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:15]=2)=[CH:11]1)[CH2:26][CH2:27][CH3:28]
Reactant: CCCCBr
Reactant: CC(C)(C)c1cc(C(=O)c2cc[nH]c2)cc(C(C)(C)C)c1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCn1ccc(C(=O)c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)c1
Reaction time: 1 h

Procedure:
2 G (6.6 mmol) of 3-(3,5-di-t-butyl-4-hydroxybenzoyl)pyrrole were added to a cooled, stirred suspension of 0.69 g of sodium hydride (50% in mineral oil) in 50 ml of anhydrous dimethylformamide under nitrogen. After 1 hour at 20° C., 0.8 ml of n-butyl bromide was added. Stirring was continued for an additional 18 hours at room temperature. The reaction mixture was poured over a 10% HCl--ice mixture, then extracted three times with 250 ml ethyl acetate. The organic layer was washed five times with 200 ml water, dried and evaporated to dryness. The residue was purified on a silica column (200 g) eluting with hexane:ethyl acetate (9:1). Crystallization from acetone-hexane gave 1.52 g of N-n-butyl-3-(3,5-di-t-butyl-4-hydroxybenzoyl)pyrrole (mp 101°-103° C.).
Reaction SMILES: [H-].[Na+].[CH2:3]([C:7]1[C:11]([CH2:12][OH:13])=[C:10]([CH3:14])[O:9][N:8]=1)[CH2:4][CH2:5][CH3:6].[CH:15]([NH:18][C:19]([C:21]1[S:25][C:24](Cl)=[N:23][CH:22]=1)=[O:20])([CH3:17])[CH3:16].O>C1COCC1>[CH:15]([NH:18][C:19]([C:21]1[S:25][C:24]([O:13][CH2:12][C:11]2[C:7]([CH2:3][CH2:4][CH2:5][CH3:6])=[N:8][O:9][C:10]=2[CH3:14])=[N:23][CH:22]=1)=[O:20])([CH3:17])[CH3:16]
Reactant: CCCCc1noc(C)c1CO
Reactant: CC(C)NC(=O)c1cnc(Cl)s1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCc1noc(C)c1COc1ncc(C(=O)NC(C)C)s1
Temperature: 0 °C
Reaction time: 1 h
Yield: 43 %

Procedure:
To a suspension of NaH (55%, 58 mg, 2.4 mmol) in THF (3 mL) at 0° C., was added a solution of (3-butyl-5-methyl-isoxazol-4-yl)-methanol (169 mg, 1.0 mmol) in THF (3 mL) dropwise. The resulting mixture was stirred for 1 h and then cooled to 0° C. and then a solution of 2-chloro-thiazole-5-carboxylic acid isopropylamide (205 mg, 1.0 mmol) in THF (3 mL) added dropwise and the resulting mixture stirred at room temperature overnight. Water was then added and the resulting mixture extracted with ethyl acetate. The combined organic extracts were dried, filtered and concentrated. Purification by chromatography (silica, 0 to 30% methanol in dichloromethane, then 0 to 60% ethyl acetate in heptane) gave the title compound (145 mg, 43%) as a white solid. MS: m/e=338.4 [M+H]+.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[O:13]1[C:18]2[CH:19]=[CH:20][C:21]([CH:23]=O)=[CH:22][C:17]=2[O:16][CH2:15][CH2:14]1.C(O)(C(F)(F)F)=O>>[O:13]1[C:18]2[CH:19]=[CH:20][C:21]([CH:23]3[C:5]4[NH:6][C:7]5[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=5)[C:4]=4[CH2:3][CH2:2][NH:1]3)=[CH:22][C:17]=2[O:16][CH2:15][CH2:14]1
Reactant: O=Cc1ccc2c(c1)OCCO2
Reactant: NCCc1c[nH]c2ccccc12
Solvent: O=C(O)C(F)(F)F
Product: c1ccc2c3c([nH]c2c1)C(c1ccc2c(c1)OCCO2)NCC3
Yield: 75 %

Procedure:
This product was prepared using the same procedure as for Intermediate 1 with tryptamine (4.92 g, 30.7 mmol), 2,3-dihydrobenzo[1,4]dioxin-6-carboxaldehyde (5.05 g, 1.0 equiv.) and TFA (5.0 mL, 2 equiv.) to give the title compound (7.05 g, 75%) as white crystals after recrystallization from iPr2O. MP: 144° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.CC(C)([O-])C.[K+]>CN(C)C=O.O1CCCC1>[N+:12]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][CH:3]=[C:2]2[O:22][C:19]1[CH:20]=[CH:21][C:16]([NH2:15])=[CH:17][CH:18]=1)([O-:14])=[O:13]
Reactant: Nc1ccc(O)cc1
Reactant: O=[N+]([O-])c1cccc2c(Cl)ccnc12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: Nc1ccc(Oc2ccnc3c([N+](=O)[O-])cccc23)cc1
Temperature: 110 °C
Reaction time: 7 h
Yield: 58.8 %

Procedure:
4-Chloro-8-nitroquinoline (176 mg, 0.85 mmol) and 4-aminophenol (93 mg, 0.85 mmol) were dissolved in dimethylformamide, and to which 1.0 M potassium tert-butoxide (0.95 mL) in tetrahydrofuran was slowly added dropwise at room temperature, which was then heated and stirred at 110° C. for seven hours. When the reaction was completed, the resultant was extracted with ethyl acetate and aqueous sodium chloride, and the combined organic layers were dried with anhydrous sodium sulfate, and then filtered. The solvent was removed by vacuum distillation, and the residue was purified by a column chromatography (ethyl acetate/n-hexane=½) to obtain 140.6 mg of the desired compound as a reddish brown solid (yield 59.0%).
Reaction SMILES: Br[CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH:5][CH3:6])=[O:4].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]2[C:28]3[C:29]([CH3:33])=[C:30]([CH3:32])[S:31][C:27]=3[CH2:26][CH2:25][NH:24]2)=[CH:17][CH:16]=1>>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]2[C:28]3[C:29]([CH3:33])=[C:30]([CH3:32])[S:31][C:27]=3[CH2:26][CH2:25][N:24]2[CH:2]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([NH:5][CH3:6])=[O:4])=[CH:17][CH:16]=1
Reactant: COc1ccc(CCC2NCCc3sc(C)c(C)c32)cc1
Reactant: CNC(=O)C(Br)c1ccccc1
Product: CNC(=O)C(c1ccccc1)N1CCc2sc(C)c(C)c2C1CCc1ccc(OC)cc1

Procedure:
(MS(m/e): 449.1 (MH+)), were prepared from 2-bromo-N-methyl-2-phenyl-acetamide (commercially available) and 4-[2-(4-methoxy-phenyl)-ethyl]-2,3-dimethyl-4,5,6,7-tetrahydro-thieno [3,2-c]pyridine both as light brown solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4]([OH:7])(=[O:6])=[O:5].[OH-].[Na+:9].[Br:10][CH:11]([CH3:15])[C:12](Br)=[O:13]>O.ClCCl>[Br:10][CH:11]([CH3:15])[C:12]([NH:1][CH2:2][CH2:3][S:4]([O-:7])(=[O:6])=[O:5])=[O:13].[Na+:9]
Reactant: CC(Br)C(=O)Br
Reactant: NCCS(=O)(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CC(Br)C(=O)NCCS(=O)(=O)[O-]
Reaction time: 1 h

Procedure:
25.6 g of taurine (204 mmol) and 16.38 g of NaOH (409 mmol) were dissolved in 20 ml of deionized water. 2-Bromopropionyl bromide (44 g, 21.36 ml, 204 mmol) dissolved in 50 ml of dichloromethane was then added to the solution drop wise at 0° C. over 30 minutes. During the addition, a large amount of solid was produced. The reaction flask was manually agitated to thoroughly mix the compounds until no more exotherm was observed with additional agitation. The reaction mixture was then allowed to sit for 1 hour. The solid was filtered and washed with a small amount of absolute ethanol and then ethyl ether and then dried in vacuo. The compound can be used in this state or recrystallized from methanol.