Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[C:11]([CH2:12][OH:13])=[C:10]([N:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]2=[O:20])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:21])[CH:8]=2)[O:3]1.[C:23](OC(=O)C)(=[O:25])[CH3:24]>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:22])[C:11]([CH2:12][OH:13])=[C:10]([N:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]2=[O:20])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:21][C:23](=[O:25])[CH3:24])[CH:8]=2)[O:3]1
Reactant: CC(=O)OC(C)=O
Reactant: CC1(C)Oc2ccc(N)cc2C(n2ccccc2=O)=C1CO
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc2c(c1)C(n1ccccc1=O)=C(CO)C(C)(C)O2
Reaction time: 24 h

Procedure:
A mixture of 1 g of 2,2-dimethyl-3-hydroxymethyl-4-(1,2-dihydro-2-oxo-1-pyridyl)-6-amino-3-chromene, 10 ml of acetic anhydride and 10 ml of pyridine is allowed to stand at 20° C. for 24 hours. The mixture is evaporated, and customary working up gives 2,2-dimethyl-3-hydroxymethyl-4-(1,2-dihydro-2-oxo-1-pyridyl)-6-acetamido-3-chromene.
Reaction SMILES: [N+:1]([C:4]1[C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[O:12][C:13](=O)[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH3:25].O>CC(O)C>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:9]=1[N:10]=[C:11]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)[NH:25][C:13]2=[O:12])([O-:3])=[O:2]
Reactant: N
Reactant: O=c1oc(-c2cccc(C(F)(F)F)c2)nc2c([N+](=O)[O-])cccc12
Solvent: O
Solvent: CC(C)O
Product: O=c1[nH]c(-c2cccc(C(F)(F)F)c2)nc2c([N+](=O)[O-])cccc12
Temperature: 25 °C
Yield: 60.3 %

Procedure:
8-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-one 3 (150 mg, 0.45 mmol) was added to a solution of ammonia (5.0 mL, 10 mmol) in IPA. The reaction mixture was heated under gentle reflux for 12 h then cooled to room temperature. The reaction mixture was poured into H2O and the resulting precipitate was collected by filtration rinsed with H2O and dried under vacuum. The crude residue was recrystallized from EtOAc to give 8 (91 mg, 62% yield) as a yellow solid.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:28])([CH3:27])[CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:15]=2)=[CH:6][CH:5]=1.Cl[CH2:30][O:31][CH2:32][CH3:33].O>O1CCCC1>[CH2:32]([O:31][CH2:30][O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([CH3:28])([CH3:27])[CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH:15]=2)=[CH:8][CH:9]=1)[CH3:33]
Reactant: CCOCCl
Reactant: CC(C)(COCc1cccc(Oc2ccccc2)c1)c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOCOc1ccc(C(C)(C)COCc2cccc(Oc3ccccc3)c2)cc1
Temperature: 25 °C

Procedure:
To 50 ml dry tetrahydrofuran was added 1.0 g of sodium hydride (60% in oil) and then 5.0 g of 3-phenoxybenzyl 2-(4-hydroxyphenyl)-2-methylpropyl ether in 15 ml of dry tetrahydrofuran was added dropwise to the mixture under reflux over a period of 30 minutes. The mixture was further refluxed for 10 minutes and 5.0 ml of ethyl chloromethyl ether was added dropwise to the mixture for 30 minutes. And the resulting mixture was further refluxed for 10 minutes, cooled to room temperature, poured into water, and extracted with benzene. The benzene extract was washed with water, dried over Na2SO4, and evaporated to give the oily residue which was purified by column chromatography on 150 g silica gel (20:1 mixed solvent of benzene and ether was used as eluent) to give 5.0 g of 3-phenoxybenzyl 2-(4-ethoxymethoxyphenyl)-2-methylpropyl ether.
Reaction SMILES: [OH:1][CH2:2][C:3]1[S:4][C:5](I)=[CH:6][C:7]=1[CH3:8].[Na].[CH3:11][OH:12]>>[OH:1][CH2:2][C:3]1[S:4][C:5]([O:12][CH3:11])=[CH:6][C:7]=1[CH3:8]
Reactant: Cc1cc(I)sc1CO
Reactant: CO
Agent: [Na]
Product: COc1cc(C)c(CO)s1
Temperature: 80 °C

Procedure:
10.0 G. (0.125 mol) of cupric oxide and 11.0 g. (0.0433 mol) of 2-hydroxymethyl-3-methyl-5-iodothiophene was added to a solution of 10.0 g. (0.435 mol) of sodium in 90 ml. of methanol. The resulting reaction mixture was heated to 80° C. for 18 hrs. with vigorous stirring. The cold solution was filtered, the filtrate poured into ice water and extracted with ether/hexane (ratio 4:1). The organic extracts were washed with 10% sodium thiosulfate solution and saturated sodium chloride solution, dried and evaporated to yield 2-hydroxymethyl-3-methyl-5-methoxythiophene as a colorless oil.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[OH:11][C:12]1[CH:13]=[CH:14][C:15]2[C:19]([C:20]([O-:22])=[O:21])=[C:18]([CH3:23])[S:17][C:16]=2[CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>>[CH3:23][C:18]1[S:17][C:16]2[CH:24]=[C:12]([O:11][C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[CH:8]=[CH:9][S:10][C:3]=34)[CH:13]=[CH:14][C:15]=2[C:19]=1[C:20]([OH:22])=[O:21]
Reactant: Cc1sc2cc(O)ccc2c1C(=O)[O-]
Reactant: Clc1ccnc2ccsc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: Cc1sc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)O
Yield: 27.2 %

Procedure:
This material was prepared by reacting 7-chlorothieno[3,2-b]pyridine (170 mg, 1.0 mmole) with methyl 6-hydroxy-2-methylbenzo[b]thiophene-3-carboxylate 11a (267 mg, 1.2 mmole) and Cs2CO3 (488 mg, 1.5 mmole) in a manner similar to that previously described for example 1. Silica gel chromatography (10% MeOH/CHCl2) provided the title compound as a brown viscous oil (93 mg, 27%) of. 1H NMR (DMSO-d6, 300 MHz) δ 8.47 (1H, d, J=5.27 Hz), 8.41 (1H, d, J=8.85 Hz), 8.11 (1H, d, J=5.46 Hz), 7.93 (1H, d, J=2.07 Hz), 7.55 (1H, d, J=7.55 Hz), 7.32 (1H, dd, J=2.26, 8.85 Hz), 6.64 (1H, d, J=5.27 Hz), 2.77 (3H, s).
Reaction SMILES: Br[C:2]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[C:9]2[CH2:8][CH2:7][N:6]([N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:5](=[O:25])[C:4]=2[C:3]=1[CH3:26].[OH:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[N:10]1[C:9]2[CH2:8][CH2:7][N:6]([N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:5](=[O:25])[C:4]=2[C:3]([CH3:26])=[C:2]1[C:31]1[CH:32]=[CH:33][C:28]([OH:27])=[CH:29][CH:30]=1
Reactant: OB(O)c1ccc(O)cc1
Reactant: Cc1c2c(n(-c3ccc(Cl)cc3Cl)c1Br)CCN(N1CCCCC1)C2=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Cc1c2c(n(-c3ccc(Cl)cc3Cl)c1-c1ccc(O)cc1)CCN(N1CCCCC1)C2=O
Temperature: 60 °C
Yield: 86.8 %

Procedure:
2-Bromo-1-(2,4-Dichlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-4-one (450 mg, 0.98 mmol), 4-hydroxyphenylboronic acid (150 mg, 1.09 mmol) and tetrakis(triphenylphosphine)palladium(0) (150 mg) were dissolved in DME (20 ml) and 1 M Na2CO3 (5 ml)). The resulting solution was degassed and heated at 60° C. under nitrogen overnight. Water and EtOAc were added after cooling and the aqueous phase extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered and concentrated to give a crude product that was purified by flash chromatography (heptane:EtOAc gradient) to afford 0.40 g (87%) of the product as a pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:16]([O-])=O)=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:15])[N:10]=2)[CH:7]=1.O.O.[Sn](Cl)Cl>C(O)C>[NH2:16][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][C:6]=1[NH:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([NH2:15])[N:10]=1
Reactant: Nc1nccc(Nc2cc(Br)ccc2[N+](=O)[O-])n1
Agent: Cl[Sn]Cl
Solvent: CCO
Solvent: O
Product: Nc1nccc(Nc2cc(Br)ccc2N)n1
Temperature: 65 °C
Reaction time: 2 h

Procedure:
To a solution of 4-N-(5-bromo-2-nitrophenyl)pyrimidine-2,4-diamine (5.06 g, 16.32 mmol) in ethanol (110 mL) was added tin(II) chloride dihydrate (12.89 g, 57.11 mmol). The reaction mixture was stirred at 65° C. for 2 hr. The reaction mixture was evaporated to dryness and ice-water added. The pH of the mixture was adjusted to 10 using saturated aqueous Na2CO3 solution. EtOAc was added followed by saturated aqueous Rochelles salt (potassium sodium tartrate). The resulting mixture was stirred until separate layers were observed. The organic layer was extracted and the extraction repeated (2×) with EtOAc and DCM. Combined organic layer were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as a pale yellow solid: 1H NMR (250 MHz, DMSO) δ 5.05 (2H, br. s), 5.79 (1H, d, J=5.79 Hz), 6.08 (2H, br. s), 6.68 (1H, d, J=8.53 Hz), 7.02 (1H, dd, J=8.60, 2.36 Hz), 7.36 (1H, d, J=2.28 Hz), 7.75 (1H, d, J=5.63 Hz), 8.15 (1H, s); LC-MS: m/z=+279.9, 281.9 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[C:3]([Cl:10])=[C:4]([CH:8]=O)[CH:5]=[N:6][CH:7]=1.[CH2:11]([S:13]([NH2:16])(=[O:15])=[O:14])[CH3:12].[BH4-].[Na+]>CO>[Br:1][C:2]1[C:3]([Cl:10])=[C:4]([CH2:8][NH:16][S:13]([CH2:11][CH3:12])(=[O:15])=[O:14])[CH:5]=[N:6][CH:7]=1
Reactant: O=Cc1cncc(Br)c1Cl
Reactant: CCS(N)(=O)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCS(=O)(=O)NCc1cncc(Br)c1Cl

Procedure:
In analogy to the procedure described for the preparation of intermediate A-11, 5-bromo-4-chloro-pyridine-3-carbaldehyde has been reacted first with ethanesulfonamide, followed by reduction of the thus formed imine with NaBH4 in MeOH to give the title compound as a light orange solid. MS: 313.2 and 315.1 (M+H+).
Reaction SMILES: Cl[C:2]1[N:3]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:4](=[O:11])[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[OH:27].CO>C(Cl)Cl>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[O:27][C:2]1[N:3]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:4](=[O:11])[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1
Reactant: Oc1ccc(F)cc1F
Reactant: O=c1c2ncsc2nc(Cl)n1-c1ccc(F)cc1
Solvent: ClCCl
Solvent: CO
Product: O=c1c2ncsc2nc(Oc2ccc(F)cc2F)n1-c1ccc(F)cc1
Temperature: 140 °C
Reaction time: 48 h

Procedure:
5-Chloro-6-(4-fluorophenyl)[1,3]thiazolo[5,4-d]pyrimidin-7(6H)-one (0.2 mmol) and 2.4-difluorophenol (0.4 mmol) are added to a vial, and the sealed mixture is heated with stirring at 140° C. for 48 h. Silica gel column chromatography (MeOH:CH2Cl2=0.5:99.5) gives the title compound as a slightly yellow solid. 1H NMR (400 MHz, CDCl3) 8.70 (1H, s), 7.36 (2H, m), 7.26 (2H, m), 7.14 (1H, m), 6.94 (2H, m). MS (M+1): 376.03; RT=1.33 min.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18](O)=[O:19])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH2:54]([O:56][C:57](=[O:65])[C:58]1[CH:63]=[CH:62][C:61]([NH2:64])=[CH:60][CH:59]=1)[CH3:55]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18](=[O:19])[NH:64][C:61]3[CH:62]=[CH:63][C:58]([C:57]([O:56][CH2:54][CH3:55])=[O:65])=[CH:59][CH:60]=3)[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: CC(C)(C)OC(=O)N1CCCc2ccc(C(=O)O)cc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1ccc(NC(=O)c2ccc3c(c2)N(C(=O)OC(C)(C)C)CCC3)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 3,4-dihydro-2H-quinoline-1,7-dicarboxylic acid 1-tert-butyl ester (1.0 g, 3.61 mmol) in dimethylformamide (20 ml) was treated with diisopropyl ethyl amine (0.51 g, 3.97 mmol, 1.1 equiv.), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (1.27 g, 3.97 mmol, 1.1 equiv.) and 4-amino-benzoic acid ethyl ester (0.65 g, 3.97 mmol, 1.1 equiv.). The mixture was stirred at room temperature overnight, then the solvent was evaporated and the residue purified by flash chromatography (heptane/ethyl acetate gradient) to afford 7-(4-ethoxycarbonyl-phenylcarbamoyl)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester as a white solid, 1.1 g (70%). MS (ISP): m/e=423.1 (M−H).
Reaction SMILES: C(OC(=O)[NH:7][N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH2:10][CH2:9]1)(C)(C)C.[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28]>ClCCl>[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].[C:20]([Si:17]([CH3:19])([CH3:18])[O:16][CH2:15][CH2:14][CH:11]1[CH2:12][CH2:13][N:8]([NH2:7])[CH2:9][CH2:10]1)([CH3:22])([CH3:21])[CH3:23]
Reactant: CC(C)(C)OC(=O)NN1CCC(CCO[Si](C)(C)C(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCC1CCN(N)CC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
{4-[2-(t-Butyl-dimethyl-silanyloxy)-ethyl]-piperidin-1-yl}-carbamic acid t-butyl ester (168 mg, 468 μmol) was at 0° C. combined with dichloromethane (2 mL) and trifluoroacetic acid (2 mL) to give a light yellow solution. The reaction mixture was stirred for 2 h at 0° C. and subsequently concentrated in vacuo to give the title compound as yellow oil, which was used without further purification in the next step.
Reaction SMILES: C(=O)(O)[O-].[Na+].[CH3:6][N:7]1[CH2:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[F:14][C:15]1[C:21](F)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1.O>CN(C=O)C>[F:14][C:15]1[C:21]([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([CH3:6])[CH2:8][CH2:9]2)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1
Reactant: CN1CCCNCC1
Reactant: Nc1cc(F)c(F)cc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN1CCCN(c2cc(N)c([N+](=O)[O-])cc2F)CC1
Temperature: 80 °C
Yield: 90.9 %

Procedure:
36.2 g of sodium bicarbonate and 29.5 g of N-methyl-homopiperazine are added to a solution of 15 g of 4,5-difluoro-2-nitroaniline in 120 mL of anhydrous DMF. The reaction medium is heated at 80° C. using an oil bath for 2H30. The reaction medium is cooled to ambient temperature, and then poured into 400 mL of water. The mixture is cooled using an ice bath and stirred, and precipitation occurs. The precipitate is filtered off through sintered glass. The yellow solid is rinsed with water. The solid is dried in an oven at 40° C. 21 g of 4-fluoro-5-(4-methylperhydro-1,4-diazepin-1-yl)-2-nitrophenylamine are obtained in the form of a yellow solid. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.90 (m, 2H); 2.27 (s, 3H); 2.50 (m masked, 2H); 2.64 (m, 2H); 3.46 (m, 2H); 3.52 (m, 2H); 6.21 (d, J=9.0 Hz, 1H); 7.24 (broad s, 2H); 7.59 (d, J=16.0 Hz, 1H). EI mass spectrum: m/z=268: M+. (base peak)—m/z=253: (M−CH3)+—m/z=198: (M−C4H8N)+—m/z=70: C4H8N+—m/z=57: C3H7N+.
Reaction SMILES: [CH2:1]([C:3]1[N:4]([CH2:16][CH2:17][CH2:18][CH2:19][NH2:20])[C:5]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:15]=1)[CH3:2].C(O)(=O)C.[S:25]1[CH2:29][CH2:28][C:27](=O)[CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH2:1]([C:3]1[N:4]([CH2:16][CH2:17][CH2:18][CH2:19][NH:20][CH:27]2[CH2:28][CH2:29][S:25][CH2:26]2)[C:5]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]=[CH:7][C:6]=2[N:15]=1)[CH3:2]
Reactant: CCc1nc2cnc3ccccc3c2n1CCCCN
Reactant: O=C1CCSC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCc1nc2cnc3ccccc3c2n1CCCCNC1CCSC1
Reaction time: 0.17 h

Procedure:
To a suspension of 4-(2-Ethyl-imidazo[4,5-c]quinolin-1-yl)-butylamine obtained in step VI in tetrahydrofuran was added acetic acid (1 eq.) and dihydrothiophen-3-one (1.1 eq.). Resulting reaction mixture was stirred for 10 min. Sodium triacetoxyborohydride (2.2 eq.) was added to reaction mixture over a period of 1 hrs and resulting suspension was then stirred for 4-5 hrs. Reaction was then quenched with methanol and concentrated to dryness. Reaction mixture was basified using aq.sodium hydroxide solution and extracted with chloroform. Organic layer was dried over sodium sulphate and concentrated under reduced pressure to yield sticky solid. Product was then purified by silica gel column chromatography to afford [4-(2-Ethyl-imidazo[4,5-c]quinolin-1-yl)-butyl]-(tetrahydro-thiophen-3-yl)-amine.
Reaction SMILES: [Na].[C:2]1([CH:8]([C:12]([NH2:14])=[O:13])[C:9]([NH2:11])=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:15](OCC)=O.O>C(O)C>[C:2]1([C:8]2[C:12]([OH:13])=[N:14][CH:15]=[N:11][C:9]=2[OH:10])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)C(C(N)=O)c1ccccc1
Reactant: CCOC=O
Agent: [Na]
Solvent: O
Solvent: CCO
Product: Oc1ncnc(O)c1-c1ccccc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 69.1 %

Procedure:
Sodium metal (0.92 g, 40 mmol) was dissolved by stirring in ethanol (30 mL) at room temperature under argon over 40 min. To the resulting solution at room temperature was added 2-phenylmalonamide (3.56 g, 20 mmol) and ethyl formate (1.9 mL, 24 mmol). The resulting suspension was heated at 50° C. under argon 16 h. After cooling the reaction mixture to room temperature, water (100 mL) was added and the mixture was stirred for 1 h. Solid was removed by filtration. The filtrate was acidified to pH˜4 with 1 M aqueous HCl. The resulting precipitate was collected by filtration and further washed with water (20 mL×2), then Et2O (10 mL×2). After drying under vacuum for 3 h, the title compound (2.6 g) was obtained as a light yellow solid. HPLC/MS: retention time=0.76 min, [M+H]+=189.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH2:4][CH2:5][CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][C:11]=1[OH:17])([CH3:9])[CH3:8].[CH2:19](O)[CH2:20][CH2:21][CH2:22][CH2:23]C.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH2:1]([O:2][C:3](=[O:18])[CH2:4][CH2:5][CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][C:11]=1[OH:17])([CH3:9])[CH3:8])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCO
Reactant: COC(=O)CCCC(C)(C)c1ccc(O)cc1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CCCCCCOC(=O)CCCC(C)(C)c1ccc(O)cc1O

Procedure:
5.5 parts of methyl-5-(2,4-dihydroxyphenyl)-5-methylhexanoate, 50 parts of n-hexanol, and 0.5 parts of p-toluene sulphonic acid are heated on a steam-bath for 6 hours. The excess hexanol is then removed under reduced pressure and then residual oil taken up in ether, washed with sodium bicarbonate solution, water, and evaporated. Short path distillation of the residual oil at a pressure of 0.5 mm of mercury yields 5.8 parts of n-hexyl-5-(2,4-dihydroxyphenyl)-5-methylhexanoate of the formula ##STR19## with the following percentage composition by weight:
Reaction SMILES: [Cl:1][C:2]1[C:12]([Cl:13])=[C:11]([C:14](=[O:22])[C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].[CH2:23](O)[CH3:24].S(=O)(=O)(O)O>C(Cl)CCl>[Cl:1][C:2]1[C:12]([Cl:13])=[C:11]([C:14](=[O:22])[C:15]2[CH:16]=[CH:17][C:18]([OH:21])=[CH:19][CH:20]=2)[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:23][CH3:24])=[O:7]
Reactant: O=C(O)COc1ccc(C(=O)c2ccc(O)cc2)c(Cl)c1Cl
Reactant: CCO
Agent: O=S(=O)(O)O
Solvent: ClCCCl
Product: CCOC(=O)COc1ccc(C(=O)c2ccc(O)cc2)c(Cl)c1Cl
Reaction time: 8 h
Yield: 93 %

Procedure:
An 85.38 g. (0.25 mole) portion of 2,3-dichloro-4-(4'-hydroxybenzoyl)phenoxyacetic acid, 34.5 g. (0.75 mole) of ethanol, and 100 ml. of ethylene dichloride, using 3.5 ml. of sulfuric acid as the catalyst was mixed and refluxed with stirring overnight according to the procedure of Clinton and Laskowski, J.A.C.S. 70 3135, 1948. The acid gradually went into solution. The reaction layer was cooled, separated and the organic layer washed successively with water, twice with KHCO3 solution and finally with water. The dried ethylene dichloride was evaporated to dryness to give an oil which solidified to give 86 g. crude ester on trituration with pentane and filtering; m.p. 127°-9° (93% yield). This material was used without further purification in subsequent experiments.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].O.Cl[CH2:17][C:18](=[O:25])[C:19]([CH3:24])([CH3:23])[CH2:20][CH2:21][Cl:22]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:17][C:18](=[O:25])[C:19]([CH3:24])([CH3:23])[CH2:20][CH2:21][Cl:22])=[CH:4][CH:3]=1
Reactant: CC(C)(CCCl)C(=O)CCl
Reactant: Sc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)(CCCl)C(=O)CSc1ccc(Cl)cc1
Temperature: 100 °C
Reaction time: 5 h
Yield: 94.4 %

Procedure:
86.7 g (0.6 mole) of 4-chlorothiophenol and 82.8 g (0.6 mole) of potassium carbonate in 500 ml of toluene are heated under reflux for 2 hours, using a water separator. 91.5 g (0.5 mole) of 1,5-dichloro-3,3-dimethyl-2-pentanone in 200 ml of toluene are then added at 100° C. The reaction mixture is stirred at 100° C. for 5 hours and is then allowed to cool, and is stirred with 500 ml of water. The organic phase is separated off, washed with dilute sodium hydroxide solution and with water, dried over sodium sulphate and concentrated. 137.4 g (94.4% of theory) of 1-(4-chlorophenylthio)-5-chloro-3,3-dimethyl-2-pentanone of refractive index nD20 1.5628 are obtained. ##STR95##
Reaction SMILES: I[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[S:4][C:3]=1[CH3:13].[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][C:3]1[S:4][C:5]2[C:10]([C:11](=[O:12])[C:2]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: Cc1sc2ccccc2c(=O)c1I
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1sc2ccccc2c(=O)c1-c1ccccc1
Yield: 93 %

Procedure:
The compound (1.0 mmol, 302 mg) obtained in (1) above, dichlorobis(triphenylphosphine)palladium (0.03 mmol, 21 mg), phenylboronic acid (1.3 mmol, 159 mg) and potassium carbonate (4.0 mmol, 552 mg) were dissolved in degassed dimethylformamide (3.2 mL) and water (0.8 mL), and the solution was stirred under a nitrogen atmosphere at 80° C. for 4 hours. After the disappearance of the starting materials was confirmed by thin-layer chromatography, water was poured into the reaction solution to terminate the reaction. The organic substances were extracted with ethyl acetate, the obtained organic layer was dried over magnesium sulfate, and the solvents were evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (0.93 mmol, 237 mg) was obtained in a 93% yield.
Reaction SMILES: O[CH:2]([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[NH3:10]>>[NH2:10][CH:2]([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)CC(C)O
Reactant: N
Product: CCOC(=O)CC(C)N
Reaction time: 0 h

Procedure:
The concentrations of the substrates prior to entering the reactor were 0.226 M for ethyl 3-hydroxy-n-butyrate and 1.630 M for aqueous ammonia. The reaction time was 0.201 second, and the aqueous solution obtained after the reaction was examined with a high performance liquid chromatography/mass spectroscopy apparatus, which confirmed that an amino group had been introduced into the ethyl 3-hydroxy-n-butyrate, and that ethyl 3-amino-n-butyrate had been produced. The ethyl 3-amino-n-butyrate concentration was 3.3 mM, and the reaction yield thereof was 1.5%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[C:4]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH:3]=1.Cl[CH2:21][CH2:22][CH2:23][N:24]1[C:29](=[O:30])[C:28]([F:31])=[CH:27][N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:25]1=[O:40]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:21][CH2:22][CH2:23][N:24]3[C:29](=[O:30])[C:28]([F:31])=[CH:27][N:26]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:39])[CH3:38])[C:25]3=[O:40])[CH2:10][CH2:9]2)=[C:4]([O:14][CH2:15][C:16]([F:18])([F:17])[F:19])[CH:3]=1
Reactant: Fc1ccc(N2CCNCC2)c(OCC(F)(F)F)c1
Reactant: C[Si](C)(C)CCOCn1cc(F)c(=O)n(CCCCl)c1=O
Product: C[Si](C)(C)CCOCn1cc(F)c(=O)n(CCCN2CCN(c3ccc(F)cc3OCC(F)(F)F)CC2)c1=O

Procedure:
substituting 1-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine and 3-(3-chloropropyl)-5-fluoro-1-[2-(trimethylsilyl)ethoxymethyl]-2,4(1H,3H)-pyrimidinedione gave 3-(3-{4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}propyl)-5-fluoro-1-[2-(trimethylsilyl)ethoxymethyl)-2,4(1H,3H)-pyrimidinedione;