Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:15]=[CH:14][C:6]2[O:7][CH2:8][C:9]([CH3:13])([CH3:12])[CH2:10][O:11][C:5]=2[CH:4]=1)#[CH:2].I[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=1>>[CH3:24][O:23][C:19]1[CH:18]=[C:17]([C:2]#[C:1][C:3]2[CH:15]=[CH:14][C:6]3[O:7][CH2:8][C:9]([CH3:12])([CH3:13])[CH2:10][O:11][C:5]=3[CH:4]=2)[CH:22]=[CH:21][CH:20]=1
Reactant: COc1cccc(I)c1
Reactant: C#Cc1ccc2c(c1)OCC(C)(C)CO2
Product: COc1cccc(C#Cc2ccc3c(c2)OCC(C)(C)CO3)c1

Procedure:
The title compound is prepared in analogy to example 1 from 7-ethynyl-3,3-dimethyl-3,4-dihydro-2H-benzo[b][1,4]dioxepine (6) (example 1d) and 1-iodo-3-methoxy-benzene. MS (ESI) 308.2 (M•)+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].CCOCC.[C:17](O)(=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]\[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].CS(O)(=O)=O>>[C:17]([O:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)(=[O:35])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]\[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: Oc1ccc2ccccc2c1
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CS(=O)(=O)O
Solvent: CCOCC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)Oc1ccc2ccccc2c1
Temperature: 220 °C

Procedure:
To a four neck round bottom flask fitted with nitrogen inlet, mechanical stirrer, temperature probe and condenser is charged 1102.84 g (1.85 moles) of the Alkoxylate from example 15 and 497.16 g (1.76 moles) of Oleic Acid. A catalytic amount of Methanesulfonic Acid (1.6 g) is charged and the reaction mixture is heated to 220° C. under nitrogen sparge. The reaction is monitored by measuring the acid value to an AV of preferably less than 5. Once the AV is reached, the temperature is cooled to 85° C. and the catalyst is neutralized with an equivalent molar amount of 45% KOH and washed once with water. The reaction is dried under vacuum yielding the desired product.
Reaction SMILES: [CH3:1][CH:2]1[CH:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[CH2:4][N:3]1[C:17](Cl)=[O:18].C(=O)([O-])[O-].[K+].[K+].[CH2:26]([NH2:29])[CH:27]=[CH2:28]>O1CCCC1.O>[CH3:1][C@H:2]1[C@@H:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[CH2:4][N:3]1[C:17]([NH:29][CH2:26][CH:27]=[CH2:28])=[O:18]
Reactant: C=CCN
Reactant: CC1C(Oc2cccc(C(F)(F)F)c2)CN1C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=CCNC(=O)N1C[C@H](Oc2cccc(C(F)(F)F)c2)[C@@H]1C
Reaction time: 0.25 h
Yield: 67.8 %

Procedure:
A stirred mixture of 4.02 g (0.01 mole) of crude (73%) 2-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarbonyl chloride cis isomer and 1.4 g (0.01 mole) of potassium carbonate in 20 ml of tetrahydrofuran was treated with 0.57 g (0.01 mole) of 2-propenylamine. After stirring for 15 minutes, a small piece of ice was added and stirring continued for 3 hr. The reaction mixture was diluted with water and the oil which separated was extracted with methylene chloride (2×50 ml). The combined extracts were dried over magnesium sulfate and concentrated in vacuo (5.2 g). The crude product was chromatographed on a 125 g silica gel column. Elution with chloroform washed impurities from the column and the product was removed by eluting with an ethyl acetate/chloroform gradient (1-20%). The combined product fractions gave a pale yellow oil which solodified on standing and was recrystallized from isopropyl ether/hexane to give an oil which slowly crystallized, yielding 2.1 g (67.8%) of white product, m.p. 74°-77° C.
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:9])([CH3:6])([CH3:5])[CH3:4].IC.[C:30](O)(=O)C>C1COCC1>[C:3]([O:7][C:8]([N:10]([CH3:30])[CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(=O)O
Reactant: CC(C)(C)OC(=O)NCCOCCOCCOCCOCCC(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Product: CN(CCOCCOCCOCCOCCC(=O)O)C(=O)OC(C)(C)C
Reaction time: 0.08 h

Procedure:
85.4 mg of NaH are added portionwise to a solution, cooled to 0° C., of 520 mg of 3-[2-(2-{2-[2-((tert-butoxycarbonyl)amino)ethoxy]ethoxy}ethoxy)ethoxy]propanoic acid in 14 ml of THF. After stirring for 5 min, 150 μl of iodomethane are added. The mixture is then stirred at AT for 2 h and then an additional 150 μl of iodomethane are added. After 12 h at AT, the mixture is hydrolysed and then brought to acidic pH by addition of aqueous acetic acid at 0° C. The aqueous phase is extracted 3× with AcOEt, the combined organic phases are dried over MgSO4 and concentrated under RP, and the crude product obtained is reacted again according to the same protocol with 85 mg of NaH and 176 μl of iodomethane for an additional 2 h. 500 mg of 3-[2-(2-{2-[2-((tert-butoxycarbonyl)(methyl)amino)ethoxy]ethoxy}ethoxy)ethoxy]propanoic acid are thus obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].Br[CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: CCOC(=O)C(C)Br
Reactant: O=[N+]([O-])c1ccc(Cl)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C(C)Oc1cc([N+](=O)[O-])ccc1Cl
Reaction time: 3.5 h

Procedure:
A mixture of 17.4 g. of 2-chloro-5-nitrophenol, 19.0 g. of ethyl α-bromopropionate, 15.2 g. of potassium carbonate and 85 ml. of acetone was refluxed with stirring for 3.5 hours and the solvent was distilled off. 2N-HCl was added to the residue to obtain a crude crystal. The product was separated by a filtration and washed with water and dried and recrystallized from n-hexane to obtain 27.4 g. of the object compound (melting point of 46° to 46.5° C.).
Reaction SMILES: [CH2:1]=[O:2].[Cl-].[Mg+2].[Cl-].[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][C:8]=1[OH:14].Cl>C(#N)C.C(N(CC)CC)C>[Cl:6][C:7]1[C:8]([OH:14])=[C:9]([C:10]([CH3:13])=[CH:11][CH:12]=1)[CH:1]=[O:2]
Reactant: Cc1ccc(Cl)c(O)c1
Reactant: C=O
Agent: Cl
Agent: [Cl-]
Agent: [Mg+2]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Cc1ccc(Cl)c(O)c1C=O
Temperature: 90 °C
Reaction time: 10 h

Procedure:
Paraformaldehyde (4.73 g, 163 mmol), magnesium chloride (7.76 g, 81.7 mmol) and triethylamine (14.2 ml, 102 mmol were added to a solution of 2-chloro-5-methylphenol (5.80 g, 40.8 mmol) in acetonitrile (100 ml) and the mixture was vigorously stirred at 90° C. for 10 hours. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. After the organic layer was successively washed with 1N hydrochloric acid, water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate, it was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluting solvent: hexane/ethyl acetate=3/1) to give crude 3-chloro-2-hydroxy-6-methylbenzaldehyde. According to a method similar to Example (28-3) and Example (28-4), from the crude compound obtained in the above, tert-butyl 2-[(tert-butoxycarbonyl)oxy]-3-chloro-6-methylbenzoate was obtained (1.82 g, three-step total yield: 13%).
Reaction SMILES: [C:1]1([CH2:13][C:14]([NH2:16])=[O:15])[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.C[O:18][C:19](=O)[C:20]([C:22]1[C:30]2[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=2)[NH:24][CH:23]=1)=O>>[C:1]1([C:13]2[C:14](=[O:15])[NH:16][C:19](=[O:18])[C:20]=2[C:22]2[C:30]3[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=3)[NH:24][CH:23]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1
Reactant: NC(=O)Cc1cn2c3c(cccc13)CCC2
Reactant: COC(=O)C(=O)c1c[nH]c2cc(F)ccc12
Product: O=C1NC(=O)C(c2cn3c4c(cccc24)CCC3)=C1c1c[nH]c2cc(F)ccc12

Procedure:
Beginning with 2-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-acetamide and (6-Fluoro-1H-indol-3-yl)-oxo-acetic acid methyl ester, the title compound was prepared essentially as described in Example 1.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([C:8](=[O:17])[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.[CH3:25][CH2:26][O:27][C:28](/[C:30](/Cl)=[N:31]\O)=[O:29]>C(O)C>[I:1][C:2]1[CH:3]=[C:4]([C:8]2[O:17][N:31]=[C:30]([C:28]([O:27][CH2:26][CH3:25])=[O:29])[C:9]=2[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)/C(Cl)=N\O
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(I)c1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1noc(-c2cccc(I)c2)c1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 35.2 %

Procedure:
tert-Butyl 3-(3-iodophenyl)-3-oxopropanoate (1.91 g, 5.52 mmol) was dissolved in ethanol (6 mL), cooled to 0° C., and Et3N (558 mg, 5.52 mmol) was added. After stirring 20 minutes, ethyl chlorooximidoacetate (836 mg, 5.52 mmol) in EtOH (3 mL) was added to the reaction mixture over 30 min. The reaction mixture was warmed to ambient temperature and stirred overnight. The mixture was concentrated in vacuo and purified by column chromatography (0–13% ethyl acetate in hexanes) to provide the titled compound (860 mg, 35%).
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=O)C=1.[CH3:12][CH:13]([CH3:41])[CH2:14][N:15]1[C:27]2[C:26]3[CH:25]=[CH:24][C:23]([O:28][C:29]4[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=4)=[CH:22][C:21]=3[N:20]=[CH:19][C:18]=2[N:17]=[C:16]1[CH2:38][CH2:39][CH3:40].[OH-].[NH4+:43]>C(Cl)(Cl)Cl.ClCCl>[CH3:12][CH:13]([CH3:41])[CH2:14][N:15]1[C:27]2[C:26]3[CH:25]=[CH:24][C:23]([O:28][C:29]4[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=4)=[CH:22][C:21]=3[N:20]=[C:19]([NH2:43])[C:18]=2[N:17]=[C:16]1[CH2:38][CH2:39][CH3:40]
Reactant: [NH4+]
Reactant: CCCc1nc2cnc3cc(Oc4ccc([N+](=O)[O-])cc4)ccc3c2n1CC(C)C
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CCCc1nc2c(N)nc3cc(Oc4ccc([N+](=O)[O-])cc4)ccc3c2n1CC(C)C
Reaction time: 0.5 h

Procedure:
Part B of the general methods described for Examples 35-40 was followed using 2.00 g of 1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-7-ol to provide 2.33 g of 1-(2-methylpropyl)-7-(4-nitrophenoxy)-2-propyl-1H-imidazo[4,5-c]quinoline as a yellow solid. Parts C and D of the general methods described for Examples 35-40 were replaced by the following procedure. mCPBA (0.853 g, 2.97 mmol) was added in one portion to a solution of 1-(2-methylpropyl)-7-(4-nitrophenoxy)-2-propyl-1H-imidazo[4,5-c]quinoline (1.00 g, 2.47 mmol) in chloroform (17 mL), and the reaction was stirred for 30 minutes. Ammonium hydroxide (17 mL) was then added, followed by/7-toluenesulfonyl chloride (0.710 g, 3.70 mmol). The reaction was stirred for 16 hours and then diluted with dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic solutions were washed sequentially with water and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown solid. The solid was recrystallized from acetonitrile to provide 0.680 g of 1-(2-methylpropyl)-7-(4-nitrophenoxy)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine as a reddish-brown, crystalline solid, mp 209-211° C.
Reaction SMILES: C(O[K])(C)(C)C.[C:7](=[O:14])([O:11][CH2:12][CH3:13])OCC.C1(C)C=CC=CC=1.[C:22]([C:25]1[S:26][CH:27]=[CH:28][CH:29]=1)(=[O:24])[CH3:23]>O>[CH2:12]([O:11][C:7](=[O:14])[CH2:23][C:22](=[O:24])[C:25]1[S:26][CH:27]=[CH:28][CH:29]=1)[CH3:13]
Reactant: CC(=O)c1cccs1
Reactant: CCOC(=O)OCC
Agent: CC(C)(C)O[K]
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)CC(=O)c1cccs1
Temperature: 62.5 °C
Reaction time: 1 h
Yield: 82.2 %

Procedure:
A 71.1 g (0.63 mol) portion of tert-butoxy potassium was added to 194.7 g (1.65 mol) of diethyl carbonate at 60 to 65° C. and stirred at 60 to 65° C. for 1 hour, and then 180 ml of toluene solution containing 50 g (0.40 mol) of 2-acetylthiophene was added dropwise thereto at 75 to 80° C. and stirred at 75 to 80° C. for 2 hours. The reaction solution was cooled down to room temperature, mixed with 725 g of water, extracted with 600 ml of ethyl acetate, washed with saturated brine, concentrated and then distilled under a reduced pressure to obtain 65.2 g of 3-oxo-3-(2-thienyl)propionic acid ethyl ester (yield 83%).
Reaction SMILES: [C:1]([C:4]1[O:5][C:6]2[CH:13]=[CH:12][C:11]([O:14]C(C)=O)=[C:10]([Br:18])[C:7]=2[C:8]=1[NH2:9])(=[O:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl>CO.O>[C:1]([C:4]1[O:5][C:6]2[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([Br:18])[C:7]=2[C:8]=1[NH2:9])(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1ccc2oc(C(C)=O)c(N)c2c1Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC(=O)c1oc2ccc(O)c(Br)c2c1N
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.7 %

Procedure:
To a mixture of 12E (6.8 g, 0.021 mol) in MeOH (40 mL) and water (20 mL) was added K2CO3 (4.5 g, 0.032 mol) in batches at room temperature. The reaction mixture was stirred at room temperature overnight, then neutralized with diluted hydrochloric acid to pH=6˜7, extracted with ethyl acetate, dried and concentrated to give 12F (5.6 g, 95.1% yield).
Reaction SMILES: [CH:1](OCC)=[O:2].[CH3:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[CH:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:10][CH2:9][C:8]1=[O:25]>ClC1C=CC=CC=1>[CH3:6][N:7]1[C:13]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:12]=2[CH:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:10]([CH:1]=[O:2])[CH2:9][C:8]1=[O:25]
Reactant: CCOC=O
Reactant: CN1C(=O)CNC(c2ccccc2)c2cc(Cl)ccc21
Solvent: Clc1ccccc1
Product: CN1C(=O)CN(C=O)C(c2ccccc2)c2cc(Cl)ccc21
Yield: 68.6 %

Procedure:
6 ml. of ethyl formate are added to a solution of 1.4 g. (5 mmoles) of 1-methyl-5-phenyl-7-chloro-1,3,4,5-tetrahydro-2H-1,4-benzodiazepine-2-one in 5 ml. of chlorobenzene, and the reaction mixture is maintained at the boiling point of the solvent for 3 hours. Thereafter the solvent is evaporated under reduced pressure, and the oily residue is solidified by treating it with 20 ml. of dry ether. 108 g. (68.6 %) of 1-methyl-4-formyl-5-phenyl-7-chloro-1,3,4,5-tetrahydro-2H-1,4-benzodiazepine-2-one are obtained; m.p.: 167°-169° C. The melting point does not change after recrystallization from ethanol. Rf2 = 0.5.
Reaction SMILES: [I:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:12])([CH3:11])[CH2:7][NH:8]2)=[CH:4][CH:3]=1.Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([Cl:24])[CH:22]=2)[N:17]=[C:16]([CH3:25])[C:15]=1[CH3:26]>>[Cl:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([CH3:25])[C:15]([CH3:26])=[C:14]2[N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=2)[C:6]([CH3:12])([CH3:11])[CH2:7]1
Reactant: Cc1nc2ccc(Cl)cc2c(Cl)c1C
Reactant: CC1(C)CNc2cc(I)ccc21
Product: Cc1nc2ccc(Cl)cc2c(N2CC(C)(C)c3ccc(I)cc32)c1C

Procedure:
Prepared according to procedure M using 6-iodo-3,3-dimethylindoline (0.604 g, 2.21 mmol) and 4,6-dichloro-2,3-dimethylquinoline (0.5 g, 2.21 mmol) to give 6-chloro-4-(6-iodo-3,3-dimethylindolin-1-yl)-2,3-dimethylquinoline as a brown solid: Mass Spectrum (ESI) m/e=463.0 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH:14][CH2:15][CH2:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[S:12][CH:13]=2)=[CH:5][CH:4]=1.[H-].[Na+].I[CH2:28][CH2:29][CH2:30][CH3:31].C(OCC)(=O)C>CN(C)C=O>[CH2:28]([N:14]([C:11]1[S:12][CH:13]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:10]=1)[CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]#[N:22])=[CH:23][CH:24]=1)[CH2:29][CH2:30][CH3:31]
Reactant: CCCCI
Reactant: COc1ccc(-c2csc(NCCc3ccc(C#N)cc3)n2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCCN(CCc1ccc(C#N)cc1)c1nc(-c2ccc(OC)cc2)cs1
Temperature: 25 °C

Procedure:
600 mg 4-{2-[4-(4-Methoxy-phenyl)-thiazol-2-ylamino]-ethyl}-benzonitrile were dissolved in 30 ml dimethylformamide. 85.9 mg sodium hydride (24% in mineral oil) were added and the reaction mixture stirred at room temperature for thirty minutes. Then 245 μl 1-Iodobutane were added and the reaction mixture stirred at room temperature for two hours. Then 100 ml ethyl acetate were added and the mixture was washed three times with portions of 50 ml water and then dried over MgSO4. The solvents were removed in vacuo and the residue purified by RP-HPLC to obtain 279 mg 4-(2-{Butyl-[4-(4-methoxy-phenyl)-thiazol-2-yl]-amino}-ethyl)-benzonitrile.
Reaction SMILES: [CH:1](=[CH:8][C:9](=[O:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1>CO>[C:2]1([CH:1]=[CH:8][CH:9]([OH:11])[CH3:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)C=Cc1ccccc1
Solvent: C1CCOC1
Solvent: CO
Product: CC(O)C=Cc1ccccc1
Yield: 34.1 %

Procedure:
In a 200 ml stainless steel autoclave were charged 5 g (34.2 mmole) of benzalacetone and 0.213 g (0.171 mmole) of ##STR24## synthesized in Example 4, and 3 ml of tetrahydrofuran and 2 ml of methanol were added thereto, followed by allowing the mixture to react at 30° C. under a hydrogen pressure of 50 kg/cm2 for 45 hours. The solvent was removed by distillation under reduced pressure (10 mmHg), and the reaction product was analyzed by GLC (PEG HT, 25 m, produced by Gasukuro Kogyo K.K.) to find the conversion to be 34.5%. The product was separated into the unreacted ketone and the hydrogenation product by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1 by volume) to obtain 1.73 g of 4-phenyl-3-buten-2-ol having a purity of 89%. [α]D25 : +18.1° (c=5, CS2).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=O)[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)=[CH:13][CH:12]=1.O.[NH2:25][NH2:26]>CCO>[N:17]1([C:14]2[CH:15]=[CH:16][C:11]([C:10]3[C:5]4[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C:3](=[O:2])[NH:26][N:25]=3)=[CH:12][CH:13]=2)[CH:21]=[CH:20][N:19]=[CH:18]1
Reactant: COC(=O)c1ccccc1C(=O)c1ccc(-n2ccnc2)cc1
Reactant: NN
Solvent: CCO
Solvent: O
Product: O=c1[nH]nc(-c2ccc(-n3ccnc3)cc2)c2ccccc12

Procedure:
A solution of methyl-2-[4-(1H-imidazol-1-yl)benzoyl]benzoate (1.3 g, 4.25 mmol) in 15 mL of EtOH is treated with hydrazine monohydrate (0.26 g, 5.20 mmol) and heated to reflux for 1 day. The white solid which precipitates is filtered and recrystallized from EtOH to give 4[4-(1H-imidazol-1-yl)phenyl]-1-oxo-1,2-dihydrophthalazine. M.P. 309.5°-311° C.
Reaction SMILES: C([O:3][C:4](=[O:24])[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])[N:13]=[CH:12][N:11]=1)=[O:8])C.[Li+].[OH-]>C1COCC1.O>[CH3:23][O:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:14]1[N:13]=[CH:12][N:11]=[C:10]([NH:9][C:7](=[O:8])[NH:6][CH2:5][C:4]([OH:24])=[O:3])[CH:15]=1
Reactant: CCOC(=O)CNC(=O)Nc1cc(-c2ccccc2OC)ncn1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccccc1-c1cc(NC(=O)NCC(=O)O)ncn1
Reaction time: 2 h

Procedure:
To a solution of {3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-acetic acid ethyl ester (LII) (190 mg, 0.57 mmol) in a mixture of THF and water (1:1) was added LiOH (50.0 mg, 1.12 mmol) solution in water at ice bath temperature over 10 min and the mixture was then allowed to stir for 2 hours. THF was evaporated and the aqueous solution was acidified with 2N HCl. This aqueous phase was then extracted with ethyl acetate (2×100 ml). The organic phases were separated, combined, washed with water and brine, dried over anhydrous sodium sulfate and concentrated in a vacuum rotavapor to afford {3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-acetic acid as a white solid. Yield: 184 mg, ˜quantitative.
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][CH:13]([C:15]([N:17]([CH2:22][CH2:23][O:24][CH3:25])[CH2:18][CH2:19][O:20][CH3:21])=[O:16])[CH2:14][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:26][C:27]1[C:36]([O:37][CH3:38])=[CH:35][C:30]2[NH:31][C:32](=[O:34])[S:33][C:29]=2[CH:28]=1>>[CH3:21][O:20][CH2:19][CH2:18][N:17]([CH2:22][CH2:23][O:24][CH3:25])[C:15]([CH:13]1[CH2:12][CH2:11][C:10]2[C:3]3[C:2]([NH:26][C:27]4[C:36]([O:37][CH3:38])=[CH:35][C:30]5[NH:31][C:32](=[O:34])[S:33][C:29]=5[CH:28]=4)=[N:7][CH:6]=[N:5][C:4]=3[S:8][C:9]=2[CH2:14]1)=[O:16]
Reactant: COCCN(CCOC)C(=O)C1CCc2c(sc3ncnc(Cl)c23)C1
Reactant: COc1cc2[nH]c(=O)sc2cc1N
Product: COCCN(CCOC)C(=O)C1CCc2c(sc3ncnc(Nc4cc5sc(=O)[nH]c5cc4OC)c23)C1

Procedure:
150 mg (391 μmol) (RS)-4-chloro-N,N-bis(2-methoxyethyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-7-carboxamide (prepared according to intermediate example 93a) were transformed in analogy to example 1 using 6-amino-5-methoxy-1,3-benzothiazol-2(3H)-one to give after working up and purification 27.1 mg (12%) of the title compound.
Reaction SMILES: CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Br:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([OH:33])=O.[CH:34]([C:37]1[CH:43]=[CH:42][CH:41]=[C:40]([CH:44]([CH3:46])[CH3:45])[C:38]=1[NH2:39])([CH3:36])[CH3:35]>CN(C=O)C>[Br:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([NH:39][C:38]1[C:40]([CH:44]([CH3:45])[CH3:46])=[CH:41][CH:42]=[CH:43][C:37]=1[CH:34]([CH3:36])[CH3:35])=[O:33]
Reactant: O=C(O)CCCCCCCCBr
Reactant: CC(C)c1cccc(C(C)C)c1N
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)c1cccc(C(C)C)c1NC(=O)CCCCCCCCBr
Temperature: 25 °C
Reaction time: 12 h
Yield: 40 %

Procedure:
WSC ( 809 mg, 4.6 mmols) and HOBt (621 mg, 4.6 mmols) were added to a DMF (20 ml) solution of the resulting carboxylic acid (1.19 g, 5 mmols) and 2,6-diisopropylaniline (738 mg, 4.2 mmols), and stirred at room temperature for 12 hours. The reaction mixture was extracted with ether. The organic layer was washed with water, 1 N HCl, an aqueous saturated solution of sodium hydrogencarbonate and saturated saline in that order, and dried with anhydrous magnesium sulfate, and the solvent was evaporated. Then, the residue was purified through silica gel column chromatography (developer:hexane/acetone=5/1), and the resulting crystals were recrystallized from ether-hexane to obtain 666 mg (yield: 34%) of 9-bromo-N-(2,6-diisopropylphenyl)nonanamide as colorless needle-like crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:15])[CH2:9][NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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>[F:16][C:17]1[CH:22]=[C:21]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:15])[CH2:9][NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][CH:3]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: CC(CNS(C)(=O)=O)c1ccc(Br)cc1
Reactant: OB(O)c1cccc(F)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(CNS(C)(=O)=O)c1ccc(-c2cccc(F)c2)cc1
Temperature: 100 °C
Yield: 9.6 %

Procedure:
To a degassed solution of 1.5 g (5.1 mmol) of material from Example 1, 1.1 g (7.7 mmol) of 3-fluorobenzeneboronic acid and 1.1 g (7.7 mmol) of potassium carbonate in 30 mL of toluene was added 0.2 g (0.3 mmol) of bis(triphenylphosphine)palladium(II) dichloride. The mixture was heated to 100° C. for 16 hours, cooled to ambient temperature and diluted with 20 mL of ethyl acetate. The mixture was washed once with 25 mL water and the organic portion was separated. The aqueous portion was extracted three times with ethyl acetate and the combined organics were dried (MgSO4), filtered and concentrated in vacuo. Chromatography on 75 g silica gel (20% ethyl acetate/toluene) followed by recrystallization from ethyl ether, filtration and drying in vacuo at 60° C. afforded 0.15 g (9%) of the title compound.