Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([Si](C)(C)C)([F:4])[F:3].[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:21]2[C:26]([C:27]#[N:28])=[C:25]([CH3:29])[N:24]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[C:23](=[O:40])[N:22]2[CH3:41])=[C:15]([S:17](Cl)(=[O:19])=[O:18])[CH:16]=1)#[N:10]>C1COCC1>[C:9]([C:11]1[CH:12]=[CH:13][C:14]([C@@H:21]2[C:26]([C:27]#[N:28])=[C:25]([CH3:29])[N:24]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[C:23](=[O:40])[N:22]2[CH3:41])=[C:15]([S:17]([C:2]([F:4])([F:3])[F:1])(=[O:19])=[O:18])[CH:16]=1)#[N:10]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2S(=O)(=O)Cl)N(C)C(=O)N1c1cccc(C(F)(F)F)c1
Solvent: C1CCOC1
Product: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2S(=O)(=O)C(F)(F)F)N(C)C(=O)N1c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The reaction was carried out under argon. Tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF; 18.4 mg, 66.7 μmol; 1.1 eq.) and (trifluoromethyl)trimethylsilane (2 M solution in THF, 60.6 μl, 121 μmol) were initially charged in THF (1.45 ml) at 0° C. 5-Cyano-2-{(4S)-5-cyano-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzenesulfonyl chloride (30 mg, 60.6 μmol) was added, and the mixture was stirred at RT overnight. More tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF; 16.7 mg, 60.6 μmol; 1.0 eq.) and (trifluoromethyl)trimethylsilane (2 M solution in THF, 65 μl, 130 μmol) were then added at 0° C., and the mixture was again stirred for 15 h with gradual warming to RT. The mixture was then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Gromsil C-18 10 μm; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The title compound was obtained as a solid (3.3 mg, 10% of theory).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH2:7][C:8](O)=[O:9].S(Cl)([Cl:18])=O>>[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH2:7][C:8]([Cl:18])=[O:9]
Reactant: O=C(O)COc1cccc(C(F)(F)F)c1
Reactant: O=S(Cl)Cl
Product: O=C(Cl)COc1cccc(C(F)(F)F)c1
Reaction time: 1 h

Procedure:
A solution of 6 g of the product of Step B in 36 ml of thionyl chloride was refluxed with stirring for one hour and was evaporated to dryness under reduced pressure to obtain 6.44 g of the desired product which was used as is for the next step.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[NH2:6][CH:7]1[NH:12][C:11]([NH2:13])=[CH:10][C:9](=O)[NH:8]1>>[Cl:3][C:9]1[N:8]=[C:7]([NH2:6])[N:12]=[C:11]([NH2:13])[CH:10]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: NC1=CC(=O)NC(N)N1
Product: Nc1cc(Cl)nc(N)n1

Procedure:
To 500 mL of freshly distilled POCl3 at a temperature of 80°-90° C. is added 100 g of 2,4-diamino-6-oxo-dihydropyrimidine (Aldrich, Milwaukee, Wis., USA). The mixture is distilled under reflux until, after approximately 2 hours, the mixture has completely dissolved. The residual POCl3 is suctioned off using vacuum and the remaining syrup is dripped slowly onto ice. The highly acidic solution is carefully neutralized by cooling it using concentrated sodium aluminate solution, and in the final stage with solid sodium carbonate. When completed the total volume of solution is approximately 1800 mL. Upon cooling a yellowish precipitate is separated out which is suctioned off and dried in a vacuum desiccator. The end product which contains mostly non-organic salts is boiled three times, each time with 1 liter of acetone to which active charcoal is added. The extracts are cooled and the resulting clear precipitate is collected. Evaporation of the filtrates yields an additional fraction.
Reaction SMILES: COC(=O)C[NH:5][C:6](=[O:37])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:35][CH2:34]3)[CH2:25][CH2:24]2)=[O:22])=[CH:9][C:8]=1[Cl:36].[CH3:39][O:40][C:41](=[O:49])[C:42]1[CH:47]=[CH:46][C:45](N)=[CH:44][CH:43]=1>CCCCCCC.C(OCC)(=O)C>[CH3:39][O:40][C:41](=[O:49])[C:42]1[CH:47]=[CH:46][C:45]([NH:5][C:6](=[O:37])[C:7]2[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[C:21]([N:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]([CH:33]4[CH2:35][CH2:34]4)[CH2:25][CH2:24]3)=[O:22])=[CH:9][C:8]=2[Cl:36])=[CH:44][CH:43]=1
Reactant: COC(=O)c1ccc(N)cc1
Reactant: COC(=O)CNC(=O)c1cc(Cl)c(Oc2ccncc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(NC(=O)c2cc(Cl)c(Oc3ccncc3C(=O)N3CCN(C4CC4)c4ccccc43)cc2Cl)cc1

Procedure:
The title compound was prepared in analogy to Example 1, from 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid (Example 29, intermediate) and 4-amino-benzoic acid methyl ester (commercially available, CAS RN 619-45-4) and using a gradient of n-heptane:ethyl acetate (100:0 to 0:100) for the chromatographic purification. Light brown foam (29%). MS (ESI): m/z=617.136 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([CH3:13])([C:7](=O)[C:8](OC)=[O:9])[C:3]([O:5][CH3:6])=[O:4].[F:14][C:15]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:16]=1[CH2:17][N:18]1[C:22]2=[N:23][C:24]([CH3:27])=[N:25][CH:26]=[C:21]2[C:20]([C:28](=[NH:31])[NH:29][NH2:30])=[N:19]1>C(O)C>[F:14][C:15]1[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:16]=1[CH2:17][N:18]1[C:22]2=[N:23][C:24]([CH3:27])=[N:25][CH:26]=[C:21]2[C:20]([C:28]2[N:29]=[N:30][C:7]([C:2]([CH3:13])([CH3:1])[C:3]([O:5][CH3:6])=[O:4])=[C:8]([OH:9])[N:31]=2)=[N:19]1
Reactant: Cc1ncc2c(C(=N)NN)nn(Cc3cccc(F)c3F)c2n1
Reactant: COC(=O)C(=O)C(C)(C)C(=O)OC
Solvent: CCO
Product: COC(=O)C(C)(C)c1nnc(-c2nn(Cc3cccc(F)c3F)c3nc(C)ncc23)nc1O
Yield: 27 %

Procedure:
374 mg (1.985 mmol) of dimethyl 2,2-dimethyl-3-oxobutanedioate were initially charged in 8 ml of ethanol and heated to reflux. Subsequently, 420 mg (1.324 mmol) of 1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidohydrazide suspended in 8 ml of ethanol were added and the mixture was heated to reflux overnight. Another 299 mg (1.588 mmol) of dimethyl 2,2-dimethyl-3-oxobutanedioate dissolved in 3 ml of ethanol were added and the mixture was boiled under reflux overnight. After cooling, the mixture was filtered and purified directly by means of preparative HPLC (eluent: acetonitrile/water, gradient 30:70→100:0). 163 mg of the target compound were obtained (purity 89%; 24% of theory).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([I:28])=[C:7]([C:19]([I:27])=[C:20]([NH:23][C:24](=[O:26])[CH3:25])[C:21]=1[I:22])[C:8]([NH:10][C@H:11]([C:16]([OH:18])=[O:17])[CH2:12][CH:13]([CH3:15])[CH3:14])=[O:9])(=[O:3])[CH3:2].[N+:29]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1O)([O-:31])=[O:30].C1(N=C=NC2CCCCC2)CCCCC1>>[N+:29]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[O:17][C:16](=[O:18])[C@H:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[NH:10][C:8](=[O:9])[C:7]1[C:6]([I:28])=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[C:21]([I:22])=[C:20]([NH:23][C:24](=[O:26])[CH3:25])[C:19]=1[I:27])([O-:31])=[O:30]
Reactant: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)N[C@@H](CC(C)C)C(=O)O)c1I
Reactant: O=[N+]([O-])c1ccccc1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)N[C@@H](CC(C)C)C(=O)Oc2ccccc2[N+](=O)[O-])c1I

Procedure:
Following the procedure of example 33, the product is synthesized from 14.6 g (20 mMol) N-(3,5-diacetamido-2,4,6-triiodobenzoyl)-L-leucine, 3,5 g (25 mMol) o-nitrophenol and 5 g (24 mMol) N,N'-dicyclohexylcarbodiimide. Yield: 12.5 g (73%).
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH:14]=[CH:13][CH2:12][N:11]1[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:24][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=1[Cl:23])[CH2:16][N:11]1[CH2:12][CH:13]=[CH:14][CH2:15][CH:10]1[CH2:9][CH2:8][NH2:7]
Reactant: CC(C)(C)OC(=O)NCCC1CC=CCN1Cc1ccc(Cl)c(Cl)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCCC1CC=CCN1Cc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of 2-[1-(3,4-dichlorobenzyl)-1,2,3,6-tetrahydropyridin-2-yl]ethylcarbamic acid tert-butyl ester (1.0 g, 2.9 mmol) dissolved in dichloromethane at 5° C. was added trifluoroacetic acid (10 mL). After stirring at room temperature for 2.5 h the solvent was evapaorated, partitioned between dichloromethane (50 mL) and saturated aqueous sodium bicarbonate solution (25 mL). The organic layer was separated, dried and evaporated to yield the title compound as a colourless gum. δH (CDCl3+D2O) 1.46-1.63 (1H, m), 1.71-1.95 (2H, m), 2.18-2.47 (1H, m), 2.68-3.07 (4H, m), 3.60 (2H, s), 5.30 (1H, s), 5.57 (1H, d, J=10.1 Hz), 5.74 (1H, d, J=10.2 Hz), 7.10-7.50 (3H, m); MS (ES+) 285 (100%) MH+.
Reaction SMILES: C([O:8][C:9]1[C:10]([O:36][CH:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:11][C:12]([CH2:15][O:16][C:17]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:13][CH:14]=1)C1C=CC=CC=1>[Pd].C(O)C>[CH:37]1([O:36][C:10]2[C:9]([OH:8])=[CH:14][N:13]=[C:12]([CH2:15][O:16][C:17]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:11]=2)[CH2:38][CH2:39][CH2:40][CH2:41]1
Reactant: c1ccc(COc2cnc(COC(c3ccccc3)(c3ccccc3)c3ccccc3)cc2OC2CCCC2)cc1
Agent: [Pd]
Solvent: CCO
Product: Oc1cnc(COC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 93.2 %

Procedure:
5% Palladium on charcoal catalyst (2 g) is added to a solution of 5-benzyloxy-4-cyclopentyloxy-2-trityloxymethylpyridine (24.2 g) in ethanol (500 mL) and the mixture stirred at room temperature under a hydrogen atmosphere for 3 hours. After filtering the filtrate is concentrated in vacuo to give a colourless oil which is purified by flash chromatography (n-pentane/ethyl acetate 7:3 v/v as eluent on silica) to give 4-cyclopentyloxy-5-hydroxy-2-trityloxymethylpyridine (18.8 g) as a colourless foam. [1Hnmr in deuterochloroform with Me4Si as standard:— 1.70, 2H, m; 1.82, 2H, m; 1.90-2.08, 4H, m; 4.25, 2H, s; 4.93, 1H, m; 7.19, 1H, s; 7.24, 7.30, 7.49, 15H, Ar; 8.04, 1H, s.].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][C:15]=2[Cl:24])[CH:3]=1.[CH2:25](S(C1C=CC(F)=C(Cl)C=1)(=O)=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH2:23][CH3:25])(=[O:21])=[O:22])=[CH:16][C:15]=2[Cl:24])[CH:3]=1
Reactant: CCS(=O)(=O)c1ccc(F)c(Cl)c1
Reactant: CS(=O)(=O)c1ccc(Nc2cc(Cl)ccc2CCC(=O)O)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Product: CCS(=O)(=O)c1ccc(Nc2cc(Cl)ccc2CCC(=O)O)c(Cl)c1

Procedure:
A solution of the product from example 49 step (iii) (0.163 g) and the product of example 4 step (i) (0.200 g) and caesium carbonate (0.239 g) in NMP (10 ml) was refluxed at 100° C. for 3 hours. The mixture was partitioned between 2M sodium hydroxide and diethyl ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate and the organic layer dried and concentrated under reduced pressure to give an oil. The residue was purified using RP prep HPLC. Yield 0.044 g.
Reaction SMILES: [C:1]([OH:13])(=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].N1C=CC=CC=1.[CH3:20][Si:21](Cl)([CH3:23])[CH3:22]>C1(C)C=CC=CC=1>[CH3:20][Si:21]([O:12][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11])([CH3:23])[CH3:22]
Reactant: C=CCCCCCCCCC(=O)O
Reactant: C[Si](C)(C)Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: C=CCCCCCCCCC(=O)O[Si](C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a 3-liter, 3-neck flask equipped with an addition funnel, mechanical stirrer and reflux condenser were added undecylenic acid (Lucidol, 480 grams, 2.6 mol), pyridine (240 grams, 3.03 mol) and toluene (900 milliliters). Trimethylsilyl chloride (326 grams, 3.0 mol) was then added slowly via the addition funnel over 2.5 hours. After stirring at 25° C. for 16 hours, the precipitate was filtered off and washed with toluene. The flitrates were combined and the toluene was removed using a rotary evaporator. The residue was distilled through a packed column under reduced pressure and four fractions were collected. A first cut was collected between 25° C. and 115° C. at 1 millimeter of mercury. A second cut was collected between 115° C. and 119° C. at 1 millimeter of mercury. The third cut, collected between 115° C. and 120° C. at 1 millimeter of mercury, was identified by infrared spectroscopy, and with 13C and 1H NMR spectrometries as the trimethylsilyl ester of undecylenic acid (320.4 grams). A fourth cut, collected between 115° C. and 121° C. at 1 millimeter of mercury, was a light-yellow oil. There was no evidence of free acid in fraction 3 using infrared spectroscopy. The carboxylic acid infrared absorption of undecylenic acid was found at 1,720 cm-1. The trimethylsilyl ester group absorbed at 1,640 cm-1.
Reaction SMILES: [C:1]([OH:12])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].Cl.[CH3:14][NH:15][O:16][CH3:17].O>ClCCl>[CH3:17][O:16][N:15]([CH3:14])[C:1](=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCC(=O)O
Reactant: CNOC
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCCC(=O)N(C)OC
Reaction time: 1.5 h
Yield: 96.1 %

Procedure:
Decanoic acid (4 g, 23.2 mmol) was dissolved in an anhydrous dichloromethane solution (80 mL), and 1,1-carbonyldiimidazole (4.5 g, 27.9 mmol) was then added to the solution, followed by stirring for 1.5 hours. Subsequently, N,O-dimethylhydroxyamine hydrochloride (2.7 g, 27.9 mmol) was added to the reaction solution, and the obtained mixture was further stirred for 3 hours. After addition of distilled water, the reaction solution was extracted with dichloromethane two times. Anhydrous magnesium sulfate was added to the organic layer to dry it, and the resultant was filtrated and was then concentrated. The obtained residue was purified using column chromatography (hexane:ethyl acetate=8:1), so as to obtain N-methoxy-N-methyldecanamide (4.8 g, 97%) as an amide body in the form of a colorless transparent liquid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:11]2[C:19]3[C:14](=[C:15]([F:29])[C:16]([O:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([CH2:27][OH:28])[CH:22]=4)=[CH:17][CH:18]=3)[CH:13]=[C:12]2[CH3:30])=[O:10])=[CH:4][C:3]=1[C:31]([F:34])([F:33])[F:32].[CH3:35][S:36](Cl)(=[O:38])=[O:37]>ClCCl.[NH4+].[Cl-]>[F:29][C:15]1[C:16]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([CH2:27][O:28][S:36]([CH3:35])(=[O:38])=[O:37])[CH:22]=2)=[CH:17][CH:18]=[C:19]2[C:14]=1[CH:13]=[C:12]([CH3:30])[N:11]2[C:9](=[O:10])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:31]([F:33])([F:32])[F:34])[CH:4]=1
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cc2c(F)c(Oc3ccnc(CO)c3)ccc2n1C(=O)Nc1ccc(F)c(C(F)(F)F)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: Cc1cc2c(F)c(Oc3ccnc(COS(C)(=O)=O)c3)ccc2n1C(=O)Nc1ccc(F)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
4-Fluoro-5-(2-hydroxymethyl-pyridin-4-yloxy)-2-methyl-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (370 mg, 0.775 mmol) is placed in dichloromethane (10 mL) and methanesulfonyl chloride (0.15 mL, 1.92 mmol) and TEA (0.4 ml, 2.87 mmol) are added. The reaction is stirred at rt for 20 min before being diluted with dichloromethane and saturated aqueous NH4Cl. The aqueous layer is extracted further with dichloromethane. The combined organic layers are washed with brine and dried over Na2SO4, filtered, and concentrated to give the title compound. MS (ESI) m/z 555.8 (M+1)
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([C:13]1[NH:17][C:16]([CH3:18])=[C:15]([CH3:19])[CH:14]=1)=[O:12].[CH3:20][CH:21]1[CH2:23][CH:22]1[CH2:24]Br>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([C:13]1[N:17]([CH2:20][CH:21]2[CH2:23][CH:22]2[CH3:24])[C:16]([CH3:18])=[C:15]([CH3:19])[CH:14]=1)=[O:12]
Reactant: CC1CC1CBr
Reactant: Cc1cc(C(=O)CCc2ccc(F)cc2F)[nH]c1C
Product: Cc1cc(C(=O)CCc2ccc(F)cc2F)n(CC2CC2C)c1C
Yield: 80.2 %

Procedure:
The title compound was prepared as a yellow oil in 80.2% yield in a similar procedure to that described in Referential Example 97 by using 5-[3-(2,4-difluorophenyl)propionyl]-2,3-dimethylpyrrole and 2-methylcyclopropylmethyl bromide.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][NH:6][CH:5]=1)([O-:3])=[O:2].[I:9][C:10](=[C:23]([I:25])[I:24])[CH2:11]OS(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+]>CN(C)C=O>[I:9][C:10](=[C:23]([I:25])[I:24])[CH2:11][N:6]1[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[CH:5]1
Reactant: Cc1ccc(S(=O)(=O)OCC(I)=C(I)I)cc1
Reactant: O=[N+]([O-])c1cc[nH]c1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccn(CC(I)=C(I)I)c1
Reaction time: 0.25 h

Procedure:
To a solution of 112 mg (1 mmole) of 3-nitropyrrole in 5.0 ml of dry N,N-dimethylformamide were added 606 mg of 2,3,3-triiodoallyl-p-toluenesulfonate and 60 mg (1.5 mmoles) of powdery sodium hydroxide and the reaction was carried out with stirring for 15 minutes.
Reaction SMILES: [NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH:6]=[N:5][C:4]2=[N:15][N:16]=[CH:17][C:3]=12.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>N1C=CC=CC=1>[NH2:1][C:2]1[N:7]([C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)[CH2:6][N:5]([C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:4]2=[N:15][N:16]=[CH:17][C:3]=12
Reactant: Cc1ccc(-n2cnc3nncc-3c2N)cc1
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Product: Cc1ccc(N2CN(C(=O)c3ccccc3)C3=NN=CC3=C2N)cc1
Reaction time: 0.75 h
Yield: 47.7 %

Procedure:
To a stirred solution of 4-amino-5-(4'-methylphenyl)pyrazolo[3,4-d]pyrimidine (0.40 g, 1.77 mmol) in pyridine (9 mL) was added benzoyl chloride (0.25 g, 1.77 mmol) dropwise. After 45 minutes, the pyridine was removed in vacuo and the resulting solids were washed with water and EtOH to afford 0.28 g of the title compound; m.p. 297°-300° C. Anal. calcd. for C19H15N5.0.75 H2O: C, 66.55; H, 4.85; N, 20.42. Found: C, 6.43; H, 4.69; N, 19.77.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[N:17]([CH2:18][CH2:19][CH3:20])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][CH2:29][C:30]4[C:35]([CH3:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=4[CH3:38])[CH:23]=3)[CH:14]=2)[N:9]=1)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:18]([N:17]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][CH2:29][C:30]4[C:31]([CH3:38])=[CH:32][C:33]([CH3:37])=[CH:34][C:35]=4[CH3:36])[CH:23]=3)[CH:14]=2)[N:9]=[C:8]1[NH2:7])[CH2:19][CH3:20]
Reactant: CCCN1Cc2cc(Oc3cccc(NCc4c(C)cc(C)cc4C)c3)ccc2N=C1NC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCN1Cc2cc(Oc3cccc(NCc4c(C)cc(C)cc4C)c3)ccc2N=C1N
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of {3-propyl-6-[3-(2,4,6-trimethyl-benzylamino)-phenoxy]-3,4-dihydro-quinazolin-2-yl}-carbamic acid tert-butyl ester (0.0001 mol) in 10% TFA in DCM (6 mL) was stirred in a reaction vial for 1 hour at room temperature and then the solvent was evaporated. The obtained residue was crystallized from CH3CN, and then the desired product was filtered off, washed with diisopropyl ether and dried under vaccum to yield the title compound as a solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>>[C:7]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1
Reactant: BrCCCOc1ccccc1-c1ccccc1
Reactant: C1COCCN1
Product: c1ccc(-c2ccccc2OCCCN2CCOCC2)cc1

Procedure:
2-(3-Bromo-propoxy)-biphenyl (1.0 g) was reacted with morpholine (5 mL) at 50° C. for 1 hour to form 4-[3-(biphenyl-2-yloxy)-propyl]-morpholine. The excess morpholine was evaporated and water was added, followed by extraction with ethyl acetate. Removal of ethyl acetate afforded 900 mg of 4-[3-(biphenyl-2-yloxy)-propyl]-morpholine (t) as an oil which was used without further purification: m/e: 297.17, MS (ES+): 298.2; 1H NMR (500 MHz, CDCl3): 7.8-7.0 (m, 9H), 4.0 (m, 2H), 3.7 (m, 4H), 2.5 (m, 6H) and 1.8 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[CH:13]([O:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:25]=1)[C:20](O)=[O:21])([CH3:15])[CH3:14]>>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][C:5]1[N:6]=[C:2]([NH:1][C:20](=[O:21])[C:19]2[CH:23]=[C:24]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:25]=[C:17]([O:16][CH:13]([CH3:14])[CH3:15])[CH:18]=2)[S:3][CH:4]=1)[CH3:12]
Reactant: CCOC(=O)Cc1csc(N)n1
Reactant: CC(C)Oc1cc(Oc2ccccc2)cc(C(=O)O)c1
Product: CCOC(=O)Cc1csc(NC(=O)c2cc(Oc3ccccc3)cc(OC(C)C)c2)n1

Procedure:
The title compound was prepared from ethyl 2-aminothiazol-4-ylacetate and 3-isopropyloxy-5-phenoxybenzoic acid following synthetic description A.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[CH:3]([C:5]1[C:14]2[CH2:13][O:12][CH2:11][N:10]([C:15]3[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=3[CH3:23])[C:9]=2[N:8]=[C:7]([CH3:24])[N:6]=1)[OH:4].[CH3:27][N:28]=[C:29]=[O:30].CN(C1C=CC=CN=1)C>ClCCl>[F:26][C:2]([F:25])([F:1])[CH:3]([O:4][C:29](=[O:30])[NH:28][CH3:27])[C:5]1[C:14]2[CH2:13][O:12][CH2:11][N:10]([C:15]3[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=3[CH3:23])[C:9]=2[N:8]=[C:7]([CH3:24])[N:6]=1
Reactant: Cc1cc(C)c(N2COCc3c(C(O)C(F)(F)F)nc(C)nc32)c(C)c1
Reactant: CN=C=O
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CNC(=O)OC(c1nc(C)nc2c1COCN2c1c(C)cc(C)cc1C)C(F)(F)F

Procedure:
A mixture of 2,2,2-trifluoro-1-[7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-5yl]-ethanol (26 mg), methyl isocyanate (0.12 ml), dimethylaminopyridine (27 mg) in dichloromethane (2 ml) was heated at reflux for 2 hrs. The mixture was quenched with water and extracted with chloroform. The organic layer was separated, dried and concentrated to give the crude material which was purified by silica gel column chromatography using chloroform as eluent to give 21 mg of the title compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[N+:12]([O-])([OH:14])=[O:13].O>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[CH:6][C:7]=1[N+:12]([O-:14])=[O:13]
Reactant: O=[N+]([O-])O
Reactant: COc1ccc(Br)cc1OC
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(Br)c([N+](=O)[O-])cc1OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To the solution of 4-bromoveratrole (20 g) in acetic acid (50 ml) was added 2M nitric acid (48 ml). It was stirred at room temperature for 30 min and then the reaction solution was poured into water. The resultant solid was filtered, washed with water and dried in vacuum.