Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:5]1[CH2:31][CH2:30][CH2:29][CH2:28][C:8]2[C:9](Br)=[C:10]3[C:19]4[CH:18]=[C:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[C:16]([O:25][CH3:26])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:32])([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:38]1[S:39][CH:40]=[CH:41][CH:42]=1)CCC>C1(C)C=CC=CC=1.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>[C:1]([N:5]1[CH2:31][CH2:30][CH2:29][CH2:28][C:8]2[C:9]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)=[C:10]3[C:19]4[CH:18]=[C:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[C:16]([O:25][CH3:26])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:32])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCS(=O)(=O)c1cc2c(cc1OC)CCn1c3c(c(Br)c1-2)CCCCN(C(C)(C)C)C3=O
Reactant: CCCC[Sn](CCCC)(CCCC)c1cccs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CCS(=O)(=O)c1cc2c(cc1OC)CCn1c3c(c(-c4cccs4)c1-2)CCCCN(C(C)(C)C)C3=O
Yield: 67.6 %

Procedure:
A solution of 50 mg of 23e, 60 mg of 2-tributylstannylthiophene and 10 mg of tetrakis(triphenylphosphine)palladium(0) in 2 ml of toluene was heated at 125° C. for 16 hr under a nitrogen atmosphere. Reaction was cooled and applied onto silica gel column and eluted with a gradient of toluene/acetone. The fractions containing the product were pooled and concentrated and the remainder crystallized from ethylacetate/ether, providing 34 mg of 23f; Mp: 223-224° C. Rf 0.55 (toluene/acetone 2/1). LC-MS-ESI: [M+1] 527.08. NMR (CDCl3) δ 6.82 and 7.63 (2×s, Ar—H), 6.92, 7.16 and 7.41 (3×m 3, thienyl-H), 1.12 (t, 3, ethyl), 3.22 (m, 3, ethyl), 3.94 (s, 3, OCH3), 4.70 (bm, 1, CH2,) 3.80 (bm, 2, CH2), 3.55 (bm, 1, CH2), 3.02 and 3.20 (2×b.m, 2, CH2), 2.55 (b.m, 2, CH2), 1.60-2.00 (b.m, 4, CH2), 1.56 (s, 9, tertC4H9).
Reaction SMILES: S(Cl)(Cl)=O.[CH2:5]([S:7]([O:10][C:11]1[CH:16]=[CH:15][C:14](O)=[C:13]([C:18]([CH3:22])([CH3:21])[CH2:19][OH:20])[CH:12]=1)(=[O:9])=[O:8])[CH3:6].O>CN(C)C=O>[CH2:5]([S:7]([O:10][C:11]1[CH:16]=[CH:15][C:14]2[O:20][CH2:19][C:18]([CH3:22])([CH3:21])[C:13]=2[CH:12]=1)(=[O:9])=[O:8])[CH3:6]
Reactant: CCS(=O)(=O)Oc1ccc(O)c(C(C)(C)CO)c1
Solvent: O=S(Cl)Cl
Solvent: O
Solvent: CN(C)C=O
Product: CCS(=O)(=O)Oc1ccc2c(c1)C(C)(C)CO2
Temperature: 5 °C
Yield: 69.9 %

Procedure:
Thionyl chloride (4.3 g) was added dropwise to dimethylformamide (13 ml) maintained at about 5° C. To this was quickly added 4-hydroxy-3-(2-hydroxy-1,1-dimethylethyl)phenyl ethanesulphonate (9.5 g) from Example 2 in dimethylformamide (13 ml). The reaction mixture was then heated to 100° C. and maintained at that temperature for 4-5 hours, after which it was cooled and poured into water (100 ml). The oil was extracted with diethyl ether, washed with water, dried over magnesium sulphate and evaporated down to give 6.2 g of a brownish oil.
Reaction SMILES: C[O:2][CH:3](OC)[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:11][CH2:12][OH:13])=[CH:6][CH:5]=1.Cl>CO>[OH:13][CH2:12][CH2:11][CH:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:3]=[O:2])=[CH:9][CH:8]=1)[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1
Reactant: COC(OC)c1ccc(C(CCO)c2cccnc2)cc1
Agent: Cl
Solvent: CO
Product: O=Cc1ccc(C(CCO)c2cccnc2)cc1
Reaction time: 20 h
Yield: 100.4 %

Procedure:
4-[3-Hydroxy-1-(3-pyridyl)propyl]benzaldehyde dimethyl acetal (0.51 g) was dissolved in 10 ml of methanol, followed by addition of 5 ml of 6N hydrogen chloride, and stirred for 20 hours. The solvent was distilled off under reduced pressure, followed by neutralization with aqueous 2N sodium hydroxide solution, which was then extracted with methylene chloride. The organic phase was washed in saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure, to obtain 0.43 g of 4-[3-hydroxy-1-(3-pyridyl)propyl]benzaldehyde.
Reaction SMILES: [CH3:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[H-].[Na+].[Si:9]([O:16][C@@H:17]1[C:25]2[C:20](=[C:21]([C:27]3[C:28](F)=[N:29][CH:30]=[CH:31][CH:32]=3)[CH:22]=[CH:23][C:24]=2[F:26])[CH2:19][CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]>CN1CCCC1=O>[Si:9]([O:16][C@@H:17]1[C:25]2[C:20](=[C:21]([C:27]3[C:28]([O:4][CH2:3][C:2]([CH3:6])([CH3:5])[CH3:1])=[N:29][CH:30]=[CH:31][CH:32]=3)[CH:22]=[CH:23][C:24]=2[F:26])[CH2:19][CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]
Reactant: CC(C)(C)CO
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1CCc2c(-c3cccnc3F)ccc(F)c21
Agent: [H-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: CC(C)(C)COc1ncccc1-c1ccc(F)c2c1CC[C@@H]2O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
2,2-Dimethylpropan-1-ol (59 mg) is dissolved at 0° C. in N-methylpyrrolidone (NMP, 2 mL), treated with NaH (27 mg, 55% dispersion in mineral oil) and stirred for 15 minutes. The mixture is warmed to room temperature, treated with a solution of 3-((1S)-1-(tert-butyldimethylsilyloxy)-7-fluoro-2,3-dihydro-1H-inden-4-yl)-2-fluoropyridine (200 mg) in N-methylpyrrolidone (NMP, 1 mL) and stirred for 12 hours at 75° C. 2,2-Dimethylpropan-1-ol (59 mg) and NaH (27 mg, 55% dispersion in mineral oil) are added and the mixture is stirred for 4 hours at 80° C. The mixture thus obtained is directly used in the next step.
Reaction SMILES: [CH:1]1([NH:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Mo:14](=O)(=O)=O>>[Mo:14].[CH:8]1([NH:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: O=[Mo](=O)=O
Agent: C1CCC(NC2CCCCC2)CC1
Product: [Mo]

Procedure:
Dicyclohexylamine and molybdenum trioxide were reacted together in the following manner to form a dicyclohexylamine molybdate with a 2/1 molybdenum/dicyclohexylamine molar ratio. 10.00 grams of dicyclohexylamine, 15.88 grams of molybdenum trioxide, 10.94 grams of ammonium sulfate and 300 milliliters of water were charged into a 500 milliliter round-bottom flask equipped with a water-cooled condenser.
Reaction SMILES: Cl[CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:22]([NH:23][C:24](=[O:72])[C:25]([C:47]3[N:48]=[C:49]([NH:52][C:53]([C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)([C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[S:50][CH:51]=3)=[N:26][O:27][CH:28]([C:31]([O:33][CH:34]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])[CH2:29][CH3:30])[C:21](=[O:73])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[O:10].[I-:74].[Na+]>CC(C)=O>[I:74][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:22]([NH:23][C:24](=[O:72])[C:25]([C:47]3[N:48]=[C:49]([NH:52][C:53]([C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)([C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[S:50][CH:51]=3)=[N:26][O:27][CH:28]([C:31]([O:33][CH:34]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])[CH2:29][CH3:30])[C:21](=[O:73])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[O:10]
Reactant: [I-]
Reactant: CCC(ON=C(C(=O)NC1C(=O)N2C(C(=O)OCc3ccc(OC)cc3)=C(CCl)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1)C(=O)OC(c1ccccc1)c1ccccc1
Agent: [Na+]
Solvent: CC(C)=O
Product: CCC(ON=C(C(=O)NC1C(=O)N2C(C(=O)OCc3ccc(OC)cc3)=C(CI)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1)C(=O)OC(c1ccccc1)c1ccccc1

Procedure:
100 mg (0.1 mmol) of p-methoxybenzyl 3-chloromethyl-7-{2-(2-tritylamino-4-thiazolyl)-2-(1-diphenylmethoxycarbonylpropyloxyimino)acetamido}-ceph-3-em-4-carboxylate-syn isomer was dissolved in 1 ml of acetone, and 0.5 ml of acetone solution containing 28 mg (0.19 mmol) of sodium iodide was added to the resulting solution at room temperature and reacted for 40 minutes. After the reaction, the solvent was distilled out, methylene chloride was added to the residue, the insoluble materials were filtrated out, and the remaining filtrate was concentrated under reduced pressure, to obtain p-methoxybenzyl 3-iodomethyl-7-{2-(2-tritylamino-4-thiazolyl)-2-(1-diphenylmethoxycarbonyl-propyloxyimino) acetamido}-ceph-3-em-4-carboxylate-syn isomer. To this was added 18 mg (0.11 mmol) of 1-(2-fluoroethyl)-4-pyridothione, and the resulting mixture was dissolved in 1 ml of chloroform and reacted for 1 hour at room temperature. After the reaction, the chloroform was distilled out under reduced pressure, and the residue was purified by silicagel-chromatography (chloroform/methanol=10/1) and dissolved in 0.4 ml of anisole, and then 1.3 ml of trifluoroacetic acid was added thereto, while cooled with ice, and reacted for 1 hour. After the reaction, isopropylether was added to the reaction solution to form a precipitate therein. After dried, 80 mg of a powder was obtained. To this was added 1 ml of water and the pH value of the resulting solution was adjusted to 7.8 with sodium hydrogencarbonate, and the solution was purified with HP-20 resin (methanol/H2O=1/4) to obtain 45 mg of the above-entitled compound.
Reaction SMILES: [CH3:1][C:2]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:14]1[N:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[K+].C>O>[CH3:1][C:2]1[C:8]([C:9]([F:10])([F:11])[F:12])=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:14]1[C:15]([C:16]([OH:18])=[O:17])=[CH:19][CH:20]=[CH:21][N:22]=1
Reactant: Cc1c(N)cccc1C(F)(F)F
Reactant: O=C(O)c1cccnc1Cl
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Cc1c(Nc2ncccc2C(=O)O)cccc1C(F)(F)F
Temperature: 50 °C
Reaction time: 0.17 h
Yield: 83 %

Procedure:
) A mixture of 2-methyl-3-trifluoromethylaniline (368 g, 2.1 moles) and 2-chloronicotinic acid (158.0 g, 1.0 mole) in 400 ml of water is heated at 100° C. for 24 hours together with p-toluenesulfonic acid (15.0 g) monohydrate as the acid catalyst. Potassium hydroxide (ca. 145 g) in water (255 ml) is added and the pH is maintained above 11. After diluting the reaction mixture to 1.2 liters with water, the mixture is cooled to 50° C., adjusted to pH 11, treated with 7 g of a decolorizing charcoal and 15 g of a filter aid, and clarified by filtration. The flitrate is diluted with 750 ml of water and the pH is adjusted to 5.0 with concentrated sulfuric acid. Agitation of the suspension for 10 minutes and filtration gives crude, precipitated 2-[[2-methyl-3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid (flunixin) (83% yield). The compound can be further purified by crystallization in methanol and washing with water.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH2:8].[I:9][C:10]1[CH:15]=[CH:14][C:13]([S:16](O)(=[O:18])=[O:17])=[CH:12][CH:11]=1>C(Cl)Cl>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][S:16]([C:13]1[CH:14]=[CH:15][C:10]([I:9])=[CH:11][CH:12]=1)(=[O:18])=[O:17]
Reactant: N[C@@H]1CCCC[C@@H]1N
Reactant: O=S(=O)(O)c1ccc(I)cc1
Solvent: ClCCl
Product: N[C@H]1CCCC[C@H]1NS(=O)(=O)c1ccc(I)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 34.6 %

Procedure:
Cis-1,2-diaminocyclohexane (0.70 g, 6.86 mmol) was stirred in CH2Cl2 (40 mL) at 0° C. under N2. A solution of 4-iodobenzenesulfonic acid (0.85 g, 2.81 mmol) in CH2Cl2 (20 mL) was added dropwise to the above solution. It was stirred for 30 min at 0° C. LC/MS showed completion of the reaction. It was washed with 1N HCl. The aqueous solution was basified with 1N NaOH until formation of a cloudy solution. It was extracted with CH2Cl2 (3×), washed with brine, dried (MgSO4), and concentrated to dryness to give cis-N-(2-amino-cyclohexyl)-4-iodobenzenesulfonamide (0.37 g, yield: 35%). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J=6.8 Hz, 2H), 7.60 (d, J=6.7 Hz, 2H), 3.15 (m, 1H), 2.84 (m, 1H), 1.48 (m, 10H) ppm.
Reaction SMILES: [CH3:1][CH2:2][N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12](/[C:15](/[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[C:16](/Cl)\[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:13][CH:14]=1)[CH2:4][CH3:5].C([Li])(C)(C)C.[CH2:35]1[O:37][CH2:36]1.O>O1CCCC1>[CH3:1][CH2:2][N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12](/[C:15](/[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[C:16](\[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)/[CH2:35][CH2:36][OH:37])=[CH:13][CH:14]=1)[CH2:4][CH3:5]
Reactant: C1CO1
Reactant: CCN(CC)CCOc1ccc(/C(=C(/Cl)c2ccccc2)c2ccccc2)cc1
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: O
Product: CCN(CC)CCOc1ccc(/C(=C(/CCO)c2ccccc2)c2ccccc2)cc1
Reaction time: 0.08 h

Procedure:
Clomiphene (6.06 g, 14.9 mmol) was dissolved in tetrahydrofuran (100 ml) and cooled to -40° C. t-Butyl lithium (1 M in pentane, 24 mmol) was added slowly. After 5 minutes, ethylene oxide (14.6 ml, 290 mmol) was added, and the reaction mixture was stirred for 6 hours, poured into water and extracted with ether. The ether layer was evaporated and chromatographed on a silica gel column using 1:1:0.1 ether/petroleum ether/triethylamine as eluant to yield trans product (1.96 g, 27.1%, oil): and cis product (1.56 g, 21.5%, oil): Assignment of 1HNMR for aliphatic protons are presented in Table 2.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:20])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]2=[O:19])[CH:5]=[CH:6][CH:7]=1.[C:21]([O-])([O-])=O.[Cs+].[Cs+].IC>CN(C=O)C>[Br:1][C:2]1[C:3]([CH3:20])=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH3:21])[C:9]2=[O:19])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1c(Br)cccc1-n1c(=O)[nH]c2ccccc2c1=O
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cc1c(Br)cccc1-n1c(=O)c2ccccc2n(C)c1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64.9 %

Procedure:
A suspension of 3-(3-bromo-2-methylphenyl)quinazoline-2,4(1H,3H)-dione (23.02 g, 69.5 mmol) and Cs2CO3 (34.0 g, 104 mmol) in DMF (70 mL) cooled in an ice-water bath was treated portionwise with iodomethane (5.22 mL, 83 mmol). The mixture was warmed to room temperature and stirred for 30 min. The mixture was filtered and the filtrate was concentrated. The residue was partitioned between EtOAc and water. A precipitate which formed was collected by filtration. The collected solid was washed with water and dried overnight under vacuum to give a white solid. The organic phase of the filtrate was separated, washed 3 times with 10% aqueous LiCl, then was washed twice with water, dried and concentrated to give additional solid. The two solids were combined to give 3-(3-bromo-2-methylphenyl)-1-methylquinazoline-2,4(1H,3H)-dione as a white solid (15.56 g, 92% yield). Mass spectrum m/z 345, 347 (M+H)+.
Reaction SMILES: [CH2:1]([C:4]1[C:13]([OH:14])=[C:12]([CH2:15][CH:16]=[CH2:17])[CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C:8](=[O:18])[NH:9]2)[CH:2]=[CH2:3].Cl.[C:20](=[O:23])(O)[O-].[Na+]>O1C=CCCC1>[CH2:1]([C:4]1[C:13]([O:14][CH:3]2[CH2:2][CH2:1][CH2:4][CH2:20][O:23]2)=[C:12]([CH2:15][CH:16]=[CH2:17])[CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C:8](=[O:18])[NH:9]2)[CH:2]=[CH2:3]
Reactant: O=C([O-])O
Reactant: C=CCc1cc2c(c(CC=C)c1O)CCC(=O)N2
Agent: C1=COCCC1
Agent: Cl
Agent: [Na+]
Product: C=CCc1cc2c(c(CC=C)c1OC1CCCCO1)CCC(=O)N2
Temperature: 60 °C
Reaction time: 8 h
Yield: 58 %

Procedure:
5,7-Diallyl-3,4-dihydro-6-hydroxy-2(1H)-quinolinone (24.3 g) obtained in Example 26 was dissolved in 100 ml of 3,4-dihydro-2H-pyran, then 1 ml of concentrated hydrochloric acid was added thereto and stirred at 60° C. for 8 hours. The reaction mixture was cooled, and neutralized with 10% sodium bicarbonate solution, then extracted with ethyl acetate. The extract was washed with an aqueous solution saturated with sodium bicarbonate, and concentrated under reduced pressure. Recrystallized from ethyl acetate-n-hexane, there was obtained 14 g (58%) of 5,7-diallyl-3,4-dihydro-6-(2-tetrahydropyranyloxy)-2(1H)-quinolinone.
Reaction SMILES: CCCCN1C(=O)N(CCCC)C(=O)C(=C/C=C/C=C2/N(CCCS([O-])(=O)=O)C3C(O/2)=CC=CC=3)C1=O.[Na+].[CH2:39]([N:41]1[C:45](=[O:46])[C:44](=[C:47](Cl)[CH:48]=[C:49]2[N:53]([CH2:54][CH3:55])[C:52]3[CH:56]=[CH:57][CH:58]=[CH:59][C:51]=3[S:50]2)[S:43][C:42]1=[S:61])[CH3:40].C(#N)C.[I-].[Na+]>C(N(CC)CC)C>[CH2:39]([N:41]1[C:45](=[O:46])[C:44](=[C:47]=[C:48]=[C:49]2[N:53]([CH2:54][CH3:55])[C:52]3[CH:56]=[CH:57][CH:58]=[CH:59][C:51]=3[S:50]2)[S:43][C:42]1=[S:61])[CH3:40]
Reactant: CCN1C(=O)C(=C(Cl)C=C2Sc3ccccc3N2CC)SC1=S
Agent: CCCCN1C(=O)C(=C/C=C/C=C2\Oc3ccccc3N2CCCS(=O)(=O)[O-])C(=O)N(CCCC)C1=O
Agent: [I-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCN1C(=O)C(=C=C=C2Sc3ccccc3N2CC)SC1=S
Reaction time: 0.02 h

Procedure:
A mixture of the merocyanine dye of Example 9 (1 g), acetonitrile (100 ml), sodium iodide (5 g) and triethylamine (7 ml) are heated at reflux with stirring for 1 minute and chilled immediately. The dye is collected and washed sequentially with acetonitrile, water, acetonitrile and ether. After recrystallization from acetonitrile, the yield of purified dye is 0.57 g (63%).
Reaction SMILES: [CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[C:15](I)=[C:11]3[N:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CSC1N=C([Sn](CCCC)(CCCC)CCCC)C=CN=1.[F-].[K+].[CH:48]1([NH:53][C:54]2[N:59]3[N:60]=[C:61](C4C=CC(OC)=CC=4)[CH:62]=[C:58]3N=CC=2)[CH2:52][CH2:51][CH2:50][CH2:49]1.C1(NC2N3N=C(C4C=CC(OC)=CC=4)C(C4C=CN=C(SC)N=4)=C3N=CC=2)CCCC1.ClC1C=C(C=CC=1)C(OO)=O>C(OCC)(=O)C.ClCCl.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.C1(C)C=CC=CC=1>[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[C:15]([C:61]4[CH:62]=[CH:58][N:59]=[C:54]([NH:53][CH:48]5[CH2:49][CH2:50][CH2:51][CH2:52]5)[N:60]=4)=[C:11]3[N:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(-c2nn3c(NC4CCCC4)ccnc3c2I)cc1
Reactant: COc1ccc(-c2cc3nccc(NC4CCCC4)n3n2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCC[Sn](CCCC)(CCCC)c1ccnc(SC)n1
Agent: COc1ccc(-c2nn3c(NC4CCCC4)ccnc3c2-c2ccnc(SC)n2)cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COc1ccc(-c2nn3c(NC4CCCC4)ccnc3c2-c2ccnc(NC3CCCC3)n2)cc1
Temperature: 110 °C
Reaction time: 0.33 h
Yield: 11 %

Procedure:
N-Cyclopentyl-3-iodo-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine (63 mg, 0.15 mmol), dichlorobis(triphenylphosphine)palladium(II) (25 mg, 0.015 mmol), and 2-(methylsulfanyl)-4-(tributylstannyl)pyrimidine (78 mg, 0.19 mmol) were added to toluene (3 mL) and heated to 110° C. for 16 hours. Additional dichlorobis(triphenylphosphine)palladium(II) (6 mg) was added and the reaction heated to 110° C. for 24 hours. The reaction was allowed to cool to room temperature, diluted with ethyl acetate, poured into 10% aqueous potassium fluoride containing 1% methanol, and stirred for 20 minutes before being extracted with ethyl acetate. The organic phase was concentrated and the residue purified by silica chromatography, eluting with a gradient of 5% to 10% acetone in dichloromethane to yield 25 mg of an approximate 1:1 mixture of N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine and N-cyclopentyl-2-(4-methoxyphenyl)-3-[2-(methylsulfanyl)pyrimidin-4yl]pyrazolo[1,5-α]pyrimidin-7-amine. To a 0° C. solution of this mixture in dichloromethane (1 mL) was added 3-chloroperoxybenzoic acid (0.099 mg, 0.058 mmol). The mixture was allowed to warm to room temperature and stirred for 2 hours. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate, and concentrated. The residue was dissolved in cyclopentylamine and stirred at room temperature for 2.5 hours. The mixture was concentrated and the residue purified by silica chromatography, eluting with a gradient of 5% to 15% acetone in dichloromethane to yield 14 mg (11%) of N-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(4methoxyphenyl)pyrazolo[1,5-α]pyrimidin-7-amine. 1H NMR (CDCl3):δ 8.37 (d, 1H), 8.26 (d, 1H), 7.67 (d, 2H), 6.99 (d, 2H), 6.50 (d, 1H), 6.11 (d, 1H), 5.01 (m, 1H), 4.09 (m, 1H), 3.90 (s, 3H), 2.20 (m, 2H), 1.75 (m, 14H); MS m/z 470 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([O:22][CH3:23])=[O:21])[CH:10]=2)=[CH:5][CH:4]=1.[C:24](OC(=O)C)(=[O:26])[CH3:25]>N1C=CC=CC=1>[C:24]([N:13]1[C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([O:22][CH3:23])=[O:21])=[N:12]1)(=[O:26])[CH3:25]
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)c1ccccc1-c1cc(-c2ccc(OC)cc2)[nH]n1
Solvent: c1ccncc1
Product: COC(=O)c1ccccc1-c1cc(-c2ccc(OC)cc2)n(C(C)=O)n1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A mixture of 5.0 g of 5-(4-methoxyphenyl)-3-(2-carbomethoxyphenyl)pyrazole, 3.5 g of acetic anhydride, and 25 ml of pyridine was allowed to stir overnight at 25°. The mixture was poured into 100 ml of ice water, and the product was extracted with benzene. Recrystallization from hexane-ethyl acetate (2:1) gave 1-acetyl-3-(2-carbomethoxyphenyl)-5-(4-methoxyphenyl)pyrazole, mp 119°-121°.
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([Cl:10])[N:5]=[C:4]([S:11][CH3:12])[N:3]=1.[NH2:13][CH2:14][CH:15]1[CH2:17][CH2:16]1>>[Cl:10][C:6]1[C:7]([CH:8]=[O:9])=[C:2]([NH:13][CH2:14][CH:15]2[CH2:17][CH2:16]2)[N:3]=[C:4]([S:11][CH3:12])[N:5]=1
Reactant: NCC1CC1
Reactant: CSc1nc(Cl)c(C=O)c(Cl)n1
Product: CSc1nc(Cl)c(C=O)c(NCC2CC2)n1

Procedure:
Prepared as described above in Example 2 starting from 4,6-dichloro-2-methylsulfanyl-pyrimidine-5-carbaldehyde and (aminomethyl)cyclopropane to give the title compound 4-chloro-6-(cyclopropylmethyl-amino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde. 1H-NMR: δ 0.32 (m, 2H), 0.59 (m, 2H), 1.12 (m, 1H), 2.55 (s, 3H), 3.46 (m, 2H), 9.35 (br s, 1H), 10.28 (s, 1H). LC MS (m/e)=258 (MH+).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12](=[O:24])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([CH3:23])([CH3:22])[CH2:20][OH:21])=[CH:15][CH:14]=3)=[N:10][C:5]2=[CH:4][CH:3]=1.[CH3:25][C:26]1[CH:27]=[N:28][CH:29]=[CH:30][C:31]=1B(O)O>>[OH:21][CH2:20][C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:12]([NH:11][C:9]2[S:8][C:6]3[C:5]([N:10]=2)=[CH:4][CH:3]=[C:2]([C:31]2[CH:30]=[CH:29][N:28]=[CH:27][C:26]=2[CH3:25])[N:7]=3)=[O:24])=[CH:14][CH:15]=1)([CH3:23])[CH3:22]
Reactant: Cc1cnccc1B(O)O
Reactant: CC(C)(CO)c1ccc(C(=O)Nc2nc3ccc(Br)nc3s2)cc1
Product: Cc1cnccc1-c1ccc2nc(NC(=O)c3ccc(C(C)(C)CO)cc3)sc2n1
Yield: 70 %

Procedure:
The titled compound (yield=70%) was prepared using a procedure analogous to that described in connection with 9 (Example 9) except 2F (Example 2) and 3-methylpyridin-4-ylboronic acid were used as starting materials. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (s, 6H) 2.47 (s, 3H) 3.42 (s, 2H) 7.52 (d, J=8.59 Hz, 2H) 7.81-7.90 (m, 2H) 8.04 (d, J=8.59 Hz, 2H) 8.26 (d, J=8.34 Hz, 1H) 8.69 (d, J=4.29 Hz, 1H) 8.75 (br. s., 1H) 13.05 (br. s., 1H); ESI-MS: m/z 419.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:3]=1[O:4][CH:5]1[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:3]=1[O:4][CH:5]1[CH2:8][NH:7][CH2:6]1
Reactant: CC(C)(C)OC(=O)N1CC(Oc2ccc(Cl)cc2Cl)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Clc1ccc(OC2CNC2)c(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97 %

Procedure:
To a solution of tert-butyl 3-(2,4-dichlorophenoxy)azetidine-1-carboxylate (1.2 g, 3.78 mmol) in CH2Cl2 (10 mL) was added trifluoroacetic acid (TFA) (7 mL) and the reaction mixture was stirred at RT for 2 h. The mixture was concentrated under reduced pressure and filtered, washing with chloroform followed by diethyl ether to obtain 3-(2,4-dichlorophenoxy) azetidine (0.800 g, 100%) as a TFA salt.