Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)[CH:17]=1)=[O:14].[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1>>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:13]([NH:12][C:7]2[C:8]3[C:3](=[C:2]([C:33]4[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=4)[CH:11]=[CH:10][CH:9]=3)[CH:4]=[CH:5][CH:6]=2)=[O:14])=[CH:17][C:18]=1[N:24]1[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]1
Reactant: COc1ccc(NC(=O)Nc2cccc3c(Br)cccc23)cc1N1CCN(C)CC1
Reactant: OB(O)c1cccnc1
Product: COc1ccc(NC(=O)Nc2cccc3c(-c4cccnc4)cccc23)cc1N1CCN(C)CC1

Procedure:
The title compound was prepared from N-[5-bromo-1- naphthyl]-N'-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] urea (E19) and 3-pyridylboronic acid using a similar procedure to Example 4 as a white solid (28%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][C:16]4([C:22]5[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:21]=5[C:20](=[O:28])[O:19]4)[CH2:15][CH2:14]3)=[O:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Cl[CH2:30][C:31]1[C:32]([NH2:38])=[N:33][C:34]([CH3:37])=[N:35][CH:36]=1>>[NH2:38][C:32]1[C:31]([CH2:30][N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=3)[C:6]([C:11]([N:13]3[CH2:18][CH2:17][C:16]4([C:22]5[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:21]=5[C:20](=[O:28])[O:19]4)[CH2:15][CH2:14]3)=[O:12])=[CH:7]2)=[CH:36][N:35]=[C:34]([CH3:37])[N:33]=1
Reactant: O=C1OC2(CCN(C(=O)c3c[nH]c4cc(Cl)ccc34)CC2)c2ccc(F)cc21
Reactant: Cc1ncc(CCl)c(N)n1
Product: Cc1ncc(Cn2cc(C(=O)N3CCC4(CC3)OC(=O)c3cc(F)ccc34)c3ccc(Cl)cc32)c(N)n1

Procedure:
Following the general procedure III as described above, the alkylation of 1′-[(6-chloro-1H-indol-3-yl)carbonyl]-5-fluoro-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (prepared according to example 19 above) with 5-chloromethyl-2-methyl-pyrimidin-4-ylamine (described in Pharmaceutical Chemistry Journal (Translation of Khimiko-Farmatsevticheskii Zhurnal) (1999), 33(2), 101-103) gave the title compound.
Reaction SMILES: O[CH2:2][C:3]1[CH:16]=[N:15][C:6]2[C:7]3[N:8]([CH:12]=[CH:13][CH:14]=3)[C:9](=[O:11])[NH:10][C:5]=2[CH:4]=1.Cl.Cl.[CH2:19]([NH:21][C:22](=[O:36])[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[C:25]([CH3:35])[CH:24]=1)[CH3:20].[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[CH2:19]([NH:21][C:22](=[O:36])[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:30][CH2:31][N:32]([CH2:2][C:3]3[CH:16]=[N:15][C:6]4[C:7]5[N:8]([CH:12]=[CH:13][CH:14]=5)[C:9](=[O:11])[NH:10][C:5]=4[CH:4]=3)[CH2:33][CH2:34]2)=[C:25]([CH3:35])[CH:24]=1)[CH3:20]
Reactant: O=c1[nH]c2cc(CO)cnc2c2cccn12
Reactant: CCNC(=O)c1ccc(N2CCNCC2)c(C)c1
Agent: C[P+](C)(C)CC#N
Agent: Cl
Agent: [I-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCC#N
Product: CCNC(=O)c1ccc(N2CCN(Cc3cnc4c(c3)[nH]c(=O)n3cccc43)CC2)c(C)c1
Temperature: 95 °C
Reaction time: 18 h
Yield: 30.3 %

Procedure:
To a suspension of 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (7.20 mg, 0.033 mmol), N-ethyl-3-methyl-4-(piperazin-1-yl)benzamide dihydrochloride (13.40 mg, 0.042 mmol) and (cyanomethyl)trimethylphosphonium iodide (13.02 mg, 0.054 mmol) in Propiononitrile (Volume: 0.5 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.029 mL, 0.167 mmol) at 23° C. The reaction was stirred at 95° C. for 18 hr. The suspension was cooled to 23° C., filtered, rinsed with ACN (3×1 mL) and dried in vacuo to provide N-ethyl-3-methyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.004 g, 0.01 mmol, 27.0% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.20 Hz, 3H) 2.26 (s, 3 H) 2.53-2.65 (m, 4 H) 2.84-2.99 (m, 4 H) 3.20-3.27 (m, 2 H) 3.65 (s, 2 H) 6.71-6.76 (m, 1H) 7.02 (d, J=8.34 Hz, 1 H) 7.07 (dd, J=3.54, 1.26 Hz, 1H) 7.57-7.60 (m, 1 H) 7.60-7.66 (m, 2 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.22 (t, J=5.56 Hz, 1 H) 8.36 (d, J=1.52 Hz, 1 H) 11.58 (s, 1 H). ESI-MS: m/z 445.4 (M+H)+. mp=254.8-258.5° C.
Reaction SMILES: CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[NH:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C@@H:16]([C:18]([N:20]([CH3:38])[C@H:21]([C:26]([N:28]([CH3:37])[C@H:29]([C:34](O)=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:27])[CH2:22][CH:23]([CH3:25])[CH3:24])=[O:19])[CH3:17].[NH:46]([CH3:60])[C@H:47]([C:51]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:52])[CH:48]([CH3:50])[CH3:49].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[NH:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C@@H:16]([C:18]([N:20]([CH3:38])[C@H:21]([C:26]([N:28]([CH3:37])[C@H:29]([C:34]([N:46]([CH3:60])[C@H:47]([C:51]([CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)=[O:52])[CH:48]([CH3:49])[CH3:50])=[O:35])[CH2:30][CH:31]([CH3:32])[CH3:33])=[O:27])[CH2:22][CH:23]([CH3:24])[CH3:25])=[O:19])[CH3:17]
Reactant: CC(C)C[C@@H](C(=O)N(C)[C@@H](CC(C)C)C(=O)O)N(C)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
Reactant: CN[C@H](C(=O)Cc1ccccc1)C(C)C
Agent: CC(C)(C)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCOCC1
Solvent: ClC(Cl)Cl
Product: CC(C)C[C@@H](C(=O)N(C)[C@@H](CC(C)C)C(=O)N(C)[C@H](C(=O)Cc1ccccc1)C(C)C)N(C)C(=O)[C@@H](C)NC(=O)OC(C)(C)C
Temperature: -20 °C
Reaction time: 2 h

Procedure:
3.48 ml (3.18 g=31.5 m mol) N-methylmorpholine and 1.86 ml (1.8 g=15.0 m mol) pivaloyl chloride are added to a solution of 6.65 g (15.0 m mol) BOC-(D)-Ala-MeLeu-Me-Leu-OH in 60 ml chloroform, pre-cooled to -20° C. Conversion to the anhydride is completed after stirring for 2 hours at -20° C. (IR control). 3.35 g (15.0 m mol) H-MeVal-Bzl in 50 ml chloroform are then added dropwise to the reaction mixture at -20° C. The progress of the reaction is followed by means of thin-layer chromatography and IR-spectrometry and is complete after 41/2 days. The obtained solution is poured onto 200 ml 1N sodium bicarbonate on a shaker, and diluted with 300 ml chloroform. After separation of the organic phase, the aqueous phase is extracted with a further 100 ml chloroform, the combined chloroform phases dried over sodium sulphate, filtered and evaporated. The residue is chromatographed on 600 g silica gel (0.063-0.2 mm) using 2% methanol in methylene chloride as eluant to yield the title compound: rotation, [α]D25 =-143.7° (c=0.9 in chloroform).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])/[CH:5]=[C:6](/[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[C:10]=1[CH3:16])\[CH3:7])[CH3:2].[Br:18]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:17])/[CH:5]=[C:6](/[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[C:10]=1[CH3:16])\[CH2:7][Br:18])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)/C=C(\C)Oc1cccc(C)c1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)/C=C(\CBr)Oc1cccc(C)c1C
Yield: 30.9 %

Procedure:
To a stirred mixture of (E)-3-(2,3-dimethyl-phenoxy)-but-2-enoic acid ethyl ester (7.19 g, 0.031 mol) in carbon tetrachloride (40 mL) under a nitrogen atmosphere was added N-bromosuccinimide (8.19 g, 0.046 mol) and benzoyl peroxide (730 mg, 0.003 mol). Nitrogen gas was bubbled through the mixture for 5 min, and the resulting mixture was heated to reflux for 4 h. The reaction mixture was then placed in the refrigerator overnight. The solids formed were removed by filtration and the filtrate concentrated in vacuo. The crude product obtained was purified using flash column chromatography (silica gel (100-200 mesh), ethyl acetate/hexanes) to afford (E)-4-bromo-3-(2,3-dimethyl-phenoxy)-but-2-enoic acid ethyl ester (3.00 g, 31%) as a yellow oil.
Reaction SMILES: [F:1][C:2]1(F)[C:15]2(F)[C:6](F)([C:7]3(F)[C:12](F)([C:13](F)([F:19])[C:14]2(F)[F:17])[C:11](F)([F:22])[C:10](F)([F:24])[C:9](F)([F:26])[C:8]3(F)[F:28])[C:5](F)([F:32])[C:4](F)([F:34])[C:3]1(F)[F:36].[Na]>>[F:17][C:14]1[C:15]2[C:2]([F:1])=[C:3]([F:36])[C:4]([F:34])=[C:5]([F:32])[C:6]=2[C:7]2[C:12](=[C:11]([F:22])[C:10]([F:24])=[C:9]([F:26])[C:8]=2[F:28])[C:13]=1[F:19]
Reactant: FC1(F)C(F)(F)C(F)(F)C2(F)C(F)(C1(F)F)C(F)(F)C(F)(F)C1(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C12F
Agent: [Na]
Product: Fc1c(F)c(F)c2c(c1F)c(F)c(F)c1c(F)c(F)c(F)c(F)c12

Procedure:
The products from 3 reactions were analyzed by gas chromatography and for each of these reactions for which an excess of perfluoroperhydrophenanthrene (0.39 mmol) and 3.38 mmol sodium was used, yields of decafluorophenanthrene (based on sodium) ranged from 40-56%.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:11]=1[CH2:12][NH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[NH:23]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@@H:24]([C:32]([N:34]1[CH2:41][CH2:40][CH2:39][C@H:35]1[C:36](O)=[O:37])=[O:33])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1C=NC2N(O)N=NC=2C=1>CN(C)C=O>[C:45]([O:44][C:42]([NH:23][C@@H:24]([C:32]([N:34]1[CH2:41][CH2:40][CH2:39][C@H:35]1[C:36]([NH:13][CH2:12][C:11]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:10]=1[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:37])=[O:33])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:43])([CH3:48])([CH3:46])[CH3:47]
Reactant: CC(C)(C)OC(=O)NCc1ccc(Cl)cc1CN
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Agent: On1nnc2cccnc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCc1ccc(Cl)cc1CNC(=O)[C@@H]1CCCN1C(=O)[C@@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Reaction time: 8 h

Procedure:
To a solution of 2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzylamine from the previous step (0.14 mmol, 37 mg), EDC (0.21 mmol, 40 mg), and Boc-D-Phe-L-Pro-OH (0.14 mmol, 50 mg), in 0.5 mL dimethylformamide, was added HOAT (0.15 mmol, 21 mg). The solution was stirred overnight and purified by preparative reverse phase HPLC using an acetonitrile:water gradient containing 0.1% TFA to give N-(tert-buyloxycarbonyl)-D-phenylalanyl-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide. Mass Spec ES (M+1)=615.2.
Reaction SMILES: [CH2:1]([O:7][CH:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[NH:11][C:10]([CH3:17])([CH3:16])[CH2:9]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(N(CC)CC)C.[C:25]1([C:31](=[O:35])[C:32](Cl)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(Cl)Cl>[CH2:1]([O:7][CH:8]1[CH2:9][C:10]([CH3:16])([CH3:17])[N:11]([C:32](=[O:33])[C:31]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:35])[C:12]([CH3:15])([CH3:14])[CH2:13]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=C(Cl)C(=O)c1ccccc1
Reactant: CCCCCCOC1CC(C)(C)NC(C)(C)C1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCOC1CC(C)(C)N(C(=O)C(=O)c2ccccc2)C(C)(C)C1
Temperature: -10 °C
Reaction time: 4 h
Yield: 76 %

Procedure:
24.1 g (0.1 mole) of 4-hexyloxy-2,2,6,6-tetramethylpiperidine are dissolved in 100 ml of absolute methylene chloride. To this solution are added 15.2 g (0.15 mole) of absolute triethylamine and the whole solution is cooled to -10° C. At this temperature a solution of 16.8 g (0.1 mole) of phenylglyoxylyl chloride in 100 ml of methylene chloride is slowly added dropwise. When this addition is complete, the reaction mixture is allowed to warm to room temperature and stirred for about 4 hours. Precipitated hydrochloride is removed by filtration and the solution is clarified by filtration over a small amount of silica gel and concentrated by evaporation, affording 28.4 g of 1-(4-hexyloxy-2,2,6,6-tetramethylpiperidino)-2-phenyl-ethane-1,2-dione as a yellow oil (stabiliser 1).
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([NH:8][S:9]([C:12]2[CH:16]=[CH:15][S:14][C:13]=2[C:17](N(C)OC)=[O:18])(=[O:11])=[O:10])[O:4][N:3]=1.[CH3:23][C:24]1[CH:32]=[CH:31][C:27]([CH2:28][Mg]Cl)=[CH:26][CH:25]=1>>[CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([NH:8][S:9]([C:12]2[CH:16]=[CH:15][S:14][C:13]=2[C:17](=[O:18])[CH2:23][C:24]2[CH:32]=[CH:31][C:27]([CH3:28])=[CH:26][CH:25]=2)(=[O:10])=[O:11])[O:4][N:3]=1
Reactant: Cc1ccc(C[Mg]Cl)cc1
Reactant: CON(C)C(=O)c1sccc1S(=O)(=O)Nc1onc(C)c1C
Product: Cc1ccc(CC(=O)c2sccc2S(=O)(=O)Nc2onc(C)c2C)cc1
Yield: 65 %

Procedure:
N-(3,4-dimethyl-5-isoxazolyl)-2-(4-tolylacetyl)thiophene-3-sulfonamide was prepared, as described in Example 93B, by reacting N-(3,4-dimethyl-5-isoxazolyl)-2-[N-methoxy(methylaminocarbonyl)]thiophene-3-sulfonamide with 4-methylbenzylmagnesium chloride, resulting in a 65% yield, m.p. 95-100° C.
Reaction SMILES: CS(O[CH2:6][CH:7]([N:9]1[C:22]2[CH:21]=[C:20]([C:23]#[N:24])[CH:19]=[CH:18][C:17]=2[S:16][C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH3:8])(=O)=O.[NH:25]1[CH2:29][CH:28]=[CH:27][CH2:26]1>C1(C)C=CC=CC=1>[N:25]1([CH2:6][CH:7]([N:9]2[C:22]3[CH:21]=[C:20]([C:23]#[N:24])[CH:19]=[CH:18][C:17]=3[S:16][C:15]3[C:10]2=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH3:8])[CH2:29][CH:28]=[CH:27][CH2:26]1
Reactant: C1=CCNC1
Reactant: CC(COS(C)(=O)=O)N1c2ccccc2Sc2ccc(C#N)cc21
Solvent: Cc1ccccc1
Product: CC(CN1CC=CC1)N1c2ccccc2Sc2ccc(C#N)cc21
Reaction time: 18 h

Procedure:
A solution of 2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate, L series (44 g) and 2,5-dihydropyrrol (42.2 g) in anhydrous toluene (250 cc) is heated to 90° C. with stirring for 18 hours. After cooling, the reaction mixture is extracted with distilled water (2×100 cc) and then with N aqueous hydrochloric acid solution (250 cc). The combined acidic aqueous phases are alkalinized with aqueous N sodium hydroxide solution and extracted with ethyl acetate (3×100 cc). The organic phases are combined, washed successively with distilled water (100 cc) and then with saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The yellowish oily residue (30.4 g) is purified by chromatography on a column (height: 38 cm; diameter 3.8 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with a mixture (75:25 by volume) (15 liters) of cyclohexane and ethyl acetate and collecting 1-liter fractions. Fractions 6 to 11 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give 10-[1-(2,5-dihydro-1-pyrrolyl)-2-propyl]-2-phenothiazinecarbonitrile, L series (11.15 g) in the form of a yellow oil.
Reaction SMILES: C([NH:8][C:9]1[N:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:16]=2)=[CH:13][CH:14]=1)C1C=CC=CC=1.Cl.C1CCCCC=1>C(O)(=O)C.[Pd]>[NH2:8][C:9]1[N:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28]3)[CH:16]=2)=[CH:13][CH:14]=1
Reactant: COc1ccc(-c2ccc(NCc3ccccc3)nn2)cc1OC1CCCC1
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Solvent: C1=CCCCC1
Product: COc1ccc(-c2ccc(N)nn2)cc1OC1CCCC1
Reaction time: 16 h
Yield: 42.1 %

Procedure:
15 g (40 mmol) of 3-benzylamino-6-(3-cyclopentyloxy-4-methoxyphenyl)pyridazine are heated to reflux in a mixture of 100 ml of glacial acetic acid, 6.5 ml of concentrated hydrochloric acid, 9.8 g (0.12 mol) of cyclohexene and 3 spatula tips of Pd/C (10 percent) for 4 hours. 9.8 g of cyclohexene and Pd/C are added once again, and boiling is continued for 16 hours. The catalyst is filtered off, the solution is diluted with 1 l of water and neutralized with concentrated ammonia, and the resulting precipitate is filtered off with suction. The product is purified by chromatography on silica gel with dichloromethane. 4.8 g (42.1%) of 3-amino-6-(3-cyclopentyloxy-4-methoxyphenyl)pyridazine of m.p. 207° C. are obtained.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH:4]=[CH:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[NH:8][CH:7]=1>O1CCCC1.[Pd]>[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[NH:8][CH:7]=1
Reactant: COC(=O)C=Cc1c[nH]c2ccc(OC)cc12
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)CCc1c[nH]c2ccc(OC)cc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 92 %

Procedure:
To a solution of 3-(5-Methoxy-1H-indol-3-yl)-acrylic acid methyl ester 3 (3 g; 0.013 mol) in tetrahydrofuran (THF, 70 mL) was added palladium on activated carbon (10%; 0.72 g). The solution was deoxygenated under vacuum and hydrogen was introduced to the reaction flask from a balloon filled with hydrogen. The process was repeated three times and the reaction mixture was stirred for 16 h at room temperature. The mixture was filtered through celite and the filtrate was evaporated under reduced pressure to yield ester 4 as a while solid (2.78 g; 92% yield; M+1=234.0).
Reaction SMILES: CN(CCN(C)C)C.C([Li])CCC.[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.CN([CH:24]=[O:25])C>CCOCC>[Cl:14][C:15]1[C:16]([CH:24]=[O:25])=[N:17][CH:18]=[CH:19][CH:20]=1
Reactant: CN(C)C=O
Reactant: Clc1cccnc1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: CCOCC
Product: O=Cc1ncccc1Cl
Reaction time: 0.5 h
Yield: 27 %

Procedure:
To a solution of TMEDA (660 uL, 2.58 mmol) in ether (20 mL) at −78° C. was added a solution of n-butyl lithium in ether (2.5 M, 1.76 mL, 4.40 mmol). After 30 minutes at −78° C., 3-chloropyridine (419 uL, 4.40 mmol) was added. After another 2 hours at −78° C., DMF (375 uL, 4.84 mmol) was added. After a further 2 hours at −78° C., the reaction was quenched with saturated aqueous NaHCO3 (20 mL), extracted with ether (4×15 mL), dried (Na2SO4), filtered and concentrated in vacuo to give the crude oil. Purification by column chromatography on silica gel (Hexanes: EtOAc 4:1) afforded the title compound as a crystalline solid (168 mg, 27%). 1H NMR (CDCl3) 7.45 (dd, 1H, J=8.3, 4.4 Hz), 7.83 (dd, 1H, J=4.8, 1.4 Hz), 8.70 (dd, 1H, J=4.8, 1.5 Hz), 10.28 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=O)[C:5]([Cl:11])=[CH:4][N:3]=1.O=S(Cl)Cl.[C:16]([O:22][CH2:23][CH3:24])(=[O:21])[CH2:17]C([O-])=O.[K+].[Cl-].[Mg+2].[Cl-]>CN(C=O)C.C(#N)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[C:6]([C:8](=[O:10])[CH2:17][C:16]([O:22][CH2:23][CH3:24])=[O:21])[C:5]([Cl:11])=[CH:4][N:3]=1
Reactant: O=C(O)c1cc(Cl)ncc1Cl
Reactant: CCOC(=O)CC(=O)[O-]
Agent: [Cl-]
Agent: [K+]
Agent: [Mg+2]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Product: CCOC(=O)CC(=O)c1cc(Cl)ncc1Cl
Temperature: 0 °C
Reaction time: 3 h

Procedure:
A mixture of 2,5-dichloropyridine-4-carboxylic acid (2 g) and SOCl2 (10 ml) and 1 drop of DMF were heated under reflux for 2 h, and all SOCl2 and DMF removed under reduced pressure to give the crude acid chloride as the remaining residue. Separately, a suspension of potassium ethyl malonate (5 g) in acetonitrile (100 ml) was cooled to 0° C., magnesium chloride (4 g) and triethylamine (4 ml) were added, the ice bath removed and the reaction stirred at RT for 3 h. A solution of the crude acid chloride in DCM (25 ml) was carefully added to the malonate slurry and the resulting mixture stirred at RT overnight. Aqueous HCl (100 ml, 1M) was added and stiffing continued for 1 h. This mixture was then extracted with diethyl ether (200 ml×3), the organic layer washed with saturated sodium bicarbonate (200 ml×2) and brine (200 ml), dried over anhydrous magnesium sulfate, filtered and concentrated. The title compound was obtained as light yellow oil (1.6 g) which was on-reacted without further purification and without further characterization other than ascertaining that the compound was one spot by tlc with the expected molecular weight (M−1) of 260.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][C:5]([C:8](=[NH:10])[NH2:9])=[CH:4][CH:3]=1.[Cl:11][C:12]([SH:15])(Cl)Cl.[OH-].[Na+]>ClCCl.O>[Cl:11][C:12]1[S:15][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=2)[N:10]=1
Reactant: N=C(N)c1ccncc1
Reactant: SC(Cl)(Cl)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: Clc1nc(-c2ccncc2)ns1
Temperature: 25 °C
Yield: 6 %

Procedure:
To a solution of pyridine-4-carboximidamide hydrochloride (2.00 g, 12.7 mmol) and perchloromethyl mercaptan (1.75 ml, 16.3 mmol) in dichloromethane (40 ml) was added dropwise a solution of sodium hydroxide (3.26 g, 81.5 mmol) in water (6 ml) under ice-cooling. Then, the reaction mixture was stirred under ice-cooling for 1 hour and at room temperature for 1 hour. The organic layer was separated, washed with water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to give 150 mg (5.98%) of the desired product as a solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:23]=[C:10]3[CH:11]=[C:12]([NH:15]C(=O)OC(C)(C)C)[CH:13]=[CH:14][N:9]3[N:8]=2)[CH:2]=1.Cl>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:23]=[C:10]3[CH:11]=[C:12]([NH2:15])[CH:13]=[CH:14][N:9]3[N:8]=2)[CH:2]=1
Reactant: CC(C)(C)OC(=O)Nc1ccn2nc(-c3cccnc3)nc2c1
Agent: Cl
Product: Nc1ccn2nc(-c3cccnc3)nc2c1
Temperature: 25 °C
Reaction time: 7 h
Yield: 91.8 %

Procedure:
A mixture of tert-butyl 2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamate (755 mg, 2.43 mmol) in hydrochloric acid (5 N in ether, 15 ml, 75.0 mmol) is stirred for 7 hours at room temperature. The solvent is evaporated and the yellowish solid is dissolved in water and made basic with sodium hydroxide 32%; the precipitated solid is collected by filtration, washed with water and dried affording 2-(pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-7-amine (471 mg, 92%) as a light brown solid. mp.: 228-233° C. MS: m/z=212.1 (M+H+).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)[CH2:2][CH3:3].N1C=CC=CC=1.[C:17](Cl)(=[O:19])[CH3:18]>ClCCl>[CH3:3][CH2:2][CH2:1][C:4]1[CH:5]=[CH:6][C:7]([O:10][C:17]([CH3:18])=[O:19])=[CH:8][CH:9]=1
Reactant: CC(=O)Cl
Reactant: CCCc1ccc(O)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCc1ccc(OC(C)=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.3 %

Procedure:
4-n-Propylphenol (1.00 g) was dissolved in dichloromethane (10 ml) to prepare a solution. Pyridine (862 mg) and acetyl chloride (692 mg) were added to the solution, and the mixture was stirred at room temperature overnight. The solvent was removed therefrom by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous magnesium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using chloroform to give 4-n-propylphenyl acetate (1.09 g, yield 100%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([P:9]([C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)O)[CH:5]=[C:6]([F:8])[CH:7]=1.C1([SiH3])C=CC=CC=1>>[F:17][C:15]1[CH:16]=[C:11]([PH:9][C:4]2[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=2)[CH:12]=[C:13]([F:18])[CH:14]=1
Reactant: OP(c1cc(F)cc(F)c1)c1cc(F)cc(F)c1
Agent: [SiH3]c1ccccc1
Product: Fc1cc(F)cc(Pc2cc(F)cc(F)c2)c1
Temperature: 130 °C
Reaction time: 3 h

Procedure:
Bis(3,5-difluorophenyl)phosphinous acid (4.78 g=0.0174 mole) was placed in a 50 mL round bottom flask equipped with a magnetic stirring bar and a condenser with a nitrogen inlet tube. To this was added phenylsilane (1.54 g=0.014 mole). With stirring, the reaction was heated to 130° C. for three hours. As the temperature rose, the mixture became homogeneous and remained as such. After three hours, the reaction mixture was distilled, collecting the fraction boiling at 128°-138° C. at 0.05 mm Hg. The yield of bis(3,5-difluorophenyl)phosphine was 2.45 g (54%). The 31P absorption is at -37 ppm (relative to external H3PO4).