Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]([C:14](=O)[CH2:15][CH3:16])[C:10](=[O:13])[CH2:11][CH3:12].Cl.[NH2:25]O>N1C=CC=CC=1>[Cl:1][C:2]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[C:14]([CH2:15][CH3:16])=[N:25][O:13][C:10]=1[CH2:11][CH3:12]
Reactant: CCC(=O)C(CCCCOc1ccc(OC)cc1Cl)C(=O)CC
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Product: CCc1noc(CC)c1CCCCOc1ccc(OC)cc1Cl

Procedure:
4-[4-(2-Chloro-4-methoxyphenoxy)butyl]-3,5-diethylisoxazole [I; Ar is 2-Cl-4-CH3OC6H3, Y is O(CH2)4, R is C2H5 ] was prepared from 16.2 g. of 4-[4-(2-chloro-4-methoxyphenoxy)butyl]-3,5-heptanedione and 3.3 g. of hydroxylamine hydrochloride in 65 ml. of pyridine according to the procedure of Example 2, part (b), and was obtained in the form of a yellow oil, b.p. 180°-190° C. (0.1 mm.); yield 9.3 g.; MIC=6 μg/ml (herpes 2).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:17]([O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)[CH2:18][CH2:19][CH2:20][CH3:21].C(=O)([O-])[O-].[Na+].[Na+].S(=O)(=O)(O)O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O.C(O)CO>[CH2:17]([O:22][C:23]1[CH:24]=[CH:25][C:26]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=3)=[CH:4][CH:3]=2)=[CH:27][CH:28]=1)[CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCOc1ccc(B(O)O)cc1
Reactant: O=C(O)c1ccc(-c2ccc(I)cc2)cc1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: O
Solvent: OCCO
Product: CCCCCOc1ccc(-c2ccc(-c3ccc(C(=O)O)cc3)cc2)cc1
Temperature: 95 °C

Procedure:
162 g of 4′-iodobiphenyl-4-carboxylic acid are introduced together with 129 g of glycol ester of 4-n-pentoxyphenylboronic acid and 79.5 g of sodium carbonate into 1.5 l of ethylene glycol and, while stirring vigorously, 17.5 ml of a Pd(dba)2 solution are added and the mixture is stirred at 80° C. for 6 hours. The hot reaction mixture is cautiously poured into a mixture of 150 g of 37% strength sulfuric acid and 1,000 g of water, and the mixture is heated at 90-100° C. for 30 minutes. After filtration and washing with water, the crude product is dried at 80° C./100 mbar and then recrystallized from dimethylacetamide. This affords after drying 132 g (73%) of 4″-n-pentoxyterphenyl-4-carboxylic acid with a purity of >99%.
Reaction SMILES: [C:1]1(=[O:24])[N:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH:10](Cl)[C:11](=[O:17])[NH:12]3)[C:4](=[O:19])[C:3]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:2]12.C(N(CC)CC)C>[Pd].CN(C)C=O>[C:4]1(=[O:19])[N:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][C:11](=[O:17])[NH:12]3)[C:1](=[O:24])[C:2]2=[CH:23][CH:22]=[CH:21][CH:20]=[C:3]12
Reactant: O=C1Nc2cccc(CCN3C(=O)c4ccccc4C3=O)c2C1Cl
Agent: [Pd]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C1Cc2c(CCN3C(=O)c4ccccc4C3=O)cccc2N1
Temperature: 30 °C
Reaction time: 2 h
Yield: 83.3 %

Procedure:
A 10 L pressure reactor was charged with dry Pd/C (30 gm), 4-(2′-phthalimidoethyl)-3-chloro-1,3-dihydro-2H-indol-2-one (300 gm, 0.882 mol), triethylamine (133 gm, 0.952 mol) and dimethylformamide (6 L). The reaction mixture was hydrogenated at 30-50° C. and 70-75 psi for 2 hours. The catalyst was filtered at 50° C. and filtrate was concentrated in vacuum. Water (1.5 L) was added to residue and slurry was stirred for 30 minutes at 30° C. The solids were filtered at suction and washed with water, and dried in oven at 60-70° C. to give title compound as yellow solid (225 gm, 83.3%).
Reaction SMILES: [OH:1][C:2]1[C:21]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])=[C:20]([O:27]COC)[CH:19]=[C:18]([O:31]COC)[C:3]=1[C:4](=[O:17])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13]COC)=[CH:9][CH:8]=1.Cl.CO.C(=O)(O)[O-].[Na+]>>[OH:1][C:2]1[C:21]([CH2:22][CH2:23][CH:24]([CH3:25])[CH3:26])=[C:20]([OH:27])[CH:19]=[C:18]([OH:31])[C:3]=1[C:4](=[O:17])[CH:5]=[CH:6][C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1
Reactant: COCOc1ccc(C=CC(=O)c2c(OCOC)cc(OCOC)c(CCC(C)C)c2O)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CC(C)CCc1c(O)cc(O)c(C(=O)C=Cc2ccc(O)cc2)c1O
Yield: 59.3 %

Procedure:
Then, a liquid mixture of 1.45 g of 2'-hydroxy-4,4',6'-tris(methoxymethoxy)-3'-isopentylchalcone and 4 ml of a hydrochloric acid/methanol reagent was heated and refluxed for 10 minutes. The temperature of the reaction mixture was lowered to room temperature, and the reaction mixture was neutralized with a saturated aqueous solution of sodium bicarbonate, extracted with 500 ml of ethyl acetate, washed with water, shaken with a saturated aqueous solution of sodium chloride, dried with anhydrous sodium sulfate and filtered. The solvent was removed from the filtrate by distillation and the obtained residue was subjected to the silica gel column chromatography (diameter=4.5 cm, 130 g of silica gel, 9.3 kg/cm2) using a mixed solvent of n-hexane and ethyl acetate (n-hexane/ethyl acetate=3/1). Fractions of 100 ml were collected, and the 42nd to 56th fractions were combined, and the solvent was removed by distillation and the residue was recrystallized from a mixed solvent of chloroform and methanol to obtain 620 mg (yield=59.3%) of 2' ,4,4',6'-tetrahydroxy-3'-isopentylchalcone in the form of a yellow prism.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[NH:5][C:6]([CH2:8][C:9]1[CH:20]=[CH:19][C:12]([O:13][CH:14]([CH3:18])[C:15]([OH:17])=[O:16])=[CH:11][CH:10]=1)=[O:7].[CH3:25]O>C(O)C>[CH3:24][C:22]1[CH:21]=[C:4]([CH:3]=[C:2]([CH3:1])[CH:23]=1)[NH:5][C:6]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:13][CH:14]([CH2:18][CH3:25])[C:15]([OH:17])=[O:16])=[CH:19][CH:20]=1)=[O:7]
Reactant: CO
Reactant: Cc1cc(C)cc(NC(=O)Cc2ccc(OC(C)C(=O)O)cc2)c1
Solvent: CCO
Product: CCC(Oc1ccc(CC(=O)Nc2cc(C)cc(C)c2)cc1)C(=O)O

Procedure:
The mother liquor from the recrystallization of (−) 20-cinchonidine salt was concentrated under reduced pressure. The enriched (+) 20 isomer was obtained from the mother liquor by neutralizing the salt to obtain the free acid, as described previously for compound 18. The optical rotation showed that the isomer was approximately 80% enantiomeric excess, optical rotation was measured at 21° C.: [α]D +18:2° (c=1.2, methanol). A stock solution (1 mg/mL) of the racemic mixture (20) was prepared in ethanol/mobile phase (1:1). The injected sample volume was 250 μL. The compound was eluted with a mobile phase of heptane/ethanol. with 1% TFA (88:12) at a flow rate of 2.5 mL/min. Under these conditions, the (−) isomer eluted at 15.8 min and the (+) isomer eluted at 18.2 min retention times. The collected fractions were concentrated under reduced pressure at room temperature. (+) 20 was collected as a white solid, 0.14 g. mp 146-148° C. The optical rotation was measured at 21° C.: [α]D +25.3° (c=0.5, methanol).
Reaction SMILES: ClCCl.[Br:4][C:5]1[CH:6]=[C:7]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:25])([F:24])[CH:21]([F:23])[F:22])[CH:14]=2)[CH:8]=[CH:9][CH:10]=1.[F:26][C:27]([F:32])([F:31])[CH:28]1[O:30][CH2:29]1.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Yb+3]>C(OCC)C>[Br:4][C:5]1[CH:6]=[C:7]([N:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][C:20]([F:24])([F:25])[CH:21]([F:23])[F:22])[CH:14]=2)[CH2:29][CH:28]([OH:30])[C:27]([F:32])([F:31])[F:26])[CH:8]=[CH:9][CH:10]=1
Reactant: FC(F)(F)C1CO1
Reactant: FC(F)C(F)(F)Oc1cccc(CNc2cccc(Br)c2)c1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CCOCC
Solvent: ClCCl
Product: OC(CN(Cc1cccc(OC(F)(F)C(F)F)c1)c1cccc(Br)c1)C(F)(F)F
Temperature: 25 °C
Reaction time: 24 h
Yield: 99 %

Procedure:
To a dichloromethane (9 mL) solution of the EX-220A amine (3.27 g, 8.65 mmol) was added 1,1,1-trifluoro-2,3-epoxypropane (0.968 mL, 11.3 mmol) and Yb(OTf)3 (0.536 g, 0.86 mmol). The cloudy mixture was stirred at room temperature for 24 hours, then diluted with diethyl ether. The organic layer was washed with water and brine, dried (MgSO4) and evaporated to yield 4.20 g (99%) of the desired 3-[(3-bromophenyl)-[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro 2-propanol product as a pale brown oil which can be used without further purification. The formation of the desired product was confirmed by the presence of the alcohol peak (δ1.5, d) in the 1H NMR spectrum (C6D6). An analytical sample was purified by silica gel chromatography eluting with 20% ethyl acetate in hexane to give the desired pure product as a yellow oil. FABMS m/z=491 [M+H+. 1H NMR (CDCl3) δ3.55-3.63 (m. 1H), 3.88 (dd, 1H), 4.36 (m, 1H), 4.69 (s, 2H), 5.914 (tt, 1H), 6.66 (dd, 1H), 6.92 (m, 2H), 7.06 (s, 1H), 7.09 (m, 3H), 7.36 (t, 1H).
Reaction SMILES: S(Cl)(Cl)=O.[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[CH:8][CH:7]=1.[CH3:18]O>>[NH2:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:11]=1
Reactant: CO
Reactant: Nc1ccc(CCCC(=O)O)cc1
Solvent: O=S(Cl)Cl
Product: COC(=O)CCCc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 94 %

Procedure:
Thionyl chloride (2.5 mL, 4.08 g, 34.3 mmol) was added to stirred anhydrous methanol (10 mL) at 0° C. After 20 mins, 4-(4-AMINOPHENYL)BUTYRIC ACID (1.85 g, 10.3 mmol, Aldrich) was added and the mixture was stirred at rt for 16 hrs. The reaction mixture was concentrated and the residue dissolved in ethyl acetate, washed with sat. NaHCO3, water, and sat. NaCl, dried over Na2SO4 and concentrated to give methyl 4-(4-aminophenyl)butanoate (1.88 g, 94%) as a light brown solid.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([F:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[NH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl>[F:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2
Reactant: CC(=O)c1cc(F)c2cccnc2c1OS(=O)(=O)C(F)(F)F
Reactant: C1CNCCN1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(=O)c1cc(F)c2cccnc2c1N1CCNCC1
Temperature: 65 °C
Yield: 10.1 %

Procedure:
A stirred mixture of 7-acetyl-5-fluoroquinolin-8-yltrifluoromethanesulfonate (1.00 g, 2.96 mmol, from Example 53, Step 2), piperazine (0.511 g, 5.93 mmol), and cesium carbonate (2.90 g, 8.90 mmol) in tetrahydrofuran (30 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over sodium sulfate and evaporated to dryness. The resulting residue was purified on silica gel, eluting with 0 to 20% methanol in dichloromethane, to give the desired product (82 mg, 10%). LCMS calculated for C15H17FN3O (M+H)+: m/z=274.1; Found: 274.1.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]Br)=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:25]([NH:28][CH3:29])[CH:26]=[CH2:27].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:28]([CH2:25][CH:26]=[CH2:27])[CH3:29])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCNC
Reactant: CC(C)(C)OC(=O)N1CCCc2cc(OCCCCCBr)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCN(C)CCCCCOc1ccc2c(c1)CCCN2C(=O)OC(C)(C)C
Yield: 72.1 %

Procedure:
1.5 g (3.75 mmol) 6-(5-Bromo-pentyloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester were treated with 355 mg (5 mmol) N-allyl-methylamine and 830 mg (6 mmol) K2CO3 (powdered) in 8 ml DMF at 60° C. for 3 h. The mixture was concentrated in vacuo, dissolved in acetone and filtered. The filtrate was concentrated and purified by column chromatography on silica gel with CH2Cl2/MeOH 19:1 to yield 1.05 g (72%) 6-[5-(Allyl-methyl-amino)-pentyloxy]-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester as colorless oil, MS: 389 (MH+).
Reaction SMILES: [Na].Br[C:3]1[CH:8]=[CH:7][C:6]([Br:9])=[CH:5][N:4]=1.[CH2:10](O)[CH3:11]>>[Br:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:10][CH3:11])=[N:4][CH:5]=1
Reactant: CCO
Reactant: Brc1ccc(Br)nc1
Agent: [Na]
Product: CCc1ccc(Br)cn1

Procedure:
Sodium metal (4.87 g, 0.212 mol) was added to ethanol (200 mL) and stirred until completely dissolved. To this solution was added 2,5-dibromopyridine 9-1 (10 g, 0.0424 mol) and the resulting mixture was stirred at reflux for 16 hr. The solvent was removed in vacuo and the residue partitioned between water and EtOAc. After extraction with EtOAc (2×), the organic layer was washed with brine, dried (MgSO4) and concentrated to give 9-2 as a red-brown solid which was used as such in the next step.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:26][CH3:27])[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:11]=3)=[CH:4][CH:3]=1.[C:28](Cl)(=[O:31])[CH2:29][CH3:30]>N1C=CC=CC=1>[C:17]([C:16]1[C:15]2[C:10](=[CH:11][C:12]([N:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)=[CH:13][CH:14]=2)[N:9]([CH2:26][CH3:27])[C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:28](=[O:31])[CH2:29][CH3:30])=[CH:3][CH:4]=1)#[N:18]
Reactant: CCn1c(-c2ccc(N)cc2)c(C#N)c2ccc(N3CCN(C)CC3)cc21
Reactant: CCC(=O)Cl
Solvent: c1ccncc1
Product: CCC(=O)Nc1ccc(-c2c(C#N)c3ccc(N4CCN(C)CC4)cc3n2CC)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.2 %

Procedure:
To a solution of the compound obtained in step B (54 mg, 0.15 mmol) in dry pyridine (1.5 mL) is added propionyl chloride (26 μL, 0.30 mmol). The mixture is stirred at room temperature overnight and the solvent is removed in vacuo. The residue is dissolved with DCM (5 mL) and washed with water (2×4 mL) and chromatographed (silica gel, MeOH/DCM, 0.5/9.5) to provide product, {N-{4-[3-cyano-1-ethyl-6-(4-methylpiperazin-1-yl)indol-2-yl]phenyl}propionamide (45 mg, 73%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH3:10].Cl[CH:12](Cl)[O:13]C>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:9][CH3:10])=[CH:4][C:5]([CH:12]=[O:13])=[C:6]([F:8])[CH:7]=1
Reactant: COC(Cl)Cl
Reactant: CCc1ccc(F)cc1Cl
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Product: CCc1cc(C=O)c(F)cc1Cl
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
TiCl4 (0.90 mL) was added to 2-chloro-1-ethyl-4-fluorobenzene (645 mg, 4.1 mmol) at 0° C. and stirred to 10 min. Dichloro(methoxy)methane (0.725 mL) was added and the mixture was stirred overnight at ambient temperature. The mixture was diluted with CH2Cl2 (50 mL) and poured onto crushed ice (40 g). After stirring 30 min the layers were separated. The organic layer was washed with H2O (2×), brine (2×), dried (Na2SO4) and concentrated. Purification by flash chromatography (hexanes, EtOAc) yielded 440 mg of intermediate 390.2 as a light brown oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (t, J=7.58 Hz, 3H) 2.69 (q, J=7.58 Hz, 2H) 7.05-7.29 (m, 1H) 7.67 (m, 1H) 10.23 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.CC1C=CC(S(O[CH2:20][CH2:21][CH2:22][NH:23][C:24]2[C:25](=[O:41])[N:26]([C:37]([CH3:40])([CH3:39])[CH3:38])[S:27](=[O:36])(=[O:35])[C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=O)=O)=CC=1>>[C:37]([N:26]1[C:25](=[O:41])[C:24]([NH:23][CH2:22][CH2:21][CH2:20][O:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[C:28]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[S:27]1(=[O:35])=[O:36])([CH3:38])([CH3:39])[CH3:40]
Reactant: Cc1ccc(S(=O)(=O)OCCCNC2=C(c3ccccc3)S(=O)(=O)N(C(C)(C)C)C2=O)cc1
Reactant: Oc1cccc(F)c1
Product: CC(C)(C)N1C(=O)C(NCCCOc2cccc(F)c2)=C(c2ccccc2)S1(=O)=O
Yield: 65 %

Procedure:
The title compound was prepared as described for Example 12 from 3-fluorophenol and 3-[(2-tert-butyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]propyl 4-methylbenzenesulfonate with a reaction time of 15 mins. The reaction mixture was evaporated and the residue was purified by silica gel column chromatography (Horizons Biotage) using 15% EtOAc in hexane as eluent to give the title compound (0.069 g, 65%). 1H NMR (500 MHz CDCl3): δ 7.54-7.50 (m, 2H), 7.46-7.42 (m, 3H), 7.26-7.20 (m, 1H), 6.70-6.60 (m, 2H), 6.59-6.55 (m, 1H), 5.69 (t, 1H), 3.86 (t, 1H), 3.12-3.07 (q, 2H), 1.90-1.82 (m, 2H), 1.75 (s, 9H); 13C NMR (125 MHz CDCl3): δ 164.8, 162.8, 159.9, 159.8, 135.3, 131.8, 130.5, 130.4, 129.8, 128.8, 125.3, 110.4, 108.2, 108.1, 107.3, 102.5, 102.3, 66.3, 61.7, 42.3, 28.9, 27.8; Mass Spectrum: M+H+ 433.
Reaction SMILES: [CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([Cl:26])=[CH:22][C:23]=4[F:25])[N:18]([CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[N:17]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN.Cl>ClCCl.CO.ClCCl.O1CCOCC1.C(OCC)(=O)C.O>[ClH:26].[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([Cl:26])=[CH:22][C:23]=4[F:25])[N:18]([CH2:27][CH2:28][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]
Reactant: CC(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(CCN4CCOCC4)c4cc(Cl)cc(F)c34)nc12
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)NC(=O)c1c[nH]c2ncc(-c3nn(CCN4CCOCC4)c4cc(Cl)cc(F)c34)nc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 143.1 %

Procedure:
2-[6-Chloro-4-fluoro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (66 mg, 0.107 mmol) was dissolved in dichloromethane (1.4 ml) and cooled in ice bath. Trifluoroacetic acid (0.7 ml) was slowly added and the reaction was stirred at room temperature for 2 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1 ml). Ethylenediamine (0.43 ml, 6.4 mmol) was added and the mixture was stirred for 18 h. Water and then ethyl acetate were added to the mixture. The layers were separated and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane). The product thus isolated was dissolved in methanol/dichloromethane and treated with 2 eq of 4 M HCl in 1,4-dioxane. Evaporation of the solvent provided a solid which was dried under high vacuum to afford 40 mg (72%) of 2-[6-chloro-4-fluoro-1-(2-morpholin-4-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide hydrochloride. MS: (M+H)+=486; mp=190-195° C. 1H NMR (300 MHz, DMSO-d6) δ: 12.86-12.98 (m, 1H), 10.92-11.17 (m, 1H), 9.06 (s, 1H), 8.45 (d, J=3.0 Hz, 1H), 8.26 (d, J=7.9 Hz, 1H), 8.05 (s, 1H), 7.35 (d, J=10.6 Hz, 1H), 5.05 (br. s., 2H), 4.14-4.30 (m, 1H), 3.93-4.09 (m, 2H), 3.68-3.85 (m, 4H), 3.54-3.64 (m, 2H), 3.11-3.30 (m, 2H), 1.24 (d, J=6.4 Hz, 6H).
Reaction SMILES: [CH3:1][C:2]([CH3:4])=[O:3].[C:5]1([CH:11]([OH:13])C)C=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:14]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])(=[O:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>C(O)(C)C>[C:14]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])(=[O:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[C:11]([O:3][CH:2]([CH3:4])[CH3:1])(=[O:13])[CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CC(C)=O
Reactant: CC(O)c1ccccc1
Agent: CCCCCCOC(=O)CCCCC
Solvent: CC(C)O
Product: CCCCCC(=O)OC(C)C

Procedure:
Likewise, refluxing a toluene solution containing one equivalent of hexyl hexanoate, 2 equivalents of cyclohexanol and 1 mol % of the PNN complex 1 under argon atmosphere for 20 h resulted in 84% conversion of hexyl hexanoate as determined by GC analysis, with the exclusive formation of the ester cyclohexyl hexanoate in 83% yield (Table 30, entry 2). Notably, unlike the traditional transesterification methods, this reaction does not form an alcohol product; rather, an irreversible incorporation of both the acyl and alkoxo parts of the starting ester into the product ester takes place. While 2 equivalents of the alcohol with respect to the ester are sufficient, somewhat higher yields are obtained when 3 equivalents of alcohol were used. Thus, reaction of 3 equivalents of cyclohexanol with hexyl hexanoate resulted after 26 h in 96% conversion with 95% yield of cyclohexyl hexanoate, as observed by GC, and confirmed by GC-MS by comparison with an authentic sample (Table 30, entry 3). The pure product was isolated by evaporation of the solvent followed by passing through a basic alumina plug and analysis by NMR and GC-MS. Use of the PNP complexes 2 or 3 resulted after 20 h in 58% or 17% yield of cyclohexyl hexanoate, respectively. Studying the scope of this new reaction with regard to the secondary alcohol, reaction of hexyl hexanoate with cyclopentanol in the presence of 1 mol % 1 was carried out. After 26 h reflux in toluene, cyclopentyl hexanoate (70% yield) was formed, with 71% conversion of hexyl hexanoate (Table 30, entry 4). Similarly, upon reaction of hexyl hexanoate with excess of 1-phenylethanol, 50% conversion of hexyl hexanoate with the formation of 49% of the acylated product was observed (Table 30, entry 5). The lower conversion of the ester is a result of facile dehydrogenation of 1-phenylethanol to acetophenone (49%). Because of the expected easy dehydrogenation of the isopropyl alcohol to acetone, transesterification with this alcohol was performed in a closed vessel, to retard this dehydrogenation process. Thus, heating hexyl hexanoate with excess of isopropyl alcohol resulted after 19 h in 83% conversion of hexyl hexanoate with the formation of isopropyl hexanoate in 67% yield (entry 6). The reaction of hexyl hexanoate and 3-pentanol led to 91% conversion of the ester with formation of 3-pentyl hexanoate in 90% yield after 26 h reflux (entry 7).
Reaction SMILES: O=O.[OH:3][C:4]1[CH:21]=[CH:20][C:7]([C:8]2[C:17](=O)[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[CH:14][CH:15]=3)[O:10][CH:9]=2)=[CH:6][CH:5]=1>C(O)(=O)C.[Pd]>[OH:19][C:13]1[CH:12]=[C:11]2[C:16]([CH2:17][CH:8]([C:7]3[CH:20]=[CH:21][C:4]([OH:3])=[CH:5][CH:6]=3)[CH2:9][O:10]2)=[CH:15][CH:14]=1
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O)ccc12
Agent: [Pd]
Agent: O=O
Solvent: CC(=O)O
Product: Oc1ccc(C2COc3cc(O)ccc3C2)cc1
Reaction time: 0.5 h
Yield: 75.8 %

Procedure:
A suspention of Palladium-on-charcoal (10%, 2.2 g) in glacial acetic acid (15 ml) was treated with oxygen for three days. The suspention catalyst was added to the solution of 4′,7-dihydroxy isoflavone (0.5 g, mmol) in diglume (60 ml). After 30 min. of catalytic hydrogenation at atmospheric pressure, the solution was filtered and washed with diglume and hot acetic acid. The combined filtrate were evaporoted by using water vacuum pump followed by high vacuum pump. The curde was dissolved in ethylacetate and wished with sodium bicarbonate (5%) and with water till neutral, dried (MgSO4) filtred and evaporeted to give pale white crude (0.385 g) which was recrystallized in aquoes ethanol to give 22a as white crystals (0.361 g), m.p. 156–158° C. (lit. 158° C.). Rfs=IR (KBr) 3380−2720 cm−1. δH (acetone-d6) 2.89 (2H, m, C-4-H2), 3.1 (1H, m, C-3-H), 3.94 (1H, t, J=10.38 Hz, C-2-HA), 4.18 (1H, m, C-2-HE), 6.29 (1H, d, JC-8-H & C-6-H=2.44 Hz, C-8-H), 6.37 (1H, dd, JC-6-H & C-7-H=8.24 Hz, JC-6-H & C-8-H=2.44 Hz, C-6-H), 6.82 (2H, dd, JC-3′-H & C-2′-H=8.55 Hz, JC-3′ & C-5-H=2.74 Hz, C-3′-H and C-5′-H or C-2′-H and C-6′-H), 6.89 (1H, d, JC-5-H & C-6-H=8.24 Hz, C-5-H), 7.16 (2H, dd, JC-2′-H & C-5′-H=8.24 Hz, JC-2′-H & C-6′-H=2.74 Hz, C-2′-H and C-6′-H or C-3′-H and C-5′-H), 8.15 (1H, br s, C-7-OH or C-4′-OH) and 828 (1H, br s, C-4′-OH or C-7-OH).