Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:16]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[C:17]#[CH:18].C(#N)C>[Cl-].[Na+].O.CC#N.CC#N.Cl[Pd]Cl.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([CH3:9])=[CH:3][C:2]=1[C:18]#[C:17][CH2:16][O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1
Reactant: C#CCOC1CCCCO1
Reactant: Cc1ccc(F)c(Br)c1
Agent: Cl[Pd]Cl
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CC#N
Product: Cc1ccc(F)c(C#CCOC2CCCCO2)c1
Temperature: 90 °C
Reaction time: 11 h

Procedure:
A mixture of 3-bromo-4-fluorotoluene (10.0 g), cesium carbonate (45.0 g), 2-(2-propynyloxy)tetrahydropyran (11.2 ml), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (1.51 g), bis(acetonitrile)palladium(II) dichloride (274 mg) and acetonitrile (250 ml) was stirred at 90° C. for 11 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-95:5) to give the object product (8.32 g) as a pale-brown oil.
Reaction SMILES: Cl[C:2]1[C:3]2[CH:12]=[CH:11][NH:10][C:4]=2[N:5]=[C:6]([O:8][CH3:9])[N:7]=1.[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25]([C:2]3[C:3]4[CH:12]=[CH:11][NH:10][C:4]=4[N:5]=[C:6]([O:8][CH3:9])[N:7]=3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: COc1nc(Cl)c2cc[nH]c2n1
Reactant: CC1(C)OB(c2cnn([C@H](CC#N)C3CCCC3)c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COc1nc(-c2cnn([C@H](CC#N)C3CCCC3)c2)c2cc[nH]c2n1
Temperature: 100 °C

Procedure:
4-Chloro-2-methoxy-7H-pyrrolo[2,3-d]pyrimidine (0.4 g, 2.18 mmol, Toronto Research Chemicals) and (R)-3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (0.824 g, 2.61 mmol, prepared as described in Org. Lett., 2009, 11(9), 1999-2002.) were dissolved in 1,4-dioxane (4 mL) and potassium carbonate (0.903 g, 6.54 mmol) in water (2 mL) was added. The mixture was degassed and tetrakis(triphenylphosphine)palladium(0) (0.126 g, 0.109 mmol) was added. The reaction mixture was heated to 100° C. for 16 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined extracts were dried over sodium sulfate, decanted and concentrated. Flash column chromatography, eluting with a gradient from 0-10% MeOH in methylene chloride was used to purify the product (670 mg, 91%). 1H NMR (300 MHz, CD3OD): δ 8.59 (s, 1H), 8.35 (s, 1H), 7.24 (d, 1H), 6.81 (d, 1H), 4.47 (dt, 1H), 4.04 (s, 3H), 3.21 (dd, 1H), 3.10 (dd, 1H), 2.62-2.44 (m, 1H), 2.02-1.86 (m, 1H), 1.81-1.20 (m, 7H); LCMS (M+H)+: 337.0.
Reaction SMILES: [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.CCCCCC.[Cl:22][C:23]1[CH:32]=[C:31]([Cl:33])[C:30]2[C:25](=[CH:26][C:27]([Cl:34])=[CH:28][CH:29]=2)[C:24]=1[CH2:35][CH2:36][CH:37]=[O:38]>O1CCCC1>[Cl:22][C:23]1[CH:32]=[C:31]([Cl:33])[C:30]2[C:25](=[CH:26][C:27]([Cl:34])=[CH:28][CH:29]=2)[C:24]=1[CH2:35][CH2:36][CH:37]([OH:38])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)CC(C)=O
Reactant: O=CCCc1c(Cl)cc(Cl)c2ccc(Cl)cc12
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COC(=O)CC(=O)CC(O)CCc1c(Cl)cc(Cl)c2ccc(Cl)cc12
Temperature: 5 °C
Reaction time: 0.33 h
Yield: 88.5 %

Procedure:
A solution of methyl acetoacetate (0.088 g, 0.76 mmole) in dry tetrahydrofuran (2 ml) was added dropwise (5 minutes) to a mixture of sodium hydride (0.036 g, 0.75 mmole) in tetrahydrofuran (3 ml) under nitrogen and with cooling (ice bath). After stirring at about 5° C. for 20 minutes, a solution of n-butyl lithium in hexane (0.55 ml, 0.77 mole) was added dropwise (5 minutes) and the mixture stirred at 5° C. for 30 minutes. The ice bath was replaced by a dry ice-acetone bath and a solution of 3-(2,4,7-trichloronaphthalen-1-yl)propanal (0.20 g, 0.7 mmole) in tetrahydrofuran (5 ml) was added (5 minutes). The reaction mixture was stirred at -70° C. for about 10 minutes and at room temperature for 5 hours and then poured into ice water containing 0.5 ml conc. HCl. After extraction with ether, the ether extracts were combined, washed with cold water and brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give 0.25 g of the title compound as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:9][C:4]1[C:3]2[NH:10][C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:1][C:2]=2[CH:7]=[C:6]([OH:8])[CH:5]=1
Reactant: Nc1cc(O)cc(Cl)c1NC(=O)C1CCOCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: Oc1cc(Cl)c2[nH]c(C3CCOCC3)nc2c1
Reaction time: 8 h

Procedure:
0.50 g (1.85 mmol) N-(2-amino-6-chloro-4-hydroxyphenyl)tetrahydro-2H-pyran-4-carboxamide were placed in 20 mL methanol, a spatula tip of p-toluenesulphonic acid monohydrate was added and the mixture was boiled overnight. The reaction mixture was evaporated down i.vac. and purified by chromatography. The fractions containing product were combined and evaporated down i.vac.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][N:3]=1.[O:11]=[C:12]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14][N:13]1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[O:11]=[C:12]1[CH2:18][CH2:17][N:16]([C:2]2[N:3]=[CH:4][C:5]([NH2:8])=[CH:6][CH:7]=2)[CH2:15][CH2:14][N:13]1[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C1CCNCCN1Cc1ccccc1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Product: Nc1ccc(N2CCC(=O)N(Cc3ccccc3)CC2)nc1

Procedure:
Intermediate B-26 was prepared by the general procedure for intermediate B-2, by using 2-chloro-5-nitropyridine and hexahydro-5-oxo-4-(phenylmethyl)-1H-1,4-diazepine as starting materials. MS (M+1): 297.
Reaction SMILES: C[O:2][C:3](=[O:8])[CH2:4][CH2:5][CH2:6]Br.[CH3:9][O:10][C:11]1[CH:55]=[C:54]([O:56][CH3:57])[CH:53]=[C:52]([O:58][CH3:59])[C:12]=1/[CH:13]=[CH:14]/[CH:15]([S:25]([CH:28](/[CH:38]=[CH:39]/[C:40]1[C:45]([O:46][CH3:47])=[CH:44][C:43]([O:48][CH3:49])=[CH:42][C:41]=1[O:50][CH3:51])[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([NH2:37])[CH:30]=1)(=[O:27])=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([NH2:24])[CH:17]=1>>[CH3:59][O:58][C:52]1[CH:53]=[C:54]([O:56][CH3:57])[CH:55]=[C:11]([O:10][CH3:9])[C:12]=1/[CH:13]=[CH:14]/[CH:15]([S:25]([CH:28](/[CH:38]=[CH:39]/[C:40]1[C:41]([O:50][CH3:51])=[CH:42][C:43]([O:48][CH3:49])=[CH:44][C:45]=1[O:46][CH3:47])[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([NH:37][CH2:6][CH2:5][CH2:4][C:3]([OH:8])=[O:2])[CH:30]=1)(=[O:27])=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([NH:24][CH2:6][CH2:5][CH2:4][C:3]([OH:2])=[O:8])[CH:17]=1
Reactant: COc1cc(OC)c(/C=C/C(c2ccc(OC)c(N)c2)S(=O)(=O)C(/C=C/c2c(OC)cc(OC)cc2OC)c2ccc(OC)c(N)c2)c(OC)c1
Reactant: COC(=O)CCCBr
Product: COc1cc(OC)c(/C=C/C(c2ccc(OC)c(NCCCC(=O)O)c2)S(=O)(=O)C(/C=C/c2c(OC)cc(OC)cc2OC)c2ccc(OC)c(NCCCC(=O)O)c2)c(OC)c1

Procedure:
A solution of methyl-4-bromobutyrate (40 mmol) and (E)-2,4,6-trimethoxystyryl-3-amino-4-methoxybenzylsulfone (10 mmol) was reacted according to General Method B. The product obtained was purified by recrystallization from acetone. (m.p. 86-88° C.)
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]([NH:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1)=[O:5].FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH3:1][O:2][CH2:3][C:4]([NH:6][CH2:7][C:8]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1)=[O:5]
Reactant: COCC(=O)NCC1(c2ccccc2)CCN(C(=O)OC(C)(C)C)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COCC(=O)NCC1(c2ccccc2)CCNCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1 g tert-butyl 4-[(2-methoxyacetylamino)-methyl]-4-phenylpiperidine-1-carboxylate are placed in 4 ml dichloromethane. Then 1.7 ml trifluoroacetic acid are added and the mixture is stirred overnight at ambient temperature. The reaction mixture is made basic with potassium carbonate and the organic phase is evaporated to dryness. 610 mg (V-7) are obtained in the form of an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[BH4-].[Na+].[C:13](O)(=O)[CH3:14].O>C(#N)C>[CH2:13]([NH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)[CH3:14]
Reactant: Nc1ccc(C(=O)O)cc1
Reactant: CC(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CCNc1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 26 h

Procedure:
A mixture composed of 4-aminobenzoic acid (30 g), sodium borohydride (32.3 g) and acetic acid (550 cc) is left stirring for 26 hours at 25° C. The reaction mixture is then concentrated to dryness at 70° C. under reduced pressure (4 kPa). The product obtained is treated with distilled water (2000 cc) and the precipitate formed is separated by filtration, washed with distilled water (20 cc) and dried in the air. The product obtained is dissolved in boiling acetonitrile (250 cc). After 2 hours' cooling at 25° C., the crystallized solid is separated by filtration, washed with acetonitrile (10 cc) and dried at 40° C. under reduced pressure (0.07 kPa). 4-Ethylaminobenzoic acid (18 g), m.p. 174° C., is obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:9][C:8]=1[NH2:20])([CH3:4])([CH3:3])[CH3:2].[O:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1.FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>ClCCl>[C:1]([O:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:9][C:8]=1[NH:20][CH:25]1[CH2:26][CH2:27][O:22][CH2:23][CH2:24]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCOCC1
Reactant: CN1CCN(c2ccc(C(=O)OC(C)(C)C)c(N)c2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C[N+](C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN1CCN(c2ccc(C(=O)OC(C)(C)C)c(NC3CCOCC3)c2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.7 %

Procedure:
To a solution of 2-amino-4-(4-methyl-piperazin-1-yl)-benzoic acid tert-butyl ester (11.5 g, 39.5 mmol) in dichloromethane (340 mL) were added tetrahydro-pyran-4-one (4.5 mL, 49.3 mmol), trifluoroacetic acid (8.2 mL) and tetramethylammonium triacetoxyborohydride (15.57 g, 59.2 mmol). The mixture was stirred at room temperature for 2 hours then washed with 0.5N hydrochloric acid, with 0.5N NaOH and with a saturated solution of NaHCO3. The organic layer was dried over sodium sulfate and evaporated to dryness affording the title compound as a pale yellow solid (13.3 g, 90% yield).
Reaction SMILES: N[C:2]1[C:10]([Cl:11])=[CH:9][C:8]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.N([O-])=O.[Na+].[PH2](O)=O>O1CCOCC1.O>[Cl:11][C:10]1[CH:2]=[C:3]([CH:7]=[C:8]([O:12][C:13]([F:14])([F:15])[F:16])[CH:9]=1)[C:4]([OH:6])=[O:5]
Reactant: Nc1c(Cl)cc(OC(F)(F)F)cc1C(=O)O
Agent: Cl
Agent: O=N[O-]
Agent: O=[PH2]O
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)c1cc(Cl)cc(OC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 50.1 %

Procedure:
To a solution of 2-amino-3-chloro-5-trifluoromethoxybenzoic acid (60.5 g, assume 0.22 mol; see step (iii) above) in 1,4-dioxane (1000 mL) was added 6N HCl (750 mL). Some organics oiled out of solution. The dioxane solution was cooled to less than 0° C. (ice-MeOH bath). A solution of sodium nitrite (18.2 g, 0.26 mol) in H2O (250 mL) was added over 15 minutes via an addition funnel. The resulting solution was stirred for 45 min. Hypophosphorous acid (221.5 mL of 50 wt % in H2O, 291.2 g, 2.20 mol) was added slowly via an addition funnel. The solution was stirred at 0° C. for 1.5 hours, then warmed to room temperature (gas evolution observed) and stirred for 18 hours. The crude solution was transferred to a separating funnel and extracted with Et2O (4×). The combined organics were extracted with aqueous NaHCO3 (3×). The basic aqueous layer was cautiously acidified with 6N HCl and extracted with CH2Cl2 (3×). The CH2Cl2 extracts were dried (Na2SO4), filtered and concentrated in vacuo to give the crude sub-title compound (26.5 g, 46% from 3-trifluoromethoxybenzoic acid) as a solid that was used in the next step without further purification.
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[NH:4][N:3]=1.C(N(CC)CC)C.[C:27]1([CH2:33][C:34](Cl)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH-].[Na+]>O1CCCC1.CO.O>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:5]2[NH:4][N:3]=[C:2]([NH:1][C:34](=[O:35])[CH2:33][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:6]=2[C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[CH:14][CH:15]=1
Reactant: Nc1n[nH]c(-c2ccc(F)cc2)c1-c1ccncc1
Reactant: O=C(Cl)Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Cc1ccccc1)Nc1n[nH]c(-c2ccc(F)cc2)c1-c1ccncc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 21.5 %

Procedure:
254 mg of 3-amino-5-(4-fluorophenyl)-4-(4-pyridyl)pyrazole was suspended in 20 ml of tetrahydrofuran, and 306 mg of triethylamine was added thereto. Then, 5 ml of a tetrahydrofuran solution containing 464 mg of phenylacetyl chloride was added dropwise thereto, followed by stirring at room temperature for 3 hours. After the addition of water, the reaction mixture was extracted with ethyl acetate. After the organic layer was washed with water and dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. After the resulting residue was dissolved in a mixture composed of 20 ml of methanol and 2 ml of a 2 mol/L sodium hydroxide solution and stirred for 1 hour, the precipitated crystals were collected by filtration. Moreover, the crystals thus obtained were suspended in a mixture composed of 20 ml of methanol and 2 ml of a 2 mol/L sodium hydroxide solution, and heated under reflux for 5 hours. The reaction mixture was concentrated under reduced pressure and then purified by column chromatography using 20 g of silica gel [with an elution solvent comprising chloroform-methanol (30:1)]. Thus, 80 mg (22% yield) of the title compound was obtained as colorless crystals.
Reaction SMILES: [CH:1]1[C:18]2=[C:19]3[C:8]([C:9]4[C:20]5[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=5)[CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[C:5]2[C:21](O[C:24](=[O:25])[C:3](=[C:4]23)[CH:2]=1)=[O:22].[NH2:26][CH2:27][CH2:28][OH:29].N1C=CN=C1.C(C(N1C(=O)C2C3C4C(=CC=2)C2C5C(C=CC=2)=CC=CC=5C=4C=CC=3C1=O)CCCCCC)CCCCC>>[OH:29][CH2:28][CH2:27][N:26]1[C:24](=[O:25])[C:3]2[C:4]3[C:19]4[C:18](=[CH:1][CH:2]=2)[C:17]2[C:20]5[C:13]([CH:14]=[CH:15][CH:16]=2)=[CH:12][CH:11]=[CH:10][C:9]=5[C:8]=4[CH:7]=[CH:6][C:5]=3[C:21]1=[O:22]
Reactant: O=C1OC(=O)c2ccc3c4cccc5cccc(c6ccc1c2c63)c54
Reactant: NCCO
Agent: CCCCCCC(CCCCCC)N1C(=O)c2ccc3c4cccc5cccc(c6ccc(c2c36)C1=O)c54
Agent: c1c[nH]cn1
Product: O=C1c2ccc3c4cccc5cccc(c6ccc(c2c36)C(=O)N1CCO)c54

Procedure:
190 mg (0.56 mmol) of perylene-3,4-dicarboxylic anhydride are reacted with 0.85 ml (1.40 mmol) of 2-aminoethanol and 1.18 g of imidazole under an argon inert atmosphere for 96 h as in 2c, and the reaction product is worked up and dried in a drying cabinet. To remove unreacted starting material, it is boiled in 10 per cent potassium carbonate solution and washed with hot water until the filtrate run-off is colourless. The brown-red product is dried in a drying cabinet at 120° C. and then recrystallized by extraction with toluene. Yield 50 mg (23%), m.p. >260° C. UV (CHCl3): λmax =489 nm, 509. Fluorescence (CHCl3, exc. 489 nm) λmax (Irel =546 nm (1), 579 (sh, 0.46).
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]([C:20]#[C:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:16][C:17](Cl)=[O:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)C1C=CC=CC=1.[CH:37]([OH:40])([CH3:39])[CH3:38]>CCOCC>[CH:37]([O:40][C:17](=[O:18])[CH2:16][CH:15]([C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:8]=1)[C:20]#[C:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([CH3:39])[CH3:38]
Reactant: COc1ccc(C(C#Cc2ccccc2)CC(=O)Cl)cc1OC1CCCC1
Reactant: CC(C)O
Solvent: CCOCC
Solvent: CN(C)c1ccccc1
Product: COc1ccc(C(C#Cc2ccccc2)CC(=O)OC(C)C)cc1OC1CCCC1
Reaction time: 18 h

Procedure:
A solution of (+/-)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-phenylethynylpropionic acid chloride (150 mg, 0.42 mmol) and dimethylaniline (100 mg, 0.83 mmol) in Et2O (5 ml) was treated with i-propanol (1 ml) and stirred at 23° for 18 hr. The solvents were evaporated, and the residue taken up in Et2O, washed with 3N HCl, H2O, dried, and the solvent evaporated. The residue was purified by flash chromatography (silica gel, 20% EtOAc/hexane), and gave the titled compound, 82 mg (54%). MP . 1H NMR (400 MHz, CDCl3) δ 7.38 (m, 2 H), 7.30 (m, 3 H), 6.94 (m, 2 H), 6.78 (d, 1 H), 5.02 (m, 1 H), 4.78 (m, 1 H), 4.30 (t, 1 H), 3.80 (s, 3 H), 2.82 (d of d, 1 H), 2.72 (d of d, 1 H), 1.78-1.96 (m, 6 H), 1.60 (m, 2 H), 1.22 (d, 3 H), 1.16 (d, 3 H).
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12](OC)=[O:13])=[O:7].O.[NH2:25][NH2:26]>O1CCCC1>[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([NH:25][NH2:26])=[O:13])=[O:7]
Reactant: COC(=O)c1cccc(NC(=O)c2cccc(C(F)(F)F)c2)c1
Reactant: NN
Solvent: C1CCOC1
Solvent: O
Product: NNC(=O)c1cccc(NC(=O)c2cccc(C(F)(F)F)c2)c1
Yield: 78.6 %

Procedure:
To a solution of 1.0 gm (3.09 mmol) of methyl 3-(3-trifluoromethylbenzamido)benzoate in 19 mL of tetrahydrofuran was added 1.06 mL (30.9 mmol) of hydrazine hydrate. The reaction was heated to reflux for 48 hr. After cooling, the reaction mixture was concentrated under rotevaporation, and ether and water were added. The solid product was separated by filtration and dried in vacuo to give 785 mg (2.43 mmol, 79% yield) of 3-(3-trifluoromethylbenzamido)benzhydrazide as a white solid. MS m/z: 324.0 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:34]C(=O)OC(C)(C)C)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=4)=[CH:22][N:21]=[C:20]4[NH:31][CH:32]=[CH:33][C:19]=34)[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C(Cl)Cl>[NH2:34][C@H:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:22][N:21]=[C:20]3[NH:31][CH:32]=[CH:33][C:19]=23)[CH2:14][CH2:13]1)=[O:11]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2c(-c3cccc(F)c3)cnc3[nH]ccc23)CC1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2c(-c3cccc(F)c3)cnc3[nH]ccc23)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 48.3 %

Procedure:
(R)-tert-Butyl 3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxopropan-2-ylcarbamate (0.045 g, 0.078 mmol) was placed in DCM (3 mL) at room temperature. TFA (0.3 mL) was then added, and the reaction was stirred at room temperature for 1 hour. The reaction was then concentrated to dryness, dissolved in minimal DCM, and added dropwise to a stirring solution of 1M HCl in ether. The solid product was filtered, washed with ether, and dried to give (R)-2-amino-3-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)propan-1-one (0.018 g, 48% yield) as the dihydrochloride salt. MS ESI (+) m/z 478 detected.
Reaction SMILES: [CH:1]1([NH2:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:35][CH:34]=2)[C:25]2[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=2[CH:27]=O)=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+]>C(O)C>[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([C:33]2[CH:34]=[CH:35][C:36]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:37][CH:38]=2)[C:25]2[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=2[CH2:27][NH:9][CH:1]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:20][CH:19]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=Cc1ccccc1C(c1ccc(OCc2ccccc2)cc1)c1ccc(OCc2ccccc2)cc1
Reactant: NC1CCCCCCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: c1ccc(COc2ccc(C(c3ccc(OCc4ccccc4)cc3)c3ccccc3CNC3CCCCCCC3)cc2)cc1
Yield: 65.5 %

Procedure:
In 50 ml of ethanol was dissolved 3 g of cyclooctylamine. To the solution was added 11.41 g of 2-[bis-(4-benzyloxyphenyl)methyl]benzaldehyde obtained by Reference Example 8, and the mixture was heated under reflux for 2 hours. Thereafter, 1.78 g of sodium borohydride was added thereto, and the mixture was heated under reflux for 2 hours. The solvent was evaporated under reduced pressure, and water was added to the residue. The aqueous mixture was extracted with ether, and the organic layer was separated. The aqueous layer was extracted with ether, and then the organic layers were combined and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized to afford 9.19 g of the desired product (Compound 82).
Reaction SMILES: C(C(CCCC)[CH2:4][O:5][C:6](=[O:17])[CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)C>[Pd]>[CH3:4][O:5][C:6](=[O:17])[CH:7]=[CH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1
Reactant: CCCCC(CC)COC(=O)C=Cc1ccc(OC)cc1
Agent: [Pd]
Product: COC(=O)C=Cc1ccc(OC)cc1
Yield: 68 %

Procedure:
The yield of 2-ethylhexyl-p-methoxycinnamate in the process of the present invention is above about 90%. This is in contrast to the 68% yield reported by Heck et al. in the article described above, in which a homogeneous palladium catalyst was employed to produce methyl-p-methoxycinnamate. Although not wishing to be bound by any theory, it is believed that the interaction of the palladium catalyst and the 2-ethylhexyl ester as opposed to the methyl ester and soluble palladium catalyst of the literature reference, causes this beneficial, unexpected result. A possible explanation of why the reaction yield is so much higher with the process of this invention is that there is a very high affinity of the 2-ethylhexyl acrylate for the carbon support of the palladium on carbon support catalyst. Both species are very nonpolar and hydrophobic and the hydrophobic 2-ethylhexyl chain tends to absorb in the carbon matrix, expediting the reaction of the acrylate function with the palladium surface. By contrast, the methyl function of methyl acrylate has no specific attraction to the soluble palladium acetate species and yield-consuming side reactions inevitably occur.