Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].CN(C)C=O.F[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=1[N+:22]([O-:24])=[O:23]>O>[CH2:1]([N:3]([CH2:4][CH3:5])[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=1[N+:22]([O-:24])=[O:23])[CH3:2]
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1F
Reactant: CCNCC
Solvent: CN(C)C=O
Solvent: O
Product: CCN(CC)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Reaction time: 3 h
Yield: 98.3 %

Procedure:
Diethylamine (230 μl, 2.22 mmol, commercially available product) was added at room temperature to an N,N-dimethylformamide (DMF; 0.5 ml) solution of 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (211 mg, 1.01 mmol, commercially available product). The resulting mixture was stirred for three hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20 g, hexane/ethyl acetate=8/1). Thus, 1-diethylamino-2-nitro-4-(trifluoromethyl)benzene (258 mg, 98.3%) was yielded as an orange-colored oily material.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:6]=1[O:12][CH2:13][CH:14]1[CH2:16][CH2:15]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:7][C:6]=1[O:12][CH2:13][CH:14]1[CH2:15][CH2:16]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(O)cc1OCC1CC1
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)COc1ccc(C(C)(C)C)c(OCC2CC2)c1
Yield: 75.6 %

Procedure:
4-tert-Butyl-3-(cyclopropylmethoxy)phenol (444 mg, 2.0 mmol), sodium hydride (60% in mineral oil) (68 mg, 1.7 mmol) and ethyl bromoacetate (270 II, 2.4 mmol) were treated in the same procedure described in Example 31(c). The crude residue was applied to a silica gel chromatography column and eluted with a volume mixture of hexane and ethyl acetate (19/1 to 9/1) to furnish 463 mg (75% yield) of the title compound as a yellow oil.
Reaction SMILES: C1(=O)[N:5]([CH2:6][CH2:7][O:8][C@H:9]2[CH2:26][CH2:25][C@@:24]3([CH3:27])[C@H:11]([CH2:12][CH2:13][C@@H:14]4[C@@H:23]3[CH2:22][CH2:21][C@@:19]3([CH3:20])[C@:15]4([OH:33])[CH2:16][CH2:17][C@@H:18]3[C:28]3[CH:32]=[CH:31][O:30][CH:29]=3)[CH2:10]2)C(=O)C2=CC=CC=C12.O.NN.O>C(O)C>[NH2:5][CH2:6][CH2:7][O:8][C@H:9]1[CH2:26][CH2:25][C@@:24]2([CH3:27])[C@H:11]([CH2:12][CH2:13][C@@H:14]3[C@@H:23]2[CH2:22][CH2:21][C@@:19]2([CH3:20])[C@:15]3([OH:33])[CH2:16][CH2:17][C@@H:18]2[C:28]2[CH:32]=[CH:31][O:30][CH:29]=2)[CH2:10]1
Reactant: C[C@]12CC[C@H](OCCN3C(=O)c4ccccc4C3=O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](c3ccoc3)CC[C@]12O
Agent: NN
Solvent: O
Solvent: CCO
Product: C[C@]12CC[C@H](OCCN)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](c3ccoc3)CC[C@]12O
Yield: 92.7 %

Procedure:
To a solution of 0.50 g of 3β-(2-phthalimidoethoxy)-17β-(3-furyl)-5β-androstan-14β-ol in 50 ml of ethanol (96%) 0.19 g of hydrazine hydrate were added at room temperature. The mixture was kept at reflux for 4 hrs, then 10 ml of water were added and the ethanol distilled under reduced pressure. The residue was extracted with methylene chloride, the organic solution was washed with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The crude residue was purified by flash-chromatography (SiO2) using methylene chloride/methanol 90/10 as eluant to give 0.35 g of the title compound (I-aa) as a white solid.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][CH:4]=1.C(O)(=O)C.[O-:16][C:17]#[N:18].[Na+]>O1CCCC1>[CH3:1][N:2]([C:3]1[CH:4]=[CH:5][C:6]([N+:9]([O-:11])=[O:10])=[CH:7][CH:8]=1)[C:17]([NH2:18])=[O:16]
Reactant: CNc1ccc([N+](=O)[O-])cc1
Reactant: N#C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CN(C(N)=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 24 h
Yield: 25.4 %

Procedure:
A 250-mL round bottom flask was charged with N-methyl-4-nitroaniline (1.94 g, 12.7 mmol) in tetrahydrofuran (50 mL). To this stirred solution at rt was added acetic acid (14.6 mL, 255 mmol) and sodium cyanate (8.29 g, 127.5 mmol). After 24 h, the reaction mixture was concentrated under reduced pressure. The residue was suspended in water (100 mL) and the resultant solid was isolated by filtration, washing sequentially with dichloromethane and ethyl acetate to afford the title compound (0.63 g, 25%) as a yellow solid. MW=195.18. 1H NMR (DMSO-d6, 500 MHz) δ 8.19-8.14 (m, 2H), 7.58-7.54 (m, 2H), 6.54 (br s, 2H), 3.27 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([Cl:9])[CH:3]=1.[O:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.C(O)(=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:9][C:4]1[CH:3]=[C:2]([C:14]2[O:10][CH:11]=[N:12][CH:13]=2)[CH:8]=[CH:7][C:5]=1[NH2:6]
Reactant: c1cocn1
Reactant: Nc1ccc(Br)cc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)C(=O)O
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: Nc1ccc(-c2cnco2)cc1Cl
Temperature: 110 °C
Yield: 37.2 %

Procedure:
Palladium acetate (5.4 mg, 0.024 mmol) was added to a solution of 4-bromo-2-chloroaniline (0.1 g, 0.484 mmol), oxazole (0.064 mL, 0.969 mmol), di(1-adamantyl)-n-butylphosphine (0.017 g, 0.048 mmol), pivalic acid (0.020 g, 0.194 mmol) and potassium carbonate (0.201 g, 1.453 mmol) in DMA (2.4 mL). The reaction mixture was heated at 110° C. overnight before being diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude mixture was purified via Biotage silica gel column chromatography eluting with (Cyclohexane/EtOAc 80/20 to 60/40) to give the title product as a white solid (35 mg, 37%). 1H NMR (500 MHz, CDCl3): δ 4.25 (br s, 2H), 6.82 (d, J=8.3 Hz, 1H), 7.20 (s, 1H), 7.38 (dd, J=8.3, 2.0 Hz, 1H), 7.58 (d, J=2.0 Hz, 1H), 7.87 (s, 1H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH:6]=[C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][CH2:18][NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1>Cl.[Pd]>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH2:17][CH2:18][NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:7]1
Reactant: CN1CC=C(c2c[nH]c3ccc(CCNS(C)(=O)=O)cc23)CC1
Agent: [Pd]
Agent: Cl
Product: CN1CCC(c2c[nH]c3ccc(CCNS(C)(=O)=O)cc23)CC1

Procedure:
The product of stage (ii) (1.00 g) in ethanolic hydrogen chloride (200 ml) was hydrogenated for 1 h over pre-reduced 10% palladium on carbon (50% paste with water, 1.00 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][CH2:16][OH:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N+]1([O-])CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][CH:16]=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCCCC1CCCO
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCCCC1CCC=O
Reaction time: 1.5 h
Yield: 86.7 %

Procedure:
To a solution of N-tert-butoxycarbonyl-3-piperidin-2-yl-propan-1-ol (0.372 g, 1.53 mmol) in CH2Cl2 (7.5 mL), at room temperature, was added sequentially 3Å molecular sieves (0.814 g), N-methylmorpholine N-oxide (0.278 g, 2.37 mmol) and tetrapropylammonium perruthenate (56 mg, 0.16 mmol). After 90 minutes, the mixture was filtered through a short column of silica gel and the cake was washed with ethyl acetate. The solvent was removed from the filtrate under reduced pressure to provide 0.32 g (86%) of N-tert-butoxycarbonyl-3-piperidin-2-yl-propionaldehyde as a green oil which was used without further purification.
Reaction SMILES: C([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]2[CH2:14][C:13]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:12][CH2:11][C:10]=12)=[O:5])C>CCO.[Li+].[OH-].[OH-].[Na+]>[CH2:17]([C:13]1([CH2:15][CH3:16])[CH2:12][CH2:11][C:10]2=[C:6]([C:4]([OH:5])=[O:3])[S:7][CH:8]=[C:9]2[CH2:14]1)[CH3:18]
Reactant: CCOC(=O)c1scc2c1CCC(CC)(CC)C2
Agent: [Li+]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCC1(CC)CCc2c(csc2C(=O)O)C1
Yield: 23 %

Procedure:
A solution of 5,5-diethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid ethyl ester (14.2 g, 53.38 mmol) in EtOH (250 mL) and 2 N aq. LiOH (250 mL) is stirred at 65° C. for 18 h. The mixture is diluted with 1 N aq. NaOH and extracted with Et2O. The aq. phase is acidified to pH 2 with 2 N aq. HCl and extracted with DCM. The combined DCM extracts are dried over Na2SO4, filtered, and the solvent is removed in vacuo. The crude product (11.3 g) is purified by MPLC on RP-C18 silica gel to give 5,5-diethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (2.93 g) as a brown oil; LC-MS: tR=1.01 min, [M+1+CH3CN]=280.19; 1H NMR (CDCl3): δ 7.12 (s, 1H), 2.99 (t, J=7.0 Hz, 2H), 2.46 (s, 2H), 1.59 (t, J=7.0 Hz, 2H), 1.40-1.20 (m, 4H), 0.84-0.74 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](N)=[C:10]([I:15])[CH:9]=2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].C(OCC)(=O)C.[BrH:26]>O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].[Cu]>[Br:26][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:9][C:10]=1[I:15]
Reactant: Nc1ccc(-c2ccc(Cl)cc2)cc1I
Reactant: Br
Agent: [Cu+2]
Agent: [Cu]
Agent: O=N[O-]
Solvent: CCOC(C)=O
Solvent: O
Product: Clc1ccc(-c2ccc(Br)c(I)c2)cc1
Temperature: 45 °C
Reaction time: 1.5 h

Procedure:
4′-Chloro-3-iodobiphenyl-4-ylamine (13.5 g, 0.041 mol) is ground to a fine powder and suspended in a mixture of 48% aqueous hydrogen bromide (54 ml) and distilled water (42 ml). This suspension is then heated to 45° C. for 30 minutes, then cooled to 0-5° C. and a solution of sodium nitrite (3.54 g, 0.0125 mol) in distilled water (6 ml) is added dropwise, maintaining internal temperature below 5° C. throughout. This mixture is then added portionwise to a second pre-formed suspension of copper(II) sulfate pentahydrate (15 g, 0.06 mol) and copper powder (5.29 g, 0.084 mol) in 48% aqueous hydrogen bromide (80 ml) at 80° C. When the addition is complete the reaction mixture is stirred at 80° C. for an additional 90 minutes. After cooling to room temperature, ethyl acetate is added and the reaction mixture is poured into distilled water and the two layers separated. The aqueous phase is further extracted with ethyl acetate (×2), and the combined organic extracts are washed with distilled water until a neutral pH is achieved, then dried over anhydrous magnesium sulfate. The mixture is filtered, the filtrate is evaporated in vacuo, and the residue is further purified by flash column chromatography on silica gel (hexane eluant) to afford 4-bromo-4′-chloro-3-iodobiphenyl (10.5 g) as a pale orange liquid.
Reaction SMILES: Cl.Cl[C:3]1[N:8]=[C:7]([NH:9][CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[C:6]([F:20])=[CH:5][N:4]=1.[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH3:35])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH2:36])=[C:26]([F:37])[CH:25]=2)[CH2:23][CH2:22]1>CC(O)C>[CH:21]1([C:24]2[C:29]([N:30]3[C:34]([CH3:35])=[N:33][N:32]=[N:31]3)=[CH:28][C:27]([NH:36][C:3]3[N:8]=[C:7]([NH:9][CH:10]4[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]4)[C:6]([F:20])=[CH:5][N:4]=3)=[C:26]([F:37])[CH:25]=2)[CH2:22][CH2:23]1
Reactant: Cc1nnnn1-c1cc(N)c(F)cc1C1CC1
Reactant: CC1(C)CC(Nc2nc(Cl)ncc2F)CC(C)(C)N1
Agent: Cl
Solvent: CC(C)O
Product: Cc1nnnn1-c1cc(Nc2ncc(F)c(NC3CC(C)(C)NC(C)(C)C3)n2)c(F)cc1C1CC1
Temperature: 70 °C
Yield: 57.9 %

Procedure:
A mixture of 2-chloro-5-fluoro-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidin-4-amine hydrochloride (416 mg, 1.29 mmol, 1 equiv), 4-cyclopropyl-2-fluoro-5-(5-methyl-1H-tetrazol-1-yl)benzenamine (300 mg, 1.29 mmol, 1 equiv), and PTSA monohydrate (196 mg, 1.03 mmol, 0.8 equiv) in IPA (13 mL) were heated to 70° C. for 6 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness and taken in water, EtOAc, and 1N NaOH. The layers were separated. The organic layer was washed with 1N NaOH 2×, dried over Na2SO4, filtered, and concentrated to dryness. The crude product was purified by trituration from EtOAc:hexane to give compound N2-(4-cyclopropyl-2-fluoro-5-(5-methyl-1H-tetrazol-1-yl)phenyl)-5-fluoro-N4-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine (361 mg, 58%) as a solid.
Reaction SMILES: [O:1]=[C:2]1[N:14]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C@@H:24]([C:35]([OH:37])=O)[CH2:25][C:26]3[CH:31]=[C:30]([CH3:32])[C:29]([OH:33])=[C:28]([CH3:34])[CH:27]=3)=[O:22])[CH2:17][CH2:16]2)[C:5]2[CH:6]=[N:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[O:67]1[CH2:72][CH2:71][CH:70]([N:73]2[CH2:78][CH2:77][NH:76][CH2:75][CH2:74]2)[CH2:69][CH2:68]1>CN(C=O)C>[O:1]=[C:2]1[N:14]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C@H:24]([CH2:25][C:26]3[CH:31]=[C:30]([CH3:32])[C:29]([OH:33])=[C:28]([CH3:34])[CH:27]=3)[C:35](=[O:37])[N:76]3[CH2:75][CH2:74][N:73]([CH:70]4[CH2:71][CH2:72][O:67][CH2:68][CH2:69]4)[CH2:78][CH2:77]3)=[O:22])[CH2:17][CH2:16]2)[C:5]2[CH:6]=[N:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:4]=2[NH:3]1
Reactant: C1CN(C2CCOCC2)CCN1
Reactant: Cc1cc(C[C@@H](OC(=O)N2CCC(n3c(=O)[nH]c4c5ccccc5ncc43)CC2)C(=O)O)cc(C)c1O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1cc(C[C@@H](OC(=O)N2CCC(n3c(=O)[nH]c4c5ccccc5ncc43)CC2)C(=O)N2CCN(C3CCOCC3)CC2)cc(C)c1O
Reaction time: 2 h

Procedure:
A solution of 100 mg (0.15 mmol) (R)-1-carboxy-2-(4-hydroxy-3,5-dimethyl-phenyl)-ethyl 4-(2-oxo-1,2-dihydro-imidazo[4,5-c]quinolin-3-yl)-piperidine-1-carboxylate, 53 mg (0.16 mmol) TBTU and 26 μL (0.19 mmol) triethylamine in 1 mL DMF was stirred for 15 min at RT. Then 28 mg (0.16 mmol) 1-(tetrahydropyran-4-yl)-piperazine was added and the reaction solution was stirred for 2 h. The reaction solution was purified by HPLC without any further working up; the fractions containing the product were combined and lyophilised.
Reaction SMILES: [H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH:29]=[CH:30][CH:31]=1)[O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([NH2:28])=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][CH:17]=1>C1COCC1>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH:29]=[CH:30][CH:31]=1)[O:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]2[C:23]3=[N:28][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:24]3[CH:25]=[CH:26][CH:27]=2)=[CH:20][CH:21]=1
Reactant: COc1cccc(Oc2ccc(-c3cccnc3N)cc2)c1
Reactant: O=S(=O)(Cl)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cccc(Oc2ccc(C3=CC=CN4CCS(=O)(=O)N=C34)cc2)c1
Reaction time: 0.08 h

Procedure:
To a suspension of NaH (60%, 143 mg) in THF (dry) (15 mL) was added 2-chloroethanesulfonyl chloride (0.376 mL) at 0° C. and the mixture was stirred for 5 min at the same temperature. A solution of 3-(4-(3-methoxyphenoxy)phenyl)pyridin-2-amine (348 mg) in THF (dry) (15 mL) was added at 0° C. and the mixture was stirred at room temperature under nitrogen for 15 hr. The mixture was quenched with water at 0° C. carefully and water was added to form precipitates. The precipitate was crystallized from MeCN-THF-MeOH/IPE to give the title compound (304 mg) as colorless crystals.
Reaction SMILES: [I-].[I:2][C:3]1[CH:11]=[C:10]([I:12])[CH:9]=[C:8]2[C:4]=1[C:5]([CH3:16])([CH3:15])[C:6]([CH3:14])=[N+:7]2[CH3:13].Cl.[C:18]1([NH:24][CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=NC2C=CC=CC=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(OC(=O)C)(=O)C>[I-:2].[NH:24]([CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=[CH:14][C:6]1[C:5]([CH3:16])([CH3:15])[C:4]2[C:8](=[CH:9][C:10]([I:12])=[CH:11][C:3]=2[I:2])[N+:7]=1[CH3:13])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: C(=CC=Nc1ccccc1)C=CNc1ccccc1
Reactant: CC1=[N+](C)c2cc(I)cc(I)c2C1(C)C
Agent: Cl
Agent: [I-]
Solvent: CC(=O)OC(C)=O
Product: C[N+]1=C(C=CC=CC=CNc2ccccc2)C(C)(C)c2c(I)cc(I)cc21

Procedure:
100 mg (0.18 mmol) of 4,6-diiodo-1,2,3,3-tetramethyl-3H-indolium iodide and 51 mg (0.18 mmol) of N-[5-(phenylamino)-2,4-pentadienylidene]aniline monohydrochloride were stirred in 2 mL of acetic anhydride at 110-120° C. for 15 min. After cooling the product was precipitated with ether, filtered off and washed with ether. Yield: 67 mg (53%). λmax (abs) 483 nm (methanol). This product was used for following step without additional purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:11]2[CH:16]=[C:15]([C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[CH2:18])[CH:14]=[C:13]([C:27]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)=[CH2:28])[CH:12]=2)=[CH2:10])=[CH:5][CH:4]=1.C1COCC1.[H][H]>[Pd].CCO>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([CH:27]([C:13]2[CH:14]=[C:15]([CH:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH3:18])[CH:16]=[C:11]([CH:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[CH3:10])[CH:12]=2)[CH3:28])=[CH:34][CH:33]=1
Reactant: [H][H]
Reactant: C=C(c1ccc(OC)cc1)c1cc(C(=C)c2ccc(OC)cc2)cc(C(=C)c2ccc(OC)cc2)c1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: COc1ccc(C(C)c2cc(C(C)c3ccc(OC)cc3)cc(C(C)c3ccc(OC)cc3)c2)cc1

Procedure:
A mixture of 1,3,5-tris(1-(4-methoxyphenyl)vinyl)benzene (4) (19.61 g, 41 mmol), 5% Pd/C (500 mg), THF (50 mL) and EtOH (50 mL) was hydrogenated (50 torr) on a Parr® apparatus for 5 h. After this time the uptake of hydrogen ceased. The mixture was filtered through diatomaceous earth to remove the catalyst and rotary evaporated leaving the title compound as a colorless, viscous oil. Yield: 19.6 g (100%). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.06 (d, J=8.7 Hz, 6H), 6.88-6.84 (m, 3H), 6.79 (d, J=8.9 Hz, 6H), 4.0 (q, J=7.5 Hz, 3H), 3.78 (s, 9H), 1.52 (d, J=7.3 Hz, 9H). 13C NMR (75 MHz, CDCl3, δ, ppm): 157.16, 145.83, 145.78, 145.74, 138.03, 137.99, 137.97, 127.55, 123.54, 123.46, 123.41, 113.36, 54.61, 42.94, 42.92, 21.29. Anal. calcd for C33H36O3: C, 82.46; H, 7.55. Found: C, 82.23; H, 7.40.
Reaction SMILES: C[O:2][C:3](=[O:22])[CH2:4][CH2:5][O:6][N:7]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C[Si](C)(C)[O-].[K+:28]>C1(C)C=CC=CC=1>[K+:28].[CH2:15]([N:7]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[O:6][CH2:5][CH2:4][C:3]([O-:22])=[O:2])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)CCON(Cc1ccccc1)Cc1ccccc1
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: O=C([O-])CCON(Cc1ccccc1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a stirred solution of 9.75 g of the compound of Example I in 100 ml of toluene is added 3.85 g of potassium trimethylsilanolate. After stirring the mixture at room temperature for 12 hours, the mixture is concentrated under reduced pressure and the residue is triturated with ether to leave the title compound as an off-white hygroscopic solid.
Reaction SMILES: C(N)C1C=CC=CC=1.C(OC([NH:19][C@H:20]([C:28]([NH:30][C@H:31]([C:33]([NH:35][O:36][P:37]([CH3:40])(=[O:39])[OH:38])=[O:34])[CH3:32])=[O:29])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=O)C1C=CC=CC=1>>[NH2:19][C@H:20]([C:28]([NH:30][C@H:31]([C:33]([NH:35][O:36][P:37]([CH3:40])(=[O:38])[OH:39])=[O:34])[CH3:32])=[O:29])[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)NOP(C)(=O)O
Solvent: NCc1ccccc1
Product: C[C@H](NC(=O)[C@@H](N)Cc1ccccc1)C(=O)NOP(C)(=O)O

Procedure:
In a manner analogous to that given in Example 7 (b), from the benzylamine salt of [(N-benzyloxycarbonyl-L-phenylalanyl-L-alanyl)amino]-methylphosphonic acid there was obtained (L-phenylalanyl-L-alanylamino)-methylphosphonic acid of melting point 262°-264° C (decomposition); [α]D20 = - 9.6° (c = 0.5% in water).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:16](I)=[CH:15][N:14]([S:18]([C:21]4[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=4)(=[O:20])=[O:19])[C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.[CH3:41][C:42]1[CH:43]=[C:44]([CH:60]=[CH:61][CH:62]=1)[CH2:45][N:46]1[CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[CH:48]=[N:47]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:41][C:42]1[CH:43]=[C:44]([CH:60]=[CH:61][CH:62]=1)[CH2:45][N:46]1[CH:50]=[C:49]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([C:6]4[CH:7]=[CH:2][C:3]([CH:28]5[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]5)=[CH:4][CH:5]=4)[CH:9]=3)[N:14]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:15]=2)[CH:48]=[N:47]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4ccc(C5CCN(C(=O)OC(C)(C)C)CC5)c(F)c4)cnc32)cc1
Reactant: Cc1cccc(Cn2cc(B3OC(C)(C)C(C)(C)O3)cn2)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(C)c4)c3)c3cc(-c4ccc(C5CCN(C(=O)OC(C)(C)C)CC5)cc4)cnc32)cc1

Procedure:
Using similar reaction conditions as described in step-i of example-1, tert-butyl 4-(2-fluoro-4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperidine-1-carboxylate (intermediate 67B) (155 mg, 0.235 mmol) was coupled with 1-(3-methylbenzyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 64D) (105 mg, 0.353 mmol) using Pd(dppf)Cl2 (9 mg, 0.011 mol) and sodium carbonate (75 mg, 0.7070 mmol) in toluene/ethanol/water (20/10/5 ml) to afford 165 mg (crude) of the titled compound. MS: m/z=702.7 (M+1).
Reaction SMILES: O.[C:2]([C:6]1[CH:11]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:9]=[CH:8][C:7]=1[OH:16])([CH3:5])([CH3:4])[CH3:3].[C:17](O)(=[O:20])[CH:18]=[O:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:12]([C:10]1[CH:11]=[C:6]([C:2]([CH3:5])([CH3:4])[CH3:3])[C:7]2[O:16][C:18](=[O:19])[CH:17]([OH:20])[C:8]=2[CH:9]=1)([CH3:15])([CH3:14])[CH3:13]
Reactant: O=CC(=O)O
Reactant: CC(C)(C)c1ccc(O)c(C(C)(C)C)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)c1cc2c(c(C(C)(C)C)c1)OC(=O)C2O

Procedure:
A 15 l multi-necked vessel with stirrer, dropping funnel, water separator, condenser and thermometer is charged with stirring and in succession with 300 ml of toluene, 212 g of 97% 2,4-di-tert-butylphenol (Aldrich 99%), 121.9 ml of 50% strength aqueous glyoxylic acid and 0.5 g of p-toluenesulfonic acid monohydrate. The reaction mixture is subsequently refluxed vigorously with thorough stirring. This is accompanied by the separation of the water present in the glyoxylic acid, and the water of reaction from the first stage. After a reflux time of about 3 h, the separation of water ends, to leave a homogeneous, pale yellow solution of 5,7-di-t-butyl-3-hydroxybenzofuran-2-one. Thereafter, the toluene is distilled off under atmospheric pressure and with a heating-bath temperature of up to 142° C. The crystalline solid is subsequently dried at 80° C./50 mbar.