Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([C:6]1[CH:7]=[C:8]([C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][N:21]=2)[C:15]([O:17][CH3:18])=[O:16])[CH:9]=[CH:10][CH:11]=1)([CH3:5])([CH3:4])[CH3:3]>CO.[Pt](=O)=O>[C:2]([C:6]1[CH:7]=[C:8]([CH:12]2[CH2:13][CH:14]([C:15]([O:17][CH3:18])=[O:16])[CH2:19][CH2:20][NH:21]2)[CH:9]=[CH:10][CH:11]=1)([CH3:5])([CH3:3])[CH3:4]
Reactant: COC(=O)c1ccnc(-c2cccc(C(C)(C)C)c2)c1
Agent: O=[Pt]=O
Agent: Cl
Solvent: CO
Product: COC(=O)C1CCNC(c2cccc(C(C)(C)C)c2)C1
Reaction time: 13 h
Yield: 94.8 %

Procedure:
Methyl 2-(3-tert-butylphenyl)isonicotinate hydrochloride (3 g, 9.81 mmol) was dissolved in methanol (100 mL) and platinum(IV) oxide (0.111 g, 0.49 mmol) added. The resulting mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 13 h. To the mixture was added platinum(IV) oxide (40 mg), and the mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 1 h. The catalyst was filtered off and washed with MeOH and the eluate evaporated. DCM and satd NaHCO3 were added and the phases separated. Washed with brine, passed through a phase separator and evaporated to yield methyl 2-(3-tert-butylphenyl)piperidine-4-carboxylate (2.56 g, 95%) as a brown oil.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][OH:10])=[CH:7][CH:6]=1.[NH2:13][C:14]1[CH:19]=[N:18][C:17](Br)=[CH:16][N:15]=1.N>[Cu].O>[CH3:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][O:10][C:17]2[N:18]=[CH:19][C:14]([NH2:13])=[N:15][CH:16]=2)=[CH:7][CH:6]=1
Reactant: Nc1cnc(Br)cn1
Reactant: COc1ccc(CO)cc1
Agent: [Cu]
Agent: N
Agent: [H-]
Solvent: O
Product: COc1ccc(COc2cnc(N)cn2)cc1
Reaction time: 0.5 h

Procedure:
Sodium hydride (60% oily product) (78.8 mg) was added to 4-methoxybenzyl alcohol (2.14 mL) at a room temperature in an argon atmosphere, and the mixture was stirred for 30 minutes under the same conditions. Next, the reaction mixture was transferred to a metal seal tube. A copper powder (146 mg) and 2-amino-5-bromopyrazine (300 mg) were added, and the resultant mixture was heated and stirred at 160° C. for about 6 hours. After cooling, 25% aqueous ammonia and water were poured into the reaction solution. The reaction mixture was stirred for 1 hour at room temperature, and then filtrated through Celite. Water (20 mL) was added to the filtrate, and the resultant mixture was extracted with ethyl acetate (20 mL×3). The organic layer was washed with saturated brine (50 mL). The washed organic layer was dried over anhydrous sodium sulfate and filtrated, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane:ethyl acetate=3:1) to give 5-(4-methoxybenzyloxy)pyrazin-2-amine (104 mg).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[C:10](Cl)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8].[CH3:16][S:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[C:10]([C:21]2[CH:22]=[CH:23][C:18]([S:17][CH3:16])=[CH:19][CH:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8]
Reactant: CSc1ccc(B(O)O)cc1
Reactant: O=C(c1ccccn1)c1cccnc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CSc1ccc(-c2ncccc2C(=O)c2ccccn2)cc1
Temperature: 25 °C
Yield: 67.9 %

Procedure:
2-Chloro(3-pyridyl) 2-pyridyl ketone (Ryan Scientific Inc., South Carolina, U.S.) (810 mg, 3.7 mmol) and 4-(methylthio)benzeneboronic acid (830 mg, 5 mmol) were dissolved in toluene (50 mL) and ethanol (5 mL). To this solution was added 2 M Na2CO3 (6 mL, 12 mmol) followed by tetrakis (triphenylphosphine)palladium (250 mg, 0.2 mmol) and the resulting mixture was refluxed overnight under nitrogen atmosphere. The mixture was then cooled to room temperature and diluted with water (25 mL), stirred and the aqueous layer was separated and extracted with ethyl acetate (1×75 mL). The combined organic layers were washed with water (2×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated at reduced pressure to give the crude product. Purification by column chromatography over silica gel using 40% ethyl acetate in hexane gave the title compound (770 mg, 68% yield) as a white solid; mp 122-123° C.; 1H NMR (CDCl3) δ 8.87 (dd, J=4.8 and 1.7 Hz, 1H), 8.45 (d, J=4.7 Hz, 1H), 8.0 (dd, J=7.7 and 1.4 Hz, 2H), 7.75 (m, 1H), 7.45-7.3 (m, 4H), 7.12 (d, J=8.4 Hz, 2H), 2.44 (s, 3H); 13C NMR (CDCl3) δ 196.0, 157.6, 153.5, 150.7, 148.8, 139.3, 137.4, 136.6, 136.5, 133.6, 129.4 (2C), 126.5, 125.7 (2C), 123.5, 121.1, 15.3; LRMS (APIMS) m/z 307 (M+H)+.
Reaction SMILES: [C:1]([CH2:3][S:4][C@H:5]1[CH2:9][O:8][CH2:7][C@@H:6]1[C@:10]([NH:19]C(=O)C(F)(F)F)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[CH3:11])#[N:2].[BH4-].[Na+]>C(O)C>[NH2:19][C@@:10]([C@H:6]1[CH2:7][O:8][CH2:9][C@@H:5]1[S:4][CH2:3][C:1]#[N:2])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[CH3:11]
Reactant: C[C@@](NC(=O)C(F)(F)F)(c1ccccc1F)[C@H]1COC[C@@H]1SCC#N
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: C[C@@](N)(c1ccccc1F)[C@H]1COC[C@@H]1SCC#N
Temperature: 25 °C
Reaction time: 8 h
Yield: 57 %

Procedure:
A solution of the crude N-[rel-(S)-1-((3S,4R)-4-cyanomethylsulfanyl-tetrahydro-furan-3-yl)-1-(2-fluoro-phenyl)-ethyl]-2,2,2-trifluoro-acetamide (2 g, 3.19 mmol) in ethanol (60 ml) was reacted with sodium borohydride (482 mg, 12.8 mmol) at 0° C. The reaction was left to warm to room temperature and stirred overnight. For the workup, the reaction mixture was extracted with a mixture of a saturated solution of sodium hydrogencarbonate and ethyl acetate. The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The residue was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 0:100 as the eluent. The {rel-(3R,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ylsulfanyl}-acetonitrile (510 mg, 57% yield) was obtained as a light yellow oil. MS (ISP): m/z=281.0 [M+H]+.
Reaction SMILES: [CH2:1]([N:5]1[CH2:10][CH2:9][C:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)([OH:11])[CH2:7][CH2:6]1)[CH2:2][C:3]#[CH:4].I[C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=1>C(N)CCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:24][C:23]1[CH:25]=[CH:26][C:20]([C:4]#[C:3][CH2:2][CH2:1][N:5]2[CH2:10][CH2:9][C:8]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)([OH:11])[CH2:7][CH2:6]2)=[CH:21][CH:22]=1
Reactant: Nc1ccc(I)cc1
Reactant: C#CCCN1CCC(O)(c2ccc(Cl)cc2)CC1
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCN
Product: Nc1ccc(C#CCCN2CCC(O)(c3ccc(Cl)cc3)CC2)cc1
Yield: 20.8 %

Procedure:
A solution of 1-(3-butynyl)-4-(4-chlorophenyl)-4-hydroxypiperidine (263 mg, 1.00 mmol), 4-iodoaniline (208 mg, 0.950 mmol) and 50 mg of tetrakis(triphenylphosphine) palladium in 10 mL of butylamine is allowed to reflux for 20 hr. The solvent is evaporated in vacuo to give a residue, which is purified by flash chromatography giving the product as an off white solid (70 mg, 21%): mp 134-136βC; 1H NMR (CDCl3) 1.59 (m, 2 H), 1.90 (m, 2 H), 2.47 (m, 6 H), 2.67 (m, 2 H), 3.59 (s, 1 H), 3.87 (bs, 2 H), 6.46 (d, J=8.1 Hz, 1 H), 7.02 (d, J=8.1 Hz, 2 H), 7.14 (d, J=8.4 Hz, 2 H), 7.33 (d, J=8.4 Hz, 2 H).
Reaction SMILES: C(O[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)C.[ClH:14].[NH2:15][NH2:16]>C(O)C>[ClH:14].[NH:15]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][N:5]=1)[NH2:16]
Reactant: CCOC1=NCCc2ccccc21
Reactant: NN
Agent: Cl
Solvent: CCO
Product: NNC1=NCCc2ccccc21
Yield: 79.8 %

Procedure:
A mixture of 1-ethoxy-3,4-dihydroisoquinoline (1.0 g.), hydrazine monohydrochloride (0.4 g.) and absolute ethanol (15 ml.) was heated under reflux (for 40 min.). The solution was cooled, filtered and concentrated and the residue was recrystallized from ethanol-ether, affording 1-hydrazino-3,4-dihydroisoquinoline hydrochloride (0.9 g., m.p. 205°-207° C.). C. A mixture of 1-hydrazino-3,4-dihydroisoquinoline (8.0 g.), acetaldehyde (20 ml.) and ethanol (20 ml.) was allowed to stand at room temperature (for 45 min). Ethanolic sulfuric acid was added until the solution was distinctly acidic. Ether was added. The resulting oil crystallized and the crystals were recrystallized from ethanol-ether, affording 1-(2-ethylidenehydrazino)-3,4-dihydroisoquinoline (I: X=CH3, X'=Y=Y'=Z=Z'=H) sulfate in two crops (8.3 g., m.p. 152°-154° C.; 0.5 g., m.p. 152°-155° C.).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([CH2:15]O)=[C:13]([CH3:17])[CH:12]=[C:11]([CH3:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=S(Cl)[Cl:21].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][Cl:21])=[C:13]([CH3:17])[CH:12]=[C:11]([CH3:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cc(C)c(CO)c(OCc2ccccc2)n1
Reactant: O=S(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1cc(C)c(CCl)c(OCc2ccccc2)n1
Temperature: -40 °C
Reaction time: 0.5 h
Yield: 118.7 %

Procedure:
21.5 g×2 batches: To a solution of [2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methanol (Cpd Y, 21.5 g, 88.5 mmol) in anhydrous CH2Cl2 (400 mL) was added SOCl2 (16.0 g, 133 mmol) at −40° C. under N2. The mixture was stirred at the −40° C. for 30 minutes. The reaction mixture was poured into ice-water (300 mL) and adjusted pH 7˜8 with NaHCO3 (solid). The mixture was separated and the aqueous layer was extracted with CH2Cl2 (300 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 100:1) to give the title compound (Cpd Z, 27.5 g, 60%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 7.51-7.49 (d, 2H), 7.41-7.37 (t, 2H), 7.34-7.30 (t, 1H), 6.62 (s, 1H), 5.45 (s, 2H), 4.73 (s, 2H), 2.42 (s, 3H), 2.37 (s, 3H). MS 261.9 [M+H].
Reaction SMILES: Br[C:2]1[N:6]([C:7]([CH3:10])([CH3:9])[CH3:8])[N:5]=[CH:4][C:3]=1[C:11]1[S:12][CH:13]=[C:14]([CH2:16][C:17]([NH:19][CH2:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:18])[N:15]=1.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>>[C:7]([N:6]1[C:2]([C:32]2[CH:33]=[CH:34][C:29]([C:28]([F:39])([F:38])[F:27])=[CH:30][CH:31]=2)=[C:3]([C:11]2[S:12][CH:13]=[C:14]([CH2:16][C:17]([NH:19][CH2:20][CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[O:18])[N:15]=2)[CH:4]=[N:5]1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)n1ncc(-c2nc(CC(=O)NCC3CCOCC3)cs2)c1Br
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: CC(C)(C)n1ncc(-c2nc(CC(=O)NCC3CCOCC3)cs2)c1-c1ccc(C(F)(F)F)cc1

Procedure:
Using 2-(2-(5-bromo-1-tert-butyl-1H-pyrazol-4-yl)thiazol-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide and 4-(trifluoromethyl)phenylboronic acid and by reaction and purification in the same manner as in the method described in Example 30, step 9, the title compound was obtained. MS (API): 507 (M+H)
Reaction SMILES: [OH:1][CH:2]([CH2:19][CH3:20])[C:3]#[C:4][C:5]1[C:6]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:8]([C:11]([O:13][CH3:14])=[O:12])=[N:9][CH:10]=1>CO.[Pd]>[OH:1][CH:2]([CH2:19][CH3:20])[CH2:3][CH2:4][C:5]1[C:6]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:8]([C:11]([O:13][CH3:14])=[O:12])=[N:9][CH:10]=1
Reactant: CCC(O)C#Cc1cnc(C(=O)OC)cc1C(=O)OC
Agent: [Pd]
Solvent: CO
Product: CCC(O)CCc1cnc(C(=O)OC)cc1C(=O)OC
Reaction time: 4 h

Procedure:
317 mg of dimethyl 5-(3-hydroxy-1-pentinyl)-pyridine-2,4-dicarboxylate (Example 8) are dissolved in 25 ml of methanol and, after addition of the palladium catalyst (10% strength on charcoal) are hydrogenated. The reaction has ended after 4 hours (thin layer control). The catalyst is filtered off and the solution is concentrated in vacuo. The colorless oil is chromatographed on silica gel.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH3:18])=[C:8]3[C:15](=[N:16]O)[CH2:14][CH2:13][CH2:12][N:9]32)=[CH:5][CH:4]=1.[OH-].[Na+].[Cl-].[Na+]>C(O)C>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH3:18])=[C:8]3[CH:15]([NH2:16])[CH2:14][CH2:13][CH2:12][N:9]32)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(C)c3n(c2c1)CCCC3=NO
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc2c(C)c3n(c2c1)CCCC3N
Temperature: 45 °C
Reaction time: 18 h
Yield: 90.2 %

Procedure:
A solution of 6,7,8,9-tetrahydro-3-methoxy-10-methylpyrido[1,2-a]indol-9-one oxime (2.2 g, 9 mmol) in ethanol (50 mL) containing 10% sodium hydroxide (36 mL) was treated with Raney alloy (3.15 g) at 35° C. over 20 minutes. The reaction mixture was stirred at 45° C. for 18 hours, then poured into ice water (100 mL), saturated with sodium chloride. The product was extracted with ether (3×75 mL), dried, and evaporated. The residue was dissolved in toluene (30 mL), and extracted with 3% hydrochloric acid (50 mL). The aqueous layer was separated, and basified with 50% sodium hydroxide upon cooling. The product was extracted with chloroform, dried over MgSO4, filtered, and evaporated. The dark oily residue was chromatographed on silica gel (50 g). Elution with chloroform afforded 1.87 g (91%) of the desired amine as an amber oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][CH:6]=[CH2:7].I[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:34][CH3:35])[C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:23][CH:22]=1>>[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5]/[CH:6]=[CH:7]/[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:34][CH3:35])[C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)=[CH:23][CH:22]=1
Reactant: C=CCC(NC(=O)c1c(Cl)cccc1Cl)C(=O)OC
Reactant: CCN(c1ccc(I)cc1)c1ncccn1
Product: CCN(c1ccc(/C=C/CC(NC(=O)c2c(Cl)cccc2Cl)C(=O)OC)cc1)c1ncccn1
Yield: 72.9 %

Procedure:
In the same manner as in Example 1, 2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (214 mg) was reacted with N-(4-iodophenyl)-N-ethylpyrimidin-2-amine (254 mg) to obtain (E)-2-(2,6-dichlorobenzamido)-5-[4-(ethyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (258 mg). Column chromatography (silica gel, eluent: hexane/ethyl acetate=4/1→hexane/ethyl acetate=2/1→hexane/ethyl acetate=1/2) was used for purification.
Reaction SMILES: [SH:1][C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[CH2:4][OH:5].N1C=CC=CC=1[CH2:19][CH2:20][CH:21]1[CH2:26][C:25](=O)[CH2:24][CH2:23][NH:22]1>C(Cl)(Cl)Cl>[N+:10]([C:7]1[CH:8]=[CH:9][C:2]2[S:1][C:25]3([CH2:24][CH2:23][N:22]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:21][CH2:26]3)[O:5][CH2:4][C:3]=2[CH:6]=1)([O-:12])=[O:11]
Reactant: O=C1CCNC(CCc2ccccn2)C1
Reactant: O=[N+]([O-])c1ccc(S)c(CO)c1
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1ccc2c(c1)COC1(CCN(CCc3ccccn3)CC1)S2
Temperature: 25 °C
Reaction time: 48 h

Procedure:
2-Mercapto-5-nitrobenzyl alcohol (150 mg, 0.81 mmol) and 208 mg (0.80 mm) of N-[2-(2'-pyridyl ethyl]-4-piperidone was dissolved in 5 mL of CHCl3. HCl Gas was bubbled in to saturate the solution, the mixture stirred at 25° C. for 2 days, then diluted with water and the pH adjusted to 10.0 with 40% aqueous NaOH. Extraction with CHCl3 and drying the organic phase (Na2SO4) gave after concentration and recrystallization from ethyl acetate 75 mg of an orange solid.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([N:15]2[N:19]=[C:18]3[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:17]3=[N:16]2)[C:12]([OH:26])=[C:11]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:10]=1)C1C=CC=CC=1.C(O)=O.C([O-])=O.[NH4+]>C(O)C.O.[Pd]>[C:27]([C:11]1[CH:10]=[C:9]([OH:8])[CH:14]=[C:13]([N:15]2[N:19]=[C:18]3[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:17]3=[N:16]2)[C:12]=1[OH:26])([CH3:30])([CH3:28])[CH3:29]
Reactant: COc1ccc2nn(-c3cc(OCc4ccccc4)cc(C(C)(C)C)c3O)nc2c1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: O=CO
Solvent: CCO
Product: COc1ccc2nn(-c3cc(O)cc(C(C)(C)C)c3O)nc2c1
Temperature: 50 °C
Yield: 52.1 %

Procedure:
To a stirred solution of (XIII) (3.1 Kg) in ethanol (52 L), was charged a slurry of 10% Pd/C (300 g in 750 ml water) under nitrogen atmosphere. Formic acid (1.16 L) was added followed by addition of solution of ammonium formate (1.452 Kg) in DM water (755 ml). The reaction mixture was heated at 50° C. for 6 hr. The reaction mixture was cooled to room temperature and filtered. DM Water (31 L) was added to the filtrate, stirred and extracted with toluene (62 L). The organic layer was separated and washed with of (1:1) water: ethanol mixture (31 L). The organic layer was dried on sodium sulfate and evaporated up to 80%. The residual liquid was cooled to 0-5° C., filtered and dried at 50° C. for 1 hr to give the title product (XIV) (1.254 Kg). If required, the product was leached with methanol to obtain required purity.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21](C(C)C)[CH:20]=[CH:19][C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([CH3:16])([CH3:15])[O:13][B:12]([OH:17])[C:11]=2[CH:18]=1)=[O:5].[CH2:26]([Sn](CCCC)(CCCC)CCCC)[CH:27]=[CH2:28]>>[Cl:1][C:2]1[CH:22]=[C:21]([CH2:26][CH2:27][CH3:28])[CH:20]=[CH:19][C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([CH3:15])([CH3:16])[O:13][B:12]([OH:17])[C:11]=2[CH:18]=1)=[O:5]
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Reactant: CC(C)c1ccc(C(=O)Nc2ccc3c(c2)B(O)OC3(C)C)c(Cl)c1
Product: CCCc1ccc(C(=O)Nc2ccc3c(c2)B(O)OC3(C)C)c(Cl)c1

Procedure:
The title compound was prepared using a procedure similar to that of 2-chloro-N-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-4-isopropyl-benzamide with allyltributylstannane replacing isopropenyltributylstannane. Data: LCMS (M/Z): 358 (M+H); 1H NMR (DMSO-d6) δ: 0.91 (t, J=7.3 Hz, 3 H) 1.44 (s, 6 H) 1.61 (sxt, J=7.4 Hz, 2 H) 2.61 (t, J=7.8 Hz, 2 H) 7.28 (d, J=1.0 Hz, 1 H) 7.37 (d, J=8.3 Hz, 1 H) 7.40 (s, 1 H) 7.48 (d, J=7.8 Hz, 1 H) 7.68 (dd, J=8.2, 2.1 Hz, 1 H) 8.06 (d, J=1.0 Hz, 1 H) 9.03 (br. s, 1 H) 10.44 (s, 1 H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][C:32]([F:44])=[CH:31][C:30]=1[N:45]1[CH2:56][CH2:55][C:54]2[C:53]3[CH2:52][C:51]([CH3:58])(C)[CH2:50][C:49]=3[S:48][C:47]=2[C:46]1=[O:59])(=[O:26])[CH3:25].CC([O-])=O.[Na+]>CC#N.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]>[C:24]([O:27][CH2:28][C:29]1[C:30]([N:45]2[C:46](=[O:59])[C:47]3[S:48][C:49]4[CH2:50][CH2:51][CH2:58][CH2:52][C:53]=4[C:54]=3[CH2:55][CH2:56]2)=[CH:31][C:32]([F:44])=[CH:33][C:34]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:26])[CH3:25]
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cc(F)cc1N1CCc2c(sc3c2CC(C)(C)C3)C1=O
Reactant: CN1CCC(c2ccc(Nc3cc(Br)cn(C)c3=O)nc2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: CC#N
Product: CC(=O)OCc1c(-c2cc(Nc3ccc(C4CCN(C)CC4)cn3)c(=O)n(C)c2)cc(F)cc1N1CCc2c(sc3c2CCCC3)C1=O
Temperature: 110 °C
Yield: 52.3 %

Procedure:
A sealed tube was charged with the mixture of 5-bromo-1-methyl-3-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridin-2(1H)-one 130c (400 mg, 1.0 mmol), (4-fluoro-2-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-5-yl}-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 247b (534 mg, 1.0 mmol), Pd(dppf)Cl2 (87 mg, 0.1 mmol), K3PO4.3H2O(569 mg, 2.0 mmol), and NaOAc (175 mg, 2.0 mmol) in CH3CN (20 mL). The system was evacuated and then refilled with N2. And the reaction mixture was heated at 110° C. for 2 h. Then, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by column chromatography eluting with 10:1 methylene chloride/methanol to give 267a as a brown solid (350 mg, 49%). MS: [M+H]+ 670.
Reaction SMILES: Cl[C:2]1[CH:34]=[CH:33][C:5]2=[N:6][N:7]([C:9]3[CH:14]=[C:13]([C:15]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:17])[CH3:16])[CH:12]=[C:11]([C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([CH3:25])[CH3:24])[C:10]=3[OH:32])[N:8]=[C:4]2[CH:3]=1.[CH2:35]([SH:44])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>>[CH2:35]([S:44][C:2]1[CH:34]=[CH:33][C:5]2=[N:6][N:7]([C:9]3[CH:14]=[C:13]([C:15]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:17])[CH3:16])[CH:12]=[C:11]([C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([CH3:25])[CH3:24])[C:10]=3[OH:32])[N:8]=[C:4]2[CH:3]=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CC(C)(C)CC(C)(C)c1cc(-n2nc3ccc(Cl)cc3n2)c(O)c(C(C)(C)c2ccccc2)c1
Reactant: CCCCCCCCCS
Product: CCCCCCCCCSc1ccc2nn(-c3cc(C(C)(C)CC(C)(C)C)cc(C(C)(C)c4ccccc4)c3O)nc2c1

Procedure:
Using the procedure of Example 4 with 30 g of 5-chloro-2-(2-hydroxy-3-α-cumyl-5-tert-octylphenyl)-2H-benzotriazole and 17.6 g of nonyl mercaptan, the title compound is prepared.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=[O:14])[NH:11][CH:10]([C:15]3[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]([OH:24])=[C:17]([O:25][CH2:26][CH3:27])[CH:16]=3)[C:9]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[C:34]1([C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[NH:41])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:34]1([C:40](=[N:41][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[NH:13][C:12](=[O:14])[NH:11][CH:10]([C:15]4[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[C:18]([OH:24])=[C:17]([O:25][CH2:26][CH3:27])[CH:16]=4)[C:9]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:4][CH:3]=2)[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CCOc1cc(C2NC(=O)NC(c3ccc(Br)cc3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Reactant: N=C(c1ccccc1)c1ccccc1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CCOc1cc(C2NC(=O)NC(c3ccc(N=C(c4ccccc4)c4ccccc4)cc3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Yield: 34.9 %

Procedure:
A mixture of 6-(4-bromophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (Compound 33) (550 mg, 1.08 mmol), diphenylmethanimine (236 mg, 1.3 mmol), Cs2CO3 (702 mg, 2.16 mmol), Pd2(dba)3 (198 mg, 0.22 mmol), and xantphos (250 mg, 0.43 mmol) in dioxane (10 mL) was degassed and refluxed overnight under nitrogen. When LCMS indicated the starting material was consumed, the mixture was diluted with water, and extracted with EtOAc. The organic layer was concentrated, and purified by column to give 6-(4-(diphenylmethyleneamino)phenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (230 mg, yield 35%) as a yellow solid.