Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10](=[O:17])[N:11]=[C:12](SC)[NH:13][CH:14]=2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:34]=[CH:33][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH2:32])=[CH:26][CH:25]=2)=[CH:21][C:20]=1[C:35]([F:38])([F:37])[F:36]>C(O)C>[Cl:18][C:19]1[CH:34]=[CH:33][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH:32][C:12]3[NH:13][CH:14]=[C:9]([CH2:8][C:5]4[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=4)[C:10](=[O:17])[N:11]=3)=[CH:26][CH:25]=2)=[CH:21][C:20]=1[C:35]([F:36])([F:37])[F:38]
Reactant: NCCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Reactant: CSc1nc(=O)c(Cc2ccc(C)nc2)c[nH]1
Solvent: CCO
Product: Cc1ccc(Cc2c[nH]c(NCCc3ccc(Oc4ccc(Cl)c(C(F)(F)F)c4)cc3)nc2=O)cn1
Yield: 49 %

Procedure:
5-(6-methyl-pyridin-3-ylmethyl)-2-methylsulfanyl-1H-pyrimidin-4-one (50 mg, 0.202 mmol, 1 eq) and 2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamine (100 mg, 0.317 mmol, 1.57 eq) were heated in a sealed vial at 130° C. in 300 μl of absolute ethanol for 20 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 10 g normal phase silica SNAP column and DCM/20% MEOH in DCM solvent system (gradient 5-40% of 20% MeOH in DCM in 25 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the resulting crude was purified once more under the same conditions. Solvent from the gathered fractions of appropriate composition was evaporated the resulting oil was triturated with cyclohexane and diethyl ether to afford 2-{2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethylamino}-5-(6-methyl-pyridin-3-ylmethyl)-1H-pyrimidin-4-one (51 mg, yield=46.54%, purity=95%). MS: [M+H]=515.34. 1H NMR (300 MHz; CDCl3) δ/ppm 2.48 (s, 3H), 2.87 (t, J=7.23 Hz, 2H), 3.57 (s, 2H), 3.52-3.62 (m, 4H), 5.55 (br.s., 1H), 6.93 (d, J=8.23 Hz, 2H), 6.98-7.06 (m, 2H), 7.21 (d, J=8.23 Hz, 1H), 7.28 (d, J=2.84 Hz, 1H), 7.36-7.43 (m, 2H), 7.60 (br.s., 1H), 8.39 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[C@H:12]([CH3:16])[CH2:13][CH2:14]Br)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[N-:25]=[N+:26]=[N-:27].[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[C@H:12]([CH3:16])[CH2:13][CH2:14][N:25]=[N+:26]=[N-:27])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: C[C@H](CCBr)N(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: C[C@H](CCN=[N+]=[N-])N(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 22 °C
Reaction time: 96 h
Yield: 106.6 %

Procedure:
To a solution of 4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-bromopropyl]-benzenesulfonamide (1.74 g, 3.58 mmol) in THF/H2O (20/4, 24 mL) was added sodium azide (2.33 g, 35.8 mmol) at 22° C. The resulting mixture was allowed to stir at 22° C. for 4 days. The mixture was extracted with ether (3×60 mL). The combined organic extracts were washed with sat. NaHCO3, dried over MgSO4, filtered, and concentrated under reduced pressure. Silica gel chromatography (1:9 ethyl acetate:hexanes) of the concentrate afforded 1.53 g of 4-chloro-N-(2,5-difluorophenyl)-N-[(R)-1-methyl-3-azidopropyl]benzenesulfonamide as a colorless oil in 95% yield.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=O.[CH3:13][C:14]([CH3:16])=[O:15].[OH-].[Na+].O>C(O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=[CH:13][C:14](=[O:15])[CH:16]=[CH:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1
Reactant: CC(C)=O
Reactant: O=Cc1ccc2ccccc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(C=Cc1ccc2ccccc2c1)C=Cc1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 69.4 %

Procedure:
2-Naphthaldehyde (24, 1.56 g, 10.0 mmol) and acetone (19, 0.37 ml, 5.0 mmol) were combined in ethanol (10 ml) and stirred for 15 min at room temperature. A solution of sodium hydroxide (0.60 g, 15.0 mmol) and water (10 ml) was added and the mixture stirred for 18 hr at room temperature. The resulting precipitate was filtered and recrystallized from ethanol to give 1.16 g (69%) of a yellow solid: mp 244-246° C. [expected mp 243-244° C.]; 1H NMR: δ 7.23 (d, 2H, J=15.9 Hz), 7.52 (m, 4H), 7.83 (m, 8H), 7.93 (d, 2H, J=15.9 Hz), 8.03 (s, 2H); 13C NMR: δ 123.6, 125.7, 126.7, 127.3, 127.8, 128.6, 128.7, 130.5, 132.3, 133.3, 134.3, 143.1, 190.0.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([NH:10][C:11]3[O:12][CH2:13][C:14]4[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:3][CH2:2]1.[CH:22]([C:24]1[NH:25][CH:26]=[CH:27][N:28]=1)=O>>[CH:1]1([C:4]2[CH:5]=[C:6]([NH:10][C:11]3[O:12][CH2:13][C:14]4[CH:20]=[C:19]([NH:21][CH2:22][C:24]5[NH:25][CH:26]=[CH:27][N:28]=5)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:3][CH2:2]1
Reactant: Nc1ccc2c(c1)COC(Nc1cccc(C3CC3)c1)=N2
Reactant: O=Cc1ncc[nH]1
Product: c1cc(NC2=Nc3ccc(NCc4ncc[nH]4)cc3CO2)cc(C2CC2)c1
Yield: 39.2 %

Procedure:
Prepared from N2-(3-cyclopropyl-phenyl)-4H-benzo[d][1,3]oxazine-2,6-diamine (197 mg, 0.71 mmol) and 2-formylimidazole (81 mg, 0.84 mmol) according to the procedure described for example 88. Obtained the title compound as a white solid (100 mg, 39%), MS (ISP) m/e=358.5 [(M−H)+].
Reaction SMILES: C(OC([N:8]1[CH:13]([CH3:14])[CH2:12][N:11]([C:15]2[CH:16]=[N:17][C:18]([NH:21][C:22]3[N:23]=[CH:24][C:25]4[C:31]([CH3:32])=[C:30]([Br:33])[C:29](=[O:34])[N:28]([CH:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)[C:26]=4[N:27]=3)=[CH:19][CH:20]=2)[CH2:10][CH:9]1[CH3:40])=O)(C)(C)C.[Cl:41]CCl>Cl>[ClH:41].[Br:33][C:30]1[C:29](=[O:34])[N:28]([CH:35]2[CH2:36][CH2:37][CH2:38][CH2:39]2)[C:26]2[N:27]=[C:22]([NH:21][C:18]3[CH:19]=[CH:20][C:15]([N:11]4[CH2:12][CH:13]([CH3:14])[NH:8][CH:9]([CH3:40])[CH2:10]4)=[CH:16][N:17]=3)[N:23]=[CH:24][C:25]=2[C:31]=1[CH3:32]
Reactant: Cc1c(Br)c(=O)n(C2CCCC2)c2nc(Nc3ccc(N4CC(C)N(C(=O)OC(C)(C)C)C(C)C4)cn3)ncc12
Reactant: ClCCl
Agent: Cl
Product: Cc1c(Br)c(=O)n(C2CCCC2)c2nc(Nc3ccc(N4CC(C)NC(C)C4)cn3)ncc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 71.4 %

Procedure:
4-[6-(6-Bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-2,6-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.051 g, 0.083 mmol) was dissolved in dichloromethane (3 mL) to which 2 N HCl (2 mL) was added and the mixture was stirred at room temperature for 2 hours. This mixture was concentrated and allowed to sit for 10 days, it was then dissolved in 2 N HCl (2 mL) and stirred at room temperature for 5 hours. The solvent was removed to give 6-bromo-8-cyclopentyl-2-[5-(3,5-dimethyl-piperazin-1-yl)-pyridin-2-ylamino]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one hydrochloride salt as a yellow solid (0.039 g, 71.4%). 1H NMR δ(400 MHz, DMSO-d6) 9.51 (m, 1H), 9.02 (m, 1H),8.98 (s, 1H), 8.07 (s, 1H), 7.83 (s, 2H), 5.90 (m, 1H), 3.85 (d, J=11.2 Hz, 2H),3.35 (m, 2H), 2.76 (dd, J=12.0, 12.0 Hz 2H), 2.58 (s, 3H), 2.14 (m, 2H), 1.92 (m, 2H), 1.77 (m, 2H),1.58 (m, 2H), 1.28 (d, J=6.4 Hz, 6H).
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][C:7]2[N:8]=[N:9][N:10]([CH3:12])[N:11]=2)=[CH:4][CH:3]=1.FC1C=CC(CC2N(C)N=NN=2)=CC=1.[Li]CCCC.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)=[O:41])[CH:35]=1>CCOCC.O1CCCC1>[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]([C:7]2[N:8]=[N:9][N:10]([CH3:12])[N:11]=2)[C:40]([C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)([C:36]2[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=2)[OH:41])=[CH:4][CH:3]=1
Reactant: Cn1nnc(Cc2ccc(F)cc2)n1
Reactant: O=C(c1cccnc1)c1cccnc1
Agent: Cn1nnnc1Cc1ccc(F)cc1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: Cn1nnc(C(c2ccc(F)cc2)C(O)(c2cccnc2)c2cccnc2)n1
Reaction time: 1 h

Procedure:
To a 1:1 mixture of 5-(4-fluorobenzyl)-2-methyl-2H-tetrazole and 5-(4-fluorobenzyl)-1-methyl-1H-tetrazole, (0.209 g, 1.09 mmol) in 10 mL of 1:1 ether:tetrahydrofuran at −78° C. was added dropwise n-BuLi (0.434 mL of 2.5 M in hexane, 1.09 mmol). After stirring for one hour, a solution of dipyridin-3-ylmethanone (200 mg, 1.09 mmol) in 3 mL of tetrahydrofuran was added dropwise. Afterh 30 minutes, the reaction was quenched by transferring it via cannula to a −78° C. solution of 100 mL of ether containing 1 mL of concentrated aqueous HCl solution. After concentrating the mixture in vacuo, the resulting residue was taken up in EtOAc and extracted with 10% aqueous Na2CO3 solution and brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by preparative reverse-phase HPLC to provide the titled compound, along with a regioisomer (Example VII-4). 1H NMR (500 MHz, d6-DMSO): δ 8.91 (br s, 1H), 8.66 (br s, 1H), 8.36 (d, J=4.4 Hz, 1H), 8.24 (d, J=4.4 Hz, 1H), 8.07 (br d, J=8.3 Hz, 1H), 7.82 (br d, J=8.0 Hz, 1H), 7.51 (dd, J =8.7 and 5.6 Hz, 2H), 7.29 (dd, J=8.3 and 4.9 Hz, 1H), 7.16 (dd, J=8.0 and 4.6 Hz, 1H), 6.95 (t, J=9.0 Hz, 2H), 6.16 (s, 1H), 6.05 (s, 1H), 4.23 (s, 3H). HRMS [M+H] C20H18FN6O calcd 377.1521 , found 377.1527.
Reaction SMILES: [CH2:1]([Li])[CH2:2]CC.[C:6]([C:9]1[N:24]=[CH:23][C:12]2[N:13]([CH:20]([CH3:22])[CH3:21])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][CH:17]=[CH:16][CH:15]=3)([OH:8])=[O:7].CC1(C)CCCC(C)(C)N1.CI>C1COCC1>[C:6]([C:9]1[N:24]=[CH:23][C:12]2[N:13]([CH:20]([CH3:21])[CH3:22])[C:14]3[C:19]([C:11]=2[C:10]=1[CH2:1][CH3:2])=[CH:18][CH:17]=[CH:16][CH:15]=3)([OH:8])=[O:7]
Reactant: CC(C)n1c2ccccc2c2cc(C(=O)O)ncc21
Reactant: [Li]CCCC
Agent: CC1(C)CCCC(C)(C)N1
Solvent: CI
Solvent: C1CCOC1
Product: CCc1c(C(=O)O)ncc2c1c1ccccc1n2C(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 33.6 %

Procedure:
n-Butyllithium (2.5 M in hexanes, 3.2 ml, 8 mmol) and 3-carboxy-9-isopropyl-9H-pyrido[3,4-b]indole (Method 2; 504 mg, 2 mmol) were added to a solution of 2,2,6,6-tetramethyl piperidine (1.01 ml, 6 mmol) in THF (15 ml) at −50° C. The mixture was allowed to stir for 30 minutes warming to 0° C. Methyl iodide (0.15 ml, 2.4 mmol) was then added in a single portion and the mixture was left at 0° C. for a further 30 minutes and at room temperature for a further 16 hours. The mixture was concentrated in vacuo and the residue was dissolved in DCM. The solution was washed with 1 M HCl and then with water. The organic phase was separated, dried and concentrated in vacuo. The crude product was purified by preparative HPLC eluting over a gradient of 20-90% MeCN in water (0.1% TFA). The product was obtained as a yellow solid (190 mg) after evaporation of the appropriate fractions. NMR (300 MHz) 9.16 (s, 1H), 8.39 (d, 1H), 8.01 (d, 1H), 7.72 (t, 1H), 7.43 (t, 1H), 5.39 (m, 1H), 3.60 (q, 2H), 1.67 (d, 6H), 1.38 (t, 3H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.N1C=CC=CC=1.[CH2:18]([O:25][C:26](Cl)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl>[CH2:18]([O:25][C:26]([NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CCOC(=O)c1csc(N)n1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOC(=O)c1csc(NC(=O)OCc2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To an ice-cold mixture of ethyl 2-amino-1,3-thiazole-4-carboxylate (5 g), pyridine (3.36 ml) and dichloromethane (50 ml) was added benzyloxycarbonyl chloride (3.1 ml), and the mixture was stirred at ambient temperature for 1 hour. The reaction mixture was washed with saturated aqueous sodium hydrogen bicarbonate (30 ml), dried over sodium sulfate and concentrated in vacuo. The crystalline residue was collected and washed with diisopropyl ether to give ethyl 2-{[(benzyloxy)carbonyl]amino}-1,3-thiazole-4-carboxylate (5.1 g)
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:10]>[B].B#[Zr]>[C:9](=[O:10])([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Oc1ccccc1
Agent: B#[Zr]
Agent: [B]
Product: O=C(Oc1ccccc1)Oc1ccccc1

Procedure:
Example 1 was repeated with 14.1 g of a powdered zirconium diboride from H. C. Starck at 140° C. After 2 hours' reaction time, phenol conversion was 35.7%, wherein 0.4 g of phenyl chloroformate and 54.9 g of diphenyl carbonate were formed. Selectivity for carbonates was greater than 96%.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[NH:12][CH:13]=[CH:14][C:7]=12)([O-:5])=[O:4].[CH3:15]I>CC(N(C)C)=O>[CH3:15][N:12]1[C:8]2=[N:9][CH:10]=[CH:11][C:6]([N+:3]([O-:5])=[O:4])=[C:7]2[CH:14]=[CH:13]1
Reactant: O=[N+]([O-])c1ccnc2[nH]ccc12
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: Cn1ccc2c([N+](=O)[O-])ccnc21
Reaction time: 0.5 h

Procedure:
170 mg (4.29 mmol) of sodium hydride are added to a solution of 500 mg (3.06 mmol) of 4-nitro-1H-pyrrolo[2,3-b]pyridine (Antonini, Ippolito; Claudi, Francesco; Cristalli, Gloria; Franchetti, Palmarisa; Grifantini, Mario; Martelli, Sante; J. Med. Chem. 1982, 25, 1258-1261.) in 10 ml of absolute DMA, and the suspension is stirred for 30 min. A solution of 230 μl (3.68 mmol) of methyl iodide in 2 ml of absolute DMA is then slowly added dropwise, and the mixture is again stirred for 60 min. After concentration under reduced pressure, the residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[C:10](O)[N:9]=[C:8]([CH3:16])[N:7]=1)=[O:5])[CH3:2].O=P(Cl)(Cl)[Cl:19]>>[CH2:1]([O:3][C:4]([C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[C:10]([Cl:19])[N:9]=[C:8]([CH3:16])[N:7]=1)=[O:5])[CH3:2]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCCc1c(O)nc(C)nc1C(=O)OCC
Product: CCCc1c(Cl)nc(C)nc1C(=O)OCC
Temperature: 85 °C

Procedure:
A mixture of 121 (10 mmol) and POCl3 (25 ml) is heated at 85° C. for 4 hours. The solvent is removed in vacuo and EtOAc (40 ml) and water (30 ml) are added to the residue. NaHCO3 is carefully added until the pH of the aqueous layer is greater than 7. The layers are separated and the aqueous layer is extracted with EtOAc (2×30 ml). The combined extracts are washed with brine (50 ml), dried (Na2SO4) and evaporated. Flash column purification of the residue with 3:1 EtOAc, hexane provides the product (122) as a light yellow oil.
Reaction SMILES: C[C:2]1[C:3]([I:15])=[C:4]([O:13][CH3:14])[C:5]([I:12])=[C:6]([C:10]=1[I:11])[C:7](O)=[O:8].C(Cl)(=O)C([Cl:19])=O>C(Cl)Cl.CN(C=O)C>[CH3:14][O:13][C:4]1[C:5]([I:12])=[C:6]([C:10]([I:11])=[CH:2][C:3]=1[I:15])[C:7]([Cl:19])=[O:8]
Reactant: COc1c(I)c(C)c(I)c(C(=O)O)c1I
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1c(I)cc(I)c(C(=O)Cl)c1I
Temperature: 25 °C
Reaction time: 4 h

Procedure:
In a 25 mL round-bottom flask equipped with a condenser, methyl 3-methoxy-2,4,6-triiodobenzoic acid (0.250 g) was suspended in 3 mL anhydrous methylene chloride. Oxalyl chloride (0.58 mL) and one drop of DMF was added. The reaction mixture was stirred for 4 h at RT. The solvent and excess oxalyl chloride were removed by rotary evaporation. The desired acyl chloride was dried under vacuum to give a pale yellow solid which was used in the next step without any further purification. Yield 0.272 g (crude ˜100%)
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].C1C2NC3C(=CC=CC=3)C=2C=CC=1.[CH3:18][SiH:19]([O:22][CH3:23])[O:20][CH3:21]>C(O)C>[NH2:4][CH2:1][CH2:2][CH2:3][Si:19]([CH3:18])([O:22][CH3:23])[O:20][CH3:21]
Reactant: C=CCN
Reactant: CO[SiH](C)OC
Agent: c1ccc2c(c1)[nH]c1ccccc12
Solvent: CCO
Product: CO[Si](C)(CCCN)OC
Temperature: 60 °C
Reaction time: 4 h
Yield: 74 %

Procedure:
Into the same reactor as used in Example 1, 17.1 parts of allylamine, 0.3 part of carbazole, 0.00005 part as platinum atom of the same platinum complex as in Example 1 were charged, 31.8 parts of methyldimethoxysilane were added dropwise at 40° C. over 5 minutes, followed further by continuing stirring for 4 hours while maintaining the liquid temperature at 60° C. After cooling, 1.7 parts of ethanol were added and distillation was carried out to give 36.2 parts of γ-aminopropylmethyldimethoxysilane boiling at 105° to 109° C./50 Torr. This corresponded to 74% yield based on the theoretical amount.
Reaction SMILES: C([O:3][C:4]([CH:6]1[NH:30][CH2:29][C@:28]2([C:31](=[O:34])[CH2:32][OH:33])[C@H:7]1[CH2:8][C@H:9]1[C@H:22]3[C@@:13]([F:26])([C@:14]4([CH3:25])[C:19]([C@@H:20]([F:23])[CH2:21]3)=[CH:18][C:17](=[O:24])[CH:16]=[CH:15]4)[C@@H:12]([OH:27])[CH2:11][C@@:10]12[CH3:35])=[O:5])C.Cl>C1COCC1.O.[Cl-].[Na+].O>[CH2:8]([N:30]1[CH2:29][C:28]2([C:31](=[O:34])[CH2:32][OH:33])[CH:7]([CH2:8][CH:9]3[CH:22]4[C:13]([F:26])([C:14]5([CH3:25])[C:19]([CH:20]([F:23])[CH2:21]4)=[CH:18][C:17](=[O:24])[CH:16]=[CH:15]5)[CH:12]([OH:27])[CH2:11][C:10]32[CH3:35])[CH:6]1[C:4]([OH:3])=[O:5])[C:9]1[CH:22]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CCOC(=O)C1NC[C@]2(C(=O)CO)[C@H]1C[C@H]1[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]12C
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC12C=CC(=O)C=C1C(F)CC1C3CC4C(C(=O)O)N(Cc5ccccc5)CC4(C(=O)CO)C3(C)CC(O)C12F
Temperature: 25 °C
Reaction time: 8 h
Yield: 15 %

Procedure:
To a solution of compound 119 (66 mg; 0.113 mmol) in dry THF (3 ml) and water (1 ml) 1 N NaOH (400 μl) is added and the reaction mixture is stirred at RT overnight. The reaction mixture is poured into 1 N HCl (10 ml) and brine (10 ml), and the aqueous phase is extracted with AcOEt (3×40 ml). The combined organic extracts are dried and concentrated. Crude is purified by preparative HPLC, to afford title compound (15% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13](=[O:14])[CH2:12][C:11]([CH3:15])=[N:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:23][C:24]1[CH:25]=[C:26]([N:31]=[C:32]=[O:33])[CH:27]=[CH:28][C:29]=1[Cl:30]>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13](=[O:14])[CH:12]([C:32](=[O:33])[NH:31][C:26]3[CH:27]=[CH:28][C:29]([Cl:30])=[C:24]([Cl:23])[CH:25]=3)[C:11]([CH3:15])=[N:10]2)=[CH:7][CH:8]=1
Reactant: COc1ccc(N2N=C(C)CC2=O)cc1
Reactant: O=C=Nc1ccc(Cl)c(Cl)c1
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: COc1ccc(N2N=C(C)C(C(=O)Nc3ccc(Cl)c(Cl)c3)C2=O)cc1
Reaction time: 4 h

Procedure:
The stirred solution of 4.1 g of 1-(p-methoxyphenyl)-3-methyl-2-pyrazolin-5-one in 75 ml of warm benzene and 2.4 g of triethylamine is combined with the solution of 3.8 g of 3,4-dichlorophenylisocyanate in 50 ml of benzene. After standing at ambient temperature for 4 hours, the benzene is evaporated, the residue taken up in methanol and the solution poured into 100 ml of 0.3 N hydrochloric acid. The mixture is allowed to stand overnight at room temperature, the precipitate is collected, washed with water, dried, triturated with benzene-ethyl acetate and recrystallized from methanol to yield the 1-(p-methoxyphenyl)-3-methyl-4-(3,4-dichlorophenylcarbamoyl)-2-pyrazolin-5-one of Formula II with R=OCH3, R'=3--Cl and R"=Cl, melting at 120°-125°, resolidifying and remelting at 228°-232° (dec.).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][C:29]=1[S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([S:38]([C:29]3[CH:30]=[CH:31][C:32]4[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:28]=3)(=[O:40])=[O:39])[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Reactant: CC(C)(C)OC(=O)c1ccc(NC2CCNCC2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1ccc(NC2CCN(S(=O)(=O)c3ccc4ccccc4c3)CC2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 96.4 %

Procedure:
Compound (49) (0.056 g, 0.2 mmol) and triethylamine (0.14 mL, 1 mmol) were added sequentially to a solution of 2-naphthalene sulfonyl chloride (0.136 g, 0.6 mmol) in CH2Cl2 (5 mL) at 25° C. The mixture was stirred at 25° C. for 12 h then was concentrated under reduced pressure. Purification of the residue by flash column chromatography (gradient elution 0 to 30% EtOAc in hexanes) provided the title compound (0.09 g, 92.5%): TLC (Rf =0.50; 40% EtOAc/Hexanes); 1H NMR (CDCl3) δ 8.35 (s, 1H), 7.98 (m, 3H) 7.73 (m, 5H), 6.43 (d, 2H, J=8.7), 3.86 (d, 2H, J=9.2), 3.78 (s, 1H), 3.60 (m, 1H), 2.60 (t, 2H, J=10.5), 2.11 (d, 2H, J=13.4), 1.60 (m, 2H), 1.54 (s, 9H); 13C NMR (CDCl3) δ 165.9, 149.9, 135.0, 133.2, 132.2, 131.4, 129.3, 129.2, 129.0, 128.9, 128.0, 127.7, 123.0, 121.1, 111.9, 79.9, 49.0, 45.2, 31.7, 28.4; HRMS (FAB) m/z 467.2019 (M+H)+ (C26H30N2O4S requires 467.2005).
Reaction SMILES: [CH3:1][Mg]Br.[F:4][C:5]([F:44])([F:43])[C:6]1[CH:7]=[C:8]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:9][N:10]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]=[O:33])[CH:29]=[CH:28][C:27]=1[O:34][CH3:35])[C:11](=[O:14])[O:12][CH3:13].[Cl-].[NH4+]>O1CCCC1>[F:4][C:5]([F:43])([F:44])[C:6]1[CH:7]=[C:8]([CH:36]=[C:37]([C:39]([F:40])([F:42])[F:41])[CH:38]=1)[CH2:9][N:10]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([OH:33])[CH3:1])[CH:29]=[CH:28][C:27]=1[O:34][CH3:35])[C:11](=[O:14])[O:12][CH3:13]
Reactant: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc(C(F)(F)F)ccc1-c1cc(C=O)ccc1OC
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc(C(F)(F)F)ccc1-c1cc(C(C)O)ccc1OC
Temperature: 25 °C

Procedure:
Methylmagnesium bromide (0.59 mL, 0.83 mmol) was added dropwise to a solution of methyl [3,5-bis(trifluoromethyl)benzyl]{[5′-formyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (Example 73, 289 mg, 0.49 mmol) in anhydrous tetrahydrofuran at 0° C. The solution was allowed to warm to room temperature. Once the reaction was complete, saturated ammonium chloride solution was added to quench the reaction. The mixture was extracted with methylene chloride, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The title compound was obtained by flash chromatography using 30% acetone/hexane. 1H NMR (CDCl3, 600 MHz) δ 7.73 (s, 1H), 7.58 (m, 1H), 7.32-7.51 (m, 5H), 7.11 (m, 1H), 6.94 (m, 1H), 4.87 (m, 1H), 4.25-4.43 (m, 4H), 3.69 (m, 6H), 1.48 (d, J=4.2 Hz, 3H). LC-MS (M+Na) 632.0 (4.18 min).
Reaction SMILES: [N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([OH:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH2:34][C:35]1[CH:40]=[C:39]([CH2:41]O)[CH:38]=[CH:37][N:36]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[NH2:34][C:35]1[CH:40]=[C:39]([CH2:41][O:14][C:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH:38]=[CH:37][N:36]=1
Reactant: O=[N+]([O-])c1ccc(O)c2ccccc12
Reactant: Nc1cc(CO)ccn1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Nc1cc(COc2ccc([N+](=O)[O-])c3ccccc23)ccn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.3 %

Procedure:
To a solution of 4-nitronaphthol (5.17 g, 27.3 mmol), PPh3 (10.75 g, 41.0 mmol) and 2-aminopyridine-4-methanol (1) (5.09 g, 41.0 mmol) in THF (50 mL) was added dropwise DIAD (8.07 mL, 41.0 mmol) at −15° C. The mixture was stirred overnight at RT and the volatiles removed in vacuo. The crude product was triturated from EtOAc (150 mL), filtered off and washed with EtOAc (100 mL). A second trituration from MeOH (100 mL) gave 2-amino-4-((4-nitronaphthalen-1-yloxy)methyl)pyridine (2) (4.54 g, 56%) as a yellow solid: m/z 296 (M+H)+ (ES+).